Predictors Of Outcome Research Articles

Risk Factors for ARDS in Hospitalized Burn Patients: An Analysis of the National Trauma Data Bank.

Acute Respiratory Distress Syndrome (ARDS) is a common complication among mechanically ventilated adult burn patients; however, the risk factors associated with its development are not well understood. Conflicting evidence also exists regarding ARDS as an independent predictor of poor hospital outcomes. The purpose of this study is to identify risk factors for ARDS in mechanically ventilated adult burn patients and characterize the impact of ARDS on hospital course. The National Trauma Data Bank (NTDB) was queried for patients >=18 years with International Classification of Diseases (ICD) codes corresponding to burn injury from 2007-2016. Hospitalized patients with at least 48 hours of mechanical ventilation were included. Multivariate logistic regression were used to identify risk factors for ARDS. Propensity score-matched analysis at a 1:3 ratio was used to determine the impact of ARDS on hospital course. This sample included 13928 patients, of which 1437 (10.3%) developed ARDS. Hypotension in the Emergency Department, alcohol use disorder, total body surface area (TBSA), Injury Severity Score (ISS), and inhalation injury were independently associated with ARDS. In the propensity score-matched cohort, ARDS patients had a significantly longer median (interquartile range) length of stay (31 [15-54] vs. 22 [9-43], p<0.001). In-hospital mortality was also significantly higher in the ARDS cohort (203 [35%] vs. 325 [24%], p<0.001). These findings highlight the impact of patient and injury characteristics on developing ARDS and support the consideration of ARDS when estimating mortality risk in burn patients.

Preoperative Tumor Growth Rate Does Not Predict Overall or Progression-free Survival in Patients With Glioblastoma.

Presurgical tumor volume progression in glioblastoma (GBM) may be a predictor of survival. This study aims to evaluate the potential impact of preoperative tumor growth and other clinical as well as laboratory parameters on overall survival (OS) of GBM patients. We retrospectively analyzed 98 adult patients with GBM who received two magnetic resonance imaging (MRI) scans between 2013 and 2023, before primary surgery and concurrent Stupp chemoradiotherapy. Tumor growth rates were calculated to classify GBM into slower and faster growing categories. Statistical analyses, including Kaplan-Meier and multivariable Cox regression survival analyses, were performed to evaluate the impact of various clinical and treatment-related factors on OS and progression-free survival (PFS). Slower growing tumors had a significantly longer doubling time than faster growing lesions. Univariable analysis showed no significant differences in OS (p=0.12) or PFS (p=0.4) when analyzed according to tumor growth. When stratified by O6-methylguanin-DNA-methyltransferase (MGMT) status, there were still no differences in OS (p=0.14), but in PFS (p=0.009). In the multivariable Cox regression analysis, radiation dose (p=0.02) and the number of adjuvant cycles of temozolomide (TMZ) (p=0.002) were significantly associated with OS. MGMT status (p=0.02) and the number of adjuvant TMZ cycles (p<0.001) were significantly associated with prolonged PFS. Specific volume growth rate (SVGR), patient age, baseline tumor volume, Karnofsky performance status, extent of resection, and total radiation dose were not significantly associated with PFS. SVGR was not significantly associated with OS or PFS. In contrast, MGMT status, radiation dose, and number of adjuvant TMZ cycles were identified as predictors of treatment outcomes. These factors can guide physicians when designing personalized treatment concepts for patients with GBM.

Neutrophil-to-lymphocyte ratio predicts poor prognosis in patients with chronic kidney disease-related pulmonary hypertension: A retrospective study.

Inflammation plays a crucial role in chronic kidney disease (CKD) and pulmonary hypertension (PH). Considering that the neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a powerful predictor of adverse outcomes in many chronic diseases, we aimed to investigate the association between NLR and all-cause mortality in patients with CKD-related PH. A total of 176 hospitalized patients with predialysis CKD-related PH were recruited retrospectively from January 2012 to June 2020 by reviewing electronic medical records. The NLR and clinical characteristics of the patients were included in the current analysis. The Kaplan-Meier method and univariate and multivariate Cox regression analyses were performed to identify the association between NLR and the incidence of all-cause mortality. Baseline NLR values were associated with hemoglobin, estimated glomerular filtration rate and C-reactive protein. During a median follow-up period of 32.5 (11.3-53.0) months, 23 patients died. Regardless of whether the NLR acted as a continuous variable with a hazard ratio of 1.408 (95% confidence interval: 1.124-1.763) or a categorical variable (NLR ≤4.3 vs NLR >4.3) with a hazard ratio of 3.100 (95% confidence interval: 1.299-7.402), an elevated NLR was significantly associated with all-cause mortality in different models. A greater NLR at baseline was remarkably associated with a higher all-cause mortality in hospitalized patients with CKD-related PH.

Low skeletal muscle density assessed by abdominal computerized tomography predicts outcome in children with chronic kidney disease.

Skeletal muscle loss and abnormal fat distribution are predictors of poor clinical outcomes in adults with chronic kidney disease (CKD). However, the relationship between body composition (muscle mass and adipose tissue) and prognosis in children with CKD has not been well elucidated. The retrospective single-center study enrolled children with CKD and healthy group who underwent an abdominal Computerized tomography (CT) examination and compared the body composition of the third lumbar spine (L3) between the two groups. We defined the primary outcome as hemodialysis, peritoneal dialysis, kidney transplantation, or death. Logistic regression analysis was applied to assess the connection between low skeletal muscle density (SMD) and clinical and demographic variables. Multivariate Cox regression analysis was used to evaluate the risk factors for progression to the primary outcome. Kaplan-Meier survival analysis was performed to compare the effect of different body composition on event-free survival rate. 32 patients with CKD [eGFR: 14.89(8.86, 29.88) (mL/min/1.73m2)] and 66 heathy subjects [eGFR: 135.72(121.70, 161.29) (mL/min/1.73m2)] were recruited in our study. From the assessment of body composition assessed by CT, skeletal muscle area, SMD and skeletal muscle index (SMI) in CKD group was lower than those in healthy group (P<0.05). On the other hand, visceral fat area and visceral fat index in CKD group were significantly higher than those in healthy group (P<0.05). In logistic regression analysis, triglyceride (OR: 8.635, 95%CI: 1.153-64.687) was independently associated with low SMD. After adjusting clinical data and body composition, high serum albumin (HR: 0.873, 95%CI: 0.798-0.955) and high SMD (HR: 0.895, 95%CI: 0.822-0.974) were protective factors for delaying renal failure. Based on the Kaplan-Meier analysis, only the group with low SMD had lower event-free survival in comparison to the reference group (P<0.05). These findings suggest that there is significant skeletal muscle loss and decrease in SMD in CKD children. Notably, low SMD is indicative of poor prognosis in CKD children.

Transitioning to fatherhood: Prospective effects of wellbeing on future depression symptoms.

Becoming a father is a critical period of life transition. Evidence suggests that lifetime history of mental health disorder/s and elevated depressive symptoms prior to conception increase risk for men's postnatal depression. Less is understood about the role of positive mental health, or wellbeing, as a protective factor for future depressive outcomes during the transition to fatherhood. The present study investigated whether men's post-natal depressive outcomes were associated with pre-conception levels of wellbeing and whether wellbeing during the post-natal period predicted depressive outcomes post-infancy. Secondary analysis of data from a national, longitudinal cohort study of men's health, namely, The Ten to Men Study (TTM), was conducted. Participants in the pre-conception sample were n = 350 men for whom data were available at both a pre-conception baseline and post-natal follow-up. The post-natal sample were n = 427 men with post-natal baseline data and post-infancy follow-up. Multivariate negative binomial regressions and logistic regression models were used to determine pre-conception and post-natal predictors of future depressive outcomes. Men's pre-conception depressive symptoms were the best predictor of post-natal depressive symptoms (IRR = 1.089, p < 0.001) and risk of moderate-severe depression (IRR = 1.193, p = 0.005) the latter of which was also predicted by a previous mental health diagnosis (IRR = 3.079, p = 0.029). Similarly, post-natal depressive symptoms were the best predictor of post-infancy depressive symptoms (IRR = 1.089, p < 0.001) and risk of moderate-severe depression (IRR = 1.193, p = 0.005) alongside lifetime prevalence of a mental health disorder (symptoms: IRR = 1.317, p = 0.011; moderate-severe depression: IRR = 2.606, p = 0.023). Preconception levels of wellbeing predicted lower post-natal depressive symptoms (IRR = 0.988, p < 0.001) and reduced risk of moderate-severe depression (IRR = 0.940, p = 0.002) after controlling for baseline symptoms and sociodemographic and behavioural confounds; however, wellbeing during the post-natal period did not predict either depressive outcome post-infancy. Fatherhood-specific risk factors for mental health outcomes (e.g., conception difficulties, maternal postnatal mental health) were not assessed in the present study, and only one aspect of wellbeing was captured. Screening for history of common mental health disorders and current symptoms is recommended to inform preventative approaches to paternal mental health care during early fatherhood. Inclusion of wellbeing in such screening procedures may be beneficial, however, further research is required to elucidate the prospective associations between wellbeing and depressive symptoms during the transition to fatherhood.

NOVEL DRUG COMBINATIONS AND DONOR LYMPHOCYTE INFUSIONS ALLOW PROLONGED DISEASE CONTROL IN MULTIPLE MYELOMA PATIENTS RELAPSING AFTER ALLOGENEIC TRANSPLANT: New treatments for Multiple Myeloma patients relapsing after Allo transplant

BackgroundEven if allogeneic stem cell transplantation (allo-SCT) is curative for a minority of patients with multiple myeloma (MM), the patients who have relapsed after allo-SCT can experience long-term survival, suggesting a synergy between anti-myeloma drugs administered after allo-SCT and donor T cells. ObjectivesWe retrospectively evaluated the outcome of MM patients reported to the “Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare” (GITMO) network, who underwent allo-SCTs between 2009 and 2018 in order to identify predictors for long-term outcome in the whole population (242 patients) and for prolonged overall survival (OS) after relapse in the subgroup of relapsed patients (118 patients). ResultsAt a median follow-up of 40.9 months after allo-SCT median OS and progression free survival (PFS) of the whole population were respectively 39.4 and 19.0 months from allo-SCT. The cumulative incidence (CI) of non-relapse mortality (NRM) was 10.3 % at one year and 27.6% at five years. Grade 2-4 acute GVHD CI was 19.8% and 5-year CI of moderate or severe chronic GVHD was 31.8%. In the multivariate model older age at transplant (p=0.020), treatment with more than 2 lines of therapy before allo-SCT (p=0.003) and transplant from unrelated or haploidentical donor (p=0.025) were significant factors associated with reduced OS. Relapse after allo-SCT occurred in 118 (59%) patients at a median of 14.3 months (IQR 7.2-26.9). Twenty (17%) received only steroids, radiotherapy or supportive care, 41 (35%) received 1 line, 23 (19%) 2 lines and 34 patients (29%) 3 or 4 lines of salvage treatment. Nine patients were exclusively treated with chemotherapy, 9 received at least one salvage treatment including immunomodulating agents (Imids), 43 patients were treated with at least one rescue therapy including proteasome inhibitors (PIs) and 37 patients received at least one salvage treatment including monoclonal antibodies (33 daratumumab, 1 elotuzumab, 1 isatuximab, 2 belantamab). Median OS of relapsed patients was 38.5 months from allo-SCT and 20.2 months from relapse. In multivariate analysis, OS after relapse was significantly prolonged in patients with a longer time to relapse after allo-SCT (time to relapse 6-24 months p=0.016; time to relapse ≥ 24 months p< 0.001) and in those who had received at least 3 salvage treatment lines (p<0.036) and donor lymphocyte infusions (DLI) (p=0.020). ConclusionsIn our study, patients transplanted in early phases of disease and with HLA identical sibling donors had the best chance of long-term survival. Late relapse after allo-SCT, multiple courses of salvage treatment and the association with DLI could allow long disease control in patients who experienced relapse after allo-SCT.

Critical care EEG monitoring in children with abusive head trauma: a retrospective study of seizure burden and predictors of neurological outcomes

Critical care EEG monitoring in children with abusive head trauma: a retrospective study of seizure burden and predictors of neurological outcomes

The Preoperative Patient-Reported Outcomes Measurement Information System (PROMIS)-10 Global Mental Health T-Score: An Independent Predictor of Immediate Post-Surgical Outcomes Following Elective Total Knee Arthroplasty

The Preoperative Patient-Reported Outcomes Measurement Information System (PROMIS)-10 Global Mental Health T-Score: An Independent Predictor of Immediate Post-Surgical Outcomes Following Elective Total Knee Arthroplasty

Lower urinary tract symptoms (LUTS) as a clinical feature of lumbar spinal stenosis (LSS): a prospective study with lumbar spine morphometry analysis

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To investigate clinical and morphometric characteristics of patients with lower urinary tract symptoms (LUTS) due to lumbar spinal stenosis (LSS).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; This study evaluated LSS patients using clinical assessments of motor, sensory, bladder, and bowel functions, and functional disability scores from the Oswestry Disability Index (ODI) and Swiss Spinal Stenosis Questionnaire (SSSQ). Morphometric analysis included MRI measurements of the anteroposterior diameter of the intervertebral disc and dural sac, and the modified Torg-Pavlov ratio (mTPR), with follow-up re-evaluations at 6 months.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; Of 159 patients, 49 (30.8%) had LUTS and 110 (69.2%) were in the control group. LUTS patients had a significantly higher prevalence of neurogenic claudication (100% vs. 47.3%; p&amp;amp;lt;0.001), lower back pain (93.9% vs. 77.3%; p=0.011), and lower extremity pain (57.1% vs. 34.5%; p=0.008). The LUTS group also had higher ODI (54.0 vs. 50.0; p=0.019) and SSSQ score (44.0 vs. 34.0; p&amp;amp;lt;0.001). Morphometric analysis showed significantly lower mTPR in LUTS patients (median 0.31 vs. 0.45; p&amp;amp;lt;0.001), with an AUC of 0.704 (95%CI 0.627-0.774). mTPR&amp;amp;le;0.31 predicted surgical revision within 6 months (OR:3.4, CI: 1.2-9.8), motor deficiency (OR:2.1, 95%CI: 1.4-5.2), and persistent LUTS post-surgery (OR:4.5, 95%CI: 1.1-18.9). mTPR&amp;amp;le;0.34 was associated with worse follow-up outcome, including increased ODI (&amp;amp;beta;:3.2; 95%CI: 1.1-5.3; p=0.004) and SSSQ score (&amp;amp;beta;:4.8; 95%CI:2.1-7.5).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; LUTS patients with LSS exhibit more severe symptoms and poorer outcome, with mTPR&amp;amp;le;0.34 being a predictor of adverse clinical outcome and the need for surgical revision within 6 months.&amp;lt;/p&amp;gt;

Plate Osteosynthesis of Proximal Humerus Fracture is Associated with Significant Complications and Poor Functional Score for Patients Older than 45 Years Old: A Cohort Study

BackgroundDespite the introduction of new implants and biomechanical improvements for proximal humerus fractures (PHF), the complication rate remains significant, particularly in older adults. This study aimed to identify risk factors for complications and failure following plate osteosynthesis for PHF and discuss an age cut-off that surgeons should consider for complications. MethodsAdults with PHF treated with the proximal humerus internal locking system (PHILOS) at our large tertiary academic referral center between 2015 and 2020 were retrospectively identified. Univariate analysis was used to compare patients with and without complications. Then, a multivariate regression analysis was conducted to assess the possible complication risk factors. The receiver operating characteristic (ROC) curve of age was drawn to predict complication-free and favorable functional outcomes at the most recent follow-up. Oxford Shoulder Score (OSS) was considered favorable if OSS<10. ResultsA total of 135 patients were identified, with a mean age of 44 years (range 18-85 years) and a mean follow-up duration of 4.6 years (range 2-8 years). Complications were observed in 19 cases (14.1%), namely nonunion (n=5), avascular necrosis (n=1), infection (n=1), intra-articular screw perforation (n=1), arthritic changes (n=5), and superior humeral head migration (n=5). Eight patients (5.9%) needed revision surgery. Older age (OR=1.09) and Neer IV class (OR= 8.3) were associated with an increased likelihood of complication (P<0.001, P=0.02, respectively) in logistic multinominal regression analysis. The ROC curve for age in predicting complication-free cases had an area under the curve (AUC) of 0.829, indicating age as a significant predictor of ORIF outcomes in PHF (P<0.05). The optimalcut-off for age was 44 years, which yielded a sensitivity of 100% and a specificity of 65.7. The age ROC curve for predicting favorable OSS (OSS<10) had an of 0.829, indicating that age could predict the favorable OSS outcomes of ORIF in PHF. The optimal age cut-off was 46 years, yielding a sensitivity of 70.0% and a specificity of 78.6%. ConclusionThe outcomes of ORIF for PHF in patients older than 45 years are associated with significantly higher complication rates and poorer functional outcomes. Surgeons should possibly consider other treatment options for PHF in each older patient individually, especially with Neer type IV fractures.

Preoperative Prediction of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors Using a Combined CT Radiomics-Clinical Model.

PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs). An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally. Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2cm). Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible.

Growth velocity of fetal sacrococcygeal teratoma as predictor of perinatal morbidity and mortality: multicenter study.

To identify prenatal predictors of poor perinatal outcome in fetuses with isolated sacrococcygeal teratoma (SCT). This was a retrospective study of fetuses with isolated (non-syndromic) SCT managed at one of five pediatric surgery and/or fetal medicine centers between January 2007 and December 2017. The primary outcome was the occurrence of poor perinatal outcome, defined as prenatal death (including termination), or neonatal death or severe compromise (hemorrhagic shock). Data regarding prenatal diagnosis (sonographic features both at referral and at the last ultrasound examination before pregnancy outcome, assessment of SCT growth velocity), perinatal complications and outcome, and neonatal course were analyzed to determine prenatal SCT characteristics associated with adverse perinatal outcome. Fifty-five fetuses were included, diagnosed with isolated SCT at a median gestational age of 22 (interquartile range, 18-23) weeks. There was a poor perinatal outcome in 31% (n = 17) of these cases, including intrauterine fetal demise (4%, n = 2), pregnancy termination (13%, n = 7) and neonatal severe compromise (15%, n = 8), leading to neonatal death in five cases. The overall survival rate after prenatal diagnosis of isolated SCT was 75% (n = 41 of 55). Earlier gestational age at diagnosis (P = 0.02), large tumor volume at referral (P < 0.001), presence of one or more hemodynamic complications (P = 0.02), fast tumor growth velocity (P < 0.001) and high tumor grade (highest tumor grade ≥ 3) (P = 0.049) were associated with poor perinatal outcome on univariate analysis. On stepwise logistic regression analysis, tumor growth velocity was the only remaining independent factor associated with poor perinatal outcome (odds ratio (OR) (per 1-mm/week increase), 1.48 (95%CI, 1.22-1.97), P = 0.001). The best predictive cut-off of tumor growth velocity for poor perinatal outcome was 7 mm/week (OR, 25.7 (95%CI, 5.6-191.3), P < 0.001), yielding a sensitivity of 88% and a specificity of 77%. Approximately 30% of fetuses with a diagnosis of isolated SCT have poor perinatal outcome. Tumor growth velocity ≥ 7 mm/week appears to be an appropriate discriminative cut-off for poor perinatal outcome. These results could help to inform prenatal management and counseling of parents with an affected pregnancy. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

С-РЕАКТИВНЫЙ БЕЛОК КАК ПРЕДИКТОР НЕОБРАТИМОГО ПОВРЕЖДЕНИЯ ГОЛОВНОГО МОЗГА

Background. As for now, the level of C-reactive protein (CRP), which may be present in donors with traumatic and non-traumatic brain injuries, has not been reliably established, and its dynamics in patients upon the occurrence of brain death (BD) have not been studied. Objective of this study is to investigate the dynamics of CRP levels in patients with severe irreversible brain damage, which subsequently led to brain death. Material and methods. The prospective study included 106 patients with severe brain damage who were diagnosed with BD despite treatment. The CRP level was determined for patients on the 1st to 10th days of intensive therapy. Results. The CRP level upon admission to the ICU was 13.3 (3.86; 29.1) mg/l. CRP values were within normal limits only in 14 (13.2%) patients. On the 2nd day of intensive therapy, the level of CRP was higher statistically significant – 85 (45.4; 140.6) mg/l, p =0.00004 vs 1 day. On the 3rd day of intensive therapy, the level of CRP was also higher statistically significant – 135.3 (73.6; 238.2) mg/l, p =0.00001 vs 2 days. The CRP values in all patients were higher than the reference values. On the 4th day, the level of CRP in patients became 219.7 (112.7; 326.4) mg/l (p=0.00006 vs 3 days) and did not significantly change in the following days in terms of statistics. Conclusion. The dynamics of CRP levels in patients with severe brain damage can be used as a predictor of unfavorable outcome of intensive care and brain death.

Surgical Predictors of Clinical Outcome 6 Years After Revision ACL Reconstruction

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown. Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient’s outcome at 6-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Patients who underwent revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline patient characteristics, surgical technique and pathology, and a series of validated patient-reported outcome instruments: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) subjective form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity rating score. Patients were followed up for 6 years and asked to complete the identical set of outcome instruments. Regression analysis was used to control for baseline patient characteristics and surgical variables to assess the surgical risk factors for clinical outcomes 6 years after surgery. Results: A total of 1234 patients were enrolled (716 men, 58%; median age, 26 years), and 6-year follow-up was obtained on 79% of patients (980/1234). Using an interference screw for femoral fixation compared with a cross-pin resulted in significantly better outcomes in 6-year IKDC scores (odds ratio [OR], 2.2; 95% CI, 1.2-3.9; P = .008) and KOOS sports/recreation and quality of life subscale scores (OR range, 2.2-2.7; 95% CI, 1.2-4.8; P < .01). Use of an interference screw compared with a cross-pin resulted in a 2.6 times less likely chance of having a subsequent surgery within 6 years. Use of an interference screw for tibial fixation compared with any combination of tibial fixation techniques resulted in significantly improved scores for IKDC (OR, 1.96; 95% CI, 1.3-2.9; P = .001); KOOS pain, activities of daily living, and sports/recreation subscales (OR range, 1.5-1.6; 95% CI, 1.0-2.4; P < .05); and WOMAC pain and activities of daily living subscales (OR range, 1.5-1.8; 95% CI, 1.0-2.7; P < .05). Use of a transtibial surgical approach compared with an anteromedial portal approach resulted in significantly improved KOOS pain and quality of life subscale scores at 6 years (OR, 1.5; 95% CI, 1.02-2.2; P≤ .04). Conclusion: There are surgical variables at the time of ACL revision that can modify clinical outcomes at 6 years. Opting for a transtibial surgical approach and choosing an interference screw for femoral and tibial fixation improved patients’ odds of having a significantly better 6-year clinical outcome in this cohort.

Multinucleated tumor cells and micropapillary morphology appear to be predictors of poor prognosis in renal cell carcinoma with papillary and oncocytic features

Renal cell carcinoma with papillary and oncocytic features (RCC-PO) are poorly understood, partially due to conflicting results in multiple studies. The histological features that predict behavior of RCC-PO have not been elucidated. The aim is to review clinicopathologic features and to correlate clinical outcomes of patients with RCC-PO to further expand our knowledge on these heterogeneous tumors. An archival search was done for “RCC” and “papillary,” and tumors with >50% papillary and oncocytic features were included. Clinicopathologic data including tumor size, grade, stage, molecular and immunohistochemical testing when performed, and follow-up data were collected. Using multivariate analyses, correlation between histological features, tumor stage and prognosis were analyzed. Sixty-one patients with RCC-PO were identified of which 49 (80%) were male with a median age of 65 (range: 36–93) years, and a mean tumor size of 5.2 (range: 1–21.5) cm. Micropapillary features were seen in 4, bizarre nuclei (at least 3 times larger or with irregular shape) in 6, multinucleated tumor cells (MTC) in 15, single or small clusters (SSC) (made of 2–3 tumor cells) located away from areas of necrosis in 16, and striking eosinophilic cytoplasmic inclusions in 3 tumors, respectively. Thirty-six (59%) tumors were high-grade (WHO/ISUP grade 3–4), and 23 (38%) had a high stage (≥pT3 or pN1). Tumors were positive for AMACR (15/16) and CK7 (13/17), with preserved FH (7/7) staining and were all negative for CD117 (0/7), ALK, TFE3, cathepsin K, Melan A, and HMB45 (0/4, each). Three tumors underwent chromosomal microarray (CMA) plus gene fusion assay, and FISH and germline testing for FLCN and MET gene alterations by PCR were done on 1 each. Ten (16%) patients had a local recurrence (LR) or metastasis after nephrectomy; 4 died of disease (2 had tumors with micropapillary features), with a median follow-up of 7 (range: 0.01–19) years. Tumors with micropapillary features showed significantly higher RCC-PO-related mortality (50% vs. 3.5%, p < 0.001). In multivariable analysis, SSC correlated with a higher stage (HR: 11.95; p = 0.005); micropapillary features (HR: 18.42; p = 0.017) and MTC (HR: 180.22; p = 0.036) with presence of metastasis/LR; and micropapillary features with a higher RCC-PO-related mortality (HR: 60.35; p = 0.036). RCC-PO are cytogenetically heterogeneous with overlapping features of various renal neoplasms. Micropapillary features and MTC appear to be independent predictors of poor outcomes in these tumors.

Improving Surgical Outcomes for Older Adults with Adoption of Technological Advances in Comprehensive Geriatric Assessment

Frailty is a well-recognized predictor of poor surgical outcomes for older adults, yet effective measurements and interventions remain limited. Technological advances offer an opportunity to address this gap and improve surgical care for older adults. This paper reviews the background of frailty and comprehensive geriatric assessments in surgery, and how technological innovations can advance frailty measurement and intervention in surgical settings. We review two broad areas of technological advancement as applied to frailty in surgery: 1) Innovation in the use of electronic health records (EHR) using Artificial Intelligence (AI) and Machine Learning (ML), and 2) Novel uses for wearable sensors and mobile health (mHealth) applications. We explore the integration of AI and ML with EHR systems, which can surpass traditional comorbidity indices by providing comprehensive health assessments and enhancing prediction models. Innovations like the electronic Frailty Index (eFI) show promise in expanding the reach of frailty assessments and facilitating real-time screening. Additionally, wearable devices and mobile health (mHealth) applications offer new ways to monitor and improve physical activity, nutrition, and psychological well-being, supporting perioperative rehabilitation. While these technologies present challenges, such as the need for infrastructure, training, and data interoperability, they offer promising strategies to facilitate the assessment and management of frailty among surgical patients. Continued research and tailored implementation strategies will be essential to fully realize the potential of these advancements in improving surgical outcomes for frail older adults.

The Association Between Accelerated Biological Aging and Cardiovascular Outcomes in Older Adults with Hypertension.

Current hypertension treatments rely on chronological age, which may not reflect individual differences in aging and its impact on cardiovascular health. This study aimed to determine whether biological age can predict adverse outcomes in older adults with hypertension, independent of traditional risk factors including chronological age. An analysis of a prospective cohort was conducted using data from the Health and Retirement Study, a longitudinal survey of older adults in the United States. The Klemera-Doubal method was employed to calculate the biological age of the participants with hypertension at the time of enrollment in 2016. Discrete-time survival analysis was conducted to analyze the relationship between accelerated biological aging and the risk of mortality, heart disease, and stroke over four years of follow-up. A total of 4,442 individuals were analyzed. Of these, 2,438 showed decelerated aging, whereas 2,004 experienced accelerated aging (biological age > chronological age). The median age of the patients in both groups was around 70 years. Both groups had similar racial and ethnic distributions and predominantly consisted of non-Hispanic whites. The accelerated aging group had a higher prevalence of chronic diseases, lower education levels, and less wealth than the decelerated aging group. After adjustment for these differences, accelerated aging was associated with a higher risk of a composite outcome of death, heart disease, and stroke, with an adjusted hazard ratio (a-HR) of 1.62 (95% confidence interval: 1.27-2.06, p= 0.001). Accelerated biological age is a predictor of cardiovascular outcomes and death in patients with hypertension.

Efficacy of Dual Antiplatelet therapy after Ischemic Stroke According to hsCRP Levels and CYP2C19 Genotype

BackgroundBoth high-sensitive C-reactive protein (hsCRP) and CYP2C19 genotypes are independent predictors of clinical outcomes after ischemic stroke. We aim to evaluate the association of CYP2C19 loss-of-function alleles (LoFA) carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels using the CHANCE trial. MethodsSubjects with both of CYP2C19 major alleles information (*2, *3, and *17) and hsCRP measurements were enrolled from the prespecified subgroup. CYP2C19 LoFA carriers were defined as patients with either*2 or *3 allele. Cox proportional hazards models were used to assess the interaction of CYP2C19 LoFA carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels. The primary outcome was recurrent stroke within 90 days. ResultsAmong 2801 patients, 1646 (58.8%) were LoFA carriers, and 922 (32.9%) had elevated hsCRP. In patients with non-elevated hsCRP, there was a significant interaction effect between CYP2C19 LoFA carrying status and dual/single antiplatelet regimens for prevention of recurrent stroke and combined vascular events (p =0.048, 0.048, respectively), but, not in patients with elevated hsCRP (p =0.502, 0.472, respectively). Only among patients with non-elevated hsCRP and non-carrier of CYP2C19 LoFA, dual antiplatelets significantly reduced the risk of recurrent stroke compared with aspirin alone (hazard ratio= 0.44 [0.26-0.74], p=0.003). No significant differences in bleeding were found. ConclusionsNon-elevated hsCRP and non-carrier of CYP2C19 LoFA may predict a better response to dual antiplatelet therapy in reducing stroke recurrence and composite vascular events for patients with minor stroke and high-risk TIA. TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT00979589

Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia

AbstractVenetoclax, a first-in-class BH3 mimetic drug that targets BCL-2, has improved the outcomes of patients with chronic lymphocytic leukemia (CLL). Early measurements of the depth of the venetoclax treatment response, assessed by minimal residual disease, are strong predictors of long-term clinical outcomes. However, there are limited data on the early changes induced by venetoclax treatment that might inform strategies to improve responses. To address this gap, we conducted longitudinal mass cytometric profiling of blood cells from patients with CLL during the first 5 weeks of venetoclax monotherapy. At baseline, we resolved CLL heterogeneity at the single-cell level to define multiple subpopulations in all patients based on proliferative, metabolic, and cell survival proteins. Venetoclax induced a significant reduction in all CLL subpopulations and caused rapid upregulation of the prosurvival BCL-2, BCL-XL, and mantle cell lymphoma-1 proteins in surviving cells, which had reduced sensitivity to the drug. In mouse models, the venetoclax-induced elevation of survival proteins in B cells and CLL-like cells that persisted was recapitulated, and genetic models demonstrated that extensive apoptosis and access to the B cell cytokine, B cell activating factor (BAFF), were essential. Accordingly, in patients with CLL who were treated with venetoclax or the anti-CD20 antibody obinutuzumab there was marked elevation in BAFF and an increase in prosurvival proteins in leukemic cells that persisted. Overall, these data highlight the rapid adaptation of CLL cells to targeted therapies through homeostatic factors and support cotargeting of cytokine signals to achieve deeper and more durable long-term responses.

Change in vaping, smoking and dual-use identities predicts quit success and cigarette usage: A prospective study of people quitting smoking with electronic cigarette support.

Electronic cigarettes (ECs) are an efficacious support for some but not all people wishing to stop using tobacco. While advice and practical support have been identified as increasing quit success, little research has explored the role of changes in smoking and EC-related social identities. A prospective study following 573 people attempting to quit smoking with EC support. Self-report measures of identification with being a smoker, non-smoker, vaper and dual user (people using ECs and tobacco products) were taken prior to the quit attempt and at a 12-week follow-up. Baseline identifications with being a smoker, non-smoker or dual user were not associated with smoking outcomes. Baseline vaper identity baseline was linked to more frequent tobacco abstinence at follow-up and lower levels of cigarette smoking. Levels of social identification at follow-up were consistently linked with outcomes, with vaper identity and non-smoking identities being protective and dual user identity being related to lower abstinence rates but decreased tobacco usage. Changes in identity over time were the most consistent predictor of outcomes. Findings have implications for smoking cessation practice, informing how and when identity-based interventions may be effective and our understanding of how identity transitions occur.