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Background: Incomplete mesorectal excision during rectal cancer surgery often leads to positive circumferential margins, with uncertain prognostic impacts. This study examines whether negative margins can mitigate the poorer prognosis typically associated with incomplete total mesorectal excision (TME) in rectal cancer surgery, thus potentially challenging the prevailing emphasis on complete mesorectal excision. Patients and methods: A retrospective analysis was conducted on patients who underwent proctectomy for rectal adenocarcinoma with incomplete TME at a single center from 2010 to 2022. Patients were stratified by margin status as determined by pathologic analysis into three groups: involved, not involved with closest margin distance ≤ 2 mm, and not involved with closest margin distance > 2 mm. Outcomes included recurrence and survival. Effects of neoadjuvant therapy protocols on margin status were also assessed. Results: From 2010 to 2022, 7941 patients underwent proctectomy for rectal cancer, with 236 (3%) having incomplete TME. The median age of these patients was 64 years, and 63% were male. Overall, margin involvement was observed in 54 (23%) patients. The median tumor size was 3.05 cm (interquartile range (IQR): 2–6) for the whole group. Involved margins (23.2%) had reduced overall survival (60.5 months versus 87.3 months, p < 0.001), increased local recurrence (20.4% versus 9.4%, p = 0.024), and lower disease-free survival (45.2 versus 58.9 months, p = 0.006) versus uninvolved margins. Margin involvement was prognostic for decreased survival even after adjusting for confounders (p < 0.05). Among uninvolved margins, distance (> 2 mm versus ≤ 2 mm) did not affect outcomes. Total neoadjuvant therapy (versus standard chemoradiation) was associated with lower involved margins (p = 0.007). Conclusions: Positive margins retain negative prognostic impact with incomplete TME. Optimization of surgical resection remains vital. Total neoadjuvant therapy was associated with a lower rate of margin involvement. [ABSTRACT FROM AUTHOR]

Craters on Mars are a window into Mars' past and the time they were emplaced. Because the crust is heated and shocked during impact, craters can demagnetize or magnetize the crust depending on the presence or absence of a dynamo field at the time of impact. This concept has been used to constrain dynamo timing. Here, we investigate magnetic anomalies associated with craters larger than 150 km. We find that most of those craters, independent of age, exhibit demagnetization signatures in the form of a central magnetic low. We demonstrate a statistically significant association between such signatures and craters, and hypothesize that the excavation of strongly magnetic crustal material may be an important contribution to the dominance of demagnetized craters. This finding implies that the simple presence or absence of crater demagnetization signatures is not a reliable indicator for the activity of the Martian dynamo during or after crater formation. Plain Language Summary: Craters on Mars allow studying the time at which they were emplaced and as such they are a window into Mars' past. Because the crust is heated and shocked during impact and thus recrystallization occurs, craters can demagnetize or magnetize the crust depending on the presence or absence of a dynamo field at the time of impact. A classic magnetization signature is expressed by a magnetic high in the crater interior and the youngest of those craters have been used to constrain dynamo timing. Here, we investigate magnetic anomalies associated with all craters larger than 150 km. We find that most of those craters and independent of age exhibit a demagnetization signature, and fewer a magnetization signature. In general, the largest craters show a demagnetization signature. To explain the dominance of demagnetization signatures we hypothesize that the excavation of strongly magnetic crustal material may be an important process. This finding implies that the simple presence or absence of crater magnetization signatures is not a reliable indicator for dynamo activity and magnetic signatures of craters are dependent on multiple parameters such as crustal thickness. Key Points: Craters on Mars dominantly show demagnetization signaturesLarge craters and thin crust promote magnetic lows in the crater interior irrespective of dynamo activityCrustal excavation is likely an important process that promotes demagnetization signatures [ABSTRACT FROM AUTHOR]

Introduction: Allan Hills 84001 (ALH 84001) is an orthopyroxenite Martian meteorite containing coarse-grained inclusions of chromites, carbonates and plagioclase feldspar, in addition to fine-grained iron oxides and sulfides that host a heterogeneously oriented natural remanent magnetization (NRM) [1]-[4]. The meteorite contains several shockinduced textures and mineral thermometers indicative of one or more impact events. The NRM hosted in the iron oxides and chromite-sulfide assemblages within the meteorite is understood to be a thermoremanent magnetization (TRM) and has two strongly magnetized components that do not share common alignment, in addition to several incoherent, weakly magnetized grains, indicative of an underlying mechanism capable of localized (~200 nm) heating [5]. We have developed a methodology, using thermal constraints from paleomagnetism and petrologic observation, where we are able to place new constraints on the shock pressures associated with multiple impacts suffered by the meteorite up to and including its ejection from Mars. To reconcile the reported thermal histories of the meteorite, we have simulated planar shock wave propagation through computational analogs of two samples of ALH 84001. Modeling: Using the iSALE-2D shock physics code [6]-[8], we have performed a suite of 'mesoscale' simulations to quantify the effects of impact-induced shockwaves likely to have been experienced by the meteorite. The materials used in our simulations are each described by an equation of state and strength model. As the availability of accurate equations of state for meteoritic materials is limited, we have used the closest analog materials possible. Results: We found strong and complex material shear responsible for steep thermal gradients throughout the sample. Shearing occurs principally in the rock matrix, using the (weaker) inclusions as nucleation points (Fig. 1). We see both intraand inter-material variations in temperature on length scales of tens of microns. Subsequent modeling of post-impact thermal equilibration reveals that the constituent materials reach equilibrium ~3 seconds after the release wave has passed through the meteorite (Fig. 1). This has implications for paleomagnetism: small fractions of the meteorite may be remagnetized in low-pressure impacts, meaning the meteorite is capable of hosting NRMs recorded at different times. Implications for Paleomagnetism: Palaeomagnetic studies of this meteorite have found a heterogeneously oriented pattern of remanent magnetization, indicative of remagnetization in the meteorite on the sub-millimeter scale, but the mechanism for such heterogeneous heating was unclear. We observe that portions of chromite grains close to shear zones will experience temperatures significantly higher than those elsewhere in the meteorite which only warm up to the equilibrium temperature. Since the meteorite was magnetized in an initial extensive thermal event where the whole meteorite was heated above the curie point of the chromite-sulfide assemblages, our simulations suggest that a subsequent impact with a bulk shock pressure between 25-45 GPa would achieve partial remagnetization. [ABSTRACT FROM AUTHOR]

Aims: This study aims to assess the changes in cardiac damage stage in a real-world cohort of patients undergoing transcatheter aortic valve implantation (TAVI) and to investigate the prognostic value of cardiac damage stage evolution., Methods and Results: Patients with severe AS undergoing TAVI were retrospectively analyzed. A 5-stage system based on the presence and extent of cardiac damage assessed by echocardiography was applied before and 6 months after TAVI. Multivariable Cox regression analyses were used to examine independent prognostic value of the changes in cardiac damage after TAVI. A total of 734 patients with severe AS (mean age 79.8±7.4 years, 55% male) were included. Before TAVI, 32 (4%) patients did not show any sign of extra-valvular cardiac damage (Stage 0), 85 (12%) had left ventricular damage (Stage 1), 220 (30%) left atrial and/or mitral valve damage (Stage 2), 227 (31%) pulmonary vasculature and/or tricuspid valve damage (Stage 3), and 170 (23%) right ventricular damage (Stage 4). Six months after TAVI, 39% of the patients improved at least 1 stage in cardiac damage. Staging of cardiac damage at 6 months after TAVI (HR per 1-stage increase 1.391; P = 0.035) as well as worsening in the stage of cardiac damage (HR 3.729, P = 0.005) were independently associated with 2-year all-cause mortality., Conclusion: More than one third of patients with severe AS showed an improvement in cardiac damage 6 months after TAVI. Staging cardiac damage at baseline and follow-up may improve risk stratification in patients undergoing TAVI., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Scotland currently has amongst the highest rates of drug-related deaths in Europe, leading to increased advocacy for safer drug consumption facilities (SDCFs) to be piloted in the country. In response to concerns about drug-related harms in Edinburgh, elected officials have considered introducing SDCFs in the city. This paper presents key findings from a feasibility study commissioned by City of Edinburgh Council to support these deliberations., Methods: Using a multi-method needs assessment approach, we carried out a spatial and temporal analysis of drug-related data in Edinburgh including health, mortality, consumption, crime and service provision indicators; and 48 interviews including 22 people with lived/living experience (PWLE) of drug use in the city, five family members affected by drug-related harms, and 21 professional stakeholders likely to be involved in commissioning or delivering SDCFs. Data were collected using a convergent parallel design. We carried out a descriptive analysis of quantitative date and a thematic analysis of qualitative data. Quantitative data provides an overview of the local context in terms of recorded harms, service provision and consumption patterns as reported in prior surveys. Qualitative PWLE and families data captures the lived experiences of people who use drugs, and affected loved ones, within that local context, including perceived consumption trends, views on the practicality of SDCF provision, and hopes and anxieties regarding potential service provision. Professional stakeholders data provides insights into how people responsible for strategic planning and service delivery view the potential role of SDCF provision within the context described in the quantitative data., Results: In Edinburgh, drug-related harms and consumption patterns are dispersed across multiple locations, with some areas of higher concentration. Reported levels of opioid use, illicit benzodiazepine use and cocaine injecting are high. Qualitative interviews revealed strong support for the provision of SDCFs, and a preference for services that include peer delivery. However, PWLE also expressed concerns regarding safety and security, and professional stakeholders remained uncertain as to the prioritisation of facilities and possible opportunity costs in the face of restricted budgets., Conclusion: There is a strong case for the provision of SDCFs in Edinburgh. However, service design needs to reflect spatial distributions of consumption and harm, patterns of consumption by drug type, and expressed preferences for both informality and security among potential service users. Models of SDCF provision used elsewhere in Scotland would therefore need to be adapted to reflect such considerations. These findings may apply more broadly to potential SDCF provision in the UK and internationally, given changing patterns of use and harm., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest., (© 2025. The Author(s).)

Background: Endoscopic submucosal dissection (ESD) is increasingly being adopted for the treatment of early-stage colorectal cancer (CRC) lesions., Methods: We retrospectively analyzed patients with early-stage CRC treated between 2015 and 2023, using ESD and colectomy databases, categorizing them into three groups: ESD only (n ​= ​24), oncological colorectal resection (OCR) only (n ​= ​90), and OCR after ESD (n ​= ​59). We compared pathological and oncological outcomes among these groups., Results: The OCR after ESD group demonstrated higher non-granular lesions, and deeper submucosal invasion compared to ESD only group. The primary OCR group showed higher 2-year overall survival compared to ESD-only group (98.9 ​% vs 85.6 ​%, p ​= ​0.01), with no colorectal cancer-related mortality in any of the groups. Notably, 2-year disease-free survival rates were comparable across all groups (93.8 ​% ESD only, 88.0 ​% primary OCR only, and 97.8 ​% for OCR after ESD, p ​= ​0.27)., Conclusion: The current study highlights feasibility the promising potential and oncologic safety of ESD in carefully selected patients with early malignant lesions., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Vasculitides are diseases marked by inflammation of the blood vessel walls across various organ systems. The mesenteric vasculitis (MV) affects localized mesenteric vessels of the gastrointestinal tract. It usually occurs as part of a systemic inflammatory process but could also present in isolation. There are very few published reports of isolated mesenteric artery vasculitis. Presenting symptoms often include nausea, vomiting, diarrhea, abdominal pain, rectal bleeding, often complicating the diagnostic process. Diagnosing MV as the cause of abdominal pain can be challenging, and failure to diagnose can result in significant morbidity and mortality. A timely and accurate diagnosis of MV is essential for administering the appropriate immunosuppressive therapy and preventing unnecessary surgical interventions. This review aims to provide a comprehensive discussion of MV, including its clinical presentation, diagnostic approaches, and treatment options, with a focus on achieving early diagnosis to enhance outcomes and prevent complications. Furthermore, this review addresses the diagnostic challenges associated with MV, including the lack of specific criteria and symptom overlap with other gastrointestinal disorders such as atherosclerotic mesenteric ischemia, infections, malignancies, adverse medication effects, and other vessel occlusive processes. It also emphasizes the gaps in current literature regarding optimal diagnostic strategies and the necessity for standardized treatment protocols. By addressing these gaps and challenges, we aim to optimize patient care and improve prognosis for individuals affected by MV., Competing Interests: Declaration of competing interest FZ: No Conflict of Interest related ot the submitted work. MB: No Conflict of Interest related ot the submitted work. YS: No Conflict of Interest related ot the submitted work. SM: No Conflict of Interest related ot the submitted work. RF: No Conflict of Interest related ot the submitted work. BS: No Conflict of Interest related ot the submitted work. SNA:No Conflict of Interest related ot the submitted work. BR: No Conflict of Interest related ot the submitted work. PB: No Conflict of Interest related ot the submitted work. VKT: No Conflict of Interest related ot the submitted work. GK: No Conflict of Interest related ot the submitted work. SH: No Conflict of Interest related ot the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Among rectal cancer patients treated with Total Neoadjuvant Therapy, it is unclear whether early, post-induction restaging is associated with final tumor response. If so, interim restaging may alter rectal cancer decision-making., Objective: To determine if post-induction restaging with endoscopy and magnetic resonance imaging is associated with final tumor response., Design: Retrospective cohort study., Settings: US tertiary care institution accredited by the National Accreditation Program for Rectal Cancer., Patients: Biopsy-proven rectal cancer patients who underwent Total Neoadjuvant Therapy with interim (post-induction) restaging., Main Outcome Measures: Association between response assessment on post-induction restaging and final treatment response., Results: 107 patients were analyzed. Patients with post-induction magnetic resonance tumor response grade 1 - 2 or complete endoscopic response were significantly more likely (odds ratio 5.4 [p < 0.01] and odds ratio 3.7 [p = 0.03], respectively) to ultimately achieve a final complete response. Likewise, the odds of a final incomplete response were significantly higher for patients with post-induction composite partial (odds ratio 4.1, p < 0.01) or minimal (odds ratio 12.0, p < 0.01) responses., Limitations: Retrospective analysis and lack of detailed subclassification of partial endoscopic response may have limited the conclusions of this data. Limited sample size may also have biased these conclusions., Conclusion: Tumor response to induction therapy is associated with ultimate treatment response to Total Neoadjuvant Therapy among complete or minimal responders; the significance of a partial interim response remains unclear. See Video Abstract., (Copyright © The ASCRS 2024.)

Background: The pulmonary vein (PV) flow pattern is influenced by the presence of mitral regurgitation (MR). After a successful reduction in MR severity, the pattern is expected to be changed. We aimed to evaluate the prognostic value of a change in the PV flow pattern in patients with primary MR undergoing mitral valve repair (MVR)., Methods: The PV flow pattern was assessed with transthoracic echocardiography in 216 patients (age 65 [IQR 56-72] years, 70% male) with primary MR before and after surgical MVR. The population was divided according to a change in the PV flow pattern following MVR into 'improvers' and 'non-improvers'., Results: Non-improvers (15%) had a higher prevalence of paroxysmal AF at baseline (46% vs. 22%, p = 0.004), left ventricular dysfunction (LVEF ≤60%) (39% vs. 21%, p = 0.020), and had lower systolic pulmonary artery pressure (28[IQR 25-38] vs. 35[IQR 26-48] mmHg, p = 0.018) compared to improvers (85%). After a median follow-up of 83[IQR 43-140] months, 26(12%) patients died. Non-improvers had higher mortality rates than improvers (p = 0.009). On multivariable Cox regression analysis, a lack of improvement in the PV flow pattern remained independently associated with all-cause mortality (HR 2.322, 95% CI 1.140 to 4.729, P = 0.020)., Conclusion: A lack of improvement in the PV flow pattern is independently associated with worse long-term survival in patients with primary MR undergoing MVR., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Patients with multiple sclerosis and Parkinson's disease may experience pelvic floor dysfunction and constipation which can affect ileoanal pouch emptying. This can lead to complications such as pouchitis, pouch dysfunction, and failure. We hypothesized that patients with neurological diseases have a higher rate of pouch failure and complications than healthy controls., Methods: Data were sourced from the institutional ileoanal pouch database. Patients with multiple sclerosis or Parkinson's disease, diagnosed before or after pouch construction, were matched to a control group of patients without neurological disease using propensity score-optimal matching. Demographics, postoperative and functional outcomes, and quality of life were analyzed., Results: Twenty-six patients (38%) with multiple sclerosis and 16 (62%) with Parkinson's disease were matched with 42 healthy controls. The overall median age was 39 years, median BMI was 25.3 kg/m 2 , and most patients were female (61.9%). Preoperative colorectal diagnoses included ulcerative colitis (83.3%), indeterminate colitis (9.5%), and Crohn's disease (7.1%). Patients with neurological diseases had higher ASA scores (class III, 57.1% vs. 21.4%; p < 0.01), fewer nocturnal bowel movements (median 0 vs. 2; p < 0.001), fewer bowel movements over 24 h (median 6 vs. 8; p = 0.01), and were less likely to recommend IPAA construction (72.7% vs. 97%; p = 0.01) than the controls. Other surgical, functional, and quality-of-life outcomes were similar., Conclusion: Patients with multiple sclerosis or Parkinson's disease might differ in pouch function compared with healthy controls. These neurological diseases might affect pouch function. The rate of pouch failure was similar, showing its feasibility despite multiple sclerosis and Parkinson's disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Multimorbidity - having 2 or more chronic diseases - is a national public health concern that entails burdensome and costly care for patients, their families, and public health programs. Adults residing in socially deprived areas often have limited access to social and material resources. They also experience a greater multimorbidity burden., Methods: We conducted a retrospective cohort analysis of electronic health record (EHR) data from 678 community-based health centers (CHCs) in 27 states from the Accelerating Data Value Across a National Community Health Center (ADVANCE) Network, a clinical research network, from 2012-2019. We used mixed-effects Poisson regression to examine the relationship of area-level social deprivation (eg, educational attainment, household income, unemployment) to chronic disease accumulation among a sample of patients aged 45 years or older (N = 816,921) residing across 9,362 zip code tabulation areas and receiving care in safety-net health organizations., Results: We observed high rates of chronic disease among this national sample. Prevalence of multimorbidity varied considerably by geographic location, both within and between states. People in more socially deprived areas with Social Deprivation Index (SDI) scores in quartiles 2, 3, and 4 had greater initial chronic disease counts - 17.1%, 17.7%, and 18.0%, respectively - but a slower rate of accumulation compared with people in the least-deprived quartile. Our findings were consistent for models of the composite SDI and those evaluating disaggregated measures of area-level educational attainment, household income, and unemployment., Conclusion: Social factors play an important role in the development and progression of multimorbidity, which suggests that an assessment and understanding of area-level social deprivation is necessary for developing public health strategies to address multimorbidity.

Background: The ultimate aim of medical education is to produce successful practitioners, which is a goal that educators, students and stakeholders support. These groups consider success to comprise optimum patient care with consequently positive career progression. Accordingly, identification of the common educational features of such high-achieving doctors will facilitate the generation of clinical excellence amongst future medical trainees. In our study we source data from British clinical merit award schemes and subsequently identify the medical school origins of anaesthetists who have achieved at least national distinction., Methods: Britain operates Distinction Award/Clinical Excellence Award schemes which honour National Health Service doctors in Scotland, Wales and England who are identified as high achievers. This quantitative observational study used these awards as an outcome measure in an analysis of the 2019-20 dataset of all 901 national award-winning doctors. Where appropriate, Pearson's Chi-Square test was applied., Results: The top five medical schools (London university medical schools, Edinburgh, Dundee, Aberdeen and Glasgow) were responsible for 56.4% of the anaesthetist award-winners, despite the dataset representing 85 medical schools. 93.6% of the anaesthetist merit award-winners were from European medical schools. 8.06% of the anaesthetist award-winners were international medical graduates compared with 11.5% non-anaesthetist award-winners being international medical graduates., Conclusions: The majority of anaesthetists who were national merit award-winners originated from only five, apparently overrepresented, UK university medical schools. In contrast, there was a greater diversity of medical school origins among the lower grade national award-winners; tier 3 award-winners represented 20 different medical schools from three continents. As well as ranking educationally successful university medical schools, this study assists UK and international students, by providing a roadmap for rational decision making when selecting anaesthetist and non-anaesthetist medical education pathways that are more likely to fulfil their career ambitions., (© 2024. The Author(s).)

Francisella tularensis is a Gram-negative facultative intracellular bacterial pathogen that is classified by the Centers for Disease Control and Prevention as a Tier 1 Select Agent. F. tularensis infection causes the disease tularemia, also known as rabbit fever. Treatment of tularemia is limited to few effective antibiotics which are associated with high relapse rates, toxicity, and potential emergence of antibiotic-resistant strains. Consequently, new therapeutic options for tularemia are needed. Through screening a focused chemical library and subsequent structure-activity relationship studies, we have discovered a new and potent inhibitor of intracellular growth of Francisella tularensis , D8-03. Importantly, D8-03 effectively reduces bacterial burden in mice infected with F. tularensis . Preliminary mechanistic investigations suggest that D8-03 works through a potentially novel host-dependent mechanism and serves as a promising lead compound for further development.

Background: The ultimate aim of medical education is to produce successful practitioners, which is a goal that educators, students and stakeholders support. These groups consider success to comprise optimum patient care with consequently positive career progression. Accordingly, identification of the common educational features of such high-achieving doctors will facilitate the generation of clinical excellence amongst future medical trainees. In our study we source data from British clinical merit award schemes and subsequently identify the medical school origins of pathologists who have achieved at least national distinction., Methods: Britain operates Distinction Award/Clinical Excellence Award schemes which honour National Health Service doctors in Scotland, Wales and England who are identified as high achievers. This quantitative observational study used these awards as an outcome measure in an analysis of the 2019-20 dataset of all 901 national award-winning doctors. Where appropriate, Pearson's Chi-Square test was applied., Results: The top five medical schools (London university medical schools, Aberdeen, Edinburgh, Oxford and Cambridge) were responsible for 60.4% of the pathologist award-winners, despite the dataset representing 85 medical schools. 96.4% of the pathologist merit award-winners were from European medical schools. 9.0% of the pathologist award-winners were international medical graduates in comparison with 11.4% of all 901 award-winners being international medical graduates., Conclusions: The majority of pathologists who were national merit award-winners originated from only five, apparently overrepresented, UK university medical schools. In contrast, there was a greater diversity in medical school origin among the lower grade national award-winners; the largest number of international medical graduates were in these tier 3 awards (13.9%). As well as ranking educationally successful university medical schools, this study assists UK and international students, by providing a roadmap for rational decision making when selecting pathologist and non-pathologist medical education pathways that are more likely to fulfil their career ambitions., (© 2024. The Author(s).)

Objective: We examine differences on the Self-Injury Implicit Association Test (SI-IAT) by history of non-suicidal self-injury (NSSI), in a test-retest design, to examine short-term temporal stability of SI-IAT scores., Method: Treatment-seeking participants ( N  = 113; 58% female; 89% White; M age = 30.57) completed the SI-IAT and self-report measures at two time points ( M Timeframe = 3.8 days)., Results: Data suggested NSSI (51% of the sample endorsed lifetime NSSI) was related to Time 1 (T1) identity and attitude, and affected stability of scores. T1 and T2 SI-IAT identity and attitude were more strongly related for participants with NSSI history. NSSI characteristics (recency; number of methods) affected stability., Conclusions: The short-term test-retest reliability of the SI-IAT is strong among those with NSSI history from T1 to T2. However, the SI-IATs use with participants without a history of NSSI was not supported beyond its established ability to differentiate between groups by NSSI history. This test may provide clinically-relevant assessment among those with a history of NSSI.

Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by cytochrome P450 (CYP) 2B6 enzyme. Several other enzymes are also involved in its bioactivation and affect its kinetics. Previous studies have shown the effect of the enzymes' genetic polymorphisms on Cy kinetics and its clinical outcome. These results were controversial primarily because of the involvement of several interacting enzymes in the Cy metabolic pathway, which can also be affected by several clinical factors as well as other drug interactions. In this review article, we present the effect of CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating enzyme, as well as discussing all previously reported enzymes and clinical factors that can alter Cy efficacy. Additionally, we present explanations for key Cy side effects related to the nature and site of its bioactivation. Finally, we discuss the role of busulphan in conditioning regimens in the Cy metabolic pathway as a clinical example of drug-drug interactions involving several enzymes. By the end of this article, our aim is to have provided a comprehensive summary of Cy pharmacogenomics and the effect on its kinetics. The utility of these findings in the development of new strategies for Cy personalized patient dose adjustment will aid in the future optimization of patient specific Cy dosages and ultimately in improving clinical outcomes. In conclusion, CYP2B6 and several other enzyme polymorphisms can alter Cy kinetics and consequently the clinical outcomes. However, the precise quantification of Cy kinetics in any individual patient is complex as it is clearly under multifactorial genetic control. Additionally, other clinical factors such as the patient's age, diagnosis, concomitant medications, and clinical status should also be considered., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Ibrahim El-Serafi and Sinclair Steele.)

Background and Objectives: Factors associated with physician practice choice include residency location, training experiences, and financial incentives. How length of training affects practice setting and clinical care features postgraduation is unknown., Methods: In this Length of Training Pilot (LoTP) study, we surveyed 366 graduates of 3-year (3YR) and 434 graduates of 4-year (4YR) programs 1 year after completion of training between 2013 and 2021. Variables assessed included reasons for practice setting choice, practice type, location, practice and community size, specialty mix, and clinical care delivery features (eg, integrated behavioral health, risk stratified care management). We compared different length of training models using χ2 or Fisher's exact tests for categorical variables and independent samples, and t test (unequal variances) for continuous variables., Results: Response rates ranged from 50% to 88% for 3YR graduates and 68% to 95% for 4YR graduates. Scope of practice was a predominant reason for graduates choosing their eventual practice, and salary was a less likely reason for those completing 4 years versus 3 years of training (scope, 72% vs 55%, P=.001; salary, 15% vs 22%, P=.028). Community size, practice size, practice type, specialty mix, and practice in a federally designated underserved site did not differ between the two groups. We found no differences in patient-centered medical home features when comparing the practices of 3YR to 4YR graduates., Conclusions: Training length did not affect practice setting or practice features for graduates of LoTP programs. Future LoTP analyses will examine how length of training affects scope of practice and clinical preparedness, which may elucidate other elements associated with practice choice.

Abstract: Swimming-induced pulmonary edema (SIPE) is a rare but life-threatening acute illness that can occur in otherwise healthy athletes and individuals. Also known as immersion pulmonary edema, SIPE presents in swimmers, snorkelers, and SCUBA divers. It occurs in persons under heavy exertion in cold water temperatures, leading to coughing, shortness of breath, and sometimes blood-tinged sputum. Under these conditions, there is increased pulmonary vascular pressure, which may ultimately lead to pulmonary edema. This article synthesizes the latest data on the prevalence, pathophysiology, etiology, risks, short- and long-term complications, and the efficacy of supportive medical treatment interventions., (Copyright © 2024 by the American College of Sports Medicine.)

Aims: Hand hygiene (HH) is an essential practice to evade the transmission of germs and minimize community-acquired infections. This study assesses the knowledge, attitude and practice (KAP) of HH and other health and safety measures before, during, and after the COVID-19 pandemic. in university students in the United Arab Emirates (UAE)., Methods: A cross-sectional questionnaire study was conducted between December 2022 and March 2023, targeting university students from all disciplines and study levels. A 44-item questionnaire was used which included student demographics, knowledge, attitude, and practice of HH, as well as the anticipated risk of COVID-19 morbidity and mortality. Participants consented before commencing the questionnaire, and the collected data were analysed using the student's t-test and ANOVA test, as required., Results: A total of 378 responses were received nationwide, with a valid response rate of 98%. The HH knowledge revealed an average score of 62%, which was significantly higher in students with moderate family income. Additionally, the average attitude score was 74.7%, as measured on the Likert scale, and the score lacked any correlation with the other variables. HH practice showed an average score of 86.8%, which was correlated with the students' gender and field of study., Conclusions: This study showed a moderate level of knowledge, a good attitude, and good practice around HH and other safety measures among the UAE's university students. Socioeconomic status, gender, and field of study influenced the study outcomes. This study highlights the need for effective awareness campaigns to reinforce students' health and safety, especially for male and non-health science students, in order to protect against communicable diseases., (© 2024 The Authors.)

Aim: Surgeons often have strong opinions about how to perform colorectal anastomoses with little data to support variations in technique. The aim of this study was to determine if location of the end-to-end (EEA) stapler spike relative to the rectal transection line is associated with anastomotic integrity., Method: This study was a retrospective analysis of a quality collaborative database at a quaternary centre and regional hospitals. Patients with any left-sided colon resection with double-stapled anastomosis were included (December 2019 to August 2022). Our primary endpoint was a composite outcome including positive air insufflation test, incomplete anastomotic donut, or thin/eccentric donut. Our secondary endpoint was clinical leak., Results: Overall, 633 patients were included and stratified by location of the stapler spike relative to the rectal transection line. Of note, 86 patients had an end-colon to anterior rectum ("reverse Baker") anastomosis with no crossing staple lines. The rates of the composite endpoint based on position of the stapler spike were 12.4% (anterior), 8.1% (through), 12.8% (posterior), 5.1% (corner), and 2.3% for the "reverse Baker" (p = 0.03). The overall rate of clinical leak was 3.8% and there were no differences between methods. In a multivariate analysis, the "reverse Baker" anastomosis was associated with decreased odds of poor anastomotic integrity when compared to anastomoses with crossing staple lines (OR 0.20, 95% CI: 0.05-0.87, p = 0.03)., Conclusions: For anastomoses with crossing staple lines, the position of the stapler spike relative to the rectal staple line is not associated with differences in anastomotic integrity. In contrast, anastomoses with no crossing staple lines resulted in significantly lower rates of poor anastomotic integrity, but no difference in clinical leaks., (© 2023 Association of Coloproctology of Great Britain and Ireland.)

Background: The use of intraoperative intra-articular morphine has been suggested to lower postoperative pain scores and opioid use. We sought to evaluate the effectiveness of intra-articular morphine with 0.75% ropivacaine when compared to the use of ropivacaine alone. Our study's purpose was to determine the efficacy of intra-articular morphine on pain control, opioid consumption, and discharge times in the immediate post-operative period., Methods: We retrospectively reviewed the charts of 100 patients who underwent hip arthroscopy with repair for femoroacetabular impingement (FAI) between 2021 to 2023. 50 patients who received 5 mg of intra-articular morphine injections intraoperatively were identified, and 50 who did not. Patients undergoing hip arthroscopy without repair, revision surgery, or combined hip arthroscopy and femoral osteotomy or periacetabular osteotomy were excluded. Demographics including age, sex, race, ethnicity, BMI, and tobacco use were recorded. Procedural factors included total operative time, traction time, and time to discharge. Pain scores were assessed using the Visual Analog Scale (VAS), and the initial Post-Anesthesia Care Unit (PACU) and final VAS score prior to discharge were recorded. Total acute opioid use was recorded using morphine milligram equivalents (MME) during post-operation to discharge. We used the Wilcoxon rank sum test and chi-square statistics on continuous and categorical variables, respectively. Statistically significant level was set as p<0.05., Results: No significant differences were found between demographics, operative time, traction time, or discharge time. The median age of patients in the non-morphine group was 29 (48% M, 52% F) and 24.5 (34% M, 66% F) in the morphine group. Differences between the morphine and non-morphine group in postoperative VAS scores were insignificant, with the mean initial PACU VAS scores (4.6 ± 3.0 vs 5.5 ± 3.0) and mean final PACU VAS scores (3.5 ± 1.9 vs 3.7 ± 1.4) respectively. Postoperative MME consumption difference was also insignificant (17.1 ± 7.4 vs 17.9 ± 7.3)., Conclusion: Intraoperative intra-articular morphine injection with ropivacaine does not provide a significant reduction in acute postoperative pain scores or opioid use when compared to ropivacaine use alone. Further investigation into the efficacy of intra-articular morphine is warranted. Level of Evidence: III ., Competing Interests: Disclosures: RW: Consultant – Smith and Nephew, Consultant – Conmed, Consultant – Responsive Arthroscopy, Research Support – Smith and Nephew R2018120186, Research Support – DOD W81XWH-18-PRORP-CTRA, Editorial Board - Arthroscopy Journal, Editorial Board – AJSM, Committee – AOSSM, Committee – ISHA, Committee – AANA. All other authors have no disclosures., (Copyright © The Iowa Orthopaedic Journal 2024.)