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BACKGROUND: Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration. OBJECTIVE: To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin. DESIGN: Retrospective, population-based cohort study using new-user and active-comparator design. SETTING: General population. SUBJECTS: Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018. METHODS: Data were extracted from Taiwan's National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs. RESULTS: We included 13 586 5ARIs users (mean age: 69 years) and 54 344 tamsulosin users (mean age: 68.37 years). After a mean follow-up of 3.7 years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98-1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02-1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87-1.12], in the subgroup analyses. CONCLUSIONS: We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence.
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Inibidores de 5-alfa Redutase , Dutasterida , Finasterida , Degeneração Macular , Hiperplasia Prostática , Tansulosina , Humanos , Inibidores de 5-alfa Redutase/efeitos adversos , Inibidores de 5-alfa Redutase/uso terapêutico , Masculino , Idoso , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/epidemiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Incidência , Degeneração Macular/epidemiologia , Degeneração Macular/diagnóstico , Degeneração Macular/induzido quimicamente , Dutasterida/uso terapêutico , Dutasterida/efeitos adversos , Tansulosina/uso terapêutico , Tansulosina/efeitos adversos , Finasterida/efeitos adversos , Finasterida/uso terapêutico , Fatores de Risco , Pessoa de Meia-Idade , Medição de Risco , Bases de Dados FactuaisRESUMO
In this study, a simple and facile procedure using the all or none formation of double-stranded DNA-templated copper nanoclusters on specific-primer PCR fragments was designed to fluorescently identify the T315I single nucleotide variant on the BCR-ABL1 gene. Chronic myeloid leukaemia (CML), a disease caused by the BCR-ABL1 fusion of tyrosine kinase, is well known for the T315I mutation that causes tyrosine kinase inhibitors (TKIs) to be resisted due to the alternative structure of the drug-binding site. Therefore, it is an important single nucleotide variant for clinical detection. In this study, only specific functional primers and the digestion of the wild genotype from the T315I mutation site with specific restriction enzymes were designed, and the different digested products could then be captured using magnetic beads. The final products would allow for fluorescent sensing via the all or none formation of double-stranded DNA-templated copper nanoclusters for the detection of the T315I mutation. This study has been successfully applied for identifying wild and mutant homozygotes and the mutant/wild heterozygote of the T315I mutation. It is expected that this analytical system can serve as a tool for the clinical diagnosis of T315I mutations and be applied to real samples of CML patients in the future.
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Cobre , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Reação em Cadeia da Polimerase , Proteínas de Fusão bcr-abl/genética , Corantes , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Nucleotídeos , Fenômenos MagnéticosRESUMO
AIMS: To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We conducted a retrospective cohort study by analysing a large multi-institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO. RESULTS: We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61-81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4-108.7] mL/min/1.73 m2 and urine albumin-creatinine ratio [UACR] 26.1 [9.7-117.6] mg/g) and 1067 new users of GLP-1RAs (mean [SD] age 58.4 (41.5) years, median [IQR] HbA1c 73 [64-84] mmol/mol, eGFR 91.6 [68.6-114.0] mL/min/1.73 m2 and UACR 37.6 [11.1-153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person-years), compared to those receiving GLP-1RAs (10.7/1000 person-years) with an HR of 0.75 (95% CI 0.64-0.88). CONCLUSIONS: Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP-1RAs. Future studies are necessary to confirm this observation.
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Diabetes Mellitus Tipo 2 , Edema Macular , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Glucose , Humanos , Hipoglicemiantes/efeitos adversos , Lactente , Edema Macular/induzido quimicamente , Edema Macular/epidemiologia , Estudos Retrospectivos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Taiwan/epidemiologiaRESUMO
With a typical sample size of a few thousand subjects, a single genome-wide association study (GWAS) using traditional one single nucleotide polymorphism (SNP)-at-a-time methods can only detect genetic variants conferring a sizable effect on disease risk. Set-based methods, which analyze sets of SNPs jointly, can detect variants with smaller effects acting within a gene, a pathway, or other biologically relevant sets. Although self-contained set-based methods (those that test sets of variants without regard to variants not in the set) are generally more powerful than competitive set-based approaches (those that rely on comparison of variants in the set of interest with variants not in the set), there is no consensus as to which self-contained methods are best. In particular, several self-contained set tests have been proposed to directly or indirectly "adapt" to the a priori unknown proportion and distribution of effects of the truly associated SNPs in the set, which is a major determinant of their power. A popular adaptive set-based test is the adaptive rank truncated product (ARTP), which seeks the set of SNPs that yields the best-combined evidence of association. We compared the standard ARTP, several ARTP variations we introduced, and other adaptive methods in a comprehensive simulation study to evaluate their performance. We used permutations to assess significance for all the methods and thus provide a level playing field for comparison. We found the standard ARTP test to have the highest power across our simulations followed closely by the global model of random effects (GMRE) and a least absolute shrinkage and selection operator (LASSO)-based test.
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Estudo de Associação Genômica Ampla/métodos , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética , Simulação por Computador , Predisposição Genética para Doença , Humanos , Análise de Regressão , Risco , Tamanho da AmostraRESUMO
INTRODUCTION: Mammographic density (MD) is a strong biomarker of breast cancer risk. MD increases after women start estrogen plus progestin therapy (EPT) and decreases after women quit EPT. A large interindividual variation in EPT-associated MD change has been observed, but few studies have investigated genetic predictors of the EPT-associated MD change. Here, we evaluate the association between polymorphisms in hormone metabolism pathway genes and MD changes when women quit EPT. METHODS: We collected mammograms before and after women quit EPT and genotyped 405 tagging single nucleotide polymorphisms (SNPs) in 30 hormone metabolism pathway genes in 284 non-Hispanic white participants of the California Teachers Study (CTS). Participants were ages 49 to 71 years at time of mammography taken after quitting EPT. We assessed percent MD using a computer-assisted method. MD change was calculated by subtracting MD of an 'off-EPT' mammogram from MD of an 'on-EPT' (that is baseline) mammogram. Linear regression analysis was used to investigate the SNP-MD change association, adjusting for the baseline 'on-EPT' MD, age and BMI at time of baseline mammogram, and time interval and BMI change between the two mammograms. An overall pathway and gene-level summary was obtained using the adaptive rank truncated product (ARTP) test. We calculated 'P values adjusted for correlated tests (P(ACT))' to account for multiple testing within a gene. RESULTS: The strongest associations were observed for rs7489119 in SLCO1B1, and rs5933863 in ARSC. SLCO1B1 and ARSC are involved in excretion and activation of estrogen metabolites of EPT, respectively. MD change after quitting was 4.2% smaller per minor allele of rs7489119 (P = 0.0008; P(ACT) = 0.018) and 1.9% larger per minor allele of rs5933863 (P = 0.013; P(ACT) = 0.025). These individual SNP associations did not reach statistical significance when we further used Bonferroni correction to consider the number of tested genes. The pathway level summary ARTP P value was not statistically significant. CONCLUSIONS: Data from this longitudinal study of EPT quitters suggest that genetic variation in two hormone metabolism pathway genes, SLCO1B1 and ARSC, may be associated with change in MD after women stop using EPT. Larger longitudinal studies are needed to confirm our findings.
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Neoplasias da Mama/genética , Estrogênios/uso terapêutico , Glândulas Mamárias Humanas/anormalidades , Transportadores de Ânions Orgânicos/genética , Progestinas/uso terapêutico , Esteril-Sulfatase/genética , Adulto , Idoso , Densidade da Mama , Neoplasias da Mama/epidemiologia , Terapia de Reposição de Estrogênios , Feminino , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado , Estudos Longitudinais , Pessoa de Meia-IdadeRESUMO
Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1,004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study, we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repair (BER), nucleotide excision repair (NER), non-homologous end-joining (NHEJ) and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and POLB rs7832529 (BER) (pACT = 0.003; ppathway = 0.021) among all, and SNPs in XPC (NER) and OGG1 (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER p = 0.034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (POLB, OGG1) and NER genes (XPC). A SNP that tags both the XRCC6 and SREBF2 genes strongly modifies the association between bladder cancer risk and smoking.
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Antígenos Nucleares/genética , Carcinoma de Células de Transição/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Fumar/efeitos adversos , Fumar/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , China , Feminino , Predisposição Genética para Doença , Humanos , Autoantígeno Ku , Los Angeles , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
PURPOSE: This study aimed to explore the incidence and severity of vincristine-induced peripheral neuropathy (VIPN) in non-Hodgkin lymphoma (NHL) survivors (primary aim) and its impact on daily life by comparing common cancer symptoms, functional status, and quality of life (QoL) among survivors with acute, long-term, and non-VIPN (secondary aim). METHODS: This cross-sectional study examined 144 NHL survivors. Standardized questionnaires were used to assess common cancer symptoms, functional status, and QoL with the European Organization for the Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC-QLQ-C30). VIPN (Chemotherapy-Induced Peripheral Neuropathy) status was classified using EORTC-QLQ-CIPN20. A self-designed interference scale was developed to determine the impact of the VIPN on daily activities. The Kruskal-Wallis test and Spearman rank correlation were used in this study. RESULTS: Among the survivors of acute and long-term VIPN, the highest incidences and most severe symptoms were found for hand numbness and foot cramps. A significant moderate correlation was found between disturbances in daily activities and acute or long-term VIPN, including gait changes, going up or down the stairs, and imbalance-related falls. Acute and long-term VIPN survivors showed worse symptoms (fatigue, insomnia, and constipation) and lower QoL than non-VIPN survivors did. In acute VIPN, social function was significantly affected, whereas in long-term VIPN, emotional and cognitive functions were affected. CONCLUSION: Numbness and cramps should be addressed in survivors of acute and long-term VIPN. Preventing falls is recommended for NHL survivors with VIPN, and psychological support is suggested for long-term VIPN survivors.
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Linfoma não Hodgkin , Neoplasias , Doenças do Sistema Nervoso Periférico , Humanos , Vincristina/efeitos adversos , Qualidade de Vida/psicologia , Estudos Transversais , Estado Funcional , Hipestesia , Cãibra Muscular , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/psicologia , Sobreviventes , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologiaRESUMO
Multiple mating by avian females may increase hatching and overall brood success; however, reproductive effort and parental investment are costly, and females may be gradually depleted, with lowered outputs over time. Thus, males in social polyandry systems may differ greatly in their reproductive gains. In the present study, we investigated the reproductive outputs of social polyandrous and sex-role-reversed pheasant-tailed jacanas, Hydrophasianus chirurgus, to assess the effects of polyandry, seasonality, and male mating order on breeding success. Female jacanas produced multiple clutches, either by leaving two or more clutches with an individual male (22%), or by mating with two or more males (78%). The polyandrous females laid both the first and second clutches earlier and showed a breeding period more than twice as long as that of monandrous females. Both polyandry and seasonality affected the fate of a clutch, where clutches from polyandrous females and the early season had higher hatching and brood success rates, but the number of polyandrous females declined over the season. Polyandrous females not only laid more clutches and eggs, and gained more hatchlings and fledglings, but also achieved higher per-clutch outputs and hatching rates than monandrous females. In polyandry groups, males gained higher total hatchlings and fledglings, although not total clutches or eggs, than males in monandry or bi-andry groups. Moreover, males in polyandry groups achieved higher hatchlings and fledglings per clutch and higher hatching and brood success rates. In polyandry groups, the first-mating males obtained more clutches, eggs, and hatchlings; however, they did not have higher success rates, nor total fledglings and per-clutch outputs, than males who mated later. Overall, the results indicate a selective advantage of polyandry for the jacanas studied, particularly in the early breeding season. This advantage, however, differs both between the sexes and intra-sexually, suggesting strong connections with certain ecological/environmental conditions in addition to the jacanas' own quality.
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BACKGROUND: Previous studies suggested an association between cataract surgery and retinal vascular occlusion. However, the association may be attributable to detection bias because postoperative monitoring may be more frequent for those who receive cataract surgery than for those who do not. DESIGN: Population-based cohort study using target trial emulation framework. METHODS: We included patients with cataract aged 50 years and older receiving cataract surgery or non-surgical interventions identified from the Taiwan National Health Insurance Research Database between 2003 and 2018, matched by propensity score. The primary outcome was retinal vascular occlusion. Cox proportional hazards models were used to compare surgery and control groups. Additional analyses were restricted to patients who had undergone fundoscopic examination within 6 months prior to cataract surgery to address the issue of detection bias. RESULTS: We included 577,129 cataract surgery and control pairs. We found the hazard ratio (HR) for retinal vascular occlusion after cataract surgery was 1.23 (95% confidence interval (CI): 1.17-1.29), compared with the control group. Secondary outcome analyses yielded similar results for retinal artery occlusion (HR: 1.13, 95% CI: 1.02-1.26) and retinal vein occlusion (HR: 1.26, 95% CI: 1.20-1.33). However, no risk of retinal vascular occlusion was observed among patients who had received fundoscopic examinations (HR: 1.06, 95% CI: 0.98-1.15) at baseline. CONCLUSIONS: Our study underscored the importance of conducting complete baseline fundoscopic examinations before cataract surgery to clarify whether postoperative conditions are due to patients' underlying diseases or unintended complications of cataract surgery.
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OBJECTIVE: To investigate differences in outcomes between active-fluidics and gravity-fluidics phacoemulsification systems. METHODS: We searched PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) published no later than December 1, 2021. The Cochrane Collaboration risk of bias tool was used for quality assessment. We presented the outcomes as standardized mean differences (SMDs) with 95% confidence intervals (CI). Sensitivity analysis was performed by removing studies that included ≥2 types of phacoemulsification tips. RESULTS: We analyzed six RCTs that totally enrolled 884 patients. Patients undergoing lens extraction with active-fluidics systems exhibited lower cumulative dissipated energy (CDE), total aspiration time (TAT), and estimated fluid usage (EFU) compared with patients who did not (SMD [95% CI]: CDE, - 0.818 [ - 1.054 to - 0.582]; TAT, - 0.664 [ - 0.850 to - 0.479]; EFU, - 0.655 [ - 0.932 to - 0.378]). A sensitivity analysis revealed similar results for CDE, TAT, and EFU. For endothelial cell density (ECD) 1 week after surgery, ECD 1 month after surgery, and central corneal thickness (CCT) 1 week after surgery, outcomes of both systems were comparable (ECD at 1 week, 0.074 [ - 0.177 to 0.325]; ECD at 1 month, 0.069 [ - 0.167 to 0.305]; CCT 1 week after surgery, 0.077 [ - 0.173 to 0.328]). No severe adverse events in patients treated with either system were reported in the studies. CONCLUSION: Active-fluidics systems are superior to gravity-fluidics systems with respect to CDE, TAT, and EFU; no differences in postoperative ECD and CCT were observed. Future studies are required to determine the reasons for heterogeneity and to detect rare adverse events.
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Extração de Catarata , Facoemulsificação , Humanos , Acuidade Visual , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Facoemulsificação/métodosRESUMO
BACKGROUND: The main objective of this study was to investigate the risk of falls among middle-aged and older adults with dynapenic abdominal obesity. METHODS: A systematic literature search was conducted to review and analyze relevant studies. Dynapenia was measured by handgrip strength, and abdominal obesity was measured by waist circumference. The search keywords included "older people" OR "elderly" OR "middle age" AND "dynapenia" AND "abdominal obesity" AND "fall." The search was not limited by time and included articles published up until April 2023. The literature search process followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, involving extraction and examination of the retrieved relevant articles. Systematic literature searches were performed in databases such as Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library. RESULTS: This study collected a total of eight articles with a combined sample size of 15,506 participants. The findings revealed that the average follow-up period for falls was 6.6 years (SD = 3.67). The overall results of the study showed that individuals with dynapenic abdominal obesity had a higher risk of falls compared to those without dynapenic abdominal obesity (RR = 6.91, 95% CI: 5.42-8.80). Subgroup analysis demonstrated that both prospective studies (HR = 6.61; 95% CI = 4.29-10.20) and retrospective studies (OR = 7.37; 95% CI = 5.13-10.59) consistently found a higher risk of falls among individuals with dynapenic abdominal obesity. However, there was no significant difference in fall risk between community-dwelling individuals with dynapenic abdominal obesity and hospitalized individuals with dynapenic abdominal obesity (Qbetweenx2 = 0.29, p = 0.58). Additionally, there was no difference in fall risk between individuals with dynapenic abdominal obesity residing in Europe and Latin America compared to those residing in Asia (Qbetweenx2 = 0.05, p = 0.81). It was worth noting that male individuals with dynapenic abdominal obesity had a higher risk of falls compared to females (Qbetweenx2 = 4.73, p = 0.03). CONCLUSIONS: Empirical studies have demonstrated that individuals with dynapenic abdominal obesity have a higher risk of falls. Therefore, healthcare professionals should conduct early fall risk assessments and develop effective preventive strategies specifically targeted at individuals with dynapenic abdominal obesity.
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BACKGROUND: Hepatitis B virus (HBV) affects the occurrence and survival outcome of various malignant disorders. The study aimed to evaluate the survival outcome of head and neck squamous cell cancer (HNSCC) patients with or without HBV infection. METHODS: This study included patients with HNSCC who visited Taichung Veterans General Hospital from 2007 to 2015. HBV infection was defined by hepatitis B surface antigen (HBsAg) seropositivity. By propensity score matching, we compared survival outcomes, including progression-free survival (PFS) and overall survival (OS), among patients with or without HBV infection. RESULTS: The prevalence of HBV infection in our cohort was 12.3%. Among the 1,015 patients included in the matched analysis, a higher risk of baseline liver cirrhosis (11.3% vs. 3.4%, p < 0.001) and initial hepatic dysfunction (10.8% vs. 5.4%, p = 0.005) rates were observed than those without HBV infection at baseline. The 5-year OS was 43.1% and 53.2% (p < 0.001) and the 5-year PFS was 37.4% and 42.3% (p = 0.007) in patients with and without HBV infection, respectively. The incidence of subsequent hepatic dysfunction showed no difference between patients with and without HBV infection (29.6% vs. 26.8%, p = 0.439). CONCLUSIONS: Patients with HNSCC and HBV infection were younger and had a higher risk of cirrhosis compared to those without HBV infection. Moreover, HBV infection significantly influenced the OS and PFS outcomes but not subsequent hepatic dysfunction in patients with HNSCC.
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Neoplasias de Cabeça e Pescoço , Hepatite B , Neoplasias de Células Escamosas , Humanos , Vírus da Hepatite B , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Estudos Retrospectivos , Hepatite B/complicações , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Cirrose Hepática/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologiaRESUMO
To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy.
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Epstein-Barr virus (EBV) replicates its genome in the nucleus and undergoes tegumentation and envelopment in the cytoplasm. We are interested in how the single-stranded DNA binding protein BALF2, which executes its function and distributes predominantly in the nucleus, is packaged into the tegument of virions. At the mid-stage of virus replication in epithelial TW01-EBV cells, a small pool of BALF2 colocalizes with tegument protein BBLF1, BGLF4 protein kinase, and the cis-Golgi marker GM130 at the perinuclear viral assembly compartment (AC). A possible nuclear localization signal (NLS) between amino acids 1100 and 1128 (C29), which contains positive charged amino acid 1113RRKRR1117, is able to promote yellow fluorescent protein (YFP)-LacZ into the nucleus. In addition, BALF2 interacts with the nucleocapsid-associated protein BVRF1, suggesting that BALF2 may be transported into the cytoplasm with nucleocapsids in a nuclear egress complex (NEC)-dependent manner. A group of proteins involved in intracellular transport were identified to interact with BALF2 in a proteomic analysis. Among them, the small GTPase Rab1A functioning in bi-directional trafficking at the ER-Golgi interface is also a tegument component. In reactivated TW01-EBV cells, BALF2 colocalizes with Rab1A in the cytoplasmic AC. Expression of dominant-negative GFP-Rab1A(N124I) diminished the accumulation of BALF2 in the AC, coupling with attenuation of gp350/220 glycosylation. Virion release was significantly downregulated by expressing dominant-negative GFP-Rab1A(N124I). Overall, the subcellular distribution of BALF2 is regulated through its complex interaction with various proteins. Rab1 activity is required for proper gp350/220 glycosylation and the maturation of EBV. IMPORTANCE Upon EBV lytic reactivation, the virus-encoded DNA replication machinery functions in the nucleus, while the newly synthesized DNA is encapsidated and transported to the cytoplasm for final virus assembly. The single-stranded DNA binding protein BALF2 executing functions within the nucleus was also identified in the tegument layer of mature virions. Here, we studied the functional domain of BALF2 that contributes to the nuclear targeting and used a proteomic approach to identify novel BALF2-interacting cellular proteins that may contribute to virion morphogenesis. The GTPase Rab1, a master regulator of anterograde and retrograde endoplasmic reticulum (ER)-Golgi trafficking, colocalizes with BALF2 in the juxtanuclear concave region at the midstage of EBV reactivation. Rab1 activity is required for BALF2 targeting to the cytoplasmic assembly compartment (AC) and for gp350/220 targeting to cis-Golgi for proper glycosylation and virion release. Our study hints that EBV hijacks the bi-directional ER-Golgi trafficking machinery to complete virus assembly.
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Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Citoplasma/metabolismo , Proteínas de Ligação a DNA/metabolismo , Herpesvirus Humano 4/genética , Proteômica , Proteínas Virais/genética , VírionRESUMO
The main purpose of this study was to investigate the relationship between sarcopenia and injury events (falls, fractures, hospitalization, disability, and death). This study systemically searched the literature from Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library and analyzed the collected literature using the random effects model to demonstrate the relationship between sarcopenia and injury events. This study followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and collected a total of 38 prospective studies, and the results showed that, when compared to robust individuals, the risk of injury events for older individuals with sarcopenia was significantly higher for fractures (HR = 9.66, CI: 5.07-18.38), hospital admissions (HR = 11.80, CI: 4.86-28.65), and death (HR = 9.57, CI: 3.17-28.94). In consideration of the negative impact of sarcopenia on the subsequent health of older adults, professional nursing personnel should assess older adults for sarcopenia as early as possible and propose relevant care policies to further reduce negative health impacts.
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Double-hit (DH) genetics induces a reduction in the complete remission (CR) and, consequently, in poor overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Unfortunately, DH identification is time-consuming. Here, we retrospectively reviewed 92 newly diagnosed DLBCL patients, stratified them into the DH (n = 14) and non-DH groups (n = 78), and compared their clinical features and outcomes. The results revealed that the DH group had a higher percentage of bulky disease than the non-DH group (64.3% vs. 28.2%; p = 0.013). More patients in the DH group tested positive for double expresser (DE) (50.0% vs. 21.8%; p = 0.044). The three-year OS rates of patients with and without DH were 33.3% and 52.2%, respectively (p = 0.016). Importantly, advance stage and multiple comorbidities were correlated with a high mortality rate in multivariate analysis. Furthermore, by combining DE and the bulky disease, a specificity of 89.7% for DH prediction was achieved. In summary, DH genetics, not DE immunopositivity, could be a factor for an inferior OS in DLBCL. A combination of bulky disease and a positive DE immunophenotype could facilitate DH genetics prediction in newly diagnosed DLBCL patients.
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Background: Phacoemulsification is an effective and widely performed technique in cataract surgery, but the comparative anatomical outcomes, including endothelial cell loss (ECL), central corneal thickness (CCT), and central macular thickness (CMT), between high-flow and low-flow phacoemulsification cataract surgery remain unclear. Methods: This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Random-effects models were applied to measure pooled mean differences (MD) with 95% confidence intervals (CI) of anatomical outcomes between high-flow and low-flow phacoemulsification cataract surgery. We judged overall certainty of evidence (CoE) based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Results: We included six randomized controlled trials (RCTs) totaling 477 participants. The meta-analysis showed similar changes associated with these two surgery types in both ECL at postoperative days 2-14 (MD: -1.63%; 95% CI: -3.73 to 0.47%; CoE: very low), days 15-42 (MD: -0.65%; 95% CI -2.96 to 1.65%; CoE: very low) and day 43 to month 18 (MD: -0.35%; 95% CI: -1.48 to 0.78%; CoE: very low), and CCT at postoperative day 1 (MD: -16.37 µm; 95% CI: -56.91 to 24.17 µm; CoE: very low), days 2-14 (MD: -10.92 µm; 95% CI: -30.00 to 8.16 µm; CoE: very low) and days 15-42 (MD: -2.76 µm; 95% CI: -5.75 to 0.24 µm; CoE: low). By contrast, low-flow phacoemulsification showed less increase in CMT at postoperative days 15-42 (MD, -4.58 µm; 95% CI: -6.3 to -2.86 µm; CoE: low). Conclusions: We found similar anatomical outcomes, except in CMT, for both high-flow and low-flow phacoemulsification cataract surgery. Future head-to-head RCTs on visual outcomes should confirm our findings. Systematic review registration: PROSPERO, identifier: CRD42022297036.
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PURPOSE: Type 2 diabetes (T2D) is an important risk factor for glaucoma, and sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to protect the optic nerves. We therefore aimed to evaluate the association between SGLT2 inhibitors and incident glaucoma. METHODS: This retrospective cohort study analyzed the largest multi-institutional electronic medical records database in Taiwan, containing data of over a million individuals. We included T2D patients newly prescribed SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Our primary outcome was incident glaucoma diagnosis between initiation of SGLT2 inhibitors or GLP-1 RAs, and 31st March 2021. After applying inverse probability of treatment weighting (IPTW) to increase homogeneity between the two treatment groups, we estimated hazard ratios (HR) with 95% confidence intervals (CI) for the risk of glaucoma, based on Cox proportional hazards regression models. RESULTS: We included 9,927 and 1,065 T2D patients who had been newly prescribed SGLT2 inhibitors or GLP-1 RAs, respectively. Lower risk of incident glaucoma was observed in patients receiving SGLT2 inhibitors (7.9 events per 1,000 person-years), compared to those receiving GLP-1 RAs (10.0 events per 1,000 person-years), with an HR of 0.81 (95% CI: 0.69-0.95). Multiple sensitivity analyses and a negative control outcome analysis confirmed the robustness of our main findings. CONCLUSION: This study suggests that T2D patients newly prescribed SGLT2 inhibitors have a reduced risk of incident glaucoma, compared to those prescribed GLP-1 RAs, in clinical practice. Future prospective studies are suggested to confirm this association.
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Diabetes Mellitus Tipo 2 , Glaucoma , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Glaucoma/induzido quimicamente , Glaucoma/tratamento farmacológico , Glaucoma/epidemiologia , Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Simportadores/uso terapêutico , Taiwan/epidemiologiaRESUMO
Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to improve low-grade systemic and tissue inflammation; however, the association between SGLT2 inhibitor use and the incidence of dry eye disease (DED) has not been explored. Objective: To investigate the association between SGLT2 inhibitor use and dry eye disease in patients with type 2 diabetes (T2D). Design, Setting, and Participants: A retrospective cohort analysis of the largest multi-institutional electronic medical records database in Taiwan was conducted to identify patients with T2D newly receiving SGLT2 inhibitors or glucagonlike peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Data analysis was performed from March 1 to May 31, 2022. Propensity scores with inverse probability of treatment weighting were generated to enable homogeneous comparisons between the 2 groups. Exposures: Treatment with SGLT2 inhibitors or GLP-1 RAs. Main Outcomes and Measures: Incident dry eye disease, which was defined by clinical diagnoses, plus the related drug prescription. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for the risk of DED. Results: A total of 10â¯038 and 1077 T2D patients newly receiving SGLT2 inhibitors (mean [SD] age, 59.5 [12.1] years; 5689 [56.7%] men) or GLP-1 RAs (mean [SD] age, 58.5 [41.2] years; 587 [54.5%] men), respectively, were included in the analysis. The incidence of DED was lower in patients newly receiving SGLT2 inhibitors (9.0 events per 1000 person-years) compared with those receiving GLP-1 RAs (11.5 events per 1000 person-years), yielding a hazard ratio of 0.78 (95% CI, 0.68-0.89). Subgroup analyses indicated that the lowered DED risks associated with SGLT2 inhibitors in patients with T2D were similar across different age, sex, blood glucose level, and kidney function groups. Results from the sensitivity analyses (including the propensity score-matching approach, on-treatment analyses, and different follow-up periods of 1, 2, and 3 years) were similar to the main analyses. Conclusions and Relevance: The findings of this study suggest that patients with T2D newly receiving SGLT2 inhibitors may have a lower risk for DED compared with those receiving GLP-1 RAs. Prospective studies are needed to analyze these results.
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Diabetes Mellitus Tipo 2 , Síndromes do Olho Seco , Receptor do Peptídeo Semelhante ao Glucagon 1 , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/complicações , Síndromes do Olho Seco/epidemiologia , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Taiwan/epidemiologiaRESUMO
We utilized the Longitudinal Health Insurance Database which was stemmed from the Taiwan's National Health Insurance Research Database to conduct a retrospective cohort study investigating the risk of becoming dialysis dependent after receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents for retinal diseases. Patients newly receiving intravitreal ranibizumab or aflibercept from 2000 to 2017 for age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, retinal vein occlusions, or myopic choroid neovascularization were included as the study group, and patients with same retinal diseases but did not receive intravitreal anti-VEGFs served as controls extracted by age- and sex-matched (1:4) and further propensity score matching (PSM). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the risk of dialysis. A cohort of 2447 anti-VEGF users and 2447 controls by PSM were evaluated. Higher dialysis risks were observed among patients newly receiving anti-VEGF agents compared to controls (adjusted HR: 1.849; 95% CI: 1.378-2.482) in the PSM cohort. For subgroup analysis, patients newly receiving anti-VEGF treatment for diabetic macular edema had significant risk (adjusted HR: 1.834; 95% CI: 1.448-2.324) of becoming dialysis-dependent, while patients in other subgroups demonstrated similar risks as the controls. In conclusion, intravitreal anti-VEGF agents might increase the risk of becoming dialysis-dependent, especially in patients who are treated for diabetic macular edema.