Determinant Of Survival In Patients Research Articles

Clinical determinants of survival in patients with stage II-III pancreatic cancer.

56 Background: We sought to identify the clinical determinants of overall survival (OS) in patients diagnosed with stage II-III pancreatic cancer not undergoing surgery. We curated a relatively homogenous cohort of patients who did not undergo surgical resection, but instead underwent chemotherapy in sequence with stereotactic body radiation therapy (SBRT) to examine the features that differentiated those with poor OS. Methods: In a retrospective study, we examined a cohort of 259 patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT without surgery at a single institution (Stanford Health Care). We conducted both univariate and multivariate Cox regression analyses to assess the relationships between OS and individual clinical and tumoral variables, including: age, sex, stage, Karnofsky performance status (KPS), body mass index, vessel involvement, tumor location, and biological equivalent dose [BED] of SBRT as potential determinants. Results: The study cohort consisted of 136 men (52.5%) and 123 women (47.5%) with a median age of 69 (range 38-94). Tumor histology was predominantly ductal adenocarcinoma (n=249, 96.1%), with tumor sites of involvement spanning: uncinate (n=35, 13.5%), head (n=160, 61.8%), body (n=59, 22.8%), and tail (n=5,1.9%). More patients had stage III (n=171, 66%) than stage II (n=88, 34%) disease, and their tumor resectability by NCCN criteria were rated as: unresectable (n=145, 56%), borderline (n=28, 10.8%), resectable (n=11, 4.2%), or unrecorded (n=75, 29%). Tumor progression was observed in local (n=71, 27.4%), regional (n=29, 11.2%), and distant (n=150, 57.9%) sites during the median follow up period of 17 months (range 15-18 months) from diagnosis and 12 months (10-13 months) from SBRT. Death (n=213, 82.2%) during this period was more common than survival (n=46, 17.8%). In univariate analyses, clinical features impacting OS included: KPS (hazard ratio [HR] 0.14, p=0.007); male sex (HR 1.44, p=0.01), pancreatic head tumors (HR 1.44, p=0.011), BED (HR 1.33, p=0.035), and age (HR 1.013, p=0.044). In the multivariate analysis, which incorporated only features significant in the univariate analyses, tumor location at the pancreatic head (HR 1.412, p=0.021) and male sex (HR 1.360, p=0.03) conferred the highest risks for poor OS, with BED bordering on significance (p=0.059) (Table). Conclusions: Among patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT, but not surgery, the most significant clinical determinants of poor OS were location of the tumor in the pancreatic head and male sex. Prioritizing additional disease monitoring and alternative therapies for this subset of patients at higher risk of poor survival may be warranted. [Table: see text]

Outcome of Primary Lung Salivary Gland-Type Carcinoma: A Population-Based Study.

Introduction. Primary pulmonary salivary gland-type carcinomas are rare malignancies arising from minor salivary gland tissue in the lower respiratory tract. Given their rarity, constituting <1% of all primary lung malignancies, their epidemiological features and outcomes remain poorly documented. This study analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify primary pulmonary salivary gland carcinomas, including the most prevalent tumor types. Methods. All patients diagnosed with mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, with the lung designated as the primary site between 1975 and 2019, were subject to analysis. Overall and disease-specific survival were calculated using Kaplan-Meier curves and Cox proportional hazards models. Results. The study identified 323 mucoepidermoid carcinoma, 284 adenoid cystic carcinoma, and 6 epithelial-myoepithelial carcinoma diagnosed as pulmonary salivary gland-type carcinoma. An analysis of age distribution revealed a unimodal pattern for both mucoepidermoid carcinoma and adenoid cystic carcinoma, with most patients diagnosed after age 40. Most patients were Caucasians (77% for mucoepidermoid carcinoma and 83% for adenoid cystic carcinoma). Both disease-specific and overall survival were worse for patients diagnosed at the age of 60 years or above. Race or sex did not significantly impact patient survival. High-grade mucoepidermoid carcinoma demonstrated a significantly worse prognosis than low or intermediate-grade mucoepidermoid carcinoma. Conclusion. A comprehensive review of clinical and epidemiological features of pulmonary salivary gland-type carcinomas reveals that the age of diagnosis and tumor grade are the most significant factors in determining patient survival.

#1578 Left ventricular ejection fraction: association with risk of mortality and the incidence of AVF dysfunction

Abstract Background and Aims Ejection fraction (EF) and chronic heart failure (HF) are often considered as criteria for the possibility of arteriovenous fistula (AVF) creation in relation to an increased risk of death, without sufficient evidence for this. There is, however, rare but compelling evidence that low EF increases the risk of AVF dysfunction. Aims: to evaluate the association between EF at the time of AVF creation and the incidence of adverse cardiovascular events, all-cause mortality, as well as AVF dysfunction Method This retrospective cohort study included 962 adult patients who had a first-time created functioning AVF. Only patients with a more than three months period after AVF creation and within a five-year period were included. The mean follow-up period was 34 ± 13 months. Four groups were identified based on EF and the presence of HF at the time of AVF creation (transthoracic echocardiogram): HF with reduced EF (rEF) &amp;lt;40%, with mid-range (mrEF) of 40-49%, or with preserved EF (pEF) ≥50% + HF, and a “no HF” group with EF ≥50% and no HF. Results In the univariate analysis, a reduced EF was associated with an increased risk of mortality, with the hazard ratios (HRs) of 2.706 [95% CI 1.330; 5.507], p = 0.006 for mrEF and 8.250 [95% CI 2.621; 25.97], p &amp;lt; 0.001 for rEF, compared to the “no HF” group (here and thereafter)—Fig. 1. However, after adjusting for age, sex, and Charlson Comorbidity Index (CCI), the EF was not significantly associated with the risk of death. Only the CCI score remained a significant factor (HR = 1.748 [95% CI 1.482; 2.063], p &amp;lt; 0.001). A decreased EF was associated with the incidence of AVF dysfunction both in the univariate analysis and after adjustments. In the univariate analysis, the incidence rate ratios (IRRs) of 6.88 [95% CI 3.88; 12.1], p &amp;lt; 0.001 for mrEF, and 19.9 [95% CI 8. 64; 41.6], p &amp;lt; 0.001 for rEF, were shown. After adjusting for age, sex, and CCI, the IRR for mrEF was 8.96 [95% CI 5.81; 13.7], p &amp;lt; 0.001, and for rEF it was 23.4 [95% CI 13.8; 38.6], p &amp;lt; 0.001. Even in the presence of polycystic kidney disease and diabetes mellitus in the fully adjusted model, the association between EF and the incidence of AVF dysfunction remained statistically significant: the IRR was 8.61 [95% CI 5.61; 13.1], p &amp;lt; 0.001 for mrEF, and 33.4 [95% CI 19.5; 56.2], p &amp;lt; 0.001 for rEF. The findings were confirmed in a sensitivity analysis that included adjustments for unplanned onset of dialysis and competing risks survival analysis (death—outcome of interest, conversion of HD to PD or kidney transplantation and conversion of AVF to CVC—competing events). According to our results patients with EF&amp;lt;40% will inevitably lose AVF function for various reasons within 3.5 years—Fig. 2. Meanwhile, this approach will give the patient additional time of HD via AVF, but not CVC, without increasing the risk of death, subject to Qa monitoring. Conclusion In patients with CKD 5 who are initiating treatment with maintenance hemodialysis, a decreased EF is associated to a greater extent with a higher risk of AVF dysfunction than with an increased risk of mortality. The burden of comorbidities, rather than a standalone assessment of EF, is one of the major risk factors determining patient survival.

Clinical Outcomes and Determinants of Survival in Patients with Hematologic Malignancies Admitted to Intensive Care Units with Critical Illness.

The online version contains supplementary material available at 10.1007/s12288-024-01757-3.

Influence of protein intake on clinical and nutritional parameters in pancreatic cancer

Introduction Nutritional status is an important determinant of survival in patients with advanced pancreatic cancer. However, the effects of protein intake on nutritional status are largely unknown.

Factors Underlying Impaired Organ Recovery Despite a Deep Hematologic Response in Patients with Systemic AL Amyloidosis

Background: Amyloid-mediated organ dysfunction is the main determinant of survival for patients with light chain (AL) amyloidosis. Reducing the production of amyloidogenic light chains with plasma cell-directed therapy is a prerequisite for organ response. Despite achieving a hematologic complete response (hemCR), some patients have enduring organ dysfunction. A better grasp of the mechanisms underlying organ recovery is needed, especially as attention moves to novel therapeutics that trigger removal of existing amyloid deposits, and as graded organ response criteria to gauge improvement more precisely than traditional binary systems are adopted. Aims: We designed this study to identify the (1) rates of organ non-response and (2) possible reasons for impaired organ recovery in patients with AL amyloidosis with hemCR after treatment. Methods: Patients with biopsy confirmed AL amyloidosis who presented to our center for post-treatment assessment between February 2019 and June 2023 were included if they had major organ involvement (heart, kidney and/or liver) and were evaluable for organ response (Palladini, 2012). Graded cardiac response was assessed by validated criteria (Muchtar, 2022). We excluded patients who received amyloid fibril-targeted antibody therapies. To eliminate the possibility of insufficient hematologic response as a confounder for organ non-response, we focused only on patients with hemCR. Organ response was measured as best response &amp;gt;3 months from hemCR achievement. Reasons for organ non-response were postulated by our multidisciplinary team after extensive workup and review of clinical data. Results: Among 143 patients with hemCR, the median age at diagnosis was 58 years (range 30-78); 94 (66%) were male; and 24 (17%) identified as non-white race. Kidney, heart and liver involvement was present in 117 (82%), 68 (48%) and 17 (12%) patients, respectively; 54 (38%) had ≥2 major organs affected. Final treatment granting hemCR was high-dose melphalan and stem cell transplantation for 49 (34%); bortezomib-based for 37 (26%); daratumumab monotherapy for 31 (22%); daratumumab-CyBorD for 18 (13%); and an immunomodulatory drug for 8 (6%) patients; 58 (41%) required ≥2 lines of therapy to achieve hemCR. Failure to attain organ response was observed in 40/117 (34%), 19/68 (28%) and 3/17 (18%) of patients with kidney, heart and liver involvement, respectively. Of 42 patients with both kidney and heart involvement, 21 (50%) had concordant responses of both organs; 6 (14%) had concordant non-responses; and 15 (36%) had discordant responses. Among 49 heart responders, 14 (29%) attained CarCR (nadir BNP ≤80 pg/mL); 16 (33%) CarVGPR (&amp;gt;60% reduction); and 19 (39%) CarPR (31-60% reduction); 40/77 (52%) kidney responders attained proteinuria &amp;lt;500 mg/24h. Clinical features of organ non-responders in relation to responders are reported in Table 1. Notably, kidney non-responders had more advanced disease at baseline, whereas heart non-responders more often had lambda-typic amyloidogenic light chains. Among kidney non-responders, 2 had stable and another 2 had rising proteinuria level; the remaining 36 had improved proteinuria but were categorized as non-response due to &amp;gt;25% worsening of eGFR. Among heart non-responders, 5 had stable elevation of BNP and 14 experienced organ progression (BNP increase &amp;gt;30% and &amp;gt;50 pg/mL); 2 required heart transplantation. The two most common factors believed to underlie kidney non-response were permanent kidney damage at diagnosis needing dialysis and treatment-related toxicity (Table 2). For 10 (25%) kidney non-responders, there was no apparent explanation, 7 of whom had detectable measurable residual disease (MRD) by multiparametric flow cytometry. Most cases of heart non-response had no apparent explanation; 6 of these 8 patients had detectable MRD. Conclusions: Despite effective treatment of the plasma cell clone, a considerable number of patients with AL amyloidosis in hemCR have enduring organ dysfunction. We found that the reasons for organ non-response differed across organ systems. Response was not always concordant for all involved organs, suggesting heterogeneity in organ biology in terms of mechanisms for amyloid-mediated injury and intrinsic ability to repair. Careful scrutiny of reasons for organ non-response is warranted before providing further hematologic treatments, which may be ineffective for organ recovery.

Epidemiological Insights into Large Granular Lymphocyte Leukemia: A Nationwide SEER Database Study

Background: Large granular lymphocytic (LGL) leukemia is a rare hematological malignancy that arises from cytotoxic T lymphocytes (T-LGL) or natural killer (NK) cells. LGL leukemia accounts for 2% to 5% of chronic lymphoproliferative disorders in the United States of America. LGL leukemia can either present as an indolent type or an aggressive type. Most patients remain asymptomatic and often have associated autoimmune diseases, such as rheumatoid arthritis and hematologic dyscrasias. We analyzed the demographic characteristics of LGL leukemia patients and investigated the influence of social determinants on their survival. Methods: We performed a retrospective cohort study of the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with LGL leukemia between years 2000 and 2020. Patient demographics, year of diagnosis, and timeline of treatment were analyzed by descriptive statistics. Cox proportional hazards regression analysis was performed to identify the factors influencing the survival of these patients. Results: A total of 2589 patients were diagnosed with LGL leukemia. Median age of diagnosis was 67 years. 59.4% were aged more than 65 years of age at the time of diagnosis, 52.7% were males, 81.5% were Caucasians, 64% had an annual income of more than $65,000, and 84.2% lived in metropolitan areas. 91.8% were diagnosed in the past decade after 2010. It is worth noting that 64.5% of the patients received treatment more than six months after diagnosis of LGL leukemia. 81.5% of patients were Caucasians, 9.6% were African Americans, 5.3% were Asians/Pacific Islanders, followed by 2% Hispanics and 1.5% American Indians. At the time of the last follow-up, 65.5% of patients were alive, with an overall median survival of forty months. 70% of patients had LGL leukemia as the only primary malignancy. Age less than 65 years had better outcomes than the older age group (HR 0.32). Female gender was protective (HR 0.69). Poor outcomes were seen in patients with an annual income of less than $65,000 (HR 1.21). The year of diagnosis and residence had no significant effect on survival. Marriage improved the outcomes of patients (HR 0.78) (Table 1). Patients receiving treatment within six months of diagnosis had higher mortality (HR 1.43) than the rest of the population. Caucasians comprised majority of the patient population and had better prognoses (HR 0.11) than Asians/Pacific Islanders (HR 0.49), Hispanics (HR 0.82), and African Americans (HR 0.97) (Figure 1). Conclusion: We present a population-based analysis and the determinants of survival in patients with LGL leukemia, a rare malignancy. The number of cases has increased in the past decade. Significant patient factors influencing survival in LGL leukemia patients include younger age at diagnosis, female gender, marriage and higher annual income.

Safety and Tolerability of Cael-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia Therapy in Patients with Light-Chain Amyloidosis: 24-Month Results of a Phase 2 Study

Background: Light-chain (AL) amyloidosis is a rare, systemic disease caused by plasma cell dyscrasia (PCD). Immunoglobulin light chains misfold and deposit in organs as insoluble amyloid fibrils. The extent of cardiomyopathy due to amyloid deposition determines patient survival. Current therapies target PCD to halt amyloid formation but do not treat existing amyloid deposits in organs. CAEL-101 is a novel, investigational, potentially first-in-class therapy to remove amyloid fibrils from organs. Aims: To present safety, tolerability, and biomarker data after 110 weeks of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab. Methods: Adult patients with AL amyloidosis (European Modification of Mayo Stage I-IIIa) and measurable hematologic disease were eligible for this ongoing, open-label, phase 2 study (NCT04304144). Other forms of amyloidosis and multiple myeloma were excluded. CAEL-101 ≤1000 mg/m 2 was administered with CyBorD therapy ± daratumumab as directed by the investigator. In addition to safety assessments, cardiac response was assessed by change over time in N-terminal pro-brain natriuretic peptide (NT-proBNP). Results: Patients (N = 25; mean age 65 years; 72% male) with Mayo Stage I (n = 2; 8%), II (n = 19; 76%), and IIIa (n = 4; 16%) AL amyloidosis were enrolled to be treated with CAEL-101. All 25 patients experienced treatment-emergent adverse events (TEAEs); 6 (24%) experienced TEAEs possibly related to CAEL-101, 17 (68%) experienced ≥1 adverse event of ≥Grade 3 severity, and 15 (60%) experienced ≥1 serious adverse event. There were a total of 447 TEAEs reported of which only 67 (15%) were Grade ≥3. As of the cutoff date of 22 May 2023, 12 (48%) patients had discontinued the study due death (n = 3), patient withdrawal (n = 3), physician decision (n = 2), heart transplant (n = 2), heart and kidney transplant (n = 1), and adverse event (n = 1). The most common adverse events reported by ≥5 (20%) patients were fatigue (n = 12), anemia (n = 10), nausea (n = 10), constipation(n = 9), diarrhea (n = 9), cough (n = 8), dizziness (n = 8), insomnia (n = 7), peripheral neuropathy (n = 7), dyspnea (n = 6), hypokalemia (n = 6), rash (n = 6), and headache (n = 5), peripheral edema (n = 5), vomiting (n = 5). There were 22 cardiac-evaluable patients (baseline NT-proBNP &amp;gt;332 ng/L) enrolled in this trial. After 110 weeks of CAEL-101 treatment, 6 (27%) patients were cardiac responders (&amp;gt;30% NT-proBNP decrease and more than 300 ng/L decrease, if baseline NT-proBNP ≥650 ng/L), 7 (32%) patients were stable (neither response nor progression), and 2 (9%) patients showed cardiac disease progression (&amp;gt;30% increase and ≥300 ng/L increase from baseline in the absence of eGFR decline of ≥25%); data for 7 (32%) patients were missing. Cardiac response over time to 110 weeks of CAEL-101 treatment is shown in Figure). Conclusions: Patients in this analysis have been treated for ≥24 months and CAEL-101 was generally well tolerated without evidence of organ toxicity. Long-term safety evaluation of CAEL-101 continues in this study. Most TEAEs (85%) were mild to moderate. Two phase 3 trials (NCT04504825 and NCT04512235) are in progress to study the efficacy and safety of CAEL-101 in cardiac AL amyloidosis European Modification Mayo Stages IIIa and IIIb.

Incidence, risk factors and outcomes of Acute Kidney Injury in Chronic Obstructive Pulmonary Disease patients with Acute exacerbation

Background: There is little data on the incidence, risk factors and outcomes of the AKI among COPD patients who are admitted to critical care units with exacerbation of symptoms. This observational study was conducted to evaluate the incidence and outcome of AKI with AECOPD.&#x0D; Method: We performed an observational study of patients who were admitted in the intensive care unit from August 2021 to February 2023 for acute exacerbation of COPD.&#x0D; Results: During the study period, a total of 108 patients were admitted to the ICU with acute respiratory failure attributed to COPD exacerbation. AKI occurred in 49 patients (45.4%). Independent risk factors for AKI in patients with AECOPD were advanced age, coronary artery disease, anemia, acute respiratory failure, and mechanical ventilation. Patients with AKI had worse prognostic implications and were more likely to require mechanical ventilation (42.8% vs 22.03%, P&lt;0.05), had a longer ICU stay (6 ±1.3 days vs 5.41±1.1 days, P&lt;0.05) and longer hospitalization (7.65±1.42 days vs 6.9±1.2 days, P&lt;0.05); and higher in-hospital mortality (28.5 % vs 11.8 %, P&lt;0.05) than those without AKI. Compared to patients without AKI who had in-hospital mortality rate of 11.8%, those with stage 2, or 3 AKI had rates of 41.6% and 85.7% respectively, that is 2.1- fold and 6.0-fold increased risk of in-hospital death, respectively.&#x0D; Conclusion: Incidence of AKI is relatively high in patient with AECOPD requiring intensive care. Patient with AKI had poor outcomes compared to non-AKI patient with AECOPD. AKI can be a prognostic factor for determining patient survival.

Determinants of survival in patients with chronic heart failure: a population-based study in Reggio Emilia, Italy.

We aim to monitor and improve the quality of the heart failure (HF) integrated assistance model defined by national and regional guidelines and implemented in the province of Reggio Emilia, Italy. Specific aims of the audit were to estimate the prevalence of HF, describe the characteristics of patients with HF and the rate of patients enrolled in the integrated care treated in primary care, and identify socioeconomic and geographic determinants of the 4-year survival of these patients. Retrospective analysis of a cohort of prevalent cases of HF, diagnosed before 31 December 2015 in Reggio Emilia, Italy, alive on 1 January 2016, and residing at the time of diagnosis on the provincial territory. Age and sex-adjusted prevalence of HF by area of residence were calculated according to the standard European population 2013. Patients were followed until death or 31 December 2019, whatever came first. The outcome measure of the study was four-year case fatality. Cox proportional hazards models, adjusted for age, sex, and duration of disease were used to determine the association between socio-geographic factors and death. The 4-year case-fatality rate was 36.7%, and it was the highest in the mountains (50.8%) compared with hills (34.6%), lowland (35.4%) and city (37.7%). The prevalence of HF was the lowest in the mountain [149.9, 95% confidence interval (CI) 112.1-187.7] and the highest in the lowland (340.8, 95% CI 308.7-372.9) and city (308, 95% CI 276.0-321.2). Patients living in the mountains had a lower deprivation index, and fewer hospitalizations prior to official diagnosis, although these characteristics were not statistically significant determinants of HF death in multivariate analysis. Behavioural (smoking and obesity) and socio-geographic characteristics (educational level, deprivation index and area of residence) were not significantly associated with mortality in both univariable and multivariable analysis; however, patients who live in mountains (hazard ratio 1.10, 95% CI 0.73-1.66) or hills (hazard ratio 1.11, 95% CI 0.90-1.37) had a slightly higher risk of death than those living in the city. Only 197 (12.1%) of patients in the cohort were enrolled in the integrated care pathway over the course of 4years. Although clinical determinants outweigh the geographic and behavioural disparities in the survival of patients with CHF treated in primary care, effective prevention strategies are needed to address environmental and socio-geographic inequalities in access to primary care and to hasten equitable linkage to integrated care.

Deep learning to predict lymph node status on pre-operative staging CT in patients with colon cancer.

Lymph node (LN) metastases are an important determinant of survival in patients with colon cancer, but remain difficult to accurately diagnose on preoperative imaging. This study aimed to develop and evaluate a deep learning model to predict LN status on preoperative staging CT. In this ambispective diagnostic study, a deep learning model using a ResNet-50 framework was developed to predict LN status based on preoperative staging CT. Patients with a preoperative staging abdominopelvic CT whounderwent surgical resection for colon cancer were enrolled. Data were retrospectively collected from February 2007 to October 2019 and randomly separated into training, validation, and testing cohort 1. To prospectively test the deep learning model, data for testing cohort 2 was collected from October 2019 to July 2021. Diagnostic performance measures were assessed by the AUROC. A total of 1,201 patients (median [range] age, 72 [28-98 years]; 653 [54.4%] male) fulfilled the eligibility criteria and were included in the training (n = 401), validation (n = 100), testing cohort 1 (n = 500) and testing cohort 2 (n = 200). The deep learning model achieved an AUROC of 0.619 (95% CI 0.507-0.731) in the validation cohort. In testing cohort 1 and testing cohort 2, the AUROC was 0.542 (95% CI 0.489-0.595) and 0.486 (95% CI 0.403-0.568), respectively. A deep learning model based on a ResNet-50 framework does not predict LN status on preoperative staging CT in patients with colon cancer.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

Estimated plasma volume is not a robust indicator of the severity of congestion in patients with heart failure

BackgroundCongestion is the main cause of morbidity and a prime determinant of survival in patients with heart failure (HF). However, the assessment of congestion is subjective and estimation of plasma volume (ePV) has been suggested as a more objective measure of congestion. This study aimed to explore the relationships and interactions between ePV, the severity of congestion and survival using a nationwide registry. MethodsOf the 1054 patients with HF enrolled in the registry, 769 had sufficient data to calculate ePV (using the Duarte, Kaplan, and Hakim equations) and relative plasma volume status (rPVS), and these patients were subsequently included in the present analysis. The severity of congestion was assessed using a 6-point congestion score (CS). Patients were divided into three groups according to the degree of congestion. ResultsOut of four equations tested, only ePVDuarte and rPVS were statistically higher in patients with severe congestion as compared to patients with no congestion (p<0.001 for both). Both ePVDuarte (r = 0.197, p<0.001) and rPVS (r = 0.153, p<0.001) showed statistically significant correlations with CS and both had a modest accuracy (70.4% for ePVDuarte and 69.4% for rPVS) to predict a CS ≥3. After a median follow up of 496 days, both ePVDuarte (OR:1.14,95%CI:1.03–1.26, p = 0.01) and rPVS (OR:1.02, 95%CI:1.00–1.03, p = 0.03) were associated with all-cause mortality after adjusting for demographic and clinical variables. However, none of the indices were associated with mortality following the introduction of CS to the models (p>0.05 for both). ConclusionsElevated ePVDuarte and rPVS were indicators of congestion but with a limited robustness, and either parameter could be clinically useful when a comprehensive clinical evaluation of congestion is not feasible.

Monocyte-to-lymphocyte ratio as a determinant of survival in patients with gastric cancer undergoing gastrectomy: A cohort study.

The monocyte-to-lymphocyte ratio (MLR) is an important prognostic determinant of various malignancies. However, the prognostic role of MLR in patients with gastric cancer undergoing gastrectomy remains unclear. Patients with stage I to III gastric cancer who underwent curative-intent gastric resection were enrolled in this study. Cox regression analysis was used to determine the independent variables for overall survival (OS) and disease-free survival (DFS). The established models were validated internally. Inter-model comparisons were performed using the integrated area under the receiver operating characteristic curve and the concordance index. Multivariate Cox regression analysis revealed that age, tumor-node-metastasis (TNM) stage, perineural invasion, serum albumin level, and MLR were prognostic factors for OS and DFS and constituted the full model. The full model was internally validated using calibration curves and decision curve analysis. The integrated area under the curve and concordance index of the full model outperformed those of TNM stage. The full model was a significant determinant of OS and DFS. Additionally, the full model was suggested to outperform TNM stage in predicting patient survival outcomes.

ACUTE RIGHT HEART FAILURE IN MEDICAL INTENSIVE CARE UNITS, A CRITICAL CARE PERSPECTIVE

Acute right heart failure in patients admitted to the intensive care unit with acute or chronic pulmonary disease is common, occasionally unrecognized, and difcult to manage. Right ventricular function is a major determinant of survival in patients with pulmonary diseases and this has been recently highlighted with critically ill patients infected with Covid. Basic understanding of the physiology of the right heart as related to pulmonary disorders and approach to management is required. Right heart failure can be classied as acute or chronic based on acuity and pathophysiology. Right heart failure is associated with poor clinical outcomes independent of the etiology; early identication and management can potentially improve outcomes. Shareholders for right heart failure include cardiologists, physicians and intensivists managing right heart failure in critical care. The focus of this review is on acute heart failure in the setting of Medical Intensive Care units.

Ca2+ handling remodelling in a porcine model of right ventricular dysfunction

Increased afterload is the primary pathophysiologic mechanism for right ventricular failure (RVF), which is the most critical determinant of survival in patients with pulmonary hypertension (PH). The cellular and molecular processes involved in the RV remodeling, including Ca2+ handling as an instrumental actor in the heart, remain incompletely understood. We gain insights into the cellular Ca2+ signaling in a large animal model of RV failure, the chronic thromboembolic pulmonary hypertension (CTEPH) piglet model, to develop specific therapy targeting RVF. CTEPH piglet model consisted of a primary left pulmonary artery ligation followed by weekly embolization in the right lower lobe leading to PH and progressive RV hypertrophy and failure. After six weeks, the piglet model replicated all the features of human CTEPH: increased pulmonary vascular resistance, mean pulmonary arterial pressure (PAP), and RV wall thickness associated with RV dysfunction as assessed by the reduced tricuspid annular plane systolic excursion (TAPSE). RV histological analyses revealed hypertrophied cardiomyocytes and aberrant fibrosis. At the cell level, RV myocytes from CTEPH piglets presented reduced L-type Ca2+ currents and CACNA1C mRNA, lower and slower [Ca2+]i transients, decreased sarcoplasmic reticulum Ca2+ content, and cell shortening to myocytes from sham piglets. This was related to reduce Sarco/Endoplasmic Reticulum Ca2+-ATPase isoform 2a (SERCA2a) protein expression. We found that store-operated Ca2+ entry is increased in hypertrophied RV myocytes, which is correlated with a de novo expression of the SR Ca2+ sensor STIM1L (long stromal interacting molecule 1). Finally, we found that Ca2+ sparks are larger and longer in RV myocytes from CTEPH piglets, whereas their frequencies and amplitude were unchanged compared to myocytes from sham. This was associated with profound disorganization of T tubules and ryanodine receptors (RyR) clustering without changes in RyR phosphorylation status. Our data highlight a cellular Ca2+ cycling remodeling that participates to the pathogenesis of RVF in CTEPH piglets.

Association between factor of parotid lymph node and prognosis in parotid cancer

IntroductionSurvival significance of parotid lymph node (LN) factors in parotid cancer remains unclear, our goal was to assess the impact of number, size, and extranodal extension (ENE) of metastatic parotid LNs on prognosis in parotid cancer. Materials and methodsPatients with surgically treated parotid cancer were retrospectively enrolled. Primary outcome variable was recurrence-free survival (RFS) and overall survival (OS). The hazard ratios (HRs) of main predictive variables including the number, size, and ENE of positive parotid LNs on RFS and OS were analyzed using Cox model. The secondary outcome variable was ENE of metastatic parotid LN, its association with clinicopathologic variables were evaluated using Chi-square test. ResultsIn total, 453 patients (186 male and 267 female) were included. The 10-year RFS and OS rates were 73% (95%CI: 69%–77%) and 61% (95%CI: 55%–67%), respectively. In Cox model, compared none parotid LN metastasis, one metastatic parotid LN did not offer additional compromise of RFS (p = 0.224) or OS (p = 0.135), but two or more positive LNs decreased the control of RFS (HR: 2.017; 95%CI: 1.378–4.632) and OS (HR: 2.173; 95%CI: 1.367–4.275). When accounting for the number of metastatic LNs, LN size or ENE was no longer related to RFS or OS. ENE of parotid LN tended to develop if there was presence of T3/4 stage, lymphovascular invasion, high histologic grade, N2/3 stage, and three or more positive parotid LNs. ConclusionQuantitative parotid LN burden but not ENE or LN size is an important determinant of survival in patients with parotid cancer.

Is lobectomy sufficient for multifocal papillary thyroid microcarcinoma?

ImportanceMultifocal papillary thyroid microcarcinoma (PTMC) has been associated with a higher incidence of lymph node involvement, bilateral involvement, and extrathyroidal extension compared to unifocal papillary thyroid cancer (PTC). ObjectiveTo describe the incidence and determinants of survival for patients with multifocal PTMC using the Surveillance, Epidemiology, and End Result (SEER) database. Design, setting, participantsThe SEER registry was utilized to calculate survival trends for patients with PTMC between 2010 and 2015. Patient data was then analyzed with respect to age, sex, race, multifocality, and types of surgery rendered. Main outcomes and measuresOverall Survival (OS) and Disease Specific Survival (DSS). Results22,283 cases of papillary thyroid microcarcinoma (T1a N0 M0) were identified. The cohort was composed of 82.6 % females, and about 82 % of patients were of white race. The mean age at diagnosis was 51.9 years. Multifocal PTMC was present in 32.2 % of the tumors (n = 7186). 73.9 % of patients underwent total thyroidectomy and 23.0 % received lobectomy. OS at 2 and 5 years was 98 % and 95 %, respectively. Multivariate analysis revealed that age, sex, and multifocality were determinants of OS. Only age was a determinant of DSS. Kaplan-Meier survival analysis revealed that multifocal PTMC had similar mean OS between lobectomy and total thyroidectomy patients (69.59 months versus 69.82 months). Conclusions and relevancePTMC has a good prognosis. Our analysis revealed that age was a determinant of OS and DSS; sex and multifocality were also prognosticators for OS. The type of surgery, whether lobectomy or total thyroidectomy, was not a determinant of survival in multifocal PTMC.

Early Lactate Clearance as a Determinant of Survival in Patients with Sepsis: Findings from a Low-resource Country.

Single lactate measurements have been reported to have prognostic significance, however, there is a lack of data in local literature from Pakistan. This study was done to determine prognostic role of lactate clearance in sepsis patients being managed in our lower-middle income country. This prospective cohort study was conducted from September 2019-February 2020 at the Aga Khan University Hospital, Karachi. Patients were enrolled using consecutive sampling and categorized based on their lactate clearance status. Lactate clearance was defined as decrease by 10% or greater in repeat lactate from the initial measurement (or both initial and repeat levels <=2.0 mmol/L). A total 198 patients were included in the study, 51% (101) were male. Multi-organ dysfunction was reported in 18.6% (37), 47.7% (94) had single organ dysfunction, and 33.8% (67) had no organ dysfunction. Around 83% (165) were discharged and 17% (33) died. There were missing data for 25.8% (51) of the patients for the lactate clearance, whereas 55% (108) patients had early lactate clearance and 19.7% (39) had delayed lactate clearance.On univariate analysis, mortality rate was higher in patients with delayed lactate clearance (38.4% vs 16.6%) and patients were 3.12 times (OR = 3.12; [95% CI: 1.37-7.09]) more likely to die as compared with early lactate clearance. Patients with delayed lactate clearance had higher organ dysfunction (79.4% vs 60.1%) and were 2.56 (OR = 2.56; [95% CI: 1.07-6.13]) times likely to have organ dysfunction. On multivariate analysis, after adjusting for age and co-morbids, patients with delayed lactate clearance were 8 times more likely to die than patients with early lactate clearance [aOR = 7.67; 95% CI:1.11-53.26], however, there was no statistically significant association between delayed lactate clearance [aOR = 2.18; 95% CI: 0.87-5.49)] and organ dysfunction. Lactate clearance is a better determinant of sepsis and septic shock effective management. Early lactate clearance is related to better outcomes in septic patients.

A Single-Center Experience With Kidney Transplantation in Patients Who Had Low Left Ventricular Ejection Fraction.

Left ventricular hypertrophy is one of the most typical cardiac abnormalities detected in patients with end-stage renal disease. In patients with congestive heart failure, the most crucial factor determining patient survival is left ventricular ejection fraction. Herein, we present our experience with living donor kidney transplant recipients with a left ventricular ejection fraction of <50%. Patients who underwent living donor kidney transplant in our center between November 2008 and November 2021 and had pretransplant left ventricular ejection fraction <50% were included. All patients had dialysis the day before surgery. All patients underwent 2-dimensional echocardiograms after dialysis and were categorized according to New York Heart Association classification, pretransplant and on posttransplant day 5. Demographic parameters and additional data, including pretransplant and posttransplant day 5 New York Heart Association classification, left ventricular ejection fraction at 6 months, and graft survival at 6 months, as well as patient survival data, were analyzed. Our study included 31 patients (mean age of 46.6 ± 18.3; range, 11-77 years). We found significant differences in New York Heart Association classifications before and after transplant, indicating that kidney transplant had a positive effect on pretransplant congestive heart failure in patients with low left ventricular ejection fraction (P = .001). The mean pretransplant left ventricular ejection fraction was 32 ± 9.9% (range, 1%-45%), whereas the mean 6-month posttransplant left ventricular ejection fraction was 52 ± 8.7% (range, 28%-63%) (P < .001). Both graft loss and all-cause mortality rates were 12.9%. Low left ventricular ejection fraction is not a contraindication for kidney transplant. We suggest that myocardial scintigraphy should be performed in patients with end-stage renal disease and low left ventricular ejection fraction, and kidney transplant should be considered in those without ischemic findings.