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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.)

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).)

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).)

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).)

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.

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).)

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: 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).)

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).)

This meta-analysis compared the outcomes of transradial access (TRA) and transfemoral access (TFA) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in recent decades. We searched multiple databases for articles published between January 1, 2015, and December 31, 2020. Six observational studies with 11,736 patients were analyzed. Data included baseline demographics, Japan-chronic total occlusion (J-CTO) score, sheath size, PCI vessel, retrograde method, procedural time, fluoroscopy time, and contrast volume. The more prevalent target CTO vessel was the left coronary artery in the TRA group and the right coronary artery in the TFA group. Higher J-CTO score, longer procedural time, and more contrast volume were seen in the TFA group. In comparison, the TRA group had better procedural success rate (odds ratio (OR), 0.846; 95% confidence interval (CI) 0.749-0.956) and less vascular complications (OR, 0.323; 95% CI 0.203-0.515), but similar retrograde success rate (OR, 0.965; 95% CI 0.382-2.435). In-hospital death (OR, 0.527; 95% CI 0.187-1.489) and major adverse cardiovascular events (OR, 0.729; 95% CI 0.504-1.054) did not differ between the groups. Overall, fewer vascular complications and higher procedural success rates were noted in the TRA CTO PCI population. However, similar retrograde success rates and clinical outcomes were noted between the groups., (© 2022. The Author(s).)

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used in treating cardiovascular diseases. Previous studies indicated that ACEIs/ARBs may benefit cancer patients by inhibiting tumor angiogenesis and proliferation. The effect of ACEIs/ARBs on cancer survival in esophageal and gastric cancer is still unclear. This study is to investigate the association between ACEIs/ARBs usage and esophageal and gastric cancer prognosis., Methods: This retrospective cohort study identified esophageal and gastric cancer patients during 2008-2016 from the Taiwan Cancer Registry, and obtained medication usage and follow-up information from the National Health Insurance Research Database and Death Registry. Analysis groups were defined as ACEIs/ARBs user or non-user based on the usage of ACEIs/ARBs within the 6 months after cancer diagnosis. The stabilized inverse probability of treatment weighting using propensity scores was applied to balance covariates between study groups. We also used Kaplan-Meier estimates and Cox regression to compare survival outcome and estimate hazard ratios (HRs)., Results: We identified 14,463 and 21,483 newly-diagnosed esophageal and gastric cancer patients during 2008-2016. ACEIs/ARBs users were associated with lower risk of cancer-specific mortality, although only significantly in gastric cancer (gastric: adjusted HR = 0.87, 95% CI = 0.78-0.97; esophageal: adjusted HR =0.88, 95% CI = 0.76-1.02). A better survival outcome was observed among patients who received higher cumulative defined daily dose of ACEIs/ARBs., Conclusions: We found that using ACEIs/ARBs after cancer diagnosis were associated with lower risk of mortality. Our results add to the knowledge of the benefit of ACEIs/ARBs against mortality in individuals with esophageal/gastric cancer patients with hypertension., (© 2022. The Author(s).)

This study aims to assess the metal fume exposure of welders and to determine exposure rates for similar exposure groups in a shipyard through the use of Near-field/Far-field (NF/FF) mathematical model and Bayesian decision analysis (BDA) technique. Emission rates of various metal fumes (i.e., total chromium (Cr), iron (Fe), lead (Pb), manganese (Mn), and nickel (Ni)) were experimentally determined for the gas metal arc welding and flux cored arc welding processes, which are commonly used in shipyards. Then the NF/FF field model which used the emission rates were further validated by welding simulation experiment, and together with long-term operation condition data obtained from the investigated shipyard, the predicted long-term exposure concentrations of workers was established and used as the prior distribution in the BDA. Along with the field monitoring metal fume concentrations which served as the likelihood distribution, the posterior decision distributions in the BDA were determined and used to assess workers' long-term metal exposures. Results show that the predicted exposure concentrations (C p ) and the field worker's exposure concentrations (C m ) were statistically correlated, and the high R 2 (= 0.81-0.94) indicates that the proposed surrogate predicting method by the NF and FF model was adequate for predicting metal fume concentrations. The consistency in both prior and likelihood distributions suggests the resultant posterior would be more feasible to assess workers' long-term exposures. Welders' Fe, Mn and Pb exposures were found to exceed their corresponding action levels with a high probability (= 54%), indicating preventive measures should be taken immediately. The proposed approach provides a universal solution for conducting exposure assessment with usual limited number of personal exposure data., (© 2022. The Author(s).)

Background: Cancer-related fatigue (CRF) is the most common concomitant symptom in the treatment of colorectal cancer (CRC). Such patients often present with subjective fatigue state accompanied by cognitive dysfunction, which seriously affects the quality of life of patients., Aim: To explore the effects of cognitive behavior therapy (CBT) combined with Baduanjin exercise on CRF, cognitive impairment, and quality of life in patients with CRC after chemotherapy, and to provide a theoretical basis and practical reference for rehabilitation of CRC after chemotherapy., Methods: Fifty-five patients with CRC after radical resection and chemotherapy were randomly divided into either an experimental or a control group. The experimental group received the intervention of CBT combined with exercise intervention for 6 mo, and indicators were observed and measured at baseline, 3 mo, and 6 mo to evaluate the intervention effect., Results: Compared with the baseline values, in the experimental group 3 mo after intervention, cognitive function, quality of life score, and P300 amplitude and latency changes were significantly better ( P < 0.01). Compared with the control group, at 3 mo, the experimental group had significant differences in CRF, P300 amplitude, and quality of life score ( P < 0.05), as well as significant differences in P300 latency and cognitive function ( P < 0.01). Compared with the control group, at 6 mo, CRF, P300 amplitude, P300 latency, cognitive function and quality of life score were further improved in the experimental group, with significant differences ( P < 0.01). The total score of CRF and the scores of each dimension were negatively correlated with quality of life ( P < 0.05), while the total score of cognitive impairment and the scores of each dimension were positively correlated with quality of life ( P < 0.05)., Conclusion: CBT combined with body-building Baduanjin exercise can improve CRF and cognitive impairment in CRC patients after chemotherapy, and improve their quality of life., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Burnout and suicidality are known risks for vascular surgeons above other surgical subspecialties, with surgical trainees at risk for exposure to factors that increase burnout. This study aimed to inform initiatives to improve wellness by assessing the prevalence of hazards in vascular training (mistreatment, duty-hour violations) and the rates of wellness outcomes (burnout, thoughts of attrition/specialty change/suicide). We hypothesized that mistreatment and duty-hour violations would predispose trainees to increased burnout., Methods: We performed a cross-sectional study of residents and fellows enrolled in accredited United States vascular surgery training programs using a voluntary, confidential survey administered during the 2020 Vascular Surgery In-Training Examination. The primary outcome assessed was burnout symptoms reported on a weekly basis or more frequently. The rates of wellness outcomes were measured. The association of mistreatment and duty hours with the primary outcome was modeled with multivariable logistic regression., Results: A total of 475 residents and fellows who were enrolled in one of 120 vascular surgery training programs completed the survey (84.2% response rate). Of 408 trainees completing burnout survey items, 182 (44.6%) reported symptoms of burnout. Fewer trainees reported thoughts of attrition (n = 42 [10.0%], specialty change (n = 35 [8.4%]), or suicide (n = 22 [4.9%]). Mistreatment was reported by 191 vascular trainees (47.3%) and was more common in female trainees (n = 63 [48.5%] reporting monthly or more frequently) compared with male trainees (n = 51 [18.6%]; P < .001). Duty-hour violations were also more commonly reported by female trainees (n = 31 [21.4%] reporting 3+ months in violation) compared with male trainees (n = 50 [16.2%]; P = .002). After controlling for race/ethnicity, postgraduate year, program type, and geography, female trainees were less likely to report burnout (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28-0.86). Trainees experiencing mistreatment monthly or more were three times more likely to report burnout (OR, 3.09; 95% CI, 1.78-5.39). Frequency of duty-hour violations also increased the odds of reporting burnout (1-2 months in violation: OR, 2.09; 95% CI, 1.17-3.73; 3+ months in violation: OR, 3.95; 95% CI, 2.24-6.97)., Conclusions: Nearly one-half of vascular surgery trainees reported symptoms of burnout, which was associated with frequency of mistreatment and duty-hour violations. Interventions to improve well-being in vascular surgery must be tailored to the local training environment to address trainee experiences that contribute to burnout., (Copyright © 2021 Society for Vascular Surgery. All rights reserved.)

Background: Radiotherapy (RT) might lead to atherosclerotic plaque buildup and coronary artery stenosis of breast cancer (BC) survivors, and coronary artery calcium (CAC) might be a sign of preclinical atherosclerosis. This study explores possible determinants affecting the acceleration of CAC burden in BC patients after adjuvant RT., Methods: Female BC patients receiving adjuvant RT from 2002 to 2010 were included. All patients received noncontrast computed tomography (NCCT) of thorax before and after adjuvant RT. Their CAC burden was compared with healthy controls from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The progression of the CAC burden was manifested by the increment of CAC percentiles (%CACinc)., Results: Ninety-four patients, including both left- and right-side BC, were enrolled in this study. From undergoing the first to second NCCT, the %CACinc in BC patients significantly increased rather than non-BC women. In addition, the %CACinc was significantly higher in left-side than right-side BC patients (p < 0.05), and significant differences in most heart outcomes were found between the two groups. Besides, the lower the mean right coronary artery (RCA) dose, the lower the risks of CAC percentiles increase ≥ 50% after adjusting the disease's laterality., Conclusions: A significantly higher accelerated CAC burden in BC patients than non-BC women represents that BC could affect accelerated CAC. A higher risk of accelerated CAC burden was found in left-side than right-side BC patients after adjuvant RT. A decrease of the mean RCA dose could reduce more than 50% of the risk of accelerated CAC burden in BC patients., (© 2021. The Author(s).)

Probiotic intake has been shown to improve certain physiological health indicators. We aimed to examine effects of Lactobacillus &nbsp; casei LTL1879, obtained from long-lived elderly volunteers, on blood biochemical, oxidative, and inflammatory markers and gut microbiota in twenty healthy, young volunteers. Volunteers were randomly divided into equal probiotic and placebo groups and changes in blood biochemical indicators, oxidative and inflammatory markers, and gut microbiota were examined after three weeks of probiotic intervention. The probiotic group's antioxidant levels were significantly enhanced post-intervention. Total antioxidant capacity (T-AOC) levels were significantly increased ( p < 0.0001), while malondialdehyde (MDA) levels decreased ( p < 0.05), and total superoxide dismutase (T-SOD) levels increased, but with no significant difference. In addition, Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) levels were significantly up-regulated and down-regulated ( p < 0.05, respectively). Escherichia coli , Enterococcus , and Bacteroides expression was significantly reduced ( p < 0.05), while Clostridium leptum , Bifidobacterium , and Lactobacillus expression increased ( p < 0.05). Volunteer health status was quantified using principal components and cluster analysis, indicating that the probiotic group's overall score was higher than that of the placebo group. The results of this pilot study suggest L. casei LTL 1879 can significantly improve specific immune, oxidative, and gut microbiota characteristics related to health factors.

The pathogenesis of nephrotic syndrome is unclear. We conducted a nationwide population-based cohort study to examine the associations between preterm births and subsequent development of NS. NS was defined as ≥ 3 records with ICD-9-CM codes for NS in hospital admission or outpatient clinic visits. To avoid secondary nephrotic syndrome or nephritis with nephrotic range proteinuria, especially IgA nephropathy, we excluded patients with associated codes. A total of 78,651 preterm infants (gestational age < 37 weeks) and 786,510 matched term infants born between 2004 and 2009 were enrolled and followed until 2016. In the unadjusted models, preterm births, maternal diabetes, and pregnancy induced hypertension were associated with subsequent NS. After adjustment, preterm births remained significantly associated with NS (p = 0.001). The risk of NS increased as the gestational age decreased (p for trend < 0.001). Among the NS population, preterm births were not associated with more complications (Hypertension: p = 0.19; Serious infections: p = 0.63, ESRD: p = 0.75) or a requirement for secondary immunosuppressants (p = 0.61). In conclusion, preterm births were associated with subsequent NS, where the risk increased as the gestational age decreased. Our study provides valuable information for future pathogenesis studies., (© 2021. The Author(s).)

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan's National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1-28, 29-56, 57-84, 85-168, 169-252, and 253-280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients' baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57-16.55), especially 57-84 days (IRR: 17.29, 95% CI: 3.11-96.25) and 85-168 days (IRR:10.55, 95% CI: 1.90-58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57-168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid., (© 2021. The Author(s).)

Background: Ocular adverse events are common dose-limiting toxicities in cancer patients treated with HSP90 inhibitors, such as AUY922; however, the pathology and molecular mechanisms that mediate AUY922-induced retinal toxicity remain undescribed., Methods: The impact of AUY922 on mouse retinas and cell lines was comprehensively investigated using isobaric tags for relative and absolute quantitation (iTRAQ)‑based proteomic profiling and pathway enrichment analysis, immunohistochemistry and immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, MTT assay, colony formation assay, and western blot analysis. The effect of AUY922 on the Transient Receptor Potential cation channel subfamily M member 1 (TRPM1)-HSP90 chaperone complex was characterized by coimmunoprecipitation. TRPM1-regulated gene expression was analyzed by RNAseq analysis and gene set enrichment analysis (GSEA). The role of TRPM1 was assessed using both loss-of-function and gain-of-function approaches., Results: Here, we show that the treatment with AUY922 induced retinal damage and cell apoptosis, dysregulated the photoreceptor and retinal pigment epithelium (RPE) layers, and reduced TRPM1 expression. Proteomic profiling and functional annotation of differentially expressed proteins reveals that those related to stress responses, protein folding processes, regulation of apoptosis, cell cycle and growth, reactive oxygen species (ROS) response, cell junction assembly and adhesion regulation, and proton transmembrane transport were significantly enriched in AUY922-treated cells. We found that AUY922 triggered caspase-3-dependent cell apoptosis, increased ROS production and inhibited cell growth. We determined that TRPM1 is a bona fide HSP90 client and characterized that AUY922 may reduce TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex. Additionally, GSEA revealed that TRPM1-regulated genes were associated with retinal morphogenesis in camera-type eyes and the JAK-STAT cascade. Finally, gain-of-function and loss-of-function analyses validated the finding that TRPM1 mediated the cell apoptosis, ROS production and growth inhibition induced by AUY922., Conclusions: Our study demonstrates the pathology of AUY922-induced retinal toxicity in vivo. TRPM1 is an HSP90 client, regulates photoreceptor morphology and function, and mediates AUY922-induced cytotoxicity., (© 2021. The Author(s).)

Objective: To establish a method for extracting Listeria monocytogenes membrane vesicles (LM-MVs) and to analyze the characteristics of LM-MVs and their ability to induce innate immune effect in vitro so as to lay the foundation for research into using LM-MVs as vaccine carrier and drug delivery platform., Methods: The membrane vesicles secreted by Listeria monocytogenes were extracted through a continuous process, including culturing, centrifugation, filtration, ultrafiltration concentration and ultracentrifugation. The morphological characteristics of LM-MVs were observed with transmission electron microscope, and particle size distribution were measured by dynamic light scattering analysis. SDS-PAGE and Western blot were used to analyze the protein composition of LM-MVs. CCK-8 cell proliferation and toxicity determination experiments were done to analyze their effect on the proliferation of innate immune cells, and qPCR was used to analyze their ability to induce innate immune responses., Results: A method for extracting LM-MVs was successfully established. Under the transmission electron microscope, LM-MVs presented a nearly circular film-like structure, and dynamic light scattering analysis showed that their sizes were between 65 and 190 nm. SDS-PAGE and Western blot showed that LM-MVs contained proteins, including listeriolysin O (LLO). CCK-8 cell proliferation and toxicity experiment showed that after intervention with 10, 20 and 50 μg/mL of LM-MVs for 24 hours, the proliferation rate of DC 2.4 mouse dendritic cell line was higher than that of non-interventional DC 2.4 cells ( P <0.05); after intervention with 0.1, 1, 10, 20 and 50 μg/mL of LM-MVs for 24 hours, the proliferation rate of RAW 264.7 cells was higher than that of non-interventional RAW 264.7 cells ( P <0.01). The results of qPCR showed that, after intervention with 50 μg/mL of LM-MVs, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in RAW 264.7 cells were higher than those of non-intervention control cells ( P <0.05)., Conclusions: The method established in the study can be used to extract LM-MVs. The extracted LM-MVs have a diameter of 65-190 nm and a nearly circular membrane-like structure. They can secrete a variety of protein components and stimulate innate immune responses., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Premature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose-response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

Background: The optimal surgical technique for the fixation of inferior pole patellar fracture remains controversial. The aims of this study were (1) to compare clinical and radiological outcomes following fixation of inferior pole patellar fracture by using tension band wire (TBW) and transosseous reattachment (TOR) without excision of the bony fragment and (2) to determine the risk factors for postoperative radiological loss of reduction., Methods: For this retrospective cohort study, consecutive patients with inferior pole patellar fracture between January 2010 and December 2017 were recruited. The patients were grouped according to their fixation method (TBW or TOR), and demographic data, clinical outcomes, and postoperative Insall-Salvati (IS) ratio were analyzed. Then, the patients were grouped according to radiological loss of reduction, the possible risk factors for loss of reduction were identified, and odds ratios were calculated., Result: This study included 55 patients with inferior pole patellar fracture; 30 patients were treated using TBW and 25 were treated using TOR. Clinical failure occurred in two patients in the TBW group (7%) and three in the TOR group (12%). The rate of radiological loss of reduction was significant higher in the TOR group, whereas removal of implants was significantly more common in the TBW group. Patella baja was noted immediately after surgery in the TOR group, but the IS ratios of the two groups were similar after 3 months. Fracture displacement of more than 30 mm was the only independent risk factor for postoperative radiological loss of reduction., Conclusion: For treating inferior pole patellar fracture, both TWB and TOR were effective and had a low clinical failure rate. In 60% of patients undergoing TBW fixation, however, additional surgery was required to remove the implants. Patella baja occurred immediately following TOR, but the patellar height was similar to that in the TBW group after 3 months. Surgeons should be aware of the high risk of postoperative radiological loss of reduction, especially when the fracture displacement is more than 30 mm.

Ratooning is an important cultivation practice in sugarcane production around the world, with underground buds on the remaining stalk acting as the source for establishment of a subsequent ratoon crop. However, the optimal depth of cutting during harvest in terms of yield and root growth remains unknown. We carried out a two-year field study to determine the effects of three cutting depths (0, 5 and 10 cm below the surface) ratoon cane root and yield. Results showed that cutting to a depth of 5 cm increased the root fresh weight and root volume by 21-59% and 41-127%, respectively, compared to cutting depths of 0 and 10 cm. Remarkably, cutting to a depth of 5 cm also had a significant effect on the development of fine roots, which is closely linked to cane yield. The effect was particularly noticeable in terms of two root traits, root volume and the surface area of roots with a diameter of 1.0-2.0mm, and root length and the number of root tips in roots with a diameter of 0-0.5mm. As a result, a cutting depth of 5 cm below the surface increased cane yield by 43 and 28% compared to depths of 0 and 10 cm below the surface, respectively. Overall, these findings suggest that a cutting depth of 5 cm is optimal in terms of sugarcane yield, largely due to the enhanced effect on root traits, especially the development of fine roots. These findings will help optimize sugarcane ratoon management and improve the ratoon cycle., Competing Interests: The authors have declared that no competing interests exist.

The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Hepatitis B is the most prevalent viral hepatitis worldwide, affecting approximately one-third of the world's population. Among HBV factors, the surface protein is the most sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases. The large HBV surface protein (LHBs) contains the integral pre-S1 domain, which binds to the HBV receptor sodium taurocholate co transporting polypeptide on the hepatocyte to facilitate viral entry. The accumulation of viral LHBs and its prevalent pre-S mutants in chronic HBV carriers triggers a sustained endoplasmic reticulum (ER) overload response, leading to ER stress-mediated cell proliferation, metabolic switching and genomic instability, which are associated with pro-oncogenic effects. Ground glass hepatocytes identified in HBV-related hepatocellular carcinoma (HCC) patients harbor pre-S deletion variants that largely accumulate in the ER lumen due to mutation-induced protein misfolding and are associated with increased risks of cancer recurrence and metastasis. Moreover, in contrast to the major HBs, which is decreased in tumors to a greater extent than it is in peritumorous regions, LHBs is continuously expressed during tumorigenesis, indicating that LHBs serves as a promising biomarker for HCC in people with CHB. Continuing efforts to delineate the molecular mechanisms by which LHBs regulates pathological changes in CHB patients are important for establishing a correlation between LHBs biomarkers and HCC development.