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Background and objective: Metabolic syndrome (MetS) is a clinical condition associated with higher rates of overall and cardiovascular mortality. There is scarce evidence regarding the impact of MetS on surgical and functional outcomes for patients undergoing partial nephrectomy (PN) for clinically localized small renal masses (SRMs). Methods: We analyzed data from a prospectively maintained institutional database for 690 patients with cT1a renal cancer undergoing PN between 2000 and 2023 at a tertiary referral center. MetS was defined according to international guidelines. Cumulative incidence curves were used to estimate the 5-yr risk of stage IIIB–V chronic kidney disease (CKD) stage and other-cause mortality (OCM). Multivariable regression models were used to analyze the impact of MetS on the risk of complications, acute kidney injury (AKI), stage IIIB–V CKD, and OCM. Key findings and limitations: Overall, 10% of the PN cohort had MetS. The MetS group was older (median age 70 yr, interquartile range [IQR] 65–74 vs 61 yr, IQR 50–69; p

Introduction: Acute myeloid leukemia is a challenging disease, due to a poor prognosis in developing countries. Herein, we aim to describe the clinical characteristics and outcomes after chemotherapy and transplantation. Methods: A retrospective analytic observational study was performed with patients under 18 years of age with newly diagnosed acute myeloid leukemia treated at a referral center in Colombia. Two groups were compared: induction therapy (IT) and induction therapy plus consolidation (IT + C). The survival analysis was performed using the Kaplan–Meier method. Results: We analyzed 34 patients diagnosed with acute myeloid leukemia; 20 received hematopoietic stem cell transplantation. Most were French-American-British (FAB) classification types M1, M5 and M0. The transplantation was haploidentical in 65%, conditioning was myeloablative in 67% and graft-versus-host disease prophylaxis was performed with post-transplant cyclophosphamide in 70%. Overall, the 5-year survival was 52% and the overall 5-year survival in the transplanted group was 80%. There were 16 deaths; in the IT group, n = 12, and in the IT + C group, n = 4. In the former, the main cause of death was septic shock and in the latter, it was relapse. Conclusion: Transplantation is a safe option. Receiving treatment and supportive measures in hematopoietic stem cell transplantation units is necessary to avoid infections, especially during induction cycles.

Background and objective: Prostate-specific antigen (PSA) is of limited value as a surrogate marker for overall survival (OS) in prostate cancer (PC). Serum thymidine kinase 1 (sTK1) is an enzyme expressed by actively dividing cells. Our aim was to evaluate the value of sTK1 as prognostic biomarker in metastatic hormone-sensitive PC (mHSPC) and metastatic castration-resistant PC (mCRPC). Methods: sTK1 was examined in three cohorts: (1) 43 men with de novo mHSPC managed with androgen deprivation monotherapy; (2) 99 patients with mCRPC managed with androgen receptor signaling inhibitors (ARSIs); and (3) 98 patients with mCRPC treated with docetaxel. sTK1 levels were determined at treatment initiation. OS was evaluated using Cox regression analysis. Key findings and limitations: In the mHSPC cohort, sTK1 levels in the highest quartile were associated with OS (hazard ratio [HR] 7.77, 95% confidence interval [CI] 2.25–26.9) in comparison to the lowest quartile after multivariable adjustment for age, Gleason score, and PSA. Similarly, sTKI was associated with poor OS in the mCRPC group treated with ARSIs (upper quartile: HR 5.22, 95% CI 2.23–12.2) after multivariable adjustment for age, PSA, and Eastern Cooperative Oncology Group performance status. In the docetaxel-treated mCRPC group the association between OS and sTK1 was lower but still significant (multivariable-adjusted HR 2.28, 95% CI 1.13–4.60). Limitations include the nonrandomized inclusion of patients for different treatments, which could lead to selection bias. Conclusions and clinical implications: sTK1 predicted OS in mHSPC and mCRPC, demonstrating additional value over established clinical risk factors. sTK1 should be measured in randomized clinical trials of treatments for advanced PC to validate its predictive value. Patient summary: We found that for patients with metastatic prostate cancer, high levels of a protein called TK1 that is involved in cell division was linked to higher risk of death. Our findings need to be confirmed in other studies.

Objectives: The role of timing of coronary artery bypass grafting after acute myocardial infarction on early and late outcomes remains uncertain. Methods: We reviewed 1631 consecutive adult patients who underwent isolated coronary artery bypass grafting with information on timing of acute myocardial infarction. Early and late mortality were compared between patients receiving coronary artery bypass grafting within 24 hours after acute myocardial infarction, between 1 and 7 days after acute myocardial infarction, and more than 7 days after acute myocardial infarction. Sensitivity analyses were performed in subgroups of patients with ST-segment elevation myocardial infarction or non–ST-segment elevation myocardial infarction, and other high-risk groups. Results: A total of 124 patients (5.7%) underwent coronary artery bypass grafting within 24 hours, 972 patients (51.2%) received coronary artery bypass grafting between 1 and 7 days after acute myocardial infarction, and 535 patients (43.2%) underwent coronary artery bypass grafting more than 7 days after acute myocardial infarction. Overall operative mortality was 2.7% with comparable adjusted early mortality among 3 groups. Over a median follow-up of 13.5 years (interquartile range, 8.9-17.1), compared with patients receiving coronary artery bypass grafting between 1 and 7 days after acute myocardial infarction, those receiving coronary artery bypass grafting at 7 days had greater adjusted risk for late overall mortality (hazard ratio, 1.39, 95% CI, 1.16-1.67; P 7 days had a higher risk of late mortality [hazard ratio, 1.38, 95% CI, 1.14-1.67, P

Objectives: Reprogramming of energy metabolism is a well-established hallmark of cancer, with aerobic glycolysis classically considered a prominent feature. We investigate the heterogeneity in glucose metabolism pathways within resectable primary lung adenocarcinoma and its clinical significance. Methods: Using The Cancer Genome Atlas data, RNA expressions were extracted from 489 primary lung adenocarcinoma samples. Prognostic influence of glycolytic, aerobic, and mitochondrial markers (monocarboxylate transporter [MCT]4, MCT1, and translocase of outer mitochondrial membrane 20, respectively) was assessed using Kaplan-Meier analysis. Clustering of 35 genes involved in glucose metabolism was performed using the k-means method. The clusters were then analyzed for associations with demographic, clinical, and pathologic variables. Overall survival was assessed using the Kaplan-Meier estimator. Multivariate analysis was performed to assess the independent prognostic value of cluster membership. Results: Classical statistical approach showed that higher expression of MCT4 was associated with a significantly worse prognosis. Increased expression of translocase of outer mitochondrial membrane 20 was associated with a nonsignificant trend toward better prognosis, and increased expression of MCT1 was associated with a better outcome. Clustering identified 3 major metabolic phenotypes, dominantly hypometabolic, dominantly oxidative, and dominantly mixed oxidative/glycolytic with significantly different pathologic stage distribution and prognosis; mixed oxidative/glycolytic was associated with worse survival. Cluster membership was independently associated with survival. Conclusions: This study demonstrates the existence of distinct glucose metabolism clusters in resectable lung adenocarcinoma, providing valuable prognostic information. The findings highlight the potential relevance of considering metabolic profiles when designing strategies for reprogramming energy metabolism. Further studies are warranted to validate these findings in different cancer types and populations.

Resumen: Introducción y objetivos: El carcinoma hepatocelular (CHC) es una neoplasia maligna primaria de células epiteliales hepáticas que constituye la neoplasia primaria hepática más frecuente. La ampliación de criterios de trasplante y resecabilidad han hecho más complejas las decisiones terapéuticas. Nos proponemos describir las características clínicas y la supervivencia de los pacientes con CHC tratados mediante resección hepática (RH) o trasplante hepático ortotópico (THO) en nuestro hospital, e identificar la presencia de factores que permitan predecir el pronóstico y facilitar las decisiones terapéuticas. Material y métodos: Se identificaron retrospectivamente los pacientes con CHC intervenidos con intención curativa en el Hospital Universitario Marqués de Valdecilla entre 2007 y 2017. Se analizaron la supervivencia, la mortalidad, el intervalo libre de enfermedad, así como distintas variables relacionadas con el pronóstico. Resultados: Se registraron 96 pacientes con un seguimiento medio tras cirugía de 44 meses. La mortalidad global y la recidiva fueron superiores en el grupo de resección. La supervivencia media fue de 51.4 meses en el grupo de TOH y de 37.5 meses en el de RH, y el tiempo libre de enfermedad alcanzó los 49.4 ± 37.2 y 27.4 ± 28.7 meses, respectivamente (p: 0.002). La carga tumoral, valorada a través del «tumor burden score», presentó una relación significativa con el riesgo de recidiva y la mortalidad específica. Conclusiones: No parece existir un subgrupo de pacientes en los que la resección quirúrgica presente resultados de supervivencia superiores o equiparables al trasplante. La carga tumoral podría ser una herramienta útil para subclasificar y ayudar a guiar las decisiones terapéuticas. Abstract: Introduction and aims: Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation and resectability criteria has made therapeutic decisions more complex. Our aim was to describe the clinical and survival characteristics of patients with HCC treated through resection or liver transplantation at our hospital and identify the presence of factors that enable outcome prediction and facilitate therapeutic decision-making. Materials and methods: Patients with HCC that underwent surgery with curative intent at the Hospital Universitario Marqués de Valdecilla, within the time frame of 2007 and 2017, were retrospectively identified. Survival, mortality, disease-free interval, and different outcome-related variables were analyzed. Results: Ninety-six patients with a mean follow-up after surgery of 44 months were included. Overall mortality and recurrence were higher in the resection group. Mean survival was 51.4 months in the liver transplantation group and 37.5 months in the resection group, and the disease-free interval was 49.4 ± 37.2 and 27.4 ± 28.7 months, respectively (p = 0.002). The tumor burden score was statistically significant regarding risk for recurrence and specific mortality. Conclusions: There appears to be no patient subgroup in whom the results of surgical resection were superior or comparable to those of transplantation. Tumor burden determination could be a useful tool for patient subclassification and help guide therapeutic decision-making.

ABSTRACT: For beef semen usage on dairy cows, much of the research has focused on the performance of the crossbred calves, yet little focus has been given to the subsequent performance of the cow herself. This study aimed to evaluate the performance of dairy cows for milk yield, fertility, and survival traits after giving birth to beef × dairy crossbred calves and compare this with the performance after giving birth to purebred dairy calves. Further, we aimed to study if the effect of a difficult calving was the same regardless of whether the calf was purebred dairy or beef × dairy crossbred. Phenotypic records from 587,288 calving events from 1997 to 2020 were collected from the Swedish milk recording system from cows of the dairy breeds Swedish Red (SR) and Swedish Holstein. The sire beef breeds studied were Aberdeen Angus, Hereford (combined in category LHT), Charolais, Limousin, and Simmental (category HVY). Sixteen traits were defined and grouped in 3 categories: cumulative and 305-d milk, fat, and protein yield, daily milk yield, and 75-d milk yield as yield traits; calving to first insemination interval, calving to last insemination interval, first to last insemination interval, calving interval, and number of inseminations as fertility traits; and survival to 75 d or to next calving and lactation length as measures of survival. The data were analyzed for all traits for first and second parities separately using mixed linear models, with a focus on the estimates of cow breed by service sire breed combinations. All traits in parity 2 were adjusted for previous 305-d milk yield based on the expectation that low-yielding cows would more likely to be inseminated with beef semen. Overall, milk yield was lower after beef × dairy calvings compared with the purebred dairy calvings. The largest effects were found on cumulative yields and in second parity, with lower effects for yields early in lactation and yields in first parity. The largest decrease was 13 to 14 kg (0.12 phenotypic SD) for cumulative fat yield when breeding beef breed sires with purebred SR dams. For fertility traits, for most breed combinations, the effects were not large enough to be significant. Conversely, all beef × dairy crossbred combinations showed significantly lower results for survival to the next lactation, and mostly also for lactation length. There was some indication that dairy cows with beef × dairy calvings in parity 2 that were the result of maximum 2 inseminations in parity 1, had lower survival than corresponding calvings resulting from more than 2 inseminations. This could indicate that the former cows were marked for culling already when inseminated. There was generally an unfavorable effect of a difficult calving on all traits, however, there were almost no significant interactions between calving performance and dam by sire breed combination, and these interactions were never significant in first parity.

Background: Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment. Methods: From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed. Results: Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7–6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003). Conclusion: ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.

Background: Retinoblastoma is associated with mortality in resource-poor nations due to disparities and poor access to treatment. The aim was to determine the relationships between patient-related factors and clinical outcomes of retinoblastoma in a tertiary hospital in Nigeria. Material and methods: It was a retrospective study of all children diagnosed and treated for retinoblastoma from January 2017 through December 2022. Information obtained from their records included bio-socioeconomic data, symptoms, lag time from initial symptoms, staging, treatment, and survival outcome. Results: Fifty-three patients, aged 6–88 months on first hospital presentation were recruited. There were 29 (54.7%) females. Twenty (37.7%) patients died. The majority were the last child of their parents (62.3%) with a low socioeconomic class (86.8%) and lived in rural areas (50.9%). The median (interquartile) age at diagnosis [24 (18–36) months, p = 0.005] and lag time [13 (6–20) months, p = 0.274] were lower in those who survived than in those who died. The prevalence of bilateral disease (20.8%, p = 0.002), brain metastasis (22.6%, p

الملخص: أهداف البحث: تهدف هذه الدراسة إلى تحديد معدل فشل نزع الأنبوب في وحدة العناية المركزة للأطفال والتأكيد على المسببات وعوامل الخطر المرتبطة بها والنتيجة. طريقة البحث: أجرينا دراسة بأثر رجعي على 335 مريضا من الأطفال الذين تم إدخالهم إلى مستشفى جامعة الملك عبد العزيز في الفترة من 2018 إلى 2020، وتتراوح أعمارهم بين شهر واحد و14 عاما، ويحتاجون إلى تهوية ميكانيكية غزوية لمدة تزيد عن 24 ساعة. تم تحديد جاهزية نزع الأنبوب للمرضى من قبل طبيب العناية المركزة للأطفال المعالج بناء على الحالة السريرية ومعايير الاستعداد لنزع الأنبوب. النتائج: ومن بين مجموعة مكونة من 335 مريضا، واجه 42 فردا مشكلات أثناء عملية نزع الأنبوب، وبلغت ذروتها بمعدل فشل قدره 12.5%. كانت أمراض القلب والأوعية الدموية (42.9٪) هي حالة القبول الأولية الملحوظة إلى حد كبير لدى مرضى فشل نزع الأنبوب. كان المرضى الأصغر سنا مرتبطين بشكل كبير بحدوث فشل نزع الأنبوب مقارنة بالمرضى الذين تم نزع أنبوبهم بنجاح مع ارتفاع معدل الوفيات المتوقع ودرجة معيار خطر وفيات الأطفال 3. علاوة على ذلك، لوحظت فترات الإقامة الطويلة في وحدة العناية المركزة ومتطلبات أطول للتهوية الميكانيكية قبل نزع الأنبوب لدى مرضى فشل نزع الأنبوب المرتبطين بمعدل وفيات مرتفع. ومن المثير للاهتمام أن إعطاء الديكساميثازون قبل عملية نزع الأنبوب خفف بشكل كبير من خطر فشل نزع الأنبوب لدى المرضى. الاستنتاجات: توضح دراستنا ارتفاع معدل فشل نزع الأنبوب لدى المرضى الأصغر سنا الذين يحتمل أن يكونوا مرتبطين بإقامات أطول في وحدة العناية المركزة، ومتطلبات طويلة الأمد للتهوية الميكانيكية قبل نزع الأنبوب، وحالة التشخيص الأولية. وقد لوحظ أن الديكساميثازون فعال في التخفيف من حدوث فشل نزع الأنبوب. هناك حاجة إلى مزيد من البحث الذي يتضمن تصميم دراسة أكثر جوهرية قائمة على الأدلة لإثبات العوامل المذكورة كمنبئات لفشل نزع الأنبوب ووضع استراتيجيات للحد منه. Abstract: Objectives: This study was aimed at determining the extubation failure (EF) rate in a pediatric intensive care unit (PICU), and assessing the etiology, associated risk factors, and outcomes. Methods: We conducted a retrospective study on 335 pediatric patients admitted to King Abdulaziz University Hospital between 2018 and 2020, ranging in age from 1 month to 14 years, who required invasive mechanical ventilation (MV) for >24 h. Extubation readiness was determined by the attending pediatric intensive care physician, according to the patients’ clinical status and extubation readiness criteria. Results: In the cohort of 335 patients, 42 experienced issues during extubation (failure rate, 12.5%). Cardiovascular disease (42.9%) was the main primary admission condition in patients with EF. Younger age (median, interquartile range [IQR]: 4, 1.38–36 months) was strongly associated with EF compared with successful extubation (median, IQR: 12, 2–48; p = 0.036), and with a high predicted mortality rate (10.9%; p

Background: Liver transplantation is the treatment for many end-stage liver diseases and hepatocellular carcinoma but shortage of available organs poses significant challenge. Many centers have used grafts from donors with positive anti-HBc serology but concerns about potential hepatitis B virus reactivation and de novo hepatitis B infection have raised questions about the safety of this approach. This study aimed to evaluate the survival of liver transplant recipients from anti-HBc-positive-donors and assess the risk of hepatitis B reactivation and de novo hepatitis B. Patients and methods: A retrospective single-center cohort study was conducted from 2002 to 2018, comparing who received grafts from anti-HBc-positive-donors to those from anti-HBc-negative-donors. The primary outcome was survival and description cases of hepatitis B reactivation/de novo hepatitis B. Results: We analyzed 1,111 liver transplants, in which 993 (89 %) received grafts from anti-HBc-negative-donors and 118 (11 %) from anti-HBc-positive-donors. Median age of recipients from anti-HBc-positive donors was 56 years and from anti-HBc-negative donors was of 53 years (p = 0.001). Male sex was predominant in both groups. Factors associated with death in multivariate analysis were retransplantation, early allograft dysfunction, high MELD, recipient over 60 years and female donor. The utilization of grafts from anti-HBc-positive-donors did not increase mortality. The majority of HBV reactivation and de novo hepatitis B occurred in anti-HBc positive recipients. The risk of hepatitis B reactivation/de novo hepatitis B was low and manageable. Conclusion: The study supports safety of liver grafts from anti-HBc-positive donors when employing antiviral prophylaxis. These findings contribute to expand donor options and improve patient outcomes

Summary: Background: In isocitrate dehydrogenase (IDH)-mutant low-grade gliomas (LGGs), awake functional-based resection (i.e., resection based on intraoperative functional responses rather than anatomical margins) has emerged as an efficient method to reduce tumour volume (TV) while minimizing postoperative deficits. Here, our goal was to assess the long-term onco-functional outcomes after awake functional-based resection in IDH-mutant LGGs, in conjunction with clinico-radiological and molecular factors. Methods: We retrospectively studied a consecutive cohort (June 1997–January 2023) of 949 patients. Six hundred patients with IDH-mutant LGGs benefited from an awake functional-based resection with a median follow-up of 7.8 years (95% Confidence interval [CI]: 7.1–8.4 years). The main outcomes were the overall survival (OS), the OS with Karnofsky performance status ≥80% (OSKPS≥80%), cognition measures, and professional activities at 12 months post-surgery. Findings: 600 patients were included in the cohort (274 female [46.0%], median age: 36 years [Interquartile range, IQR: 30–44 years]). The rate of return to work was 93.7%. The impact of surgery on cognition was of limited magnitude. The median postsurgical TV of 2.5 mL (IQR: 0–8.0 mL). The median OS was over 20 years (median: NA, 95% CI: 17.0-NA years). The median OSKPS≥80% was 14.7 years (95% CI: 13.2–17.2 years). Factors associated with longer OS and OSKPS≥P80% were 1p19q codeletion (Hazard ratio [HR]OS: 0.27, 95% CI: 0.16–0.43, HRKPS≥80%:0.25, 95% CI: 0.17–0.36), supratotal resection (HROS: 0.08, 95% CI: 0.005–0.40, HRKPS≥80%:0.12, 95% CI: 0.03–0.34) and total resection (HROS: 0.31, 95% CI: 0.16–0.59, HRKPS≥80%:0.21, 95% CI: 0.12–0.36). Recursive partitioning analyses established three OS and OSKPS≥80% prognostic groups, highlighting the contributions of histomolecular status, extent of resection, postsurgical and presurgical TV. Further propensity-matching analyses confirmed the oncological benefits of supratotal resections. Interpretation: Awake functional-based resection surgery in newly diagnosed IDH-mutant grade 2 LGG, was an effective strategy associated with long survival (median OS over 20 years) and long-term preservation of autonomy. More complete tumor resections favored better onco-functional outcomes across all molecularly-defined subtypes. Short-term effects were of limited magnitude regarding postoperative cognitive and professional outcomes. Supratotal functional-based resections offered additional survival benefits. Funding: None.

Background: Donor organ shortage is a barrier to lung transplantation. Donation after circulatory death (DCD) may offer a solution, although it is underutilized. The objective of this study was to compare survival and other postoperative outcomes between DCD and donation after brain death (DBD). Methods: We performed a multicenter analysis of Multi-Institutional Extracorporeal Life Support (ECLS) Registry data from 11 lung transplant centers in the United States and Europe. Demographics and clinical parameters were compared using chi-square test and Fisher's exact test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching. Results: Of 1,585 patients included in the study, 135 (8.5%) received DCD lungs and 1,450 (91.5%) received DBD lungs. DCD recipients had higher rates of obstructive lung disease (p = 0.042), longer total ischemic time (p

Background: Complications occurring during the first postoperative year after lung transplantation increase the risk of long-term mortality. These events often lead to prolonged and repeated hospitalizations. We sought to assess the relationship between days outside the hospital or hospital-free days (HFD) during the first post-transplant year among 1-year survivors and subsequent retransplant-free survival. Methods: In a single-center study, we derived total inpatient days (initial transplant episode, readmission, and emergency room/observation) from the electronic medical record of lung transplant recipients who survived 1 year. The cohort was divided into HFD quartiles and Kaplan-Meier curves of subsequent transplant-free survival were compared with log-rank analysis. A Cox proportional hazards model was used to test the association of HFD with outcome and adjusted for selected variables. Results: Among 238 patients, 42 deaths and 2 retransplants occurred after a median of 3.6 years post-transplant. The median HFD was 341 (interquartile range: 324, 348). Estimated transplant-free survival at 3 and 5 years post-transplant in the lowest quartile of HFD (79% and 56%, respectively) was considerably worse compared with the first quartile (98% and 94%; p

Background: Bone metastasis is a significant concern in advanced solid tumors, contributing to diminished patient survival and quality of life due to skeletal-related events (SREs). Denosumab (DMAB), a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL), is used to prevent SREs in such cases. The RANK/RANKL axis, crucial in immunological processes, has garnered attention, especially with the expanding use of immune checkpoint inhibitors (ICI) in modern oncology. Objective: Our study aims to explore the potential synergistic antitumor effects of combining immunotherapy with denosumab, as suggested by anecdotal evidence, small cohort studies, and preclinical research. Methods: We conducted a retrospective analysis using the IMMUCARE database, encompassing patients receiving ICI treatment since 2014 and diagnosed with bone metastases. We examined overall survival (OS), progression-free survival (PFS) and switch of treatment line based on denosumab usage. Patients were stratified into groups: without denosumab, ICI followed by denosumab, and denosumab followed by ICI. Survival curves and multivariate Cox regression analyses were performed. Results: Among the 268 patients with bone metastases, 154 received treatment with ICI alone, while 114 received ICI in combination with denosumab at some point during their oncological history. No significant differences were observed in overall survival (OS) or progression-free survival (PFS) between patients receiving ICI monotherapy and those receiving ICI with denosumab (p = 0.29 and p = 0.79, respectively). However, upon analyzing patients who received denosumab following ICI initiation (17 patients), a notable difference emerged. The group receiving ICI followed by denosumab exhibited a significant advantage compared to those without denosumab (154 patients) or those receiving denosumab before ICI initiation (72 patients) (p = 0.022). Conclusion: This retrospective investigation supports the notion of potential benefits associated with sequential administration of ICI and denosumab, although statistical significance was not achieved. Future studies, including prospective trials or updated retrospective analyses, focusing on cancers treated with first-line immunotherapy, could provide further insights into this therapeutic approach.

Background & Aims: Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic livers remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods: A total of 354 cases of MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018 were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results: Of HCC cases, 35% occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Patients without cirrhosis were older, had a greater tumor burden, but also better liver function than patients with cirrhosis. Patients without cirrhosis showed better overall survival than those with cirrhosis (p = 0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Patients without cirrhosis underwent surgery more frequently than patients with cirrhosis (41% vs. 11%, p

Polyethylene terephthalate (PET) fibers are contaminated in wastewater from various primary sources, such as washing textile waters. PET fibers in the environment can be degraded into microfibers because of weathering processes such as sunlight, physical wear, and heat. Although recent studies reported adverse effects of PET microfibers on aquatic organisms, the lack of information on their toxicity and mode of action hampers the risk assessment of PET microfibers. Therefore, this study aimed to investigate the biological effects of PET microfibers and their underlying mechanisms in early-staged sheepshead minnows (Cyprinodon variegatus). PET microfibers (about 13 μm diameter × 106 μm length) were prepared by cutting PET threads and treated to sheepshead minnow larvae at 10 and 100 mg/L for 10 days. No acute toxicity was found in the minnow, but PET microfibers significantly produced reactive oxygen species and reduced behavioral responses of traveled distance and maximum velocity. The transcriptomic data suggested that Merkel cells (flow sensors) and corpuscles of Stannius (calcium regulator) are putative targets, which were derived from oxidative stress, sensory neuropathy, cognitive impairment, and movement disorders. These findings underscore that although PET microfibers are not directly lethal to sheepshead minnows, they could impact their survival by damaging swimming-related key genes. This study provides new insights into how PET microfibers are toxic to aquatic organisms and disrupt ecosystems beyond survival and pathological changes.

Objectives: Persistent and significant swallowing impairment can occur in individuals with dementia. Determining prognosis and establishing realistic goals of care in this population is complex and comfort feeding may be recommended. This study aimed to establish evidence relating to patient outcomes following recommendation of comfort feeding to aid informed decision making. Design: A multi-centre, retrospective audit was conducted for a two-year period to establish the survival and readmission rates for hospitalised people with dementia, following recommendation of a comfort feeding plan. Setting: The study was conducted at three acute care hospitals in Adelaide, South Australia. Participants: A total of 163 participants were included, 90 male and 73 female, with a median age of 88 years. Measurements: Mortality within 30 and 90 days of admission and readmission rates within 30 days of discharge were calculated. Results: Forty-two percent of participants died during the admission during which a comfort feeding plan was recommended. Overall median survival time and one month survival was 13 days and 25%, respectively. Readmission rates were low (7.4% of those discharged). Comfort feeding recommendations aligned with dysphagia severity and those for whom Nil By Mouth (NBM) or ice chips only were recommended were at highest risk of dying in hospital, those recommended thickened fluids +/− ice chips were most likely to be alive 30 days after their original admission date. Conclusion: Dementia and comfort feeding were associated with high mortality rates, high rates of discharge to a supportive care facility and low readmission rates. Dysphagia severity associated with the consistency of fluids recommended.

Sarcopenia, characterized by the loss of skeletal muscle mass and function, is a significant complication in patients with cirrhosis. This condition not only exacerbates the overall morbidity and mortality associated with liver disease but also complicates patient management, increasing the risk of hospitalization, infections, and hepatic encephalopathy. Despite its clinical significance, sarcopenia in cirrhotic patients remains underdiagnosed and undertreated. This review aims to summarize current knowledge on the pathophysiology of sarcopenia in cirrhosis, including mechanisms such as altered metabolism, hormonal imbalances, and inflammation. Additionally, we explore diagnostic challenges and discuss emerging therapeutic strategies, including nutritional support, exercise, and pharmacological interventions. By highlighting the gaps in existing research and proposing directions for future studies, this review seeks to improve the management and outcomes of cirrhotic patients affected by sarcopenia.

Field-packing of cantaloupes involves numerous food contact surfaces that can contamination melons with foodborne pathogens; the soil on these surfaces increases throughout the harvest day. Data are lacking on the cross-contamination risk from contaminated food contact surfaces under the dry conditions typical of cantaloupe field-packing operations. This study sought to evaluate the survival of Salmonella and Listeria monocytogenes on cantaloupe field-pack food contact surfaces using both a wet and dry inoculum to provide insights into managing foodborne pathogen contamination risks. Five clean or fouled materials (cotton gloves, nitrile gloves, rubber gloves, cotton rags, and stainless steel) were inoculated with a cocktail of either Salmonella or L. monocytogenes. A wet inoculum was spot inoculated (100 µL) onto coupons. A dry inoculum was prepared by mixing wet inoculum with 100 g of sterile sand and shaking the coupons with the inoculated sand for 2 min. Coupons were held at 35°C (35% RH) and enumerated at 0, 2, 4, 6, and 8 h. Significant differences in pathogen concentrations over time were calculated, and the GInaFiT add-in tool for Excel was used to build Log-linear, Weibull, and Biphasic die-off models. Depending on the material type, coupon condition, and inoculum type, Salmonella and L. monocytogenes reductions over 8 h ranged from 0.3 to 3.3 and −0.4 to 4.2 log10 CFU/coupon, respectively. For all material types, Salmonella reductions were highest on wet-inoculated clean coupons; L. monocytogenes varied by material type. Weibull and biphasic models were a better fit of respective pathogen die-off curves than linear models. Overall, faster die-off rates were seen for wet inoculated and clean materials. Since pathogen populations remained viable over the study duration and both inoculum type and coupon condition impacted survival, frequent sanitation or replacement of food contact surfaces during the operational day is needed to reduce the risk of cross-contamination.

Summary: Background: Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50 mg/kg (150, 100, 50, 0 mg/kg) in combination with total body irradiation (TBI) 2 Gy, anti-thymocyte globulin (ATG) and fludarabine. Methods: Ninety-six patients with severe aplastic anaemia aged ≤65 years with adequate organ function enrolled on a trial of human leukocyte antigen (HLA)-matched or 1 HLA-locus mismatched unrelated donor marrow transplantation conducted between 02/2006 and 12/2013 in the United States (NCT00326417). Exclusion criteria were Karnofsky performance status of less than 60, clonal cytogenetic abnormalities and inherited marrow failure syndormes. The primary outcome was day-100 engraftment (achievement of absolute neutrophil recovery to at least 0.5 × 109/L without subsequent decline) and day-100 survival. The trial determined the lowest effective Cy dose as 50 mg/kg (n = 38) for day-100 engraftment and survival. Cy dose 100 mg/kg (n = 41) was also acceptable. Accrual to Cy doses 150 mg/kg (n = 15) and 0 mg/kg (n = 3) was terminated early for toxicities. The current study is an extended follow up of patients enrolled on the trial (NCT00326477) and includes 76 of 96 patients alive ≥1 year after transplantation. There were 20 deaths in the first year after transplantation (Cy 0 mg/kg [n = 2], Cy 50 mg/kg [n = 1], Cy 100 mg/kg [n = 10], Cy 150 mg/kg [n = 7]). Patients were followed prospectively from transplantation and data reported using standardized data collection forms until death, loss to follow up or last contact through November 2023. The incidence of graft failure was calculated using the cumulative incidence estimator and the probability of survival using the Kaplan–Meier estimator. Findings: The median follow up of the cohort is 8.02 (IQR) 5.16–10.12) years. With Cy 50 mg/kg, there was one graft failure and five deaths ≥1 year after transplantation. With Cy 100 mg/kg there was only one late death and no graft failure. The 8-year probabilities of survival were 85.0% (95% CI 67.3–93.5) and 75.6% (95% CI 59.4–86.1) after Cy 50 mg/kg and 100 mg/kg, respectively, P = 0.31. With Cy 0 mg/kg and 150 mg/kg, there were no graft failures or death ≥1 year after transplantation. Regardless of Cy dose 12 of 15 patients aged ≥50 years died. Interpretation: Cy 50 mg/kg or 100 mg/kg with TBI 2 Gy, ATG and fludarabine are effective conditioning regimens for unrelated donor marrow transplants for aplastic anaemia. Identification of an optimized transplantation approach for patients aged ≥50 years is needed. Funding: US National Institutes of Health.

Background: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions. Methods: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales. Results: Throughout a median follow-up of 37.60 (interquartile: 24.77–50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend

The United Network for Organ Sharing (UNOS) heart transplant allocation policy was changed in 2018. This study examines the impact of the change in UNOS heart transplant allocation policy on the use of temporary mechanical circulatory support (MCS) devices and post-transplant survival.The analysis included a total of 26,481 patients listed and transplanted between January 2013 and June 2022. The results showed a decrease in waiting time for transplant after the policy change, indicating a successful reduction in waitlist time for high-priority status patients. However, the length of hospital stays from transplant to discharge increased following the policy change. The study also found an increase in the frequency of ECMO and IABP use both at the time of listing and at the time of transplant following the policy change.Cumulative patient and graft survival at 1000 days decreased following the policy change (86.1 per cent versus 83.7 per cent at 1000 days, p = 0.002). However, the survival curves showed similar survival trends in the first 2 years, with late divergence in survival occurring after 2 years.In conclusion the latest UNOS heart transplant allocation policy change led to a decrease in waiting times and an increase in the use of temporary MCS devices. There was a decrease in cummulative survival at 1000 days following the policy change.

Background: Time-to-event (TTE) endpoints are evaluated as the primary endpoint in single-arm clinical trials; however, limited options are available in statistical software for sample size calculation. In single-arm trials with TTE endpoints, the non-parametric log-rank test is commonly used. Parametric options for single-arm design assume survival times follow exponential distribution or Weibull distribution. Methods: The exponential- or Weibull-distributed survival time assumption does not always reflect hazard pattern of real-life diseases. We therefore propose gamma distribution as an alternative parametric option for designing single-arm studies with TTE endpoints. We outline a sample size calculation approach using gamma distribution with a known shape parameter and explain how to extract the gamma shape estimate from previously published resources. In addition, we conduct simulations to assess the accuracy of the extracted gamma shape parameter and to explore the impact on sample size calculation when survival time distribution is misspecified. Results: Our simulations show that if a previously published study (sample sizes ≥ 60 and censoring proportions ≤ 20 %) reported median and inter-quartile range of survival time, we can obtain a reasonably accurate gamma shape estimate, and use it to design new studies. When true survival time is Weibull-distributed, sample size calculation could be underestimated or overestimated depending on the hazard shape. Conclusions: We show how to use gamma distribution in designing a single-arm trial, thereby offering more options beyond the exponential and Weibull. We provide a simulation-based assessment to ensure an accurate estimation of the gamma shape and recommend caution to avoid misspecification of the underlying distribution.

Avian pathogenic Escherichia coli (APEC) can spread beyond the intestines and cause systemic infections, leading to various clinical manifestations, including airsacculitis, pericarditis, perihepatitis and colisepticemia. The mechanisms facilitating this extraintestinal infections are not fully understood. In this study, we investigate how the tolA gene affects APEC virulence by encoding a protein involved in maintaining outer membrane integrity. We constructed a tolA deletion mutant of APEC strain E058 and evaluated its growth and survival in various environments, including in vitro cultures and in vivo infection models in chickens. We found that the motility-defective ΔtolA mutant exhibits reduced biofilm formation ability and weakened resistance to the environmental stresses, suggesting an important role for TolA in APEC's survival. The lack of tolA gene affects the bacterial ability to resist the host's immune system, such as complement-mediated serum killing or phagocytosis, as shown by the serum killing and macrophage phagocytosis assays. Additionally, in vivo infection studies using chickens demonstrated that the ΔtolA mutant displayed attenuated virulence, evidenced by reduced mortality and lower tissue bacterial burden. Reverse transcription quantitative real-time PCR (RT-qPCR) analysis revealed that inactivation of tolA led to downregulation of virulence genes associated with serum resistance (traT) and flagellar biosynthesis (fliR). Taken together, our findings demonstrate the multifaceted role of TolA protein in promoting the survival, immune evasion, biofilm formation, and virulence of APEC E058. This suggests that targeting TolA could potentially offer new strategies for combating APEC infections.

Objectives: There is an active debate regarding whether metformin use improves survival in people with ovarian cancer. We examined this issue using methods designed to avoid immortal time bias—as bias that occurs when participants in a study cannot experience the outcome for a certain portion of the study time. Methods: We used time-dependent analyses to study the association between metformin use for all 4,951 patients diagnosed with ovarian cancer in 1997 through 2018 in the province of British Columbia, Canada. Cox proportional hazards models were run to estimate the association between metformin and survival in the full cohort of ovarian cancer patients and among a cohort restricted to patients with diabetes. Results: Metformin use was associated with a 17 % better ovarian cancer survival in the full cohort (adjusted hazard ratio (aHR) = 0.83 (95 %CI 0.67, 1.02)), and a 16 % better ovarian cancer survival for serous cancers patient's cohort (aHR = 0.84 (95 %CI 0.66, 1.07)), although both were not significant. However, a statistically significant protective effect was observed when restricting to the diabetic cohort (aHR = 0.71 (95 %CI 0.54–0.91)), which was also seen among serous cancers (aHR = 0.73 (95 %CI 0.54–0.98)). Conclusion: Metformin use was associated with improved ovarian cancer survival. The lack of statistical significance in the full cohort may reflect that diabetes is associated with reduced cancer survival, and thus diabetes itself may offset the benefit of metformin when examining the full cohort. Future research should examine metformin use among non-diabetic ovarian cancer patients.

Background: A one-time gait speed measurement predicts mortality risk. A framework for updating a clinician’s mortality risk perception with new information from each clinic visit is needed. We used joint modeling of longitudinal and survival data for dynamic prediction of mortality risk. Methods: We fit sex-stratified joint models to 20-meter (bi)annual longitudinal gait speed measured every 6 months and 14-year survival data from the Health, Aging and Body Composition Study allowing for non-linear fluctuations of gait speed and controlling for important covariates such as age, recent hospitalization, blood pressure, obesity, and comorbidities. Results: Participants (N = 3048) were 74 years old with gait speed 1.18 m/s. They were 42% Black, and 52% died over 14 years. Higher gait speed of 0.1 m/s was associated with 23% (95% confidence interval or CI = 20–25%) and 25% (CI = 21–28%) reductions in mortality risk in men and women; and a 0.05 m/s annualized slowing (slope) with 31% (CI = 13–51%) increase in men (all p < 0.05), with findings persisting after covariate adjustment. Distant gait speed history over a year prior contributed little for mortality risk prediction with mean change of only 1–2% in 5-year risk. Conclusion: The two most recent gait speeds appear sufficient to consider for mortality risk in the present initial analysis. More frequent gait speeds need to be considered in mortality risk prediction before definitive conclusions supporting real-world application.

Ovarian cancer (OC) is one of the most common malignancies and a leading cause of death among women worldwide. The ubiquitin pathway plays an important role in OC development. Using the single nucleotide polymorphism data obtained using the prevalence and dominance strategies, four ubiquitin marker genes were identified according to their expression levels: BARD1, BRCA2, FANCA, and BRCA1. Based on these four genes, a consensus clustering of OC expression data was performed. The significant differences in the survival analysis, ESTIMATE, and CIBERSORT results among the clusters indicated the pivotal role of these four genes in OC development. Of the ubiquitin-representative genes in each cluster, two ubiquitin genes, TOP2A and MYLIP, were identified in the survival risk model after univariate survival, Least Absolute Shrinkage and Selection Operator regression, and multivariate survival analyses. The reliability and robustness of both the training and validation data were confirmed by comparing the significant survival difference between high- and low-risk patients. We further explored the association between our risk model and clinical outcomes as well as predicted potentially interacting drugs. The co-expression network showed clear interactions among the four marker genes and two model genes and between high- and low-risk differentially expressed genes. Significantly enriched genes were found in pathways associated with ion channels, channel activity, and neuroactive ligand–receptor interactions. Therefore, suggesting the involvement of ubiquitin genes in the survival and development of OC through neurohumoral regulation. Our results will provide valuable reference or supplementary information for studies investigating OC diagnosis and therapies.

Introduction: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is recommended for staging and defining target volume in limited-stage SCLC, though the impact on outcomes compared with CT staging and elective nodal irradiation (ENI) is not well documented. We analyzed patients receiving 45 Gy/30 fractions in two randomized trials of thoracic radiotherapy (TRT) in limited-stage SCLC (HAST and THORA trials) to evaluate whether PET-CT for staging and radiotherapy planning reduces radiotoxicity and improves survival. Methods: Patients in HAST were staged with CT of the thorax and upper abdomen and brain magnetic resonance imaging of the brain. Patients in THORA were staged with PET-CT in addition. All patients were to receive four courses of platinum/etoposide chemotherapy and concurrent TRT starting three to four weeks after the first chemotherapy course. In HAST, target volumes included pathological lesions on CT plus ENI of lymph node stations 4–7 (bilateral). In THORA, target volumes were limited to PET-CT-positive lesions (selective nodal irradiation [SNI]). Results: A total of 149 patients were included (PET-CT/SNI: n = 76, CT/ENI: n=73); the median age was 64 years, 56% were women, 85% had PS 0 to 1, and 81% had stage III disease. The PET-CT/SNI group experienced less grade 3-4 esophagitis (18% versus 33%, p = 0.043), less grade >=1 pneumonitis (5% versus 16%, p = 0.028), and less dysphagia after TRT (mean scores on European Organisation for Research and Treatment of Cancer 13-item lung cancer module: 45 versus 72). There was no difference in median overall survival (24 versus 25 mo, p = 0.59) or progression-free survival (11 versus 11 mo, p = 0.23). Conclusions: Using PET-CT for staging and target volume definition of TRT reduces acute radiotoxicity but does not improve overall or progression-free survival in limited-stage SCLC.

Summary: Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I–IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8–46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9–62.8) and 35.7% (95% CI 23.8–53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43–42.54, P

Introduction: The molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs. Materials and methods: On July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores. Results: A total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05–1.1). Conclusions: Our review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.

Background: The high prevalence of HIV infection and the deaths caused by it is one of the challenges for the healthcare systems throughout the world. In this study, we analyzed the survival of people living with HIV and co-infections, and related factors. Methods: This retrospective cohort study was performed on 3030 people living with HIV admitted to Imam Khomeini Behavioral Disease Counseling Center, Tehran, Iran, during 2004–2018. Required data were obtained from the individuals’ files. Kaplan Meier diagrams and Log-rank tests were used to assess the relationship between different factors and survival. In addition, Cox regression analysis was performed to determine the effective factors in HIV mortality. Data were analyzed using STATA software, version 14. Results: The mean age of studied population was 43.2 ± 9.5 [years] and 77.3 % were male. Among the subjects, 3.2 % were infected with hepatitis B, 31.5 % with hepatitis C, and 13.9 % with Tuberculosis (TB). One, five, ten, and fifteen-year survival rates were 97.0 %, 93.0 %, 86.0 %, and 54.0 %, respectively. The mean survival time was 154.2 ± 0.9 months. Age more than 35, history of imprisonment, Unsafe sexual behavior, TB, and hepatitis C are independently associated with death in people living with HIV (p

Background: History of coronary artery disease (CAD) and/or atrial fibrillation (AF) and/or valvular replacement (VR) are prevalent among patients admitted to intensive care units (ICUs). The impact of these conditions on outcomes in patients with acute respiratory distress syndrome (ARDS) remains insufficiently explored. Methods: We performed a retrospective study on prospectively collected data from patients with ARDS and a PaO2/FiO2 ratio ≤150 mmHg. Patients were admitted between January 2006 and March 2022. We used multivariable logistic regression analysis. The primary outcome was 1-year mortality from admission to the ICU; secondary outcomes included mortality at 28 days and 90 days. Results: Among 1.033 patients, 181 (17.5 %) had a history of CAD and/or AF and/or VR. History of CAD and/or AF and/or VR was independently associated with 1-year mortality (Odds-Ratio (OR) = 2.59, 95 % confidence interval (CI) 1.76–3.82, p

The development of renewable and low-carbon energy sources means that strategic elements such as lithium (Li) are increasingly being used. The data available on the effects of Li on aquatic organisms are relatively scarce. The copepod Eurytemora affinis, widely distributed in the brackish estuarine waters of the northern hemisphere, is a species of choice in ecotoxicology but in fact constitutes a cryptic species complex, composed of at least six cryptic species. Cryptic diversity can lead to misinterpretation and alter the reproducibility of routine ecotoxicological tests. In the present study, two cryptic species of the E. affinis complex from the Seine (European clade) and the St. Lawrence (North-Atlantic clade) estuaries were used to assess Li toxicity and to compare their differential sensitivity. Larvae were exposed to different concentrations of Li (0.4, 4.39, 35.36 and 80.83 mg L−1) under semi-static conditions for 96 h. Larval development stages were determined and log-logistic functions were fitted to evaluate mortality (LC50) and growth (EC50) parameters. After 96 h of exposure, the results showed that the European and North-Atlantic clades had LC50 values of 55.33 and 67.81 mg L−1 and EC50 values of 28.94 and 41.45 mg L−1, respectively. A moderate difference in sensitivity to Li between the European and North-Atlantic clades of the E. affinis complex was observed. Thus, the cryptic species diversity should be considered using E. affinis to avoid bias in the interpretation of the data. Despite environmental concentrations of Li are expected to increase over the next years, EC50 and LC50 found for E. affinis cryptic species are largely higher than Li environmental concentrations to provoke extreme effects.

Background: The adult congenital heart disease (ACHD) population is growing and risk prediction is important to predict adverse outcome and consult patients during their lifecourse. Objectives: This study aims to describe the long-term prognostic value of blood biomarkers in ACHD. Methods: In this prospective observational cohort study, 602 patients with moderate or complex ACHD were included (median age 32.5 years [IQR: 24.7-41.2], 42% female, 90% New York Heart Association I). N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive-troponin T, growth differentiation factor 15, high-sensitive-C-reactive protein, suppression of tumorigenicity-2 and galectin-3, as well as full blood count, renal function, LDL, and HDL were measured. Cox models were applied to relate the selected biomarkers with the primary end point of all-cause mortality and secondary end point of mortality or heart failure. Standardized HRs adjusted for relevant prognostic factors, including age, sex, and complexity of diagnosis, were reported. Results: Abnormal biomarker levels were present in 424 (70.4%) patients. During a median follow-up of 10.1 years, 41 (6.8%) patients died and 81 (13.5%) developed heart failure. Associations were observed between the primary and secondary end point and red cell distribution width, NT-proBNP, and growth differentiation factor 15. In a multibiomarker model, only NT-proBNP remained associated with mortality (HR: 2.74; 95% CI: 2.01-3.74). NT-proBNP significantly improved the C-statistic of the clinical prediction model (0.85-0.92). Based on NT-proBNP alone, low-risk patients could be identified. Patients with NT-proBNP

Background: Out-of-hospital cardiac arrest (OHCA) incidence and survival often vary within regions according to patient-related and contextual factors. This study aims to establish the overall spatial dependence of incidence, bystander cardiopulmonary resuscitation (BCPR) and 48-h survival of OHCA with their associated demographic and socioeconomic characteristics in a Swiss region. Methods: We conducted a retrospective study using data of all OHCAs recorded between 2007 and 2019 in the canton of Vaud and, more specifically, in the Lausanne area. Provision of BCPR and 48-h survival were analysed using Getis-Ord Gi statistics and OHCA incidence by local Moran’s I with empirical Bayes standardised rates. Demographic and socioeconomic characteristics were compared between incidence clusters generated by local Moran’s I method. Results: Significant spatial variations of OHCA incidence, BCPR and 48-h mortality were observed. Although BCPR was statistically more likely in rural areas, 48-h survival was improved in a few main cities. At the cantonal level, postcode areas with a higher incidence of OHCAs were less densely inhabited with lower salary levels, more Swiss citizens, and an older population. At city level, small area variations were detected within urban neighbourhoods. The more affected hectares with more OHCAs were less inhabited, with a better median salary, more Swiss citizens, and off-centre. Conclusions: Spatial variations associated with demographic and socioeconomic factors were observed for OHCA incidence and survival, with sparsely populated areas particularly at risk. These data suggest an unmet need for targeted prevention interventions and structural modifications of the existing prehospital system at the cantonal level.

Introduction: Out-of-hospital cardiac arrests (OHCA) witnessed by Emergency Medical Services (EMS) are reported to have more favourable survival than bystander-witnessed arrests, even after adjusting for patient and arrest factors known to be associated with increased OHCA survival. This study aims to determine whether the survival advantage in EMS-witnessed arrests can be attributed to differences in the EMS response time to the arrest. Methods: Using registry data we conducted a retrospective, population-based cohort study of bystander- and EMS-witnessed OHCAs of medical aetiology who received an EMS resuscitation attempt in Western Australia between 2018–2021. EMS response time to arrest was assumed to be zero for EMS-witnessed arrests. Multivariable logistic regression was used to compare 30-day OHCA survival by witness and bystander CPR (B-CPR) status, adjusting for EMS response time to arrest, and patient and arrest characteristics. Results: Of 2,130 OHCA cases, 510 (23.9%) were EMS-witnessed and 1620 were bystander-witnessed: 1318/1620 (81.4%) with B-CPR, and 302/1620 (18.6%) with no B-CPR. The median EMS response time to bystander-witnessed arrests who received B-CPR was 9.9 [Q1,Q3: 7.4, 13.3] minutes. After adjusting for the EMS response time and patient and arrest factors, 30-day survival remained significantly lower in both the bystander-witnessed group with B-CPR (aOR 0.56; 95% CI 0.34 – 0.91) and bystander-witnessed group without B-CPR (aOR 0.23; 95% CI 0.11 – 0.46). Conclusion: An increased EMS response time does not fully account for the higher OHCA survival in EMS-witnessed arrests compared to bystander-witnessed arrests.

Rationale: Severe pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is currently defined by an elevated mean pulmonary arterial pressure and strongly elevated pulmonary vascular resistance >5 wood units. Clinically, these patients show a male predominance, and usually present with very severe dyspnea, severe hypoxemia, strongly decreased exercise capacity and poor prognosis, even though the clinical picture is frequently associated with less severe airflow obstruction. Explanted lung samples of patients with COPD and severe PH show severe remodeling of small pulmonary arterioles, predominantly in the intima and media of the vessels. In this concise review, we discuss the clinical and histopathological evidence of severe PH in COPD.

Introduction and Objectives: Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. Patients and Methods: This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017–2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999–2016) to assess the correlation with mortality. Results: In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. Conclusions: The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.

Propionic acidemia (PA) is a rare metabolic disorder affecting amino acid metabolism. Liver transplantation improves some outcomes, but the impact on long-term survival remains unclear. A systematic literature review and survival analysis, identifying 94 PA patients who underwent transplantation, revealed a survival probability of 62% at age 33; while median survival was estimated at 40 years. These findings highlight a substantial survival deficit of PA patients compared to the general population despite liver transplantation.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p

Objective: To develop and internally validate a nomogram to predict recurrence-free survival (RFS) including the time to radical cystectomy (RC) and perioperative blood transfusion (PBT) as potential predictors. Methods: Patients who underwent open RC and ileal conduit between January 1996 to December 2016 were split into developing (n=948) and validating (n=237) cohorts. The time to radical cystectomy (TTC) was defined as the interval between the onset of symptoms and RC. The regression coefficients of the independent predictors obtained by Cox regression were used to construct the nomogram. Discrimination, validation, and clinical usefulness in the validation cohort were assessed by the area under the curve, the calibration plot, and decision curve analysis. Results: In the developing dataset, the 1-, 5-, and 10-year RFS were 83.0%, 47.2%, and 44.4%, respectively. On multivariate analysis, independent predictors were TTC (hazards ratio [HR] 1.07, 95% confidence interval [CI] 1.05–1.08, p

Background: Sudan is a country with limited resources. The pattern of malignancies is unknown due to the lack of a national registry. Khartoum's oncology hospital is the largest in the country. Large hospital data might reflect the country's profile. This study investigates the 15-year disease distribution and survival rates of children with malignant diseases at Khartoum Oncology Hospital (KOH). Material and methods: Children 0–15 years with histologically confirmed malignancy were followed from 2005 to 2019 in KOH, Sudan. The disease pattern and overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan–Meier method. Results: We studied 4343 electronically registered and hard copies of patients. Children constitute 4% of all center patients. The male-to-female ratio was 1.5.Seventy-two percent of patients are between 1 and 10 years old. The abandonment rate is high (32.2%) and contributes to low survival. Acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, Wilms tumor, and retinoblastoma were the most common malignancies. The EFS was 47.4%, and OS was 49.3%. Conclusion: Malignancy was more common in males. The malignancy pattern was similar to that in other African countries. Abandonment rates are high. A cancer registry is needed to determine the malignancy pattern in the pediatric population.

Microvascular free tissue transfer surgery is a frequently used technique for head and neck reconstruction involving anticoagulants, and the present study aimed to analyse the postoperative outcomes of aspirin use in conjunction with this procedure. We searched databases for articles published between 2007 and 2022 on microvascular free tissue transfer surgery using aspirin and assessed them for primary and secondary outcomes. Odds ratios (ORs) and 95 % confidence intervals (CIs) were determined through analyses, followed by constructing a forest plot for complication rates. A total of 617 articles were retrieved from the databases, including 14 original full-text articles. Overall complication rates ranged from 0.7–38 % (95 % CI, 17.85 ± 0.503 (±2.8 %) [17.347–18.353]), while flap survival rates ranged from 95–99.2 % (95 % CI, 96.28 ± 0.0956 (±0.10 %) [96.184–96.376]). Two studies reported similar complication rates of 38 %, the highest among all reported studies. The ORs between the studies for the complications and flap survival rates were 2.614 and 0.722, respectively. Although the complication rates associated with aspirin use were not significantly high among the studies, they cannot be ignored. Flap survival rates were independent of the dose and type of anticoagulants used during surgery.

Introduction and Objectives: There are limited recent data on the burden of chronic hepatitis B (CHB) in the North American general population. We aimed to identify the CHB burden from a Canadian population-based perspective. Patients and Methods: Using a retrospective cohort design, we searched Alberta Analytics administrative databases including the Provincial Laboratory database, to describe CHB epidemiology and natural history in Alberta, Canada between fiscal years 2012-2020. We analyzed incidence and prevalence trends using a Poisson regression model and conducted Kaplan-Meier analyses to examine the incident cohort's survival. Results: The age/sex-adjusted incidence of CHB between 2015-2020 was 27.1/100,000 person/years (29.6/100,000 in males and 24.5/100,000 in females) and was highest among individuals aged 45-64 years. Despite a decrease in annual incidence of CHB from 36.4 to 13.4/100,000 between 2015-2020, prevalence increased from 98.9 to 210.3/100,000 in the same period. Of 6,860 incident cases, 2.1% died, and 0.2% underwent liver transplantation during a median follow-up of 3.6 years (interquartile range 2.0-4.9 years). CHB patients had significantly lower survival rates compared to age/sex-matched Canadians, with a standardized mortality ratio of 3.9 (95% confidence interval [CI] 3.3-4.6). Male sex (hazard ratio [HR] 1.7; 95% CI 1.2-2.5), older age at diagnosis (HR, 1.08; 95% CI 1.07-1.09) independently predicted mortality. Conclusions: CHB incidence decreased in Alberta, which is consistent with nationwide trends. Males and individuals aged 45-64 had higher CHB incidence and prevalence. CHB patients’ lower survival rates emphasize the need to address barriers to guideline recommended HBV care linkage.

Background: The main aim of this study was to analyse the 6-month survival rates in peri-acetabular metastasis patients undergoing total hip arthroplasty (THA) with an acetabular cage and without curettage. The secondary objectives were to analyse the global survival rates, the factors influencing patient survival and to evaluate mechanical complication rates after THA. Methods: This study was carried out on a cohort of 93 consecutive patients who underwent THA with an acetabular cage without curettage for acetabular metastasis or multiple myeloma lesions between 2010 and 2020. The National Death Registry was consulted to obtain the exact date of death of the patients; the minimum follow-up time was 2 years. Results: The 6-month survival rate for all types of cancer was 78 % [68 – 85], the 1-year survival rate was 66 % [55 – 74], and the 5-year survival rate was 26 % [17 – 36]. The median overall survival for the cohort was 24.37 months [16.10 – 32.63]. The mean overall survival was 46.02 months [32.89 – 59.16]. At last contact, 86 % of the operated patients were walking again.No patient died from surgery. The ECOG performance status score, the number of bone metastatic sites, the presence of visceral metastases and the number of lines of systemic therapy undertaken prior to surgery were negative survival factors. Three patients (3.2 %) had early prosthetic dislocation, 2 patients (2.2 %) showed aseptic loosening of her partial hip implant after 10 and 11 years respectively and 4 patients (4.3 %) had an early infection treated by debridement, antibiotics and implant retention to control the infection. During the follow-up period, no new femoral metastases were detected in any patient. Conclusion: Surgery without curettage is an effective treatment for periacetabular metastasis. It gives reliable results, regardless of the type of acetabular lesion, allowing most patients to walk again and does not modify the patient’s survival.

Introduction: Various pieces of evidence suggest an elevation in the levels of EGFR and HER2 in different cancers leading to the proliferation, invasion, and metastasis of cancer cells. In this study, we conducted a comprehensive investigation into the expression alterations of these two receptors in various cancers using in silico data. In addition, we investigated the therapeutic potential of lapatinib as an inhibitor of these receptors in various cancer types. Methods: RNAseq data for prevalent cancers were downloaded from The Cancer Genome Atlas (TCGA). After initial preprocessing, expression changes of HER2, EGFR, and candidate genes—identified based on their association with EGFR and HER2 signaling pathways—were examined. Human protein atlas data were utilized to assess the protein expression of HER2 and EGFR. GSE129254 was employed to identify molecular pathways and candidate genes associated with lapatinib. The protein-protein interaction network was used to identify lapatinib-influenced hub genes. Clinical data for common cancers were used to investigate the correlation between the expression of candidate genes and patients' mortality rates by Cox regression test. Results: The findings clearly indicated a significant increase in the expression levels of HER2 and EGFR in cancers such as kidney, lung, breast, bladder, pancreas, head and neck, stomach, and endometrial, both at the mRNA and protein levels (p-value