Grading Criteria Research Articles

Evaluation of Changes in Laboratory Parameters from a Phase 2b Trial of Zasocitinib (TAK-279), an Oral, Selective TYK2 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective tyrosine kinase 2 inhibitor. In a recent phase 2b trial (NCT04999839), more patients with moderate-to-severe plaque psoriasis treated with zasocitinib 15 and 30 mg once daily achieved 75% improvement in the psoriasis area and severity index at Week 12 (primary endpoint) than those receiving placebo (PBO; p < 0.001). Here we report an assessment of laboratory parameters from this study. Methods: In this randomized, multicenter, double-blinded, PBO-controlled study, adults with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30 mg) or PBO once daily for 12 weeks. The safety analysis set included all patients who received ≥1 dose of the assigned study treatment. Laboratory parameters assessed throughout the trial included creatine kinase (CK), as well as hematologic (neutrophils, lymphocytes, hemoglobin, platelets), hepatic and renal (alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, estimated glomerular filtration rate), and lipid (cholesterol, triglycerides) parameters. Results: In total, 259 patients were included in the safety analysis set. Longitudinal changes in all laboratory parameters were generally similar in the PBO and zasocitinib groups. Mean values of most laboratory parameters remained within normal ranges during the study. There was no relationship between zasocitinib treatment and cytopenia. Some CK elevations were observed in both the PBO and zasocitinib groups, but most were transient or reversible and of Common Terminology Criteria for Adverse Events Grade 1 or 2 (Grade ≥2 events occurred in 2 [3.8%], 2 [4.0%], 6 [11.5%], 4 [7.5%] and 3 [5.8%] patients, in the PBO, and 2, 5, 15 and 30 mg groups, respectively), and were not associated with rhabdomyolysis. Mean triglyceride values were slightly higher than normal ranges at baseline and Week 12 in all treatment groups, including PBO, and were mainly asymptomatic, mild-to-moderate elevations. These changes were not accompanied by increases in serum cholesterol levels. Conclusion: Zasocitinib treatment did not result in adverse changes in hematologic, hepatic, renal or lipid parameters that are associated with Janus kinase (JAK) inhibition, suggesting that the mechanism of action of zasocitinib is distinct from that of JAK1/2/3 inhibition. Further phase 3 studies of zasocitinib in psoriasis are ongoing to confirm these observations (NCT06088043; NCT06108544).

2024 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

Systemic antimicrobials as an adjunct in the management of periodontitis - which drug is best?

This study is a systematic review and meta-analysis that assesses systemic antimicrobials: azithromycin (AZT) and amoxicillin/metronidazole (AMX/MTZ), as adjuvants to subgingival instrumentation in the treatment of periodontitis. The aim is to establish if one antimicrobial is superior as an adjuvant therapy in the management of periodontal disease. This systematic review and meta-analysis included randomised controlled trials (RCTs), controlled clinical trials, and prospective and retrospective human studies. Participants had to be adults (≥18 years of age) with a diagnosis of periodontitis in the categories: chronic/aggressive, stages II/III, grades B/C. All participants completed full mouth subgingival instrumentation (SI) with the use of adjunct systemic antimicrobial therapy: the intervention group: AZT and the control group: AMX/MTZ. A total of 779 studies were retrieved from the data search; following the application of selection criteria and independent review duplicated by two authors, seven studies were eligible for review. Two studies were subsequently excluded due to insufficient information. Therefore five studies were included in the review, all were self-funded and four were conducted in recognised universities. The primary outcome measure was probing pocket depth changes at 1-12 months. Secondary outcome measures were: the number of residual sites with pocket depths ≥5 mm, clinical attachment levels, bleeding on probing, plaque indices (at 1-12 months), and occurrence of adverse events. Review Manager Software (The Cochrane Collaboration, Copenhagen, Denmark) was used to conduct meta-analysis. Heterogeneity between studies was expected, therefore the random-effects model was utilised to pool results from multiple studies. Statistical heterogeneity was assessed by I2 and Cochrane's test for heterogeneity. The certainty of evidence was assessed and a summary of GRADE criteria: risk of bias, inconsistency, imprecision, indirectness and publication bias. Bias was graded for the five studies included in this meta-analysis and systematic review. Two studies were low risk, two were moderate risk and one was high risk. The study rated high for risk of bias was due to an incomplete description of blinding. Three of the studies were rated low bias for outcome measurement as they reported blinding of data assessors. No studies had deviations from the intended interventions and all outcomes were detected; therefore, all studies were rated as low bias for these domains. All five of the studies demonstrated changing in probing pocket depths at 1-3 months, however, the intervention and control cohorts showed no significant difference. One study showed a statistically significant difference in probing pocket depths at 12 months, in favour of AZT. This systematic review and meta-analysis demonstrates no statistically significant difference between the two cohorts: AZT and AMX/MTZ for mean changes in clinical attachment level, probing pocket depths or bleeding on probing at 1-3 months; when used as an adjunct to mechanical intervention in the treatment of periodontitis. It was recorded, evidence of low to moderate certainty, that for the AZT cohort: fewer adverse events were evident and fewer sites with residual probing pocket depths of ≥5 mm at 1-3 months were recorded. Based on this systematic review and meta-analysis, there is no statistically significant superior drug therapy, comparing the use of AZT versus AMX/MTZ as an adjunct in the treatment of periodontists. However, evidence of low to moderate certainty demonstrates fewer adverse events and fewer sites with residual pocket depths ≥5 mm at 1-3 months in the AZT cohort, compared to the AMX/MTZ cohort. A greater number of clinical trials and a stronger evidence base in the future will allow for authentication of current findings.

Grading assistance for a handwritten thermodynamics exam using artificial intelligence: An exploratory study

[This paper is part of the Focused Collection in Artificial Intelligence Tools in Physics Teaching and Physics Education Research.] Using a high-stakes thermodynamics exam as the sample (252 students, four multipart problems), we investigate the viability of four workflows for AI-assisted grading of handwritten student solutions. We find that the greatest challenge lies in converting handwritten answers into a machine-readable format. The granularity of grading criteria also influences grading performance: employing a fine-grained rubric for entire problems often leads to errors and grading failures, as the model appears to be unable to keep track of scores for more than a handful of rubric items, while grading problems in parts is more reliable but tends to miss nuances. We also found that grading hand-drawn graphics, such as process diagrams, is less reliable than mathematical derivations due to the difficulty in differentiating essential details from extraneous information. Although the system is precise in identifying exams that meet passing criteria, exams with failing grades still require human grading. We conclude with recommendations to overcome some of the encountered challenges. Published by the American Physical Society 2024

Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (<440ms), Grade 1 (440-480ms), and Grade ≥2 (>480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation

The Effect of Spirulina Supplementation on Blood Pressure in Adults: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Previous studies have yielded controversial results regarding the effect of spirulina on blood pressure (BP), which need updating. So, this updated systematic review and meta-analysis of randomized controlled trials (RCTs) carry out a more accurate estimation of the effect of spirulina on BP in adults. This systematic searches (in PubMed/Medline, Scopus, and ISI Web of Science) until April 1, 2024, to identify related RCTs based on PICOS guidelines (population (individuals > 18 years old), the intervention (spirulina), the comparison (control or placebo group), the outcomes (systolic BP (SBP) and diastolic BP (DBP)), the study design (RCTs)), and PRISMA-checklist (Supporting Information, data S2). We evaluated the impact of spirulina on DBP and SBP. Conventional procedures were employed for analyzing publication bias, heterogeneity, and sensitivity. The GRADE criteria and the Cochrane assessment method were employed to evaluate the risk of bias (ROB) and certainty of evidence across the studies, respectively. The result shows spirulina consumption decreases SBP (WMD: -4.41 mmHg, 95% CI: -6.74 to -2.07, I2 = 66.1%) and DBP (WMD: -2.84 mmHg, 95% CI: -4.65 to -1.03, I2 = 62.3%). Subgroup analysis demonstrated SBP and DBP were still lower in individuals with ≥ 120 and ≥ 80 mmHg, hypertension (HTN) individuals, overweight individuals, age > 50 years, and > 8 weeks of intervention. Indeed, we do not observe publication bias, ROB, or interference studies in the overall results of BPs, and based on GRADE, our outcomes have moderate quality. Because of the low number of studies and participants, the dose-response and meta-regression are not significant. His study demonstrated spirulina intervention decreased SBP and DBP in HTN and overweight individuals, age > 50 years, and > 8 weeks of intervention. So, spirulina intake decreases BP and could be used in clinical practice. Furthermore, more and high-quality RCTs are needed to establish the clinical efficacy of the spirulina and determine cutoff spirulina interventions based on dose and duration. Trial Registration: PROSPERO: CRD42024534608.

BIOM-30. NOVEL HISTOLOGIC AND MOLECULAR BIOMARKERS FOR OLIGODENDROGLIOMA

Abstract Oligodendrogliomas are progressive, infiltrative gliomas. While new molecular criteria were introduced in 2016 for diagnosing oligodendroglioma, the grading criteria remains largely unchanged. We evaluated histologic and molecular features for new biomarkers of aggressive behavior, using a cohort of 184 specimens diagnosed as low grade oligodendroglioma within the Duke Brain Tumor Center Biorepository. To identify tumors meeting current molecular criteria for oligodendroglioma, IDH1/2 status was confirmed by whole exome sequencing and 1p/19q codeletion confirmed using inferred copy number variation. First, we assessed for a histologic feature called hypercellular nodules (HCN), which are foci of increased cellularity in regions of otherwise lower cellularity tumor. In patients with newly diagnosed grade 2 oligodendroglioma, 16% (15/92) had HCN. While the median overall survival (OS) was 24.1 years without HCN, the median OS with HCN was only 13.6 years (p<0.02, Mantel-Cox test). We then assessed for homozygous deletion of CDKN2A. Cases with potential CDKN2A homozygous deletion by inferred copy number variation were validated by fluorescence in situ hybridization. In patients with newly diagnosed grade 2 oligodendroglioma, 2% had homozygous CDKN2A deletion (2/107). While the median OS with intact or hemizygous CDKN2A loss was 21 years, it decreased to 3.8 years with homozygous CDKN2A deletion (p<0.0001, Mantel-Cox test), although interpretation is limited given the rarity of homozygous CDKN2A loss at initial diagnosis. For recurrent grade 2 oligodendroglioma, 6% had homozygous deletion (5/77). While the median OS with intact or hemizygous CDKN2A loss in recurrent oligodendroglioma was 25.4 years, it decreased to 6.7 years with homozygous CDKN2A deletion (p< 0.04, Mantel-Cox test). These studies provide support for using HCN and CDKN2A homozygous deletion as grading criteria for oligodendroglioma. Further studies are ongoing, including covariate analysis, expanded cohorts, and ongoing analysis of whole exome sequencing data to identify additional genetic alterations correlated with overall survival.

PATH-56. LOSS OF HETEROZYGOSITY OF CDKN2A/B DEFINES AN AGGRESSIVE SUBSET OF RECURRENT, HIGH-GRADE MENINGIOMAS

Abstract INTRODUCTION Loss of heterozygosity (LOH) occurs when one gene allele is lost, leaving the cell with a single functional copy. This genetic alteration drives tumor progression by disabling critical regulatory pathways. Currently, CDKN2A/B homozygous loss is a criterion for WHO Grade 3 meningiomas. However, the impact of CDKN2A/B LOH and other copy-number alterations remains unclear. This study investigates the effects of LOH in the CDKN2A/B tumor suppressor gene on progression-free survival (PFS) and overall survival (OS) in meningiomas. METHODS The study included adult patients with sporadic primary or recurrent meningiomas who underwent resection and whole exome sequencing. LOH and copy-number alterations were confirmed on visual inspection of b-allele frequency and mean ratio graphs. Samples of unsuitable quality for evaluation were excluded. CDKN2A/B copy number and LOH were associated with PFS and OS. RESULTS The sample included 333 meningiomas (64.6% female [n=215], 18.8% recurrent meningiomas [n=61], and 50 cases of postoperative recurrence [15%]). CDKN2A/B was intact in 88.5% of samples (n=295), while 38 samples (11.4%) exhibited CDKN2A/B LOH. This included homozygous deletions (n=2, 5.2%), heterozygous deletions (n=11, 28.9%), amplifications (n=12, 31.6%), and copy-neutral LOH (n=13, 34.2%). All copy-number alterations were associated with an increased risk of recurrence compared to CDKN2A/B intact samples, so CDKN2A/B LOH was used for subsequent analysis. CDKN2A/B LOH was more frequently associated with prior recurrence (22.9% vs. 8.8%; p=0.004), prior radiation (46% vs. 15.6%; p<0.0001), and WHO Grade 2 and 3 tumors (63.2% vs. 42.7%; p=0.02). CDKN2A/B LOH was associated with worse PFS (HR 3.97 [1.3-11.9]; p=0.01) and worse OS (HR 2.9 [1.03-8.2]; p=0.0429) only in recurrent, high-grade meningiomas, independent of the fraction of the genome altered, mutation count, and Simpson grade. Postoperative radiation therapy did not improve PFS (HR 3.24 [1.06-9.85]; p=0.038). CONCLUSION CDKN2A/B LOH is enriched in high-grade, recurrent meningiomas and confers worse PFS and OS despite postoperative radiotherapy. CDKN2A/B LOH is a high-risk biomarker that predicts tumor behavior and patient outcome.

Outcomes of Radiosurgery for WHO Grade 2 Meningiomas: The Role of Ki-67 Index in Guiding the Tumor Margin Dose.

The management of World Health Organization (WHO) grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited but suggests that a higher dose is better for tumor control. We characterize the predictors of post-SRS outcomes that can help guide planning and management. We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. Ninety-nine patients (median age 62 years) underwent SRS, 11 of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received previous irradiation. The median follow-up was 49 months. The median overall survival was 119 months (95% CI 92-NA) with estimated 5- and 10-year survival of 83% and 27%, respectively. The median progression-free survival (PFS) was 40 months (95% CI 32-62), with 3- and 5-year rates at 54% and 35%, respectively. The median locomarginal PFS was 63 months (95% CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 Common Terminology Criteria for Adverse Events grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session cohort, Ki-67 significantly predicted both overall survival and intracranial PFS. Tumors with Ki-67 >10% had 2.17 times the risk of locomarginal progression compared with Ki-67 ≤10% (P = .018) adjusting for covariates. Sex, prescription dose, tumor volume, and location also predicted tumor control. In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control but not for tumors with Ki-67 ≤10%. The management of WHO grade 2 meningiomas requires a multimodality approach. This study demonstrates the value of a targeted SRS approach in patients with limited disease and further establishes predictive biomarkers that can guide planning through a personalized approach.

PATH-28. KI-67 INDEX AS A PREDICTIVE MARKER OF MENINGIOMA RECURRENCE FOLLOWING SURGICAL RESECTION

Abstract BACKGROUND Meningiomas are the most common primary intracranial tumors in adults. Although benign in a majority of cases, they have a variable clinical course and may recur even after a thorough surgical resection. Ki-67, a nuclear protein involved in cell cycle regulation, has been widely studied as a marker of cellular proliferation in various cancers. Here, we investigate the Ki-67 index, as a predictive marker of meningioma recurrence following resection. METHODS The medical records of 451 patients with previously untreated cranial meningiomas who underwent resections from January 2011 to January 2021 at North Shore University Hospital (NSUH) were reviewed. Collected data included WHO grade, Ki-67 proliferative index, degree of resection - gross (GTR) vs subtotal (STR) - as judged by the surgeon, tumor location, and meningioma recurrence. This study was approved by the NSUH Institutional Review Board IRB 21-1107. RESULTS There were 290 patients with grade I, 154 with grade II, and 7 with grade III meningiomas. Higher WHO grades were associated with higher rates of recurrence, with rates of 11.4 %, 27.9 %, and 71.4 % for grades 1, 2, and 3, respectively, and subtotal resection corresponded to a higher rate of recurrence than total resection (34.3 % and 13.4 %, respectively). Higher WHO grades also correlated with higher Ki-67 scores (2.59, 10.01, and 20.71) for grades 1, 2, and 3, respectively. A multivariate logistic regression model identified Ki-67 and degree of resection as independent predictive variables for meningioma recurrence, with Ki-67 specifically predicting recurrence in the WHO grade II subset when analyzed separately for WHO grades I and II. CONCLUSION Our 10-year retrospective study suggests that the Ki-67 index is an important predictive marker for recurrence of intracranial meningiomas following surgical resection, particularly among patients with WHO grade II tumors. Our findings add to a growing body of data that support inclusion of Ki-67 index in the WHO grading criteria for patients with meningiomas.

PATH-45. TREATMENT OF FGFR1 – ALTERED WHO GRADE 1 GLIONEURONAL TUMORS WITH FGFR INHIBITOR ERDAFITINIB

Abstract INTRODUCTION Low-grade mitogen-activated protein kinase (MAPK) pathway-altered glioneuronal tumors carry distinct molecular alterations, which may represent therapeutic opportunities to avoid or delay toxic treatments like radiation. Erdafitinib is a pan-FGFR tyrosine kinase inhibitor, regulatorily approved in recurrent urothelial carcinoma, and is under clinical investigation for recurrent FGFR-altered gliomas (NCT05859334). METHODS We report two patients with FGFR1-altered rosette-forming glioneuronal tumors (RGNT) treated with erdafitinib. RESULTS Patient 1 is a 32-year-old woman who presented with obstructive hydrocephalus and a non-enhancing pineal tumor. She underwent a subtotal resection, with histopathology initially consistent with a low grade dysembryoplastic neuroepithelial tumor. She was under observant management for 7 years, and developed worsening symptoms with slow non-enhancing growth, although stable per RANO low grade criteria. The initial tissue was sent for next-generation sequencing (NGS) and DNA methylation profiling, revealing an FGFR1 pathogenic variant with DNA methylation profiling matching with RGNT. Patient began Erdafitinib 8 mg daily, and had stable disease per RANO at 6 months. She developed CTCAE grade 1 toxicities of subretinal fluid, fatigue, dry skin, and paronychia. Patient 2 is a 34-year-old man diagnosed 1 year prior with a tectal tumor, who underwent biopsy due to non-measurable/ non-enhancing progression. Histopathology was consistent with RGNT. NGS revealed FGFR1 mutation, PIK3CA mutation, and NF1 pathogenic variant, described in the literature as characteristic of RGNT. There was insufficient tissue for DNA methylation profiling. Patient started erdafitinib 8 mg daily and remains clinically stable for 1 month. He developed asymptomatic hyperphosphatemia (CTCAE grade 1). Both patients have tolerated treatment without interruptions or dose reductions. CONCLUSION Erdafitinib is a well-tolerated and potentially efficacious treatment of FGFR1- altered RGNT, and may avoid the need for radiation. Diagnosis of MAPK- altered low-grade glioneuronal tumors, specifically RGNT, is increasingly reliant on molecular data, and can significantly impact treatment options.

Early minimal residual disease eradication in light chain amyloidosis generates deeper and faster cardiac response

Minimal residual disease (MRD) is of growing interest in light chain (AL) amyloidosis and is associated with higher rates of cardiac response. A new graded cardiac response criteria has been proposed for better assessment of cardiac improvement. We evaluated MRD status in 63 patients with cardiac AL amyloidosis using next generation flow cytometry (sensitivity ≥ 1*10–5) within four cycles after treatment initiation and cardiac response kinetics. All patients were treated with first-line proteasome inhibitor (100%) and predominantly bortezomib (87.3%). The overall early MRD negative rates were 33.3%. Patients who achieved early MRD negativity were less likely to harbor t(11;14) (21.1% vs 57.5%, P = 0.009). The MRD negative rates amongst patients in hematologic complete response were 66.7% (14/21), and in very good partial response 29.2% (7/24). Early MRD negativity was associated with a higher likelihood of achieving ≥ cardiac partial response (≥ CarPR) (66.7% vs 38.1%, P = 0.032) and ≥ cardiac very good partial response (≥ CarVGPR) (38.1% vs 11.9%, P = 0.023) throughout first-line therapy. The cumulative incidence curve of achieving ≥ CarPR (P = 0.034) and ≥ CarVGPR (P = 0.026) showed significant difference between early MRD negative and positive group. After a median follow-up time of 27.2 months, the median progression free survival was longer in early MRD negative group (not reached vs 31.3 months, P = 0.033). Early MRD eradication in cardiac AL amyloidosis generated deeper and faster cardiac organ response.

Biomarkers of cardiohepatic syndrome in the cardiac intensive care unit

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p <0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p <0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.

A Meta-analysis Exploring the Efficacy of Neuropathic Pain Medication for Low Back Pain or Spine-Related Leg Pain: Is Efficacy Dependent on the Presence of Neuropathic Pain?

Highly variable pain mechanisms in people with low back pain or spine-related leg pain might contribute to inefficacy of neuropathic pain medication. This meta-analysis aimed todetermine how neuropathic pain is identified in clinical trials for people taking neuropathic pain medication for low back pain or spine-related leg pain and whether subgrouping based on the presence of neuropathic pain influences efficacy. EMBASE, MEDLINE,Cochrane Central,CINAHL[EBSCO], APA PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry weresearched from inception to 14 May, 2024.Randomized and crossover trials comparing first-line neuropathic pain medication for people with low back pain or spine-related leg pain to placebo or usual care were included. Two independent authors extracted data. Random-effects meta-analyses of all studies combined, and pre-planned subgroup meta-analyses based on the certainty of neuropathic pain (according to the neuropathic pain Special Interest Group [NeuPSIG] neuropathic pain grading criteria) were completed. Certainty of evidence was judged using the grading of recommendations assessment development and evaluation [GRADE] framework. Twenty-seven included studies reported on 3619 participants. Overall, 33% of studies were judged unlikely to include people with neuropathic pain, 26% remained unclear. Only 41% identified people with possible, probable, or definite neuropathic pain. For pain, general analyses revealed only small effects at short term (mean difference [MD] - 9.30 [95% confidence interval [CI] - 13.71, - 4.88], I2 = 87%) and medium term (MD - 5.49 [95% CI - 7.24, - 3.74], I2 = 0%). Subgrouping at short term revealed studies including people with definite or probable neuropathic pain showed larger effects on pain (definite; MD - 16.65 [95% CI - 35.95, 2.65], I2 = 84%; probable; MD - 10.45 [95% CI - 14.79, - 6.12], I2 = 20%) than studies including people with possible (MD - 5.50 [95% CI - 20.52, 9.52], I2 = 78%), unlikely (MD - 6.67 [95% CI - 10.58, 2.76], I2 = 0%), or unclear neuropathic pain (MD - 8.93 [95% CI - 20.57, 2.71], I2 = 96%). Similarly, general analyses revealed negligible effects on disability at short term (MD - 3.35 [95% CI - 9.00, 2.29], I2 = 93%) and medium term (MD - 4.06 [95% CI - 5.63, - 2.48], I2 = 0%). Sub-grouping at short term revealed larger effects in studies including people with definite/probable neuropathic pain (MD - 9.25 [95% CI - 12.59, - 5.90], I2 = 2%) compared with those with possible/unclear/unlikely neuropathic pain (MD -1.57 [95% CI - 8.96, 5.82] I2 = 95%). Medium-term outcomes showed a similar trend, but were limited by low numbers of studies. Certainty of evidence was low to very low for all outcomes. Most studies using neuropathic pain medication for low back pain or spine-related leg pain fail to adequately consider the presence of neuropathic pain. Meta-analyses suggest neuropathic pain medication may be most effective in people with low back pain or spine-related leg pain with a definite/probable neuropathic pain component. However, the low to very low certainty of evidence and poor identification of neuropathic pain in most studies prevent firm recommendations.

Palliative rehabilitation and quality of life: systematic review and meta-analysis

ImportanceInternational guidelines recommend the integration of multidisciplinary rehabilitation into palliative care services but its impact on quality of life across disease types is not well understood.ObjectiveTo determine the effect of...

2024 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

Is axillary web syndrome a risk factor for breast cancer-related lymphedema of the upper extremity? A systematic review and meta-analysis.

To systematically review the available literature to determine if axillary web syndrome (AWS) is a risk factor for breast cancer-related lymphedema (BCRL) of the upper extremity. The study is Prospero-registered (ID CRD42024508169) and follows PRISMA guidelines. Ovid MEDLINE, PubMED, CINAHL, Embase, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform were searched February 24, 2024. Original studies including a cohort of females > 18 years of age diagnosed with AWS after breast cancer surgery and assessing BCRL outcome were included. Scoping, mapping, systematic or qualitative reviews, dissertations without peer-review and conference abstracts were excluded. Methodological quality was assessed using the Modified Downs and Black Checklist and overall certainty in the body of evidence was assessed using Cochrane's GRADE criteria (Grading of Recommendations Assessment, Development and Evaluation). Nine cohort studies representing 3218 participants were included. The median incidence of AWS and BCRL was 31.79% (IQR 8.90%) and 14.29% (IQR 19.01%), respectively, across all studies. Pooled analysis indicated an odds ratio of 1.19 (95% confidence interval 0.60,2.37), with substantial heterogeneity across studies (Chi2 p < 0.0001, I2 = 82%). Methodological quality of the included studies was poor to fair, and there was very low certainty evidence indicating no difference in AWS for BCRL risk. The strongest study included, found that AWS more than doubles BCRL risk in the upper extremity. The available evidence base cannot definitively determine whether AWS imparts risk of BCRL. AWS should be considered a potential risk factor for BCRL, until definitive conclusions from future research are available.

Oral corticosteroid dosage and taper duration at onset in myelin oligodendrocyte glycoprotein antibody-associated disease influences time to first relapse

BackgroundWe sought to identify an optimal oral corticosteroid regimen at the onset of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which would delay time to first relapse while minimising cumulative corticosteroid...

Rare Seminal Vesicle Cystadenoma: Case Report and Literature Review

Abstract Introduction/Objective Primary neoplasms of seminal vesicles (SV) are rare, with the majority being metastatic tumors, often from prostatic carcinoma. SV cystadenoma is an exceedingly rare benign epithelial tumor that arises from the remnants of the Mullerian duct. The tumor formed of cysts of variable sizes lined by bland cuboidal epithelium. Herein we present a case of SV cystadenoma in a 38-year-old male, underscoring its rarity and risk of progression to higher grades, as outlined in literature review. Methods/Case Report A 38-year-old male with a history of left atrophic kidney and intermittent pelvic pain due to recurrent obstruction of the SV. Pelvic Magnetic Resonance Imaging revealed a 5.3 cm benign unilocular cyst within the SV, along the posterior aspect of the urinary bladder. The patient underwent successful laparoscopic excision of the left SV. Gross examination of the excised SV demonstrated a 3.5X 2.7X 1.5 cm cyst within the SV. Microscopic examination displayed a benign cyst lined by single to multiple layers of cuboidal epithelium, surrounded by unremarkable SV stroma. The epithelial lining cells exhibited round nuclei with inconspicuous nucleoli, lacking dysplasia. Immunohistochemistry revealed positive staining for cytokeratin 7 and PAX 8 in the epithelial cells, whereas prostatic specific antigen staining was negative. Results (if a Case Study enter NA) NA Conclusion Cystadenoma and mixed epithelial stromal tumors of the SV (MEST) are rare entities, with approximately 30 reported cases. This case demonstrates classic histologic features consistent with low-grade MEST, as per recently proposed grading criteria. Notably, a recent case report has suggested a potential for malignant transformation to high-grade dysplasia and adenocarcinoma in SV cystadenoma, as evidenced by focal epithelial dysplasia.

Analysis of postoperative complications and long term survival following radical gastrectomy for patients with gastric cancer

This study aimed to analyze the complications and long-term survival outcomes in patients who underwent radical gastrectomy for gastric cancer, as well as to identify the risk factors associated with postoperative complications. After conducting a comprehensive search within the medical records system, a total of 2508 patients who underwent radical gastrectomy and met the inclusion criteria were enrolled. Of the 2508 patients, 301 were diagnosed with postoperative complications. The pathological data, postoperative recovery, and survival outcome were compared between complication and control group. Subsequently, univariate and multivariate logistic regression analyses were conducted to identified the risk factors. According to the Clavien-Dindo grading criteria for postoperative complications, the proportions of grade I, II, III, IV, and V complications following radical gastrectomy were observed to be 28.2%, 42.9%, 19.6%, 8.0%, and 1.3%, respectively. The presence of postoperative complications significantly prolonged the duration of gastrointestinal decompression (P < 0.001), catheter retention (P < 0.001), fasting (P < 0.001), and hospitalization (P < 0.001). Additionally, it had a detrimental impact on survival outcomes. Age > 65years [odds ratio (OR) = 1.378, P = 0.020], presence of diabetes (OR = 2.042, P < 0.001), operative duration > 215 min (OR = 1.450, P = 0.006), intraoperative blood loss > 275 ml (OR = 1.474, P = 0.004), and Roux-en-Y anastomosis for both whole stomach (OR = 1.567, P = 0.021) and distal gastric cancer (OR = 2.083, P = 0.003) were identified as independent risk factors for postoperative complications. This study analyzed the complications and survival outcomes following radical gastrectomy, and investigated the predictors for postoperative complications, thereby providing valuable guidance on the prevention and management of surgical complications in gastric cancer.