Artificial intelligence (AI) is increasingly used in electrocardiography (ECG) to assist in diagnosis, stratification, and management. AI algorithms can help clinicians in the following areas: (1) interpretation and detection of arrhythmias, ST-segment changes, QT prolongation, and other ECG abnormalities; (2) risk prediction integrated with or without clinical variables ; (3) monitoring ECG signals from cardiac implantable electronic devices and wearable devices in real time and alerting clinicians or patients when significant changes occur according to timing, duration, and situation; (4) signal processing, improving ECG quality and accuracy by removing noise/artifacts/interference, and extracting features not visible to the human eye ; (5) therapy guidance, assisting in patient selection, optimizing treatments, improving symptom-to-treatment times, and cost effectiveness ; (6) facilitating the integration of ECG data with other modalities . In the future, AI is expected to play an increasingly important role in ECG diagnosis and management, as more data become available and more sophisticated algorithms are developed. Artificial intelligence (AI) refers to the idea of a computer model that makes decisions using a priori information and improves its performance with experience . In the Cardiovascular diseases (CVD) are the leading cause of death worldwide and have a particularly strong impact among patients with other comorbidities, such as diabetes mellitus or chronic kidney disease . Their pIn 1970, before the authors of this manuscript were born, an AI-based model that analyzed ventricular repolarization abnormalities showed a high correlation with serum potassium levels . Since tThe basis of the detection of ECG abnormalities and arrhythmia diagnosis is the identification of normal versus abnormal individual heart beats and their correct classification into different diagnoses according to ECG morphology. It is challenging and time-consuming to distinguish these heartbeats on ECG and even more in long-duration ambulatory and Holter monitoring as these signals are typically corrupted by noise. AI-powered ECG interpretation has shown promising results, improving detection of arrhythmias, ST-segment changes, QT prolongation, and other ECG abnormalities. In addition, AI can also detect cardiac structural damage, such as myocardial hypertrophy or left ventricular systolic dysfunction.Arrhythmia detection is one of the fields where AI has better shown its value, enabling multi-class arrhythmia detection  with impThe AI-based strategy for the analysis of Holter recordings is faster and at least as accurate as a conventional analysis by electrophysiologists . AcharyaAI detection of ventricular arrhythmia has achieved an accuracy, sensitivity, and specificity of 99.2–98.8% , which iArrhythmia classification performance of AI software can be measured using regular performance metrics, such as false positives, false negatives, true positives, true negatives, accuracy (which is the proportion of examples that were correctly classified), global accuracy, precision , recall (which is the proportion of examples of a certain class that have been predicted by the model as belonging to that class), confidence threshold, area under the receiver operating characteristic curve (AUROC), the area under the precision recall curve (AUPRC), accuracy (defined here as the fraction of correctly classified recordings), F-measure, and in some research challenges a concrete “challenge evaluation metric”. Usually, the metric of choice for most people in AI to measure the performance of neural networks is F1 score. F1 score for a certain class is the harmonic mean of its precision and recall; thus, it is an overall measure of the quality of a classifier. F1 score measure or the average of the F1 values from each classification type is the score used in the PhysioNet/Computing in Cardiology Challenge (CinC), which is an annual platform to gather international competitors for forced development of open-source AI applications for specific ECG diagnosis .Those challenges try to solve relevant clinical problems, such as arrhythmia classification using different lead sets ranging from two to twelve ECG leads amongst the vast amount of twelve-lead ECG recordings in the PhysioNet CinC Challenges 2020 and 2021. They are presently known as the largest freely available repository of standard 12-lead ECG records and consistent annotations for 30 clinical diagnoses of cardiac abnormalities ,47,48,49Those metrics are a simple way to track or compare the performances of different models dealing with the same dataset in controlled environments (binary or multi-class scenarios). Performance results in real-life scenarios may vary depending on the heterogeneity of new data and the ability to generalize as concrete algorithm, the input duration or environments dealing with multi-label classification scenarios. For multi-label scenarios, confusion matrix may be very useful to evaluate performance.Left ventricular hypertrophy AI also has high testing accuracy, precision, sensitivity, and specificity of 0.96–0.97 . AI algoAI algorithms based solely on ECG data can be used for risk prediction. For instance, ECG data from implantable devices can accurately predict electrical remodeling, forecasting the progression from paroxysmal to persistent atrial fibrillation , and a dAI analyses of ECG of patients with ventricular fibrillation have been able to correlate spectral changes with acute cerebral injury, early prediction of mortality, and cerebral performance in comatose survivors after cardiac arrest , currentAI-based risk predictions have been shown to be accurate even in the general population. An ECG AI model has been shown to predict heart failure . Using dDevices in real-time can alert clinicians or patients when significant changes occur according to timing, duration, and situation , laying a promising foundation for real-time computational clinical decision support systems regulated under the umbrella of software as a medical device. In addition, continuous ECG monitoring might detect changes in heart rate associated with medical interventions, such as hemodialysis .AI algorithms can use these ECG data to detect atrial fibrillation or bradycardia and notify patients to seek medical attention and can track ECG changes during exercise, sleep, or stress tests. AI can also be used to accurately monitor QT duration  or to clDifferent commercial and research-based AI solutions are available for ECG monitoring or ECG analysis. Single-lead ECG wearables and smartwatches are increasingly used; some examples include Apple Watch, Kardia (AliveCor), Zio (iRhythm Technologies), BioHarness, Faros 360 (Bittium), CAM , Fitbit AI ECG can enhance the quality and accuracy of ECG recordings by removing noise, artifacts, and interference. Portable and wearable devices often record ECG signals strongly corrupted with noise and artifacts; their signals are particularly attractive to implement AI algorithms. AI algorithms can detect QRS complex  and can AI can be used to perform denoising block, acquiring the ECG signal from the patient and denoising it . AI may Physiological Measurement [A stacked denoising autoencoder based on deep neural networks (DNN) is a powerful technique used for classifying ECG heartbeats. The stacked denoising autoencoder (SDAE) is an artificial neural network consisting of multiple layers of encoding and decoding units. In the encoding stage, the input ECG signal is transformed into a compact representation, and in the decoding stage, the original signal is reconstructed from this compressed representation. Denoising is an essential pre-processing step to remove noise from the ECG signal before feeding it into the SDAE. This is because ECG signals are often corrupted by various types of noise, such as baseline wander, powerline interference, and muscle artifacts, which can significantly affect classification accuracy. The SDAE is trained using a large dataset of ECG signals with known labels. During training, the SDAE learns to extract relevant features from the input signal and accurately reconstruct the original signal. This process is repeated multiple times, and the network weights are adjusted each time to minimize the reconstruction error. Once trained, the SDAE can be used for ECG heartbeat classification. This is done by feeding a noisy ECG signal into the network and obtaining the compressed representation. This compact representation is then classified using a classifier to determine the type of heartbeat ,86. Liu,surement .AI-based ECG analysis also has the potential to be used to detect or track non-cardiovascular disorders and to diagnose metabolic disorders, such as dyskalaemias , for nonAI-based analyses of ECG can rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with an under the curve for detection of acute COVID-19 infection of 0.78 with a negative predictive value of 99.2% .AI can help in treatment guidance, assisting in patient selection, optimizing therapies, improving symptom-to-treatment times, and cost effectiveness. Some examples include earlier activation of code infarction in patients with ST-segment elevation and predicting the response to antiarrhythmic drugs or cardiac implantable device therapies, reduce the risk of cardiac toxicity associated with cancer immunotherapy and biological drugs, or predict the risk of drug-induced arrhythmias or long QT syndrome .The accurate diagnosis of acute coronary occlusion is probably the main challenge for deep learning AI systems . CurrentAI may be used to better classify patients into high- and low-risk subgroups and identify those most likely to derive benefit with the least side effects of medical therapy. AI might optimize patient selection for device therapy. Up to 40% of patients are non-responders to cardiac resynchronization therapy and AI models can improve patient selection by highlighting patients who are most likely to derive benefit from it . AI modeAI facilitates the integration of ECG data with other diagnostic modalities, mainly imaging techniques, genomics, proteomics, and biomarkers. The ability of AI and cloud high-performance computing to extract and analyze large volumes of data facilitates the integration not only with clinical variables but also with diagnostic techniques, different types of wearables, and even facial recognition . For insECG and photoplethysmography data can provide valuable information on the cardiovascular system, including heart rate, blood flow, and arterial stiffness. By using this data in a deep learning regression model, the model can learn to estimate blood pressure values based on these physiological parameters accurately. Using ECG and photoplethysmography data for blood pressure estimation offers potential advantages due to their non-invasive and easy-to-obtain nature. ECG data can be recorded using electrodes placed on the skin, while photoplethysmography data can be obtained using wearable devices, such as smartwatches or fitness trackers. This enables continuous real-time monitoring of blood pressure without the need for invasive procedures.Using deep learning regression models can also improve the accuracy of blood pressure estimation compared to traditional methods; deep learning regression models using ECG and photoplethysmography may be useful for the real-time estimation of systolic blood pressure and diastolic blood pressure values .Using the impedance cardiogram (ICG) signal also known as cardioimpedance and the temporal location of the characteristic points B, C, and X provide crucial diagnostic information that can be used to determine cardiac output or stroke volume. However, there are several challenges to accurately identifying these characteristic points. The ICG signal is often noisy, and the morphology of the signal can vary significantly between patients. These factors make it challenging to identify the characteristic points accurately. Some methods have been demonstrated to be effective in identifying the characteristic points of the ICG signal. The process uses signal processing techniques and machine learning algorithms to determine the characteristic points with high accuracy and reliability. The proposed methods involve preprocessing the ICG signal using a bandpass filter to remove noise and extract relevant frequency components. Then, the signal is segmented into individuals’ heartbeats using a peak detection algorithm. Machine learning algorithms are finally used to classify each heartbeat and identify the characteristic points B, C, and X. The effectiveness of the proposed method has been confirmed in clinical pilot studies, demonstrating high accuracy and reliability in identifying the characteristic points of the ICG signal . The tecMultimodal wearable sensing, leveraging the seismocardiogram, a sternal vibration signal associated with cardiomechanical activity, together with ECG offers a means to monitoring continuous stroke volume and may enable remote monitoring of cardiac function .Cost effectiveness is relevant. Subclinical arrhythmias and cardiovascular disease are frequent. The fact that they might be detected by the widespread use of AI algorithms to detect conditions, such as atrial fibrillation, in large populations continuously wearing smartwatches would result in a substantial increase in new diagnoses. While there may be increased costs associated with the care of those patients, the potential reduction in cardiovascular events, such as strokes, could ultimately provide cost savings. There may be long-term clinical benefits of some cardiovascular disease screenings, such as in the case of atrial fibrillation or heart failure. Currently it is not cost effective to conduct systematic atrial fibrillation screening; however, AI-automated atrial fibrillation diagnosis has been achieved using a variety of rhythm modalities, including 12-lead ECGs, ambulatory ECGs, and photoplethysmography, and seems to improve cost effectiveness .AI-ECG algorithms may also be used to expedite the evaluation of complex clinical cases in which multiple confounding factors are present and multiple diagnoses are under consideration  Studies AI-based ECG analyses can improve diagnosis and patient management. AI diagnostic performance is already similar to that of experienced cardiologists. AI ECG analyses seem to be cost effective and are able to reduce the rate of misdiagnosed computerized ECG interpretations and improve clinical efficiency, patient characterization, risk stratification, treatment selection, and optimization. As shown in Most AI algorithms have been developed and tested on very controlled retrospective test and validation datasets; more work to test them prospectively and to assess their impact on real-world and real-time data is needed. Particularly, in the case of the possible applications of AI in selecting patients for medical and device therapies and optimizing care prospective testing in randomized controlled trials prior to clinical uptake seems mandatory. In the future, AI is expected to play an increasingly important role in ECG diagnosis and management, as more data become available and more sophisticated algorithms are developed. Physionet/Computing in Cardiology Challenge is an annual platform to gather international competitors from research centers and private companies for forced development of open-source AI, waveform, and rule-based algorithms for specific ECG diagnosis. The published databases for the challenge further become an open platform for many other research teams on AI .


In the patient who complained of dizziness, thrombus was observed in the right vertebral artery. Compression was detected in the nerve root due to compensatory hypertrophy in the left vertebral artery.In conclusion, in cases of unilateral vertebral artery thrombosis, should be aware of the pathologies that may develop in adjacent structures due to compensatory hypertrophy.An occluded vertebral artery (VA) can cause contralateral VA hypertrophy, which can cause various pathologies including nerve root compression. A 79-year-old male patient was admitted to the hospital with complaints of dizziness. Computed tomography angiography showed no contrast opacification of the right vertebral artery (VA) (red arrow in VA loop is a rare vascular condition that may be associated with nerve root compression and may occur due to congenital or acquired causes. Usually, symptoms such pain, numbness, and decreased muscle strength result from cervical discopathies and spondylosis-associated cervical nerve compression. However, compensatory vascular hypertrophy secondary to controlateral thrombosis as in our case is very rarely reported in the literature . The theIn conclusion, in cases of unilateral VA thrombosis, secondary pathology may develop in adjacent structures due to chronic compression by a benign hypertrophic vascular structure.


Rotator cuff tears, particularly involving the supraspinatus muscle and/or tendon, are highly prevalent among individuals engaged in repetitive shoulder motions. Occupations demanding constant and repetitive shoulder movements are especially susceptible to rotator cuff injuries, potentially leading to prolonged joint wear and tear and an increased likelihood of joint replacement. Considering the impact of social determinants of health, including access to healthcare and socioeconomic status, it is imperative to explore conservative treatment modalities that alleviate financial burdens and reduce lengthy recovery periods. In this report, we present a case of a 64-year-old female hairdresser diagnosed with a chronic partial thickness rotator cuff tear who remained unresponsive to physical therapy and chiropractic manipulation but exhibited improvement following osteopathic manipulative treatment. Additionally, osteopathic considerations and pertinent literature are reviewed to provide insight into the broader context of shoulder pain management. Rotator cuff tears can elicit considerable pain and impede shoulder function, significantly impacting an individual's daily activities and overall quality of life. In the United States, rotator cuff tears are observed in approximately 10% of patients aged 60 and above and can encompass a spectrum of presentations, ranging from asymptomatic incidentalomas to severely debilitating shoulder pain and pathological conditions . TypicalFor more severe instances or when conservative measures prove ineffective, surgical intervention may be recommended, involving the repair and/or reattachment of affected muscles or tendons . RecoverIn this context, here we present a case of chronic rotator cuff tear in a 64-year-old Caucasian woman, who exhibited inadequate response to conservative management and faced financial barriers hindering surgical intervention. Notably, the patient experienced improvement following OMM treatments in which exploration of shoulder pathology from an osteopathic standpoint is reviewed as well as its implications for patient care.A 64-year-old right-handed female with a three-year history of chronic right shoulder pain and limited range of motion, presented to outpatient primary care for evaluation. She had a past medical history of hypertension, migraines, hiatal hernia, and gastroesophageal reflux disease, and did not have any significant surgical or family history. Social history was significant for occupational exposure to repetitive overhead and shoulder motions as a self-employed hairdresser, working six to nine-hour shifts, five days a week. Two years prior, she was evaluated by orthopedic surgery in which magnetic resonance imaging showed a two-millimeter partial tear of the distal supraspinatus tendon Figure . She wasVitals were within normal range. Physical exam revealed reduced shoulder flexion between 15-90 degrees on the right, however, was ultimately able to maintain shoulder flexion at 90 degrees with the assistance of her other arm, which was a coping mechanism that the patient created to keep up with her hairdressing work. In the right arm, she reported pain at the greater and lesser tubercles of the humerus, with the worst subjective pain experienced at the deltoid tuberosity during abduction. Muscle strength was 5/5 in the left upper extremity and bilateral lower extremities. In the right upper extremity, initial abduction strength was 1/5, with improvement to 5/5 after 75 degrees of abduction. The patient denied any other muscle weakness, abnormal sensation, or pain in locations other than her right shoulder. Special tests for rotator cuff and shoulder pathology were positive in the drop arm and empty can test, while O'Briens, Hawkins, and cross-body adduction tests were negative.An osteopathic structural exam revealed hypertonic and tender trapezius on the right on palpation as well as an exquisitely tender bicipital point. Complete findings are detailed in Figure Osteopathic manipulative treatment was offered to address the somatic dysfunctions found in Figure Currently, the patient is two years of status post initial orthopedic assessment and subsequent osteopathic treatment undergoes monthly maintenance treatment with only mild residual pain, and has retained a complete range of motion.Rotator cuff tendinopathy is the most common cause of shoulder pain, especially among patients who have occupations that require repetitive motion of the shoulder . In addiSomatic dysfunction is defined as impaired components of the somatic (body framework) system and can include the musculoskeletal, nervous, and lymphatic systems. In osteopathic medicine, its core tenets recognize that “rational treatment is based upon an understanding of the basic principles of body unity, self-regulation, and the interrelationship of structure and function”. TherefoStudies have demonstrated that patients with rotator cuff tendinopathy benefit from osteopathic manipulative treatment, particularly in pain reduction and the need for further intervention . While fChronic rotator cuff tears may benefit from osteopathic manipulative treatment. As seen in this case, the patient was able to resume occupational activities with diminished restrictions and alleviated pain. In the context of managing patients with shoulder pain, osteopathic healthcare providers should contemplate integrating osteopathic treatment into their therapeutic protocols. Furthermore, non-osteopathic healthcare practitioners should consider the referral of patients to osteopathic manipulative medicine specialists as a viable non-invasive alternative for managing shoulder pain. Further studies are needed in the future to validate osteopathic treatment for chronic rotator cuff tears.


Face-to-face communication is one of the most common means of communication in daily life. We benefit from both auditory and visual speech signals that lead to better language understanding. People prefer face-to-face communication when access to auditory speech cues is limited because of background noise in the surrounding environment or in the case of hearing impairment. We demonstrated that an early, short period of exposure to audiovisual speech stimuli facilitates subsequent auditory processing of speech stimuli for correct identification, but early auditory exposure does not. We called this effect “perceptual doping” as an early audiovisual speech stimulation dopes or recalibrates auditory phonological and lexical maps in the mental lexicon in a way that results in better processing of auditory speech signals for correct identification. This short opinion paper provides an overview of perceptual doping and how it differs from similar auditory perceptual aftereffects following exposure to audiovisual speech materials, its underlying cognitive mechanism, and its potential usefulness in the aural rehabilitation of people with hearing difficulties. Language understanding is fundamentally a multisensory process, as face-to-face communication in humans aids language understanding by providing not only verbal cues but also non-verbal cues such as emotional expression, body gesture, and facial expression. The importance of face-to-face interactions is evident in adverse listening conditions when access to verbal cues is limited because of external noise or hearing loss.Sumby and Pollack  were theIn addition, studies have also found audiovisual aftereffects following exposure to audiovisual speech materials ,7. BerteWe found a specific audiovisual facilitation effect on subsequent auditory speech-processing tasks. Moradi et al. , in a beIn a randomized control study, Lidestam et al.  divided Using the same gated audiovisual and auditory gated speech stimuli as employed by Lidestam et al. , Moradi Finally, using data from the n200 study , which cWe have dubbed this rapid type of perceptual learning “perceptual doping”, arguing that even a short exposure to audiovisual speech stimuli recalibrates or retunes phonological and semantic processing maps in semantic long-term memory in a way that facilitates subsequent auditory processing of speech stimuli for correct identification .This audiovisual facilitation effect on subsequent auditory speech processing cannot be explained by concepts like perceptual learning only or using lexical knowledge to learn how to categorize speech sounds . PerceptHere, we reason that the perceptual doping notion differs from the audiovisual phonetic recalibration effect. First, the audiovisual speech materials in our prior research were different from the work by Bertelson et al. . The audThe perceptual doping effect can be understood in terms of the Ease of Language Understanding (ELU) model. In particular, within the ELU framework, there is a perceptual-linguistic component that assumes a Rapid, Automatic, Multimodal Binding of PHOnological information RAMBPHO ,15,16). ,16. 15,1Most recent studies used auditory (and cognitive) training to enhance speech intelligibility in people with hearing loss. Stropahl et al. , in theiHowever, the maintenance of auditory (and cognitive) training effects on auditory speech tasks requires further research. To our knowledge, only a few studies have investigated the efficiency of audiovisual speech training on subsequent auditory speech processing tasks. As mentioned above, Moradi et al.  showed tTye-Murray et al.  studied Sato et al.  studied We reason that the addition of visual cues to auditory (and cognitive) training speech materials boosts the effectiveness of aural rehabilitation programs for people with hearing loss in terms of both efficiency and the maintenance of training effects on the listening capacities of persons with hearing loss. This speculation requires further investigation; future studies should consider the transfer of the learning effect from trained to non-trained speech materials, subjective hearing satisfaction in daily life, cognitive function in people with hearing loss, and the maintenance of training effects.As prior audiovisual speech exposure boosts the subsequent auditory identification of speech stimuli, caution should be taken when collecting auditory and audiovisual speech data in within-subjects studies when the modality of presentation  is randomized across participants. In addition, caution should be taken if the participants are first tested in an audiovisual and then an auditory modality. In fact, the perceptual doping may cause a type II error  in a within-subjects design, which may result in non-significant differences between auditory and audiovisual speech data or even lead to better performance of auditory speech stimuli than audiovisual stimuli. We suggest that future studies adopting a within-subjects experimental design consider collecting data using a fixed-order presentation (instead of a randomized-order presentation) by collecting auditory speech data first and then audiovisual speech data. Nevertheless, although a between-subject experimental design can be used to control perceptual doping and priming effects, individual differences across participants  are methodological disadvantages that should be taken into account when comparing auditory and audiovisual groups.(1)The extent to which a short period of exposure to audiovisual speech stimuli facilitates visual-only and/or audiovisual speech processing for correct identification is an interesting research topic for future studies. Knowledge is scarce concerning how audiovisual speech stimulation can enhance the processing of visual-only speech cues for correct identification, particularly in people with hearing loss. In face-to-face communication, people with hearing difficulties rely more on visual speech cues, as access to the auditory component of audiovisual speech signals is limited by background noise or hearing loss.(2)The extent to which audiovisual speech training can improve cognitive function is another interesting research topic for future studies. Fergusson and colleagues ,26 were


It is based on administering aradioisotope that emits heavy  particles. After administration, theradioisotope is deposited in the target organ through natural tropism or throughtransport by a vector molecule.Cellular damage can occur as a result of the radiation emitted. The desired conditionsto maximize exposure of the target organ and preserve adjacent tissues of varyingradiation sensitivities are intimately associated with several factors that can beidentified in advance during an internal dosimetry-based planning process.Treatment with radioisotopes, also known as targeted radionuclide therapy (TRT), ischallenging to implement safely and optimally in clinical practice and published in the current issue of RadiologiaBrasileira, sought to explore one of those factors and its impact on the definition ofthe estimated absorbed dose after nuclear medicine imaging, addressing imageco-registration as an essential preprocessing step for effective planning of TRT.Commercial applications such as the Organ Level INternal Dose Assessment for EXponentialModeling (OLINDA/EXM) quantification platform offer end-to-end features for estimatingthe absorbed dose, promising to guarantee that the processes for estimating internaldosimetry factors will be more precise, rapid, and reproducible. There is a growing demand fortechnologies that enable image co-registration for internal dosimetry calculations.Various studies have investigated the impact that the stages of image preprocessingintended for dose estimation, including spatial transformation of the original data,have on the patient,6.The study “Validation of automated image co-registration integrated into in-housesoftware for voxel-based internal dosimetry on single-photon emission computedtomography images”, conducted by Leitão et al. studyintroduces a technological advance by developing and testing an automaticco-registration method for single-photon emission computed tomography (SPECT) images,which could be integrated with their in-house software, designated NMDose-coreg. Theauthors investigated the need for fiducial markers, which are commonly used to enhancethe precision of image alignment, and concluded that there was no significant differencein the quality of the co-registration with or without them. This implies that usingthese markers might be dispensable in SPECT/CT co-registration, simplifying the processand saving time. The authors also compared the performance of NMDose-coreg with that ofOLINDA/EXM, which is considered the standard software for estimating the renal dose inpatients undergoing 177Lu-DOTATATE therapy-for the target organ and for thesurrounding tissues. They demonstrated that NMDose-coreg reduced the total processingtime without compromising image quality after co-registration. These results arepromising for applying NMDose-coreg in clinical practice, especially considering itspractical implications in time-saving and process simplification. However, there weresignificant differences between the two methods, in terms of the doses calculated,underscoring the need for multicenter studies involving larger samples in order tounderstand the exact causes of those differences.The Leitão et al. study alsoopens new perspectives for preprocessing methods that enable greater accuracy whenestablishing absorbed dose values, for the target organ and for other tissues.Artificial intelligence resources applied in structural segmentation or rigid imageregistration hold promise for optimizing absorbed dose planning for TRT. That innovationcould facilitate the incorporation of internal dosimetry as a standard practice inpersonalized medicine. The list of therapies involving radioisotopes continues toexpand, which makes maintaining high radiological protection standards for patients ofparamount importance. This movement aligns with rigorous, optimized protocols andharmonizes with initiatives like the one established in European Council Directive2013/59/Euratom.The Leitão et al.Although many challenges lie ahead, a thorough understanding of the workflow forimplementing personalized internal dosimetry planning will contribute significantly todeveloping and refining planning models. Ideally, such models will be standardized,replicable, and traceable, which will enhance the safety and effectiveness ofradioisotope therapies.


Long-read DNA sequencing technologies have been rapidly evolving in recent years, and their ability to assess large and complex regions of the genome makes them ideal for clinical applications in molecular diagnosis and therapy selection, thereby providing a valuable tool for precision medicine. In the third-generation sequencing duopoly, Oxford Nanopore Technologies and Pacific Biosciences work towards increasing the accuracy, throughput, and portability of long-read sequencing methods while trying to keep costs low. These trades have made long-read sequencing an attractive tool for use in research and clinical settings. This article provides an overview of current clinical applications and limitations of long-read sequencing and explores its potential for point-of-care testing and health care in remote settings. First- and second-generation short-read sequencing (SRS) has been the gold standard for genetic profiling in the last two decades , 2. ShorThese limitations were the motivation and driving force for the development and application of long-read sequencing (LRS), also known as third-generation sequencing, with the ability to generate sequence reads tens of thousands of bases in length. The LRS process occurs in real time, and both the sequencing and library preparation are conducted without the need for PCR amplification, therefore being free from any PCR-related bias. Also, with the DNA remaining in its native state, LRS technologies can detect base modifications such as methylation directly, without the base conversions required for SRS which are known to degrade DNA .Currently, the two main technologies for LRS are Pacific Biosciences’ (PacBio) single-molecule real-time (SMRT) sequencing and Oxford Nanopore Technologies’ (ONT) nanopore sequencing  see Fig.Fig. 1ScPacBio’s SMRT sequencing technology was the first LRS technology to reach widespread utilisation . The SMRThe latest PacBio sequencing platform, the Revio system, now delivers up to 360 Gb of HiFi reads per day, equivalent to ~ 1300 human whole genomes per year . With imStaphylococcus aureus, to manipulate a lipid bilayer and detected DNA translocation through an α-HL nanopore [The next successful LRS technology was established by Oxford Nanopore Technologies (ONT). The idea of nanopore sequencing dates back to the 1990s, when Branton and Deamer  developenanopore . This bek-mer of consecutive nucleotides [Nanopore sequencers  and their application in basic and clinical research have undergone substantial growth since ONT provided the first commercially available nanopore sequencer in 2014 . Their tONT has also made significant innovations in long-read sequencing. One notable advancement is the introduction of adaptive sampling, a computational enrichment technique . AdaptivNanopore sequencing also allows for the identification of base modifications both at DNA and RNA level. Modified bases such as 5-methylcytosine in DNA or N6-methyladenine in RNA sequences can be detected based on differences in the current flow  between modified and unmodified bases . The higONT continuously develops new, improved chemistries for their sequencing kits with the latest being the V14 chemistry . The V14Overall, due to its unparalleled utility in reading genomes, transcriptomes and epigenomes, providing major opportunities for all areas of medical and biological research, LRS was named “Method of the Year 2022” by the journal Nature Methods . This arGenomic testing in clinical settings is used to identify underlying genetic causes and inheritance of diseases. However, about 50% of all suspected Mendelian conditions remain undiagnosed  thereby Recent research has shown that LRS technology may play an important role in discovering novel pathogenic mutations in human diseases with a previously unknown underlying genetic cause. A pilot study conducted by Stevanovski et al.  demonstrPRKAR1 gene [To further identify and diagnose rare genetic diseases within the population, there has been a drive for the implementation of whole-genome sequencing (WGS) for screening and diagnosis of genetic conditions . The firAR1 gene . Single-AR1 gene .OPN1LW/OPN1MW gene cluster. Many individuals with genetic variants in these genes often remain genetically undiagnosed due to the inability of short-read sequencing to differentiate between the highly homologous OPN1LW and OPN1MW genes. Through the use of copy number analysis via multiplex ligation-dependent probe amplification and sequence analysis via long-read circular consensus sequencing, Haer-Wigman et al. were able to identify both structural and nucleotide variants in the OPN1LW/OPN1MW gene cluster. Their assay has the potential to be streamlined into clinical settings and improve diagnostic care of individuals with visual impairment.Another promising emerging application of LRS is the diagnosis of genetic conditions such as those affecting colour vision as demonstrated in the study by Haer-Wigman et al. . The genSLC12A3 variants lead to dysfunction of the Na1-Cl2 cotransporter (NCC), resulting in a salt-losing renal tubulopathy characterised by hypokalaemic alkalosis and hypomagnesemia [SLC12A3 is currently found, depending on the techniques used. However, Viering et al. through LRS identified a second likely pathogenic intronic variant in 67% of patients previously identified to apparently harbour only one variant. Those with two SLC12A3 variants had a more severe electrolyte phenotype than other patients [A recent example of a successful application of LRS to reveal the underlying cause of a rare genetic condition was presented by Viering et al. in Gitelman syndrome. In this rare autosomal-recessive syndrome, biallelic disease-causing gnesemia , 27. In patients . These fAnother great potential of long-read sequencing technology lies in the rapid diagnosis of rare genetic diseases to guide the clinical management of critically ill patients. Researchers from Stanford University recently presented an ultra-rapid nanopore whole-genome sequencing workflow that was able to diagnose rare genetic diseases in an average of eight hours. Their pilot study involved 12 critical care patients, five of whom received a genetic diagnosis from the sequencing information, guiding in clinical decision-making such as heart transplantation and change of medication . In one Cancer genomics is one of the representative fields in which LRS technologies have already achieved significant results and proven to have considerable clinical potential. SVs in cancer genomes, similar to somatic mutations, can affect the function of oncogenes and tumour suppressor genes. A large number of cancer patients are routinely screened for pathogenic SVs in clinical practice, most often by copy number profiling or karyotyping . AlthougCDKN2A and SMAD4 tumour suppressor genes in pancreatic cancer cell lines [ERBB2 amplification appeared within complex rearrangements at chromosome 8, which could only be precisely identified by LRS.A pioneering study by Norris et al. used MinION LRS to analyse SVs in the ll lines . From rell lines . InteresEGFR, PDGFRA, and CDK4 [Euskirchen et al. developed a method to diagnose central nervous system (CNS) tumours using MinION technology . They imand CDK4 . This stTP53 and ABL1 genes. Cumbo et al. developed a nanopore-based assay for rapid (24 h) targeted sequencing of six genes  that are frequently mutated in acute myeloid leukaemia [The benefits of a fast turnaround using the portable MinION sequencer were emphasised in several studies testing the diagnostic yield of nanopore sequencing in patients with haematological malignancies, such as chronic lymphocytic leukaemia and chronic myeloid leukaemia –36. In teukaemia . The naneukaemia .Another clinical application of LRS in the field of oncology that has shown significant promise is the multilayer analysis of the transcriptome and the epigenome. Transcriptomics has benefited from the application of LRS as it allows full coverage of transcript sequences, and thus, structures of transcript isoforms can be determined by sequencing full-length complementary DNAs (cDNAs). In the field of oncology, fusion transcripts are of particular interest since they have been identified as major drivers of carcinogenesis . IdentifBCR-ABL1 fusion transcripts with > 100 reads within 15 min of sequencing [In a study by Jeck et al., real-time long-read data generated using the MinION sequencing system enabled the identification of quencing . Their nBMPR2-TYW5-ALS2CR11, in the lung cancer cell line H838 [To take full advantage of new LRS technologies for fusion identification and characterisation, fusion detection algorithms have been developed. For example, Davidson et al. developed JAFFAL, a novel pipeline to identify fusions in long-read transcriptome sequencing data . JAFFAL ine H838 .Furthermore, LRS can be applied to detect and screen for epigenetic changes in cancer. Epigenetic changes have important roles in the control of cellular function through transcriptional regulation. Epigenetic alterations can lead to aberrant gene expressions or splicing dysregulation and promote tumorigenesis , 42. TheKuschel et al. demonstrated that LRS can be used to determine the methylation of brain tumours and their classification . In theiAn emerging important clinical application of LRS is its use in infectious diseases. The speed of LRS via ONT platforms, providing results in just a few hours, makes it an attractive option for the in situ diagnosis of infectious pathogens facilitating a potential rapid response for the identification and management of disease sources and disease spread. Real-time genomic surveillance of pathogens has therefore become a new tool to assist difficult epidemiological investigations and to provide an environmental context to emerging infectious diseases. This has the potential to improve the efficiency of resource allocation and the timeliness of epidemiological investigations through genomically informed investigations of transmission chains.Arguably, the most inspirational clinical application of the MinION sequencer for infectious disease monitoring has been in the Ebola virus outbreak in West Africa in 2015. The portability and capacity to sequence when simply plugged into a laptop allowed real-time genomic surveillance of the epidemic in the field , 49. ThiLeading on from the experience in the Ebola outbreak, LRS has also been increasingly employed during the COVID-19 pandemic. As SAR-CoV-2 is a highly infectious virus that is prone to mutations, viral WGS is recognised as a critical tool for studying its transmission and evolution . NanoporMore recently, nanopore sequencing has also shown to be a valuable tool in the monitoring and the management of the 2022 monkeypox virus (MPXV) outbreak . As withKelch13 genes in Plasmodium parasites diagnosing the C580Y mutation of P. falciparum and in combination with loop-mediated isothermal amplification in diagnosing human malaria parasites. To achieve malaria elimination, early examination of parasites’ genotypes to avoid the spread of drug-resistant parasite strains and unravelling the disease dynamics at the vector level are important. However, these can only be made possible by a sequencing approach that is accessible, affordable, and easy to use, which is embedded in ONT technology. The technology could therefore be part of the solution to malaria elimination in malaria-endemic regions across low-income countries.The ability to identify target DNA of pathogens in clinical samples in a timely fashion and not being limited by the length of DNA fragments to be sequenced, has made the MinION sequencer also an attractive technology for expediting malaria elimination and reducing the global malaria burden . Its usa28. They utilised the MinION sequencer to identify drug resistance in M. tuberculosis to improve its treatment in the field. The MinION sequencer was shown to be a cost-effective way to detect well-established drug resistance variants and undertake phylogenetic reconstruction with potential application in transmission analysis. Their study demonstrated that the MinION portable sequencer represents a feasible cost-effective approach for personalising treatment of infectious diseases in remote settings.LRS can also make a significant contribution to the treatment and diagnosis of tuberculosis. This was demonstrated in the 2022 study by Gómez-González and colleaguesMycobacterium tuberculosis [Klebsiella pneumoniae and Escherichia coli isolates [Additionally, hybrid long-read and short-read sequencing is used to leverage benefits and overcome limitations of both technologies in the field of antibiotic resistance research, enabling comprehensive and accurate characterisation of microbial genomes. Several studies have utilised hybrid sequencing to investigate antibiotic resistance mechanisms and identify novel resistance genes. For instance, a study by Marco et al. employed hybrid sequencing to reveal a large diversity of antibiotic resistance in rculosis . Similarisolates . This stChlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum and Trichomonas vaginalis bacterium or parasites are all curable with existing, effective single-dose antibiotic regimes. However, recently there has been a surge in the number of antimicrobial resistant (AMR) strains of STIs, which has made them difficult to treat and stop their spread [N. gonorrhoeae DNA directly from urine samples from men with symptomatic urethral gonorrhoea to achieve the nearly complete reconstruction of the N. gonorrhoeae genome [Sexually transmitted infections (STIs) remain a major public health problem and are therefore high on the global health agenda . STIs inr spread . Limitatr spread . An impoe genome . But theAnother promising application of LRS in the clinical setting is the analysis of microbiota. For example, microbiota of the female reproductive organs can have vast associations with conditions such as genital infections, endometritis, and threatened miscarriage . Komiya Long-read sequencing has emerged as a valuable tool in the field of transplantation, particularly in understanding the complex interplay between donor and recipient immune systems. With the advent of PacBio and ONT LRS, researchers have been able to perform highly accurate and comprehensive human leukocyte antigen (HLA) typing. Cornaby et al. utilised LRS to analyse the HLA diversity in a large cohort of transplant patients, shedding light on the importance of donor-recipient matching and its impact on post-transplant outcomes .LRS has revolutionised HLA typing by allowing for the identification of rare and complex HLA alleles, which were previously very hard to detect using traditional SRS methods. For instance, a study by Lehmann et al. employed PacBio LRS to characterise HLA alleles in a cohort of kidney transplant recipients . The resIn addition, LRS has played a crucial role in unravelling the causes of graft versus host disease (GVHD). GVHD is a serious complication that can occur after transplantation, where the donor's immune cells attack the recipient's tissues. A recent study by Zhang et al. utilised nanopore sequencing to perform transcriptome analysis of immune cells involved in GVHD . They idFurthermore, LRS has proven instrumental in elucidating the role of killer-cell immunoglobulin-like receptor (KIR) genes in transplantation biology. KIR genes encode receptors expressed on natural killer (NK) cells, which play a crucial role in immune surveillance and regulation. Through LRS researchers have gained a comprehensive understanding of KIR gene diversity and its impact on transplantation outcomes. A notable study by Roe et al. used the technology to investigate KIR gene expression patterns in a cohort of hematopoietic stem cell transplant recipients . The finA major disadvantage of traditional short-read genome sequencing technology has been the need for high capital investment, which resulted in sequencing infrastructure being located in dedicated sequencing centres. Consequently, the shipment of samples can become the most time-consuming step of an investigation, rather than the sequencing or analysis work itself . ResearcImportantly, the utility of portable sequencing has already been proven in field situations, such as diagnostic tent laboratories during the Ebola epidemic. Using the MinION system, it was possible to generate results in under 24 h, with sequencing taking 13–60 min . This shAdditionally, in the field of infectious diseases, whole-genome sequencing has rapidly become the new gold standard in scientific research and a clinical diagnostic tool, particularly in industrialised countries. LRS enhances the detection, diagnosis, and management of infectious parasitic pathogen outbreaks, leading to the containment of many infectious diseases and, thus, improving public health. Such diseases include pneumonia, Ebola, cholera, COVID-19, tuberculosis, and malaria , 58, 71.Another promising application of long-read sequencing and in particular nanopore sequencing has been in the critical care setting where recent reports from intensive care units (ICUs) have shown improved patient outcomes with this new technology. Long-read sequencing was shown to identify pathogens in ICU patients with serious infections with a high degree of accuracy in a timely fashion, even in cases where traditional methods fail . In one While long-read sequencing technologies offer significant potential in health care, several challenges need to be addressed to enable healthcare providers to confidently adopt these technologies. One major concern is the validation of data generated through LRS. Accurate and reliable data are crucial for making informed clinical decisions. A recent study by Mahmoud et al. evaluated the accuracy of LRS platforms in detecting clinically relevant genetic variations . The resThe incorporation of LRS into standard clinical practice also very much depends on the stability and reliability of the sequencing platforms. Carbo et al. evaluated the stability and performance of ONT's sequencing platform over an extended time period . Their sFurthermore, to overcome the challenges associated with LRS, it is crucial to establish standardised protocols and quality control measures. Fukasawa et al. proposed a comprehensive quality control framework for LRS data . The resIn addition to validation and stability, another critical factor for the adoption of LRS technologies in health care is their practical implementation and integration into existing clinical workflows. A recent study by Marwaha et al. evaluated the feasibility and cost-effectiveness of incorporating LRS into the diagnostic pathway for genetic disorders . The resAnother challenge poses the data from long-read platforms which is qualitatively different from SRS data. LRS requires tailored analysis tools and bioinformatics approaches that enable to take full advantage of the technology. Consequently, various tools for base calling, error correction, de novo genome assembly, mapping, and phasing using long-read data continue to be developed . A scienFuture clinical applications, especially in regional, rural, and remote settings, will most likely require the development of highly intuitive bioinformatics analysis platforms so that clinicians are able to perform analyses without major disruption to existing clinical workflows. Regulatory, accreditation and credentialing frameworks for clinical applications close to the bedside would need review and revision, not dissimilarly to what is evolving for point-of-care ultrasound as distinct from traditional ultrasound examination and reporting.Another limitation of LRS platforms such as nanopore is the high “cost per base” . This meFurthermore, with increasing research and development of LRS, it has become evident that the platform is not necessarily the limiting factor for the length of the sequenced DNA but the DNA extraction and library preparation. Production of long reads largely depends on using high‐quality DNA of high molecular weight. While saliva has been demonstrated as a reliable common non-invasive DNA source for short-read analyses, most of the library preparation protocols for LRS require high molecular weight DNA from blood or other invasive tissue collection. As the DNA once extracted from the sample is no longer bound and protected by its histones, simple disruptions and processes such as pipetting can lead to fragmenting of DNA strands to < 100 kb . This ulGenomic testing does not only involve a laboratory testing component but also associated upstream and downstream services, including the provision of information, counselling, interpretation of test results, and clinical decision-making. Implementation of LRS-based genomic testing into a health system will therefore require consideration of these additional services in alignment with evidence-based best practices see Fig. . This woWith the advent of LRS as a key technology for personalised medicine, healthcare services must make the decision whether to perform the testing in the community or hospital, to outsource the testing to centralised laboratories, or to create a hybrid model, where part of the testing is done on-site, and tertiary laboratories are used for data analysis and interpretation. With portable LRS devices, genomic testing has become cheaper and more user-friendly. A community-based approach would enable a much faster diagnostic turnaround and decrease the risk of losing important material or information during sample shipment. However, on-site genomic testing would require robust protocols and control of pre-analytical parameters, sample specimen selection, and sample quality.There are ongoing collaborative national and international efforts to integrate genomic technologies into clinical and healthcare settings. Some of these efforts include Australian Genomics, Genomics England, the French Plan for Genomic Medicine 2025, the Global Alliance for Genomics and Health, and the Global Genomic Medicine Collaborative –85. CurrBoth nanopore long-read sequencing and SMRT sequencing have their unique advantages and applications, and choosing between these technologies depends on the specific application, associated requirements, and experimental conditions. PacBio sequencing is known for its high accuracy, making it well-suited for applications where precise SNP detection and haplotype phasing are essential. However, PacBio sequencing often requires higher DNA input amounts, making it more suitable for samples with abundant starting material.In contrast, ONT long-read sequencing provides real-time sequencing capabilities and portability, making it advantageous in field-based or point-of-care settings. It has the ability to generate long reads with a more rapid turnaround time, enabling fast SNP detection and characterisation. Moreover, nanopore sequencing has a low input material requirement and is suitable for low-concentration analytes.The choice between PacBio and ONT long-read sequencing depends on various factors. If high accuracy, longer read lengths, and complex genomic variations are the primary focus, PacBio sequencing is often preferred. However, if rapid turnaround time, real-time analysis, portability, and lower input material requirements are critical, nanopore sequencing can be the more suitable option.Both, PacBio and ONT are continuously evolving, and enhancements are being made to improve their technological capabilities. Therefore, it is important to consider the requirements of a specific LRS application and monitor recent developments to determine the most suitable platform.In addition to PacBio and ONT long-read sequencing technologies, hybrid long-read/short-read sequencing approaches have emerged as a powerful tool in genomic research. By combining the strengths of both long-read and short-read sequencing, hybrid approaches offer improved accuracy, read length, and cost-effectiveness.Long reads provide information about complex genomic variations, while the short reads offer high accuracy for base-level resolution and enable efficient error correction. This combination of technologies is particularly valuable for de novo genome assembly, where the long reads help in resolving repetitive regions and complex structural variations, while the short reads aid in accurate consensus generation. Additionally, hybrid sequencing can be beneficial in studying complex genomes, such as those with high levels of heterozygosity or polyploidy, where accurate phasing and haplotyping are essential.Hybrid long-read/short-read sequencing approaches continue to evolve, with improvements in protocols, library preparation methods, and bioinformatics tools. These advancements enhance the quality and utility of the generated data, making hybrid sequencing an increasingly attractive option for a wide range of genomic applications.Overall, the choice between short-read, long-read, or hybrid sequencing depends on the specific research goals, experimental conditions, and technological advancements. Staying informed about the latest developments in sequencing technologies and understanding the unique advantages of each approach is crucial for making informed decisions in genomic research.LRS technologies such as nanopore and SMRT sequencing are opening new exciting avenues in the diagnosis and treatment of genetic disorders, cancer and infectious diseases. To integrate this technology in health care, funding is required for sequencing devices, technology development, workforce upskilling, and increased integration between academic centres of research excellence, hospitals and health services. The associated rapid scientific and technological developments will require an environment where healthcare providers work closely together with highly specialised physicians and clinical molecular geneticists who are supported by experts in laboratory medicine, genomics, and bioinformatics. Once the current limitations such as costs, complexity and amount of data, availability and lack of clinical validation are overcome, it is widely expected that LRS will become the breakthrough technology and standard of care for genomic analysis, allowing a widespread implementation of precision medicine in a large number of clinical and remote settings.


Hernia reconstruction is one of the most frequently practiced surgical procedures worldwide. Plastic surgery plays a pivotal role in reestablishing desired abdominal wall structure and function without the drawbacks traditionally associated with general surgery as excessive tension, postoperative pain, poor repair outcomes, and frequent recurrence. Surgical meshes have been the preferential choice for abdominal wall hernia repair to achieve the physical integrity and equivalent components of musculofascial layers. Despite the relevant progress in recent years, there are still unsolved challenges in surgical mesh design and complication settlement. This review provides a systemic summary of the hernia surgical mesh development deeply related to abdominal wall hernia pathology and classification. Commercial meshes, the first-generation prosthetic materials, and the most commonly used repair materials in the clinic are described in detail, addressing constrain side effects and rational strategies to establish characteristics of ideal hernia repair meshes. The engineered prosthetics are defined as a transit to the biomimetic smart hernia repair scaffolds with specific advantages and disadvantages, including hydrogel scaffolds, electrospinning membranes, and three-dimensional patches. Lastly, this review critically outlines the future research direction for successful hernia repair solutions by combing state-of-the-art techniques and materials.  It has a pivotal role in the protection of postural assistance and abdominal pressure stabilization ,2. An abEpidemiological datasets show that hernia repair brings a tremendous economic burden to countries annually . AnatomiClinically, surgeons usually strengthen the defect and restore the normal anatomical structure with sutures or surgical meshes . Direct Looking through the hernia repair evolution history over the decades, an optimal approach should be designed with low risks of infection and visceral adhesion, high mechanical characteristics to support internal content, cost efficiency for broad applications, and easy handling properties to conveniently implant and fix to the abdominal wall. The urgent, yet unmet need, for patient-friendly and tissue-biocompatible repairing approaches then shifted to tissue engineering as it brought new insights into disease treatment and prevention.Hydrogels, with simple composition ,23 or chThis review aims to summarize and update, in a deep critical manner, on major evolutions in hernia repair material design and application. Abdominal wall anatomy and hernia pathogenesis is first shortly introduced, followed by the hernia classifications, clinical solutions, and the accompanying complications. Then, the revolution in commercial meshes is described. Next, the biological tissue grafts used for hernia repair are presented. Afterward, we highlighted the smart engineering materials, including hydrogels, electrospun fibrous membranes, and 3D scaffolds that have been investigated in recent years . A ratio22.1The human abdominal wall is composed of skin, subcutaneous fat, several fascia layers, and interconnected muscle layers in proper sequence . The exaThe structure integrity of human abdominal wall is primarily maintained by a set of muscles that provide sufficient mechanical strength and elasticity to hold the intraabdominal organs . In gene2.2To compare different studies and publications on hernias and develop evidence-based therapeutic strategies, it is of great importance to make definitive classifications of abdominal wall hernia. According to the European Hernia Society classification system, the primary and incisional abdominal hernias are classified based on localization and size ,51. The Despite the variety of abdominal hernias, the reported incidence of different types can differ. For instance, umbilical hernias are the most common ventral hernias, resulting from abnormal closure of abdominal wall defect as a primary hernia or a postoperative abdominal wall gap as an incisional hernia. This is a key anatomic landmark to precisely locate the hernia help making an accurate diagnosis for immediate treatment.Surgery is the most common solution for abdominal wall hernia repair, and sutures or meshes can achieve hernia closure ,53. Sutu3With the rapid development of health services, the progress of medical science and technology, and the improvements in materials research, new hernia repair meshes are constantly emerging. The surgeons choose the most reasonable meshes among the different options because the implant variables determine or affect treatment choice and the prognosis of hernia. Before the introduction of hernia materials, simple suture was first adopted by surgeons to close the abdominal wall. Hernia repair was first carried out with silk sutures, later transitioning to silver ones. There were other suture techniques such as fascial closure, fascial overlapping, and retention suture. Despite the certain successful rate, suturing under excessive tension brought about unbearable pain, suture rupture and ischemia in hernia patients with high recurrence rates. Given the unacceptable outcomes of suture operation, the tension-free repair concept had cut a striking figure as early as in the beginning of last century. The plastics became the leading role in hernia repair area. The early hernia meshes were classified into two categories from the prospective of degradation performance: non-absorbable and absorbable meshes .Table 2T3.1Hernia reconstructive surgery is one of the most commonly practiced surgical procedures per year, with consistently increasing inpatient costs. Prosthetic meshes combined with “tension-free hernioplasty” is the general approach for hernia repair ,162. The3.1.1Metal prosthesis is the earliest repair material used for hernia repair. In 1900, Witzel and Goepel used a silver mesh to repair hernia for the first time which was continuously practiced in clinic until 1960s . However3.1.2Polyester (PET)-based prostheses were the first non-metallic approaches in abdominal hernia repair by Wolstenholme in 1956  and have3.1.3Polytetrafluoroethylene (PTFE), first discovered in 1938, was a slippery and inert substance that made its way into herniology in 1959. But the extremely low mechanical strength and high recurrence rate became the reason for its abandonment. However, W.L Gore et al. refined the process to expand the Teflon into a porous structure with improved tensile strength and made a vascular prosthesis before introducing it into hernia repair field in 1980 . Clinica3.1.4Hitherto, the polypropylene (PP) mesh was the most commonly used hernia prothesis in clinics. The American surgeon Usher first experimented the strong, inert, and non-wettable polymer in animal models to confirm its effectiveness for hernia repair as early as in 1950s. After being refined, the PP mesh was utilized in clinics several years later and strengthened the defect area by initial inflammation and the follow-up fibrosis but without encapsulation. The repair mechanism avoided most of the complications of the earlier hernia prostheses making the PP mesh become the best prosthetic hernia material. A number of technical innovations have been made along the decades to enhance its tissue integrability, anti-infectious property and chemical stability. Despite the excellent hernia repair outcomes of PP mesh, the multiple complications such as mesh-induced inflammation and fibrosis A, foreigMost of the non-degradable polypropylene filaments knitted tightly together was inherently inert and inevitable to create a local inflammatory response, resulting in tissue fibrosis, scar formation, and mesh contraction. Despite many variables of interest for proposing a classification of the early prototype meshes , the four critical parameters, including filament constitution, pore size, and mesh weight , are ado3.2The increasing need for novel hernia repair materials with the aim of reducing mesh-related complications require a thorough evaluation of the hernia meshes that are presently available in clinical use so as to create new surgical mesh alternatives. In this context, the application of absorbable meshes is a new trend in abdominal wall reconstruction surgery. Compared with non-absorbable, absorbable hernia meshes can be gradually absorbed by the host tissue after being implanted in the body. They can provide temporary scaffolds for tissue reconstruction posing a great potential for abdominal wall hernia repair. The absorbable meshes can be divided into synthetic or biological meshes according to the material source.3.2.1co-glycolide) (PLGA), poly-p-dioxanone (PDO), and poly-4-hydroxybutyrate (P4HB) . . 302]. T5.1.2With the gradual rise of precise medicine, regenerative medicine has stepped into concise structural and functional regulation of damaged tissues. Synthetic hydrogels, with optimal functionalities, can meet the desired requirements for regenerating target tissues with similar biochemical and structural properties. Synthetic hydrogels are generally obtained by chemical modification of specific bonds, functional groups or responsive sites. The complexity of synthetic hydrogels also affords ECM mimetics a large range of possibilities to explore, in the demand for novel biomaterials for hernia repair. Importantly, in the area of biomaterials research, sensitive hydrogels or smart hydrogels has been gaining greater momentum. Scholars have recently designed various functional synthetic hydrogels for abdominal wall defect reconstruction in recent years, including immuno-regulation , angiogeOne of the most challenging issues regarding hernia implants is their foreignness to surrounding tissue and aptness to cause visceral adhesion. Engineers have proposed some strategies to circumvent these undesirable effects, such as collagen coating polyester or PP scaffolds, providing a smooth visceral side that can act as an anti-adhesive, non-erosive, and antibacterial barrier . NeverthDespite the marvelous achievements made in hydrogel hernia repair scaffolds, including a myriad of chemical and physical strategies for anti-adhesive hernia repairing E, the fa5.2Although the mainstay surgical meshes for hernia repair have changed over decades from synthetic prosthetics, engineered surgical meshes, and biological tissue grafts to smart devices, tension-free abdominal wall reconstruction is the final goal. Mechanical support and tissue ingrowth are the least basic requirements for hernia reconstruction material design. Hydrogels promoted successful tissue integration due to the ECM-like 3D structure and tunable morphology. However, the weak mechanical strength and fast biodegradation have limited its wide application in clinics. Electrospinning, another tissue engineering approach, brought dawn to mechanical performance problems for hernia repair. Electrospinning is a simple and versatile technique to fabricate scaffolds diameters ranging from several nanometers to micrometers that architecturally resemble ECM and consequently contribute to the emerging field of nanotechnology .Biological active components can be incorporated through polymer selection, chemical modification, and parameter adjustment . Electro5.2.1Tunable fiber morphology, membrane geometry, mechanical property, and in vivo degradability have made electrospinning fibrous membranes popular target for hernia tissue engineering. Compared with the non-absorbable hernia meshes that rely on the fibrotic tissue that composed of disorganized collagen with poor mechanical strength and high recurrence rate, the electrospun fibrous membranes that mimics the natural ECM with porous, nonwoven microstructures. The lightweight substrates are cost-effective, easy to fabricate with great translational potential. Ebersole et al. fabricated PCL electrospun fibrous hernia scaffold with an appropriate mechanical strength . The sut5.2.2l -lactide-co-caprolactone) (PLCL) mixed with fibrinogen. An optimal blending rate was selected to obtain mechano-physical characteristics  of this hybrid mesh. After being implanted in a canine abdominal wall defect model, the inflammatory response was significantly reduced while increased myofiber formation with a well-tuned degradation rate. Considering the mesh shrinkage that can be caused by blending polymer with biological components , the team measured the shrinkage rate of the hybrid mesh a slow as 8% which can retain its mechanical strength after implantation in vivo. Blending the natural components in the electrospun fibrous membranes can provide favorable cell-to-cell and cell-matrix interactions for effective wound healing.The hydrophobicity of the inert polymers is the main reason for adhesion formation, inflammatory reaction and re-herniation due to the poor cell affinity and/or slow degradation. In this regard, mixing the inert polymers with hydrophilic, biocompatible and biodegradable components and fabricating a hybrid mesh is a better option. The hydrophilic and biocompatible components such as fibrin, silk fiber and ureidopyrimidinone can not only improve the cellular aptness of the fibrous mesh, but can be made into biomimetic scaffolds while not sacrificing the mechanical strength of the polymer fiber. As such, developing a functional fibrous patch with appropriate mechanical properties has been a clinically relevant solution. In their recent study, Liu et al. reported a hybrid mesh composed of polycaprolactone (PCL) and silk fibroin (SF) for abdominal wall defect repair . The amo5.2.3Electrospinning is a globally accepted technique for nano-to-microfiber fabrication given its simplicity, cost-effectiveness, and ability to design multiple applications. What's more, the drugs or other components that solve in the electrospinning solvents can simply functionalize the fibrous structures as effective carriers to treat diseases. Drugs, peptides and even cells can be loaded onto the lectropunk fibrous membranes for specific purposes. The long-term and short-term drug release can be designed according to the disease treatment models by tuning the fiber structural and physicochemical properties. Direct blending, surface modification, core-shell structure fabricating by micro-sol technique is the most commonly adopted strategies for designing electrospun carriers.One of the severe side effects of non-degradable hernia meshes is implant-related surgical site infection and which causes intraabdominal infection, abdominal pain, intestinal obstruction, and even fistula. To reduce the unacceptable complication with electrospun fiber meshes, antibiotics were loaded to repair hernia in infectious context. In such a study conducted by Barrientos, antibiotic agent levofloxacin or irgasan were loaded onto PCL fibrous meshes. The in vitro release studies showed different release behavior of these two kinds of antibiotics due to different drug release mechanisms. The drug release files of electropsun fibers can be different in different fiber material matrices, release medium and the drug component. So, there can be a wide range of loading choices to achieve higher treatment efficacies. For example, some hydrophilic drugs that cannot be solved inorganic reagents can be loaded to hydrogels such as hyaluronic acid, gelatin or collagen before being packaged into polymers by special ways such as emulsification. In this way, a core-shell structure can be fabricated ensuring the drug loaded in the core layer can be released in a much slower manner. Our group recently loaded puerarin to reduce inflammation by micro-sol electrospinning B. The drThe unique porous interconnected 3D structure of electrospun fibrous scaffolds has always inspired bioengineers to design biomimetic wound healing materials. To overcome the quick degradation of biological tissue grafts and capitulate their excellent biocompatibility, biologically functional fibrous meshes have been developed by loading bioactive components  and even cells D. In a s5.2.4The biological tissue grafts reduced the adhesion formation to some extent thanks to their excellent biocompatibility—however, fast degradation and failure to provide mechanical support during the tissue remodeling process. Most biodegradable polymers can provide the required mechanical strength, but the instinctive inertness can cause foreign body reactions that end in abdominal organ adhesion. These consequences pushed researchers to rethink material design based on the abdominal wall's anatomical structure properties. The abdominal wall is anatomically composed of several layers, including the skin, subcutaneous fascia, muscle, and peritoneum. To achieve functional recovery, it is of great importance to consider the abdominal wall's structural differences, such as subcutaneous muscle and fascial tissue regeneration for resisting abdominal pressure and parietal peritoneum reconstruction, preventing internal organ adhesion, respectively. Given that, using multi-layered hernia meshes can replicate the structure and function of the abdominal wall and hopefully achieve a good outcome of abdominal wall reconstruction. Driven by such a design concept, Wang's team reported a double-layer nanofibrous scaffold consisting of polycaprolactone, graphene oxide, and chitosan using a consecutive electrospun approach C 319]. . 319]. GThe endless possibilities of electrospinning strategies have been adapted as an exceptional regenerative medicine platform providing cutting-edge drug delivery vehicles, tissue repair scaffolds, and dynamic monitoring systems while minimizing undesired side effects . However5.3So far, numerous meshes used for hernia repair made of both synthetic and biological materials have been presented in various shapes and compositions. However, there is no ideal mesh choice in the market possessing optimal tissue repair potential and mechanical performance while minimizing mesh-related side effects. On the other hand, the rise of the individualized treatment concept has pushed scholars to engineer a new generation of tissue repair materials to match individual organs and even with each patient. Consequently, intense efforts are still needed to engineer and develop cutting-edge meshes for hernia repair. 3D printing, or additive manufacturing, has come into the engineering world right under such high demands in the healthcare industry . PatientIn recent years, innumerable 3D printed biomedical devices have been produced for tissue engineering, including but not limited to nerve, heart, skin, cartilage, and bone. Some experimental 3D printed devices have been approved by the US Food and Drug Administration for clinical use . BesidesIn a study conducted by Liu et al., a cell-laden 3D printed scaffold was developed using a self-healing hydrogel composed of injectable chitosan ink. Before 3D printing, the chitosan was functionalized by phenol to render an increased gelling rate, enhanced self-healing property, and post-printing crosslinking capability . After sJust like other regenerative materials developed for tissue engineering, 3D printing is entitled to tailor a highly accurate patient-oriented biomedical material. This state-of-the-art technology aids in developing more complex and precise devices that cannot be fabricated by conventional techniques with easier modifiability. Gu's group reported a smart hernia repair mesh composed of a PCL 3D printing scaffold and collagen electrospinning membrane . The intPost-implantation adhesions have been the main obstacle in plastic surgery for decades, and numerous strategies were proposed with the joint efforts of engineers and surgeons. Despite the variety of anti-adhesive solutions, there isn't an effective one yet. However, scholars did not stop exploring new ways of preventing adhesion; on the contrary, they kept searching for solutions by looking deeply into the mechanism of visceral adhesion. Most surgical operation within the peritoneal cavity triggers an intense inflammatory reaction caused both by the implant-related foreign body reaction and destruction of the peritoneal protective layer, which will expose the cavity organs to an unregulated inflammatory process, eventually ending in adhesion formation . The perTo sum up, 3D printing technology facilitates a wide variety of highly customized and even patient-oriented biocompatible scaffolds that can be further functionalized by combining distinct structures and biological contents ,353. Alt61)The focus in hernia repair has been put on the development of ideal hernia materials over the past decades. However, as the precise treatment concept has entered into the clinical practice, it is of great importance to pay attention to the prevention side of the diseases. Although hernia has been viewed as a pure surgical problem that caused by the local weak areas in the abdomen, the findings made in basic research shed light on its molecular developing mechanisms. Recent evidence showed there is decrease of certain microelement in hernia sites such as copper and zinc. This indicates that it’s of great importance to take actions to screen relevant indicators and design some smart materials before its occurrence. This is a future direction for both the clinicians and engineers to develop practical devices that can either precisely screen or regulate hernia indicators.2)As biomaterial science begins to enter the stage of precise regulation through disease mechanisms, more efforts need to be paid to unveil the biological basis of hernia development and even hernia recurrence. For instance, there are certain genes, proteins and enzymes that regulate the process that can be intervened by well-designed engineering materials. For example, the lysis oxidase (LOX) family of enzymes that participate in collagen and elastin crosslinking are important regulative factors during the ECM maturing process. Any abnormalities in LOX can result in ECM-related diseases like pelvic organ prolapse and abdominal wall hernia. Besides, the recent progress in single-cell RNA sequencing, metabolomic analysis, and bioinformatics analysis can help researchers to deepen the understanding of the unveiled mechanism of abdominal wall hernia. Given the fact, smart meshes can be designed to upregulate or downregulate the key molecules to achieve more effective and precise treatment of hernia. In addition, different smart materials can be designed according to the hernia classification because of the different development mechanisms.3)A more effective evaluation system on the clinical applicability, safety, and biocompatibility is expected both before designing and premarketing hernia repair meshes. The evaluation methods published works regarding hernia repair mainly includes three aspects: characterization of prepared materials; in vitro biocompatibility experiments; in vivo reconstructive efficacy evaluation. Although the approaches of material characterization and cell compatibility analysis relatively centralized, the in vivo evaluation system changes between countries and even research groups. For example, some studies report the collagen deposition as an indicative of successful reconstruction in animal studies as the defect area filled with newly generated collagen tissue. However, in other research results, the collagen is considered to be the marker of fibrous tissue which is caused by inflammation. There has not a unified standard for animal study results to make further improvements to the existing strategies.4)The engineered hernia materials that have been developed are mostly limited to the traditional tissue engineering techniques. Nonetheless, the future hernia repair materials should be even more intelligent by combining photosensitive, electro-magnetic responsive, sonodynamic and mechanosensitive components to on-demand control the hernia materials rather than passively reconstruct the damaged tissues. Advanced biotechnologies need to be developed to improve host tissue response and mesh integration, along with improved manufacturing to make custom hernia meshes to meet the desired demand of precise treatment.With the development of basic surgical theory and surgical techniques, understanding of human anatomy, progress in bio-functional materials, modern hernia repair has made rapid progress. The concept of “tension-free repair” was proposed in 1980s, bringing hernia surgery into a new era. Since then, the principles of modern surgery advocated using prosthetic materials to repair hernia defects, so as to save lives, improve treatment effects, and improve quality of life. Although huge progress has been made in recent decades in tension-free hernia repair using various prosthetics such as absorbable, non-absorbable or partially absorbable with different functionalities, and the tissue engineering smart hernia meshes made by different approaches, there are still unsolved challenges that must be taken into consideration to achieve the ultimate goal of replacing the like with like. The challenges and future perspectives in engineering science for hernia repair materials are summarized as follows:7Myriad materials and techniques correlated with various approaches have been adopted to functionalize hernia repair meshes. The scientific advances in this research field have been enormous and it became clear that tissue engineering approaches reported to date are only the tip of the iceberg. Based on the evaluation of safety and effectiveness, the modern era of hernia repair mesh keeps evolving towards the improvement of patient care.Up-to-date, polypropylene hernia repair mesh is believed to be the most frequently used porous polymer construct in clinical practice owing to its good physicochemical and biological properties and cost-effectiveness. However, unexpected surgical complications include mesh-related adhesion, pain, erosion, and infection. To overcome these clinical complications, surgeons and engineers have proposed a series of hernia repair strategies throughout these decades. In this paper, we reviewed the history of hernia repair meshes that evolved from synthetic non-absorbable protheses, absorbable synthetic materials, biological grafts, partially absorbable engineered polypropylene meshes to smart hernia reconstructive scaffolds, such as hydrogel scaffolds, electrospun fibers, and 3D printing patches with the hope of fabricating precise, customized, and optimal hernia repair materials. The effects regarding to their functionalization with advantages and disadvantages were also discussed systemically. Despite a long history of evolution and great advances made in hernia mesh designing, significant challenges remain, and the exploration of novel materials and designs are still critical to improving abdominal wall reconstruction in the future.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Two pillars in modern oncology are treatment personalization and the reduction in treatment-related morbidity. For decades, the one-fits-all concept of radical hysterectomy has been the cornerstone of early-stage cervical cancer surgical treatment. However, no agreement exists about the prevalent method of parametrial invasion, and the literature is conflicting regarding the extent of parametrectomy needed to achieve adequate surgical radicality. Therefore, authors started investigating if less radical surgery was feasible and oncologically safe in these patients. Two historical randomized controlled trials (RCTs) compared classical radical hysterectomy (RH) to modified RH and simple hysterectomy. Less radical surgery showed a drastic reduction in morbidity without jeopardizing oncological outcomes. However, given the high frequency of adjuvant radiotherapy, the real impact of reduced radicality could not be estimated. Subsequently, several retrospective studies investigated the chance of tailoring parametrectomy according to the tumor’s characteristics. Parametrial involvement was shown to be negligible in early-stage low-risk cervical cancer. An observational prospective study and a phase II exploratory RCT have recently confirmed the feasibility and safety of simple hysterectomy in this subgroup of patients. The preliminary results of a large prospective RCT comparing simple vs. radical surgery for early-stage low-risk cervical cancer show strong probability of giving a final answer on this topic. Despite a drastic reduction in incidence and mortality, cervical cancer still represents a major cause of death worldwide, especially in developing countries . Thanks The term “radical hysterectomy” defines the wide variety of procedures requiring the removal of the uterus together with the anterior, posterior, and lateral parametria. Since the parametrial tissue is the most frequent site of local diffusion of cervical carcinoma, the rationale is to resect the cervix with healthy tissue borders as far away as possible from the tumor. Depending on the presence of risk factors such as tumor size, lymphovascular space invasion (LVSI), depth of cervical invasion, and pelvic node metastases, clinically unidentified parametrial spreading may be identified at the final pathology report in up to 30% of patients with early-stage tumors (tumor size < 4 cm confined to the cervix) [The extent of the parametrial resection affects the radicality of the procedure. Many modifications of the historical Wertheim’s RH technique  have beeParametrial invasion can occur (i) continuously, via direct infiltration of paracervical tissue, or (ii) discontinuously, via tumor emboli within parametrial lymphatic vessels and parametrial node involvement. However, no agreement exists on the prevalent way cervical cancer metastasizes in the parametrium nor as to its main pattern of parametrial spread . Thus, the different opinions about parametrial function reflect the debate on the ideal extent of radical surgery in early cervical cancer treatment.Historically, complete removal of the parametria was recommended, according to the evidence that parametrial metastasis can occur equally in both the lateral and medial parametria. In 1978, Burghardt et al. introduced a technique to process the parametria using giant sections. They demonstrated the existence of lymph nodes with a scattered and unpredictable location within the parametrium, and positive parametrial lymph nodes were detected even in patients with small cervical tumors. Thus, they advocated complete parametrectomy as the cornerstone of surgical management of cervical carcinoma ,13. SimiOther authors expressed some concerns about the radical removal of the parametrium. In 1995, Sartori et al.  studied Landoni et al.  evaluateParametrectomy is the main cause of intra- and post-operative complications in the surgical treatment of cervical carcinoma. The incidence of surgery-related morbidity is irrespective of the surgical approach . RH may In the 1990s, evidence started arising regarding the therapeutic appropriateness and oncologic safety of modified RH. Like Photopulos’ previous findings , MagrinaDespite limitations in these data and the fact that differences in opinion still exist on the amount of parametrium that should be removed at surgery, surgical management of cervical carcinoma has nearly universally changed, abandoning the “one-fits-all” concept in favor of tailored surgical radicality. The recently updated 2023 ESGO/ESTRO/ESP Guidelines [However, it is worth noticing that, among the risk factors mentioned above, only tumor size can accurately be assessed pre-operatively by clinical evaluation, MRI, and transvaginal ultrasound (TV-US) imaging. In contrast, conclusive information about LVSI and depth of stromal invasion need histologic examination. Pre-operative histologic diagnosis of clinically evident cervical cancer is routinely performed by cervical biopsy that is inconclusive for LVSI and cannot give any information about stromal invasion depth. On the other hand, conization would provide more details on LVSI but is often omitted in pre-operative diagnostic management. However, it cannot comprehensively evaluate the depth of stromal invasion, which can be truly assessed only if a simple trachelectomy is performed with the removal of the entire width of cervical stroma.As previously observed, we believe that depth of invasion does not give consideration to cervical size and tumor location in the cervix, and poorly represents the risk of parametrial invasion. Conversely, in agreement with Landoni et al.’s previous findings , we thinGiven the relationship between morbidity and the extent of radical hysterectomy, gynecologic oncologists have begun questioning if a subgroup of patients with low risk disease could be treated without performing parametrectomy.In the first prospective study addressing this issue, Stark et al. enrolled 210 patients with stage IB cervical carcinoma between 1971 and 1979, who alternatively underwent Wertheim’s procedure or the less radical Galvin–TeLinde hysterectomy . In theiGiven these limitations, many authors started exploring less radical surgical options for early-stage cervical cancer. Multiple retrospective studies showed very low rates of parametrial invasion in patients with early-stage cervical carcinoma with favorable prognostic features ,35,36,37In 1995, Kinney et al. evaluated 387 patients with squamous cervical carcinoma treated by radical hysterectomy. They found that none of the 83 patients with tumor size less than 2 cm and without LVSI had parametrial involvement, either via direct invasion or discontinuously in parametrial nodes . SubsequDespite some differences in study design and results, when analyzed comprehensively, these studies demonstrate that the rate of parametrial involvement is less than 1% in patients with low-risk features. Therefore, there could be a subset of patients with early-stage cervical cancer for whom RH could be avoided. Further data from two more recent large retrospective studies strengthened these findings. Derks et al.  evaluateIn 2012, Landoni et al.  publisheTo date, it is a firm oncologic principle that the best way to treat cancer is to use a single approach to reduce complications and save other treatment options in case of failure of the first choice. Therefore, the selection of patients eligible for a less radical surgical approach is essential to avoid the need for subsequent adjuvant therapy.Recently, two prospective studies have been published evaluating the oncological safety of non-radical surgery in selected cases of early cervical cancer. The Concerv trial  was a prThe results of the Radical versus Simple Hysterectomy and Pelvic Node Dissection with Low-Risk Early-Stage Cervical Cancer (SHAPE) Trial (NCT01658930) were presented at the 2023 ASCO Annual Meeting , hypotheIn the present research, we reviewed current evidence on the role of radical parametrectomy in the management of early-stage cervical carcinoma. RH has been the cornerstone of surgical treatment of cervical carcinoma in the last century. However, no agreement exists about the prevailing way of parametrial invasion, and the literature is conflicting regarding the extent of parametrectomy needed to achieve adequate surgical radicality. Although the two historical RCTs that compared less extensive with more extensive radical surgery could not assess the real impact of surgical radicality, their results guided a near-universal shift in the surgical management of early-stage cervical cancer. Current guidelines state that the extent of parametrial resection should be tailored according to pre-operative risk stratification, and classical radical hysterectomy  is reserved as an alternative to Q-M type B2-C1 only in patients at high risk of treatment failure. The risk definition reported in the recently updated 2023 ESGO/ESTRO/ESP Guidelines ,32. SecoThe cornerstone of curative oncological surgery is complete tumor resection with clear margins, and further surgical or adjuvant treatment is warranted if adequate free margins are not achieved. Since tumor-positive margins are invariably associated with recurrence and poor prognosis, the minimal tumor-free margin is an essential clinical issue in several tumor types  ,46,47,48One of modern oncology’s pillars is reducing treatment-related morbidity without impairing oncologic outcomes. Many historical retrospective series have addressed whether any subgroup of patients could be treated, avoiding radical parametrectomy and its sequelae. In patients with low-risk characteristics, the parametrial involvement rate was less than 1%, suggesting that a subgroup of patients could be adequately cured, avoiding RH. The results of two prospective trials, the Concerv trial  and the Curative surgical treatment of early-stage cervical cancer does not implicate inevitably extended radical parametrectomy. In the era of personalized medicine, surgical radicality and the choice of primary treatment, whether surgical or not, should be tailored according to the patient’s tumor characteristics. Well-established risk factors have been extensively reported as predictive of treatment failure. Although little data are available addressing this issue, we believe that implementing the classical risk factors with TFD and evaluating the tumor’s growth pattern within the cervix will guide the clinician in tailoring the treatment. This would mean better triage of the patients to the adequate surgical procedure, to achieve safe clear surgical margins, and better identification of patients who should be excluded from surgery and be transitioned directly to exclusive chemo-radiation.