Kaplan-Meier Survival Analysis Research Articles

Characteristics and prognosis of small bowel tumors: A retrospective study

BACKGROUND Small bowel tumors (SBTs) are a heterogeneous group of difficult-to-diagnose tumors that account for 2%-5% of all gastrointestinal tumors. Single-balloon enteroscopy greatly enhances the diagnosis and treatment of SBTs. However, few epidemiological studies have been conducted in Taiwan to determine the clinical profile of SBTs. AIM To investigate the clinical characteristics, managements and prognosis of SBTs in a medical center in Taiwan. METHODS The study enrolled 51 patients aged 58.9 ± 8.8 years (range, 22-93) diagnosed with SBTs from November 2009 to July 2021. We retrospectively recorded clinical characteristics, indications, endoscopic findings, pathological results, management, and outcomes for further analysis. RESULTS A male preponderance was observed (56.8%). The most common indications were suspected small intestinal tumors (52.9%) and obscure gastrointestinal bleeding (39.2%). The most common tumor location was the ileum (41.2%). The performance of imaging studies (P = 0.004) and the types of findings (P = 0.005) differed significantly between malignant and benign SBTs. The most frequent imaging finding was a small intestinal mass (43.1%). The top three malignant tumor types were gastrointestinal stromal tumors (GISTs), adenocarcinomas, and lymphomas. Moreover, the proportions of benign and malignant tumors were 27.5% and 72.5%, respectively. The survival rates of patients with malignant tumors in the GIST and non-GIST groups differed significantly (P = 0.015). Kaplan–Meier survival analysis showed a significant difference in survival between patients in the malignant and benign groups (P = 0.04). All patients with lymphoma underwent chemotherapy (n = 7/8, 87.5%), whereas most patients with GISTs underwent surgery (n = 13/14, 92.8%). CONCLUSION Patients with GISTs have a significantly higher survival rate than those with other malignant SBTs. Therefore, a large-scale nationwide study is warranted to evaluate the population-based epidemiology of SBTs.

Unraveling molecular signatures and prognostic biomarkers in glioblastoma: a comprehensive study on treatment resistance and personalized strategies

BackgroundGlioblastoma (GBM) is a highly aggressive primary brain tumor with limited treatment success and poor prognosis. Despite surgical resection and adjuvant therapies, GBM often recurs, and resistance to radiotherapy and temozolomide presents significant challenges. This study aimed to elucidate molecular signatures associated with treatment responses, identify potential biomarkers, and enhance personalized treatment strategies for GBM.MethodsWe conducted a comprehensive analysis using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The GEO dataset (GSE206225) was used to identify differentially expressed genes (DEGs) between radiation-sensitive/resistant and temozolomide-sensitive/resistant GBM samples. TCGA data were utilized for subsequent analyses, including Lasso-Cox regression, risk score model construction, Kaplan–Meier survival analysis, and gene set enrichment analysis (GSEA). Hub genes were identified through survival analysis, and a gene prognostic nomogram was developed. Additionally, validation of the three-gene risk signature through multiple external cohorts and validation of protein expression levels were performed.ResultsDEG analysis identified 111 genes associated with chemoradiotherapy resistance, providing insights into the complex landscape of GBM treatment response. The risk score model effectively stratified patients, showing significant differences in overall survival and progression-free survival. GSEA offered a deeper understanding of pathway activities, emphasizing the intricate molecular mechanisms involved. NNAT, IGFBP6, and CYGB were identified as hub genes, and a gene prognostic nomogram demonstrated predictive accuracy.ConclusionThis study sheds light on the molecular intricacies governing GBM treatment response. The identified hub genes and the gene prognostic nomogram offer valuable tools for predicting patient outcomes and guiding personalized treatment strategies. These findings contribute to advancing our understanding of GBM biology and may pave the way for improved clinical management.

Obesity Impacts the Likelihood of Symptom Resolution in Patients with Esophagogastric Junction Outflow Obstruction.

Esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder characterised by an elevated integrated relaxation pressure (IRP) with preserved peristalsis. Most functional EGJOO symptoms are self-limiting. This study aimed to evaluate the risk factors associated with non-resolution of symptoms for functional EGJOO. A retrospective single institution cohort study was performed on patients diagnosed with functional EGJOO on high-resolution manometry (HRM). Clinical, demographic, endoscopic and imaging parameters were recorded. Univariate and multivariate analyses were performed to identify factors associated with reduced likelihood of symptom resolution. Time to symptom resolution was then plotted on a Kaplan-Meier survival analysis. Over a 5-year period, 53 patients (41.5% male, 58.5% female) were diagnosed with functional EGJOO. The median age, body mass index and IRP at 4s were 47.0years (interquartile range (IQR): 36.0-58.0), 23.3kg/m2 (IQR: 20.9-26.5) and 39.9mmHg (IQR: 28.6-52.3) respectively. Dysphagia and atypical chest pain accounted for 36.5% and 21.2% of symptoms respectively. On the univariate analysis, obesity (p = 0.002), heartburn (p = 0.098) and lack of epigastric pain (p = 0.090) were potentially correlated with failure of symptom resolution. In the multivariate analysis, only obesity (OR 0.11, 95% CI: 0.02-0.77; p = 0.026) was significantly associated with reduced likelihood of symptom resolution for EGJOO. On the survival analysis, 87.2% of non-obese patients, in contrast 37.5% of obese patients reported symptom resolution at up to 41-month follow-up period (p = 0.039). Patients with obesity are at an increased likelihood of having persistent symptoms. This association appeared to persist for patients with both manometric and clinically relevant EGJOO.

Mitral valve transcatheter edge-to-edge repair in the elderly-A safe and effective therapy.

Prevalence of mitral regurgitation (MR) and comorbidity burden rise with age. Mitral valve transcatheter edge-to-edge repair (M-TEER) is increasingly performed in elderly patients, but only limited data are available for this specific subgroup. In this study, outcomes of octogenarians and nonagenarians undergoing M-TEER were analysed using a large real-world dataset. This retrospective study included consecutive patients undergoing M-TEER at the Ulm University Heart Center between January 2010 and December 2021. The cohort was divided into an elderly group and a younger group based on the cohorts' median age. Group differences regarding 1 and 3year mortality and heart failure hospitalization rates were assessed using Kaplan-Meier survival analysis and Cox proportional hazard models. A total of 1118 patients [median age 79 (inter-quartile range 74-83) years; 42% female] were included and divided into 513 elderly (≥80years) and 605 younger (<80years) patients. Primary MR was more frequent in the elderly group (56% vs. 27%, P<0.001). Pre-procedural and post-procedural MR grades were comparable between groups (pre-procedural MR grade 4: 69% in the elderly group vs. 71% in the younger group, P=0.67; post-procedural MR grade 1: 60% in the elderly group vs. 58% in the younger group, P=0.77) as well as in-hospital mortality rates (0.2% vs. 0.3%, P=0.66). Three-year heart failure hospitalization rates did not differ significantly between both groups (30.7% in the older age cohort vs. 36.0% in the younger cohort, P=0.191). While 1year all-cause mortality rates were comparable (18% vs. 16.4%, P=0.577), 3year all-cause mortality was significantly higher in the elderly [43.1% vs. 33.0%; hazard ratio (HR) 1.29 (95% confidence interval 1.02-1.65), P=0.035]. Pre-procedural N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥3402pg/mL [HR 2.29 (95% CI 1.34-3.90), P=0.002], pre-interventional MR grade [HR 1.79 (95% CI 1.01-3.17), P=0.045] and European System for Cardiac Operative Risk Evaluation (EuroSCORE) II [HR 1.06 (95% CI 1.03-1.08), P<0.001] were identified as independent predictors of 3year mortality in the elderly. M-TEER displays a safe and effective treatment option for elderly patients with symptomatic MR, offering symptom relief and comparable 1year outcomes to younger patients. Elderly patients with elevated EuroSCORE II and advanced heart failure might benefit from additional care to further reduce 3year mortality.

Robotic salvage radical hysterectomy for locally recurrent cervical cancer: A comparison with open surgery in a single-surgeon series.

To compare the surgical and oncologic outcomes between patients with locally recurrent cervical cancer undergoing robotic-assisted salvage radical hysterectomy (RH) and those undergoing conventional open salvage RH, performed by a single surgeon. This retrospective comparative observational study utilized data obtained from consecutive patients with locally recurrent cervical cancer, developed after definitive radiotherapy. These patients either underwent robot-assisted RH (robotic group) or conventional open RH (open group). Clinicopathological characteristics, surgical outcomes, and oncological outcomes were compared between the two groups. The operative time was slightly longer in the robotic group; however, this difference was not statistically significant. Estimated blood loss was significantly lower in the robotic group (median; 0 mL [robotic group] vs. 700 mL [open group]: p < 0.01). The incidence of intraoperative and early and late complications did not statistically differ between the two groups. The mean follow-up was 29.0 and 17.1 months in the open and robotic groups, respectively. Disease recurrence rates were similar between the two groups (40% [robotic group] vs. 44.4% [open group]). Kaplan-Meier survival analysis for progression-free survival and overall survival did not show statistically significant differences between the two groups. Robot-assisted salvage RH in women with locally recurrent cervical cancer showed perioperative and oncological outcomes comparable to those of the open procedure. Although our results suggest that the robot-assisted approach is as good as or better than the open approach, further investigation is required to establish a more robust conclusion.

Post-prostatectomy Magnetic Resonance-guided Radiotherapy on a 1.5 Tesla Magnetic Resonance Integrated Linear Accelerator: Feasibility, Toxicity, and Preliminary Clinical Outcomes.

This study aimed to prospectively investigate magnetic resonance (MR)-guided radiotherapy (MRgRT) for post-prostatectomy prostate cancer and report preliminary clinical outcomes. All included patients underwent salvage or adjuvant adaptive MRgRT on a 1.5T MR integrated linear accelerator (MR-LINAC). Gastrointestinal and genitourinary toxicities were assessed. The primary endpoint was the progression-free survival (PFS) rate estimated by Kaplan-Meier (KM) survival analysis. A progression event was defined as the first occurrence of biochemical failure, radiological progression, or death. Secondary endpoints were biochemical failure-free survival (bFFS) rate, radiological PFS (rPFS) rate, and ≥G2 adverse events. Thirty post-prostatectomy patients were enrolled and followed (median follow-up: 32.0 months; 3.0-48.1 months). Three patients had biochemical failure during follow-up. One patient developed pelvic node metastases. All patients were alive. The estimated PFS rates were 96.4% (95% confidence interval [95%CI]: 89.8%-100.0%) at 2 years and 78.8% (95%CI: 61.3%-100%) at 3 years. The estimated bFFS rates were 96.4% (95%CI: 89.8%-100%) /86.6%(95%CI: 73.4%-100%) at 2/3 years, respectively. The corresponding rPFS rates were 100% at 2 years and 92.3% (95%CI: 78.9%-100%) at 3 years, respectively. There was only one acute G2 GI adverse event (1/30, 3.33%) of abdominal pain occurred. Two late G2 events (one rectal bleeding and one urinary frequency) were scored (2/30, 6.67%). No ≥G3 events were observed. Our findings suggest the feasibility, excellent patient tolerance, and encouraging efficacy of post-prostatectomy MRgRT, extending our knowledge of the clinical outcomes of MRgRT and serving as a benchmark for future investigation.

Influence of Household Roof Types on the Development of Plasmodium vivax in Anopheles stephensi Mosquitoes.

Urbanization and microclimate variation in cities can influence mosquito behavior and parasite development, thus affecting malaria transmission. This study investigates how the impact of microclimate variations due to household roof types can aid in the survival of Anopheles stephensi and the development of Plasmodium vivax in an urban slum setting. Understanding these vital environmental interactions is essential for devising effective control strategies to achieve malaria elimination. Anopheles stephensi (F1) mosquitoes were membrane-fed with blood collected from P. vivax-infected patients before (day 0) and during (day 1) antimalarial treatment. The parasite development and mosquito survival were monitored in simulated microclimatic conditions of a variety of household roof types (thatched, asbestos, tiled) against standard laboratory conditions. Mosquito dissections were undertaken to detect oocysts and sporozoites in An. stephensi mosquitoes (oocyst: day 3-5, sporozoites: day 7-11). The maximum number of oocysts were detected in infected mosquitoes in thatched-roof conditions, whereas the largest oocyst was in the asbestos roof type. Circumsporozoite-ELISA results indicated the presence of sporozoites in infected mosquitoes for up to 29 days under standard conditions, 18 days in thatched-roof and asbestos roof conditions, and 14 days in tiled conditions. The univariate binary logistic regression model indicated a significant influence of microclimatic conditions of thatched roofs on parasite development. The Kaplan-Meier survival analysis revealed that the median survival of P. vivax-infected An. stephensi in thatched-roof conditions was 14 days, followed by asbestos (11 days) and tiled (10 days) roof conditions. In conclusion, thatched-roof houses were favorable for the development and survival of P. vivax-infected An. stephensi.

Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface

BackgroundTumor Budding (TB) and Immunoscore are independent prognostic markers in colon cancer (CC). Given their respective representation of tumor aggressiveness and immune response, we examined their combination in association with patient disease-free survival (DFS) in pTNM stage I-III CC.MethodsIn a series of pTNM stage I-III CCs (n = 654), the Immunoscore was computed and TB detected automatically using a deep learning network. Two-tiered systems for both biomarkers were used with cut-offs of 25% and ten buds for Immunoscore and TB according to clinical guidelines, respectively. Associations of Immunoscore with TB with 5-year DFS were examined using Kaplan–Meier survival analysis in addition to multivariable modeling and relative contribution analysis using Cox regression.ResultsImmunoscore and TB independently are prognostic with hazard ratio (HR) = 2.0, 95% confidence interval (CI) 1.4–2.8 and HR 2.5, with 95% CI 1.4–4.5, respectively; P value < 0.0001. By combining Immunoscore with TB, patients with Immunoscore Low, TB High tumors had a significantly poorer DFS (HR 5.6, 95% CI 2.6–12.0; P value < 0.0001) than those with Immunoscore High, TB Low tumors. The combined Immunoscore with TB score was independently prognostic (P value = 0.009) in comparison to N-stage, T-stage, and MSI. Immunoscore with TB had the highest relative contribution (35%) to DFS in pTNM stage I-II CCs.ConclusionsThe association of Immunoscore and TB with patient survival suggests that both biomarkers are complementary and should be interpreted in combination to identify high-risk Stage I-II patients who should be considered for adjuvant therapy or further diagnostic testing.

Vitamin D supplementation may be beneficial in improving the prognosis of patients with sepsis-associated acute kidney injury in the intensive care unit: a retrospective study

BackgroundVitamin D, an essential fat-soluble micronutrient, exerts diverse physiological effects including the regulation of calcium ion homeostasis, modulation of immune response, and enhancement of resistance against infectious pathogens. Empirical investigations have elucidated an association between inadequate levels of vitamin D and adverse clinical outcomes in critically ill cohorts, with a noteworthy prevalence of vitamin D deficiency observed among patients afflicted with acute kidney injury (AKI). In the context of this retrospective inquiry, our aim was to assess the potential correlation between vitamin D supplementation administered during admission to the intensive care unit (ICU) and the improvement of outcomes specifically in cases of severe AKI.MethodsThis study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV), a repository of ICU patient records from Beth Israel Deaconess Medical Center (BIDMC) in the United States. We focused on patients diagnosed with epsis-associated acute kidney injury (SA-AKI), dividing them into those who received vitamin D supplementation during their ICU admission and those who did not. Our primary analysis evaluated in-hospital mortality using various statistical methods, such as Kaplan–Meier survival curves, Cox proportional hazards regression models, and subgroup analyses. To enhance the robustness of our findings, we used propensity score matching (PSM) to reduce potential biases. Secondary outcomes included 28-day, 90-day mortality rates and norepinephrine-free days at 28 days.ResultsIn this investigation, a cohort of 11,896 individuals diagnosed with SA-AKI was studied. Among them, 2,724 patients received vitamin D supplementation (the vitamin D group) while 9,172 did not (the no-vitamin D group). Kaplan–Meier survival analysis indicated a significant difference in survival probabilities between the two cohorts. Upon adjusting for potential confounders using Cox regression modeling, a notably decreased risk of hospitalization and ICU mortality was observed in the vitamin D group compared to the no-vitamin D group, with an adjusted risk ratio for in-hospital mortality of 0.56 (95% CI: 0.5–0.63). These findings were consistent following PSM and subsequent adjustments for propensity score, pairwise algorithm (PA), and overlapping weights (OW) analyses, yielding hazard ratios ranging from 0.53 to 0.59, all with p-values &amp;lt;0.001. Notably, E-value analyses underscored the robustness of these results against potential unmeasured confounders.ConclusionThis study suggests that vitamin D supplementation may be associated with a reduced in-hospital mortality rate among SA-AKI patients in the ICU. Furthermore, the 28-day, 90-day mortality rates and norepinephrine days were significantly reduced in the group receiving vitamin D supplementation.

Increased risk of open angle glaucoma in patients with moyamoya disease from a nationwide population-based cohort in Korea

This nationwide population-based retrospective cohort study aims to investigate the association between Moyamoya disease (MMD) and open-angle glaucoma (OAG). In this study using the Korean National Health Insurance Service database, a total of 36,432 patients having diagnostic code with MMD between 2002 and 2022, and their age-, sex-matched non-MMD controls (n = 346,769) were included. We used a Cox proportional hazard model to determine the association between MMD and subsequent OAG after excluding cases with preexisting diagnosis of MMD for the initial 2-year. Kaplan-Meier survival analyses with log-rank test were performed to compare the incidence probability of OAG based on the MMD diagnosis. Cox regression analysis showed that the diagnosis of MMD was associated with increased risk of subsequent diagnosis of OAG (adjusted HR, 1.26; 95% CI, 1.14–1.38; P < 0.001). The cumulative incidence probability of OAG was 3.7% in MMD group and 2.9% in control group at the end of the study period, and was significantly higher among MMD patients than controls consistently during the study period (P < 0.001).In conclusion, the nationwide longitudinal data of Korean population revealed a significant association between MMD and OAG. Presence of MMD may increase the risk of developing OAG.

Organ-confined pT2 ISUP4/5 vs. nonorgan confined pT3/4 ISUP2 vs. ISUP3 prostate cancer: Differences in biochemical recurrence-free survival after radical prostatectomy

BackgroundTo test for differences in organ-confined pathological tumor stage (pT) and intermediate International Society of Urological Pathologists (ISUP) grade vs. nonorgan confined pT stage and high ISUP grade and biochemical recurrence (BCR) after radical prostatectomy (RP). MethodsRelying on a tertiary-care database, prostate cancer patients undergoing RP between January 2014 and December 2021 were stratified according to their combination of pT stage and ISUP grade in RP specimens (pT2 ISUP4/5 vs. pT3/4 ISUP2 vs. pT3/4 ISUP3). As Active Surveillance is recommended in ISUP1, these patients were excluded. Moreover, patients with pT2 ISUP2/3 are known for their good prognosis and pT3/4 ISUP4/5 patients for their poor prognosis. Therefore, these patients were also excluded from analyses. Kaplan–Meier survival analyses and multivariable Cox regression models addressed BCR after RP. ResultsOf 215 RP patients, 29 (13%) exhibited pT2 ISUP4/5 vs. 122 (57%) pT3/4 ISUP2 vs. 64 (30%) pT3/4 ISUP3 pathology. In survival analyses, 3-year BCR-free survival rates were 95% in pT2 ISUP4/5 vs. 88% in pT3/4 ISUP2 vs. 65% in pT3/4 ISUP3 patients (P < 0.001). In multivariable Cox regression models addressing BCR, pT3/4 ISUP3 pathology was associated with higher BCR rate relative to pT2 ISUP4/5 pathology (hazard ratio 3.42, 95% confidence interval 1.07-10.94; P = 0.039), but not pT3/4 ISUP2 pathology (P = 0.6). ConclusionCompared to prostate cancer patients with pT2 ISUP4/5 pathology, the combination of pT3/4 ISUP3 pathology is associated with higher risk of BCR after RP. In consequence, patients with pT3/4 ISUP3 pathology should be considered for a closer postoperative follow-up.

SQLE promotes osteosarcoma progression via activating TGFβ/SMAD signaling pathway

BackgroundThe prognosis of advanced osteosarcoma (OS) has remained stagnant in last decades, requiring the identification of novel therapeutic targets. Recently, much attention was paid to the role of squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol metabolism, in the field of oncology, while the specific role of SQLE in OS has not been sufficiently elucidated. The present study aims to investigate the role of SQLE in the progression of OS and explore the potential mechanisms. MethodsThe expression levels of SQLE in OS tissues and adjacent normal tissues were compared using bioinformatic methods and experiments. Kaplan-Meier survival analysis and univariate and multivariate Cox analysis were performed to detect the association of SQLE expression and patient’ prognosis. Stably cell lines with SQLE knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and Transwell invasion assays were carried out to explore the effect of SQLE knockdown or overexpression on the proliferation, migration, and invasion of OS cells. Gene set enrichment analysis was conducted to reveal signaling pathways associated with SQLE expression. The effect of SQLE on TGFβ/SMAD signaling pathway were explored by Western blot assay. ResultsHere, we found a notable rise of SQLE expression in OS tissues and cell lines. Survival analysis showed that individuals with high SQLE expression had a lower median overall survival time compared to those with low SQLE expression. Univariate and multivariate Cox regression analyses showed that SQLE might have the potency to serve as an independently prognostic biomarker in OS. Loss- and gain-of-function experiments indicated that silence of SQLE suppressed OS cell proliferation, migration, and invasion, while overexpression of SQLE exerted the opposite effects. Mechanistically, TGF-β signaling pathway was identified as the downstream pathway of SQLE through bioinformatic methods, and the results of Western blot assay showed that SQLE positively regulated the activity of TGFβ1/SMAD2/3 signaling in OS. Resue experiments demonstrated that SB431542, a small molecule that inhibits TGFβ/SMAD signaling, could partly reverse the promoting effects of SQLE on OS cell proliferation, migration, and invasion. ConclusionOur results provided preliminary evidences that SQLE was a tumor-promoting factor and prognosis predictor in OS. SQLE promoted OS cell proliferation, migration, and invasion via activating TGFβ/SMAD signaling and targeting SQLE might be a potential strategy for the treatment of OS.

Older Children Undergoing Inguinal Hernia Repair Have Higher Recurrence Rates Than Younger Children and Adults: A Nationwide Cohort Study

BackgroundHigh ligation is the standard practice for inguinal hernia repair in children while adults undergo a floor repair. There is limited data to guide recommendations on the age at which floor repair should be considered. This is a hypothesis-generating study to understand the correlation of age and other factors with inguinal hernia recurrence in children. Materials and MethodsChildren aged 6-17 years who underwent inguinal hernia repair by a pediatric surgeon between 2010-2022 were identified in the PearlDiver Mariner database, as were adults aged 18-25 years treated by an adult surgeon. Kaplan-Meier survival analysis and Cox proportional hazards modeling was used to determine the risk of hernia recurrence by age, sex, and obesity status. ResultsA total of 15,114 children and 20,863 adults were included. Children aged 16-17 years had a significantly increased five-year risk of hernia recurrence compared to children aged 6-10 years (2.5% vs 0.8%, adjusted hazard ratio [AHR]: 3.00, 95% confidence interval [CI]: 1.98-4.56) as well as compared to the adult group (2.5% vs 1.2%, AHR 1.90, 95% CI: 1.31-2.74). Obese males aged 14-17 years had the highest five-year rate of hernia recurrence of any group at 4.7%. ConclusionsChildren 16-17 years of age who underwent inguinal hernia repair with pediatric surgeons have an increased risk of hernia recurrence compared to younger children as well as compared to adults treated by general surgeons. We hypothesize that high ligations, commonly performed by pediatric surgeons, may be inappropriate in some groups of older children. Type of StudyCohort Level of EvidenceLevel III

A multicenter retrospective study on comparing the efficacy and safety of the therapy of intermittent cyclophosphamide and corticosteroids versus rituximab for primary membranous nephropathy.

Few clinical studies compare the long-term remission, relapse, and safety of rituximab (RTX) or a combination of intermittent intravenous infusion of cyclophosphamide (CTX) and oral corticosteroid for primary membranous nephropathy (PMN) patients. We collected multicenter retrospective data on PMN patients with nephrotic syndrome who received RTX or intermittent intravenous CTX with oral corticosteroids between 1 January 2019 and 31 January 2024. Patients were followed up until two years after receiving immunotherapy. The primary outcomes were a composite of complete or partial remission rates at 6, 12, and 24months. The secondary outcomes were the relapse and safety evaluation. Forty patients treated with RTX and 27 with the CTX regime were available for analysis. No significant difference in the remission rate at 6, 12, or 24months was observed between the two groups (p>.05). Kaplan-Meier's survival analysis showed that the relapse-free cumulative survival rate of the RTX group was superior to that of the CTX group (p=.023). Compared with baseline, both the media of urine protein and serum albumin levels in the two groups showed a significant improvement at 6months and maintained through to the second year. No significant difference in the occurrence of total side effects between the two groups (p=.160). There was no difference in remission rates and safety between RTX versus intermittent intravenous CTX combined with oral corticosteroid treatment for patients with PMN within 2years. RTX appeared to have benefits in terms of prolonging relapse-free survival.

Vitamin D supplementation can improve the 28-day mortality rate in patients with sepsis-associated acute kidney injury.

Vitamin D levels are generally lower in septic patients and are associated with poor prognosis. Observational studies suggest improved renal recovery in acute kidney injury (AKI) patients with increased vitamin D levels. Still, large RCTs did not show significant clinical benefits, possibly due to the limited number of sepsis or AKI patients included. This study aimed to examine the impact of vitamin D supplementation on 28-day all-cause mortality in patients with sepsis-associated acute kidney injury (S-AKI). A retrospective cohort study was conducted using data from the MIMIC-IV (v2.0) database, which included 18,713 ICU patients with S-AKI. Propensity score matching (PSM) was used to adjust for confounding factors, and multivariate Cox regression was employed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Patient survival and clinical characteristics will be assessed utilizing Kaplan-Meier curves, with comparisons conducted using the log-rank test. Kaplan-Meier survival analysis revealed significant differences in survival between the groups. Multivariate Cox regression indicated a reduced risk of 28-day mortality associated with vitamin D supplementation (HR: 0.73, 95% CI: 0.67-0.80, p < 0.001). The results after PSM were consistent with those of the original cohort. Similar results were observed for in-hospital mortality and 90-day mortality. The Restricted Cubic Spline curve (RCS) indicated an increasing trend in the therapeutic effect of vitamin D with increasing SOFA score. Vitamin D supplementation is associated with decreased all-cause mortality in patients with S-AKI, and those with more severe conditions may benefit even more.

Evaluating KLHDC8A as a biomarker for glioma: impact on survival and proliferation through the Wnt/β-catenin pathway

Glioma is one of the most common malignant tumors and shows a high metastasis rate and poor prognosis. KLHDC8A has been implicated in several cancers, but its role in glioma and its potential as a biomarker remain unclear. We conducted a pan-cancer analysis of KLHDC8A using multiple databases and assessed its expression levels, survival associations, and diagnostic utility. Kaplan–Meier survival analysis and Receiver Operating Characteristic (ROC) curves were utilized to evaluate KLHDC8A’s prognostic and diagnostic potential. Additionally, we investigated KLHDC8A's role in glioma cell proliferation and its involvement in the Wnt/β-catenin signaling pathway. Our pan-cancer analysis revealed significant dysregulation of KLHDC8A across various tumors. Elevated KLHDC8A expression was associated with poor overall survival (OS) in cancers including ACC, KIRP, LGG, and STAD. Disease-specific survival (DSS) analysis indicated worse outcomes in ACC, KIRP, and LGG with high KLHDC8A levels. ROC curve analysis demonstrated KLHDC8A's strong diagnostic potential for glioblastoma multiforme (GBM) and lower-grade gliomas (LGG), with AUC values of 0.920 and 0.748, respectively. In glioma patients, high KLHDC8A expression correlated with shorter OS and DSS in LGG, while no significant correlation was observed in GBM. Multivariate Cox regression confirmed KLHDC8A as an independent prognostic factor for OS and DSS in LGG. Knockdown experiments in glioma cell lines U251 and U87 showed that KLHDC8A silencing led to reduced cell proliferation and colony formation, which was associated with downregulation of key proteins in the Wnt/β-catenin pathway. Overall, KLHDC8A is a promising biomarker for the diagnosis and prognosis of LGG, and its high expression is linked to poor survival outcomes. The gene's involvement in the Wnt/β-catenin signaling pathway underscores its role in glioma progression, highlighting KLHDC8A’s potential as a therapeutic target and diagnostic marker, particularly for LGG.

Assessment of predictive factors in endoscopic internal urethrotomy for bulbar urethral strictures

IntroductionDirect vision internal urethrotomy (DVIU) is usually the first treatment offered to patients with bulbar urethral strictures (US). Advances in devices and surgical techniques have contributed to reducing associated complications. Despite the favorable success rate of DVIU, various factors predicting better outcomes have been studied, including patient characteristics, stricture features, and procedural aspects. The main aim of our study is to assess predictive factors for success. MethodsWe conducted a retrospective descriptive study of patients who underwent endoscopic internal urethrotomy at our hospital over a 30 year period. Out of 788 DVIU performed, we selected 491 (62.3%) conducted for bulbar US with a minimum follow-up of 12 months. We examined clinical outcomes obtained, and assessed the relationship between different patient characteristics, stricture-related factors and procedural aspects related with clinical success -considered as the avoidance of further interventions for stricture recurrence-. Descriptive statistics were calculated and parametrical and non-parametrical comparative tests were applied. Kaplan-Meier survival analysis was used for evaluating time until recurrence. ResultsMean stricture length was 1.2 cm (SD 0.5), with only 12 patients presenting with more than 1 US in the bulbar area during DVIU. After a median follow-up of 170 months, 67.4% of patients did not experience clinical recurrence. Severe postoperative complications appear in 0.4% of cases, and need for overnight admission was 4.5%. A positive association was observed between clinical recurrence and a history of prior pelvic radiotherapy (OR 2.8, 95%IC 1.3-22.2), active smoking (OR 2.1, 95%IC 1.6-2.4), infectious etiology of stricture (OR 2.3, 95%IC 1.6-8), history of previous urethroplasty (OR 2.5, 95%IC 1.7-3.2), and higher postoperative urinary catheter sizes (OR 1.8 95%IC 1.1-2.9). Median time until recurrence after the first DVIU was 65 months, after the second was 60 months, after the third was 32 months, and after the fourth was 6 months. ConclusionsBulbar US could be safely managed with DVIU. The best clinical success is achieved in non-irradiated, non-smoker patients, without prior urethroplasties. The repetition of the procedure is significantly associated with a shorter time to clinical recurrence.

Retreatment predictors after percutaneous balloon gangliolysis for trigeminal neuralgia

Percutaneous balloon ganglyolysis (PBG) for trigeminal neuralgia (TN) is an inexpensive and minimally invasive treatment modality that is effective and safe. While there are reports of its efficacy, there is still a lack of evidence of which patients are at a higher risk of treatment failures and needing retreatment. We performed a retrospective study at a major academic institution from 2012 to 2023, including TN patients who underwent PBG procedures to evaluate predictors of retreatment. Patients without imaging available from the PBG were excluded. Fifty-two patients who underwent 83 procedures in total were included in the analysis. All patients had typical TN and were primarily female (59.6%), with a median age of 61.5 years. Immediately after PBG, 42.3% had pain resolution, and 57.7% had improved but persistent pain. 30.8% underwent retreatment with PBG in a median of 32 months. From multiple factors assessed, TN disease duration ≤ 6 months and trigeminal nerve enhancement on pre-operative MRI were identified as significant retreatment predictors on univariate analysis. However, after performing logistic regression, only TN disease duration ≤ 6 months remained significant OR 3.99 (95% CI 1.59–10.0; p = 0.003). This was further confirmed in a Kaplan-Meier survival analysis, which showed that patients with TN duration ≤ 6 months require retreatment earlier (22 vs. 41 months; p = 0.01). Retreatment after PBG occurs roughly in a third of patients, and TN disease duration of ≤ 6 months is an important predictor in this study. Further studies should be performed to confirm these findings, which may impact treatment considerations in the future.

Redefining low-threshold buprenorphine access in an integrated mobile clinic program: Factors associated with treatment retention

IntroductionThe Spot mobile clinic provides low-threshold buprenorphine integrated with clinical and social services in Baltimore City, MD. In 2021, The Spot modified practices to improve engagement including providing extended prescriptions, reducing frequency of toxicology testing, giving up to six months to stabilize on medication, offering maximum doses (up to 32 mg total) daily, and utilizing telemedicine. This study characterizes care retention by examining both the total time in care and the percentage of time with buprenorphine prescription coverage during these practice changes, and examines factors associated with retention. MethodsThis retrospective cohort study includes patients (n = 341) who received a buprenorphine prescription who initiated care on The Spot mobile clinic from September 2021 to October 2022, with follow-up through October 2023. We utilized the Cox proportional hazards model and Kaplan-Meier survival analyses to assess differences in care retention by the factors of patient demographics and clinical characteristics. Additionally, we performed sensitivity analyses using Poisson regression to examine differences between patients with 80 % or greater time with active prescription coverage versus <80 % of time with active prescription coverage. ResultsAfter practice setting changes, retention in care at 90 days was 60 %. Patients whose maximum daily buprenorphine dose was 28 to 32 mg were 80 % less likely to discontinue treatment over the study period than those prescribed ≤16 mg (adjusted hazard ratio of discontinuation: 0.2 [95 % CI: 0.1–0.3]). Engaging in wound care or hepatitis C treatment was associated with higher retention in care, and individuals experiencing homelessness remained engaged at rates comparable to stably housed patients. ConclusionPractice changes aimed to improve access to patient-centered, low-threshold buprenorphine treatment may increase retention in care. Notably, higher doses of buprenorphine and integrated treatment with wound care and hepatitis C treatment were associated with increased retention. Due to gaps in patient care, retention metrics should incorporate total time in care as well as percentage of time with an active buprenorphine prescription.

Mechanism of atorvastatin in treating hepatocellular carcinoma: a study based on network pharmacology, molecular docking, and bioinformatics analysis.

Hepatocellular carcinoma (HCC) is a tumor with high morbidity and mortality. Current research suggests that statins may aid in its prevention and treatment, while studies on the associated mechanisms remain limited. Therefore, we aim to reveal the mechanism of atorvastatin treatment for HCC by using network pharmacology and bioinformatics methods. The databases SwissTargetPrediction, PharmMapper, and DrugBank were utilized to obtain targets of atorvastatin, while GSE169289, GSE135631, and GSE207435 were used to identify differentially expressed genes (DEGs) for HCC. The overlap between the two groups was used to identify atorvastatin's target for treating HCC. Following protein-protein interaction (PPI) analysis, hub genes were identified using Cytoscape software and LASSO analysis. The hub genes were further validated using data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) databases. To evaluate the clinical significance of the hub genes, Kaplan-Meier (KM) survival analysis and Cox analysis were conducted. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to investigate potential mechanisms. Finally, molecular docking analysis was performed to validate the interaction between atorvastatin and the hub genes. A total of 1948 DEGs of HCC and 380 targets of atorvastatin were identified, respectively. After taking the intersection, 79 genes were identified as potential targets of atorvastatin for HCC treatment. After multiple screening methods, CYP2C9 was ultimately identified as the hub gene. Analysis of data from TCGA and HPA databases showed reduced expression of CYP2C9 in HCC tissues. KM and Cox analysis showed a favorable prognosis for HCC patients with high CYP2C9 expression. KEGG and GSEA indicated that metabolism of xenobiotics by cytochrome P450, and PPAR signaling pathway could be the potential mechanisms for atorvastatin in treating HCC. Molecular docking analysis revealed that atorvastatin binds to CYP2C9 with a binding energy of - 8.837, indicating highly stable binding. CYP2C9 is associated with the prognosis of HCC patients and could serve as a potential target for atorvastatin treatment in HCC.