Internal Medicine (IM) programs offer elective subspecialty rotations in which residents may enroll to supplement the experience and knowledge obtained during general inpatient and outpatient rotations. Objective evidence that these rotations provide enhanced subspecialty specific knowledge is lacking. The purpose of this study was to determine whether exposure to an endocrinology subspecialty rotation enhanced a resident’s endocrinology-specific knowledge beyond that otherwise acquired during IM residency.Data were collected on internal medicine resident scores on the American College of Physicians Internal Medicine In-Training Examinations (IM-ITE) for calendar years 2012 through 2018 along with enrollment data as to whether residents had completed an endocrinology subspecialty rotation prior to sitting for a given IM-ITE. Three hundred and six internal medicine residents in the University of Minnesota Internal Medicine residency program with 664 scores total on the IM-ITE for calendar years 2012 through 2018. Percentage of correct answers on the overall and endocrine subspecialty content areas on the IM-ITE for each exam were determined and the association between prior exposure to an endocrinology subspecialty rotation and percentage of correct answers in the endocrinology content area was analyzed using generalized linear mixed-effects models.Two hundred and thirty-three residents (76%) completed an endocrinology subspecialty rotation at some point during their residency; 121 (40%) residents had at least one IM-ITE both before and after exposure to an endocrine subspecialty rotation. Exposure to an endocrinology subspecialty rotation exhibited a positive association with the expected IM-ITE percent correct on the endocrinology content area (5.5% predicted absolute increase). Advancing year of residency was associated with a predicted increase in overall IM-ITE score but did not improve the predictive model for endocrine subspecialty score.Completion of an endocrinology subspecialty elective was associated with an increase in resident endocrine specific knowledge as assessed by the IM-ITE. These findings support the value of subspecialty rotations in enhancing a resident’s subspecialty specific medical knowledge. In the United States, following four years of medical school newly graduated physicians who wish to practice in the specialty of Internal Medicine (IM)  first complete an additional three post-graduate years of IM specific training in an accredited IM residency program. In the US, these programs are accredited by the Accreditation Council for Graduate Medical Education (ACGME) which sets standards for residency and fellowship programs and the institutions that sponsor them. As part of the ACGME standards, residency programs are charged with the task of preparing residents with the knowledge and skills to practice independently. Such programs must also provide regular objective assessment of resident competence . ResidenTo alleviate such limitations, IM programs offer elective rotations in specific subspecialty areas, allowing for focused clinical experience and education in a particular subspecialty. However, whether these elective rotations provide enhanced knowledge in the subspecialty beyond knowledge acquired during typical inpatient rotations or outpatient general medicine clinics is either unknown or is based on residents’ own perceptions of their knowledge .The annual American College of Physicians (ACP) Internal Medicine In-Training Examination (IM-ITE) provides a standardized assessment of resident knowledge in eleven content areas including general medicine . First o20 >0.90) across administrations similar to national certifying exams [Attesting to the validity of the exam, resident scores have been shown to increase with increasing time in training and overall scores on the IM-ITE predict subsequent performance on the ABIM-CE . Test reng exams . In-traing exams . Since tTargeted curricula have previously been reported to improve overall IM-ITE scores. Mathis et al. compared overall IM-ITE scores between PGY-2 and PGY-3 residents before and after implementation of a structured 12 month program of multiple choice tests and board review type questions. IM residents exposed to the program showed a significantly greater improvement in PGY-2 to PGY-3 ITE percentile scores compared to the unexposed historical control group . SimilarWith regard to the effect of more targeted, topic specific curriculum interventions, Trickey et al. reported that an intervention of research and statistics lectures provided to surgery residents resulted in a significant improvement in scores for the research and statistics items on the American Board of Surgery ITE . ImplemeTo our knowledge, the effectiveness of IM subspecialty rotations to improve corresponding IM-ITE content area scores has not been studied. For the current study, we sought to determine whether IM residents who completed an endocrinology subspecialty elective rotation subsequently scored a higher percentage correct (“score”) on the endocrinology content area of the IM-ITE in comparison to their peers who had not enrolled in the rotation prior to the exam.The study was approved as exempt from review by the University of Minnesota Institutional Review Board (IRB ID: STUDY00004872).The University of Minnesota IM residency program offers a four-week endocrinology elective rotation residents can take at any point during their three-year residency. Residents can choose to do the rotation at one of three teaching hospitals and their affiliated outpatient specialty clinics: (1) the University of Minnesota Medical Center, the primary academic teaching hospital; (2) the Minneapolis VA Medical Center; and (3) the HealthPartners Regions Hospital in St. Paul, MN.The educational curriculum at all sites includes clinical experience in both the outpatient and inpatient settings. At the University of Minnesota site, residents receive 8 h of scheduled didactic lectures delivered by faculty in the areas of type 1 and type 2 diabetes; hyperlipidemia; osteoporosis and calcium disorders; and disorders of pituitary, gonadal, adrenal, and thyroid function. At the Minneapolis VA Medical Center, residents receive didactic lectures in the areas of thyroid and adrenal disorders, osteoporosis, and obesity. At the Regions Hospital site, the educational experience is primarily delivered through informal teaching by faculty in the outpatient clinics and inpatient consult settings.All IM residents take the IM-ITE during each year of their residency. For each academic year from 2012 to 2018, we collected IM-ITE overall and endocrinology content area scores (reported as percent correct) for each resident and determined whether the resident completed an endocrinology subspecialty elective rotation over the course of residency prior to taking the exam for the given year.The University of Minnesota’s Medical Education Outcomes Center (MEOC) merged resident IM-ITE score data with resident demographic data from the University of Minnesota’s Department of Medicine resident management systems.Overall, 306 residents Table  with a tConventional hypothesis tests on linear regression coefficients, such as the t-test and ANOVA, assume independence of all response variable measurements . AssuminTo incorporate these sources of dependence, we used generalized linear mixed-effects models (GLMM) with normal random component and logit link to analyze the association of a resident’s years of residency and exposure to an endocrinology elective rotation with either a resident’s overall expected IM-ITE score or the resident’s expected endocrinology content area IM-ITE score . For eacWe considered the following fixed-effect covariates for each GLMM: (1) a fixed effect denoting whether the student took the IM-ITE exam after an endocrinology rotation , (2) a fixed effect denoting the PGY level at the time of the IM-ITE , and (3) a fixed effect for the interaction of these two variables. In each model, we included two random effects: one incorporating year dependence of IM-ITE exams, and another to incorporate student dependence. Data for PGY-4 and PGY-5 were excluded due to small sample sizes.P < 0.01 to denote statistical significance of model parameters. We used R 4.0.2  to perform all computations.We used With regard to overall IM-ITE scores, we found the GLMM using PGY level as the only fixed effect provided the best fit to the overall IM-ITE score. Table Table We found a positive association between exposure to an endocrinology subspecialty rotation and expected subsequent performance on the endocrinology content area of the IM-ITE. We found no evidence of an association between exposure to the endocrinology subspecialty rotation and expected performance on the overall IM-ITE, suggesting that the rotation enhanced endocrinology-specific knowledge. Conversely, adding PGY level did not result in an improved model for the expected endocrinology content area score. Thus, completion of an endocrinology elective rotation appears to enhance resident knowledge in endocrinology beyond that otherwise attained during other resident experiences.As expected, there is evidence of a positive association between PGY level and the overall IM-ITE score. In our cohort, each year of residency has an association with an absolute increase in the expected overall IM-ITE score of 5.4–5.9%. These values are consistent with previous studies which have reported increases in resident ITE scores with each progressing year of residency , 14. IntWe are not aware of prior studies that examine the effect of subspecialty rotations or other factors which impact performance on IM-ITE content area scores. Prior studies have demonstrated evidence of an association between overall IM-ITE performance and age at start of residency, US versus international medical-school training, conference attendance, and self-directed use of online resources . In addiOur study does not allow us to identify what individual elements of an endocrine subspecialty rotation result in improved scores on the endocrine subspecialty section of the ITE. Potential elements include exposure to structured endocrine didactic lectures provided by endocrine faculty, increased exposure to endocrine disorders through participation in endocrine outpatient clinics and inpatient consults, exposure to weekly endocrine teaching, research and clinical conferences during the rotation and possibly resident initiative to increase outside reading on endocrine topics during the rotation. It is possible that all of these elements play a role.A limitation of our study is that residents were not randomized to enroll or not enroll in the endocrinology subspecialty rotation during their residency; enrollment in the rotation was voluntary. Therefore, it is possible that residents electing to take an endocrinology rotation were residents more interested in endocrinology and were more motivated than their counterparts to perform well on the endocrinology IM-ITE content area. However, 233 (76%) residents did have the rotation at some point during residency, and 121 (40%) residents had IM-ITE scores both before and after an endocrinology rotation, allowing us to make resident-level comparisons before and after residents enrolled in a rotation. In addition, we did not see evidence of a difference in overall IM-ITE scores at any given PGY level between exposed and non-exposed residents.We see the purpose of subspecialty rotations during IM residency training as threefold: (1) to expose residents to the subspecialty field as a potential career path, (2) to provide clinical experience in the subspecialty at a level they might not encounter during inpatient hospital rotations or in the primary care clinic setting, and (3) to provide a basic level of knowledge in the field that should be attained by all internists. Our results suggest that subspecialty rotations can help to achieve this last purpose.We found in our program that exposure to an endocrinology subspecialty rotation was associated with an improvement in endocrinology-specific knowledge as assessed by resident performance on the IM-ITE. Our findings support the value of subspecialty rotations as part of an IM resident’s postgraduate education. IM residency programs may want to use similar methods and metrics as one way to document the effect of their curriculum on resident medical knowledge competency.


We explore the tunneling transport properties of a quantum dot embedded in an optical microcavity and coupled to a semiconductor-superconductor one-dimensional nanowire (Majorana nanowire) hosting Majorana zero modes (MZMs) at their edges. Conductance profiles reveal that strong light-matter coupling can be employed to distinguish between the cases of highly nonlocal MZMs, overlapped MZMs and MZMs with less degree of nonlocal feature. Moreover, we show that it is possible to access the degree of Majorana nonlocality  by changing the dot spectrum through photon-induced transitions tuned by an external pump applied to the microcavity. In such devices, each isolated ‘half-fermionic’ MZM appears at one of the opposite nanowire ends when the bulk of the system undergoes a topological phase transition8.Over the past decade, a huge effort in both theoretical and experimental fields has been performing in the quest for an unquestionable signature of exotic ‘half-fermionic’ states, the so-called Majorana zero-modes (MZMs) in quasi-one dimensional hybrid semiconductor-superconductor nanowires with strong spin-orbit coupling subject to external magnetic field, termed as Majorana nanowires15, the emergence of a quantized zero-bias peak (ZBP) robust to changing of relevant system parameters such as magnetic field and gate voltages is considered as a strong evidence supporting the emergence of the isolated MZMs. However, it has been extensively demonstrated that other physical mechanisms such as the formation of trivial zero-energy Andreev bound state (ABS) at wire ends due to inhomogeneous smooth confining potentials25 and disorder-induced bound states27 can produce a robust quantized ZBP, leading to an ambiguity of the MZM signature.In tunneling spectroscopy measurements performed through a Majorana nanowire21. This kind of trivial ABS formed by two half-fermionic states with small spatial separation between them has been dubbed as partially separated ABS (ps-ABS)20 or quasi-Majoranas (quasi-MZM)21. Despite some recent advances, distinguishing ZBPs resulting from genuine topological MZMs, trivial quasi-MZMs and disorder still remains a challenge25.The emergence of a trivial zero-energy ABS can be mathematically described as resulting from two half-fermionic states with some spatial separation between them. In this scenario, a quantized ZBP may arise if one of these half-fermionic states couples to a tunneling spectroscopy probe stronger than the other28, the possibility of performing decoherence-free quantum computing operations lies on the ability of storing the information nonlocaly31, once each MZM is far apart from each other for the ideal situation of longer and pristine nanowires. Hereupon, it is crucial to obtain the information about the spatial localization of the wave functions corresponding to these MZMs. This can be achieved by measuring the so-called degree of Majorana nonlocality32, which indirectly quantifies the information about the localization of the MZMs wavefunctions along the nanowire. This quantity can be accessed by means of a quantum dot (QD) working as a local tunneling spectroscopy probe at one of the ends of a Majorana nanowire35. The degree of Majorana nonlocality is defined as 37. Highly nonlocal MZMs are characterized by 32, the degree of Majorana nonlocality  can be accessed by measuring the corresponding energies of anticrossing patterns appearing in tunneling conductance profiles as functions of both applied bias-voltage through the QD-nanowire and QD gate-voltage.From the perspective of Majorana-based qubits36.In the present work, we show that light-matter coupling can be employed as an alternative to probe the degree of Majorana nonlocality through tunneling conductance experiments. We consider the system schematically shown in Fig. mentclass2pt{minim39 and, in recent years, some theoretical works have employed cavity QED for studying MZMs43. In such theoretical proposals, the whole Majorana nanowire is placed in a (microwave) cavity, whereas in our approach only the QD is sandwiched between the mirrors that form an optical microcavity. Moreover, in our theoretical approach we introduce a new  degree of freedom in the system such that, on the one hand, it affects only a small part of the full system in contrary to the previous approaches, and on the other hand, allows one optical manipulation of the electrical conductance, thus providing an alternative to access degree of Majorana nonlocality via optical means. It’s worthy noticing that the bridging between cavity QED and topological superconductors supporting Majorana excitations not only opens new possibilities for MZMs detection schemes, but also can pave a new way for performing quantum computing operations with photons45 in Majorana based qubit schemes.To the best of our knowledge, experimental setups which combine optical and electrical methods to explore the underlying physics of MZMs have not been considered previously. However, QDs in microcavity quantum electrodynamics (QED) devices are routinely studied in optical experimentseV, in presence of a photonic field in the cavity  is a fast indirect way of tuning the QD energy without applying any gate-voltage due to renormalization of the QD spectrum in the strong light-matter coupling regime, which bridges Quantum Optics and the physics of MZMs.The colormap of Fig. entclass1pt{minimaentclass1pt{minima48 shown in the conductance profiles of Fig. 25. This difference comes from the underlying mechanism of electronic transport for each case. For characteristic setups of tunneling spectroscopy experiments15, the 3. In our proposal otherwise  , with a64.The part of the self-energy associated with the direct coupling between the QD conduction level and MZMs reads:The presence of d in Eq.  means thSupplementary Information.


The United States designated the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) a variant of concern on November 30, 2021, and the first U.S. Omicron COVID-19 case was reported on December 1  comprises 43 health departments funded by CDC to provide data on presence of and trends in SARS-CoV-2 infections that are independent of clinical testing. In addition to total SARS-CoV-2 testing, some health departments track SARS-CoV-2 variants by detecting variant-associated mutations in wastewater. Health departments in four states  were the first wastewater surveillance programs to detect evidence of Omicron in community wastewater. This report describes the initial detections in wastewater during November 21–December 16, 2021, and the interpretative framework for these types of data. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.,The California Department of Public Health and academic partners use mutation-specific reverse transcription–polymerase chain reaction (RT-PCR) and sequencing to track variants in wastewater collected daily from 10 sewersheds.The Colorado Department of Public Health and Environment conducts biweekly SARS-CoV-2 wastewater testing at 21 sewersheds,,The New York City Department of Environmental Protection tracks variants in wastewater by sequencing weekly samples collected from 14 sewershedsThe Houston Health Department conducts weekly wastewater testing at 39 sewersheds in the city and uses sequencing to track variants.The wastewater surveillance programs in these four states were the first to detect evidence of Omicron in community wastewater. Variant tracking data from wastewater cannot confirm the presence of a specific variant because the methods used cannot determine whether all variant-defining mutations are present on a single genome. However, conditions that increase confidence in the results include detection of multiple variant-associated mutations; linked mutations , or unique mutations not shared by other known variants; RNA concentration data consistent with emergence ; the reporting of clinical cases in the area; detections in consecutive samples or via multiple methods; and RNA concentration or sequence abundance data for multiple variant-associated mutations trending together. Limitations of variant tracking in wastewater include detections inconsistent with the current epidemiology, low quality sequence data, sporadic detections, detection of a single variant-associated mutation, and conflicting trends in concentration or abundance data for mutations associated with the same variant. Reporting times >1 week can limit the usefulness of this data.The detection of Omicron-associated mutations in community wastewater provides strong early evidence that the Omicron variant was likely present or more widely distributed in these communities than originally indicated by clinical testing alone; Omicron-associated mutations were documented during November 2021, at least a week before the first U.S. case identified via clinical testing on December 1. Variant tracking data from wastewater can be used as a complement to clinical testing for early detection of emerging variants, which can help guide decisions about allocation of clinical and public health resources, testing strategies, and public health messaging.


Major advances in molecular profiling for available targeted treatments and immunotherapy for lung cancer have significantly increased the complexity of tissue-based diagnostics. Endobronchial ultrasound-guided transbronchial needle aspirations (EBUS-TBNA) are commonly performed for diagnostic biopsies and lymph node staging. EBUS-TBNA has increasingly become one of the main sources of tumor cells for molecular analyses. As a result, there is a growing need for high quality EBUS-TBNA samples with adequate cellularity. This has increased the technical demands of the procedure and has created additional challenges, many of which are not addressed in the current EBUS guidelines. This review provides an overview of current evidence on the technical aspects of EBUS-TBNA in light of comprehensive sample processing for personalized lung cancer management. These include sonographic lymph node characterization, optimal needle choice, suction biopsy technique, and the role of rapid on-site evaluation. Attention to these technical details will be important to maximize the throughput of EBUS-TBNA biopsies for molecular testing. Linear endobronchial ultrasound (EBUS) is a well-established diagnostic tool for the workup and staging of lung cancer ,2. The dEndobronchial ultrasound-guided transbronchial needle aspirations (EBUS-TBNAs) are becoming one of the main sources for tissue-based biomarker analysis. Time is of the essence for the management of lung cancer, and there should be a close partnership between the pulmonary, surgical, and medical specialties responsible for the management of lung cancer. Ideally, EBUS samples can be simultaneously sent by the practitioner for diagnosis, staging, and molecular analysis so that these data will be available to the medical oncologist at the first visit rather than being ordered post hoc, further delaying therapeutic decision making. To accomplish these goals, there is a growing need for high quality EBUS-TBNA tissue samples, which has created additional challenges and has increased technical demands, many of which are not reflected in the current EBUS guidelines. In this review, we sought to review technical aspects of EBUS as they relate to lung cancer diagnostics and treatment in the current era of personalized cancer care.The identification and characterization of lymph nodes by EBUS is the first step in the selection of lymph nodes for biopsy, which is paramount considering the importance of accurate mediastinal staging. Ultrasonographic features to distinguish potentially metastatic lymph nodes from likely benign lymph nodes were first described by Fujiwara and colleagues in 2010 . They reWhile the most widely used ultrasonographic features to distinguish malignant from benign lymph nodes remains the size (short axis of >1 cm), smaller lymph nodes may still harbor malignancy. A systematic sampling of mediastinal, hilar, and interlobar lymph nodes should therefore be performed even in light of false negative rates of radiologic and nuclear staging ,23. For Thoughtful procedural planning and the flexibility to adapt available biopsy techniques is needed to satisfy increasing tissue demands for EBUS-TBNA. A suggested workflow is illustrated in ® needle (Medi-Globe) and in the Acquire Pulmonary® needle . All other needle types have a rounded or beveled single-point needle tip.The needle choice is the next important technical consideration because it may affect quality of the EBUS-TBNA biopsy samples. EBUS needles are now available from several manufacturers , and they are also available in various sizes . The earThe needle size and number of needle passes are both related factors that may determine the tissue yield of the EBUS-TBNA biopsies. Current recommendations of three needle passes to be performed for optimal diagnostic yield were derived from a study by Lee at al. published in 2008, which used the 22G EBUS-TBNA needle from Olympus. At that time, the main focus of EBUS-TBNAs was to provide the best possible diagnostic yield when comparisons to the previously established mediastinoscopy were underway and when molecular testing was still in its infancy ,26. In tThe CHEST guidelines from 2016 recommended a minimum of three needle passes with a 21G or 22G needle and additional samples for molecular analysis. However, as demonstrated by Ortaköylü and colleagues, more than 40% of EBUS-TBNA samples may be insufficient for pathological work up . TherefoA recently introduced technique using transbronchial mediastinal cryobiopsy using a channel created with a TBNA needle, similar to the previously described needle forceps technique, may be used in selected patients to yield additional tissue .Current guidelines leave the decision of whether suction should be applied during EBUS-TBNA sampling up to the bronchoscopist. While the use of suction may cause bleeding and potentially increased tissue damage, it may also result in the aspiration of more cells, particularly in lymph nodes with liquified consistencies. The existing evidence on the benefits of suction are limited to studies that are focused on the ability to secure the diagnosis as opposed to tissue yield ,37. CasaA further technical consideration that may affect the quality of EBUS-TBNA samples is the use of a rapid on-site evaluation (ROSE). The first randomized study to test the impact of ROSE on the diagnostic yield of EBUS-TBNAs was performed by Oki and colleagues. A total of 108 patients receiving EBUS-TBNA for suspected lung cancer were randomized for the additional use of ROSE during their EBUS procedure. Since a sample-size calculation had not been conducted and since the difference between the diagnostic yields of the two groups was small (sensitivity: 88% versus 86%), the authors admitted that this study was underpowered . FurtherMost larger studies on this topic have been retrospective in nature. Nakajima and colleagues analyzed 965 lymph node samples of 438 patients obtained via EBUS-TBNA. Eighty-four lymph nodes (8.7%) were determined to be insufficient for definitive diagnosis by final cytologic evaluation, the non-diagnostic sampling rate was 4.0%, and the rate of false-negative ROSE results was 5.7%. The concordance rate for staging between ROSE and final pathologic diagnosis was 94.3% . AnotherChoi et al. demonstrated that the adequacy of ROSE from EBUS-TBNA samples could be significantly increased when an algorithm with the following four criteria was implemented: (1) ≥3 punctures per lymph node, (2) the presence of tumor cells, (3) the presence of microscopic anthracotic pigments (MAP), and (4) lymph node (LD) density of ≥40 cells/field  in smears. On permanent tissue histology, a core tissue size ≥ 2 cm, MAP, and LD ≥ 40 cells/field in smears were significantly related to adequate results. The diagnostic sensitivity of the specimen was increased from 64.7% using a core size ≥ 2 cm as the only criterion to 97% using all four criteria, while the lymph node density >40 cells/field only increased the adequacy by 2% (95% compared to 97%) . The stuEGFR and KRAS testing by next-generation sequencing (NGS), followed by ALK testing (FISH) for EGFR and KRAS wild-type disease. ROSE was associated with a higher percentage of patients for whom the institution’s clinical protocol for lung cancer genotyping was completed  and a decrease in the number of samples that could only be used for diagnostic purposes  [More recently, the impact of ROSE on molecular workup has been demonstrated in several studies. In addition to the qualitative assessment for establishing cytologic diagnostic, ROSE may also allow for a quantitative evaluation of the percentage of tumor cells in the smear to gauge suitability for molecular testing. As such, Yarmus and colleagues reported that 95.3% of EBUS-TBNA samples were sufficient for KRAS, EGFR by polymerase chain reaction (PCR), and/or ALK mutation analyses via fluorescence in situ hybridazition (FISH) when four passes were sampled with a 21G needle in the presence of ROSE . Trisoli = 0.05) . These dIn the current era of personalized pulmonary oncology and immunotherapies, the necessary amount of tumor DNA and lymphocytes for thorough evaluation via next-generation sequencing (NGS) to detect multiple genes and PD-L1 immunostaining have likely increased beyond what is typically achieved with four sample passes with a 21G needle. The input DNA requirement for NGS analysis varies by testing platform but ranges between 10 ng for Ion Torrent PGM  for the detection of 50 genes and 250 ng for Illumina MiSeq  platforms for the detection of 48 genes . DependiImmunohistochemical staining with anti-PD-L1 antibodies has become an integral part of EBUS-TBNA pathology workup in lung cancer patients. Single-agent immunotherapy with the anti-PD-1 drug pembrolizumab has been approved by the FDA for the front-line treatment of patients with advanced EGFR/ALK wild-type NSCLC whose tumors have ph nodes . The conG needle . EBUS-TBG needle ,53. YoshG needle . With reG needle .While EBUS-TBNA has been established and widely adopted in clinical practice, there is an ongoing need for high-quality research. Randomized-controlled prospective trials are crucial to define the benefits of technical advancements such as navigational techniques, new robotic platforms, needle designs, and new refinements in cytopathological processing. Study designs need to reflect the increasing demands of lung cancer precision diagnostics by shifting the primary focus from diagnostic yield to cellular quality and quantity. Implementation research will help to further enhance procedural techniques and lead to the widespread adoption of best practices.The role of EBUS-TBNA in the management of lung cancer has evolved from a primarily diagnostic and staging modality to also serve as an effective vehicle for molecular testing for the growing number of actionable genetic alterations and for the testing of diagnostic and/or predictive biomarkers. It enables concurrent diagnosis, staging, and molecular analysis, speeding up therapeutic decision-making. The lymphocyte and tumor cell amounts of EBUS-TBNAs matter for molecular work-up and PD-L1 staining can best be estimated when ROSE is used. Because NGS panels differ between institutions, the amount of required DNA varies as well. In general, an addition two to three sample passes with the use if a 21G needle or using an even larger needle design should be considered to optimize the throughput of EBUS-TBNA samples for comprehensive molecular testing, especially when PD-L1 staining is added. The use of suction may also additionally increase the amount of sampled material. Further studies on EBUS-TBNA are needed to establish universal protocols that maximize the yield of cytology material for molecular workup while maintaining the established reliable diagnostic workflow.


Enhanced CO emissions along with plume evolution and transport from the fire ground site locations were captured by moderate vertical and high horizontal resolution observations obtained from the NAST-I IR spectrometer; these were intercompared and verified by the cloud physics lidar and the enhanced MODIS airborne simulator also hosted on the NASA ER-2 aircraft. This study will be beneficial to the science community for studying wildfire-related topics and understanding similar remotely sensed observations from satellites, along with helping to address the broader FIREX-AQ experiment objectives of investigating the impact of fires on air quality and climate.The fire influence on regional to global environments and air quality (FIREX-AQ) field campaign was conducted during August 2019 to investigate the impact of wildfire and biomass smoke on air quality and weather in the continental United States. One of the campaign’s scientific objectives was to estimate the composition of emissions from wildfires. Ultraspectrally resolved infrared radiance measurements from aircraft and/or satellite observations contain information on tropospheric carbon monoxide (CO) as well as other trace species present in fire emissions. A methodology for retrieving tropospheric CO from such remotely sensed spectral data has been developed for the National Airborne Sounder Testbed-Interferometer (NAST-I) and is applied herein. Retrievals based on NAST-I measurements are used to demonstrate CO retrieval capability and characterize fire emissions. NAST-I remotely sensed CO from ER-2 flights are evaluated with concurrent  I.4), and ozone (O3) with those of the hydroxyl radical (OH) and hydroperoxyl radical (HO2)  for for7] foribution . Currentribution , and theribution  also hav-1) measurements within the spectral region of 645–2700 cm-1. It serves as an ideal validation sensor since it measures the same Level-1 data product as many of the sensors it helps to validate  and does so at higher spectral and spatial resolutions [Similar ultraspectral infrared sounders flown on high-altitude aircraft can provide such measurements with a higher spectral resolution and much smaller footprint size. The National Airborne Sounder Testbed-Interferometer (NAST-I) has been successfully operating on high-altitude aircraft since 1998 -14]. NA. NA14]. olutions . NASA Laolutions . Airbornolutions –[19].in situ CO measurements . An. An32]. IV.in situ and remotely sensed observations provides the characterization of distributions of chemical species, such as CO, induced by wildfires. This unique dataset is very much desirable in validating CO retrieval algorithms and results with an elevated CO amount. Two wildfire cases from the FIREX-AQ experiment dataset are reported herein, one is from the Sheridan fire and the other is from the Williams Flats fire. Several major summary items and conclusions can be obtained from this work.The FIREX-AQ field campaign with multiple aircraft Wildfire-induced CO plumes in the troposphere, in conjunction with their evolution and transport, are readily identified with NAST-I measurements.NAST-I retrieval ability is demonstrated showing the contrast between nominal atmospheric background levels and fire-induced elevated CO profiles.in situ CO measurements, which show a positive agreement.NAST-I remotely sensed CO is evaluated by favorable intercomparisons with the DACOM Plume characterization correlation between CO and smoke-dust detected by the CPL and eMAS is assessed and presented a good correspondence.Elevated tropospheric CO induced by the wildfire is associated and correlated with the total carbon emission from biomass burning.in situ measured CO as they observe different spatial–temporal parts of the atmosphere, but remotely sensed measurements do have the advantage of giving broader spatial and temporal context by rapidly covering a large field of observation, as shown in First-of-a-kind wildfire-induced CO plume measurements obtained by the NAST-I ultraspectral remote sensor on board the ER-2 suborbital aircraft have shown the intensity and size of wildfire plumes in a high spatial resolution of 2.6 km. Remotely sensed CO from NAST-I is different from NAST-I was successfully operated during all ER-2 flights of the FIREX-AQ experiment . NAST-I retrievals , together with experiment data from other satellite/aircraft/ground measurements and analysis from the FIREX-AQ campaign are available  for the


Blunt carotid injury (BCI) injury is a rare sequel of trauma and could result in ischemic complication if not detected and treated early. The presence of high-grade solid organ injury with ongoing bleeding represents additional challenge in treating BCI.A 25-year-old victim of motor vehicle collision resulted in grade IV liver, grade III left kidney and grade I spleen injury. He underwent an urgent laparotomy with transient liver packing at local hospital. A full body Contrast-Enhanced Computer Tomography (CECT) upon arrival revealed right internal carotid intimal tear with intra and extra-cranial thrombosis and a 3 cm aneurysm. With a decreased level of consciousness, the patient showed a GCS of 13 and left-sided hemiplegia. After complex multidisciplinary treatment sessions, patient recovered with a partial regain of left-sided muscle power.Selective embolization of active liver bleeding was a turning point in the management of our patient as it deferred the need for a second operative intervention. It was a necessary step before endovascular stenting and recanalization of the BCI to restore the circulation to the right cerebral hemisphere. Dual anti-platelet therapy (DAPT) was necessary to prevent thrombosis of the stent and continuity of carotid recanalization.BCI with traumatic ischaemic hemiplegia associating a sum of life-threatening multiple injuries including high grade liver trauma with ongoing bleeding could still be managed non-operatively with acceptable outcome in the presence of a comprehensive specialized multidisciplinary service. •Early detection and high susception of blunted carotid injury (BCI) prevent deterioration and promote better prognosis.•BCI associated with polytraumatic injuries can be managed non-operatively with acceptable outcome.•The use of dual antiplatelet therapy in anticoagulant contraindicated patients is essential to prevent stent-related thrombosis. The work has been reported in line with the SCARE criteria 2a & b, V, VI and VIII, longitudinal mesenteric laceration and retroperitoneal haematoma at zone-II. Liver packing for 15 min was performed with approximation of mesenteric defect and insertion of two large abdominal drains. The abdomen was closed and the patient was admitted to the intensive care unit.A 25-year-old male patient, a victim of a motor vehicle collision, was brought to the emergency department of the nearest medical facility which was a private hospital due to haemodynamic instability. The patient underwent immediate laparotomy which revealed 2 l of intra-peritoneal free blood, deep liver laceration involving segments IVThe patient was transferred to our facility ventilated, in a stable condition, he underwent full body Contrast-Enhanced Computer Tomography (CECT)  upon arrAs the patient was haemodynamically stable, selective interventional embolization of the active liver bleeding  followedThe patient stayed in ICU for three weeks before being discharged to the regular ward with very critical times of increase in haematoma size. With appropriate physiotherapy, the patient started after one month to move the lower limbs (grade-II power) and evidence of complete healing of intra-abdominal injuries.3Traumatic ischaemic hemiplegia secondary to BCI in the presence of severe multiple solid organ injuries was not reported in literature based on a comprehensive the literature search. Reports of high-grade liver trauma associated with major vascular trauma were only found in relation to aortic trauma Selective embolization of active liver bleeding was a turning point in the management of our patient as it deferred the need for a second operative intervention. It was a necessary step before endovascular stenting and recanalization of the BCI to restore the circulation to the right cerebral hemisphere. DAPT was necessary to prevent thrombosis of the stent and continuity of carotid recanalization The presence of interventional angioembolization and neuro-endovascular hybrid unit at our facility supported the non-operative approach on our patient. Lack of comprehensive specialized multidisciplinary service under one roof made the initial damage control laparotomy, a justified approach In conclusion, BCI with traumatic ischaemic hemiplegia associating a sum of life-threatening multiple injuries including high grade liver trauma with ongoing bleeding could still be managed non-operatively with acceptable outcome in the presence of a comprehensive specialized multidisciplinary service.The authors deny any source of funding in this project.The institutional review board approved the publication of this case report with a reference number: IRB-2021-01-291.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.Ayman Nasr: Treating consultant, main author, writing the manuscript.Turki Al Harbi: Data collection and writing the manuscript.Fatimah AlRamadan: Data collection and writing the manuscript.N/A.Dr. Ayman Nasr.Not commissioned, externally peer-reviewed.The authors declare that there is no conflict of interest regarding the publication of this paper.


Faults are generally represented in conventional upscaled models as 2D planar surfaces with transmissibility multipliers used to represent single-phase fault properties. However, faults are structurally complex 3D zones in which both single-phase and two-phase fault rock properties can be significant. Ignoring this structural and petrophysical complexity within faults may impart considerable inaccuracy on the predictive performance of upscaled models. This study has developed a two-phase flow-based geometrical upscaling method capable of representing simultaneously the complex geometry and saturation-dependent two-phase flow properties of realistic fault zones. In this approach, high-resolution sector models are built of small portions of the fault zones and assigned appropriate single-phase and two-phase fault rock properties. Steady state two-phase flow simulations at different fractional flows of oil and water are used to determine the saturation dependent upscaled pseudo relative permeability functions which are incorporated into upscaled models. The method is applied to an example model containing two 3D fault zone components and tested by comparing the flow results of upscaled model with those of a high-resolution truth model. Results show that two-phase flow-based geometrical upscaling is a promising method for representing the effects of two-phase fault rock properties and complex 3D fault zone structure simultaneously. Both single-phase and two-phase fault rock properties sometimes need to be considered in flow modeling. The single-phase fault rock properties of interest in production flow simulation models of conventional clastic reservoirs are the absolute permeability and thickness of the fault rock. A geologically meaningful method to include these properties as transmissibility multipliers was developed by Manzocchi et al.7. Attempts have been made to circumvent this restriction. For example, Al-Busafi et al.5 presented a workflow to represent two-phase fault rock properties using local grid refinements and have shown that two-phase fault rock properties are more influential than the single-phase ones for a compartmentalized gas reservoir produced by gas expansion. Zijlstra et al.14 introduced a simple approach called "capillary entry height" method to incorporate two-phase effects by modifying single-phase multipliers. This method was developed for gas reservoirs in the Southern North Sea produced by gas expansion and is inappropriate for oil reservoirs produced by waterflooding. The present study applies the method developed by Manzocchi et al.11, in which the effects of two-phase fault rock properties are included in directional, irreversible upscaled relative permeability functions attached to the grid-blocks adjacent to faults. This method is summarized in Fig. Two-phase fault rock properties are difficult to include in a flow simulation model because they depend on the water saturation of the fault rock which changes over the course of the simulation run. Since faults are usually included in flow models as zero-volume interfaces between grid-cells, there is no explicit definition of water saturation to which the two-phase fault rock properties can be indexed and this is the source of the difficulty in including them16. The intervening fault lenses are generally too small to be imaged on seismic but can provide across-fault and along-fault flow paths that are not present if the fault is simplified to a single surface. In the case of laterally compartmentalized or vertically heterogeneous reservoirs with low kV/kH ratios, these may significantly affect reservoir production17. Two types of approach have been proposed to represent three-dimensional fault zone structure in full-field flow simulation modeling: representation of the fault zone geometries using local grid refinements18 or representation by upscaling11. This study considers a type of upscaling called “geometrical upscaling”, which is defined as the process of capturing the transmissibilities of all the tortuous flow paths within, across and along the components of the fault zone, and representing them in the simulation model as neighbor and non-neighbor connections20.In addition to the usual practice of omitting two-phase fault rock properties, another simplifying aspect of fault inclusion in conventional flow simulation models is the representation of faults as single planar surfaces accommodating all the fault offset. In reality, fault zones are complicated three-dimensional volumes containing numerous subordinate fault segments each accommodating a portion of the total fault offset11, but combining them to upscale two-phase fault rock properties and fault zone structure simultaneously via two-phase geometrical upscaling has not previously been attempted. This paper addresses the technical challenges associated with doing this using a simple model of a single fault  range between about 10–1000 mD and kv/kh ratio is 0.0001, porosity ranges about 3–50%, and net-to-gross ranges about 2–90%, based on a correlated random field modeled independently in each of the five layers using Schlumberger's Petrel software22. The oil and water relative permeability functions  of 0.001 mD and a thickness (tf) modeled as a constant ratio of fault throw , using the expression, tf = D/170. These single-phase fault rock properties are included in the truth model as transmissibility multipliers calculated in the TransGen software24 following the procedure defined in Fig. 11, for a connate water saturation of 0.8. As explained in introduction section, two-phase fault rock properties cannot be included directly in a flow simulation model without an explicit representation of the fault as grid-cells since these properties are tied to the water saturation of the fault rock. Hence, Manzocchi et al.7 devised a procedure for upscaling the two-phase fault rock properties and representing them as directional, irreversible pseudo-relative permeability curves attached to the cells upstream of faults  when compared to the truth model. Interestingly, Manzocchi et al.21 and TransGen24 have been used for these steps). Additionally, many hundreds of individual flow simulation models must be run to derive the two-phase upscaled properties of the sector models for inclusion in the final upscaled relative permeability functions that include both fault zone geometry and fault rock properties. None of these steps are particularly intensive computationally  but, because there are many steps and models, automating the workflow would be challenging.An important factor that should be considered in any attempts to apply this new method to a full-field scale model is its complexity. The workflow developed involves many different steps Fig. , includiThis study has defined and tested a procedure for upscaling the geometry of three-dimensional fault zones and the single-phase and two-phase petrophysical properties of associated fault rocks, to the resolution at which faults are generally represented in full-field flow simulation models of conventional clastic reservoirs . The new approach combines previously defined methods for (1) single-phase flow-based geometrical upscaling of fault zones and (2) two-phase upscaling of fault rocks. A series of flow simulation models are run at different fractional flow rates using injector and producer wells located in different model layers within sector models of the fault zone. Results of these models allow calculation of pseudo-relative permeability functions of across-fault non-neighbor connections as a function of the water saturation of the up-stream grid blocks. These upscaled two-phase functions supplement the transmissibility values calculated for the same flow paths using the single-phase flow-based geometrical upscaling approach. A comparison of the flow responses between a truth model and a model upscaled with the newly developed method shows that the proposed method provides an 84% solution to the problem, since a model including the two-phase upscaled properties is 84% closer to the truth model than it is to a model that includes only single-phase fault zone properties.11, and the single-phase flow-based geometrical upscaling method developed by Islam and Manzocchi10. Single-phase geometrical upscaling is concerned with determining the transmissibilities of flow paths through complex three-dimensional fault zones  and the individual across-fault transmissibilities calculated for each flow path in Step 1 . Results of Step 3 are shown in Fig. In this equation, T10). The main difference is that instead of running one single-phase simulation model to deduce the transmissibilities of multiple flow paths out of a single cell , and the across-fault transmissibility (T3) calculated in Step 1, to determine water and oil pseudo-relative permeability values  and pseudo-relative permeabilities functions  for 50 across-fault flow paths  and water-phase  pressures in this cell are known (Fig. 30 have concluded that it is most appropriate to use the original unaltered capillary pressure curve rather than an upscaled one, and this is the approach taken in this study.As well as calculating upscaled pseudo-relative permeability functions for each connection out of the upstream cell containing the injector well, the two-phase flow-based geometrical upscaling method is capable of calculating an upscaled pseudo-capillary pressure function for the cell following the Kyte and Berryown Fig. c. Howeve


The ongoing COVID-19 crisis due to the SARS-Cov-2 virus gained a pandemic status on March 11th, 2020 . It led Robot assisted laparoscopic surgeries (RAS) have revolutionized urological cancer care. The da Vinci surgical system  was approved by US FDA on July 2000 and the first robotic surgery for Urological cancers in India was performed in All India Institute of Medical Sciences, New Delhi way back in July 2006 in the form of a Robotic Radical prostatectomy . Since tThere are some major concerns surrounding minimally invasive surgeries that include laparoscopy and robotics during the pandemic. These surgeries involve abdominal insufflation with CO2, which increase intra-abdominal pressure and thus may increase the generation of aerosol leading to the risk of contamination with COVID-19 virus to the surgical team. The robotic surgeries can safely be performed with intra-abdominal pressure at 5mm of Hg using an intelligent integrated flow system , as compared to traditional laparoscopy, which requires a pressure of 10-15 mm of Hg thus RAS can reduce contamination risk by reduced aerosol generation . HoweverMachine learning and AI platform from the data generated from the newer surgical robotic systems may pave in the way for autonomous robotic system in the future . ResearcThe mortality from COVID-19 infection is around 2-3%, but due to the delay in diagnosis and treatment the mortality from different cancers have increased significantly during the pandemic . We know


Immunotherapy of cancer using chimeric antigen receptor-engineered T-cells has transformed the management of selected haematological malignancies, triggering intense clinical trial activity in this arena. This article summarises trial activity that has been published to date across the spectrum of haematological and solid tumour types. In recent years, we have witnessed a paradigm shift in cancer treatment with the advent of effective immunotherapies for both haematological and solid cancers. Alongside traditional therapeutic modalities, immune checkpoint inhibitors, and cell-based therapies are increasingly being used in mainstream clinical practice. In what would have been an unthinkable development some 20 years ago, cell-based immunotherapies have now become the largest area of drug development in immuno-oncology. Moreover, it is particularly noteworthy that the largest year on year increase in this activity has involved the Chimeric antigen receptors (CAR) T-cell sector .CAR T-cells are synthetic receptors that bind one or more native cell surface target(s), obviating the need for human leukocyte antigen (HLA)-dependent antigen presentation or restriction. While this limits targeting potential to the subset of proteins found on the cell surface, CAR specificity can also be directed against non-proteinaceous antigens (e.g. tumour-associated gangliosides) or peptide/HLA complexes. The first CAR was described over 30 years ago and entailed the substitution of the variable domains of an antibody heavy and light chain for the corresponding regions within an α β T-cell receptor (TCR) heterodimer . Eshhar Clinical development of CAR T-cell immunotherapy was pioneered in the USA, at a speed reminiscent of the space race. Intense clinical trial activity at multiple centres was initiated on the back of encouraging early case reports which demonstrated the therapeutic promise of CD19-specific second-generation CAR T-cells against B-cell malignancy , 6. The Given the ever-increasing number of clinical trials involving CAR T-cell immunotherapy of cancer, we set out here to capture published studies in a simple tabular format. Had this task been undertaken 10 years ago, a very short list indeed would have been generated. In total, we identified more than 150 CAR T-cell clinical trials that involved a minimum of six patients (published in abstract or full manuscript format) and these are presented chronologically in Solid tumours represent the bulk of human cancers and represented the primary focus of early CAR T-cell clinical trial activity. However, even with the advent of second-generation CAR systems, we have only seen sporadic responses in a small number of patients. While the list of targets under study in B-cell and plasma cell malignancy is limited, there is much greater diversity in target selection in solid tumour-based clinical trials. This sub-optimal efficacy justifies the need for additional innovation around CAR design, the nature and fitness of the cellular host, and complementary use of additional interventions that may help to render the tumour microenvironment more favourable.An important enabling attribute of CAR T-cell technology is the tremendous potential for innovation around this highly modular framework. Illustrating this, we are seeing the emergence of many switchable systems in which a universal CAR-engineered cell is utilised in combination with a bridging molecule that confers the desired tumour antigen specificity. A range of drug controllable, logic-gated, and split-signalling CAR systems are also in development that offer the potential to improve therapeutic specificity and control. A further key point is the compatibility of CAR technology with other cutting-edge innovations. These include genome editing technologies, systems to precisely modulate host cell gene expression, cytokine armouring approaches and potential for metabolic manipulation and modulation of epigenetic properties of host cells.The landscape of clinical CAR T-cell immunotherapy continues to evolve rapidly. Recently, there has been a tremendous expansion of clinical CAR T-cell activity in China, which overtook the USA in 2017 as the country with the greatest number of registered CAR T-cell clinical trials . A cursoImmunotherapy using CAR-engineered immune cells has emerged as a transformative therapeutic intervention for human cancer and is now increasingly under study in other disease arenas, such as autoimmunity and transplantation. We look forward to the increasing clinical translation of these flexible and transformative therapies in the coming years.ltab004_suppl_Supplementary_Table_1Click here for additional data file.


Sudden sensorineural hearing loss (SSHL) is a common otolaryngology emergency that significantly affects the patient’s quality of life. Although in most cases its etiology remains unknown (idiopathic SSHL), viral infections and vascular compromise constitute the most widely accepted etiopathogenic mechanisms. Specifically, occlusion of the internal auditory artery has been reported in cases of sudden deafness. Thrombotic events following the Oxford-AstraZeneca COVID-19 vaccine are rare. There have been reports of SSHL following immunization with Pfizer and Moderna COVID-19 vaccine; however, no etiologic relationship has been established between the two entities yet. We present a unique case of SSHL following the second dose of the Oxford-AstraZeneca COVID-19 vaccine. A 61-year-old female was referred to our department with a four-day history of the right-sided sense of fulness combined with almost complete hearing loss that had started two days after the second dose of Oxford-AstraZeneca COVID-19 vaccine. Pure tone audiometry showed profound right-sided sensorineural hearing loss. Magnetic resonance imaging of the brain and internal auditory canal and magnetic resonance angiography were both normal. The combination of glucocorticoids and acetylsalicylic acid leads to almost full recovery 15 days after deafness. The COVID-19 era is full of new challenges and clinical dilemmas. In our case, the addition of acetylosalicid acid to the patient’s initial treatment may have contributed to the hearing restoration; however, this fact will remain a hypothesis. Sudden sensorineural hearing loss (SSHL) is defined as the rapid onset of hearing of at least 30 dB across three consecutive frequencies occurring within a period of 72 hours based on the US National Institute for Deafness and Communication Disorders (NICDC) . Its annVascular compromise due to hemorrhage, thrombosis, and vasospasm in the inner ear vessels may lead to cochlear ischemia and potentially SSHL . HoweverA 61-year-old female was referred to our Department with a four-day history of the right-sided sense of fulness combined with almost complete hearing loss that had started two days after the second dose of Oxford-AstraZeneca COVID-19 vaccine. She did not report any history of earache, trauma, or discharge. Hearing loss was not accompanied by tinnitus or vertigo. She had a medical history of hypertension, dyslipidemia, and Hashimoto's thyroiditis all under medical treatment. None of her prescribed medication had been commenced within the previous six months. She denied tobacco use or alcohol consumption.Otoscopy was unremarkable on both sides. Weber tuning fork test lateralized to the left ear while Rinne test was positive on both sides. Pure tone audiometry showed profound right-sided SSHL of at least 85 dB in every frequency  Figure .The initial routine diagnostic workup did not reveal any abnormal findings.The patient received systemic intravenous glucocorticoids (Dexamethasone 8 mg three times per day for three days with tapering over a week). However, due to her recent history of vaccination with Oxford-AstraZeneca COVID-19 vaccine, neurologists and internists were asked to assess the patient. Anticoagulant therapy with 100 mg of acetylsalicylic acid once daily was commenced. The hearing was evaluated every two days with new pure tone audiometry, which did not reveal any remarkable improvement. One week after treatment initiation, magnetic resonance imaging (MRI) of the brain and internal auditory canal and magnetic resonance angiography (MRA) were conducted. Both imaging tests were normal Figures -2C.The patient was discharged from the hospital after seven days and was prescribed a nine-day course of oral glucocorticoids and acetylsalicylic acid. After completing the treatment, the patient returned to our Audiology Clinic for a new pure tone audiogram. The patient reported significant improvement in her hearing (15 days after deafness onset and 11 days after initiation of treatment). The new audiogram showed a significant increase in her threshold   provides effective immunization against SARS-CoV-2 in the general population . HoweverIn the USA, a Johns Hopkins study concluded that COVID-19 vaccines are not associated with an increased risk for SSHL, based on the evaluation of 40 cases  of confirmed SSHL among 86,553,330 vaccinations. The incidence of SSHL following the COVID-19 vaccination was estimated to be 0.3% and not only did it not exceed that of the general population, but it could be deemed lower [The COVID-19 era is full of new challenges and clinical dilemmas. A case of SSHL two days after the COVID-19 vaccination should be evaluated carefully and should not be dismissed as a coincidental event. The addition of acetylosalicid acid to the patient’s initial treatment may have contributed to the hearing restoration; however, this fact will remain a hypothesis, as no objective test can ascertain the occlusion of such a microcirculation.


Within 5 years after curative surgery for stage II colon cancer 25% of patients will relapse due to minimal residual disease (MRD). MRD is the net result of the biological properties of subpopulations of primary tumour cells which enable them to disseminate, implant in distant tissues and survive and the immune system’s ability to eliminate them. We hypothesize that markers of immune dysfunction such as the systemic inflammation index (SII) are associated with the sub-type of MRD defined by bone marrow micro-metastasis (mM) and circulating tumour cells (CTCs). A higher immune dysfunction being associated with a more aggressive MRD and worse prognosis. Blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti-CEA one month after surgery. The SII, absolute neutrophil, platelet and lymphocyte counts  were determined immediately pre-surgery and one month post-surgery. These were compared with the sub-types of MRD; Group I MRD (-); Group II mM positive and Group III CTC positive; cut-off values of SII of >700 and >900 were used. Follow-up was for up to 5 years or relapse and survival curves using Kaplan-Meier (KM) were calculated. One hundred and eighty one patients (99 women) participated, mean age 68 years, median follow up 4.04 years; I: = 105 patients, II: N= 36 patients, III: N=40 patients. The SII significantly decreased post-surgery only in Group I patients. The frequency of SII >700 and >900 was significantly higher in Group III, between Groups I and II there was no significant difference. The SII was significantly associated with the number of CTCs detected. The 5-year KM was 98% Group I, 68% Group II and 7% Group III. The results of the study suggest that the severity of immune dysfunction as determined by the SII is associated with differing sub-types of MRD and a worse prognosis; increasing immune dysfunction is associated with a more aggressive CTC positive MRD sub-type; a more severe immune dysfunction is associated with a higher number of CTCs detected. Stage II patients have been classified as low or high risk based on the pathological findings in the surgical specimen; high risk tumours have been classified as having one or more of the following features; stage pT4, poorly differentiated tumour; intestinal perforation; lympho-vascular / peri-neural invasion; a high number of lymph nodes examined and positive surgical margins . The overall survival rates vary significantly in stage II colon cancer patients, from 66.7% in those patients with stage IIA to 45.7% in those with stage IIC .Colon cancer is the fourth most common cancer worldwide, representing 6.1% of all cancers and is the third commonest cause of cancer mortality in males and females . Stage II colon cancer as defined by the American Joint Committee on Cancer . The presence of MRD depends on two principal factors; firstly the biological characteristics of differing tumour cells within the primary cancer, that is their ability to disseminate, survive in the circulation, implant in distant tissues and survive in their new environment. Secondly the ability of the host immune response to eliminate these disseminated tumour cells. Three groups of MRD can be identified, those patients positive for bone marrow micro-metastasis have an increased risk for delayed relapse, those with circulating tumour cells (CTCs) detected in blood are at high risk of early treatment failure and finally those patients negative for both have a very high 5-year disease free survival .The systemic immune-inflammation index (SII) has been proposed to reflect the balance between pro-tumour inflammation and anti-tumour immune function such as T-cytotoxic lymphocytes and thus serve as an index of host immune status . It is based on the absolute peripheral neutrophil, lymphocyte and platelet counts and calculated using the formula SII=(N x P/L) where N= absolute neutrophil count, P= absolute platelet count and L=absolute lymphocyte count. An elevated SII is the result of either an increased neutrophil and /or platelet count or a decrease in the lymphocyte count. In the published reports a high serum SII was associated with an unfavourable prognosis, a decreased to time to relapse and decreased progression free (PFS) and overall (OS) survival . We present the hypothesis that immune dysfunction as determined by an altered SII is associated with a more aggressive sub-type of MRD and thus is one reason for a worse prognosis. The study was designed to determine if the SII pre and post-surgery was associated with the sub-type of MRD and patient outcome.A prospective observational single centre study of consecutive patients referred for evaluation of minimal residual disease between January 2007 and December 2014 and who complied with the following inclusion criteria: Pathological Stage II colon cancer, negative surgical margins, negative CT scan of thorax, abdomen and pelvis for metastasis. The study complied with the STROBE guidelines on cohort studiesFor each patient, after giving written informed consent, the following were recorded; age, sex, date of surgical treatment, depth of primary tumour invasion (T), and nodal infiltration (N) of the TNM classification . Lympho-vascular and peri-neural infiltration in the primary tumour was recorded as present or absent and the grade of differentiation recorded as well, moderate or poor.CTC detection®, USA). The samples were transported at room temperature and processed within 24 hours.Blood samples were collected one month after curative surgery; the first 5ml was discarded to prevent possible contamination by epithelial cells and the second 8ml was collected into tubes containing EDTA  according to the manufacturer’s instructions and re-suspended in 100μl of autologous plasma. 25μl aliquots of cell suspension were used to prepare 4 slides , air dried for 24 hours and finally fixed using a solution of 70% ethanol, 5% formaldehyde and 25% phosphate buffered saline (PBS) pH 7.4  for five minutes and washed twice with PBS.Mononuclear cells were obtained using differential gel centrifugation with Histopaque 1,077The slides were processed within one hour of fixation and incubated with monoclonal anti-CEA clone 11-7  for one hour at room temperature. CTCs were identified using an alkaline phosphatase-anti-alkaline phosphatase based system  with neofuschin as the chromogen. Positive samples underwent a second process using anti-CD45 clone 2B11 + PD7/26 ; incubated for one hour at room temperature and identified using a peroxidase based system  with DAB  as the chromogen.A CTC was defined according to the morphological criteria of ISHAGE , as a nucleated cell expressing CEA but not CD45. A positive test was defined as the detection of at least one cell/8ml venous blood  and 2.Bone marrow micro-metastasis detectionUsing sedation with intravenous midazolam and anaesthesia local with 2% lidocaine a bone marrow biopsy was taken from the posterior superior iliac crest one month after surgery and the sample used to prepare four ”touch preps” using sialinized slides . All four slides were processed as described for CTCs, a micro-metastasis was defined as cells staining positive for CEA and negative for CD45  and 4.The patients were divided into three MRD sub-groups according to the presence or absence of CTCs and bone marrow micro-metastasis. Group I negative for both CTCs and micro-metastasis patients; Group II CTC negative, micro-metastasis positive; Group III CTC positive with or without bone marrow micro-metastasis detected.Systemic Inflammatory IndexA full blood count was taken at the same time as the same for CTC analysis and the absolute neutrophil, platelet and lymphocyte counts were determined  and the SII calculated as the absolute neutrophil count x absolute platelet count/absolute lymphocyte count. A cut off value of >700 and >900, based on previously reported studies, was used to analyse the differing parameters .Follow-upPatients were followed up three monthly for the first 2 years, then six monthly until five years. Relapse was defined as a new lesion detected on CT scanning of thorax, abdomen or pelvis. The patients were followed up until 5 years or until relapse, the date of the CT scan detecting relapse was used to define the time to treatment failure. Patients were censured at the time of relapse or after 5 years of disease free progression.Study end point: The primary study end point was the presence of treatment failure defined as a positive imaging study using CT scanning of the thorax, abdomen and pelvis. The secondary end point was the restricted mean time to failure after primary treatment defined as the time from surgery to the first appearance of an image consistent with metastasis on CT scanning.Statistical AnalysisThe analysis was performed using the program Stata , describing according to the nature and distribution of the quantitative and ordinate variables with measurements of central tendency (mean and median) and of dispersion using the inter-quartile range (IQR) and standard deviation (SD). The Shapiro-Wilk Test was used to define the null hypothesis with respect to the normal distribution. The nominal dichotomous variables were described as proportions with their respective confidence intervals.The three MRD prognostic groups were compared for age, sex, primary tumour differentiation, lymphovascular infiltration, peri-neural infiltration and serum CEA pre-surgery. The Kruskal–Wallis test was used to test whether samples originated from the same distribution and the Pearson’s chi-squared test was used to compare frequencies between MRD sub-groups. A p value <0.05 was taken to signify statistical significance and all tests were two tailed. A SII cut-off value of 700 and 900 was used to determine high and low risk patients and compare with the different clinical-pathological and MRD parameters.A nonparametric survival analysis was performed at three and five years of follow-up to determine the DFS (Kaplan-Meier) and median DFS of the whole cohort and by MRD sub-groups. The Restricted Mean Survival Time (RMST) for treatment failure was determined for five years of follow-up for the whole cohort and by prognostic group. The RMST establishes the expected time to relapse during the 5-year observation period and its value is the area under the Kaplan-Meier nonparametric survival curve . Ethical Considerations: The study was approved by the local ethics committee and all patients signed written informed consent.One hundred and eighty one patients participated in the study between January 2007 and December 2014; the last follow up was completed in October 2018. The minimum and maximum follow up times were 0.6-5.0 years with a median of 4.0 years (IQR 2.7 years). 82 (46%) of the cohort were male and the median age for the study population was 68 years (IQR 16 years). The median SII was 753 (IQR 551-1135) and 667 (IQR 449-996) pre and post surgery respectively with no significant difference between pre and post-surgical values for the cohort as a whole (p=0.54). One hunded and five patients (58%) formed Group I, 36 patients (20%) Group II and 40 patients (22%) Group III. Of the study group 53 (29%) patients relapsed. There were no significant differences between the median SII pre or post-surgery when comparing patients who relapsed with those who did not; 870 (IQR 538-1224) versus 753 (565-1029) (p=0.11) pre-surgery and 919 (IQR 530-1090) versus 618 (380-910) (p=0.72) post-surgery respectively.Association of SII and MRD and MRD There were no significant differences in the median SII when comparing pre and post-surgery values for each MRD sub-group. Nor was there a significant difference in the median SII between the different MRD subgroups pre-surgery. However, one month post-surgery there were significant differences in the SII between MRD subgroups.Patients in Group III had a significantly higher median SII post surgery than either Group I 947 versus 617 (p=0.04) and Group II 947 versus 687 (p=0.03) respectively. There was no significant difference between Group I and Group II (p=0.73). In Group III patients the number of CTCs detected was positively associated with the SII; the sub-group with 1-2 CTCs/blood sample had a significantly lower median SII compared with patients with ≥ 3 CTCs/blood sample 739 (IQR 634-1081) versus 1084 (IQR 947-2032) respectively (p<0.05). Using a SII >700 as a cut-off value f value There was no significant difference in the frequency of patients with a SII >700 comparing pre and post-surgery values for each positive MRD sub-type (Groups II and III). However in patients MRD negative, the frequency of patients with a SII > 700 significantly decreased after curative surgery from 41% to 27% (p=0.04). The frequency of patients in Group III with a SII >700 was significantly higher both pre and post-surgery when compared to Groups I and II; there was no significant difference between Groups I and II.Using a SII > 900 as a cut-off value f value There was no significant difference in the frequency of patients with a SII >900 comparing pre and post-surgery values for each positive MRD sub-type (Groups II and III). However in patients MRD negative, the frequency of patients with a SII > 900 significantly decreased after curative surgery from 35% to 21% (p=0.03). The frequency of patients in Group III with a SII >900 was significantly higher both pre and post-surgery when compared to Groups I and II; there was no significant difference between Groups I and II.Disease free progression survival according to MRD sub-typeMRD is the net result of the biological characteristics of the primary tumour cancer cells and the immune response to cancer. The primary tumour not only is the source of disseminated tumour cells but also is responsible for preparing the pre-metastatic niche  and modulating the host immune system (Whiteside. 2013). Even in stage IV disease removal of the primary tumour has been reported to increase overall survival and decrease or normalize immune dysfunction . In this study of stage II patient’s removal of the primary tumour did not significantly change the SII in the cohort as a whole, nor was there a significant difference in the SII of patients who relapsed compared with those who did not. Pre-surgery there was no significant difference in the SII between MRD sub-groups. This could be explained by the fact that the effect of the primary tumour on the SII was much greater than whatever effect caused by the presence of disseminated tumour cells. However, post surgery where the effect of the primary tumour had been eliminated revealed significant differences in the SII between MRD sub-groups. In Group I MRD negative patients the SII significantly decreased following surgical resection, this was not seen in Groups II and III. This suggests that residual micro-metastatic tumour cells are still able to exert an immunosuppressive effect as seen by an unchanged SII. Comparing MRD subtypes with the SII, Group III (CTC positive MRD) patients had a significantly higher SII when compared with MRD negative (Group I) and patients with micro-metastasis positive MRD (Group II). This suggests that the immune dysfunction is significantly worse in CTC positive patients, whereas those with only micro-metastasis had a similar immune function as in MRD negative patients. This was similarly seen in the frequency of patients with a SII higher than 700 and 900. Group III patients had the worse progression free survival and shortest mean time to disease progression. Both a higher SII  and the presence of CTCs  have been reported to be associated with a worse prognosis. An association between immune dysfunction and the number of CTCs has been reported in patients with metastatic breast cancer  but not in patients with colon cancer. The results presented here imply that immune dysfunction and the presence of CTCs is associated, with increasing immune dysfunction being associated with an increased number of CTCs. The resulting immune dysfunction caused the presence of residual tumour cells permitting the escape of CTCs from immune destruction. However, patients with only micro-metastasis had a similar SII as MRD negative patients, this suggests that the biological properties of these tumour cells were unable to produce immune dysfunction as in Group III patients. From the Kaplan-Meier survival curves it can be seen that Group II patients have a similar survival curve as Group I patients for the first two years after surgery. Thus it may not be surprising that one month after surgery the SII values were similar. Although beyond the scope of this study it is possible that with time immune dysfunction increases, as a result of clonal evolution of the tumour cells and thus permits disease progression. Differing from Group I patients, in Group II patients there was no decrease in immune dysfunction as a result of surgical resection, implying that although the micro-metastasis were able to maintain the immune dysfunction it was not sufficient to cause the appearance of CTCs. In breast cancer it has been reported that there is a correlation between the number of disseminated tumour cells detected in bone marrow and T-cell dysfunction, possibly through the production of immunosuppressive cytokines . This immune dysfunction may permit the survival of micro-metastasis without causing disease progression, this is clinically termed dormancy where the patient is asymptomatic and with no evidence of disease but later relapses. In experimental mouse models the ablation of T-lymphocytes accelerates the re-activation and proliferation of disseminated tumour cells and subsequent development of metastasis . This may explain why the presence of bone marrow micro-metastasis arte associated with a worse outcome in stage I-III colon cancer .It is important to acknowledge the limitations of the study; firstly, we used an in house method for the detection of CTCs. The detection of CTCs is method dependent, the frequency of CTCs detected in patients with localized colon cancer using the EpCAM  based CellSearch® system has been reported to be between 5-25%  whereas the size based Metacell® system detected CTCs in 80% of stage II patients . Comparing flow-cytometry, CellSearch®, quantatitivereal time PCR and cytomorphology, cytomorphology ® CTCs were detected in 75% versus 20% respectively and only 14% using gene mutation analysis . The method we used would not detect CEA negative CTCs and bone marrow micro-metastasis but has the advantage of being relatively cheap and although it is 10-100 fold less sensitive than RT-PCR based methods it could be implemented in the routine laboratory of a general hospital. We suggest that the sensitivity may not be a limiting factor, the important question is clinical utility. As yet, independent of the method used to detect tumour cells, there is not an established lower limit of detection with regards to predicting future relapse. Detecting every cancer cell may not be important; patients post allogeneic bone marrow transplantation for leukemia may have very small numbers of leukemic cells detected by RT-PCR in bone marrow samples but remain in remission for many years. Furthermore these leukemia cells may survive for prolonged periods before being eradicated by host defenses . As such ultra-sensitive methods to detect tumor cells may over-estimate clinically important minimal residual disease in patients with solid tumours. The method we used was manual and thus inter- and intra-observer variability is higher when compared to automatic or semi-automatic methods. For this reason we used a postive-negative based classification system rather than a cut-off value of x CTCs/sample as used, for example, in the CellSearch® system to limit this potential variability. showed the least sensitivity and specificity in detecting CTCs, there were no significant differences between the other three methods . Comparing RT-PCR with CellSearchIn conclusion, the results of the study suggest that a) the different sub-types of MRD have differing PFS and mean times to treatment failure, corresponding to early and late failure.; b) the severity of immune dysfunction as determined by the SII is associated with differing sub-types of MRD and a worse prognosis; c) increasing immune dysfunction is associated with a more aggressive MRD sub-type, that of CTC positive MRD. Higher numbers of CTCs detected are associated with a more severe immune dysfunction and d) that immune dysfunction has an important role in the type of MRD and prognosis of patients with stage II colon cancer. These results warrant further studies in a larger number of patients.Concept - N.P.M.; Design - N.P.M. RV; Supervision - N.P.M., RV.; Resources - N.P.M.; Materials - N.P.M., RV; Data. Collection and/or Processing – RV, EG, SO,; Analysis and/or Interpretation - N.P.M., RV.,; Literature Search-SO, EG,; Writing Manuscript-NPM, RV,; Critical review-SO, EG,; Final Approval- NPM,; RV,; SO,; EG.


This study evaluated the efficacy of a 10-hour intergenerational service-learning program administered to undergraduates to determine if it would increase knowledge about aging, improve attitudes about older adults, and reduce ageism more than a course with less service-learning activity. Making maximum impact on students in these areas in a short amount of time is particularly relevant in short, quarter-based university programs. A quasi-experimental design using a convenience sample compared pre-test and post-test scores between an experimental intervention (N=68) and a comparison (N=71) group on The Facts on Aging Quiz Multiple Choice version, Aging Semantic Differential, and Fabroni Scale on Ageism. Qualitative data via open-ended survey questions was also collected. The experimental intervention, the Lives Well Lived project, was based on a documentary film by the same name, which incorporates themes of successful aging. During the project students and older adults interviewed one another about living a life well lived, participated in a photo shoot, and created a Memoir for the older adult. The comparison group included two social visits to a congregate meal program. Results from multiple regression analysis showed that students in the intervention group had less ageist stereotypes and less negative bias about aging at post-test and qualitative data indicated they were more inclined to participate in intergenerational relationships in the future. Programs like this one that are longer and more relational may be useful for consideration in undergraduate gerontology courses in reducing ageism and promoting intergenerational relationships which benefit those of all ages.


The unique anatomy and flexibility of the cervical spine predispose it to a risk of injury. Trauma to the cervical spine encompasses a wide range of injuries from minor muscular strains to life-threatening fracture-dislocations associated with spinal cord lesions. Initial assessment and management should follow the Advanced Trauma Life Support (ATLS) protocols with adequate protection of the cervical spine through triple immobilisation to prevent any unnecessary movement, which can make the patient susceptible to further neurological injuries. Although the presence of cervical spine injury is very often overt, reliance on clinical examination alone is sometimes not sufficient and potentially requires further imaging. Clinical decision rules such as the Canadian C-Spine Rule are frequently used to risk-stratify patients needing radiography. The level of cervical spine instability and knowledge of their unique classification systems is of paramount importance and assists in the decision-making process to guide definitive management. In this review, we also propose an algorithm to aid the initial management of a patient with suspected cervical spine injury in the emergency department. Cervical spine (C-spine) trauma constitutes a variety of injuries ranging from relatively mild ligamentous and muscular strains to fractures and dislocations of the bony vertebrae, which can result in significant spinal cord injuries (SCIs). C-spine injuries account for half of all spinal injuries, with approximately 500-600 people enduring acute traumatic SCIs every year in the United Kingdom . SpecialC-spine injuries are sustained following low-energy incidents such as a simple innocuous fall to higher energy traumas, such as in motor vehicle accidents. Passias et al. showed that motor vehicle accidents were the most prevalent cause in the United States, responsible for 29.3% of C-spine fractures and most frequently occurring at the C2 (32.0%) and C7 (20.9%) levels [Initial assessment of suspected C-spine fracturePatients with suspected C-spine fracture are invariably managed in the pre-hospital setting with the application of a rigid brace to the C-spine (hard collar) in a neutral position to achieve cephalic immobilisation and keep the spinal column ‘in-line’ in order to prevent undue movement.On presentation to the emergency department, any suspected C-spine fracture patient should be assumed to have a C-spine injury until proven otherwise. A detailed history, from either the emergency crew or the conscious patient, is of paramount importance and should be solicited whenever possible prior to clinical examination. The history should aim to elicit the type of trauma (high energy v/s low energy), mechanism of injury, and the presence, onset and progression of any neurological or physical symptoms including consideration of any factors that may impair the patient’s ability to recall the sequence of events.The goal of the initial assessment of suspected C-spine fractures is the prompt recognition and identification of the primary injury and adequate protection of the C-spine to prevent subsequent neurological deficit. While unconscious patients are primarily assessed using trauma CT series , initial assessment of the conscious, suspected C-spine fracture patient should be performed using a prioritising sequence based on the Advanced Trauma Life Support (ATLS) protocols. The ATLS algorithm begins with maintenance of the airway with restriction and stabilisation of the C-spine using triple immobilisation technique with a hard collar, sandbags, head blocks and tape anchored to the trolley.Once the C-spine and airway has been secured, next steps include assessment of breathing for adequate oxygenation followed by circulation for satisfactory perfusion. Systemic hypotension due to haemorrhagic or neurogenic shock is often a complication and sign of SCIs . This shReliance on clinical examination of the C-spine alone is not sufficient to diagnose any secondary or unrecognised injuries to the C-spine, and imaging is required to allow identification of further clinically relevant injuries. In accordance with the National Institute for Health and Care Excellence (NICE) guidelines, suspected cervical trauma patients in hospital are risk-stratified for cervical spinal injury using the Canadian C-Spine Rule (CCR) . The CCRRadiographs used in the CCR studies included plain films, but imaging of the C-spine has since evolved from plain films to CT scans. CT scan not only provides good visualisation, especially of the transitional zones  as compared to standard radiographs, but also has a high sensitivity of about 87.5% for any C-spine lesion and sensitivity of about 100% for any unstable lesion [Initial management of a patient with C-spine fracturesThe management of C-spine fractures is guided by the severity of the fracture. The urgency of treatment is dependent on life-threatening airway, respiratory or circulatory compromise along with the presence of a neurological lesion and/or instability. Thus, appropriate initial management plays a crucial role in dictating the long-term prognosis of patients with C-spine fracture.Patients with C-spine fracture require early and effective analgesia to control pain in the acute setting. The NICE guidelines advocate the use of intravenous morphine as the first-line analgesic, wherever appropriate, or intra-nasal diamorphine or ketamine if intravenous access has not been established . The maiThe application of a cervical collar while a decision is being made is not without complications, which include increase in cerebrospinal fluid pressure, skin ulceration, reduced tidal volume and dysphagia . AdditioC-spine fractures can often result in anatomic displacement and instability, which is described as the loss of ability of the spine under physiological loads to maintain its pattern of displacement . A highePatients with cervical injuries are particularly at risk of cardiorespiratory compromise. High cervical injuries C1 to C5) are especially prone to deterioration, which can lead to respiratory depression and carbon dioxide retention as a result of diaphragmatic function insufficiency. Respiratory compromise, which can develop within the first 5 days secondary to ascending oedema, is the principal cause of death in patients with SCI . Therape are espeDefinitive treatment focusing on principles of managementThe definitive management of C-spine fractures is primarily guided by the grade of instability conferred by the injury . Any traUnique classification systems are available for fractures occurring in different regions of the C-spine to assist in the decision-making process regarding the most appropriate definitive management. The C-spine can be viewed as two distinct regions owing to their markedly different anatomical structures - the upper C-spine (occiput to C2) and the subaxial or lower C-spine (C3-7).The upper C-spine has a distinct set of articulations enabled by the highly specialised atlas (C1) and axis (C2), which provides a great deal of mobility for the skull. This highly mobile region derives its stability from ligaments, and consequently surgical interventions are frequently required in fracture patterns that disrupt ligamentous integrity.Fracture to the base of the skull or occipital condylar fractures can be classified using the Anderson and Montesano classification system . Type I Atlas (C1) fractures account for 2% to 13% of all C-spine injuries. Although several fracture classification systems for atlas fractures are available , the degree of instability and thus requirement for surgery is determined by the integrity of the transverse ligament of the atlas, which is key in providing stability to the C1-C2 region. Dickman et al. classified transverse ligamentous injuries of the atlas into two types . Type I Axis (C2) fractures include odontoid peg fractures and traumatic spondylolisthesis of the axis (Hangman’s fracture). Anderson and D’Alonzo classified odontoid peg fractures into three subtypes. Type II fractures through the waist of the odonotoid peg have a high rate of non-union, which occurs as a result of disruption to the blood supply. These fractures are subsequently managed operatively with techniques such as posterior C1-C2 fusion or anterior odontoid screw osteosynthesis. Type I (oblique fracture through the odontoid tip) and type III (fracture through the body) injuries can be managed with a cervical collar . HangmanIn the lower or subaxial C-spine C3-7), the ligamentous and bony structures play an equal role in stability . Definit, the ligThe priority in every patient with suspected C-spine injury is to stabilise the C-spine and prevent undue movement which can cause further neurological injury using triple immobilisation as per the ATLS algorithm. Cardiorespiratory compromise, which can arise as a result of spinal shock, should be addressed and managed, while intensive care input must be sought wherever necessary. Urgent reduction of the fracture-dislocation and surgical decompression of the spinal cord may be necessitated to improve neurological outcomes. Definitive management of C-spine injuries is guided by the degree of instability of the fractures and can be addressed conservatively or operatively. Surgical management aims to achieve a balanced stable spine to prevent painful deformity, preservation and improvement of neurological function and facilitation of the rehabilitation process by enabling early mobilisation. The benefits of surgery must be weighed against its potential risks on a case-by-case basis.