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Objectives: The Vascular Surgery In-Training Examination (VSITE) is a yearly exam evaluating vascular trainees' knowledge base. While multiple studies have evaluated variables associated with exam outcomes, few have incorporated training program-specific metrics. The purpose of this study is to evaluate the impact of the learning environment and burnout on VSITE performance., Methods: Data was collected from a confidential, voluntary survey administered after the 2020-2022 VSITE as part of the SECOND Trial. VSITE scores were calculated as percent correct then standardized per the American Board of Surgery. Generalized estimating equations with robust standard errors and an independent correlation structure were used to evaluate trainee and program factors associated with exam outcomes. Analyses were further stratified by integrated and independent training paradigms., Results: A total of 1385 trainee responses with burnout data were collected over three years (408 in 2020, 459 in 2021, 498 in 2022). On average, 46% of responses reported at least weekly burnout symptoms. On unadjusted analysis, burnout symptoms correlated with a 14 point drop in VSITE score (95% confidence interval (CI) -24- -4, p=0.006). However, burnout was no longer significant after adjusted analysis. Instead, higher PGY level, being in a relationship, identifying as male gender with or without kids, identifying as non-Hispanic white, larger programs, and having a sense of belonging within a program were associated with higher VSITE scores., Conclusions: Despite high rates of burnout, trainees generally demonstrate resilience in gaining the medical knowledge necessary to pass the VSITE. Performance on standardized exams is associated with trainee and program characteristics, including availability of support systems and program belongingness., (Copyright © 2024. Published by Elsevier Inc.)

Background: There is a push toward shorter length of stay (LOS) after surgery by hospitals, payers, and policymakers. However, the extent to which these changes have shifted the occurrence of complications to the postdischarge setting is unknown. The objectives of this study were to (1) evaluate changes in LOS and postdischarge complications over time and (2) assess factors associated with postdischarge complications., Study Design: Patients who underwent surgery across five specialties (colorectal, esophageal, hepatopancreatobiliary [HPB], gynecology, and urology) were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) procedure-targeted database (2014-2019). Trends in the proportion of postdischarge complications within 30 days of surgery and predictors of postdischarge complications were assessed using multivariable logistic regression., Results: Among 538,172 patients evaluated, median LOS decreased from 3 (2014) to 2 days (2019) (p < 0.001). Overall, 12.2% of patients experienced a 30-day complication, with 50.4% occurring postdischarge. with the highest in hysterectomy (80.9%), prostatectomy (74.6%), and cystectomy (54.6%). The overall postoperative complication decreased, but the proportion of postdischarge complications increased from 44.6% (2014) to 56.4% (2019) (p < 0.001), including surgical site infection (superficial/deep/organ space/wound dehiscence), other infection (pneumonia/urinary tract infection/sepsis), cardiovascular (myocardial infarction/cardiac arrest/stroke), and venous thromboembolism. Factors associated with an increased odds of postdischarge complications included Hispanic or other race, higher American Society of Anesthesiologists class, dependent functional status, increased body mass index, higher wound class, inpatient complication, longer operation, and procedure type (HPB/colorectal/hysterectomy/esophagectomy, vs. prostatectomy) (all p < 0.001)., Conclusion: This comprehensive retrospective analysis across five representative surgical specialties highlighted that although LOS has decreased over time, the proportion of postdischarge complications has increased over time. Focusing on the development of a comprehensive, proactive, postdischarge monitoring system to better identify and manage postdischarge complications is necessary., (Copyright © 2024 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

The α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an ionotropic glutamate receptor recognized for its active involvement in epilepsy. Through AMPAR functional alterations, multiple factors contribute to the increased susceptibility to seizures in the geriatric population. These factors include changes in the hippocampus, neuroinflammation, ischemic insults, amyloid deposition, previous seizures, alterations in the microenvironment, and neurovascular unit dysfunction. Perampanel, a noncompetitive AMPAR antagonist, has been approved for the treatment of focal and generalized epilepsy. However, a complete understanding of AMPAR's role in epileptogenesis and the pharmacotherapy of perampanel in the geriatric population remains elusive. To address this gap, we conducted a comprehensive literature review, screening 1557 articles and ultimately selecting 94 relevant ones. We provided insights into AMPAR functionality changes and perampanel's role in treating geriatric epilepsy. Various clinical trials and retrospective studies have demonstrated that the safety and efficacy of perampanel in the older population are comparable to those in the younger population, with overall good tolerability. It is also effective for treating focal and generalized onset seizures and possibly for managing status epilepticus. In conclusion, the existing body of evidence supports the safety and efficacy of perampanel in the geriatric population, indicating its potential as a valuable therapeutic option for focal and generalized epilepsy. Additional research is warranted to deepen our understanding of AMPAR's involvement in epileptogenesis and to refine the pharmacotherapeutic nuances in this specific demographic., Competing Interests: Declaration of competing interest None, there are no conflicts of interest to be declared by the authors., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Implicit bias is a potential factor in the severity of examinee rating during oral examinations. Ratings may be impacted by examinee characteristics, such as gender, that are independent of examinee knowledge base, clinical judgment, or test-taking ability. The effects of examiner-examinee gender concordance in the Vascular Surgery Certifying Examination (VCE) have not been previously studied. We explored whether examiner ratings and likelihood of passing the examination were influenced by gender concordance among examiners and examinees., Methods: Data collected from examinees who first attempted the VCE between 2018 and 2023 were analyzed. There were 1005 examinees (69.3% male and 30.1% female) and 121 examiners (71.9% male, and 28.1% female). Linear mixed-effects models and generalized linear mixed-effects models were used to evaluate the effects of examinee and examiner gender on VCE ratings and likelihood of passing the examination., Results: Examiner-examinee gender concordance had no significant impact on examiner ratings or likelihood of passing the examination. In addition, examinee gender alone had no significant impact on VCE rating or pass rates. Only Vascular Qualifying Examination scores explained more than 1% of the variance in total VCE scores for the gender model (F(1, 1003.5) = 71.08, P < .01, R 2  = 3%). Vascular Qualifying Examination scores were positively related to total VCE scores., Conclusions: Although implicit bias has the potential to impact examiner scoring, there is no evidence that this is the case with respect to gender in the VCE of the American Board of Surgery., Competing Interests: Disclosures None., (Copyright © 2024. Published by Elsevier Inc.)

Importance: The ability to pursue family planning goals is integral to gender equity in any field. Procedural specialties pose occupational risks to pregnancy. As the largest procedural specialty, general surgery provides an opportunity to understand family planning, workplace support for parenthood, obstetric outcomes, and the impact of these factors on workforce well-being, gender equity, and attrition., Objective: To examine pregnancy and parenthood experiences, including mistreatment and obstetric outcomes, among a cohort of US general surgical residents., Design, Setting, and Participants: This cohort study involved a cross-sectional national survey of general surgery residents in all programs accredited by the Accreditation Council for Graduate Medical Education after the 2021 American Board of Surgery In-Training Examination. Female respondents who reported a pregnancy and male respondents whose partners were pregnant during clinical training were queried about pregnancy- and parenthood-based mistreatment, obstetric outcomes, and current well-being (burnout, thoughts of attrition, suicidality)., Main Outcomes and Measures: Primary outcomes included obstetric complications and postpartum depression compared between female residents and partners of male residents. Secondary outcomes included perceptions about support for family planning, pregnancy, or parenthood; assisted reproductive technology use; pregnancy/parenthood-based mistreatment; neonatal complications; and well-being, compared between female and male residents., Results: A total of 5692 residents from 325 US general surgery programs participated (81.2% response rate). Among them, 957 residents (16.8%) reported a pregnancy during clinical training (692/3097 [22.3%] male vs 265/2595 [10.2%] female; P < .001). Compared with male residents, female residents more frequently delayed having children because of training (1201/2568 [46.8%] females vs 1006/3072 [32.7%] males; P < .001) and experienced pregnancy/parenthood-based mistreatment (132 [58.1%] females vs 179 [30.5%] males; P < .001). Compared with partners of male residents, female residents were more likely to experience obstetric complications (odds ratio [OR], 1.42; 95% CI, 1.04-1.96) and postpartum depression (OR, 1.63; 95% CI, 1.11-2.40). Pregnancy/parenthood-based mistreatment was associated with increased burnout (OR, 2.03; 95% CI, 1.48-2.78) and thoughts of attrition (OR, 2.50; 95% CI, 1.61-3.88). Postpartum depression, whether in female residents or partners of male residents, was associated with resident burnout (OR, 1.93; 95% CI, 1.27-2.92), thoughts of attrition (OR, 2.32; 95% CI, 1.36-3.96), and suicidality (OR, 5.58; 95% CI, 2.59-11.99)., Conclusions and Relevance: This study found that pregnancy/parenthood-based mistreatment, obstetric complications, and postpartum depression were associated with female gender, likely driving gendered attrition. Systematic change is needed to protect maternal-fetal health and advance gender equity in procedural fields.

Competing Interests: Disclosures None.

Exposure to cadmium may increase risk of urolithiasis, but the results remain inconclusive. This systematic review and meta-analysis aimed to access the association between cadmium exposure and urolithiasis. We searched Medline/PubMed, Embase, Web of Science Core Collection, and Cochrane Central for studies. The primary outcome was the incidence of urolithiasis compared to reference groups. We used relative risk as the summary effect measure. This meta-analysis included eight observational studies and divided into 39 study populations. Among 63,051 subjects, 5018 (7.96%) individuals had urolithiasis. The results indicated that people with an increment of 0.1 μg/g creatinine in urinary cadmium had a 2% increased risk of urolithiasis (pooled relative risk [RR], 1.02; 95% confidence interval [CI], 1.01-1.03) and there is no difference in the risk of urolithiasis in high and low cadmium exposure levels. Meanwhile, people with an increment of 0.1 μg/L in urinary cadmium had a 4% increased risk of urolithiasis (pooled RR, 1.04; 95% CI, 1.02-1.07). Our findings also showed similar associations in both sex, different region (Sweden, China, and Thailand), general and occupational population. The results indicate that cadmium exposure was significantly associated with an elevated risk of urolithiasis. Therefore, it is imperative to take steps to minimize cadmium exposure., 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 Inc.)

Background: Gastric cancer is a common malignant tumor of the digestive system worldwide, and its early diagnosis is crucial to improve the survival rate of patients. Indocyanine green fluorescence imaging (ICG-FI), as a new imaging technology, has shown potential application prospects in oncology surgery. The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice., Aim: To assess the diagnostic efficacy of optical imaging in conjunction with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy for gastric cancer., Methods: Electronic databases such as PubMed, Embase, Medline, Web of Science, and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy. Stata 12.0 software was used for analysis by combining the "bivariable mixed effect model" with the "midas" command. The true positive value, false positive value, false negative value, true negative value, and other information from the included literature were extracted. A literature quality assessment map was drawn to describe the overall quality of the included literature. A forest plot was used for heterogeneity analysis, and P < 0.01 was considered to indicate statistical significance. A funnel plot was used to assess publication bias, and P < 0.1 was considered to indicate statistical significance. The summary receiver operating characteristic (SROC) curve was used to calculate the area under the curve (AUC) to determine the diagnostic accuracy. If there was interstudy heterogeneity ( I 2 > 50%), meta-regression analysis and subgroup analysis were performed., Results: Optical imaging involves two methods: Near-infrared (NIR) imaging and fluorescence imaging. A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis. The positive likelihood ratio was 30.39 (95%CI: 0.92-1.00), the sensitivity was 0.95 (95%CI: 0.82-0.99), and the specificity was 1.00 (95%CI: 0.92-1.00). The negative likelihood ratio was 0.05 (95%CI: 0.01-0.20), the diagnostic odds ratio was 225.54 (95%CI: 88.81-572.77), and the SROC AUC was 1.00 (95%CI: The crucial values were sensitivity = 0.95 (95%CI: 0.82-0.99) and specificity = 1.00 (95%CI: 0.92-1.00). The Deeks method revealed that the "diagnostic odds ratio" funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical ( P = 0.01), suggesting significant publication bias. Further meta-subgroup analysis revealed that, compared with fluorescence imaging, NIR imaging had greater sensitivity (0.98 vs 0.73). Compared with optical imaging immediately after ICG injection, optical imaging after 20 minutes obtained greater sensitivity (0.98 vs 0.70). Compared with that of patients with an average SLN detection number < 4, the sensitivity of patients with a SLN detection number ≥ 4 was greater (0.96 vs 0.68). Compared with hematoxylin-eosin (HE) staining, immunohistochemical (+ HE) staining showed greater sensitivity (0.99 vs 0.84). Compared with subserous injection of ICG, submucosal injection achieved greater sensitivity (0.98 vs 0.40). Compared with 5 g/L ICG, 0.5 and 0.05 g/L ICG had greater sensitivity (0.98 vs 0.83), and cT1 stage had greater sensitivity (0.96 vs 0.72) than cT2 to cT3 clinical stage. Compared with that of patients ≤ 26, the sensitivity of patients > 26 was greater (0.96 vs 0.65). Compared with the literature published before 2010, the sensitivity of the literature published after 2010 was greater (0.97 vs 0.81), and the differences were statistically significant (all P < 0.05)., Conclusion: For the diagnosis of stomach cancer, optical imaging in conjunction with ICG-guided SLN biopsy is a therapeutically viable approach, especially for early gastric cancer. The concentration of ICG used in the SLN biopsy of gastric cancer may be too high. Moreover, NIR imaging is better than fluorescence imaging and may obtain higher sensitivity., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

DLL3 acts as an inhibitory ligand that downregulates Notch signaling and is upregulated by ASCL1, a transcription factor prevalent in the small-cell lung cancer (SCLC) subtype SCLC-A. Currently, the therapeutic strategies targeting DLL3 are varied, including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies. Although rovalpituzumab tesirine (Rova-T) showed promise in a phase II study, it failed to produce favorable results in subsequent phase III trials, leading to the cessation of its development. Conversely, DLL3-targeted BiTEs have garnered significant clinical interest. Tarlatamab, for instance, demonstrated enhanced response rates and progression-free survival compared to the standard of care in a phase II trial; its biologics license application (BLA) is currently under US Food and Drug Administration (FDA) review. Numerous ongoing phase III studies aim to further evaluate tarlatamab's clinical efficacy, alongside the development of novel DLL3-targeted T-cell engagers, both bispecific and trispecific. CAR-T cell therapies targeting DLL3 have recently emerged and are undergoing various preclinical and early-phase clinical studies. Additionally, preclinical studies have shown promising efficacy for DLL3-targeted radiotherapy, which employs β-particle-emitting therapeutic radioisotopes conjugated to DLL3-targeting antibodies. DLL3-targeted therapies hold substantial potential for SCLC management. Future clinical trials will be crucial for comparing treatment outcomes among various approaches and exploring combination therapies to improve patient survival outcomes., (© 2024. The Author(s).)

Background: An enriching learning environment is integral to resident wellness and education. Integrated vascular (VS) and general surgery (GS) residents share 18 months of core GS rotations during the postgraduate years 1-3 (PGY1-3); differences in their experiences may help identify practical levers for change., Methods: We used a convergent mixed-methods design. Cross-sectional surveys were administered after the 2020 American Board of Surgery In-Training Examination and Vascular Surgery In-Training Examination, assessing eight domains of the learning environment and resident wellness. Multivariable logistic regression models identified factors associated with thoughts of attrition between categorical PGY1-3 residents at 57 institutions with both GS and VS programs. Resident focus groups were conducted during the 2022 Vascular Annual Meeting to elicit more granular details about the experience of the learning environment. Transcripts were analyzed using inductive and deductive logics until thematic saturation was achieved., Results: Surveys were completed by 205 VS and 1198 GS PGY1-3 residents (response rates 76.8% for VS and 82.5% for GS). After adjusting for resident demographics, PGY level, and program type, GS residents were more likely than their VS peers to consider leaving their programs (odds ratio [OR]: 2.61, 95% confidence interval [CI]: 1.37-4.99). This finding did not persist after adjusting for differences in perceptions of the learning environment, specifically: GS residents had higher odds of mistreatment (OR: 1.99, 95% CI: 1.36-2.90), poorer work-life integration (OR: 2.88, 95% CI: 1.41-5.87), less resident camaraderie (OR: 3.51, 95% CI: 2.26-5.45), and decreased meaning in work (OR: 2.94, 95% CI: 1.80-4.83). Qualitative data provided insight into how the shared learning environment was perceived differently: (1) vascular trainees expressed that early specialization and a smaller, more invested faculty allow for an apprenticeship model with early operative exposure, hands-on guidance, frequent feedback, and thus early skill acquisition (meaning in work); (2) a smaller program is conducive to closer relationships with co-residents and faculty, increasing familiarity (camaraderie and work-life integration); and (3) due to increased familiarity with program leadership, vascular trainees feel more comfortable reporting mistreatment, allowing for prompt responses (mistreatment)., Conclusions: Despite sharing a learning environment, VS and GS residents experience training differently, contributing to differential thoughts of attrition. These differences may be attributable to intrinsic features of the integrated training paradigm that are not easily replicated by GS programs, such as smaller program size and higher faculty investment due to early specialization. Alternative strategies to compensate for these inherent differences should be considered (eg, structured operative entrustment programs and faculty incentivization)., Competing Interests: Disclosures None., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Work-related pain is a known risk factor for vascular surgeon burnout. It risks early attrition from our workforce and is a recognized threat to the specialty. Our study aimed to understand whether work-related pain similarly contributed to vascular surgery trainee well-being., Methods: A confidential, voluntary survey was administered after the 2022 Vascular Surgery In-Service Examination to trainees in all Accreditation Council for Graduate Medical Education-accredited vascular surgery programs. Burnout was measured by a modified, abbreviated Maslach Burnout Inventory; pain after a full day of work was measured using a 10-point Likert scale and then dichotomized as "no to mild pain" (0-2) vs "moderate to severe pain" (3-9). Univariable analyses and multivariable regression assessed associations of pain with well-being indicators (eg, burnout, thoughts of attrition, and thoughts of career change). Pain management strategies were included as additional covariables in our study., Results: We included 527 trainees who completed the survey (82.2% response rate); 38% reported moderate to severe pain after a full day of work, of whom 73.6% reported using ergonomic adjustments and 67.0% used over-the-counter medications. Significantly more women reported moderate to severe pain than men (44.3% vs 34.5%; P < .01). After adjusting for gender, training level, race/ethnicity, mistreatment, and dissatisfaction with operative autonomy, moderate-to-severe pain (odds ratio, 2.52; 95% confidence interval, 1.48-4.26) and using physiotherapy as pain management (odds ratio, 3.06; 95% confidence interval, 1.02-9.14) were risk factors for burnout. Moderate to severe pain was not a risk factor for thoughts of attrition or career change after adjustment., Conclusions: Physical pain is prevalent among vascular surgery trainees and represents a risk factor for trainee burnout. Programs should consider mitigating this occupational hazard by offering ergonomic education and adjuncts, such as posture awareness and microbreaks during surgery, early and throughout training., Competing Interests: Disclosures None., (Published by Elsevier Inc.)

Background: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure., Methods: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed., Results: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (β = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (β = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival., Conclusions: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: Occupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear., Objectives: This study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers., Methods: Questionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models., Results: Among 65 participants, the mean cumulative silica exposure was 3.61 mg/m 3 -year (range 0.0001 to 44.4). Each 1 mg/m 3 -year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03-1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p < 0.0001), and weighted tenure was associated with lung function abnormalities (aOR = 1.04, 95% CI = 1.01-1.09). Of 37 high-exposure workers, 19 underwent chest CT, with 12 (63%) showing abnormal opacities. Combining respiratory symptoms, lung function, and chest X-ray achieved 91.7% sensitivity and 75% specificity for predicting chest CT abnormalities., Conclusion: Lung function and chest CT abnormalities occur commonly in artificial stone workers. For high-exposure individuals, abnormalities on health screening could prompt further chest CT examination to facilitate early silicosis detection., (© 2024. The Author(s).)

Arterial thoracic outlet syndrome (TOS) is a condition in which anatomic abnormalities in the thoracic outlet cause compression of the subclavian or, less commonly, axillary artery. Patients are usually younger and typically have an anatomic abnormality causing the compression. The condition usually goes undiagnosed until patients present with signs of acute or chronic hand or arm ischemia. Workup of this condition includes a thorough history and physical examination; chest x-ray to identify potential anatomic abnormalities; and arterial imaging, such as computed tomographic angiography or duplex to identify arterial abnormalities. Patients will usually require operative intervention, given their symptomatic presentation. Intervention should always include decompression of the thoracic outlet with at least a first-rib resection and any other structures causing external compression. If the artery is identified to have intimal damage, mural thrombus, or is aneurysmal, then arterial reconstruction is warranted. Stenting should be avoided due to external compression. In patients with symptoms of embolization, a combination of embolectomy, lytic catheter placement, and/or therapeutic anticoagulation should be done. Typically, patients have excellent outcomes, with resolution of symptoms and high patency of the bypass graft, although patients with distal embolization may require finger amputation., 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 article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Many treatments against breast cancer decrease the level of estrogen in blood, resulting in bone loss, osteoporosis and fragility fractures in breast cancer patients. This retrospective study aimed to evaluate a novel opportunistic screening for cancer treatment-induced bone loss (CTIBL) in breast cancer patients using CT radiomics. Between 2011 and 2021, a total of 412 female breast cancer patients who received treatment and were followed up in our institution, had post-treatment dual-energy X-ray absorptiometry (DXA) examination of the lumbar vertebrae and had post-treatment chest CT scan that encompassed the L1 vertebra, were included in this study. Results indicated that the T-score of L1 vertebra had a strongly positive correlation with the average T-score of L1-L4 vertebrae derived from DXA (r = 0.91, p < 0.05). On multivariable analysis, four clinical variables (age, body weight, menopause status, aromatase inhibitor exposure duration) and three radiomic features extracted from the region of interest of L1 vertebra (original&#95;firstorder&#95;RootMeanSquared, wavelet.HH&#95;glcm&#95;InverseVariance, and wavelet.LL&#95;glcm&#95;MCC) were selected for building predictive models of L1 T-score and bone health. The predictive model combining clinical and radiomic features showed the greatest adjusted R 2 value (0.557), sensitivity (83.6%), specificity (74.2%) and total accuracy (79.4%) compared to models that relied solely on clinical data, radiomic features, or Hounsfield units. In conclusion, the clinical-radiomic predictive model may be used as an opportunistic screening tool for early identification of breast cancer survivors at high risk of CTIBL based on non-contrast CT images of the L1 vertebra, thereby facilitating early intervention for osteoporosis., (© 2024. The Author(s).)

Background: Cervical spinal injury often disrupts the supraspinal vasomotor pathways projecting to the thoracic sympathetic preganglionic neurons, leading to cardiovascular dysfunction. The current guideline is to maintain the mean arterial blood pressure at 85 to 90 mmHg using a vasopressor during the first week of the injury. Some studies have demonstrated that this treatment might be beneficial to alleviate secondary injury and improve neurological outcomes; however, elevation of blood pressure may exacerbate spinal hemorrhage, extravasation, and edema, exacerbating the initial injury., Purpose: The present study was designed to (1) examine whether vasopressor administration exacerbates spinal hemorrhage and extravasation; (2) evaluate whether spinal decompression surgery relieves vasopressor-induced spinal hemorrhage and extravasation., Study Design: In vivo animal study., Methods: Animals received a saline solution or a vasopressor (phenylephrine hydrochloride, 500 or 1000 μg/kg, 7 mL/kg/h) after mid-cervical contusion with or without spinal decompression (ie, incision of the dura and arachnoid mater). Spinal cord hemorrhage and extravasation were examined by expression of Evans blue within the spinal cord section., Results: The results demonstrated that cervical spinal contusion significantly reduced the mean arterial blood pressure and induced spinal hemorrhage and extravasation. Phenylephrine infusion significantly elevated the mean arterial blood pressure to the preinjury level within 15 to 60 minutes postcontusion; however, spinal hemorrhage and extravasation were more extensive in animals that received phenylephrine than in those that received saline. Notably, spinal decompression mitigated spinal hemorrhage and extravasation in contused rats who received phenylephrine., Conclusions: These data indicate that, although phenylephrine can prevent hypotension after cervical spinal injury, it also causes excess spinal hemorrhage and extravasation., Clinical Significance: Spinal decompressive surgery seemed to minimize the side effect of phenylephrine as vasopressor treatment during acute spinal cord injury., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mucin-1 is a multi-functional glycoprotein expressed by type II alveolocytes and may be detectable in the circulation following pulmonary fibrosis. The prognostic utility of baseline pre-treatment blood levels of mucin-1 in patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotics has not yet been fully established. We retrospectively studied a cohort of patients (from two hospitals) with IPF who were receiving pirfenidone for >12 weeks. Baseline blood mucin-1 levels were measured via sandwich enzyme-linked immunosorbent assays. We investigated the performance of mucin-1 levels in longitudinally predicting the risks of acute exacerbation of IPF (AE-IPF) and severe adverse outcomes (SAO), including lung transplantation and death. Seventy patients were included; 20 developed AE-IPF; and 31 had SAO during the follow-up period. Patients with baseline mucin-1 levels ≥2.5 ng/mL had enhanced risks of AE-IPF (adjusted hazard ratio [aHR], 14.07; 95% confidence interval [CI], 4.26-46.49) and SAO within 2 years (aHR, 7.87; 95% CI, 2.86-21.70) and anytime during the follow-up (aHR, 4.68; 95% CI, 2.11-10.39). The risks increased across subgroups with increasing mucin-1 levels. Patients in the "mucin-1 ≥ 2.5" group also exhibited an accelerated decline in D LCO . This study supports baseline blood mucin-1 levels as a biomarker for IPF that predicts adverse outcomes during pirfenidone treatment.

Osteoarthritis (OA) of the knee is a common degenerative articular disorder and is one of the main causes of pain and functional disability. Cartilage damage is frequently linked to elevated osteoarthritis incidence. Supercritical carbon dioxide (scCO 2 ) decellularized cartilage graft produced from the porcine cartilage is an ideal candidate for cartilage tissue engineering. In the present study, we derived collagen type II (Col II) solution from the scCO 2 decellularized porcine cartilage graft (dPCG) and compared its efficacy with hyaluronic acid (HA) in the surgical medial meniscectomy (MNX) induced post-traumatic osteoarthritis (PTOA) model. Dose-dependent attenuation of the OA (12.3 ± 0.8) progression was observed in the intra-articular administration of Col II solution (7.3 ± 1.2) which significantly decreased the MNX-induced OA symptoms similar to HA. The pain of the OA group (37.4 ± 2.7) was attenuated dose-dependently by Col II solution (45.9 ± 4.1) similar to HA (43.1 ± 3.5) as evaluated by a capacitance meter. Micro-CT depicted a dose-dependent attenuation of articular cartilage damage by the Col II solution similar to HA treatment. A significant (p < 0.001) dose-dependent elevation in the bone volume was also observed in Col II solution-treated OA animals. The protective competence of Col II solution on articular cartilage damage is due to its significant (p < 0.001) increase in the expression of type II collagen, aggrecan and SOX-9 similar to HA. To conclude, intra-articular administration of type II collagen solution and HA reestablished the injured cartilage and decreased osteoarthritis progression in the experimental PTOA model., (© 2024. The Author(s).)

Background: Non-surgical methods such as percutaneous drainage are crucial for the treatment of patients with severe acute pancreatitis (SAP). However, there is still an ongoing debate regarding the optimal timing for abdominal paracentesis catheter placement and drainage., Aim: To explore the influence of different timing for abdominal paracentesis catheter placement and drainage in SAP complicated by intra-abdominal fluid accumulation., Methods: Using a retrospective approach, 184 cases of SAP complicated by intra-abdominal fluid accumulation were enrolled and categorized into three groups based on the timing of catheter placement: group A (catheter placement within 2 d of symptom onset, n = 89), group B (catheter placement between days 3 and 5 after symptom onset, n = 55), and group C (catheter placement between days 6 and 7 after symptom onset, n = 40). The differences in progression rate, mortality rate, and the number of cases with organ dysfunction were compared among the three groups., Results: The progression rate of group A was significantly lower than those in groups B and groups C (2.25% vs 21.82% and 32.50%, P < 0.05). Further, the proportion of patients with at least one organ dysfunction in group A was significantly lower than those in groups B and groups C (41.57% vs 70.91% and 75.00%, P < 0.05). The mortality rates in group A, group B, and group C were similar ( P > 0.05). At postoperative day 3, the levels of C-reactive protein (55.41 ± 19.32 mg/L vs 82.25 ± 20.41 mg/L and 88.65 ± 19.14 mg/L, P < 0.05), procalcitonin (1.36 ± 0.51 ng/mL vs 3.20 ± 0.97 ng/mL and 3.41 ± 0.98 ng/mL, P < 0.05), tumor necrosis factor-alpha (15.12 ± 6.63 pg/L vs 22.26 ± 9.96 pg/L and 23.39 ± 9.12 pg/L, P < 0.05), interleukin-6 (332.14 ± 90.16 ng/L vs 412.20 ± 88.50 ng/L and 420.08 ± 87.65ng/L, P < 0.05), interleukin-8 (415.54 ± 68.43 ng/L vs 505.80 ± 66.90 ng/L and 510.43 ± 68.23ng/L, P < 0.05) and serum amyloid A (270.06 ± 78.49 mg/L vs 344.41 ± 81.96 mg/L and 350.60 ± 80.42 mg/L, P < 0.05) were significantly lower in group A compared to those in groups B and group C. The length of hospital stay in group A was significantly lower than those in groups B and group C (24.50 ± 4.16 d vs 35.54 ± 6.62 d and 38.89 ± 7.10 d, P < 0.05). The hospitalization expenses in group A were also significantly lower than those in groups B and groups C [2.70 (1.20, 3.55) ten-thousand-yuan vs 5.50 (2.98, 7.12) ten-thousand-yuan and 6.00 (3.10, 8.05) ten-thousand-yuan, P < 0.05). The incidence of complications in group A was markedly lower than that in group C (5.62% vs 25.00%, P < 0.05), and similar to group B ( P > 0.05)., Conclusion: Percutaneous catheter drainage for the treatment of SAP complicated by intra-abdominal fluid accumulation is most effective when performed within 2 d of onset., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The definition of irreparable rotator cuff tear (IRCT) is controversial. This scoping review provides definitions used to describe IRCT in the literature. This scoping review (1) identified criteria used in the definition of IRCT and (2) investigated the current state of those criteria in prospective surgical therapeutic trials., Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, Scopus, and Web of Science were searched in March 2023. Studies were screened against predetermined inclusion and exclusion criteria. Criteria regarding clinical symptoms, preoperative images, and intraoperative findings were captured respectively., Results: A total of 41 prospective studies were eligible for inclusion, and 35 studies (85.4%) defined IRCT. IRCT was defined on the basis of the following main criteria: preoperative image findings (28/35), intraoperative findings (24/35), and symptoms (16/35). With regard to preoperative images, IRCT was mainly defined on the basis of retraction of the tendon in the coronal plane (22/28), the severity of fatty degeneration (19/28), and ruptured tendon number or width of the defect in the sagittal plane (17/28)., Conclusion: This scoping review highlights the lack of a standardized definition for IRCT in clinical practice, with common predictive criteria including a duration of over 6 months, retraction beyond 5 cm, Goutallier grade 3 fatty infiltration, and the rupture of two or more tendons. However, surgeons should apply more than one criterion when examining preoperative images and confirm reparability during surgery. A more objective manner of evaluating intraoperative reparability is necessary., (© 2023. The Author(s).)

The development of microglial endotoxin tolerance (ET) is a critical event in protecting neurons against excessive immune responses when microglia are administered two consecutive lipopolysaccharide (LPS) challenges. However, the intrinsic mechanisms of microglia shape ET programs and protect neurons remain unclear. This study aimed to determine whether extracellular autocrine cascades or intracellular signaling pathways are involved in ET microglia-mediated tumor necrosis factor-alpha (TNF-α) reduction and neuroprotection. Neuron-glia cultures composed of astroglia, neurons, and microglia were performed in different conditions: with or without serum or LPS-binding proteins (LBP), along with an induction approach of ET. Enzyme-linked immunosorbent assay results revealed that LPS induced TNF-α tolerance of microglia in an LBP-dependent manner. Furthermore, we determined whether the early pro-inflammatory cytokines induced by LPS might contribute to the development of microglial ET. Our data showed that the neutralization of TNF-α using an anti-TNF-α antibody had no change in the TNF-α tolerance of microglia during the ET challenge. Furthermore, pre-incubation of TNF-α, interleukin-1 beta, and prostaglandin E2 failed to induce any TNF-α tolerance in microglia after LPS treatment. Moreover, using three specific chemical inhibitors that respectively blocked the activities of the mitogen-activated protein kinases (MAPKs) namely p38, c-Jun N-terminal kinase and extracellular signal-related kinases revealed that inhibition of p38 MAPK by SB203580 disrupted the tolerated microglia-mediated TNF-α reduction and neuroprotection. In summary, our findings demonstrated that the LPS pre-treatment immediately programmed the microglial ET to prevent endotoxin-induced TNF-α production and neuronal damage through the intracellular p38 MAPK signaling pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Mistreatment among vascular surgery trainees is a known risk factor for physician burnout. This study aims to characterize forms of and identify sources of mistreatment., Methods: This is a cross-sectional study of United States vascular surgery trainees who voluntarily participated in an anonymous survey administered after the 2021 Vascular Surgery In-Training Examination. The primary outcome measures were self-reported mistreatment and sources of mistreatment between genders. Logistic regression was used for multivariable analysis., Results: Representing all 125 vascular surgery training programs, 510 trainees (66.9% male) participated in the survey (83.6% response rate). Mistreatment was reported by 54.8% of trainees, with twice as many women reporting as men (82.3% vs 41.0%; P < .001). Women reported higher rates of being shouted at (44.1% vs 21.1%; P < .001); repeatedly reminded of errors (24.3% vs 16.1%; P = .04); ignored/treated hostilely (28.9% vs 10.5%; P < .001); subjected to crude/sexually demeaning remarks, stories, jokes (19.2% vs 2.1%; P < .001); evaluated by different standards (29.3% vs 2.1%; P < .001); and mistaken for a non-physician (75.2% vs 3.5%; P < .001). Among trainees reporting bullying, attendings were the most common source (68.5%). Patients and their families were the most common source of sexual harassment (66.7%), gender discrimination (90.4%), and racial discrimination (74.4%). Compared with men, women identified more patients and families as the source of bullying (50.0% vs 29.7%; P = .005), gender discrimination (97.2% vs 50.0%; P < .001), and sexual harassment (78.4% vs 27.3%; P = .003). Compared with men, women more frequently felt unprepared to respond to the behavior in the moment (10.4% vs 4.6%; P = .002), did not know how to report mistreatment at their institution (7.6% vs 3.2%; P = .04), and did not believe that their institution would take their mistreatment report seriously (9.0% vs 3.9%; P = .002). On multivariable analysis, female gender was an independent risk factor for both gender discrimination (odds ratio, 56.62; 95% confidence interval, 27.89-115) and sexual harassment (odds ratio, 26.2; 95% confidence interval, 3.34-14.8) when adjusting for children, training year, relationship status, and training program location., Conclusions: A majority of vascular surgery trainees experience mistreatment during training. Sources and forms of abuse are varied. Understanding the sources of mistreatment is critical to guide intervention strategies such as faculty remediation and/or sanctions; allyship training for staff, residents, and faculty; and institutional procedures for patient-initiated abuse., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Nutcracker syndrome is an extrinsic compression of the left renal vein by the superior mesenteric artery anteriorly and aorta posteriorly, resulting in hallmark manifestations of hematuria, proteinuria, and flank and/or pelvic pain. This report illustrates the case of a patient with a history of left flank pain and intermittent gross hematuria every 2 weeks. The patient denies any pelvic pain or gastrointestinal or lower extremity symptoms. Urinalysis revealed red blood cells, but no infection was noted. The cystoscopy findings were normal. Computed tomography urography showed left renal vein and duodenal compression between the aorta and superior mesenteric artery with a narrow aortic-superior mesenteric artery angle. The patient underwent left renal vein transposition to the distal inferior vena cava via a transabdominal approach. The left renal vein was transected at the inferior vena cava; however, the length was too short to create a tension-free anastomosis. Thus, a bovine pericardium sheet was tubularized and used as an interposition graft. The patient recovered well and is symptom-free. Left renal vein transposition is a well-described surgical technique in the treatment of nutcracker syndrome. The use of a vein or prosthetic graft has been described. This case demonstrates the use of an alternate conduit for reconstruction., (© 2023 The Author(s).)

Endovascular aortic aneurysm repair and thoracic endovascular aortic repair have been shown to reduce blood loss, operative time, length of hospital stay, mortality, and morbidity compared with open surgical repair for abdominal aortic aneurysms and thoracic aortic aneurysms. However, there are anatomical constraints that limit the application of the endovascular approach in 30% to 40% of patients, including those with short necks, excessive angulation, or aneurysms with the involvement of aortic side branches such as supra-aortic trunks, arch aneurysms, visceral arteries, or internal iliac arteries., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The second-and third-generation drug-eluting stents (DESs) in-stent restenosis (ISR) genetic risk score (GRS) model has been previously validated. However, the model has not been validated in geriatric patients. Therefore, we conducted this study to test the feasibility of the DES-ISR GRS model in geriatric patients with coronary artery disease (CAD) in Taiwan., Methods: We conducted a retrospective, single-center cohort study and included geriatric patients (age ≥ 65 years) with CAD and second-or third-generation DES(s) deployment. Patients undergoing maintenance dialysis were excluded. ISR was defined as ≥ 50% luminal narrowing on the follow-up coronary arteriography. The DES-ISR GRS model included five selected exonic single-nucleotide polymorphisms (SNPs): CAMLG, GALNT2, C11orf84, THOC5, and SAMD11. The GRS was defined as the sum of the five selected SNPs for the risk allele., Results: We enrolled 298 geriatric patients from January 2010 and December 2019 in this study. After propensity score matching, there were 192 geriatric patients with CAD in the final analysis, of which 32 patients had ISR. Patients were divided into two groups based on their GRS values: low (0-2) and high (≥ 3) GRS. A high GRS was significantly associated with DES-ISR in geriatric patients., Conclusion: Those geriatric patients with a high GRS had significantly higher second-or third-generation DES ISR rates. The five SNP-derived DES-ISR GRS model could provide genetic information for interventional cardiologists to treat geriatric patients with CAD., Trial Registration: The primary study protocol was registered with clinicaltrials.org. with registration number: NCT03877614; on March 15, 2019. ( http://clinicaltrials.gov/ct2/show/NCT03877614 )., (© 2023. The Author(s).)

Purpose: This study aimed to comprehensively review the existing evidence concerning surgical treatment of inferior pole fractures of the patella and to report the outcomes and complications of different fixation techniques., Method: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches of PubMed, Scopus, and Web of Science were conducted in March 2023. Studies were screened against predecided inclusion and exclusion criteria. The extracted data included fracture characteristics, surgical techniques, and radiographic and functional outcomes. The Methodological Index for Non-Randomized Studies (MINORS) quality assessment tool was used to assess the eligible literature. The primary outcome was postoperative range of motion of different surgical methods, and the secondary outcomes were other clinical results and complications., Results: A total of 42 studies satisfied all the inclusion criteria and were deemed suitable for review. Fourteen case-control studies and 28 case series were selected, for a total of 1382 patients with a mean age of 51.0 years (range = 11-90). The follow-up period ranged from 6 to 300 months. The surgical techniques were categorized based on the device used as follows: (1) rigid fixation device; (2) tensile fixation device; (3) mixed device; and (4) extra-patella device., Conclusion: Regarding the outcomes following surgical treatment of inferior pole fractures of the patella, the postoperative range of motion (ROM) of each technique ranged from 120° to 135°, with the exception of that involving the patellotibial wire which had poorer outcomes. The lowest functional score was also found in those using the patellotibial wire. Complications after surgery are rare, but approximately half of the patients required additional surgery for implant removal, particularly those whose initial surgery involved rigid fixation devices. It's worth noting that bony fragment excision is no longer recommended, and the combined use of multiple surgical devices is now more common., (© 2023. The Author(s).)

Background: Liver transplantation (LT) is the "cure" therapy for patients with hepatocellular carcinoma (HCC). However, some patients encounter HCC recurrence after LT. Unfortunately, there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy. The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population, and to evaluate whether these patients are suitable for adjuvant targeted therapy., Methods: Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed., Results: A total of 201 patients were included in the study. The multivariate Cox analysis suggested that preoperative alpha-fetoprotein (AFP) > 200 µg/L (HR = 2.666, 95% CI: 1.515-4.690; P = 0.001), glutamyl transferase (GGT) > 96 U/L (HR = 1.807, 95% CI: 1.012-3.224; P = 0.045), and exceeding the Hangzhou criteria (HR = 2.129, 95% CI: 1.158-3.914; P = 0.015) were independent risk factors for poor disease-free survival (DFS) in patients with HCC who underwent LT. We established an AFP-GGT-Hangzhou (AGH) scoring system based on these factors, and divided cases into high-, moderate-, and low-risk groups. The differences in overall survival (OS) and disease-free survival (DFS) rates among the three groups were significant (P < 0.05). The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria, UCSF criteria, Milan criteria, and TNM stage. Only in the high-risk group, we found that lenvatinib significantly improved prognosis compared with that of the control group (P < 0.05)., Conclusions: The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China. Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT., (Copyright © 2022. Published by Elsevier B.V.)

Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, reduces skeletal-related events (SREs) and is approved for solid tumors with bone metastases. We studied long-term denosumab efficacy and safety because real-world data is scarce. This single-arm, single-center retrospective study included denosumab-treated breast cancer patients with bone metastases. Kaplan-Meier survival curves assessed exposure, SREs, osteonecrosis of the jaw (ONJ), and death. 132 patients were enrolled. The median denosumab exposure was 28.3 months (range 1.0-84.9). In the first year, 11.1% experienced SREs. This increased to 18.6% in the second, 21% in the third, and 35.1% in the fourth year and beyond. The median time to first on-study SRE has not been reached. 10 denosumab users (7.6%) developed ONJ. ONJ incidence was 0.9% in the first year, 6.2% in the second, 13.6% in the third, and 16.2% in subsequent years. The median time to first on-study ONJ has not been reached yet. Seven patients resumed denosumab after careful management of ONJ. Our data suggest that long-term treatment with denosumab may further prevent or postpone SREs at the cost of an increased risk of ONJ. The majority of patients who resumed denosumab did not experience a recurrence of ONJ., (© 2023. The Author(s).)

The magnitude of drug-drug interaction between tacrolimus and voriconazole is highly variable, and individually tailoring the tacrolimus dose when concomitantly administered with voriconazole remains difficult. This study aimed to develop a semiphysiologically based population pharmacokinetic (semi-PBPK) model and a web-based dashboard to identify the dynamic inhibition of tacrolimus metabolism caused by voriconazole and provide individual tacrolimus regimens for Chinese adult liver transplant recipients. A total of 264 tacrolimus concentrations and 146 voriconazole concentrations were prospectively collected from 32 transplant recipients. A semi-PBPK model with physiological compartments including the gut wall, portal vein, and liver was developed using the nonlinear mixed-effects modeling software NONMEM (version 7.4). A web-based dashboard was established in R software (version 3.6.1) to recommend the individual tacrolimus regimens when concomitantly administered with voriconazole. The reversible inhibition of tacrolimus metabolism caused by voriconazole was investigated in both the liver and the gut wall. Moreover, voriconazole could highly inhibit the CYP3A activity in the gut wall more than in the liver. BMI and postoperative days were identified as significant covariates on intrinsic intestinal and hepatic clearance of tacrolimus, respectively. Age and postoperative days were identified as significant covariates on the volume of distribution of voriconazole. The individual tacrolimus regimens when concomitantly administered with voriconazole could be recommended in the dashboard (https://tac-vor-ddi.shinyapps.io/shinyapp3/). In conclusion, the semi-PBPK model successfully described the dynamic inhibition process between tacrolimus and voriconazole, and the web-based dashboard could provide individual tacrolimus regimens when concomitantly administered with voriconazole., (Copyright © 2023. Published by Elsevier B.V.)

With an ageing population, healthy longevity is becoming an important scientific concern. The longevity phenomenon is closely related to the intestinal microflora and is highly complicated; it is challenging to identify and define the core gut microbiota associated with longevity. Therefore, in this study, 16S rRNA sequencing data were obtained from a total of 135 faecal samples collected as part of the latest sampling and pre-collection initiative in the Guangxi longevity area, and weighted gene co-expression network analysis (WGCNA) was used to find a mediumpurple3 network module significantly associated with the Guangxi longevity phenomenon. Five core genera, namely, Alistipes , Bacteroides , Blautia , Lachnospiraceae NK4A136 group , and Lactobacillus , were identified via network analysis and random forest (RF) in this module. Two potential probiotic strains, Lactobacillus fermentum and Bacteroides fragilis , were further isolated and screened from the above five core genera, and then combined and used as an intervention in naturally ageing mice. The results show a change in the key longevity gut microbiota in mice toward a healthy longevity state after the intervention. In addition, the results show that the probiotic combination effectively ameliorated anxiety and necrosis of hippocampal neuronal cells in senescent mice, improving their antioxidant capacity and reducing their inflammation levels. In conclusion, this longer-term study provides a new approach to the search for longevity hub microbiota. These results may also provide an important theoretical reference for the healthification of the intestinal microflora in the general population, and even the remodelling of the structure of the longevity-state intestinal microflora.

This study aimed to develop and evaluate a population pharmacokinetic (PPK) combined machine learning approach to predict tacrolimus trough concentrations for Chinese adult liver transplant recipients in the early posttransplant period. Tacrolimus trough concentrations were retrospectively collected from routine monitoring records of liver transplant recipients and divided into the training data set (1287 concentrations in 145 recipients) and the test data set (296 concentrations in 36 recipients). A PPK model was first established using NONMEM. Then a machine learning model of Xgboost was adapted to fit the estimated individual pharmacokinetic parameters obtained from the PPK model with Bayesian forecasting. The performance of the final PPK model and Xgboost model was compared in the test data set. In the final PPK model, tacrolimus daily dose, postoperative days, hematocrit, aspartate aminotransferase, and concomitant voriconazole, were identified to significantly influence the clearance. The postoperative days along with hematocrit significantly influence the volume of distribution. In the Xgboost model, the first 5 predictors for predicting the clearance were concomitant with voriconazole, sex, single nucleotide polymorphisms of CYP3A4*1G and CYP3A5*3 in recipients, and tacrolimus daily dose, for the volume of distribution were postoperative days, age, weight, total bilirubin and graft : recipient weight ratio. In the test data set, the Xgboost model showed the minimum median prediction error of tacrolimus concentrations, less than the PPK model with or without Bayesian forecasting. In conclusion, a PPK combined machine learning approach could improve the prediction of tacrolimus concentrations for Chinese adult liver transplant recipients in the early posttransplant period., (© 2022, The American College of Clinical Pharmacology.)

Bronchopulmonary dysplasia (BPD) has been a critical morbidity in preterm infants. To improve our definition and prediction of BPD is challenging yet indispensable. We aimed to apply machine learning (ML) to investigate effective models by using the recently-proposed and data-driven definition to predict late respiratory support modalities at 36 weeks' post menstrual age (PMA). We collected data on very-low-birth-weight infants born between 2016 and 2019 from the Taiwan Neonatal Network database. Twenty-four attributes associated with their early life and seven ML algorithms were used in our analysis. The target outcomes were overall mortality, death before 36 weeks' PMA, and severity of BPD under the new definition, which served as a proxy for respiratory support modalities. Of the 4103 infants initially considered, 3200 were deemed eligible. The logistic regression algorithm yielded the highest area under the receiver operating characteristic curve (AUROC). After attribute selection, the AUROC of the simplified models remain favorable (e.g., 0.801 when predicting no BPD, 0.850 when predicting grade 3 BPD or death before 36 weeks' PMA, and 0.881 when predicting overall mortality). By using ML, we developed models to predict late respiratory support. Estimators were developed for clinical application after being simplified through attribute selection., (© 2023. The Author(s).)

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed., (© 2023. The Author(s).)

Background: Percutaneous endovascular treatment for arterial vascular diseases has revolutionized vascular care. While these procedures offer improved morbidity, mortality, and length of stay (LOS), their effect on postdischarge complications is unknown. The objectives of the study were to evaluate trends in LOS and postdischarge complications over time and to assess factors associated with postdischarge complications., Methods: Patients who underwent surgery for common vascular pathologies (abdominal aortic aneurysm, aortoiliac occlusive disease, lower extremity disease, and carotid stenosis) were identified from the American College of Surgeons National Surgical Quality Improvement Program procedure-targeted database (2014-2019). Outcomes included LOS, 30-day complications, and proportions of postdischarge complications. Predictors of postdischarge complications were assessed using a multivariable logistic regression., Results: Of 80,311 patients evaluated, median LOS did not change from 2014 to 2019 (2, interquartile range 1-5). Overall, 15.7% of patients experienced any 30-day complication, with 31.3% occurring after discharge. The proportion of postdischarge complications increased from 29.1% (2014) to 35.9% (2019), P < 0.001. With exception of carotid procedures, endovascular procedures had lower overall complication rates than open procedures; however, there was an increased proportion of postdischarge complications for endovascular procedures (all P < 0.001). Factors associated with an increased odds of postdischarge complications included female, Black or other race, dependent functional status, underweight or obesity, increased LOS, and procedural time, all P < 0.05., Conclusions: Across 4 representative common vascular pathologies, endovascular treatments had a higher proportion of postdischarge complications compared to open procedures. Early identification and evaluation of postdischarge complications for endovascular patients may be warranted to avoid unplanned readmission., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Little is known about the patterns of child maltreatment change over time and vary according to gender and child protective services (CPS) experience in Taiwan., Objective: To examine the latent status and the trajectories of child maltreatment and to identify effects that gender and CPS have on these statuses and trajectories in Taiwan., Participants and Setting: A national proportionately stratified sample of 6233 4th-grade students were recruited from 314 elementary schools in Taiwan, and followed up at 6th and 8th graders. A total of 1908 students completed valid data at all three time points was analyzed., Methods: Latent class analysis and latent transition analysis were used to identify the number of latent variables and the patterns of child maltreatment. Multiple-group model was used to test with gender difference., Results: Four latent maltreatment statuses were identified: high all maltreatment, high psychological maltreatment, high neglect, and no/low maltreatment. A reduction in maltreatment severity occurred over time was found. The percentage of students in the "high all maltreatment" and "high neglect" groups decreased whereas those in the "high psychological maltreatment" and "no/low maltreatment" groups increased. Differences in the transition probabilities of latent maltreatment status by gender was revealed. The percentage of CPS recipients in the "high all maltreatment" decreased over time., Conclusions: This study highlighted the dynamic nature of child maltreatment and described the timing, continuity, and change that characterizes children's exposure to maltreatment in Taiwan. Policies and interventions geared toward early detection, mitigation, and prevention of child maltreatment are needed., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Racial/ethnic discrimination is one form of mistreatment and a known risk factor for physician burnout. In the present study, we aimed to characterize the forms and identify the sources of racial/ethnic discrimination among vascular surgery trainees., Methods: We performed a cross-sectional study of U.S. vascular surgery trainees who had voluntarily participated in an anonymous survey administered after the 2021 Vascular Surgery In-Training Examination. The primary outcome measures were self-reported mistreatment and sources of mistreatment between race and ethnicity groups. We used χ 2 tests and logistic regression for bivariate and multivariable analyses, respectively., Results: Representing all 123 vascular surgery training programs, 510 trainees (66.9% men) participated in the survey (83.6% response rate). Most of the trainees had self-identified as White (53.1%), followed by Asian (24.4%), Hispanic/Latinx (7.6%), Black (4.2%), and other/prefer not to say (10.8%). No significant differences were found in the self-reported duty hour violations among the groups. Black (56.3%) and Asian (36.3%) trainees reported higher rates of racial/ethnic discrimination compared with the White, Hispanic/Latinx, and other/prefer not to say groups (P < .001). Patients and their families were reported as the most common source (74.7%). Other reported sources of discrimination included nurses or staff (60%), attendings (37.4%), co-residents (31.3%), and administration (16.9%). Regarding specific forms of racial discrimination, Black and Asian trainees reported the highest rates of different standards of evaluation (20% and 5.9%, respectively), being mistaken for a nonphysician (50.0% and 5.9%, respectively), slurs and/or hurtful comments (13.3% and 5.9%, respectively), social isolation (13.0% and 1.0%, respectively), and being mistaken for another trainee of the same race/ethnicity (60.0% and 33.7%, respectively). Only 62.5% of Black trainees reported their program/institution would take their mistreatment report seriously compared with the White (88.9%), Hispanic/Latinx (88.2%), Asian (83.2%), and other/prefer not to say (71.4%) trainees (P = .01). On multivariable analysis, female gender (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.44-4.33), Asian race (OR, 6.9; 95% CI, 3.53-13.3), Black race (OR, 13.6; 95% CI, 4.25-43.4), and training in the Southeastern United States (OR, 3.8; 95% CI, 1.17-12.80) were risk factors for racial/ethnic discrimination., Conclusions: The results from the survey revealed that racial/ethnic discrimination persists in surgical training programs, with Asian and Black trainees reporting higher rates than other racial and ethnic groups. Overall, patients and family members were the most common source of racial/ethnic discrimination. However, faculty, staff, and co-trainees also contributed to racial/ethnic discrimination. Further interventions that optimize diversity, equity, and inclusion strategies and policies to address all forms of racial/ethnic discrimination with faculty, staff, and patients within the hospital are critically needed., (Published by Elsevier Inc.)

Tyrosine kinase inhibitors (TKIs) improve the prognosis of patients with gastrointestinal stromal tumors (GISTs). We conducted a retrospective cohort study using cancer registries linked with health utilization data in Japan and Taiwan to assess TKI usage in older and non-older patients. Patients diagnosed with GIST (2012-2014) were categorized into the following: adjuvant and advanced/metastatic settings. The duration and patterns of imatinib therapy were compared between the older (aged ≥ 75 years) and non-older (< 75 years) groups. We included 232 Japanese and 492 Taiwanese patients in the adjuvant setting, and 235 Japanese and 401 Taiwanese patients in the advanced/metastatic setting. Older patients had higher proportions of starting with lower doses (< 400 mg/day) than the non-older patients (adjuvant: 22.5% vs. 4.3% [Japan]; 22.5% vs. 10.9% [Taiwan]; advanced/metastatic: 29.6% vs. 7.2% [Japan]; 32.6% vs. 8.1% [Taiwan]; all p < 0.01). The median time to stop imatinib was shorter in the older than in the non-older patients (adjuvant: 301 vs. 975 days [Japan], 366 vs. 1028 days [Taiwan]; advanced/metastatic: 423 vs. 542 days [Japan]; 366.5 vs. 837 days [Taiwan]). More older patients with GIST tended to have TKIs at a lower initial dose and a shorter imatinib duration than the non-older patients., (© 2022. The Author(s).)

Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms. Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM ® . Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis-Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens. Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h -1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate ( V max ) of the nonlinear MM model was 6.62 mg day -1 ; the average concentration at steady state at half- V max ( K m ) was 6.46 ng ml -1 . The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations. Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Li, Li, Tao, Zhang, Shen, Zhang, Wang and Jiao.)

Background: Ischemic stroke is a devastating complication of thoracic endovascular aortic repair (TEVAR). This risk may be higher in more proximal aneurysms that require arch manipulation. The purpose of this study is to (1) describe 30-day stroke and death rates in patients undergoing TEVAR, (2) compare stroke rates in patients undergoing TEVAR for arch versus descending aneurysm pathology, and (3) identify predictive factors associated with stroke after TEVAR., Methods: The Vascular Quality Initiative registry was queried (2015-2021) for TEVAR procedures performed for degenerative aneurysms. Our primary outcomes were any stroke or death at 30 days. Patient-, procedure-, and hospital-level predictors of stroke were assessed using multivariable Poisson regression., Results: Among 3,072 patients with degenerative aneurysms (197 [6.4%] arch versus 2,875 [93.6%] descending) treated with elective TEVAR, the median age was 73 years (interquartile range 67-79) and 54.8% were male. Within the arch aneurysm group, there were 27.4% zone 0, 22.8% zone 1, and 49.8% zone 2 interventions. Overall 30-day stroke and death rates were 3.2% and 3.8%. The distribution of stroke events was bilateral (52.9%), left carotid (20.7%), left vertebrobasilar (11.5%), right carotid (9.2%), and right vertebrobasilar (5.7%). Although mortality was similar between groups, the rate of ischemic stroke was higher for patients undergoing TEVAR for arch aneurysm versus descending aneurysms (7.1% arch versus 2.9% descending, P = 0.001). Factors that were associated with ischemic stroke after TEVAR included age (>79 years, relative risk [RR] 1.79, 95% confidence interval [CI] 1.08-2.98 vs. <79 years), dependent functional status (RR 1.73, 95% CI 1.07-2.78), procedural time (RR 1.25, 95% CI 1.15-1.36), and endovascular intervention for supra-aortic trunk revascularization (RR 2.66, 95% CI 1.06-6.70 versus no intervention)., Conclusions: Ischemic stroke risk after TEVAR was increased for arch aneurysms compared to descending aneurysms. More proximal zone coverage and endovascular interventions on the supra-aortic trunks were associated with increasing risk for stroke. Adequate preparation for stroke prevention is necessary prior to TEVAR with supra-aortic trunk revascularization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients., Methods: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively., Results: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor., Conclusions: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015)., (© 2022. The Author(s).)

Background: Radiation-induced hypothyroidism (RIHT) is a common, but underestimated, late adverse effect in head and neck cancer. We investigated the value of early post-treatment 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting RIHT., Methods: We searched our institutional database for patients aged ≥ 20 years who had undergone definitive radiotherapy for nasopharyngeal or oropharyngeal cancer between 2005 and 2017, followed by 18 F-FDG PET/CT within 180 days of radiotherapy completion. We visually assessed and compared PET/CT and baseline characteristics in patients with and without RIHT using the chi-square test for categorical variables and the t-test for continuous variables. Variable predictive ability was evaluated by measuring the area under receiver operating characteristic curves., Results: Fifty-two patients were included; 22 (42%) developed RIHT and 30 (58%) did not. Two patients presented with diffuse thyroid uptake on PET/CT via visual assessment, and both developed RIHT later. Among the PET/CT variables, thyroid functioning volume was significantly higher in patients without RIHT than in patients with RIHT (16.30 ± 6.03 cm 3 vs. 10.61 ± 3.81 cm 3 , p < 0.001). The maximum standard uptake values of the thyroid and pituitary glands did not differ significantly between the groups. Two patient characteristics, pretreatment thyroid volume and mean radiotherapy dose to the thyroid, also showed significant differences between the groups. An algorithmic approach combining visual grading of thyroid 18 F-FDG uptake and thyroid functioning volume cutoff of 14.01 yielded an area under curve of 0.89 (95% confidence interval, 0.80-0.98); the sensitivity, specificity, positive predictive value, and negative predictive value were 87.0%, 82.3%, 80.0%, and 88.9%, respectively., Conclusion: Early post-treatment PET/CT-derived thyroid functioning volume was a good predictor of RIHT development. Diffusely increased thyroid 18 F-FDG uptake on PET/CT may indicate impending RIHT. Routine surveillance of thyroid function is warranted in patients at high risk of developing RIHT., (© 2022. The Author(s).)

To investigate the effects of gravel content on runoff and sediment yield on Lou soil accumulation slopes, we conducted indoor simulation rainfall experiments and examined the characteristics of runoff and sediment yield on accumulation slopes with five gravel contents (10%, 20%, 30%, 40%, 50%) under four rainfall intensities (1.0, 1.5, 2.0, 2.5 mm·min -1 ), with a no gravels slope as control. The average runoff rate under different test conditions ranged from 2.18 to 13.07 L·min -1 . The average runoff rate was the maximum under the gravel content of 10% (or 20%) and the minimum under the 50% gravel content. The average flow velocity ranged from 0.06 to 0.22 m·s -1 . The variation of flow velocity was complex. The smaller the gravel content, the larger the range of variation and the coefficient of variation. The average flow velocity reached the maximum when the gravel content was 10%. The presence of gravel effectively inhibited the sediment yield, and the sediment reduction benefit reached 84.2%. The rainfall intensity had more influence on the average sediment yield rate than gravel content. Results of partial correlation analysis showed that gravel content was significantly negatively correlated with the ave-rage runoff rate, the average flow velocity, and the average sediment yield rate. The relationships between the ave-rage sediment yield and the average runoff rate, the average flow velocity, and their interaction were all extremely significant linear functions, with the strongest relationship between the average sediment yield and the average runoff rate. This study could provide references for the control of soil erosion and the establishment of erosion models for engineering accumulations in Lou soil areas.

Introduction: With widespread adoption of enhanced recovery protocols and a push toward shorter length of stay (LOS) following colon surgery, the extent to which complications have shifted to the post-discharge setting is unknown. The objectives of this study were to (1) characterize changes in LOS and post-discharge complications over time and (2) evaluate risk factors associated with post-discharge complications., Methods: Patients who underwent elective colon resection from 2012 to 2018 were identified from the ACS NSQIP Colectomy-Targeted Dataset. Changes in LOS and the proportion of post-discharge complications were evaluated over time, and predictors of post-discharge complications were assessed using multivariable logistic regression., Results: Of the 98,136 patients who underwent colon resection, median LOS decreased from 5 days in 2012 to 4 days in 2018. Overall, 30-day complication rate was 21.5%, which decreased during the study period (25.8 to 19.1%, p < 0.001). Of the 13 individual complications evaluated, 4 demonstrated a significant increase in the proportion of post-discharge events including overall SSI (55.8 to 63.3%, p = 0.002), superficial SSI (57.3 to 75.7%, p < 0.001), wound disruption (46.0 to 62.1%, p = 0.047), and UTI (41.5 to 62.7%, p < 0.001). Factors associated with the development of any post-discharge complication included female sex, ASA III/IV/V, dependent functional status, and higher BMI. Intraoperative factors included wound class, operation time, and approach., Conclusions: Although LOS and 30-day complications decreased over time, the proportion of events occurring post-discharge increased for several complications. We identified specific factors associated with post-discharge complications which emphasize the importance of a patient monitoring program to early identify and manage post-discharge complications., (© 2022. The Society for Surgery of the Alimentary Tract.)

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2 , GPAA1 , NDUFA4L2 , NEDD9 , and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2 , GPAA1 , and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Tao, Shen, Li, Wang, Xing, Ma, Xue, Zhang, Ma and Wang.)

Concurrent chemoradiotherapy is the established treatment for locally advanced nasopharyngeal carcinoma (NPC). However, there is no evidence supporting routine adjuvant chemotherapy. We aimed to demonstrate the effect of adjuvant chemotherapy on survival and distant metastasis in high-risk N3 NPC patients. We linked the Taiwan Cancer Registry and Cause of Death database to obtain data. Clinical N3 NPC patients were divided as those receiving definitive concurrent chemoradiotherapy (CCRT) with adjuvant 5-fluorouracil and platinum (PF) chemotherapy and those receiving no chemotherapy after CCRT. Patients receiving neoadjuvant chemotherapy were excluded. We compared overall survival, disease-free survival, local control, and distant metastasis in both groups using Cox proportional hazards regression analysis. Propensity-score matching was also performed to evaluate the independent effect of adjuvant PF in a matched cohort with similar baseline characteristics. We included 431 patients (152 and 279 patients in the adjuvant PF and observation groups, respectively). Median follow-up was 4.3 years. The 5-year overall survival were 69.1% and 57.4% in the adjuvant PF chemotherapy and observation groups, respectively (p = 0.02). Adjuvant PF chemotherapy was associated with a lower risk of death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43-0.84; p = 0.003), even after adjusting for baseline prognostic factors (HR 0.61, 95% CI 0.43-0.86; p = 0.005). Distant metastasis-free survival at 12 months was higher in the adjuvant PF chemotherapy group than in the observation group (98% vs 84.8%; p < 0.001). After adjusting for baseline prognostic factors, adjuvant PF chemotherapy was associated with freedom from distant metastasis (HR 0.11, 95% CI 0.02-0.46; p = 0.003). Adjuvant chemotherapy was also associated with a decreased risk of death (HR 0.59, 95% CI 0.41-0.85, p = 0.004) in a propensity score-matched cohort. Prospective evaluation of adjuvant PF chemotherapy in N3 NPC patients treated with definitive CCRT is warranted because adjuvant PF chemotherapy was associated with improved overall survival and decreased risk of distant metastasis., (© 2022. The Author(s).)