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Background: In patients with advanced osteoarthritis (OA) of the bilateral knees, uncertainty remains as to whether simultaneous bilateral total knee arthroplasty (SiTKA) or staged TKA (StTKA) is the treatment of choice. The purpose of this study was to investigate the safety and relative cost of SiTKA vs StTKA in Taiwan patients., Methods: Using the Big Data Center of Taipei Veterans General Hospital, we retrospectively reviewed all patients who underwent SiTKA or StTKA due to OA or spontaneous osteonecrosis of the knee from January 2011 to December 2016. We assessed length of stay, transfusion rate, early postoperative complications, 30- and 90-day readmission rate, 1-year reoperation rate, and the indication for reoperation. Furthermore, we analyzed the total cost of the two groups, including reimbursement from the national health insurance (NHI), cost of the procedures, and net income from each case., Results: A total of 2016 patients (1565 SiTKA and 451 StTKA) were included in this study. The two groups had no significant differences in rates of complications, 30- and 90-day readmission, or 1-year reoperation. The length of stay was on average 5.0 days longer for StTKA ( p < 0.01). In terms of cost, all categories of medical costs were significantly lower for SiTKA, while the net hospital income was significantly higher for StTKA., Conclusion: SiTKA is a safe and cost-effective surgery. Both SiTKA and StTKA have similar rates of postoperative complications, readmission and reoperation, but SiTKA significantly reduces medical expenses for both the patient and the NHI., Competing Interests: Conflicts of interest: Dr. Wei-Ming Chen, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Purpose: To elucidate the association of presurgical sarcopenia and long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia., Methods: We conducted this population-based propensity score matched to investigate the effects of sarcopenia and long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia between 1 October 2016 and 31 December 2019 from Taiwan's National Health Insurance Research Database. Sarcopenia is a disease and coded as M62.84 in the International Classification of Diseases, 10th Revision, Clinical Modification. The primary outcome was the combined rate of the long-term use of all non-opioid analgesics or opioids over 3 and 6 months after elective surgery. By performing a logistic regression analysis, we calculated the adjusted ORs (aORs) with 95% CIs to identify the independent predictors for long-term non-opioid analgesic and opioid use after surgery., Results: In total, 2860 patients underwent elective surgery. The 3-month non-opioid analgesic and opioid use rates were respectively 49.7% and 1.8% in the sarcopenia group and 37.9% and 0.9% in the non-sarcopenia group; by contrast, 6-month non-opioid analgesic and opioid use rates were respectively 31.6% and 1.2% in the sarcopenia group and 17.2% and 0.3% in the non-sarcopenia group. Moreover, presurgical sarcopenia increased the risk of long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia (aORs for non-opioid analgesic use over 3 and 6 months after surgery: 1.17 (95% CI 1.05 to 2.23) and 1.26 (95% CI 1.04 to 1.45), respectively; aORs for opioid use over 3 and 6 months after surgery: 1.17 (95% CI 1.07 to 2.21) and 1.23 (95% CI 1.10 to 3.64), respectively)., Conclusion: Sarcopenia is associated with higher rates of long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia., Summary: The aim of this study was to compare the long-term use of non-opioid analgesics and opioids after elective surgery under general anesthesia between patients with and without sarcopenia. Results suggest that patients with sarcopenia are more likely to have increased use of non-opioid analgesics and opioids after surgery. Further research is needed to determine if sarcopenia can be modified prior to surgery and if this impacts the need for long-term pain management with these medications., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Three new constituents: 1,5 R -dihydroxy-3,8 S -dimethoxy-5,6,7,8-tetrahydroxanthone (1), (3 S ,4 R ,16 S ,17 R )-3,16,23-trihydroxyoleana-11,13(18)-dien-28-aldehyde-3- O - β -D-glucopyranoside (2), and new natural product ( S )-gentiandiol (3), along with 41 known compounds were isolated from Tujia ethnomedicine Shuihuanglian, namely, the whole plant of Swertia punicea . Structures of all these compounds were established through extensive spectroscopic techniques, namely 1D, 2D-NMR spectroscopy, HRESIMS analysis, and the absolute configuration of the new compounds was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated by using the DPPH radical scavenging method, compounds 7 , 9 and 14 showed antioxidant activities with IC 50 values of 68.9, 50.8 and 48.2 μM, respectively.

Background and Objectives: Human platelet antigens (HPAs) are alloantigens associated with antiplatelet alloantibodies and the risk of immune thrombocytopenia (ITP). However, few studies have investigated associations among HPAs, antiplatelet autoantibodies, and cryoglobulins., Methods: We enrolled 43 patients with primary ITP, 47 with hepatitis C virus-associated ITP (HCV-ITP), 21 with hepatitis B virus-associated ITP (HBV-ITP), 25 controls with HCV, and 1013 normal controls. We analyzed HPA allele frequencies, including HPA1-6 and 15, antiplatelet antibodies binding to platelet glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX, IV, human leukocyte antigen class I, cryoglobulin IgG/A/M, and their associations with thrombocytopenia., Results: In the ITP cohort, HPA2ab, rather than HPA2aa, predicted a low platelet count. HPA2b was associated with the risk of developing ITP. HPA15b was correlated with multiple antiplatelet antibodies. In HCV-ITP patients, HPA3b was correlated with anti-GPIIb/IIIa antibodies. HCV-ITP patients with anti-GPIIb/IIIa antibodies had a higher positive rate of cryoglobulin IgG and IgA compared with those without anti-GPIIb/IIIa antibodies. Overlapping detection was also found among other antiplatelet antibodies and cryoglobulins. Like the antiplatelet antibodies, cryoglobulins were associated with clinical thrombocytopenia, implying their close relationship. Finally, we extracted cryoglobulins to confirm the exhibition of cryoglobulin-like antiplatelet antibodies. In contrast, in primary ITP patients, HPA3b was correlated with cryoglobulin IgG/A/M rather than anti-GPIIb/IIIa antibodies., Conclusion: HPA alleles were associated with antiplatelet autoantibodies and had different impacts in primary ITP and HCV-ITP patients. HCV-ITP was considered to be a symptom of mixed cryoglobulinemia in HCV patients. The pathophysiology may differ between these two groups., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Purpose: To investigate the dose-dependent protective effects of statins, specific classes of statins, and different intensities of statin use on sepsis risk in patients with type 2 diabetes mellitus (T2DM)., Methods: We included patients with T2DM aged  ≥ 40 years. Statin use was defined as the use of statin on most days for  > 1 months with a mean statin dose of  ≥ 28 cumulative defined daily doses (cDDDs) per year (cDDD-year). An inverse probability of treatment-weighted Cox hazard model was used to investigate the effects of statin use on sepsis and septic shock while considering statin use status as a time-dependent variable., Results: From 2008 to 2020, a total of 812 420 patients were diagnosed as having T2DM. Among these patients, 118,765 (27.79%) statin nonusers and 50 804 (12.03%) statin users developed sepsis. Septic shock occurred in 42,755 (10.39%) individuals who did not use statins and 16,765 (4.18%) individuals who used statins. Overall, statin users had a lower prevalence of sepsis than did nonusers. The adjusted hazard ratio (aHR) of statin use was 0.37 (95% CI 0.35, 0.38) for sepsis compared with no statin use. Compared with the patients not using statins, those using different classes of statins exhibited a more significant reduction in sepsis, with aHRs (95% CIs) of sepsis being 0.09 (0.05, 0.14), 0.32 (0.31, 0.34), 0.34 (0.32, 0.36), 0.35 (0.32, 0.37), 0.37 (0.34, 0.39), 0.42 (0.38, 0.44), and 0.54 (0.51, 0.56) for pitavastatin, pravastatin, rosuvastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin use, respectively. In the patients with different cDDD-years of statins, multivariate analysis indicated a significant reduction in sepsis, with aHRs of 0.53 (0.52, 0.57), 0.40 (0.39, 0.43), 0.29 (0.27, 0.30), and 0.17 (0.15, 0.19) for Q1, Q2, Q3, and Q4 cDDD-years (P for trend < 0.0001). The optimal daily statin dose of 0.84 DDD was associated with the lowest aHR. Similar trends of higher cDDD-year and specific statin types use were associated with a decrease in septic shock when compared to statin non-users., Conclusion: Our real-world evidence demonstrated that the persistent use of statins reduced sepsis and septic shock risk in patients with T2DM and a higher cDDD-year of statin use was associated with an increased reduction of sepsis and septic shock risk in these patients., (© 2023. The Author(s).)

Simultaneous bilateral total knee arthroplasty (TKA) might be associated with higher postoperative morbidity and mortality rates compared with staged bilateral TKA. However, risk factors for surgical complications and reoperations following simultaneous bilateral TKA remain elusive. We conducted this retrospective, single-surgeon case series from 2010 through 2019. A total of 1561 patients who underwent simultaneous bilateral TKA procedures were included. The outcome domains included 30-day and 90-day readmission events for medical or surgical complications and 1-year reoperation events. We performed logistic regression analysis and backward stepwise selection to identify possible risk factors, including age, sex, body mass index, diabetes mellitus (DM), rheumatoid arthritis, American Society of Anesthesiologist (ASA) classification, Charlson Comorbidity Index (CCI), receiving venous thromboembolism (VTE) prophylaxis, or blood transfusion. The overall 30-day, 90-day readmission, and 1-year reoperation rates were 2.11%, 2.88%, and 1.41%, respectively. Higher CCI score (CCI = 4+) was a risk factor for 90-day readmission (aOR: 2.783; 95% CI 0.621-12.465), 90 day readmission for surgical complications (aOR: 10.779; 95% CI 1.444-80.458), and 1 year reoperation (aOR: 4.890; 95% CI 0.846-28.260). Other risk factors included older age, higher ASA level, DM, and receiving VTE prophylaxis. In conclusion, high CCI scores were associated with increased risks of surgical complications and reoperations following simultaneous bilateral TKA procedures., (© 2023. The Author(s).)

Introduction: In the National University Cancer Institute, Singapore (NCIS), 2 pilot programs providing (i) surgical prehabilitation before cancer surgery and (ii) geriatric oncology support for older adults planned for chemotherapy and/or radiotherapy were merged to form the Geriatric Oncology Longitudinal End to eNd (GOLDEN) program in 2019 to support patients from the time of their cancer diagnosis, through their treatment process, to cancer survivorship., Methods and Materials: Older adults aged ≥65 years were enrolled in either surgical prehabilitation, the geriatric medical oncology (GO) arm, or both. All patients undergo a geriatric assessment. We assessed if patients had a change in treatment plans based on GOLDEN recommendations, and the impact on patient related outcomes., Results: There were 777 patients enrolled in the GOLDEN program over 2 years; 569 (73%) were enrolled in surgical prehabilitation, 308 (40%) were enrolled in the GO arm, with 100 (12.8%) enrolled in both. 56.9% were females. Median age was 73. Lower gastrointestinal (51.2%) and hepatobiliary cancers (24.1%) were the most common cancer types. 43.4% were pre-frail and 11.7% were frail. Of the 308 patients in the GO arm, 86.0% had geriatric syndromes, while 60.7% had a change in their treatment plans based on GOLDEN recommendations. 31.5% reported an improved global health status, while 38.3% maintained their global health status. 226 (73%) responded that they had benefited from the GOLDEN., Conclusion: More than half of the population was either pre-frail or frail. Amongst those in the GO arm, the majority had geriatric syndromes and had a change in their treatment plans based on GOLDEN recommendations. Majority reported either improvement or maintenance in global health status, with most feeling they have benefited from the program. Further evaluation of the longitudinal geriatric hematology-oncology program for cancer-related outcomes and sustainability should be carried out., (© The Author(s) 2023. Published by Oxford University Press.)

This study attempted to investigate whether exosomes derived from rat endothelial cells (EC-Exo) attenuate intimal hyperplasia after balloon injury using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence staining, Evans blue staining, and Western blotting. The results indicated that EC-Exo inhibited intimal hyperplasia in the carotid artery after balloon injury, promoted re-endothelialization, and reduced vascular inflammation and ROS-NLRP3-mediated cell pyroptosis. Thus, EC-Exo can inhibit neointimal hyperplasia after carotid artery injury in rats presumably by inhibiting the ROS-NLRP3 inflammasome and phenotypic transformation of vascular smooth muscle cells., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Two strains of Chryseobacterium identified from different experiments are proposed to represent new species. Strain WLa1L2M3 T was isolated from the digestive tract of an Oryctes rhinoceros beetle larva. Strain 09-1422 T was isolated from a cage housing the stick insect Eurycantha calcarata . Sequence analysis of the 16S rRNA and rpoB genes found both strains to be similar but not identical to other Chryseobacterium species. Whole-genome sequencing suggested the isolates represent new species, with average nucleotide identity values ranging from 74.6 to 80.5 %. Genome-to-genome distance calculations produced values below 25.3 %, and digital DNA-DNA hybridization values were 13.7-29.9 %, all suggesting they are distinct species. The genomic DNA G+C content of WLa1L2M3 T is approximately 32.53 %, and of 09-1422 T is approximately 35.89 %. The predominant cellular fatty acids of strain WLa1L2M3 T are C 15 : 0 iso, summed feature 9 (C 16 : 0 10OH or C 17 : 1 iso ω6 c ), C 17 : 0 iso 3OH, summed feature 3 (C 16 : 1 ω7 c and/or C 16 : 1 ω6c), C 15 : 0 iso 3OH, C 15 : 0 anteiso and C 13 : 0 iso, and those of strain 09-1422 T are C 15 : 0 iso, summed feature 3 (C 16 : 1 ω7c and/or C 16 : 1 ω6 c ), C 17 : 0 iso 3OH, C 15 : 0 anteiso, C 15 : 0 iso 3OH, C 16 : 1 ω7 c , C 17 : 0 2OH and C 18 : 0 . In addition, physiological and biochemical tests revealed phenotypic differences from related Chryseobacterium type strains. These cumulative data indicate that the two strains represent novel species of the genus Chryseobacterium for which the names Chryseobacterium oryctis sp. nov. and Chryseobacterium kimseyorum sp. nov. are proposed with WLa1L2M3 T (=BCRC 81350 T =JCM 35215 T =CIP 112035 T ) and 09-1422 T (=UCDFST 09-1422 T =BCRC 81359 T =CIP 112165 T ), as type strains, respectively.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent association signals at genome-wide significance ( P <5×10 -8 ) that map to 611 loci, of which 145 loci are previously unreported. We define eight non-overlapping clusters of T2D signals characterised by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial, and enteroendocrine cells. We build cluster-specific partitioned genetic risk scores (GRS) in an additional 137,559 individuals of diverse ancestry, including 10,159 T2D cases, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned GRS are more strongly associated with coronary artery disease and end-stage diabetic nephropathy than an overall T2D GRS across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings demonstrate the value of integrating multi-ancestry GWAS with single-cell epigenomics to disentangle the aetiological heterogeneity driving the development and progression of T2D, which may offer a route to optimise global access to genetically-informed diabetes care., Competing Interests: R.A.S. is now an employee of GlaxoSmithKline. G.T. is an employee of deCODE genetics/Amgen Inc. A.S.B. reports institutional grants from AstraZeneca, Bayer, Biogen, BioMarin, Bioverativ, Novartis, Regeneron and Sanofi. J.Danesh serves on scientific advisory boards for AstraZeneca, Novartis, and UK Biobank, and has received multiple grants from academic, charitable and industry sources outside of the submitted work. L.S.E. is now an employee of Bristol Myers Squibb. J.S.F. has consulted for Shionogi Inc. T.M.F. has consulted for Sanofi, Boehringer Ingelheim, and received funding from GlaxoSmithKline. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care; reports research grants from Eli Lilly, AstraZeneca, Merck, Novo Nordisk and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Roche, and Sanofi; and consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Pfizer, Sanofi, Kowa and Hanmi.lth Institute Chair in Diabetes Research and Care; reports research grants from Eli Lilly, AstraZeneca, Merck, Novo Nordisk and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; and consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Janssen, Sanofi, and Kowa. M.Ingelsson is a paid consultant to BioArctic AB. R.L.-G. is a part-time consultant of Metabolon Inc. A.E.L. is now an employee of Regeneron Genetics Center LLC and holds shares in Regeneron Pharmaceuticals. M.A.N. currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc. S.R.P. has received grant funding from Bayer Pharmaceuticals, Philips Respironics and Respicardia. N.Sattar has consulted for or been on speakers bureau for Abbott, Amgen, Astrazeneca, Boehringer Ingelheim, Eli Lilly, Hanmi, Novartis, Novo Nordisk, Sanofi and Pfizer and has received grant funding from Astrazeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics. V.S. is now an employee of deCODE genetics/Amgen Inc. A.M.S. receives funding from Seven Bridges Genomics to develop tools for the NHLBI BioData Catalyst consortium. U.T. is an employee of deCODE genetics/Amgen Inc. E.Ingelsson is now an employee of GlaxoSmithKline. B.M.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. R.C.W.M. reports research funding from AstraZeneca, Bayer, Novo Nordisk, Pfizer, Tricida Inc. and Sanofi, and has consulted for or received speakers fees from AstraZeneca, Bayer, Boehringer Ingelheim, all of which have been donated to the Chinese University of Hong Kong to support diabetes research. D.O.M.-K. is a part-time clinical research consultant for Metabolon Inc. S.Liu reports consulting payments and honoraria or promises of the same for scientific presentations or reviews at numerous venues, including but not limited to Barilla, by-Health Inc, Ausa Pharmed Co.LTD, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital and Academy of Medical Sciences, Consulting member for Novo Nordisk, Inc; member of the Data Safety and Monitoring Board for a trial of pulmonary hypertension in diabetes patients at Massachusetts General Hospital; receives royalties from UpToDate; receives an honorarium from the American Society for Nutrition for his duties as Associate Editor. K.Stefansson is an employee of deCODE genetics/Amgen Inc. M.I.M. has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda; and is now an employee of Genentech and a holder of Roche stock. J.B.M. is an Academic Associate for Quest Diagnostics R&D. A.Mahajan is an employee of Genentech, and a holder of Roche stock.

Purpose: to examine the impact of statins on reducing all-cause mortality among individuals diagnosed with type 2 diabetes. This investigation explored the potential correlations between dosage, drug classification, and usage intensity with the observed outcomes., Methods: The research sample consisted of individuals aged 40 years or older diagnosed with type 2 diabetes. Statin usage was determined as a frequent usage over a minimum of one month subsequent to type 2 diabetes diagnosis, where the average statin dose was ≥28 cumulative defined daily doses per year (cDDD-year). The analysis employed an inverse probability of treatment-weighted Cox hazard model, utilizing statin usage status as a time-varying variable, to evaluate the impact of statin use on all-cause mortality., Results: The incidence of mortality was comparatively lower among the cohort of statin users (n = 50,804 (12.03%)), in contrast to nonusers (n = 118,765 (27.79%)). After adjustments, the hazard ratio (aHR; 95% confidence interval (CI)) for all-cause mortality was estimated to be 0.32 (0.31-0.33). Compared with nonusers, pitavastatin, rosuvastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and lovastatin users demonstrated significant reductions in all-cause mortality (aHRs (95% CIs) = 0.06 (0.04-0.09), 0.28 (0.27-0.29), 0.29 (0.28-0.31), 0.31 (0.30-0.32), 0.31 (0.30-0.32), 0.36 (0.35-0.38), and 0.48 (0.47-0.50), respectively). In Q1, Q2, Q3, and Q4 of cDDD-year, our multivariate analysis demonstrated significant reductions in all-cause mortality (aHRs (95% CIs) = 0.51 (0.5-0.52), 0.36 (0.35-0.37), 0.24 (0.23-0.25), and 0.13 (0.13-0.14), respectively; p for trend <0.0001). Because it had the lowest aHR (0.32), 0.86 DDD of statin was considered optimal., Conclusions: In patients diagnosed with type 2 diabetes, consistent utilization of statins (≥28 cumulative defined daily doses per year) was shown to have a beneficial effect on all-cause mortality. Moreover, the risk of all-cause mortality decreased as the cumulative defined daily dose per year of statin increased.

Background: Oxylipins are inflammatory biomarkers derived from omega-3 and-6 fatty acids implicated in inflammatory diseases but have not been studied in a genome-wide association study (GWAS). The aim of this study was to identify genetic loci associated with oxylipins and oxylipin profiles to identify biologic pathways and therapeutic targets for oxylipins., Methods: We conducted a GWAS of plasma oxylipins in 316 participants in the Diabetes Autoimmunity Study in the Young (DAISY). DNA samples were genotyped using the TEDDY-T1D Exome array, and additional variants were imputed using the Trans-Omics for Precision Medicine (TOPMed) multi-ancestry reference panel. Principal components analysis of 36 plasma oxylipins was used to capture oxylipin profiles. PC1 represented linoleic acid (LA)- and alpha-linolenic acid (ALA)-related oxylipins, and PC2 represented arachidonic acid (ARA)-related oxylipins. Oxylipin PC1, PC2, and the top five loading oxylipins from each PC were used as outcomes in the GWAS (genome-wide significance: p  < 5×10 -8 )., Results: The SNP rs143070873 was associated with (p < 5×10 -8 ) the LA-related oxylipin 9-HODE, and rs6444933 (downstream of CLDN11 ) was associated with the LA-related oxylipin 13 S-HODE. A locus between MIR1302-7 and LOC100131146 , rs10118380 and an intronic variant in TRPM3 were associated with the ARA-related oxylipin 11-HETE. These loci are involved in inflammatory signaling cascades and interact with PLA2 , an initial step to oxylipin biosynthesis., Conclusion: Genetic loci involved in inflammation and oxylipin metabolism are associated with oxylipin levels., 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. The reviewer NL declared a shared affiliation with OF to the handling editor at the time of review., (Copyright © 2023 Buckner, Johnson, Vanderlinden, Carry, Romero, Onengut-Gumuscu, Chen, Kim, Fiehn, Frohnert, Crume, Perng, Kechris, Rewers and Norris.)

More clinical studies are needed to clarify the risk stratification by the integration of all fusion genes in adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A total of 320 consecutive adult Ph-negative BCP-ALL patients who had been tested classical fusions (KMT2A rearrangement and TCF3-PBX1) at diagnosis were further retrospectively screened novel fusion genes (Ph-like, ZNF384 and MEF2D fusions) by multiplex real-time quantitative PCR (RQ-PCR). Classical fusions were identified in 12.5% of patients, while 4.4%, 17.2% and 3.8% of patients were identified Ph-like, ZNF384 and MEF2D fusions, respectively. 1-course CR rate, relapse-free survival (RFS) and overall survival (OS) rates tended to show or showed statistically significant differences among fusion-defined subgroups (P = 0.084,  0.001 and 0.0093, respectively). Based on individual outcomes, patients with KMT2A rearrangement, TCF3-PBX1, Ph-like, and MEF2D fusions were classified into fusion-defined high-risk group (n = 66, 20.6%). High-risk group had significantly lower 3-year RFS and 3-year OS rates than standard-risk group (P 0.001 and = 0.0022), and was an independent adverse prognostic factor for RFS in the entire cohort (P 0.001). In conclusion, the spectrum of fusion genes in the current Chinese cohort was distinct from that in reports from western countries. Detection of fusion genes improved risk stratification in adult Ph-negative BCP-ALL patients.

Cancer with low survival rates is the second main cause of death among all diseases in the world and consequently, effective antineoplastic agents are urgently needed. Allosecurinine is a plant-derived indolicidine securinega alkaloid shown bioactivity. The object of this study is to investigate synthetic allosecurinine derivatives with considerable anticancer capacity against nine human cancer cell lines as well as mechanism of action. We synthesized twenty-three novel allosecurinine derivatives and evaluated their antitumor activity against nine cancer cell lines for 72 h by MTT and CCK8 assays. FCM was applied to analyze the apoptosis, mitochondrial membrane potential, DNA content, ROS production, CD11b expression. Western blot was selected to analyze the protein expression. Structure-activity relationships were established and potential anticancer lead BA-3 which induced differentiation of leukemia cells towards granulocytosis at low concentration and apoptosis at high concentration was identified. Mechanism studies showed that mitochondrial pathway mediated apoptosis within cancer cells with cell cycle blocking was induced by BA-3. In addition, western blot assays revealed that BA-3 induced expression of the proapoptotic factor Bax, p21 and reduced the levels of antiapoptotic protein such as Bcl-2, XIAP, YAP1, PARP, STAT3, p-STAT3, and c-Myc. Collectively, BA-3 was a lead compound for oncotherapy at least in part, through the STAT3 pathway. These results were an important step in further studies on allosecurinine-based antitumor agent development., 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 © 2023 Elsevier Ltd. All rights reserved.)

DNA-PKcs is a key regulator of DNA double-strand break repair. Apart from its canonical role in the DNA damage response, DNA-PKcs is involved in the cellular response to oxidative stress (OS), but its exact role remains unclear. Here, we report that DNA-PKcs-deficient human cells display depolarized mitochondria membrane potential (MMP) and reoriented metabolism, supporting a role for DNA-PKcs in oxidative phosphorylation (OXPHOS). DNA-PKcs directly interacts with mitochondria proteins ANT2 and VDAC2, and formation of the DNA-PKcs/ANT2/VDAC2 (DAV) complex supports optimal exchange of ADP and ATP across mitochondrial membranes to energize the cell via OXPHOS and to maintain MMP. Moreover, we demonstrate that the DAV complex temporarily dissociates in response to oxidative stress to attenuate ADP-ATP exchange, a rate-limiting step for OXPHOS. Finally, we found that dissociation of the DAV complex is mediated by phosphorylation of DNA-PKcs at its Thr2609 cluster by ATM kinase. Based on these findings, we propose that the coordination between the DAV complex and ATM serves as a novel oxidative stress checkpoint to decrease ROS production from mitochondrial OXPHOS and to hasten cellular recovery from OS., (© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Four novel all-in-one structured cuprous iodide hybrid materials are presented. Isomerization of the alkyl chain on the ligand improved material thermal stability and regulated their luminescence to warm and near-white light emission, with the internal quantum yield increasing from 5% to 83%. This provides a reasonable route for designing white light emitting cuprous iodide materials for solid-state lighting in future.

The prognostic significance of cytokine receptor like factor 2 ( CRLF2 ) expression at diagnosis in adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) needs to be clarified. A total of 357 bone marrow samples collected from consecutive adult cases with Ph-negative BCP-ALL at diagnosis retrospectively detected CRLF2 transcript levels by real-time quantitative PCR. Twenty percent was selected as the cutoff value for CRLF2 to divide patients into CRLF2 &#95;H and CRLF2 &#95;L groups. CRLF2 &#95;H was associated with higher WBC count, P2RY8-CRLF2 fusion and IKZF1 deletions ( IKZF1 del). In both the whole cohort and B-other patients, CRLF2 &#95;H independently predicted lower CR rates after induction. Furthermore, CRLF2 &#95;H/ IKZF1 del(+) patients had significantly lower CR, RFS, and OS rates and tended to have lower RFS and OS rates than others in the whole cohort and B-other patients, respectively. Therefore, coexistence of CRLF2 &#95;H and IKZF1 del at diagnosis predicts poor response and outcome in adult Ph-negative BCP-ALL.

The interspace between popliteal artery and the capsule of posterior knee (iPACK) block was proposed in recent years to relieve posterior knee pain. Since adductor canal block (ACB) and iPACK involve different branches of the sensory nerves, it is theoretically feasible to combine iPACK block and ACB to relief pain after total knee arthroplasty (TKA). We aim to validate the efficacy of adding iPACK block to ACB in the setting of a multimodal pain management protocol following TKA. A comprehensive literature review on Web of Science, Embase, the Cochrane Library, and PubMed was performed. Eight studies ( N  = 1,056) that compared the efficacy of iPACK block + ACB with ACB alone were included. Primary outcomes consisted of Visual Analogue Scale (VAS) score at rest or during activity at various time points. Secondary outcomes include opioids consumption, walking distance, and length of hospital stay (LOS). Compared to ACB alone, VAS scores at rest (standardized mean difference [SMD]: -1.18; 95% confidence interval [CI]: -2.05 to -0.30) and during activity (SMD: -0.26; 95% CI: -0.49 to -0.03) on the day of surgery were lower in the iPACK block + ACB group. However, the difference did not reach the minimal clinically important difference. Opioids consumption at postoperative 24 hours was lower in the iPACK + ACB group (SMD: -0.295; 95% CI: -0.543 to -0.048). VAS score on postoperative day (POD) 1 and POD2, opioids consumption from 24 to 48 hours, walking distance, and LOS were not different. In conclusion, the addition of iPACK block to ACB in a multimodal pain management protocol can effectively reduce opioids consumption in the early postoperative period. This is a level III, meta-analysis study., Competing Interests: None declared., (Thieme. All rights reserved.)

This study aimed to examine the association between the use of H1-antihistamines (AHs) and head and neck cancer (HNC) risk in patients with type 2 diabetes mellitus (T2DM). Data from the National Health Insurance Research Database of Taiwan were analyzed for the period from 2008 to 2018. A propensity-score-matched cohort of 54,384 patients each in the AH user and nonuser groups was created and analyzed using Kaplan-Meier method and Cox proportional hazards regression. The results showed that the risk of HNC was significantly lower in AH users (adjusted hazard ratio: 0.55, 95% CI: 0.48 to 0.64) and the incidence rate was also lower (5.16 vs . 8.10 per 100,000 person-years). The lower HNC incidence rate in AH users (95% CI: 0.63; 0.55 to 0.73) suggests that AH use may reduce the risk of HNC in T2DM patients., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2023 Chen et al.)

Background: Preclinical studies have indicated that anaesthesia is an independent risk factor for dementia, but the clinical associations between dementia and different types of general anaesthesia or regional anaesthesia remain unclear. We conducted a population-based cohort study using propensity-score matching to compare dementia incidence in patients included in the Taiwanese National Health Insurance Research Database who received various anaesthetic types for hip fracture surgery., Methods: Patients aged ≥65 yr who received elective hip fracture surgery from 2002 to 2019 were divided into three groups receiving either inhalational anaesthesia (GA), total intravenous anaesthesia-general anaesthesia (TIVA-GA), or regional anaesthesia (RA), and matched in a 1:1 ratio. The incidence rates of dementia were then determined., Results: Propensity-score matching yielded 89 338 patients in each group (N=268 014). Dementia incidence rates in the inhalational GA, TIVA-GA, and RA groups were 4821, 3400, and 2692 per 100 000 person-years, respectively. The dementia incidence rate ratio (95% confidence interval [CI]) for inhalational GA to TIVA-GA was 1.19 (1.14-1.25), for inhalational GA to RA was 1.51 (1.15-1.66), and for TIVA-GA to RA was 1.28 (1.09-1.51)., Conclusions: The incidence rate ratios of dementia amongst older adults undergoing hip fracture surgery were higher for those receiving general anaesthesia than for those receiving regional anaesthesia, with inhalational anaesthesia associated with a higher incidence rate ratio for dementia than total intravenous anaesthesia (TIVA)., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: The relationship between the onset of sarcopenia prior to cancer diagnosis and survival outcomes in various types of cancer is not well understood. To address this gap in knowledge, we conducted a propensity score-matched population-based cohort study to compare the overall survival of cancer patients with and without sarcopenia., Patients and Methods: In our study, we included patients with cancer and divided them into two groups based on the presence or absence of sarcopenia. To ensure comparability between the groups, we matched patients in both groups at a ratio of 1:1., Results: After the matching process, our final cohort included 20,416 patients with cancer (10,208 in each group) who were eligible for further analysis. There were no significant differences between the sarcopenia and nonsarcopenia groups in terms of confounding factors such as age (mean 61.05 years versus 62.17 years), gender (52.56% versus 52.16% male, 47.44% versus 47.84% female), comorbidities, and cancer stages. In our multivariate Cox regression analysis, we found that the adjusted hazard ratio (aHR; 95% confidence interval [CI]) of all-cause death for the sarcopenia group compared to the nonsarcopenia group was 1.49 (1.43-1.55; p < 0.001). Additionally, the aHRs (95% CIs) of all-cause death for those aged 66-75, 76-85, and >85 years (compared to those aged ≤65 years) were 1.29 (1.23-1.36), 2.00 (1.89-2.12), and 3.26 (2.97-3.59), respectively. The aHR (95% CI) of all-cause death for those with a Charlson comorbidity index (CCI) ≥ 1 compared to those with a CCI of 0 was 1.34 (1.28-1.40). The aHR (95% CI) of all-cause death for men compared to women was 1.56 (1.50-1.62). When comparing the sarcopenia and nonsarcopenia groups, the aHRs (95% CIs) for lung, liver, colorectal, breast, prostate, oral, pancreatic, stomach, ovarian, and other cancers were significantly higher., Conclusion: Our findings suggest that the onset of sarcopenia prior to cancer diagnosis may be linked to reduced survival outcomes in cancer patients.

Esophageal cancer is a common and aggressive cancer, with a five-year survival rate of approximately 20%. Therefore, identifying safe and effective medications that can reduce the risk of esophageal cancer is of great importance., Objective: To examine the association between H1-antihistamines (AHs) use and the incidence of esophageal squamous cell carcinoma (ESCC) in a head-to-head propensity score matching (PSM) comparative study., Design: Retrospective cohort study., Setting: Nationwide population-based study in Taiwan., Participants: 1289,526 adults from the National Health Insurance Research Database from 2008 to 2018., Exposures: AH use., Main Outcomes and Measures: Incidence rates (IRs), incidence rate ratios (IRRs), and adjusted hazard ratios (aHRs) of ESCC in AH users compared with nonusers., Results: AH users had a significantly higher IR of ESCC than nonusers (1.47 vs. 1.36 per 100,000 person-years). The IRR (95% CI) for ESCC was 1.18 (1.08-1.28) in AH users compared with nonusers. After adjustment for age, sex, income levels, urbanization, cigarettes smoking, alcoholic related diseases, comorbidities, medication use, and Charlson Comorbidity Index scores, the aHR (95% CI) for ESCC was 1.22 (1.12-1.33) in AH users compared with nonusers. A dose-response relationship was also observed, with aHRs for AH use at 28-182, 183-488, 489-1043, and >1043 cumulative defined daily doses (cDDDs) of 1.12, 1.20, 1.25, and 1.37, respectively, compared with <28 cDDDs., Conclusions and Relevance: Our study found a significant association between AH use and the increased risk of ESCC, with a dose-response relationship. This study suggests that AH use may increase the risk of ESCC, especially at high doses, and highlights the importance of caution when prescribing AHs.

Oxylipins, pro-inflammatory and pro-resolving lipid mediators, are associated with the risk of type 1 diabetes (T1D) and may be influenced by diet. This study aimed to develop a nutrient pattern related to oxylipin profiles and test their associations with the risk of T1D among youth. The nutrient patterns were developed with a reduced rank regression in a nested case-control study ( n = 335) within the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal cohort of children at risk of T1D. The oxylipin profiles (adjusted for genetic predictors) were the response variables. The nutrient patterns were tested in the case-control study ( n = 69 T1D cases, 69 controls), then validated in the DAISY cohort using a joint Cox proportional hazards model ( n = 1933, including 81 T1D cases). The first nutrient pattern (NP1) was characterized by low beta cryptoxanthin, flavanone, vitamin C, total sugars and iron, and high lycopene, anthocyanidins, linoleic acid and sodium. After adjusting for T1D family history, the HLA genotype, sex and race/ethnicity, NP1 was associated with a lower risk of T1D in the nested case-control study (OR: 0.44, p = 0.0126). NP1 was not associated with the risk of T1D (HR: 0.54, p -value = 0.1829) in the full DAISY cohort. Future studies are needed to confirm the nested case-control findings and investigate the modifiable factors for oxylipins.

Purpose: No large-scale prospective randomized study with a long-term follow-up period has evaluated the survival outcomes of preconcurrent chemoradiotherapy (CCRT) 18-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG PET-CT) in patients with non-human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC)., Patients and Methods: We included patients with stage I-IVA p16-negative OPSCC receiving definitive CCRT and categorized them into two groups according to pre-CCRT 18 FDG PET-CT and compared their outcomes: the case group consisted of patients who underwent pre-CCRT 18 FDG PET-CT, whereas the comparison group consisted of patients who did not receive pre-CCRT 18 FDG PET-CT., Results: The final cohort consisted of 3942 patients (1663 and 2279 in the case and comparison groups, respectively). According to multivariable Cox regression analysis, pre-CCRT 18 FDG PET-CT was not a significant prognostic factor for overall survival in patients with stages I-II of p16-negative OPSCC receiving standard CCRT. The adjusted hazard ratio (95% confidence interval) of all-cause death for the patients with advanced stages (III-IVA) of p16-negative OPSCC receiving pre-CCRT 18 FDG PET-CT was 0.75 (0.87-0.94, P = 0.0236)., Conclusions: Routine use of pre-CCRT 18 FDG PET-CT is not necessary for each patient with p16-negative OPSCC. Pre-CCRT 18 FDG PET-CT is associated with improved survival in patients with stage III-IVA p16-negative OSCC, but might be not in those with stage I-II p16-negative OPSCC. No large-scale prospective randomized study with a long-term follow-up period has evaluated the survival outcomes of preconcurrent chemoradiotherapy (CCRT) 18-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG PET-CT) in patients with p16-negative oropharyngeal squamous cell carcinoma (OPSCC). Our study is the first, largest, homogenous modality study on PET-CT including a long-term follow-up cohort to examine the survival outcomes of pre-CCRT 18 FDG PET-CT or non-pre-CCRT PET-CT for patients with p16-negative OPSCC receiving standard CCRT stratified by different clinical stages. Routine use of pre-CCRT 18 FDG PET-CT is not necessary for each patient with p16-negative OPSCC. Pre-CCRT 18 FDG PET-CT is associated with improved survival in patients with stage III-IVA p16-negative OPSCC, but might be not in those with stage I-II p16-negative OPSCC., (© 2023. The Author(s).)

Pseudomonas aeruginosa infections are often complicated by the fact that it can easily form a biofilm that increases its resistance to antibiotics. Consequently, the development of novel antibacterial agents against biofilm-associated drug-resistant P. aeruginosa is urgently needed. Herein, we report a series of 3-hydroxy-pyridin-4(1 H )-ones-ciprofloxacin conjugates that were designed and synthesized as dual antibacterial and antibiofilm agents against P. aeruginosa . A potential 2-substituted 3-hydroxy-1,6-dimethylpyridin-4(1 H )-one-ciprofloxacin conjugate ( 5e ) was identified and had the best minimum inhibitory concentrations of 0.86 and 0.43 μM against P. aeruginosa 27853 and PAO1 and reduced 78.3% of biofilm formation. In addition, 5e eradicates mature biofilms and kills living bacterial cells that are incorporated into the biofilm. Studies on the antibiofilm mechanism of conjugates showed that 5e interferes with iron uptake by bacteria, inhibits their motility, and reduces the production of virulence. These results demonstrate that 3-hydroxy-pyridin-4(1 H )-ones-ciprofloxacin conjugates are potent in the treatment of biofilm-associated drug-resistant P. aeruginosa infections.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode ® ). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs ( p -value = 6.76 × 10 -7 -7.31 × 10 -6 ) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 ( p -value = 6.76 × 10 -7 , odds ratio (OR) = 1.76), followed by rs12713768 ( p -value = 1.36 × 10 -6 , OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r 2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

Background: Implant-associated infection remains a major complication of orthopedic surgery. The treatment of such infection is complicated by bacterial biofilm formation on the metal surfaces of implants. Biofilm surrounds and protects the bacteria against the organism's endogenous defense system and from external agents such as antibiotics and mechanical debridement. This study aims to evaluate whether freezing nitrogen ethanol composite (FNEC), the combination of liquid nitrogen and 95% ethanol in a 3 to 1 ratio, used frequently in bone tumor surgery, is capable of disinfecting Staphylococcus aureus contaminated implants., Methods: The femurs of six New Zealand white rabbits were implanted with S. aureus-contaminated screws, half of which were treated with FNEC before implantation. The femurs were harvested 14 days after implantation. Histological analysis and TUNEL assay were conducted. The autoclaved screw, contaminated screw, and FNEC-treated contaminated screw were investigated using scanning electron microscopy to evaluate the biofilm structure., Results: The FNEC-treated group had significantly lower relative C-reactive protein levels. An obvious periosteal reaction at the implant site was observed in all rabbits in the non-FNEC group but none was observed in the FNEC-treated group. The FNEC-treated group exhibited fewer empty lacunae, less inflammatory infiltration, and less bone necrosis. Immunohistochemical analysis showed no S. aureus in bone tissue from the FNEC-treated group. Scanning electron microscopy showed disruption of the biofilm on the contaminated screw treated with FNEC., Conclusion: FNEC showed potential in disinfecting S.aureus-contaminated implants. Further investigation is warranted, such as the effect on the implant-cement-bone interface, for FNEC to be used clinically in treating implant-associated infection., Competing Interests: Conflicts of interest: Dr. Wei-Ming Chen, an editorial board member at the Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article, (Copyright © 2023, the Chinese Medical Association.)

Background: The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high-dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world., Methods: We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real-world setting. Patients were divided into three groups according to induction regimens., Results: The median age of the cohort was 70 (65-86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow-up of the cohort was 30 (interquartile range [IQR] 18-36) months. For the entire cohort median progression-free survival (PFS) was 26 (IQR 12.00-42.89) months and overall survival (OS) was 60 (IQR 40.00-67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy < partial remission, and no maintenance treatment were independent poor prognostic factors for OS., Conclusion: Front-line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real-world setting., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The study aims to clarify the association of sarcopenia with perioperative and postoperative complications in oral cavity squamous cell carcinoma (OCSCC) patients undergoing curative surgery and to understand the reasons causing the poor oncologic outcomes for OCSCC., Methods: We conducted a propensity score matching study to investigate the association of perioperative and postoperative outcomes in OCSCC patients with sarcopenia and without sarcopenia. A retrospective analysis of a large national data set from the Taiwan Cancer Registry Database was conducted. At least two claims for patients with a principal diagnosis of sarcopenia within the 12-month preoperative period were defined as the criteria for sarcopenia diagnosis (ICD-10-CM code M62.84). Sarcopenia was diagnosed through the measurement of low muscle strength and low muscle mass by any one of the patient's attending orthopaedic physician, rehabilitation physician, family medicine specialist or geriatrician. A multivariate logistic regression model was used to calculate the perioperative, and postoperative major complications., Results: Our final cohort included 16 293 patients with OCSCC (10 862 and 5 431 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for further analysis. The sarcopenia group was 10.40% female and 89.60% male, and the nonsarcopenia group was 9.74% female and 90.26% male. The mean age ± standard deviation (SD) were 56.44 ± 11.14 and 56.22 ± 11.29 for sarcopenia and nonsarcopenia groups. OCSCC patients with sarcopenia undergoing curative surgery had a significantly higher blood transfusion rate and volume; longer intensive care unit (ICU) stay, and hospital stay; higher postoperative 30-day mortality (adjusted odds ratio [aOR]: 1.12, 95% confidence interval [CI] [1.07, 1.56]) and rates of pneumonia (aOR: 1.34, 95% CI [1.20, 1.50]), acute renal failure (aOR: 1.45, 95% CI [1.12, 1.87]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]); higher postoperative first-year mortality (aOR: 1.18, 95% CI [1.13, 1.51]) and rates of pneumonia (aOR: 1.43, 95% CI [1.30, 1.56]), acute myocardial infarction (aOR: 1.52, 95% CI [1.06, 2.18]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45])., Conclusions: OCSCC patients with sarcopenia might exhibit more perioperative and surgical complications than those without sarcopenia., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Condensed Abstract: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). This is the first head-to-head propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18 FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era., Purpose: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects., Patients and Methods: We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18 FDG-PET-CT, and their outcomes were compared., Results: We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively)., Conclusions: Pretreatment 18 FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT., 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 © 2023 Su, Chen, Chen, Shia and Wu.)

The findings regarding changes in renal function in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are controversial. This study attempted to identify the factors associated with the large decline in renal function following DAA treatment. This retrospective cohort study included patients treated with DAAs at Chiayi and Yunlin Chang Gung Hospitals, Taiwan, from 1 January 2017 to 31 October 2020. Estimated glomerular filtration rate (eGFR) data were collected within 90 days prior to DAA therapy and 2 years after the confirmation of a sustained virologic response (SVR). We performed multiple logistic regression to evaluate the clinical or laboratory parameters associated with a large eGFR decline (≥10%). Among the enrolled 606 patients, the mean eGFR at the baseline and endpoint were 84.11 ± 24.38 and 78.88 ± 26.30 mL/min/1.73 m 2 , respectively ( p < 0.001). The factors associated with a large eGFR decline 2 years after the SVR included hypertension (OR: 1.481; 95% CI: 1.010-2.173, p = 0.044) and a higher baseline eGFR (OR: 1.016; 95% CI: 1.007-1.024, p < 0.001). A higher albumin level reduced the risk of a large eGFR decline (OR: 0.546; 95% CI: 0.342-0.872, p = 0.011). In the patients with HCV treated with DAAs, a larger renal function decline was more commonly observed in those with hypertension, a lower (but within normal range) albumin level, and a higher baseline eGFR, while DAA treatment had no effect. The clinical significance of these findings has to be further defined. Although some risk factors associated with chronic kidney disease may be alleviated after DAA treatment, the regular control and follow-up of risk factors and renal function are still recommended in at-risk patients after HCV eradication.

Phonon-phonon and electron/exciton-phonon coupling play a vitally important role in thermal, electronic, as well as optical properties of metal halide perovskites. In this work, we evaluate phonon anharmonicity and coupling between electronic and vibrational excitations in novel double perovskite Cs 2 NaFeCl 6 single crystals. By employing comprehensive Raman measurements combined with first-principles theoretical calculations, we identify four Raman-active vibrational modes. Polarization properties of these modes imply Fm 3̅ m symmetry of the lattice, indicative for on average an ordered distribution of Fe and Na atoms in the lattice. We further show that temperature dependence of the Raman modes, such as changes in the phonon line width and their energies, suggests high phonon anharmonicity, typical for double perovskite materials. Resonant multiphonon Raman scattering reveals the presence of high-lying band states that mediate strong electron-phonon coupling and give rise to intense nA 1 g overtones up to the fifth order. Strong electron-phonon coupling in Cs 2 NaFeCl 6 is also concluded based on the Urbach tail analysis of the absorption coefficient and the calculated Fröhlich coupling constant. Our results, therefore, suggest significant impacts of phonon-phonon and electron-phonon interactions on electronic properties of Cs 2 NaFeCl 6 , important for potential applications of this novel material., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The real-world benefits of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) remain unclear in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). This is a retrospective cohort study evaluating all patients with Child-Pugh class A HCV-related LC during 2013 to 2020 in the Chang Gung Medical System. A total of 215 patients fit the inclusion criteria and were enrolled. Of them, 132 (61.4%) patients achieved DAA induced-SVR and 83 (38.6%) did not receive anti-viral treatment. During a median follow-up of 18.4 (interquartile range, 10.1−30.9) months, the 2-year incidence of de novo EV occurrence was 8 (7.0%) in the SVR group and 7 (12.7%) in the treatment-naïve group. Compared to the treatment-naïve group, the SVR group was associated with a significantly lower incidence of EV occurrence (adjusted hazard ratio [aHR]: 0.47, p = 0.030) and a significantly lower incidence of EV progression (aHR: 0.55, p = 0.033). The risk of EV progression was strongly correlated with the presence of baseline EV (p < 0.001). To the best of our knowledge, this is the first study to demonstrate that DAA-induced SVR is associated with decreased risk of de novo EV occurrence and progression in the real world.

Purpose: H1-antihistamines (AHs) may exert protective effects against cancer. We investigated the association of AH use with hepatocellular carcinoma (HCC) risk in type 2 diabetes mellitus (T2DM) patients without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection., Methods: The data of patients with T2DM enrolled from Taiwan's National Health Insurance Research Database were examined for the period of January 1, 2008, to December 31, 2018. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the AH use-HCC risk association., Results: After 1:1 propensity score matching was performed, the two cohorts were each divided into AH users (n = 47,990) and nonusers (n = 47,990). The risk of HCC was significantly lower in AH users than in AH nonusers (adjusted hazard ratio [aHR]: 0.55 95% confidence interval [95% CI], 0.46 to 0.67; IRR: 0.70; 95% CI, 0.60 to 0.84), respectively. The dose-response relationship between AH use and HCC risk was also observed (aHRs: 0.58, 0.56, 0.50, and 0.41 for 28-35, 36-49, 50-77, and >77 cumulative defined daily doses of AH, respectively)., Conclusion: AH use can reduce HCC risk in T2DM patients without HBV or HCV infection in a dose-dependent manner., Competing Interests: Declaration of Competing Interest The authors have no potential conflicts of interest to declare. The datasets supporting the study conclusions are included within the manuscript., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background/purpose: Accurate staging is the first step for optimal treatment selection in patients with nasopharyngeal carcinoma (NPC). In this propensity-score-matched, population-based cohort study, we investigated the survival effects of pretreatment 8-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG-PET-CT) on patients with NPC., Methods: We included patients with stage I-IVA NPC receiving radiotherapy or concurrent chemoradiotherapy and categorized them into two 1:1 propensity score-matched groups according to whether or not they underwent pretreatment 18 FDG-PET-CT and compared their outcomes., Results: Of the 10,756 patients, propensity score matching yielded 4366 patients in each group. According to multivariable Cox regression analyses, the most prominent correlation between pretreatment 18 FDG-PET-CT and all-cause death was observed in patients with stage II NPC (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.60-0.90; P = .0433), followed by patients with stage III NPC (aHR, 0.81; 95% CI, 0.69-0.94; P = .0071) and patients with stage IVA NPC (aHR, 0.88; 95% CI, 0.79-0.97; P = .0091). This association was not significant in patients with stage I NPC (aHR, 1.20; 95% CI, 0.75-1.93; P = .4426)., Conclusion: Pretreatment 18 FDG-PET-CT is associated with longer survival in patients with clinical stage II-IVA NPC but not in stage I NPC., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to declare. The data sets supporting the study conclusions are included in the manuscript., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton's jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.

Purpose: No randomized study with a long-term follow-up has investigated the effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 FDG-PET-CT) on the survival of patients with stage IB-IIA cervical cancer receiving curative surgery. Therefore, in this propensity score-matched, population-based cohort study, we investigated the effect of preoperative 18 FDG-PET-CT on the survival outcomes of patients with potentially resectable cervical cancer., Patients and Methods: We included 2550 patients with stage IB-IIA cervical cancer receiving curative surgery with complete data on clinical stages. The patients were categorized into two 1:4 propensity, score-matched groups depending on whether they underwent pretreatment 18 FDG-PET-CT, and their outcomes were compared., Results: We included 2030 and 520 patients with cervical cancer in the non-pretreatment and pretreatment PET-CT groups, respectively. Multivariable analyses revealed that the most prominent correlation between preoperative PET-CT and all-cause death was observed in the patients with stage IB-IIA cervical cancer receiving surgery (aHR [95% CI]: 1.16 [0.83-1.63]; p = 0.3752)., Conclusions: Preoperative 18 FDG-PET-CT was not associated with longer survival in the patients with clinical stage IB-IIA cervical cancer receiving curative surgery.

Purpose: Whether preexisting sleep disorder is an independent risk factor for cancer remains unclear. Therefore, we performed this propensity score-matched population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sleep disorders., Patients and Methods: Patients were categorized into two groups on the basis of the presence or absence of sleep disorders and matched at a 1:1 ratio., Results: Propensity score matching yielded a final cohort of 289,162 patients (i.e., 144,581 and 144,581 in the sleep disorder and nonsleep disorder groups, respectively) who were eligible for further analysis. In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) of cancer risk in the sleep disorder group compared with the nonsleep disorder group was 1.07 (1.04-1.12; P = 0.0001). Furthermore, the adjusted IRRs (95% CIs) for all cancers, breast cancer, and ovarian cancer in the patients with sleep disorders were 1.08 (1.02-1.18), 1.20 (1.08-1.32), and 1.30 (1.10-1.52), respectively., Conclusion: The results suggested that sleep disorders are a significant risk factor for all cancers, breast cancer, and ovarian cancer., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to declare. The datasets supporting the study conclusions are included within the manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Whether preexisting sarcopenia is an independent risk factor for postoperative pneumonia (POP) for patients with oral cavity squamous cell carcinoma (OCSCC) remains unclear. Therefore, we conducted a propensity score-matched population-based cohort study to compare the risk of acute and late POP for patients with sarcopenic and nonsarcopenic OCSCC who underwent curative surgery., Patients and Methods: We included patients with OCSCC who underwent curative surgery and categorized them into 2 groups depending on whether they had preexisting sarcopenia. The patients in the sarcopenic and nonsarcopenic groups were matched at a ratio of 2:1., Results: The matching process yielded 16,257 patients (10,822 without sarcopenia and 5,435 with sarcopenia). In multivariate Cox regression analyses, the adjusted hazard ratio of POP for the group with OCSCC with preexisting sarcopenia was 1.20 (95% CI, 1.14-1.26; P<.0001) compared with the nonsarcopenic group. Among the patients with OCSCC who received curative surgery, those in the sarcopenic group exhibited a higher POP risk than those in the nonsarcopenic group for the following postoperative time periods: 31st to 90th day, 91st day to first year, first to second year, second to third year, third to fourth year, and fourth to fifth year., Conclusions: The high incidence of pneumonia persists for a long time in patients with OCSCC who receive curative surgery; this high incidence may even persist for 5 years after surgery, especially in patients with sarcopenia. For susceptible patients who are at risk for OCSCC, sarcopenia prevention measures (eg, exercise and early nutrition intervention) should be implemented.

Background: Whether the route of anaesthesia is an independent risk factor for dementia remains unclear. Therefore, we conducted a propensity score-matched (PSM) population-based cohort study to compare dementia incidence among surgical patients undergoing different routes of anaesthesia., Methods: The inclusion criteria were being an inpatient >20 years of age who underwent major elective surgery, defined as those requiring GA without or with inhalation anaesthetics or regional anaesthesia, and being hospitalised for >1 day between Jan 1, 2008 and Dec 31, 2019 in Taiwan. Patients undergoing major elective surgery were categorised into three groups according to the type of anaesthesia administered: noninhalation anaesthesia, inhalation anaesthesia, and regional anaesthesia, matched at a 1:1 ratio. The incidence rate (IR) of dementia was determined., Findings: PSM yielded 63,750 patients (21,250 in the noninhalation anaesthesia group, 21,250 in the inhalation anaesthesia group, and 21,250 in the regional anaesthesia group). In the multivariate Cox regression analysis, the adjusted hazard ratios (aHRs; 95% confidence intervals) of dementia for the inhalation and noninhalation anaesthesia groups compared with the regional anaesthesia group were 20.16 (15.40-26.35; p < 0.001) and 18.33 (14.03-24.04; p < 0.001), respectively. The aHR of dementia for inhalation anaesthesia compared with noninhalation anaesthesia was 1.13 (1.03-1.22; p = 0.028). The IRs of dementia for the inhalation, noninhalation, and regional anaesthesia groups were 3647.90, 3492.00, and 272.99 per 100,000 person-years, respectively., Interpretation: In this population based cohort study, the incidence of dementia among surgical patients undergoing general anaesthesia was higher than among those undergoing regional anaesthesia. Among patients undergoing general anaesthesia, inhalation anaesthesia was associated with a higher risk of dementia than noninhalation anaesthesia. Our results should be confirmed in a randomised controlled trial., Funding: The study was partially supported by Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital (Funding Number: 10908, 10909, 11001, 11002, 11003, 11006, and 11013)., Competing Interests: The authors have no potential conflicts of interest to declare., (© 2022 The Author(s).)

Objective: To analyze the clinical characteristics of the neonates infected with SARS-CoV-2 during the Omicron outbreak in Shanghai 2022. Methods: In this retrospective case series study, all the 16 neonates with SARS-CoV-2 Omicron infection who were admitted to the neonatal unit in Shanghai Public Health Clinical Center from March 1 st to May 31 st , 2022 were enrolled. Their epidemiological history, clinical manifestations, nucleic acid cycle threshold (Ct) value and outcomes were analyzed. Based on maternal vaccination, they were divided into vaccinated group and unvaccinated group. Rank sum test and Chi-square test were used for the comparison between the groups. Results: Among the 16 neonates, 10 were male, and 6 were female. All the infants were full-term. The infection was confirmed at the age of 12.5 (8.0, 20.5) days. All the neonates had a history of exposure to infected family members, and thus horizontal transmission was the primary mode. Four infants were asymptomatic, 12 were symptomatic, and there were no severe or critical cases. The most common clinical manifestation was fever (11 cases), with the highest temperature of 38.1 (37.9, 38.3) ℃ and a course of 1-5 days. Other clinical manifestations included nasal obstruction (3 cases), runny nose (2 cases), cough (2 cases), poor feeding (2 cases), vomiting (1 case), and mild tachypnea (1 case). The complete blood counts of all neonates were within the normal range, and the C-reactive protein increased slightly in 1 infant. Chest imaging was performed in 2 infants, showing mild focal exudative changes. Nucleic acid turned negative (Ct value ≥35) within 7-15 days after diagnosis. All neonates fully recovered after supportive treatment, and the length of hospitalization was 13 (10, 14) days. In the telephone follow-up 2 weeks after discharge for all 16 cases, no infant showed reoccurrence of clinical manifestations or nucleic acid reactivation. Maternal vaccination was not significantly correlated with symptomatic infection or the persistence of positive nucleic acid result in neonates (all P >0.05). Conclusions: Horizontal transmission is the primary mode for neonatal SARS-CoV-2 Omicron infection. Neonatal infections are usually mild or asymptomatic, with good short-term outcomes. And their clinical manifestations and laboratory examinations are nonspecific.

Importance: There are emerging concerns from case reports and pharmacovigilance analyses of a possible risk of interstitial lung disease (ILD) associated with the use of factor Xa (FXa) inhibitors., Objective: To evaluate the risk of incident ILD associated with the use of oral anticoagulants (OACs) in patients with nonvalvular atrial fibrillation (NVAF)., Design, Setting, and Participants: This nationwide retrospective cohort study used data from the Taiwan National Health Insurance Research Database. Patients with NVAF without preexisting lung disease who received OACs from June 1, 2012, to December 31, 2017, were included. Propensity score stabilized weighting (PSSW) was used to balance covariates across the medication groups (FXa inhibitors, dabigatran, and warfarin, with warfarin as the reference). Patients were followed up from the drug index date until the onset of ILD, death, or end of the study (December 31, 2019), whichever occurred first. Data were analyzed from September 11, 2021, to August 3, 2022., Exposures: Patients with NVAF were treated with FXa inhibitors, dabigatran, or warfarin., Main Outcomes and Measures: New-onset idiopathic ILD., Results: Among the 106 044 patients (mean [SD] age, 73.4 [11.9] years; 59 995 men [56.6%]) included in the study, 64 555 (60.9%) received FXa inhibitors (apixban [n = 15 386], edoxaban [n = 12 413], and rivaroxaban [n = 36 756]), 22 501 (21.2%) received dabigatran, and 18 988 (17.9%) received warfarin at baseline. The FXa inhibitors were associated with a higher risk of incident ILD (0.29 vs 0.17 per 100 patient-years; hazard ratio, 1.54 [95% CI, 1.22-1.94]; P < .001), whereas dabigatran was associated with a nonsignificant difference in risk of incident ILD compared with warfarin (reference) after PSSW. The higher risk of incident ILD for FXa inhibitors vs warfarin was consistent with several high-risk subgroups., Conclusions and Relevance: Results of this study suggest that FXa inhibitors were associated with lung injury among patients with NVAF who were treated with OACs. Physicians should be vigilant in monitoring for any potential adverse lung outcomes associated with the use of these drugs.

Background: The use of primary or revision stem during revision total hip arthroplasty (THA) for aseptic stem loosening with Paprosky type I/II femoral defect remains controversial. The aim of this study was to compare the outcomes of patients who underwent revision THA with a primary or revision stem., Methods: We retrospectively reviewed 78 patients who received revision THA for aseptic stem loosening using primary (N = 28) or revision stems (N = 50). The bone defects were classified as Paprosky type I or II. The mean follow-up duration was 72.3 ± 34.7 months. The primary outcome domains included surgical complications and implant failures. The secondary outcome domains included medical complications, 30- and 90-day readmission, and Harris hip score (HHS)., Results: The use of revision stem was associated with a higher incidence than primary stem of patient complications (60.0% vs. 32.1%, p = 0.018), including intraoperative femur fracture (28.0% vs. 7.1%, p = 0.029) and greater trochanter fracture (16.0% vs. 0%, p = 0.045). The implant survival rate was comparable between groups. HHS at the final follow-up was similar., Conclusion: With a lower risk of surgical complications and a similar rate of mid-term implant survival, cementless primary stem appears superior to revision stem in revision THA for aseptic stem loosening with Paprosky type I/II femoral defect., Competing Interests: Conflicts of interest: Dr. Wei-Ming Chen, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Objective: To evaluate methods of reduction using fragments of the greater tuberosity, and determine the clinical efficacy of humeral head replacement prosthesis height for proximal humerus fractures., Methods: A retrospective study of patients with proximal humerus fractures who were treated and followed up from January 2015 to December 2019, 19 patients met the indications for humeral head replacement, including 7 males and 12 females;8 on the left side and 11 on the right side. The age ranged from 58 to 84 years old with an average of (71.5±5.8 ) years old. The time from injury to operation 3 to 18 d with an average of (7.9±4.3) d. According to Neer's classification, there were 2 cases of three-part fractures with dislocations and 17 cases of four-part fractures, including 6 cases with dislocation and 2 cases with head splits. All 19 patients used the modular prosthesis. The greater tuberosity fracture fragments were reduced to determine the distance from the apex of the greater tuberosity to the humerus marking point. This distance was used as the standard for the height of the prosthesis. One year after the operation, the Constant-Murley score and the University of California, Los Angeles (UCLA) shoulder score were used to evaluate the functional status of the shoulder joint and patient satisfaction., Results: The 19 patients were followed up from 12 to 58 months with an average of (31.9±14.2) months. The length of the upper arm was 26 to 32 cm after the operation, two-sided comparison error <0.5 cm. Anteroposterior and lateral X-ray films of the shoulder joint at 3 months after operation showed that the fracture fragments were all healed. After one year follow-up, the Constant-Murley score was 80.8±8.9, and the UCLA score was 27.9±4.8. Patient satisfaction rate was 89.5%(17/19)., Conclusion: The greater tuberosity fracture fragments reduction technique, which use the distance from the apex of the greater tuberosity of humerus to the humeral marking point as the standard for the height of the prosthesis, is a simple and effective way with good outcomes in shoulder hemiarthroplasty for treatment of proximal humerus fractures.

Aftercare programs' effectiveness for suicide ideators has seldom been reported. This study assessed rates and factors related to the recurrence of suicide-related episodes after the index suicidal ideation episode, index cases, and family members receiving aftercare. This is a secondary data analysis of 1787 suicidal ideation episodes from 1557 individuals reported to the National Suicide Surveillance System in New Taipei City, Taiwan, from January 2012 to June 2013 and followed up until September 2013. Among 1787 index suicidal ideations, 19.1% had recurrences of suicide-related episodes, including suicidal ideation (11.9%), attempt (6.7%), and death (0.5%) within 2 years after index ideation. These recurrences were significantly reduced after the index cases received aftercare twice, three, and four or higher. Family members receiving aftercare twice or more were associated with reduced suicidality in the index cases. Receiving aftercare among index cases was associated with being a woman, suicide due to occupation/finance, and reporting from suicide hotlines. Receiving aftercare among family members was associated with the index cases aged ≤ 19 years old, suicide reasons related to school, occupation/finance, and reporting from schools and hospitals. Aftercare programs for suicide ideators and family members of adolescent suicide ideators (aged ≤ 19 years old) decreased subsequent episodes of suicidal behavior., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

No comparative study with a long-term follow-up period has evaluated the survival outcomes of preoperative 18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 FDG PET/CT) in patients with p16-negative OPSCC. We included patients with stage I-IVB p16-negative OPSCC undergoing surgery and categorized them into two groups based on whether they underwent preoperative 18 FDG PET/CT and compared their outcomes: the case group comprised patients who did not undergo preoperative 18 FDG PET/CT, whereas the control group comprised patients who underwent preoperative 18 FDG PET/CT. The findings of the multivariable Cox regression analysis revealed no association between preoperative 18 FDG PET/CT and overall survival (OS) in the case and control groups in the patients with stage I-III p16-negative OPSCC undergoing surgery (after multivariable adjustment, the hazard ratio [HR] was 1.12; 95% confidence interval [CI] = 0.86-1.48: P = 0.4028). However, we noted an association between preoperative 18 FDG PET/CT and OS in the case and control groups in the patients with stage IVA and IVB p16-negative OPSCC undergoing surgery (after multivariable adjustment, the HR of all-cause mortality for nonpreoperative PET/CT was 1.82 compared with preoperative PET/CT; 95% CI = 1.47-2.26; P < 0.0001). Preoperative 18 FDG PET/CT use was associated with a lower risk of mortality in the patients with stage IVA and IVB p16-negative OPSCC without metastasis., Competing Interests: None., (AJCR Copyright © 2022.)

Objective: To evaluate the effect of immune status on disease progression in patients with newly diagnosed multiple myeloma (NDMM) achieving deep response. Methods: Clinical data of 125 NDMM patients at Beijing Chaoyang Hospital from August 2015 to February 2020 were retrospectively analyzed who achieved very good partial response (VGPR) or better after front-line treatment. The immune status and its influence on progression-free survival (PFS) were analyzed. Results: (1) All patients received novel drug regimens, and 50.4% (63/125) patients followed by autologous stem cell transplantation (ASCT). The rate of complete response (CR) as best efficacy was 89.6%, in which 66.4% achieved CR and MRD negativity tested by second generation flow cytometry. (2) Cox multivariate analysis suggested that persistent severe immunoparesis 3 months and 6 months since the best response was an independent poor prognostic factor for PFS. (3) The 3-year PFS rate in the severe immunoparesis group was significantly lower than that in the control group (41.3% vs. 64.4%, P =0.021). (4) The 3-year PFS rates in patients with persistent severe immunoparesis at 3 months or 6 months were significantly lower (30.0% vs. 63.5%, P <0.001; 16.4% vs. 63.8%, P <0.001 respectively). (5) Even in those achieving CR and negative MRD, the 3-year PFS rate when severe immunoparesis lasted 6 months was significantly lower (22.2% vs. 83.2%, P =0.005). Conclusion: The immune status in NDMM patients achieving deep response is closely related to survival. Persistent severe immunoparesis indicates early progression of the disease.

Aims: Shenghua Decoction (SHD) is a well-known classic herbal formula documented in traditional Chinese medicine (TCM) that has been widely applied during the postpartum period in Chinese communities for several years. We conducted this systematic review and meta-analysis to explore the influence of SHD as an adjuvant treatment for early medical abortion using a combination of mifepristone followed by misoprostol., Methods: This systematic review and meta-analysis was reported using 2020 PRISMA guidelines. Eight databases were searched from their establishment to February 28, 2022, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, the Chinese BioMedical database, the Chinese Scientific Journal Database, and the Wanfang database. The Grading of Recommendations Assessment, Development, and Evaluation estimated the quality of evidence., Results: Sixteen RCTs involving 3016 patients were included in the meta-analysis. Overall, compared with no treatment as the control group after early medical abortion, patients treated with SHD were associated with a higher complete abortion rate (RR: 1.14; 95% CI: 1.10 - 1.18; P < 0.01, I 2 = 26%, moderate quality), lower incomplete abortion rate (RR: 0.31; 95% CI: 0.24 - 0.41; P < 0.01, I 2 = 0%, moderate quality), and lower viable pregnancy rate (RR: 0.26; 95% CI: 0.11 - 0.62; P < 0.01, I 2 = 0%, moderate quality). Additionally, SHD supplementation was associated with reduced the induction-abortion time, duration of vaginal bleeding and menstrual recovery time., Conclusion: Our findings suggest that SHD supplementation may be beneficial for women seeking a medical abortion before the 7-week gestational period and no adverse events in the experimental group were reported. However, the methodological quality of the included RCTs was unsatisfactory, and therefore it is necessary to further verify the effectiveness of SHD using standardized studies of rigorous design., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Thrombocytopenia is a common extrahepatic manifestation in chronic liver disease. However, there have been rare studies of impacts of risk for hepatitis C virus-associated thrombocytopenia (HCV-TP) and hepatitis B virus-associated thrombocytopenia (HBV-TP). The aim of this study is to evaluate different impacts of risk factors for HCV-TP and HBV-TP., Methods: We retrospectively collected 1803 HCV patients and 1652 HBV patients to examine the risk factors for time to moderate and severe thrombocytopenia (platelet counts <100 × 10 9 /L and <50 × 10 9 /L, respectively) by Cox proportional hazards models. Moreover, we prospectively enrolled 63 HCV-TP patients, 11 HBV-TP patients, and 27 HCV controls to detect specific antiplatelet antibodies by enzyme-linked immunosorbent assay and analyze their effects., Results: Prevalence of platelet <100 × 10 9 /L was 11.86% and 6.35% in HCV and HBV patients without cancer history, respectively. HCV-to-HBV incidence rate ratio for thrombocytopenia was 6.95. Initial thrombocytopenia was the most significant risk factor for HCV-TP and HBV-TP regardless of thrombocytopenia severity. Splenomegaly and cirrhosis were significant risk factors for moderate, but not severe HCV-TP. Hyperbilirubinemia was an important moderate and severe HBV-TP risk factor. Antiplatelet antibodies were correlated with HCV-TP severity, of which anti-glycoprotein IIb/IIIa antibody being associated with smaller spleen size. The antiplatelet autoantibody might contribute to thrombocytopenia either independently or with splenomegaly as the important risk in HCV-TP patients without advanced cirrhosis., Conclusion: HCV was associated with higher thrombocytopenia incidence than HBV. Thrombocytopenia risk factors varied with virus type and severity. Different management for HCV-TP and HBV-TP was suggested., Competing Interests: Conflicts of interest All authors declared no conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)