Open abdomen (OA) is a surgical strategy used for conditions such as intra-abdominal organ injury, abdominal compartment syndrome, and abdominal sepsis. However, some patients experience severe abdominal adverse events after OA, which can lead to prolonged hospital stays and the failure of primary fascial closure. This study aimed to identify practical predictors of severe abdominal adverse events in patients treated with OA. This post hoc analysis used data from the nationwide, multicenter retrospective OPTITAC study, which included adult patients (≥18years) who had undergone laparotomy requiring OA between 2010 and 2022 across 12hospitals. Severe abdominal adverse events after OA included anastomotic leakage, enteroatmospheric fistula, pancreatic and biliary fistula, and abdominal fascia dehiscence after closure. Predictive factors from preoperative, intraoperative, and postoperative phases were analyzed using generalized estimating equations to account for institutional and regional differences in the management of patients with OA. Of the 302 patients included in this study, 74 (24.5%) experienced severe abdominal adverse events after OA. Higher body mass index (BMI) and receiving <2l fluid resuscitation within 6hours before laparotomy were associated with an increased incidence of severe abdominal adverse events [odds ratios (ORs): 1.06 (1.01-1.18) and 2.39 (1.60-3.57), respectively). In contrast, greater preoperative fluid volume was associated with a decreased incidence of severe abdominal adverse events [OR: 0.73 (0.59-0.91) per 1l increase]. In addition, a fluid balance <2l within 24hours after surgery was associated with abdominal adverse events in patients with nonelevated postoperative serum lactate levels. Low preoperative fluid volume and high BMI were associated with an increased incidence of severe abdominal adverse events in patients undergoing OA. These findings underscore the importance of fluid resuscitation before surgery in patients undergoing OA.

Sepsis secondary to pneumonia is a prominent cause of intensive care unit (ICU)admissions and mortality among older adults, yet early bedside risk stratification poses significant challenges. This study aimed to evaluate the predictive value of the Acute Physiology and Chronic Health Evaluation II (APACHE II)and the National Early Warning Score (NEWS), both individually and in combination, alongside admission serum lactate levels, for predicting mortality in geriatric ICU patients with pneumonia-related sepsis. In this single-center retrospective cohort study, we analyzed patients aged 65 years and older who were admitted between January 1, 2020, and July 1, 2025. Sepsis was defined according to Sepsis-3 criteria; APACHE II (using the worst values within the first 24 hours) and NEWS (measured at ICU admission) were recorded, along with the first lactate and other biomarkers obtained within the first 24 hours. We assessed mortality predictors using logistic regression and evaluated model discrimination through receiver operating characteristic (ROC)analysis. Among the 179 patients (median age 80), the ICU mortality rate was 64.8%. Non-survivors exhibited significantly higher APACHE II and NEWS scores, as well as elevated lactate and inflammatory markers (all p<0.001). In multivariable analysis, APACHE II (OR 1.130; p<0.001), NEWS (OR 1.239; p=0.003), and a history of stroke (OR 2.856; p=0.041) were identified as independent predictors of mortality, whereas lactate did not demonstrate independent predictive capability. Although lactate improved the discrimination of a baseline clinical-laboratory model (AUC increased from 0.67 to 0.75), it offered no incremental benefit when APACHE II and NEWS were included; the combined APACHE II+NEWS model achieved the highest AUC of 0.85. Exploratory cut-offs identified very high-risk subgroups (APACHE II >21 with NEWS >8 or lactate >2 mmol/L), with mortality rates approximating 86-87%. In conclusion, APACHE II and NEWS are robust early predictors of mortality in geriatric patients with pneumonia-related sepsis, while lactate may assist in early risk stratification but provides limited prognostic value beyond these scoring systems.

Subchronic arsenic exposure induced intestinal microbiota dysbiosis and intestinal inflammation via activating the NF-κB signaling pathway.

Mechanisms underlying differential utilization of carbohydrates from diverse structures and sources in Nile tilapia (Oreochromis niloticus): Insights from glycolipid metabolism, protein deposition and liver health.

Rutin and skeletal muscle ischemia-reperfusion injury: Effects of acute treatment.

Sirt3-Bnip3 signaling axis alleviates myocardial ischemia/reperfusion-induced cardiac injury via regulating GSDME.

To compare the effects of intermittent classical blood cardioplegia and single-dose modified Del Nido cardioplegia on postoperative serum lactate levels and extubation time in patients undergoing coronary artery bypass grafts (CABG). An observational study. Place and Duration of the Study:Department of Cardiovascular Surgery, Faculty of Medicine, Kastamonu University, Kastamonu, Turkiye, from 2020 to September 2023. Forty patients who underwent CABG between 2020 and 2023 were randomly divided into two groups. Group 1 formed 20 patients who received intermittent classical blood cardioplegia, and Group 2 formed 20 patients who received single-dose modified Del Nido cardioplegia. Demographic data, bypassed vessels, cardiopulmonary bypass (CPB) time, aortic cross clamp (ACC) time, postoperative drainage, inotrope required and extubation time, glomerular filtration rate (GFR), and serum lactate levels were recorded 2 hours after surgery. The Shapiro-Wilk test was utilised to evaluate the normality of data distribution. The Mann-Whitney U test was employed for variables that did not follow a normal distribution, whereas normally distributed variables were analysed using the independent samples t-test. Additionally, the chi-square test was applied to compare categorical variables across groups. No statistically significant differences were detected between the groups with respect to demographic data, ACC time, CPB time, bypassed vessels, postoperative drainage, inotrope requirement, or GFR. Postoperatively, lactate levels were statistically lower in Group 2 than in Group 1, and extubation time was statistically shorter in Group 2 than in Group 1 (p <0.001). Modified Del Nido cardioplegia reduces postoperative lactate levels and extubation time. Therefore, modified Del Nido cardioplegia provides better patient stability and myocardial protection than the classical blood cardioplegia after CABG. Atherosclerosis, Coronary artery bypass grafting, Mortality.

Gastrointestinal Dysfunction in Critically Ill Patients: A Prospective Observational Study of Frequency, Severity, Risk Factors, and Outcomes.: Gut Dysfunction in Critical Illness.

To evaluate the prognostic performance of the Pediatric Index of Mortality 2 (PIM2), serum lactate, and Pediatric Trauma Score (PTS) for mortality in a large case series of critically ill pediatric trauma patients admitted to a specialized PICU in Brazil. Retrospective case series conducted in the Pediatric Intensive Care Unit of a tertiary trauma hospital in Brazil. All trauma patients aged 1 month to 18 years admitted between March 2018 and March 2025 and hospitalized for >24 h were eligible (n = 1495). Demographic, clinical, and laboratory data were collected, including PIM2, initial lactate, and PTS. The primary outcome was all-cause PICU mortality. Death occurred in 1.5% of patients. ROC curve analysis was performed in 620 patients with complete data for the three markers. Areas under the curve (AUCs) were: PIM2, 0.93 (95% CI, 0.91-0.95); lactate, 0.86 (95% CI, 0.83-0.88); and PTS, 0.82 (95% CI, 0.79-0.85). In univariable logistic regression, all markers were independently associated with mortality. A 10-fold increase in PIM2 and lactate raised death odds by 36-fold and 226-fold, respectively, while each point increase in PTS reduced odds by 34.6%. In the multivariable model, PIM2 and lactate remained significant predictors. In the multivariable model, PIM2 and lactate remained significant predictors. PIM2 and lactate remained independently associated with mortality after mutual adjustment in pediatric trauma patients admitted to a specialized PICU. PTS, while valuable for prehospital triage, added little once intensive care was initiated.

Objective: To investigate the correlation between serum Vitamin B12 levels and inflammatory markers in patients with sepsis. Study Design: Cross-Sectional Study. Place and Duration of Study: Department of General Medicine, Pakistan Emirates Military Hospital, Rawalpindi, Pakistan, from Sep 2024 to Jan 2025. Methodology: Patients of both genders between 18 and 65 years of age who were admitted with sepsis or septic shock were included. Blood samples were drawn on the first and third days of admission for lactate, C-reactive protein, and vitamin B12 levels. The comparison was made between first day and third-day biochemical markers. The patients were labelled as survivors and non-survivors. Results: This study included three hundred and fifteen patients (n=315) with male predominance 184(58.41%). Most patients had gastrointestinal tract infections 120(38.10%) as a source of sepsis, followed by respiratory tract infections 95(30.16%). There were 273(86.67%) survivors and 42(13.33%) non-survivors. There was a statistically substantial (p&lt;0.001) difference between median serum vitamin B12 levels in survivors 892.00 (973.50-823.50) pg/ml and non-survivors 1035.50 (1157.25-926.25) pg/ml, highlighting the raised levels in the non-survivors group. The mortality rate was found to be positively correlated with Vitamin B12 (r=0.293), serum lactate (r=0.128), and CRP levels (r=0.157), highlighting the significant role of these markers in sepsis. Conclusion: Higher vitamin B12 levels are linked to increased mortality in sepsis. Additionally, plasma lactate and C-reactive protein are also significant predictors of outcomes.

Fluid resuscitation in septic shock lacks bedside tools that simultaneously evaluate fluid distribution and cellular function, often leading to fluid overload and increased mortality. Bioelectrical Impedance Vector Analysis (BIVA) is a non-invasive bedside technique for comprehensive assessment of body composition and hydration status, but its prognostic value and application criteria in septic shock remain undefined. A prospective observational study was conducted in an intensive care unit (ICU) of a university-affiliated hospital. Consecutive adult patients meeting Sepsis-3.0 criteria for septic shock were enrolled. BIVA parameters (whole-body and segmental PhA, ECW/ICW ratio, tolerance ellipses), hemodynamic indices, and serum lactate were dynamically monitored at ICU admission (within 24h of diagnosis), 6 hours post-resuscitation (T1), 24 hours (T2), and then daily until ICU discharge or death. Receiver operating characteristic (ROC) curve analysis determined prognostic cutoffs. Spearman's correlation and linear mixed models analyzed BIVA-lactate relationships. Passive leg raising (PLR) test served as the reference for fluid responsiveness, with predictive performance analyzed for mean arterial pressure (MAP) gradient (ΔMAP) between bilateral upper arms at different lateral decubitus positions combined with BIVA parameters. Among 128 enrolled patients, multivariate Cox regression identified initial PhA ≤ 3.10° (Hazard Ratio [HR] = 3.85, 95% Confidence Interval [CI]: 2.12-6.99) and BIVA-derived hydration fraction >74% (HR = 2.41, 95% CI: 1.32-4.39) as independent predictors of 30-day mortality. The Extracellular Water/Intracellular Water ECW/ICW ratio strongly correlated with lactate levels (r = 0.71, p < 0.001), and their combination predicted acute kidney injury more effectively (Area Under the Curve [AUC] = 0.92) than either parameter alone. In 95 patients undergoing positional testing, ΔMAP≥8.00 mmHg at 40°lateral decubitus position predicted fluid responsiveness with 85.7% sensitivity and 84.2% specificity; combining this with upper-arm BIVA parameters further enhanced predictive value (AUC = 0.93). BIVA provides an effective individualized assessment tool for metabolic and fluid management in septic shock. PhA and hydration status are robust prognostic indicators; the ECW/ICW-lactate correlation reveals the pathophysiological link between tissue edema and hypoperfusion; and positional BIVA testing with upper-arm pressure gradient offers an innovative method for non-invasive assessment of fluid responsiveness.

Utilisation of nicardipine in the neonatal and infant period has been historically avoided due to a concern for a more calcium-sensitive myocardium. The aim of this study was to characterise the association between nicardipine and systolic blood pressure in neonates and infants after cardiac surgery. In this single-centre, retrospective study, patients under 12 months of age who underwent cardiac surgery and received nicardipine for at least one hour were included (September 2022 to January 2024). Patients were monitored with Etiometry. Variables of interest included haemodynamic parameters, ionised calcium, serum lactate, vasoactive infusion score, and nicardipine dose. A time series regression was conducted with each patient having 5 distinct time points. One hundred and eighty-five time points were collected across 37 patients with a mean age of 3 months. Of these patients, 22% were neonates and 32% were functionally univentricular. With nicardipine utilisation, a decrease in systolic blood pressure of 14 mmHg after an 8-hour time period was noted (p = 0.017). Heart rate, diastolic blood pressure, cerebral and renal oxygen extraction, ionised calcium, serum lactate, and vasoactive inotrope score did not significantly change over the study period. Nicardipine utilisation in neonates and infants after cardiac surgery was associated with decreased systolic blood pressure. Indirect markers demonstrate no change in cardiac function. Additional studies are needed to better elucidate nicardipine's role in this patient population.

Immune deficiency and dysregulation (IDD)-associated classical Hodgkin lymphoma (cHL) is one of the common subtypes of IDD-related lymphomas. Patients with IDD-cHL are typically treated with the same chemotherapeutic regimens as those with sporadic cHL. However, the clinical differences between these groups remain poorly elucidated. To assess the impact of immune status on clinical features and treatment outcomes, 44 patients who were newly diagnosed with cHL and treated at our institution, including 12 with IDD-cHL, were retrospectively analyzed. Epstein-Barr virus-encoded small RNA positivity was significantly more common in patients with IDD-cHL than in those with sporadic cHL. Nevertheless, the baseline laboratory parameters did not significantly differ between the two groups. Patients with IDD-cHL had significantly higher rates of neutropenia than those with sporadic cHL, resulting in reduced relative dose intensity. However, the two groups were similar in terms of complete response and progression-free survival rates. Based on a prognostic analysis, serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) levels were associated with prognosis. However, their prognostic implications were contrasting in the two immune status groups. To integrate these markers, the prognostic value of the sIL-2R-to-LDH ratio (cutoff: 3.58) was evaluated. A higher ratio was significantly associated with poorer prognosis in sporadic cHL (p < 0.01). Meanwhile, in IDD-cHL, a lower ratio was associated with worse outcomes (p = 0.07). According to these findings, the overall clinical presentation of cHL and the efficacy of its treatment are significantly consistent regardless of immune status. However, the prognostic significance of specific biomarkers is distinct. The sIL-2R-to-LDH ratio may represent a broadly applicable prognostic marker, and its interpretation should be adapted according to the patient's immune background.

Background and Objectives: Pneumonia is a leading cause of intensive care unit (ICU) admission and is associated with high mortality, particularly among patients with multiple comorbidities. Accurate early risk stratification is essential for guiding clinical decision-making in critically ill patients. However, the prognostic benefit of combining clinical scoring systems with nutritional and endothelial stress indices in ICU patients with pneumonia remains unclear. Materials and Methods: This retrospective, single-center cohort study included adult patients admitted to the ICU with a diagnosis of pneumonia between 1 January 2023 and 1 July 2025. Demographic characteristics, comorbidities, clinical variables, laboratory parameters, and prognostic scores were obtained from electronic medical records. The National Early Warning Score (NEWS), Prognostic Nutritional Index (PNI), and Endothelial Activation and Stress Index (EASIX) were calculated at ICU admission. The primary outcome was in-hospital mortality. Univariate and multivariate logistic regression analyses were performed to examine variables associated with in-hospital mortality. The discriminative performance of individual and combined prognostic models was evaluated using receiver operating characteristic (ROC) curve analysis. Results: A total of 221 patients were included; 79 (35.7%) survived and 142 (64.3%) died during hospitalization. Non-survivors had significantly higher NEWS and EASIX values and lower PNI values compared with survivors (all p < 0.05). In multivariate analysis, endotracheal intubation (OR: 12.46; p < 0.001), inotropic use (OR: 5.14; p = 0.001), and serum lactate levels (OR: 1.75; p = 0.003) were identified as being independently associated with in-hospital mortality. Models combining NEWS with PNI or EASIX demonstrated improved discriminatory performance. Conclusions: In critically ill patients with pneumonia, integrating NEWS with nutritional and endothelial stress indices provides numerically improved discrimination compared with NEWS alone, although the incremental gain did not reach statistical significance.

Serum lactate dehydrogenase (LDH) is a recognized prognostic biomarker in human lymphomas, yet its clinical significance in canine lymphoma remains insufficiently characterized. This study aimed to quantify serum LDH levels in healthy dogs and dogs with high-grade multicentric lymphoma (ML) (predominantly B-cell) and to investigate correlations between LDH levels and established clinical and laboratory prognostic indicators. Twenty-seven dogs were prospectively enrolled: healthy controls (G1, n = 7) and dogs with high-grade ML (G2, n = 20). Immunophenotyping was performed by immunohistochemistry (CD3/CD79a). LDH concentrations were measured at diagnosis (T0) and after six weeks of CHOP-based induction chemotherapy (T1). Statistical analyses included Kruskal-Wallis, Wilcoxon signed-rank, Pearson's correlation, and mixed-effects models. Dogs with high-grade ML exhibited significantly elevated LDH levels compared to controls (median 545.5 U/L, range: 288.2-2816 U/L vs. 143 U/L, range: 66-272; p < 0.001). Dogs with thrombocytopenia had higher baseline LDH (median 746 U/L, range: 612-921; p = 0.006) and greater reductions following chemotherapy (median -1011.7 U/L, range: -159 to -2064; p = 0.004). LDH levels declined significantly after treatment (overall median reduction 50.7%; post-chemotherapy range: 60.4-752 U/L; n = 15; p = 0.013), with normalization achieved in 77.8% of dogs with complete response versus 16.7% with partial or progressive disease (p = 0.02). We confirmed that serum LDH is significantly elevated in dogs with high-grade ML and declines following effective chemotherapy, supporting its utility as a dynamic biomarker of tumor burden and treatment response. Thrombocytopenic dogs may represent a biologically distinct subset warranting further investigation.

As a natural flavonoid, the flavonoid luteolin is characterized by its powerful antioxidant and anti-inflammatory effects. While its precise mechanisms require further elucidation, existing evidence confirms its efficacy in ameliorating myocardial ischemia-reperfusion injury (MIRI). This research was designed to investigate the mechanism through which luteolin protects against MIRI. We established MIRI rat models through the ligation of left anterior descending coronary artery (LAD). To evaluate the cardioprotective effects of luteolin, echocardiographic analysis was performed, Hematoxylin and Eosin (HE) staining, and serum cardiac injury markers creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Cardiac vascular permeability was determined using Evans blue staining. To mimic ischemia-reperfusion injury, endothelial cells (ECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Endothelial cell barrier function was evaluated through F-actin phalloidin staining and FITC-Dextran fluorescence leakage experiments. To elucidate the molecular mechanism, FOXP1 small interfering RNA (siRNA) and NLRP3 inhibitor MCC950 were administered. In MIRI rats, luteolin significantly improved cardiac function and preserved endothelial barrier integrity. These effects were associated with upregulation of FOXP1 and suppression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. In OGD/R-treated endothelial cells, luteolin restored barrier function and cell viability. The protective effects of luteolin were abolished after FOXP1 silencing. Pharmacological NLRP3 inhibition (MCC950) mirrored luteolin's protection. Our study indicates that luteolin enhances endothelial barrier function and attenuates MIRI via the FOXP1-NLRP3 pathway. The current study provides a potential drug for MIRI treatment.

To determine whether baseline ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) radiomic markers of thoracic tumor burden and metabolic heterogeneity predict early progression and overall survival (OS) in patients with small cell lung cancer (SCLC) receiving first-line platinum-etoposide chemotherapy. We retrospectively analyzed 45 patients with SCLC who underwent baseline ¹⁸F-FDG PET/CT before chemotherapy. Radiomic features were extracted from thoracic tumor volumes, including metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized uptake value (SUV) histogram parameters, and gray-level co-occurrence matrix (GLCM) metrics. Univariable and multivariable Cox regression assessed associations with progression-free survival (PFS) and OS. Receiver operating characteristic (ROC) analysis, with area under the ROC curve (AUC), assessed discriminatory ability for early progression (PFS < 6 months) and short-term mortality (OS < 12 months). Higher log-transformed TLG (logTLG) was correlated with shorter PFS and OS in univariable analysis. In multivariable models, logTLG independently predicted PFS (hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.12-4.30; p = 0.021) and OS (HR 2.54, 95% CI 1.24-5.20; p = 0.011). Age (HR 1.07 per year; 95% CI 1.02-1.12, p = 0.007) and stage IV vs. III (HR 2.46, 95% CI 1.06-5.71; p = 0.037) were additional OS predictors. GLCM texture features were not significant. ROC analysis showed MTV (AUC 0.88) and serum lactate dehydrogenase (LDH) (AUC 0.74) best predicted early progression, while age (AUC 0.79), stage (AUC 0.73), and SUV entropy (AUC 0.75) predicted short-term mortality. Kaplan-Meier curves confirmed poorer survival with high logTLG, advanced stage, and older age. Baseline thoracic PET/CT radiomics, particularly logTLG, independently predict survival in SCLC. MTV and LDH identify early progression, while age, stage, and SUV entropy predict short-term mortality, supporting integrated imaging-clinical risk stratification.

Trauma induces a "genomic storm" of gene expression in circulating leukocytes. We hypothesized that the neutrophil contribution to this response after blunt trauma varies with the magnitude of physiologic insult. Blunt trauma patients had blood samples taken at 0 hour, 8 hours, 24 hours, and 72 hours postinjury. Clinical data on injury pattern, treatment, and outcomes were collected. Circulating neutrophils were isolated for whole transcriptome RNAseq. Over the 72-hour study period, differentially expressed genes were compared in trauma patients with and without admission lactate levels ≥3 mmol/L. Clinical outcomes and plasma effectors of neutrophil function were correlated with transcriptomic signatures. Nineteen patients were enrolled (median Injury Severity Score, 25; interquartile range, 14-36) with 14,517 genes analyzed. Admission serum lactate correlated with Injury Severity Score, organ failure at 72 hours postinjury, and distinct transcriptional changes, with 108 genes differentially expressed in neutrophils of high vs. low admission serum lactate patients. Top biological processes associated with high admission lactate included cAMP response element binding protein, rat sarcoma viral oncogene homolog/mitogen-activated protein kinase and nitric oxide pathways. Differentially expressed genes were clustered by dynamic expression. The largest cluster of differentially expressed genes in high vs. low admission lactate patients was associated with multiple pathways involved in neutrophil migration and extravasation. Similar to septic shock, the expression of a proinvasive transcriptional transcriptome was identified following injury and was most pronounced in patients with high admission serum lactate. Cell type-specific analysis teases out the time- and insult-dependent neutrophil signal from the circulating leukocyte "storm." Neutrophil activation by severe trauma induces a proinvasive transcriptome signal, a potential link between the circulating and tissue phenotypes associated with poor clinical outcomes. Translational Prospective Cohort Study; Level IV.

Background/Objectives: Lactate, traditionally considered a byproduct of anaerobic metabolism, is increasingly recognized as a biomarker of tissue perfusion and systemic stress. While hyperlactatemia is frequent after pediatric cardiac surgery, evidence regarding its prognostic role remains controversial. This study aimed to evaluate whether serial lactate measurements predict mortality in children undergoing surgery for congenital heart disease in Southeast Mexico. Methods: We conducted a retrospective cohort study including children aged 0–210 weeks with confirmed congenital heart disease who underwent first-time cardiac surgery between January 2022 and December 2024. Serum lactate was measured intraoperatively, at intensive care unit (ICU) admission, and at 12 and 24 h postoperatively using a Gem® Premier™ 3500 analyzer. Sociodemographic, clinical, and surgical data were recorded. Associations between lactate levels and mortality were analyzed with Cox regression, adjusting for RACHS-2 category and intraoperative complications. Predictive performance was assessed with ROC curves and Harrell’s C-index. Results: 103 patients were included (median age 49.2 weeks; 60% female). Lactate levels overlapped intraoperatively but significantly discriminated against survivors from non-survivors thereafter. ICU admission lactate ≥ 4.2 mmol/L predicted mortality with 100% sensitivity and 60% specificity (AUC = 0.84). Hazard ratios confirmed that lactate at ICU admission (HR 2.17, 95% CI 1.16–4.06; p = 0.015), 12 h (HR 6.37, 95% CI 1.02–39.6; p = 0.047), and 24 h (HR 1.81, 95% CI 1.07–3.09; p = 0.028) were significant predictors of mortality. The model showed excellent discrimination (Harrell’s C = 0.986), though optimism due to the limited number of deaths should be considered. Conclusions: Serial lactate monitoring, particularly upon ICU admission, provides strong prognostic information for in-hospital mortality in pediatric cardiac surgery patients. Incorporating early postoperative lactate into routine monitoring may allow timely therapeutic adjustments. Preoperative lactate assessment warrants further evaluation as a potential risk stratification tool.

To identify pretreatment factors associated with developing primary resistance to nivolumab plus ipilimumab therapy in patients with advanced renal cell carcinoma (RCC). We retrospectively reviewed the clinical characteristics, laboratory data, and tumor-related factors in patients with advanced RCC who initiated nivolumab plus ipilimumab as first-line therapy between January 2018 and July 2021. Primary resistance was defined as radiographic or clinical progression within 3months of treatment initiation. Cases with suspected pseudoprogression were excluded. Eighty-nine patients met the inclusion criteria; 23 exhibited primary resistance. Univariate analysis identified the following significant predictive factors: body mass index (P=.006), lymph node metastasis (P=.021), sarcomatoid differentiation (P=.035), solitary metastatic organ (P=.051), liver metastasis (P=.056), and serum lactate dehydrogenase (LDH) (P=.094). Receiver operating characteristic curve analysis determined an LDH cutoff value of 174U/L, which was significantly associated with primary resistance (P=.029). Considering the number of primary resistance cases, multivariable analysis incorporated three candidate variables (lymph node metastasis, sarcomatoid differentiation, and LDH≥174U/L) and identified sarcomatoid differentiation (odds ratio, 4.264; 95% confidence interval (CI), 1.299-14.825; P=.017) and LDH≥174U/L (odds ratio, 3.634; 95% CI, 1.143-13.770; P=.028) as independent predictors of primary resistance. Sarcomatoid differentiation on pretreatment biopsy or elevated serum LDH before treatment initiation may predict primary resistance to nivolumab plus ipilimumab therapy in patients with advanced RCC. Alternative regimens should be considered in such cases, particularly for patients who are likely to experience rapid disease progression or for whom the occurrence of P-res is not clinically acceptable.