Recent ucsdsom items

Longitudinal Metabolic Trajectories in Diabetes Prevention Program Participants Reveal Subgroups With Varying Micro- and Macrovascular Complication Risks.

Thu, 24 Sep 2026 00:00:00 +0000

OBJECTIVE: Type 2 diabetes (T2D) and its associated complications develop heterogeneously over decades, but few studies span the progression from prediabetes to clinical events. We investigated whether long-term metabolic trajectories beginning in prediabetes delineate subgroups with differential complication risk. RESEARCH DESIGN AND METHODS: Clinical data from 1,732 Diabetes Prevention Program/Outcomes Study participants (follow-up 19 years) were analyzed across 12 phenotypes. Tensor decomposition was used to capture longitudinal patterns, and Gaussian mixture modeling was used to define longitudinal clusters. Cluster-specific complications were quantified with Cox and logistic regression. RESULTS: Four clusters emerged. Clusters 1 and 2 (73% of participants) maintained stable glycemia, blood pressure, and lipids. Although 49% and 71%, respectively, developed T2D, cumulative micro- and macrovascular events remained low. Cluster 3 (12%) showed the steepest rise in insulin resistance...

Adapting Research Protocols During War: The ANCHOR (Analysis of Network Composition, Health Outcomes, and Resilience) Study

Thu, 24 Sep 2026 00:00:00 +0000

BackgroundConducting longitudinal infectious disease research during armed conflicts is important for understanding transmission dynamics and preventing outbreaks. War in Ukraine started in 2014, with the escalation to full-scale invasion in 2022, resulting in massive population displacement, infrastructure destruction, mobility restriction for men, and reduced access to healthcare. The ANCHOR (Analysis of Network Composition, Health Outcomes, and Resilience) study, launched in November 2024, examines how war- and displacement-driven changes affect social networks, HIV risks, and HIV care engagement. Here, we report implementation challenges and adaptations as practical lessons that may inform infectious disease surveillance and research in conflict settings.MethodsANCHOR is a cohort study conducted in Kyiv and Lviv in 2024–2026 that enrolled sexual minority men (SMM) using respondent-driven sampling, with 6- and 12-month follow up of participants testing positive for HIV. Data...

Premature Battery Depletion of an Insertable Cardiac Monitor: A Two-Patient Case Series

Thu, 24 Sep 2026 00:00:00 +0000

Premature Battery Depletion of an Insertable Cardiac Monitor: A Two-Patient Case Series

Eating Disorders and Parkinson's Disease—2: Genetic Epidemiology and Shared Genomics

Thu, 24 Sep 2026 00:00:00 +0000

OBJECTIVE: Individuals with anorexia nervosa (AN) share premorbid traits with Parkinson's Disease (PD) (e.g., anxiety) and exhibit a two-fold relative risk of a reported family history of PD. Published estimates of intra- and inter-disorder genetic architecture were extracted and compared prior to conducting novel analyses to provide evidence for cross-disorder genetic risk. METHODS: National register or meta-analytic familial, twin, and common variant genome-wide studies were searched; estimates and findings were extracted and compared. Novel cross-disorder conditional and conjunctional false discovery rate analyses were performed. RESULTS: Sibling relative risks and additive genetic estimates of the two disorders were similar. AN had greater common variant heritability than PD whether measured via infinitesimal model (linkage disequilibrium score regression, LDSC) or causal mixture model (MiXeR). AN had greater polygenicity than PD (mean (SD) 2.50E-03 (1.64E-04) versus...

Harnessing the mental imprints of climate change for collective climate action

Thu, 24 Sep 2026 00:00:00 +0000

Harnessing the mental imprints of climate change for collective climate action

Seventy Seconds of Asystole Delayed Atrioventricular Block Post-TAVR From His-Bundle Injury and Phase 4 Block

Thu, 24 Sep 2026 00:00:00 +0000

BACKGROUND: Conduction system disturbance is a leading complication of transcatheter aortic valve replacement (TAVR). Conventional predictors of post-TAVR pacing include preexisting right bundle branch block, new left bundle branch block, and annular calcification. CASE SUMMARY: A 71-year-old woman with severe aortic stenosis and left bundle branch block (PR: 160 ms, QRS: 138 ms) underwent TAVR. The QRS paradoxically narrowed postprocedure (104 ms), and inpatient telemetry showed no high-grade atrioventricular block before discharge. Five days later, an outpatient real-time monitor captured 71 seconds of asystole due to complete heart block. She presented with syncope and underwent pacemaker implantation. DISCUSSION: The paradoxical QRS narrowing reflects His-bundle injury producing a proximal conduction delay in the His bundle, with recovery of conduction in the left bundle branch indicative of gap phenomenon. The recovery of conduction in the left bundle also highlights the...

Optimizing adolescent brain development

Thu, 24 Sep 2026 00:00:00 +0000

Optimizing adolescent brain development

A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit

Fri, 18 Sep 2026 00:00:00 +0000

The structure of the catalytic subunit of cAMP-dependent protein kinase (PKA-C), a prototype for the protein kinase superfamily, laid the foundation for the development of targeted kinase inhibitors. Here we describe the structure and biophysical characterization of a PKA-C complex with BLU0588, a small PKA-selective inhibitor. The high-resolution crystal structure not only captures the inhibitor's unusual T-shaped geometry, but also shows how the four rings of BLU0588 serve as surrogates for ATP's adenosine and phosphate-organizing sites. Each site contains two subsites. BLU0588's planar azaindole and pyridine rings, which are buried beneath the glycine-rich loop in a hydrophobic shell at the base of the active site cleft, fill the adenine and ribose subsites. In contrast, BLU0588's indane and pyrrolidine rings fill the phosphate-organizing site. The indane ring occupies the α/β-phosphate organizing site while the pyrrolidine ring fills the Mg/γ-phosphate organizing site. The...

Referral Characteristics of an Ambulatory Integrative Medicine Consultation Service at an Academic Health Center

Thu, 17 Sep 2026 00:00:00 +0000

Referral Characteristics of an Ambulatory Integrative Medicine Consultation Service at an Academic Health Center

Osteopathic Manipulative Treatment Reduces Length of Stay and Opioid Use After Vestibular Schwannoma Resection

Thu, 17 Sep 2026 00:00:00 +0000

Osteopathic Manipulative Treatment Reduces Length of Stay and Opioid Use After Vestibular Schwannoma Resection

Development of an Automated Machine Learning Algorithm for Screening of OSA in Primary Care Settings

Thu, 17 Sep 2026 00:00:00 +0000

Development of an Automated Machine Learning Algorithm for Screening of OSA in Primary Care Settings

The effects of transcranial random noise stimulation on excitation/inhibition balance in ADHD.

Fri, 11 Sep 2026 00:00:00 +0000

Background

Children with attention-deficit/hyperactivity disorder (ADHD) often show aberrant neural activity, including excitation/inhibition (E/I) imbalances, atypical event-related potentials (ERPs), and neural network dysfunction. Transcranial Random Noise Stimulation (tRNS) has shown promise in modulating neural activity in ADHD.

Methods

The current study examined differences in behavioral and EEG signals recorded during an inhibitory control task in children with (N = 23) and without (N = 33) ADHD. Changes in these signals were further assessed following a combined tRNS and cognitive training intervention targeting the right inferior frontal gyrus and left dorsolateral prefrontal cortex in a sham-controlled randomized trial within the ADHD group only (n = 11 and 12 for intervention and sham groups, respectively).

Results

At baseline, children with ADHD showed slower reaction times, and higher commission error rates compared...

What Dose of Methamphetamine Do Regular Consumers Use Daily? Estimating Oral Amphetamine Milligram Equivalents

Fri, 11 Sep 2026 00:00:00 +0000

OBJECTIVES: The purity, accessibility, and affordability of illicit methamphetamine have increased in recent decades, which has been linked to rising rates of methamphetamine-involved overdoses, psychosis, cardiovascular events, and other health consequences. Nevertheless, information about the quantity of methamphetamine used by regular consumers has been limited, despite the potential clinical utility of exposure quantification. METHODS: From August 2024 to April 2026, self-reported daily methamphetamine consumption was assessed among n = 94 individuals in Los Angeles County. Methamphetamine samples (n = 256) were analyzed for purity using liquid chromatography-mass spectrometry. Bioavailability by route of administration and stimulant equivalency were obtained from the literature. A simulation model leveraging bootstrapping with 1,000,000 draws was used to estimate oral amphetamine milligram equivalents (AME). RESULTS: The average reported methamphetamine consumption was 1.09...

Efficacy and Safety of Naloxegol in Patients with Chronic Non-Cancer Pain Who Experience Opioid-Induced Constipation: A Pooled Analysis of Two Global, Randomized Controlled Studies

Fri, 11 Sep 2026 00:00:00 +0000

Objective: This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment. Methods: This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period. Subjects: The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week. Results: Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]....

Corrigendum to: Topical analgesics for neuropathic pain: an evidence-informed guide for the practicing clinician

Fri, 11 Sep 2026 00:00:00 +0000

Corrigendum to: Topical analgesics for neuropathic pain: an evidence-informed guide for the practicing clinician

Update on Treating Painful Diabetic Peripheral Neuropathy: A Review of Current US Guidelines with a Focus on the Most Recently Approved Management Options

Fri, 11 Sep 2026 00:00:00 +0000

Painful diabetic peripheral neuropathy (DPN) is a highly prevalent and disabling complication of diabetes that is often misdiagnosed and undertreated. The management of painful DPN involves treating its underlying cause via lifestyle modifications and intensive glucose control, targeting its pathogenesis, and providing symptomatic pain relief, thereby improving patient function and health-related quality of life. Four pharmacologic options are currently approved by the US Food and Drug Administration (FDA) to treat painful DPN. These include three oral medications (duloxetine, pregabalin, and tapentadol extended release) and one topical agent (capsaicin 8% topical system). More recently, the FDA approved several spinal cord stimulation (SCS) devices to treat refractory painful DPN. Although not FDA-approved specifically to treat painful DPN, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, gabapentinoids, and sodium channel blockers are common first-line...

S497 Naloxegol Accelerates Time to First Spontaneous Bowel Movement (SBM) and Complete SBM (CSBM) With Predictable Efficacy in Patients With Extreme Opioid-Induced Constipation (OIC): A Pooled Analysis of Two Phase 3 Trials

Fri, 11 Sep 2026 00:00:00 +0000

S497 Naloxegol Accelerates Time to First Spontaneous Bowel Movement (SBM) and Complete SBM (CSBM) With Predictable Efficacy in Patients With Extreme Opioid-Induced Constipation (OIC): A Pooled Analysis of Two Phase 3 Trials

Frontline Perspectives on Buprenorphine for the Management of Chronic Pain

Fri, 11 Sep 2026 00:00:00 +0000

Due to the prevalence of chronic pain and high-impact chronic pain in the US, a significant percentage of the population is prescribed opioids for pain management. However, opioid use disorder is associated with reduced quality of life, along with fatal opioid overdoses, and is a significant burden on the US economy. Considering the clinical needs of patients with intractable chronic pain and the potential harms associated with prescribed and illicit opioids in our communities, having a deep understanding of current treatment options, supporting evidence, and clinical practice guidelines is essential for optimizing treatment selections. Buprenorphine is a Schedule III opioid with a unique mechanism of action, allowing effective and long-lasting analgesia at microgram doses with fewer negative side effects and adverse events, including respiratory depression, when compared with other immediate-release, long-acting, and extended-release prescription opioids. Due to its relatively...

Multimodal Therapies for the Treatment of Neuropathic Pain: The Role of Lidocaine Patches in Combination Therapy: A Narrative Review

Fri, 11 Sep 2026 00:00:00 +0000

Neuropathic pain (NP) has a population presence of up to 10%. Both systemic agents and topical agents are recommended as first-line therapy for the treatment of NP but monotherapy provides adequate pain relief only in < 50% of the cases. This has created the need for multimodal combination therapy, a practice that is becoming more common. Combination therapy with multiple systemic agents has a risk for drug–drug interactions and adverse events (AEs), while add-on therapy with a topical agent such as lidocaine patches minimizes such risks. The focus of this review was to find if there is evidence from trials that combination therapy of the topical lidocaine patches with systemic agents will have better efficacy and/or less risk of AEs than the combination of two systemic agents. Since gabapentinoids are one of the most common systemic agents used in first-line NP therapy, the objective of this review was to summarize the safety and efficacy data and evaluate the benefit–risk...

Founding the Pain Medicine Academy of Advanced Practice Providers

Fri, 11 Sep 2026 00:00:00 +0000

Founding the Pain Medicine Academy of Advanced Practice Providers

Topical analgesics for neuropathic pain: an evidence-informed guide for the practicing clinician

Fri, 11 Sep 2026 00:00:00 +0000

OBJECTIVE: To evaluate available evidence for the efficacy and safety of topical analgesics for neuropathic pain and to offer treatment guidance. METHODS: An expert panel searched PubMed (Medline) and reference lists of published articles for available literature assessing 8 categories of topical analgesics used to treat various neuropathic pain conditions. The panel rated the level of analgesic efficacy evidence for each treatment and considered safety, ease of use, and cost. The degree of consensus on the recommendations among the panelists was measured. RESULTS: There was strong evidence and high consensus that capsaicin 8% is effective for diabetic peripheral neuropathy and postherpetic neuralgia and that lidocaine is effective for postherpetic neuralgia. There was strong evidence and moderate consensus that capsaicin 8% could be effective for HIV-induced neuropathy. There was moderate evidence and high consensus that lidocaine is likely effective for diabetic peripheral neuropathy,...

Naloxegol (Movantik®) Provides Rapid and Sustained Improvement of Opioid-Induced Constipation Symptoms Irrespective of Opioid Dose

Fri, 11 Sep 2026 00:00:00 +0000

Aim Naloxegol (Movantik), an oral peripherally acting mu-opioid receptor antagonist has demonstrated rapid relief of opioid-induced constipation (OIC) in patients with chronic non-cancer pain in two phase 3 trials (KODIAC 4/5; NCT01309841/NCT01323790). This analysis aims to characterize the OIC symptom burden and evaluate the efficacy of naloxegol in treating symptoms of OIC based on daily opioid dosages. This is the first naloxegol analysis based on a lower opioid dose cutoff of 100 MEU/day. Methods Data were pooled from the KODIAC 4/5 intent-to-treat populations (N=1337). Subjects treated with placebo (PBO) and naloxegol (12.5mg, 25mg) QD were evaluated based on opioid dose ranges (lower dose, ≤100mg; higher dose, >100mg MEU/day). OIC symptoms assessed include number of spontaneous bowel movements (SBM/wk), complete evacuation (CSBM), straining (scale 1=not at all, 5=extreme) and stool consistency (Bristol Stool Scale: 1=hard, 7=watery). Results Baseline OIC symptom burden...

Characterization of Spirometric Response to Standard-of-care Treatment in Lung Allograft Recipients With Bronchiolitis Obliterans and the Utility of Spirometric Criteria for Rescue Therapy: Implications for the Design of Risk-stratified Clinical Trials

Fri, 11 Sep 2026 00:00:00 +0000

BACKGROUND: The spirometric response to standard-of-care (SOC) immunosuppressive therapy for the management of bronchiolitis obliterans syndrome (BOS) has been sparsely reported in the literature. Data from a Medicare-approved Registry were analyzed to characterize the effectiveness/durability of a wide range of SOC interventions to manage the decline of lung function and to validate the study spirometric criteria for initiation of rescue therapy. METHODS: Lung transplant recipients with refractory BOS at 21 US collaborating centers were enrolled in the Registry. Data included both nonspirometric (eg, demographic, Immunosuppressive Regimens for management of BOS) and spirometric parameters (ie, forced expiratory volume in 1 s [FEV 1 ] measurements and derived indices). The utility of study FEV 1 criteria for treatment (ie, statistically significant rate of FEV 1 decline >30 mL/mo) was evaluated by comparing the spirometric course between participants who met or did not meet...

Rational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain: Consensus Recommendations

Fri, 11 Sep 2026 00:00:00 +0000

Objective: To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. Methods: An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Results: Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring...

Intrathecal pain management: a team-based approach

Fri, 11 Sep 2026 00:00:00 +0000

OBJECTIVE: Physician assistants (PAs), nurse practitioners (NPs), and registered nurses (RNs) provide professional services on pain management teams. This review provides an overview of the practical management of chronic pain with intrathecal (IT) therapy using an interprofessional approach (eg, physicians and other health care professionals), with a focus on the contributions of PAs, NPs, and RNs. METHODS: Narrative review based on literature searches of the Medline database and treatment guidelines on the use of IT therapy in the management of patients with chronic pain. RESULTS: The specific roles and responsibilities of PAs, NPs, and RNs in the management of patients receiving IT therapy vary by practice. In many pain treatment centers, PAs, NPs, and RNs are responsible for patient education, postimplant maintenance, and ongoing supportive care of patients receiving IT therapy. Topics that we address include patient selection, patient expectations and goal setting, medication...

A rare case report of decompensated cirrhosis from hereditary hemochromatosis following lung transplant in a person with cystic fibrosis

Fri, 11 Sep 2026 00:00:00 +0000

A 33-year-old woman with cystic fibrosis following bilateral sequential cadaveric lung transplantation experienced prolonged intermittent liver enzyme elevation. An abdominal ultrasound revealed increased hepatic echogenicity and cirrhotic features, warranting further investigation with iron studies and liver biopsy, which confirmed hereditary hemochromatosis. This rare case underscores the importance of considering hereditary hemochromatosis post lung transplantation irrespective of not receiving multiple blood products or iron replacement.

An overview of abuse-deterrent opioids and recommendations for practical patient care

Fri, 11 Sep 2026 00:00:00 +0000

Despite advances in the treatment of severe intractable pain, opioids remain a critical and appropriate component of treatment. However, abuse, misuse, and diversion of prescription opioids are significant public health concerns. Opioid abuse-deterrent formulations (ADFs) are one component of an opioid risk management plan to manage patient's pain relief and quality of life while offering some protection against potentially harmful consequences of opioids from misuse and abuse. Opioid ADFs are designed to make manipulation more difficult and administration via non-oral routes less appealing. There are currently nine extended-release and one immediate-release opioid pain medications with US Food and Drug Administration-approved ADF labeling. All use physical/chemical barriers or agonist/antagonist combinations to deter manipulation and abuse. Evidence suggests that opioid ADFs decrease rates of abuse and diversion of opioids in the USA; however, some opioid ADFs are not yet commercially...

Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion

Fri, 11 Sep 2026 00:00:00 +0000

OBJECTIVE: An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management. METHODS: The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine. RESULTS: The panel recommended that buprenorphine's classification as a partial µ-opioid receptor agonist not be clinically translated to mean partial analgesic efficacy. The panel also recommended...

S508 Naloxegol Achieved Rapid and Sustained Improvement of Opioid-Induced Constipation (OIC) Symptoms in Patients With Extreme OIC: A Pooled Analysis of Two Pivotal Phase 3 Trials

Fri, 11 Sep 2026 00:00:00 +0000

S508 Naloxegol Achieved Rapid and Sustained Improvement of Opioid-Induced Constipation (OIC) Symptoms in Patients With Extreme OIC: A Pooled Analysis of Two Pivotal Phase 3 Trials

Is it justified to order an upfront cytomegalovirus immunohistochemical stain in patients with severe inflammatory bowel disease and ulceration?

Thu, 10 Sep 2026 00:00:00 +0000

BACKGROUND: Cytomegalovirus (CMV) infection is common amongst both immunocompetent and immunocompromised patients. Patients with inflammatory bowel disease (IBD) are more prone to suffer from CMV complications. In this study, we investigated the utility of immunohistochemistry to diagnose CMV infection in patients with severe IBD. METHODS: We searched our pathology data system to identify patients with IBD from January 1, 2017 to December 31, 2021. We identified 5782 IBD cases, out of which 784 cases had severe activity with ulceration. CMV immunohistochemical stain (IHC) was performed on all 784 cases. Hematoxylin and eosin (H&E) staining slides were reviewed to evaluate the presence of characteristic nuclear or cytoplasmic CMV inclusions. H&E and IHC results were categorized as "single" if 1 cell stained positive or had characteristic inclusions, "rare" if 2-5 cells stained positive or had characteristic inclusions and "many" if more than 5 cells stained...

Immunoaffinity‐Based Protocol to Enrich Nervous System Cell‐, Lung Alveolar Cell‐, and Hepatocyte‐Derived Extracellular Vesicles From Human Plasma

Thu, 10 Sep 2026 00:00:00 +0000

By preserving molecular information inherited from the source cell, extracellular vesicles (EVs) can serve as biomarkers for tissue health or disease, paving the way for liquid biopsy applications. The enrichment of tissue-specific EVs (TS-EVs) from human biofluids can be challenging due to technical and methodological limitations. Here, we use single and sequential immunoaffinity capture workflows to enrich antigen-specific EVs circulating in human blood. We demonstrate the specificity, efficiency, and consistency of our approach for enriching blood plasma EV subpopulations from the nervous system, alveolar cells and hepatocytes. The enriched subpopulations are characterized by canonical EV features and markers, as well as co-localization of tissue-specific and general markers on the surface. We provide a validated workflow to derive multiple EV subpopulations from circulation, leveraging their promise as informative biomarkers of tissue status and enabling liquid biopsy and...

Rising Incidence With Modest Survival Improvement in Salivary Duct Carcinoma: A Population‐Based Study in the United States, 2000–2022

Thu, 10 Sep 2026 00:00:00 +0000

BACKGROUND: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with limited population-based data. METHODS: Incidence trends and survival outcomes were analyzed using the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 955 cases were identified. The age-adjusted incidence rate increased from 0.158 in 2000 to 1.18 in 2022 (average annual percent change, 10.38%; p < 0.001), accelerating after 2012. Increases were more pronounced among females, older patients, regional-stage disease, and tumors > 2 cm. The 5-year disease-specific survival (DSS) and overall survival were 60.6% and 51.2%, respectively. Advanced age, non-parotid site, larger tumor size, lymph node metastasis, advanced stage, and non-surgical management were independent predictors of worse DSS. Patients diagnosed in 2013-2022 showed better DSS compared with those in 2004-2012 (64.7% vs. 52.0%, p = 0.048). CONCLUSION: SDC incidence has increased rapidly, possibly reflecting...

Nemtabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Phase 2 BELLWAVE-003 cohort J

Thu, 10 Sep 2026 00:00:00 +0000

Nemtabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Phase 2 BELLWAVE-003 cohort J

Management of coagulopathy among patients with cirrhosis undergoing upper endoscopy and paracentesis: Persistent gaps and areas of consensus in a multispecialty Delphi

Thu, 10 Sep 2026 00:00:00 +0000

Patients with cirrhosis have abnormal coagulation indices such as a high international normalized ratio and low platelet count, but these do not correlate well with periprocedural bleeding risk. We sought to develop a consensus among the multiple stakeholders in cirrhosis care to inform process measures that can help improve the quality of the periprocedural management of coagulopathy in cirrhosis. We identified candidate process measures for periprocedural coagulopathy management in multiple contexts relating to the performance of paracentesis and upper endoscopy. An 11-member panel with content expertise was convened. It included nominees from professional societies for interventional radiology, transfusion medicine, and anesthesia as well as representatives from hematology, emergency medicine, transplant surgery, and community practice. Each measure was evaluated for agreement using a modified Delphi approach (3 rounds of rating) to define the final set of measures. Out of...

Maternal Serum Nitrate and Nitrite Associations With Birth Outcomes: A Case‐Control Study

Thu, 10 Sep 2026 00:00:00 +0000

Nitrate and nitrite contamination of groundwater and surface water is a global public health concern, often linked to the increasing use of nitrogen-based fertilizers. In Jordan's Ghor region, where agriculture is intensive and fertilizer use is widespread, the issue is particularly relevant. This study aimed to investigate the relationship between serum nitrate and nitrite levels with low birth weight and preterm birth. A total of 659 participants were enrolled, comprising 452 controls (normal birth weight and full-term delivery) and 207 cases (low birth weight/preterm delivery). High maternal serum nitrite levels were significantly associated with increased odds of low birth weight delivery in both the unadjusted model (odds ratio [OR] = 1.43, 95% CI: 1.14-1.80, P = 0.002) and the a priori confounder set adjusted model (OR = 1.33, 95% CI: 1.02-1.74, P = 0.038). Nitrite levels were also significantly associated with the combined...

Peripheral blood biomarkers in PD-1/PD-L1 immunotherapy: distinguishing predictive from prognostic biomarkers

Thu, 10 Sep 2026 00:00:00 +0000

Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) axis have transformed cancer therapy, yet reliable biomarkers for accurately predicting therapeutic benefit remain limited. Peripheral blood biomarkers have emerged as attractive candidates because of their minimally invasive accessibility, feasibility for serial monitoring, and potential to capture dynamic systemic immune responses during treatment. However, their clinical translation has been hindered by inconsistent findings, biological heterogeneity, and the frequent conflation of prognostic associations with true predictive value. Many commonly reported biomarkers, including circulating tumor DNA (ctDNA), blood-based tumor mutational burden (bTMB), inflammatory indices, and conventional serum markers, primarily reflect tumor burden, systemic inflammation, or host physiological status rather than genuine sensitivity to PD-1/PD-L1 blockade. In contrast, immune...

Health-related quality of life impact of idelalisib in patients with relapsed chronic lymphocytic leukemia (CLL): phase 3 results

Thu, 10 Sep 2026 00:00:00 +0000

Health-related quality of life impact of idelalisib in patients with relapsed chronic lymphocytic leukemia (CLL): phase 3 results

Spindle cell (sarcomatoid) squamous cell carcinoma of the esophagus: A case report and a review of the literature.

Thu, 10 Sep 2026 00:00:00 +0000

Esophageal squamous cell carcinoma (SCC) is a significant global health issue, and spindle cell squamous cell carcinoma (SpCC) is a rare variant accounting for up to 2% of cases. SpCC is characterized by a biphasic histological pattern comprising both carcinomatous and sarcomatous components. Patients typically present with dysphagia, painful swallowing, and weight loss. Diagnosis is challenging due to sampling limitations in biopsy specimens, often leading to misclassification as conventional SCC or sarcoma. In this case, a white American 65-year-old male presented with worsening dysphagia and weight loss. Endoscopic evaluation revealed a large fungating mass in the middle third of the esophagus. Initial biopsy showed a high-grade malignant neoplasm, but immunohistochemistry (IHC) was inconclusive. Further imaging confirmed a primary esophageal tumor with regional lymph node involvement. The patient underwent neoadjuvant therapy followed by surgical resection. Post-treatment...

Intraoperative hypotension and postoperative delirium among older high-risk patients undergoing major noncardiac surgery: a retrospective single-centre cohort study

Wed, 2 Sep 2026 00:00:00 +0000

Background: Intraoperative hypotension has been associated with postoperative complications, but its relationship with postoperative delirium remains debated. Methods: This single-centre retrospective cohort study included adults (≥60 yr) with ASA physical status score of 3 or 4 undergoing major noncardiac surgery, with documented Confusion Assessment Method assessments. Patients with a history of neurosurgery, stroke, dementia, or neurocognitive disorders were excluded. The primary exposure was the cumulative duration of a mean arterial pressure <65 mm Hg (minutes). The primary outcome was postoperative delirium within 7 days, diagnosed via Confusion Assessment Method. Multivariable logistic regression was used to assess the association between intraoperative hypotension and delirium, adjusting for confounders. Results: Among 5171 patients included from 2013-2024, 632 (11.8%) developed delirium. The median (Q1-Q3) duration of surgery and time with mean arterial pressure <65...

CD47 blockade (ALX301) enhances immunoradiotherapy response in HPV negative head and neck squamous cell carcinoma.

Tue, 1 Sep 2026 00:00:00 +0000

Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide, with limited treatment options for patients with locally advanced disease. CD47 immune checkpoint inhibitors have been used to block the CD47/SIRPa interaction that inhibits antigen-presenting cell phagocytosis, thereby enhancing antigen presentation to cytotoxic T-cells, and have shown promise in combination with anti-PD1 immunotherapy in tumors, including recurrent/metastatic HNSCC. We found that CD47 expression is associated with poor prognosis in HNSCC and explored the anti-tumor activity of an anti-CD47 fusion protein in combination with anti-PD1 and lymphatic-sparing radiotherapy in a locally advanced HNSCC model. In the 4MOSC1 syngeneic HPV-negative HNSCC mouse model, ALX301 (an engineered CD47-blocking SIRPα fusion for murine models) induced complete tumor regression when combined with anti-PD-1, and produced a partial tumor response as a monotherapy. An anti-PD1...

Advances in γδ T Cells: Cutaneous Biology and Therapeutic Potential for Skin Neoplasms

Mon, 31 Aug 2026 00:00:00 +0000

γδ T cells represent an increasingly important subset of T lymphocytes in the immune response to cancer and as a platform for novel immunotherapies. The aim of this review is to synthesize recent insights into the biology and advances in therapeutic applications of γδ T cells in cutaneous malignancies, especially melanoma, within a framework of tumor immunology and recent clinical research.

Combined effective field theory interpretation of Higgs boson, electroweak vector boson, top quark, and multijet measurements

Mon, 31 Aug 2026 00:00:00 +0000

Constraints on Wilson coefficients (WCs) corresponding to dimension-6 operators of the standard model effective field theory (SMEFT) are determined from a simultaneous fit to seven sets of CMS measurements probing Higgs boson, electroweak vector boson, top quark, and multijet production. Measurements of electroweak precision observables are also included and provide complementary constraints to those from the CMS experiment. The CMS measurements, using LHC proton-proton collision data at s=13Te$$\sqrt{s}=13\,\text {Te}\text {V} $$, corresponding to integrated luminosities of 36.3 or 138fb-1$$\,\text {fb}^{-1}$$, are chosen to provide sensitivity to a broad set of operators, for which consistent SMEFT predictions can be derived. These are primarily measurements of differential cross sections which are parameterized as functions of the WCs. In measurements targeting t(t¯)X$${\text {t}} (\bar{\textrm{t}})\text {X} $$ production, SMEFT effects are modelled at the detector level. Individual...

Exploiting the CXCR3/CXCL10 axis overrides tumor immune suppression by enhancing immune trafficking and effector cell priming in HNSCC

Fri, 28 Aug 2026 00:00:00 +0000

Immune-suppressive tumor microenvironments (TMEs) limit the impact of checkpoint blockade in many cancers by restricting the infiltration and activation of CD8⁺ T, CD4⁺ T, and NK cells. Utilizing murine models of head and neck squamous cell carcinoma, we demonstrated that intratumoral (IT) delivery of CXCL10 drives tumor elimination and inhibits recurrence not only by recruiting these cells but by enhancing their antitumoral functions and stunting angiogenesis. CD8⁺ T cells also display enhanced activation, tumor-antigen specificity, and decreased T cell exhaustion. Despite administration of CXCL10 into tumors, CD8⁺ and CD4⁺ T cells show enhanced presence and proliferation in tumor-draining lymph nodes (TdLNs), consistent with T cell priming and trafficking between tumors and TdLNs. Together, the data suggest that CXCL10 promotes a mutually reinforcing feedback loop that reprograms the TME toward an immunologically responsive...

Genome-wide association studies of lifetime and frequency of cannabis use in 131,895 individuals

Fri, 28 Aug 2026 00:00:00 +0000

Cannabis is one of the most widely used drugs globally. We performed genome-wide association studies (GWASs) of lifetime (N = 131,895) and frequency (N = 73,374) of cannabis use. For lifetime cannabis use, we identified two loci, one near CADM2 (rs35827242, p = 4.63E-12) and another near GRM3 (rs12673181, p = 6.90E-09). For frequency of cannabis use, we identified one locus near CADM2 (rs4856591, p = 8.10E-09; r2 = 0.76 with rs35827242). Lifetime and frequency of cannabis use were heritable (12.88 vs. 6.63%) and genetically correlated with previous GWASs of lifetime use and cannabis use disorder (CUD), as well as other substance use and cognitive traits. Polygenic scores (PGSs) for lifetime and frequency of cannabis use predicted cannabis use phenotypes in All of Us participants. A phenome-wide association study using a PGS for lifetime cannabis use to interrogate a hospital cohort replicated prior associations with substance use and mood disorders, and uncovered novel associations...

NAVITOCLAX (ABT-263) PLUS FLUDARABINE/CYCLOPHOSPHAMIDE/RITUXIMAB (FCR) OR BENDAMUSTINE/RITUXIMAB (BR): A PHASE 1 STUDY IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)