To investigate the safety and feasibility of endoscopic nasogallbladder drainage (ENGBD) combined with laparoscopic surgery for Mirizzi syndrome type I with acute cholecystitis.  An analysis of 4 patients with type I Mirizzi syndrome with acute cholecystitis admitted to the First Hospital of Jilin University.  The patients underwent ENGBD, and laparoscopic surgery was evaluated postoperatively. All four patients successfully recovered from this combined surgical approach.  The combination of ENGBD and laparoscopic surgery is safe and feasible for the treatment of patients with type I Mirizzi syndrome accompanied by acute cholecystitis. This approach may reduce the traumatic stress on patients and is worthy of widespread implementation. Mirizzi syndrome (MS) is characterized by obstructive jaundice and cholangitis caused by stones in the cystic duct and gallbladder neck. MS also involves inflammation of the common bile duct, caused by the pressure associated with cholelithiasis . BecauseIn recent years, endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic nasobiliary drainage (ENBD) have been used in combination to treat MS. The effectiveness and safety of this combined approach have rendered it the gold standard for the treatment of MS . We honeThe objective of this report was to investigate the safety and feasibility of ENGBD combined with laparoscopic surgery for MS type I with acute cholecystitis. The present report was exempted from the ethical review by the Jilin University Ethics Review Board.All four patients were treated in the Department of Hepatobiliary and Pancreatic Surgery at the First Hospital of Jilin University during the period from May 2017 to December 2017. All four patients immediately underwent a routine blood and liver function tests, as well as color Doppler ultrasound examination, computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) after admission to the emergency department  and endoscopic papillary balloon dilation (EPBD) were performed simultaneously to remove the bile duct stones. In Case 4, the patient underwent ENGBD only. No attempt was made to remove the bile duct calculi because of the large size of the stones and the bile duct edema caused by inflammation. The clinical symptoms of Case 4, which included abdominal pain, fever, and jaundice, were significantly relieved after ENGBD treatment.After 2–5 days of recovery, all four patients underwent elective laparoscopic surgery. Cases 1, 2, and 3 underwent laparoscopic cholecystectomy (LC), while Case 4 underwent laparoscopic cholecystectomy and laparoscopic common bile duct exploration (LCBDE). The ENGBD tubes of all 4 patients were removed during surgery. A summary of the surgical plan is presented in None of the four patients experienced a severe postoperative complication. Case 4 had a minor amount of bile leakage, which was cured by ultrasound-guided abdominal puncture drainage. The T-tube was successfully removed after the results of T-tube angiography at the three-month postoperative follow-up visit confirmed the absence of any residual stones.All patients were followed up for 12 months. No stone recurrence or related complication was noted in any case, indicating excellent short-term outcomes of this surgical approach.Because of the difficulty of preoperative diagnosis and the complexity of pathological changes in patients with Mirizzi syndrome, laparoscopic treatment for the disease is difficult and is associated with high risk for complications , 5. It hAt present, first-stage ERCP and ENBD combined with second-stage surgery have become the preferred treatment for all types of Mirizzi syndrome. This is because ENBD can be performed expediently to remove the biliary obstruction and guide the shape of the common bile duct during second-stage surgery. The combination of ENBD with laparoscopic surgery is reported to be a safe and effective treatment for Mirizzi syndrome. Compared with other surgical approaches, the combination of ENBD with laparoscopic surgery results in less trauma, less pain, and faster recovery times . HoweverENGBD has a history of more than 30 years. Kozarek  completeAccording to these reports, the success rate of ENGBD was 53.8-90.0% , 15, 16.Nuzzo et al.  reportedThe ENGBD-laparoscopic approach has the following advantages. First, this technique integrates diagnostic and treatment approaches. ERCP is the preferred option for diagnosing Mirizzi syndrome. When performed promptly after the definitive diagnosis, ENGBD can enhance the effectiveness of the treatment. Second, this approach allows for precise drainage. Traditional ENBD removes pus and bile only from the common bile duct, without addressing concurrent acute cholecystitis caused by cystic duct obstruction. In severe cases, patients have symptoms such as abdominal pain and fever after the operation, in addition to complications such as gallbladder perforation. The ENGBD utilizes the multilateral hole in the nasal bile duct to sufficiently drain the gallbladder cavity and bile duct . Last buIn the clinical study reported by Arisaka et al. , jaundicThe other complications of ENGBD include acute pancreatitis and penetration of the cystic duct which is because inflammatory edema could cause the wall of the cystic duct to become weak and so caution is required . AlthougThe combination of ENGBD and laparoscopic surgery for type I Mirizzi syndrome with acute cholecystitis is safe and feasible. This approach can reduce the traumatic stress to patients and is worthy of widespread implementation. As the number of cases remains limited, we will continue to accumulate data in order to further evaluate the efficacy of this approach in the treatment of other manifestations of Mirizzi syndrome.


The surface with high-aspect-ratio nanostructure is observed to possess the bactericidal properties, where the physical interaction between high-aspect-ratio nanostructure could exert sufficient pressure on the cell membrane eventually lead to cell lysis. Recent studies in the interaction mechanism and reverse engineering have transferred the bactericidal capability to artificial surface, but the biomimetic surfaces mimicking the topographical patterns on natural resources possess different geometrical parameters and surface properties. The review attempts to highlight the recent progress in bactericidal nanostructured surfaces to analyze the prominent influence factors and cell rupture mechanism. A holistic approach was utilized, integrating interaction mechanisms, material characterization, and fabrication techniques to establish inclusive insights into the topographical effect and mechano-bactericidal applications. The experimental work presented in the hydrogel material field provides support for the feasibility of potentially broadening applications in soft contact lenses. From the first introduction to microorganisms in 1674, the continuous observations and research in microorganism aggregation have contributed to the development of microbiology and pathology, which is an essential part of modern medical science. As a functional consortium of pathogenic microbe proliferation, biofilm plays a vital role in nutrient absorption from the outer environment and security protection for the constituted cell inside. Empirical therapeutic methods to deal with microbial infection are antibiotic utilization and surface chemical property modification, which may bring a toxic appendant effect to the in vivo organism. As manifested in the relevant literature, the progress rate of research in chemical therapeutics like antibiotics and topical drugs cannot keep up with the evolution of microbes and only have limited bactericidal efficacy in killing the top layer of biofilm, while the cell community beneath the outer surface retain high functionality and viability . A 2019 For the selection process in nature, it is a challenge for flora and fauna to tackle biofilm formation and ramification. Hence, the epidermal topography of this biology has evolved to generate unique surface appendages, for instance, insect wings , marine animal skin (shark etc.), and plant leaves . Based on the investigation of the antibacterial properties of these natural occurring antimicrobial surfaces ,11,12,13As the validity of the topographical function of natural occurring antimicrobial surfaces has been confirmed by various cell incubation tests and theoretical model simulations, several biomimetic surfaces have been fabricated with surface modifications referring to antetype surface geometrical features, which has prompted the feasibility analysis of these topographical effect applications in the biomedical field. The subsequent comparative analysis of biomimetic surfaces and antetype basis has demonstrated that biomimetic surfaces possess higher antibacterial capabilities by controlling the geometrical parameters and spatial distribution of the nanostructure, so the phenomena illuminated that surface bactericidal efficacy and other surface properties could be modified by varying the surface features.Contact lens related keratitis is commonly induced by continuous pathogen adhesion from various exteriors, where the keratitis is corneal inflammation that threatens serious complications with permanent damage to vision performance and even blindness. Disposable contact lenses, especially daily disposable contact lenses, have adopted a minimal lens care design strategy that can significantly reduce care and maintenance procedures requiring complete sterile conditions. However, high risk for bacterial adhesion and inducing microbial keratitis is reserved in ubiquitous extended-wear or continuous-wear behaviors. Considering the extensive application and functionality of biomimetic surfaces, the introduction of an antibacterial nanostructure to the soft contact lens (SCL) edge area could be a potential solution to extend the expiration date of SCL and maintain a high level of hygiene when encountering a complicated service environment.Bacteria are typically classified referring to morphology  and cell wall (Gram-positive and Gram-negative bacteria) . The figMost peptidoglycan layers targeting antimicrobial agents primarily maintain sustainable clinical efficacy in Gram-positive bacterial infection, but some Gram-positive bacteria like Methicillin-resistance S. aureus (MRSA) are recently observed to possess increasing resistance rates.Microbes are ubiquitous in every corner of living quarters, and high adaptability to hostile environment increases their survivability. Parasite pathogens inhabiting plants and livestock could disperse through the airflow, and airborne bacteria could reach the normal human range of activities in an indoor environment. The major portion of bacteria may not develop a large community and low microbial concentration would have a confined impact on human health, but the nosocomial infection or neonatal infection occurring in hospitals could always lead to lethal risk which is shown in 13 mammalian cells and approximately 1014 bacteria, fungal, and protozoan cells generate a complicated symbiosis relationship [Like parasitic organisms, pathogens live and procreate based on nutrient absorption from the host organism, so microbial colonization or parasitism could have occurred in every lifeform on Earth. As the human body is commonly retained at constant temperature and continuous metabolism, microorganisms have evolved specific mechanisms to maintain sustainable parasitism activities in this desirable breeding ground . In a cotionship . These mtionship .As a majority of bacteria encountered in daily life are innoxious, common bacteria could autonomously execute most of the basic metabolic activities, as the primary reason for inhabiting the host is seeking rich nutrition . Among tEscherichia coli and Staphylococcus aureus are the conventional isolated nosocomial pathogens [E. coli is detected in a large proportion of urinary tract infection (UTI) clinically collected specimens from female patients, it rarely exists at other infection sites [Nosocomial infection mainly manifests as a clinical disease instead of microbial colonization because most of the predisposing bacteria for nosocomial are opportunistic pathogens. Based on previous study , Escheriathogens . Since Eon sites . TherefoMicroorganisms have the propensity to crowd together for biofilm formation on biotic or abiotic surfaces, which is a heterogeneous and multifunctional community that maintains firm adhesion to the befitting substratum. This assembled lifestyle presents numerous advantages compared to free-swarming planktonic cells including increased nutrient availability and higher security from predators . BiofilmBacterial adhesion is the prerequisite for biofilm formation; in the process from planktonic to the sessile state, the transition process contains two different stages that are termed as reversible adhesion and irreversible adhesion. Reversible adhesion means that the cell–substrate bonding is weak and cells could return to the aqueous medium by small external force; irreversible adhesion is initiated by multiple contacts between the cell and substrate . After iAside from the benefits from biofilm formation, the strengthened adhesion on the substratum has several lethal limitations including the inhibition of motility. When the nutrition source is depleted, the reinforced bond would become a barrier for detained bacteria with a shortage dilemma. In the conversion process from the planktonic to coaggregation state, the transcriptional regulator inversely controls the production of motility and EPS, which means that the required motility for escape switches to EPS secretion .The biosorption mechanism is critical in considering an antifouling strategy design that elucidates the cell–substrate interaction and its influence factors. The connect strength between cell and substrate depends on the microbes type, substrate condition, and surrounding environment . As initSuspended in a bulk liquid environment, bacterial transport to solid is likely dependent on the Brownian motion in sedimentation and convective diffusion process . HydrodyElectrostatic interaction involves ionic strength and pH of the surrounding liquid medium; low ionic strength could increase the energy barrier to prevent the approaching bacterial from Brownian motion or self-motility . Van derFor the substratum property, there have been abundant explorations on the impact on cell adhesion by surface chemical property modification, but the recent trend has turned to focus on the investigation of the surface topographical effect. The major reason for this shift is from the comparative analysis of cell adhesion on different surfaces with identical surface structure and distinct surface chemical characteristics, where the results revealed a narrow difference existing between the wo samples, which emphasizes the dominant influence of surface topography on antibacterial property .There are currently two main antibacterial strategies including the inhibition mechanism and detriment mechanism. The inhibition mechanism repels bacterial adhesion based on the low surface energy approach and the detriment mechanism employs a nanostructure to create an unfavorable contact interface and impairs the cell membrane structure, which causes membrane rupture and cell death.In the early stage of research into the topographical effect, some natural innate antibacterial surfaces from the flora and fauna have generally attracted mainstream attention like the lotus and shark skin. The main difference between the smooth surface with this antifouling surface is the high-aspect-ratio structure, which bestows the hydrophobic feature and self-cleaning ability. The geometrical features of the lotus or shark skin are superhydrophobic, which was nominated as the foremost factor in antibiofouling activities as a superhydrophobic surface combined with a high-aspect-ratio structure induces a low surface energy phenotype . A low sechanism .P. aeruginosa, magnetron sputtering was employed to cover the surface of the cicada wings with a 10 nm-thick gold film. Some surface characteristics like wettability were modified by the gold coating, and water contact angle substantially decreased from 158.8° to 105.5°. Results of comparative AFM roughness analysis in the processed specimen and control specimen confirmed that the surface morphology profiles of the two samples were virtually identical. The bactericidal effect of the gold-coated wing was preserved, which proved that the topographical effect of the nanostructured surface was essentially responsible for the lethality of the cicada wing instead of the surface chemistry [Unlike the inhibition mechanism, the contact-killing mechanism prevails in insect wings with a high degree of hydrophobicity like the lotus and shark skin. When investigating the antibiofouling property of the cicada wing surface, Ivanova et al.  found thhemistry . Based ohemistry  proposedhemistry  reportedhemistry  construchemistry  created hemistry . Liu et Bandara et al.  first inCurrent research into natural innate antifouling surfaces provide insights into the topographical effect and cell–substrate interaction mechanisms, which establishes avenues for reverse engineering to fabricate synthetic analogues.Instead of relatively sterilized living conditions in modern human society, dust particles and microbes are ubiquitous in the natural environment and are actively seeking opportunities to colonize and proliferate. In the process of natural selection, the retentates generally develop various strategies to cope with microbial contamination. For an initial understanding of the natural antibiofouling property, inchoate studies have focused on the relationship between non-stickiness phenomena and hydrophobicity. Hydrophobicity, as a property of expelling water, widely exists in plant leaves and insect exterior surfaces. Based on the observation of antifouling activities on hydrophobic surfaces, hydrophobicity was presumed as the primary factor of self-cleaning activities that inhibit cell adhesion.Natural flora like taro and lotus have amassed a delicate array of structures that could provide effective protection from microbial colonization. Ma et al.  first inPsaltoda claripennis) wings were discovered to be a contact-killing mechanism instead of a bacteriostatic approach accepted by plant and marine biology. In the supplementary test [Like marine and botanical biology, which possess the motility requirement in their natural inhabited environment, many insects have the inclination to minimize foreign particle adsorption for the purpose of maintaining functionality . The dusary test  against To identify versatile natural bactericidal surfaces and investigate the potential for bactericidal surfaces incorporating natural biocidal nanopatterns in a biomimicry design, Ivanova et al.  mimickedP. claripennis) specimens were collected for the validation test for both the Ivanova et al. and Hasan et al. [As shown in the n et al. ,13 modelB. catarrhalis, E. coli, P. aeruginosa, and P. fluorescens) combining three Gram-positive bacteria . The results from the cell incubation tests showed the consistent lethality to Gram-negative cells for cicada wings regardless of cell morphology (coccoid-shaped or rod-shaped), but Gram-positive cells remained viable and functional in comparison with cell attached to the glass control surface.Hasan et al.  implemenS. cerevisiae–yeast cell) to explore the prominent factors for bactericidal effect and cell rupture mechanism. Three species had different aspect-ratios  and water contact angle (hydrophobicity and hydrophilicity), and a comparison of viability loss of yeast cell on different surfaces proved that a nanostructure with a higher aspect-ratio would perform better in cell rupture activities. Resultant analysis suggested that adhesion strength between the cell and nanostructured surface is a critical impact factor in the microbial mechano-rupture process, and the high-aspect-ratio nanostructure possessed better cell affinity than one with low-aspect-ratio. Durability of the nanostructure was also first prompted in the observation of nanostructure damage by direct interaction between yeast cells and nanostructure, where nanostructure removal also provided proof of intimate adhesion between yeast cell and nanostructure.Kyle et al.  selectedTo elucidate the relationship between the nanoscale topography and the degree of bactericidal activities, Kelleher et al.  carried Like the cicada, the dragonfly also has a high-aspect-ratio nanoprotrusion structure on the wings’ epicuticle lipids. David et al.  selectedS. mutans) and Gram-negative  bacteria. The recorded data showed that both non-viable S. mutans and P. gingivalis bacteria had a significant rise  on gecko skin topography after seven days within a promotive liquid environment, and the validated promising antibacterial character of plastic resin replica design offers a potential anti-biofilm coating in biomedicine and biomedical instruments.Instead of targeting insect cuticle structure, the work of Li et al.  focused E. coli). The model depicting the cell–nanostructure interaction mechanism generated in the research showed that the membrane rupture was due to strong binding adhesion between NTSs and bacteria via secreted EPS and shear force exerted by nanopillars when the bacteria attempted to get away from the biocidal surface.Although the proposed model from Kyle et al.  revealedP. aeruginosa and S. aureus bacteria at different physiological growth phases to evaluate whether the growth phase of the tested cells had any impact on the cell susceptibility to the nanostructured surface. The selected natural antimicrobial surfaces were collected from damselfly specimens, and selected bacterial cells from different growth phases were cultivated on the wing surfaces for 3 h. It was found that both bacteria were highly vulnerable to mechanical rupture by the damselfly wing surfaces at the early (after 1 h and 6 h of growth) and late (after 24 h) stationary phase, and immature S. aureus and mature P. aeruginosa had a greater tendency to attach than those of the bacteria in the aged phase.Through the awareness of a lack of information concerning bacterial growth stage, Truong et al.  prepared−1.As the high bactericidal effect of dragonfly wings has been demonstrated in previous studies, giant unilamellar vesicles (GUVs) were designated by Cheeseman et al.  to probeDiplacodes bipunctata. The samples of the cell incubation test on the bSi surface contained Gram-negative bacteria, Gram-positive bacteria, and endospores, and the experimental results demonstrated a high bactericidal efficacy . A multilayer spore coat was also observed disrupting, so the feasibility model of the topographical effect applied in tackling bacterial adhesion was validated.Reverse engineering has contributed to the development of the biomimicry field by mimicking natural resources. In the process of investigating the relationship between antimicrobial property and topographical effect, in Inspired by the bactericidal model from bSi, Hasan et al.  preparedE. coli). Compared to flat films, the nanostructured surface had a lower density (67–91% of densities on flat films) of adhering bacteria, and a higher number of non-viable bacteria (16–141%) than the flat films. In the discussion on the major influence factors of bactericidal efficiency, the minimum threshold for the optimal interpillar distance was found to be between 130 and 380 nm through the quantitative analysis of cell orientation data, where closer spaced nanopillars performed better in antibacterial activities.As a promising polymer material, polymethylmethacrylate (PMMA) is widely applied in the construction of medical devices such as microsensors, bone cement, and drug delivery applications due to its biocompatibility and low risk for foreign body reaction. Mary et al.  used sofIto et al.  proposedP. aeruginosa and E. coli) associated with various eye diseases were selectively incubated on the fabricated nanopillars, and the highest bactericidal efficiency was observed in the test on nanopillars that were 300 nm in height and 10 nm in apex diameter. Furthermore, the properties including superhydrophilic, anti-fogging, and anti-reflective were confirmed by water contact angle and light reflectance measurement, which proposed a potential hybrid functional optical device.Bacterial deposition on optical devices like endoscopic devices, microscopic slides, and contact lenses has brought extensive concern in the hygiene problems of biomedical optical devices. Han et al.  presenteDespite lacking previous study on the bactericidal activity of moth-eye surface, several unrelated species with similar nanocone features shared the same antibacterial mode-of-action, which proposes a tendency of convergent evolution. Therefore, Felipe et al.  designedP. aeruginosa and ~83% S. aureus cells. Instead of stable bunches of nanopillars, pillar deformation was induced during the cell adhesion process. The flexibility of the individual nanopillars was hypothesized to be responsible for the increasing energy storage when increasing the pillar height, but there is a critical point where it becomes energetically cheap to assemble an effectively continuous surface packed with nanopillar tips, which is pillar collapse. Therefore, mechanical energy stored substantially increased from a 220 to 360 nm pillar height, and the bactericidal effect can be partially compensated by irreversible interpillar adhesion when it reaches 460 nm in height.The factors that determine the antibacterial capability and bactericidal efficiency of a nanostructured surface still remain ambiguous, so Ivanova et al.  executedThe limited comprehensive studies in bactericidal properties of nanostructured surfaces are due to the arbitrary nanostructure patterns and manifold selected substratum material, and there is no definite theory to describe the bactericidal effect and cell rupture mechanism. As the pertinent researches into bactericidal surfaces escalates, the numerous collected experimental data and observed results could contribute to obtaining empirical routines beneath the various phenomena and determining the predominant factors in the topographical effect.The main differences between contemporary antimicrobial surfaces regardless of natural surfaces or synthetic surfaces are the mechanical properties of the composed material and geometrical features of the nanostructures. In the beginning, Ivanova et al.  had nega−2) could have a higher bactericidal activity compared to high pillar density (~70 pillars μm−2) and low pillar density (<20 pillars μm−2). The latter two nanostructures possessed a close degree of bactericidal efficiency to the smooth control sample. This revealed that stretching degree is highly dependent on the interaction pattern of the cell membranes on the nanopillars instead of extrapolation about the linear relationship between bactericidal efficiency and surface parameters. The height inhomogeneity of the nanopillar structure was discovered to effectively stimulate the stretching degree enhancement, which is also consistent with the previous theoretical model [The current synthetic nanostructures vary simultaneously in the radius and interspace distance due to a lack of control regarding the spatial geometry parameters. The recent work reported by Ivanova et al.  made altal model .SCL has been a common means of vision correction for almost half a century, since the release of the first commercial soft hydrogel lenses by Bausch and Lomb in the early 1970s . Recent P. aeruginosa, S. aureus, S. marcescens, and Acanthamoeba spp.Microbial keratitis (MK) , contactP. aeruginosa in the absence of corneal scratch [Current empirical disinfection strategies for SCL include killing the attached microorganisms in a chemical approach and altering the SCL wearing schedule, but both strategies have limited effect on the antibacterial activities. Since the invention of daily disposable SCL, the requirements of regular maintenance and sterilization have been abandoned, which was a vital cause of microbial contamination from storage and disinfection solution. Although the novel utilization mode of daily disposable SCL has been designated as a significant innovation in the development of SCL hygiene, Dart et al.  conducte scratch . The res scratch ,77. The  scratch ,79. The The efforts of adding antimicrobial peptides in a disinfection surfactant and storage case have achieved limited progress in infection reduction ,72, hencWearing SCL alters the state of the ocular surface, so the balance of corneal homeostasis is also disrupted, compromising the natural defenses that predispose patients to bacterial infections and sight-threatening complications. As a hydrophilic surface immersed in the interface between an aquatic environment and the atmosphere, SCL are not only a barrier between the corneal epithelium and oxygen, but also an optimal hotbed of bacterial incubation. In previous studies in SCL biofouling ,100,101,Surface roughness is a crucial geometrical parameter of surface characteristics, which is in direct contact with surrounding live organisms, and has a biological influence on the bacterial adhesion manner . Higher Dk is shown below [The composed biomaterials of SCL are water-swollen, cross-linked, hydrophilic polymers, so polymerization of multiple monomers incorporate properties to form a biocompatible copolymer that provides a flexible approach to change the SCL characteristics . The equwn below :(1)EWC=wDk and EWC. The major difference between conventional hydrogel SCL and silicone hydrogel SCL is the chemical group composition, variety of chemical groups compose of the backbone of hydrogel which are used to attracting and binding water. The chemical groups containing silicon-oxygen bonds increase the oxygen permeability for silicone hydrogel SCL, because oxygen is more soluble in silicone rubber than that in water while oxygen is more soluble in water than that in polymethyl methacrylate (PMMA) [SCL with sufficient oxygen permeability can maintain normal corneal metabolism and avoiding hypoxic, different composed biomaterials shown in e (PMMA) .Dk, the thickness of the SCL should be controlled within 0.06 mm, which is unfeasible for current manufacturing technology and stable fit to wear [Increasing oxygen permeability for a hydrogel is commonly achieved by simply adding EWC that exists at upper limit, where the highest oxygen transmissibility attained via EWC modification is theoretically far too deficient to meet the requirement of overnight wearing. To obtain the required  to wear . The deh to wear , so the As vital surface characteristics of SCL, wettability has a direct effect on the interactions with tear film and biocompatibility in the ocular environment. Wettability of SCL is a measurement to describe the ability to support a continuous tear layer for corneal homeostasis and visual clarity, and can be divided into two categories including hydrophobicity and hydrophilicity. In the process of identifying the lens deposits and constituents on hydrophilic SCL, the hydrophilic property was discovered to reinforce the tear components adsorption like lipids, proteins, and mucins, which led to depreciated wearing comfort and visual clarity decline .P. aeruginosa adhering to contact lenses, Fletcher et al. [P. aeruginosa to specific charged molecules on the surface of the contact lenses. Despite the high oxygen permeability of silicone hydrogel contact lenses, the hydrophilicity of a hydrogel polymer incorporating silicone is minimized [S. epidermidis adhesion than conventional hydrogel contact lenses [In a study on the role of hydrophobic forces, Michael et al. established that hydrophobic bacteria have the tendency to adhere to hydrophobic surfaces in the process of bacterial adhesion . When exr et al.  found thinimized , and unwt lenses .Dk and dehydration rate, as the EWC of the hydrogel material is sensitive to outer environmental changes like temperature, pressure, and light. In the process of typical SCL manufacturing, there is a dry state for the inflexible monomer before immersion in saline solution [Although hygiene issues are important in SCL design, SCL is a fundamental approach for vision correction with portability. Therefore, adding the proposed antimicrobial properties to SCL must retain the original viability and functionality, and the processed SCL ought to reserve all the prerequisite mechanical and optical properties to meet the requirement of wearing comfort and vision correction. The ideal refractive index for SCL is similar to that of the corneal (~1.37); the refractive index has an adverse linear relationship with EWC that is not applicable to silicone hydrogel lenses . As descsolution , which isolution . To obtaAs above-mentioned, the nanostructure on the native insect wings was found to be damaged by cell movement where the Young’s modulus of nanostructure is much weaker than that of the substratum material. Due to the lack of relevant information about nanostructure fabrication on soft materials, the durability of the nanostructure on a hydrogel material needs further investigation. The modulus of the silicone hydrogel SCL was higher than the conventional hydrogel SCL , where aAlongside retaining the functionality of SCL, fabricating the nanostructure on a surface with a curvature is also one obstacle for industrial mass production. A nanostructure fabricated on a lens to obtain an anti-reflection coating through a combination of cast molding and the interfered femtosecond laser inscription technique provided a low-cost method ; nanorepHydrogel is one conventional material in wet condition on which it is difficult to perform direct micro- or nanofabrication. Hydrogel applications in the medical field have gained popularity in recent years due to its high similarity to in vivo soft tissues as well as characteristics like high oxygen permeability and water-soluble metabolites that contribute to remarkable biocompatibility and adjustable physico-chemical properties . Cast moAs above-mentioned, another way to obtain a nanostructured surface for hydrogel materials is to create nanofeatures on top of the monomer in anhydrous status and achieve the exact dimension after water-swallowing. Considering the swell factor of the hydrogel materials, the initial size of the nanostructure should be controlled. Therefore, the precision requirement of processing techniques is higher than direct fabrication methods, and several approaches like nanoimprint lithography  or plasmCompared to rigid contact lenses, SCL has a larger edge area surrounding the optical zone. Fabricating a high-aspect-ratio nanostructure on the edge area could be a potential solution to reduce bacterial keratitis induced by bacterial infection, but the verification of biomimetic surface functionality on a soft hydrogel material requires further investigation.Through previous studies on the bactericidal property of a biomimetic surface, the viability and feasibility of the antimicrobial model has been validated to effectively control the bacterial adhesion and biofilm formation. The threat from antibiotic-resistant germ evolution is expected to be limited by the further utilization of the mechano-ruptured mechanism in hygiene products as well as the risk of nosocomial infection. In the previous case, the bacterial incubation concentration is small and the adsorption mechanism requires further detailed investigation to provide a theoretical foundation for manufacturing. The durability of the functional nanostructure on the soft substratum is expected to differ from the hypothesized rigid model; the risk of structural distortion and deformation induced potential inner stress are needed to be supplementary. Quantification of the unique characteristics of surface morphology features and the design of a nanostructured surface contribute to providing a potential solution to impart bacterial resistance to various biomedical applications like soft contact lenses. It is also imperative that antimicrobial surfaces in real clinical cases be used judiciously to consider both biocompatibility and durability to minimize the risk of adverse effects due to intrinsic defects in design.


Sturge Weber Syndrome is characterized by the classic triad of a facial port-wine stain, leptomeningeal angiomatosis, and glaucoma. The resultant facial vascular anomaly can lead to soft tissue and bone irregularities, causing psychosocial distress and mental health morbidity. When severe, patients can opt for multi-staged surgical intervention by reconstructive surgeons to restore normal symmetry and improve the aesthetic appearance of the face. This study reports a case of surgical correction for severe facial vascular malformation resulting in poor outcomes due to the associated mental comorbidities seen in Sturge Weber Syndrome. A 37-year-old male with previously diagnosed Sturge Weber Syndrome presented to the outpatient craniofacial clinic for surgical evaluation of a large facial tuberous hemangioma. The patient underwent multiple operations for facial reconstruction including a staged full-thickness skin graft, facial recontouring, and extracranial correction of vertical orbital dystopia. The case was complicated by the patient’s poorly controlled seizure disorder and psychosocial illness, resulting in self-mutilation of the repair and poor follow-up. Over the span of 10 years, the patient’s mental illness caused him to fail numerous attempts at facial restoration and ultimately led to a poor final result. The psychosocial distress seen in patients with Sturge Weber Syndrome can adversely affect surgical outcomes. Physicians should be mindful of the possible complications that can arise in these patients and have the clinical means to address them. Sturge Weber Syndrome, also known as encephalotrigeminal angiomatosis, is a congenital neurocutaneous vascular malformation syndrome with an estimated incidence of one in every 20,000 to 50,000 live births -3. The mA 37-year-old male patient with previously diagnosed Sturge Weber Syndrome presented to the outpatient clinic inquiring about reconstructive treatment for a congenital vascular malformation that engulfed a considerable portion of his face. Past medical history was significant for a lifelong seizure disorder secondary to intracranial vascular angioma for which he was placed on several medications with poor symptom control. The patient was also medically treated for depression and anxiety and visited a psychologist regularly for the social strain his disease has caused him with family and peers. During the preoperative physical examination, the patient was noted to have a tuberous hemangioma of the right face and scalp with significant involvement in the frontal region Figure . The patProcedure no. 1A right deltopectoral flap was raised through the area of the perforators in the mid-chest, turned into a pedicle, and inserted into a donor site in the right postauricular area. In addition, a forehead flap was delayed, outlining the flap to involve the complete left forehead site. Postoperatively, the patient was assigned a home health nurse for daily wound care and dressing change. At one month follow up there was a dark area on the deltopectoral pedicle with crusting behind the ear indicating tissue damage, but the flap was otherwise healing well with no further deterioration and was deemed viable for future reconstruction Figure .Procedures no. 2 and 3The hemangioma on the right forehead, cheek, and nose was excised. The tube pedicle was then divided from the chest, opened longitudinally, and tailored to the defect in the cheek and upper lip. The previously delayed left forehead flap was elevated from the forehead and rotated to the nasal area with the pedicle maintained in the left medial brow area. Two weeks later, the postauricular portion of the deltopectoral flap was divided and the flap was untubed. The remaining area of right cheek malformation and the right eyebrow was excised, and the flap was trimmed and tailored to fit the defect in the right cheek. Then, the scalp flap was placed into position to cover the defect over the right eyebrow. Postoperatively, the skin on the nose showed evidence of self-induced trauma indicated by a linear area of excoriation Figure .Procedure no. 4The patient underwent sculpting and recontouring of the flaps to create an anatomically appropriate eyebrow, upper eyelid, nasal bridge, and upper and lower vermillion borders on the right side of the face. Postoperatively, the patient continued to pick and scratch at large portions of his scalp flap and right cheek despite numerous warnings and safety measures including shielding the flaps with heavy dressing, prescribing antibiotics and anti-inflammatory medications to alleviate the associated pain and pruritus, and coordinating care with his psychologist to address these actions during therapy sessions. This resulted in local wound breakdown and necrosis which required repeated debridement and dressing during consequent visits Figure .Procedures no. 5 and 6A tissue expander was inserted in the posterior scalp to promote the growth of additional skin to be used in the reconstitution of the anterior hairline. During the follow-up period, the patient missed several appointments for wound care and tissue expander fills. The tissue expander eventually became exposed, requiring prompt removal and further facial reconstruction Figure . PostopeProcedure no. 7The patient underwent correction of his right vertical orbital dystopia. Due to the large size of the frontal sinus discovered on imaging, an extracranial approach was chosen with orbital exploration, orbital unroofing into frontal and ethmoid sinuses, intraconal lipectomy, and medial canthopexy to establish symmetry with the contralateral unaffected side. Excision of multiple pyogenic granulomas in the right scalp was also performed followed by debulking and revision of the right facial flap, scalp flap advancement, and split-thickness skin graft for coverage of the remaining defects. Though the immediate postoperative period was well-tolerated, the patient continued to exhibit scratching/picking behavior of his facial wounds, causing severe tissue degeneration. The patient was seen at the office multiple times per week but attempts to prevent further self-injury were unsuccessful Figure .Procedure no. 8Approximately 16 months after procedure No. 7, the patient returned to the operating room for multiple revisions including reconstruction of the facial flaps, right lateral and medial canthopexies, and additional skin grafts to the face. One week following surgery, the skin grafts on the scalp, forehead, and portions of the eyebrow and nasolabial area were reportedly removed by the patient. Examination revealed poor hygiene and total loss of the skin graft on the right scalp and forehead, and partial loss of the right eyebrow and nasolabial fold Figure . The wouAfter months of encouragement, the patient agreed to undergo surgery and was admitted to the hospital but ultimately left against medical advice prior to the operation. From 1993 to 1996, the patient continued to follow-up at the office, expressing interest in further surgical intervention but not following through. The last photographic documentation from 1995 portrays the significantly poor outcome following his 10-year treatment (Figure A major component of Sturge Weber Syndrome is the significant facial disfigurement caused by soft tissue and bony overgrowth secondary to the associated vascular malformation. The surgical treatment of this deformity, however, has received little coverage in the literature -15. EvenThe current literature recognizes the effect of active mental illness on surgical outcomes, reporting that mental illness is associated with higher rates of postoperative morbidity, additional operations, and financial burden ,20. At tThis case emphasizes the importance of proper and frequent mental health assessments and counseling during the treatment of psychologically distressing conditions, such as facial reconstruction for severe disfigurement secondary to congenital vascular anomalies, which requires long-term compliance and self-motivation from the patient as well as the treating surgeon. Physicians should be aware of the psychosocial distress that accompanies patients with Sturge Weber Syndrome and have the proper means to address such issues.The surgical management of facial vascular malformations in Sturge Weber Syndrome is a complicated, multi-stage process that involves both soft tissue and bone reconstruction to restore facial symmetry. Patients with Sturge Weber Syndrome suffer from comorbidities, namely seizures and psychosocial distress related to their condition, which can manifest as self-injury and negatively affect long-term surgical outcomes. Emphasis should be placed on effective psychiatric care and seizure management during the prolonged period of surgical reconstruction.


The interest in the use of microbes as biofertilizers is increasing in recent years as the demands for sustainable cropping systems become more pressing. Although very widely used as biofertilizers, arbuscular mycorrhizal (AM) fungal associations with specific crops have received little attention and knowledge is limited, especially in the case of vineyards. In this study, the AM fungal community associated with soil and roots of a vineyard on Mallorca Island, Spain was characterized by DNA sequencing to resolve the relative importance of grape variety on their diversity and composition. Overall, soil contained a wider AM fungal diversity than plant roots, and this was found at both taxonomic and phylogenetic levels. The major effect on community composition was associated with sample type, either root or soil material, with a significant effect for the variety of the grape. This effect interacted with the spatial distribution of the plants. Such an interaction revealed a hierarchical effect of abiotic and biotic factors in shaping the composition of AM fungal communities. Our results have direct implications for the understanding of plant-fungal assemblages and the potential functional differences across plants in vineyard cropping. Arbuscular mycorrhizal (AM) fungi are an important component of the plant soil microbiome. AM fungi are a low diversity monophyletic group of fungi living in close association with many terrestrial plant species . The intDue to the low diversity of AM fungi (ca. 300 described species ) able toVitis vinifera is one of the most important crops in modern agriculture. Its economic and cultural impact is undeniable )The most interesting result of the current study was the finding that the vine cultivar, even when grafted onto the same rootstock, drove the community composition of AM fungi. Previous studies that have found effects of the plant species genotype on the associated soil microbial communities e.g., ,77,78) a,78 a77,7We found a significant portion of variance explained by the spatial position of the samples. In the context of ecological community assembly, spatial autocorrelation can be interpreted as an effect of dispersal events . HoweverAs agricultural practices advance towards more sustainable production, study and interest in the role and functions of plant-associated microbiomes have increased ,89. Soil


This study aimed to assess the performance of the Ebel standard-setting method for the spring 2019 Royal College of Physicians and Surgeons of Canada internal medicine certification examination consisting of multiple-choice questions. Specifically, the following parameters were evaluated: inter-rater agreement, the correlations between Ebel scores and item facility indices, the impact of raters’ knowledge of correct answers on the Ebel score, and the effects of raters’ specialty on inter-rater agreement and Ebel scores.Data were drawn from a Royal College of Physicians and Surgeons of Canada certification exam. The Ebel method was applied to 203 multiple-choice questions by 49 raters. Facility indices came from 194 candidates. We computed the Fleiss kappa and the Pearson correlations between Ebel scores and item facility indices. We investigated differences in the Ebel score according to whether correct answers were provided or not and differences between internists and other specialists using the t-test.The Fleiss kappa was below 0.15 for both facility and relevance. The correlation between Ebel scores and facility indices was low when correct answers were provided and negligible when they were not. The Ebel score was the same whether the correct answers were provided or not. Inter-rater agreement and Ebel scores were not significantly different between internists and other specialists.Inter-rater agreement and correlations between item Ebel scores and facility indices were consistently low; furthermore, raters’ knowledge of the correct answers and raters’ specialty had no effect on Ebel scores in the present setting. To receive specialty certification in Canada, residents must pass the Royal College of Physicians and Surgeons of Canada’s (RCPSC) certification exam. In such a high-stakes context, a rigorous and legally defensible standard-setting procedure is essential to support the validity of inferences based on performance in subsequent decision-making . StandarThe present study aimed to examine the performance of the Ebel method for standard-setting on the multiple-choice question (MCQ) component of the RCPSC internal medicine certification examination in the context of minimal rater training. More precisely, we investigated inter-rater agreement between judges’ classification of test items; evaluated the correlations between item Ebel scores and empirical item facility indices, sought to determine whether the Ebel scores were modified by the provision of correct answers, and investigated whether the judges’ specialty influenced their rating scores and inter-rater agreement.We received ethical approval for this study from Université de Moncton (certificate number 1819-061). The requirement to obtain informed consent was exempted because this study involved an analysis of test results.This study presents an analysis of test results.Ebel classification data come from the spring 2019 RCPSC certification exam in internal medicine. The judges were raters for the spring 2019 RCPSC internal medicine certification exam. Forty-nine raters out of a possible total of 62  applied the Ebel method to the 203 MCQ items.The Ebel standard-setting method is an absolute standard-setting method that involves expert judgments along 2 dimensions—difficulty and relevance to the assessment of clinical competence—for each test item. In its implementation, the following 6 steps were completed: (1) Selection of judges: Forty-nine judges volunteered to apply the Ebel method. All the raters were volunteer physicians with current professional expertise and experience of practicing internal medicine in Canada. All the judges were asked to rate each of the 203 MCQ items on its difficulty and relevance. (2) Judges’ training: Prior to rating the items, we gave a 20-minute presentation about the purpose and process of the Ebel method. Specifically, the presentation explained how items were to be rated and clarified the meaning of difficulty and relevance in the context of a certification examination for internal medicine. We also used the presentation to introduce the study and obtain consent from the judges. Although the time requirements were considerably less than what would be recommended, the time required for both training (35 minutes) and rating (3 hours on average) strained the raters in terms of available time. (3) Definition of “minimally competent” performance: After the presentation, we discussed the expectations for minimally competent candidates with the judges for 15 minutes. 4) Data collection: Judges were seated in front of a computer. They entered relevance  and difficulty  ratings for each of the 203 MCQ items, using drop-down menus in a Microsoft Excel spreadsheet. The process took approximately 3 hours, on average. The exam consisted of 2 booklets. For each judge, the correct answers to the MCQ questions were provided for one randomly chosen booklet, but not the other. From our experience with other specialties, we observed that the use of individual ratings—instead of consensus ratings—avoided the pitfall of polarizing ratings around the values suggested by more vocal examiners. (5) For each item category , judgments were collected on the proportion of marks or items expected to be correctly answered by minimally competent candidates. To save time and to reduce the burden on judges, we used the grid proposed by Ebel [ Data colWe computed empirical facility indices for all MCQ items based on the performance of 194 candidates who took the MCQ component of the examination in the spring of 2019 and were defined as “minimally competent” . The categorization as minimally competent was operationalized as an exam score falling within 1 standard error of measurement (SEM) of the unadjusted pass score of 70% SEM=4.98). The correlations of item facility indices with the Ebel scores set by judges were then analyzed. We quantified inter-rater agreement using the Fleiss kappa with the Realstats add-in for Microsoft Excel [. The corVariation was observed in ratings for both difficulty and relevance. The Fleiss kappa among the 49 raters was 0.10  for difficulty and 0.11  for relevance, which corresponded to slight agreement . To evalThe correlation between item Ebel scores and empirical item facility indices was low when correct answers were provided  and negligible when they were not  .When evaluating the correlations between item facility indices and each of the 2 Ebel ratings separately, we would expect a high, positive, statistically significant correlation with the difficulty rating and a lower correlation with the relevance rating, since it measures a slightly different construct. However, although positive, both correlations were low and non-significant . The 2 components, however, were highly correlated with each other , suggesting that judges might not have been able to disentangle the 2 constructs consistently when rating items.The Ebel score for the whole exam was practically the same (61.5) regardless of whether the correct answers were available to the raters .We hypothesized that general internal medicine specialists, being a more homogeneous group, would show greater inter-rater agreement than other specialists and that their Ebel score would be different and more accurate because of the greater congruence between their expertise and the exam content. However, inter-rater agreement was of the same order of magnitude for both groups , and theThe context in which we applied the Ebel method was typical of Royal College exam development meetings, in that the rating was performed by volunteers on a very tight schedule, which necessitated reducing training time to a minimum. The Ebel standard-setting method appeared to be easy to implement and apply while being generally accepted as valuable by raters.The correlations between Ebel scores and item facility indices were negligible and failed to reach statistical significance, even when only considering the difficulty component ratings. In the literature, the correlations between Ebel scores and item facility indices have been reported to be around 0.40  on average , which iMoreover, our analyses detected no discernable differences in inter-rater agreement and Ebel scores between general internists and other specialists. This finding is a counterintuitive outcome. It raises the question as to whether there would be differences if we were to take item content into account. More precisely, future research could explore whether the concordance (or lack thereof) between raters’ specialty and item content makes a difference in inter-rater agreement for difficulty and relevance ratings, as well as in Ebel scores. Future research should look into whether clearer and more thorough definitions, more extensive rater training, and rater calibration before the application of the Ebel method could improve inter-rater agreement. However, the issue might then become the applicability of the method given the extensive training required.The effect, if any, of knowing the correct answer before rating the item has not been explored yet in the literature on the Ebel method, although it is a relevant detail that could have repercussions on the way the method is implemented. Our results suggest that having access to the correct answer did not result in a significant difference in the Ebel score. Therefore, both options seem viable when implementing the Ebel method.The results of the present study also corroborate a sort of regression towards the mean documented by other authors ,15, wherAlthough disappointing, the results are not entirely surprising since, in the scientific literature, expert raters have generally been found to be poor at judging the difficulty of items, even with normative data available, regardless of the particular standard-setting method that is used . In our The above finding of slight inter-rater agreement should be overcome by more in-depth training of raters. It may be possible to correct the low correlation between item Ebel scores and item facility indices by producing items with more variable facility indices. There is no need to inform raters of the correct answers because knowledge of the correct answers had no effect on the Ebel score. The absence of an impact of raters’ specialty on rating scores and inter-rater agreement were favorable findings regarding the possibility of recruiting raters from a variety of specialties.


Gossypiboma denotes a mass of cotton retained in the body following surgery. Migration of gossypiboma from initial site is a rare entity and could pose some diagnostic difficulties. Migration of gauze sponge has been reported to occur in several organs of the body. There have been few reported cases but the true incidence may be much higher due to under reporting for fear of litigation.We present an unusual case of a 58-year-old grand multiparous woman who had gauze retention for 5 years following a hysterectomy and presented with acute urinary symptoms. The gauze sponge transmigrated from the peritoneal cavity to the bladder and was partially extruded through the external urethral meatus. She had laparotomy for the removal of gauze sponge with good outcome.Retained foreign body especially surgical sponges (gossypiboma) infrequently occurs and can be a source of great concern to the surgeon and patient. Foreign bodies inside the body cavities and organs can present with several non-specific clinical features that can make diagnosis difficult. Migration of surgical sponge  into the urinary bladder is uncommon when compared to other abdominal and pelvic viscus. A gossypiboma in the peritoneal cavity creates a fistulous tract through the thick wall of the urinary bladder from long period of chronic inflammation as seen in the index case where the previous surgery was performed 5 years prior to onset of symptoms. Due to the non-specific presentations of gossypiboma, especially those in the bladder, several investigative modalities need to be employed to help make a prompt diagnosis. Most long-standing cases would require laparotomy due to the dense adhesions that occur around the site of the gossypiboma. Lack of appropriate diagnosis leaves the patient with recurrence of distressful symptoms and the consequent morbidities.Transmigration of a gauze sponge over 5 years from the peritoneal cavity into the urinary bladder and through the external urethral meatus following a hysterectomy is a rare occurrence and can present diagnostic difficulties. High index of suspicion, prompt diagnosis and management will help reduce the high morbidity that is associated with the condition as in the case reported. The term was derived from Gossypium (cotton in Latin) and bom . Migration of this gossypiboma from initial site is a rare entity and diagnosis could be difficult. Migration of the gauze sponge has been reported to occur in the duodenum, ileum, stomach, urinary bladder and lungs . The incWe present the case of a 58-year-old grand multiparous woman who had laparotomy with removal of gauze that has transmigrated from the peritoneal cavity to the bladder and partially extruded through the external urethral meatus. The SCARE criteria were strictly followed to produce this case report .2A case of 58-year-old grand multiparous, 3-years postmenopausal woman, who presented with a one-month history of moderate to severe lower abdominal pain of sudden onset, continuous, crushing in character, worse with urge to defecate and micturate, relieved by intake of analgesic and not related to position. However, there was no abdominal mass or swelling, no change in bowel habit and there was no preceding trauma. There was associated urinary frequency, urgency, urge incontinence, dysuria and occasional passage of purulent fluid and blood in urine but no fever. There was no history of bleeding per vaginam, post coital bleeding and vaginal discharge; no chronic cough, bone pain but weight loss. She had total abdominal hysterectomy 5 years prior to the onset of symptoms in a private hospital due to suspected endometrial hyperplasia. However, there was no evidence of histological analysis of the tissue removed.On examination, her vital signs were stable, there was no palpable abdominal mass. Examination of the urogenital system revealed a gauze partially extruded from the urethral meatus with purulent discharge as shown in Diagnosis of cystitis secondary to foreign body in the bladder complicated by fistulous formation was made. CT urography result revealed presence of foreign body in the bladder with pelvic abscess collection. Other investigations showed normal laboratory findings. She subsequently had exploratory laparotomy for gossypiboma by a joint team of gynaecologist, urologist and general surgeons. Intraoperative findings revealed: presence of gauze shown in She remained stable throughout the post-operative days and was discharged on the 13th day post operatively. She has been seen in the Gynaecology clinic on two occasions after surgery and still remained stable.3Retained foreign body especially surgical sponges (gossypiboma) infrequently occurs and can be a source of great concern to the surgeon and patient. These foreign bodies can present with several non-specific clinical features that can make diagnosis difficult ,5,6,8. MType 1: externally introduced by self for sexual gratification or as a result of psychiatric illnessType 2: (Iatrogenic): Foreign body left at the time of major bladder surgeryType 3 (Migratory): The foreign body usually migrates from areas/structures surrounding the bladder, commonly the uterus, rectum and vaginaOur patient had vesical migration of a gauze left in the peritoneal cavity after abdominal hysterectomy 5 years prior to onset of symptoms.Four stages of gossypiboma migration has been proposed following experimental animal studies . These aFor a gossypiboma in the peritoneal cavity to create a fistulous tract through the thick wall of the urinary bladder, there would be a long period of chronic inflammation ,13 as seDue to the non-specific presentations of gossypiboma, especially those in the bladder, several investigative modalities need to be employed to help make a prompt diagnosis. These diagnostic modalities may involve ultrasonography, cystoscopy, CT scan, X-Ray and laparoscopy . ProtrusGossypiboma in the urinary bladder although rare but can be prevented through appropriate documentation and recounting of all surgical sponges and instruments used during the surgery prior to closure of surgical sites/ cavities in the body.4Transmigration of a gauze sponge over 5 years from the peritoneal cavity into the urinary bladder and through the external urethral meatus following a hysterectomy is a rare occurrence. This condition can be associated with diagnostic difficulties. High index of suspicion, prompt diagnosis and management will help reduce the high morbidity that is associated with the condition as in the case presented.This is no conflict of interest to declare.There was no external funding received during the conduct of the research. The report was fully funded by the researchers.Ethical approval was obtained from Ethic and Research Committee of the Enugu State University of Science and Technology Teaching Hospital, Parklane. Enugu with reference number: ESUTHP/C-MAC/RN034Nol.1/224 and dated 16th December, 2019.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.The contributions made by the authors are as summarised below:N/A.Enebe Joseph Tochukwu.Not commissioned, externally peer-reviewed.


The development of new technologies, and more specifically the opportunity to immerse participants in virtual controlled environments, provides a new ecological framework for researchers to study complex behaviors. This experiment aimed to compare post-immersion craving in occasional and heavy alcohol drinkers. Twenty-two occasional drinkers and eighteen heavy drinkers were recruited and immersed in a virtual bar, including alcoholic beverages. After the exposure, heavy drinkers reported a significantly higher craving than occasional drinkers. Post-immersion alcohol craving was significantly related to the levels of perceived ecological validity of the virtual environment. Finally, a moderation analysis suggested that the levels of craving more strongly increased with perceived ecological validity in heavy drinkers than in occasional drinkers. Therefore, the perceived ecological validity was an important experimental parameter to study craving in a virtual environment. These results further suggested that virtual reality might be a useful tool for both the scientific study of alcohol addiction and the treatment of alcohol dependence and relapse. Alcohol craving is defined as the irrepressible desire to consume the substance and is considered as an important element in the development of alcoholism  and post-immersion alcohol craving.n = 21) or as heavy drinkers with a score greater than or equal to 11 (n = 18). Participants who never consumed alcohol were excluded from the study. These cut off scores for occasional and heavy drinkers were defined according to the recommendations of the literature (see below). One of the participants had to quit the experiment due to physical discomfort (cybersickness). The participants did not report having neurological or psychiatric problems and were free from drugs that could affect cognitive functioning, and reported being in good health.Eighty-four participants, between 18 and 35 years old, completed an online screening questionnaire including the Alcohol Use Disorders Identification Test . As shown in When testing the moderator effect of the perceived ecological validity of the environment on the relationship between alcohol drinker groups and self-reported craving, a complete moderation was obtained. The initial model (block 1) including the alcohol drinker group and the perceived ecological validity score was significant (t(35) = 2.47, p = 0.018), perceived ecological validity (t(35) = 4.01, p < 0.001)]. Therefore, the mediation hypothesis is not supported by the present results.Finally, the mediation model was also tested to determine whether perceived ecological validity mediates the relationship between alcohol consumption (drinker groups) and self-reported craving. However, several of the basic assumptions of the mediation model were not met. Although occasional and heavy drinkers showed significant differences in their levels of self-reported craving, they did not significantly differ in the mean level of ecological validity . AdditioThe present study shows that heavy alcohol drinkers have higher craving scores than occasional drinkers after immersion in a virtual environment with alcohol-related cues, using an experimental design that reduces potential response and experimental biases associated with assessing craving before the immersion in virtual reality. Informing participants about the objectives of the study, or measuring craving before the immersion might induce different levels of craving based on alcohol consumption patterns, as previously suggested by Ryan et al. . These aSeveral studies suggested that the sense of presence affects the user experience in a virtual environment . Measuring alcohol craving immediately before immersion in the virtual environment would have informed participants that the study focused on the motivation to drink alcohol. There was a high risk of altering their behavior, for example drawing their attention towards alcohol-related cues. To conceal the real purpose of the study, the participants were told that they were taking part in a study assessing the aesthetic qualities of a virtual environment. However, there was a trade-off for avoiding these experimental biases: the lack of information regarding the levels of craving of participants before immersion. Although we cannot ensure that occasional and heavy drinkers had a similar initial level of craving before immersion, the differential correlations between the sense of presence and the craving in these two groups strongly suggest that craving in heavy drinkers is increased by the immersion in the virtual environment. Only in the heavy drinker group was the correlation between the sense of presence and the craving statistically significant. However, to definitively conclude that the increase in craving is due to the immersion in the alcohol-related virtual environment, it would be necessary to include a pre-immersion assessment of craving. So, future studies should directly test whether the assessment of craving before immersion in virtual reality alters the behavior of participants in the virtual environment and the levels of post-immersion craving. It would be also interesting to test whether the levels of pre-immersion craving are correlated with the sense of presence in the virtual environment.In summary, the current study shows that heavy drinkers have higher levels of alcohol craving than occasional drinkers after immersion in a virtual environment with alcohol cues. Furthermore, the perceived realism of the virtual environment was shown to moderate the relationship between the levels of alcohol consumption in real life and post-immersion craving. Further studies are needed to investigate the relationship between craving and attentional biases measured in a virtual reality environment and to test the long-term efficacy of virtual reality as a treatment tool (Ghiţă and Gutiérrez-Maldonado, The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Ethics Committee of the Faculty of Psychology, Speech Therapy, and Educational Science of the University of Liège. The patients/participants provided their written informed consent to participate in this study.EQ, A-ME, and SB: idea and implementation of experimental design and manuscript reviewing. SB: provision of the virtual environment. A-ME: virtual reality material and data collection. JS and EQ: statistical analyses. JS: manuscript writing.SB is the president of and own equity in Cliniques et Développement In Virtuo, a university spin-off that uses virtual reality as part of its clinical services and distributes virtual environments. The terms of this arrangement have been reviewed and approved by the Université du Québec en Outaouais in accordance with its conflict of interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Disorders of the central nervous system sometimes cause severe sensory motor paralysis accompanied by gait impairment. Recently, there are several reports on the effectiveness of robot-assisted gait training for patients experiencing these issues. The purpose of this case report was to assess the neuromechanical effect of a wearable robot suit HAL (Hybrid Assistive Limb) during post-operative gait training in a patient with gait impairment due to compressive myelopathy caused by ossification of the posterior longitudinal ligament (OPLL). For this purpose, we compared lower limb muscular activities while the patient was walking with and without the robot through a course of treatment sessions by (i) gait phase-dependent muscle usage analysis, (ii) muscle synergy analysis, and (iii) muscle network analysis. The results show (i) enhanced activity of the extensor muscles for weight-bearing in the initial sessions by using HAL and reduced knee extensor and increased hip extensor activations for achieving larger steps and faster gait in the later sessions; (ii) involvement of a greater number of synergies during walking with HAL than without HAL; and (iii) modulated muscle network property during walking with HAL remaining until the next HAL session. The patient's gait was improved after completing HAL sessions, acquiring close to normal joint profile with greater range of joint movement, faster walking speed, and larger step length. We discuss that the muscular activity modulation during walking with HAL suggests altered control of the muscles by the central nervous system during post-operative walking. Activity-dependent sensorimotor augmentation by HAL is discussed in the context of recovery of gait control by the central nervous system. The relationship between the altered control and the achieved gait recovery requires further investigation. Disorders of the central nervous system sometimes cause severe sensory motor paralysis accompanied by gait impairment. There are several recent reports on gait improvement after clinical intervention using wearable exoskeleton-type robots in patients with gait disturbance after central nervous system disorders; for example, ReWalk , Indego Robot suit HAL  assists motion of the bilateral hip and knee joints during walking in accordance with voluntary motion intension of the user . It actuOssification of the posterior longitudinal ligament (OPLL) is characterized by heterotopic ossification of the ligament usually at the cervical and thoracic spine , 20. SteAnalysis of myelopathic gait can be found for patients with cervical myelopathy due to cervical spondylosis and/or OPLL who were able to autonomously ambulate before and after decompression surgery . CompareThe spinal cord has been considered to be housing the spinal locomotor network which coordinates the rhythmic limb motion during locomotion, based on evidences from non-human species and partly from humans , 33. Forper se, as well as how it differs from training without the robot. In this study, the gait and muscle activity during walking using the robot were recorded and analyzed in a patient with gait impairment due to thoracic myelopathy caused by OPLL. The purpose of this study was to examine the immediate effect of the robot on gait control and to discuss how it varies through intervention sessions. As far as we know, this is the first study showing the muscular activity changes during walking using HAL in a patient who had post-operative gait impairment after myelopathy. In this study, we analyze and compare the lower limb muscle activities during walking with and without HAL in each session of post-surgery rehabilitation. The analysis is made of three parts: gait phase-dependent amplitude analysis, muscle synergy analysis, and muscle signal network analysis.In previous studies on the application of HAL for post-operative gait rehabilitation of OPLL patients with thoracic myelopathy , 37–39, Muscle synergy analysis is based on the idea that coordinated control of multiple muscles by the central nervous system is structured with the combination of a comparatively smaller number of basic synergy patterns  to simplMuscle network analysis  is a rat2) who had severely paralyzed lower limbs. The case, having had spent 10 years without subjective perception of symptoms after obtaining a diagnosis of cervical ossification of the posterior longitudinal ligament (OPLL) and lumbar spinal stenosis (LSS), was sent to a nearby hospital by emergency transportation after having difficulty standing. Frequent falls were experienced, about a month prior to this event. At the hospital, paralysis of the lower limbs was recognized by manual muscle test (MMT) as 0, 1, and 2 on the right and 2 and 3 on the left, together with sensory paralysis on the trunk and the lower limbs. The case was then transferred to our hospital for consideration of surgical treatment.The case was a 64-year-old male patient  were attached to the HAL's cables and pasted bilaterally on the surface of the hip flexor (tensor fasciae latae), hip extensor (gluteus maximus), knee extensor , and knee flexor (biceps femoris) muscles of the patient. The motor torques were generated in real time in accordance with the user's muscle activity: T_hip = Gait training using HAL  was applPre–post-evaluations before the first HAL session (PRE) and after the last HAL session (POST) included clinical assessment of MMT of the major lower limb muscles, Functional Independence Measure—Motor General (FIM-M), Barthel Index (BI), functional ambulation category (FAC), and the 10-m walking test. During the 10-m walk test, gait kinematics was recorded using a motion capture system  sampling at 100 Hz. Sixteen autoreflective markers were placed on the anatomical landmarks according to a Plug-in Gait marker set: anterior superior iliac spine, posterior superior iliac spine, lower lateral 1/3 surface of the thigh, flexion–extension axis of the knee, lower lateral 1/3 surface of shank, lateral malleolus for the ankle, posterior peak of the calcaneus for the heel, and the second metatarsal bone of the toe.In all HAL sessions, lower limb muscle activity was recorded during walking without HAL (NoHAL) and during walking with HAL (HAL) using a wireless surface EMG measurement system  sampling at 2 kHz. In both NoHAL and HAL, the patient walked with the All-in-One walking device. EMG sensors were placed bilaterally on the gluteus maximus, vastus medialis, medial hamstrings, tibialis anterior, and medial gastrocnemius muscles after cleaning the skin over the muscle bellies with alcohol swabs. Foot marker movements were recorded at the same time in synchronization with EMG using the motion capture system for the purpose of gait phase detection.Marker positions of the motion capture data were converted to joint angles using the Plug-in Gait model of Vicon Nexus software (version 2.2.3). The rest of the processing was performed using custom scripts on MATLAB 8.4 R2014b . The flexion/extension angle of the hip and knee joints and the dorsi/plantar flexion angle of the ankle joint were extracted and divided into steps according to the height of the toe and heel markers. EMG data were first filtered with a band-pass filter (30–400 Hz), rectified and locally integrated using a 200-ms moving window to obtain an integrated EMG (iEMG) profile, which was then divided into steps according to the height of the toe and heel markers. The joint angle and iEMG profiles of each step were time-normalized to 101 points, with 0% representing a heel strike which initiates a cycle and 100% representing the subsequent heel strike which terminates the cycle. Data of multiple steps were averaged on the normalized time domain to obtain an averaged joint angle and iEMG profile of an averaged step. The averaged angle profiles were used to compare gait between PRE and POST, and the averaged iEMG profiles were used to compare muscle activity between NoHAL and HAL of each session. Gait was also compared between NoHAL and HAL by the ratio of total iEMG during the stance phase of the measured muscles.m muscles, n data samples, and k synergies, the factorization algorithm gives a decomposition of the muscle activity matrix M (m × n) into M = SC + E, where S is an m × k matrix containing k muscle synergies, C is a matrix containing temporal coefficients, and E is residual. For each of the assumed number of synergies, the fitting of the synergy patterns to the original iEMG patterns was evaluated in terms of variances accounted for (VAF) to estimate the number of synergy patterns underlying in the measured EMG data  method  against EMG data . In equaMuscle network analysis , 55 was wij(f) IMCOH of the ith and jth muscles after normalization in frequency domain, we calculated CC as the average of triplet multiplication of the connection weights 3wij(f)wjk(f)wjk(f), sufficing i ≠ j, ≠ k, k ≠ i. GE was calculated as the average of the connection weights wij(f), sufficing i ≠ j. CC and GE were, respectively, averaged through a lower (2–22 Hz) and a higher (22–44 Hz) frequency range. CC is known to provide an indication of the extent of functional segregation of a network, while GE indicates the extent of functional integration of a network  and global efficiency (GE) of a muscle network graph whose nodes are the measured muscles and whose arcs between the nodes are weighted by the IMCOH values. This gives a network representation of the measured muscles with their pairwise connectivity in the frequency domain. Supposing  network . We thenThe patient completed 10 HAL sessions without any serious adverse events. The observed issues were redness on the skin due to attachment of the electrodes and minor scratches due to interference with belts and harnesses. All of these cutaneous issues disappeared promptly.The patient did not manage to walk using HAL in the first session, in which stand-up training was provided in place. In the third session, gait data was not recorded because the patient reported perception of fatigue. Starting from the second session, the patient monotonically increased the walking distance using HAL .Clinical assessments  showed iPre–post-joint angle comparison demonstrated greater extension of the hip joint during stance and greater range of flexion motion during swing in POST than in PRE , left. IComparing gait with HAL (HAL) and without HAL (NoHAL), the walking speed and step length were greater in HAL than NoHAL through the sessions , right. Activation of the vastus medialis (VM) and gluteus maximus (GM) during stance was greater in HAL than in NoHAL in the second session , but notp < 0.05; Muscle synergy analysis showed smaller VAF in HAL than in NoHAL in each of the sessions in cases of one and two synergy patterns . It was also the case for GE  were not recorded. On the other hand, from the view point of neuro-rehabilitation, neuromechanical observations from physiological data rather directly evaluate changes in neural control of gait. Advances in the analysis of muscle activity during assisted movements –86 may hIn conclusion, the muscular activity modulation by HAL observed in a patient with gait impairment due to severe myelopathy suggested that HAL may be effective in modulating central control of gait of the patient by its activity-based sensorimotor augmentation. The relationship between the altered gait control during walking with HAL and achievement of gait improvement requires further investigation with more cases.The datasets generated for this study are available on reasonable request to the corresponding author.This study was approved by the University of Tsukuba Hospital Ethics Committee  and implemented according to the ethical principles of the Declaration of Helsinki and the University Guidelines for Clinical Trials. Before inclusion in the study, the patient received explanation of the research contents and data usage, for which written informed consent was obtained. At the time of submission of the manuscript, the patient was shown the manuscript and the images, and received explanation according to the Frontiers consent form, which meets the ICMJE guidelines. The patient gave a written agreement to a Japanese version of the Frontiers consent form (translation done by the authors).HK collected, analyzed, and interpreted the data, and wrote and drafted the article. SK administered HAL treatment and collected the clinical scores. TA and HN diagnosed and operated the patient and prescribed HAL treatment. TA, KM, YSh, and MY reviewed and edited the article. KM, MK, YSh, and YH provided important comments on the planning and implementation of HAL treatment. YSa originally developed the robot suit HAL and conceived the idea of HAL treatment. KS provided ideas on clinical gait analysis. MY organized the study. All authors made critical revisions of the manuscript and approved the final version.YSa is the C.E.O., shareholder, and director of CYBERDYNE Inc., which produces the robot suit HAL. CYBERDYNE was not involved in the study design, data collection, analysis, writing, or submission of this article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In view of the possible disruptions in the manufacturing and supply of health products following the coronavirus disease 2019 (COVID-19) pandemic, the Tunisian medicines regulatory authority was mobilized to guarantee patient safety. Teleworking has become the ultimate way of service continuity. The planning was revised according to health priorities. Work procedures were set online. A minimum list of medicines known as "medicines of health and strategic interest" was established. The Directorate of Pharmacy and Medicines (DPM) has been working on updating medicines stock data. A provisional suspension of authorizations for medicines export for 1 mo was decided. A fast-track procedure allowing the validation of alternative sources of raw materials has been put in place. An appeal for a fast track manufacture of hydroalcoholic gel/solutions was launched. A Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) procedure has been adopted in order to dispense off-label prescriptions of hydroxychloroquine and azithromycin combination. Focus groups were organized in order to set up therapeutic trials exploring possible strategies of COVID-19 treatment, such as serotherapy and BCG vaccine. This proactive and anticipatory policy has made it possible to meet the health challenges dictated by this crisis. During the period of general containment decreed in Tunisia in early March, DPM and LNCM had to ensure services continuity and react to this public health emergency.Assessors from DPM and LNCM were forced into containment. Confronted with this unprecedented situation, an active collaboration between the Ministry of Health’s compute center (CIMS), DPM, and LNCM was urgently established to put in place logistical means for a new organization of work. Teleworking has become the ultimate way of service continuity. The planning was revised according to health priorities. Work procedures were set online.The most important challenge faced by the regulatory authority was the availability of essential medications. Indeed, confronted with the export’s interruption of health products from certain countries, especially China, and the disruption of the supply chain of some pharmaceutical products and raw materials, diplomatic efforts were made to sensitize partner countries on health situation criticality. On the other side, an essential list of medicines known as “medicines of health and strategic interest” was established in partnership with the scientific societies. These medicines were secured through close collaboration between the Central Pharmacy of Tunisia (PCT), the national purchasing office, and DPM.Concerning locally manufactured medicines to anticipate any stock fluctuations, DPM has been working on updating stock data so as to be able to respond proactively to potential supply problems. The Tunisian pharmaceutical laboratories were informed by means of a press release from DPM of the provisional suspension of authorizations for medicines export for 1 mo, renewable according to the health situation evolution in the country. However, export exemptions have been granted for certain pharmaceutical specialties for which the national stock covers several months to support partner countries.To respond to shortages of certain raw materials, a fast-track procedure allowing the validation of alternative sources has been put in place. The submission of requests for variations to marketing authorization dossiers relating to the addition of new suppliers of active substances was performed online without prior appointment. These applications are processed on a “fast track” procedure. Forty-one alternative sources of raw materials applications were validated, which represent 4 times the 2019 average.An appeal to local pharmaceutical manufacturers for the production of hydroalcoholic gel/solutions was launched by the regulatory authority following a simplified and accelerated procedure. Following an ad hoc multidisciplinary committee in partnership with the Faculty of Pharmacy of Monastir, the Order of Pharmacists and representatives of the local industries, 2 formulations were validated and published on the DPM website. To secure the national requirements for alcohol used in the formulation of antiseptics, active coordination with the alcohol authority has been established. Between January and August 2020, a total of 39 compliance decisions on hand sanitizers and surface disinfectants were issued versus 30 in 2019. The accelerated procedure put in place made it possible to reduce the processing time from 3 to 4 mo to around 15 d.To guarantee the availability of medical devices (MDs) on the Tunisian market, the regulatory authorities have worked in collaboration with the various importers of MDs to evaluate the state of the stock. The logistical support of the customs services made it possible to streamline the MD circuit subject to the temporary withdrawal authorization. At the same time, 525 new consumption authorization applications (CMAs) were submitted online and evaluated on a fast-track process by DPM and LNCM experts.To guarantee patient’s access to their medicines, a decree-law was promulgated authorizing, for the first time, the renewal and dispensing of electronic prescriptions throughout the period of general confinement. A working group involving the legal unit of the Ministry of Health and ordinary pharmaceutical structures in Tunisia was studying ways of thinking about pharmacies geolocation and the home delivery of health products.A literature review has been initiated to monitor scientific advances in COVID-19–positive patients’ management. A regulatory framework developed by the WHO and called the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) related to hydroxychloroquine procedure has been published on DPM website. This procedure was developed in collaboration with physicians, hospital pharmacists, and pharmacologists to allow clinicians to dispense off-label combined hydroxychloroquine and azithromycin prescriptions in particular clinical situations. During the first wave, approximately 100 COVID-19 patients were treated in accordance with the MEURI procedure.The marketing authorization applications for locally manufactured generic hydroxychloroquine and all medicines used in COVID-19 patients’ management were prioritized. These applications were submitted online by means of a platform shared between DPM and LNCM and evaluated by remote experts.To reduce the risk of misuse of chloroquine and hydroxychloroquine, a medical press release issued by DPM was sent to hospital and dispensary pharmacists limiting their dispensing to prescriptions with presentation of an explanatory letter. The goal of this statement was to keep the continuity of care for chronic patients using these molecules and optimize national stock distribution. In the same context, the release calls on wholesale distributors to submit a monthly report on chloroquine and hydroxychloroquine consumption to the regional inspectorate.Focus groups in collaboration with DPM were organized to set up therapeutic trials exploring possible avenues of treatment, such as serotherapy. Furthermore, clinical experts were encouraged to conduct institutional clinical trials. The procedures for granting authorizations for clinical trials relating to therapeutic strategies to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been streamlined in partnership with the Committee for the Protection of persons.Regulatory authorities faced a real challenge during the COVID-19 pandemic to ensure patient safety in a health emergency. In Tunisia, the medicines regulatory authority had to adapt quickly to the new measures related to containment. To cope with possible raw materials shortages, Tunisia should put in place a strategy to promote the local active substances industries. A new organization of remote work, digitalization, online procedures have been implemented to ensure services continuity as soon as possible. A proactive policy for securing strategic stocks of medicines, vital MDs, and antiseptics prevented shortages throughout the general containment period. The use of the MEURI procedure allowed managing patients hospitalized with severe forms of COVID-19. During the first wave of COVID-19 in Tunisia, the process ran smoothly and the measures taken by public decision-makers were efficient, despite the emergency situation.


Teaching Point: A meniscal ossicle may be misdiagnosed as a tear of the posterior horn of the medial meniscus or an intra-articular loose body. A 12-year-old boy with a known history of juvenile idiopathic arthritis (JIA) presented with pain in the left knee with associated joint effusion after a fall during ice-skating. Coronal fat-saturated (FS) proton density magnetic resonance imaging (MRI) revealed a hypointense structure at the intercondylar site of the posterior region of the medial meniscus (MM), which was initially interpreted as a meniscal fragment adjacent to a radial tear of the MM Figure . JIA wasA meniscal ossicle is rare with a prevalence around 0.15% [Meniscal ossicle can be an incidental finding in asymptomatic patients, although most patients present with intermittent pain and joint effusion. Because of frequent coexisting intra-articular lesions, it is unclear whether these symptoms can be attributed to the meniscal ossicle.Radiographs show a triangular or rectangular opacity usually at the posteromedial joint space, often misdiagnosed as a loose body. On MRI, location within the posterior horn of the MM differentiates it from a loose body, avulsion fracture of the semimembranosus tendon, and chondrocalcinosis. Furthermore, the ossicle appears isointense to bone marrow and is circumscribed by a hypointense rim on all sequences. The increased signal compared to the low signal of the fibrocartilage of the meniscus can mimic a tear. We highly recommend including T1-WI in at least one plane to the MRI protocol. This allows characterization of the fatty bone marrow content of the ossicle and to exclude chondrocalcinosis, which is of low signal on T1-WI. Because the causal relationship of the meniscal ossicle with the clinical presentation is not clear, the radiologist should scrutinize the knee for other abnormalities.Conservative treatment of the meniscal ossicle is favoured. Arthroscopic resection may be considered in case of persistent symptoms and suspicion of posttraumatic etiopathogenesis of the meniscal ossicle .


Next generation sequencing (NGS) describes the technical revolution that enabled massively parallel sequencing of fragmented nucleic acids, thus making possible our current genomic understanding of cancers. It took an international consortium, using factory-like centers and high-throughput Sanger (terminator dye sequencing), more than 10 years to release the completed reference human genome in 2003. The generation of this high quality human genome reference and associated gene model annotation was essential for cancer genomics studies. However, the scale of resources required to generate the human genome reference highlighted the need for innovative sequencing approaches that would redefine the term “high-throughput sequencing”. NGS is the term used for the new form of sequencing that emerged in the mid-2000s and is the product of competing technologies that led to increased speed, capacity, accuracy of sequencing machines and the progressive fall in the cost of sequencing per base pair. It is this sequencing revolution which enabled researchers to conceive of sequencing two samples for each individual cancer patient: one representing the inherited genome and the other the cancer genome in order to identify cancer specific genomic alterations. The ability to undertake genome-wide sequencing studies for thousands of cancer patients at base-pair resolution has had a profound impact on our understanding of the mutational landscape of cancers and the mechanisms underlying the disease.Cancer is one of the leading cause of death worldwide, and it is well accepted that cells in the human body may acquire genomic changes (mutations). These mutations may result in uncontrolled cellular growth, suppression of cell-death signaling, promote angiogenesis amongst other key hallmark characteristics that lead to the development of cancers . Over thA major outcome of the NGS exploration of cancers has been the realization that high levels of inter-tumor and intra-tumor heterogeneity are key features of malignant cancers. Much of the current research efforts focus on how to identify patients whose cancers will respond to targeted treatments and how to negate the development of treatment resistance . NGS of NGS has also revolutionized the study of the tumor transcriptome by identification of novel transcripts, fusion genes. Whole transcriptome sequencing also allow new insights into the tumor microenviroment using deconvolution methods to estimate the abundance of different cell types from a mixed cell population . NGS hasIn the research setting, new sequencing technologies that rely on the principals of NGS continue to be developed. For example: (1) ATAC-Seq (Assay for Transposase Accessible Chromatin with NGS) an approach for genome-wide chromatin accessibility profiling using hyperactive Tn5 transposase, which simultaneously cuts DNA and inserts sequencing adaptors . (2) ChiRNASeq together with single cell sequencing and spatial transcriptomics are bring new information allowing the study of subpopulations of cells and their relationships in the tumor microenvironment leading to unprecedented gain in knowledge in cancer biology . The muc