Citations

Background Malpositioned orbital implants are an underappreciated source of significant postoperative morbidity, often necessitating revision surgery. Decision-making regarding practical frameworks to guide revision remains challenging and is not well standardized or characterized. Objective To analyze clinical presentations, radiographic failure patterns, multidisciplinary surgical strategies, and outcomes of patients undergoing revision surgery for malpositioned orbital implants. Methods A single-center retrospective consecutive case series was conducted of patients who underwent removal or replacement of malpositioned orbital implants. Patient demographics, presenting symptoms, radiographic findings, surgical approaches, implant management strategies, and postoperative outcomes were reviewed. Most cases were co-managed by plastic/reconstructive and oculoplastic surgeons. Descriptive statistics were used to summarize findings. Results Five of seven patients (71.4%) were female, with a median age of 60 years (range 29–78). Diplopia was the most common presenting symptom (5/7, 71.4%) along with pain or swelling (5/7, 71.4%) followed by globe malposition (3/7, 42.9%). CT demonstrated implant protrusion into orbital soft tissue in 4/7 patients (57.1%) and peri-implant inflammatory collections in 3/7 (42.9%). Out of our 7 revision cases, four patients (57.1%) underwent explantation alone, and three (42.9%) underwent secondary reconstruction with custom or semi-custom implants. At follow-up, diplopia improved or resolved in 4/5 affected patients (80%), and pain, swelling, and globe position improved in all symptomatic patients. Conclusion Malpositioned orbital implants demonstrate heterogeneous failure mechanisms that require individualized surgical management. A multidisciplinary approach can guide decision-making regarding implant removal versus revision of reconstruction, enabling safe revision surgery and favorable clinical outcomes. Additionally, virtual surgical planning and intraoperative navigation are enablers of safe and precise revision orbital surgery.

Abstract Objectives This study aimed to characterize susceptibility profiles of both currently approved and investigational β-lactam agents against difficult-to-treat resistant Pseudomonas aeruginosa (DTR P. aeruginosa) clinical isolates, including carbapenemase-producing strains. Patients and methods A total of 502 consecutive DTR P. aeruginosa clinical isolates were collected from unique hospitalized patients between 2022 and 2024 across three tertiary care centres. Isolates originated from bloodstream, respiratory, urinary and intra-abdominal infections. Minimum inhibitory concentrations (MICs) for seven β-lactam agents were determined using triplicate reference broth microdilution. Susceptibility interpretations were based on CLSI criteria or, where applicable, investigational breakpoints. Whole-genome sequencing was performed to detect β-lactamase genes. Results Among the 502 isolates, cefepime-zidebactam exhibited the highest in vitro activity (100% susceptibility), followed by cefiderocol-xeruborbactam (98%), cefiderocol (95%), ceftolozane-tazobactam (90%), cefepime-taniborbactam (86%), ceftazidime-avibactam (85%), and imipenem-relebactam (41%). Notably, only 35% of isolates were susceptible to all seven agents. Carbapenemase genes were identified in 4% of isolates, including blaGES (n = 13), blaVIM (n = 7), blaKPC (n = 1) and blaIMP (n = 1). Among carbapenemase-producing isolates, cefepime-zidebactam retained activity against all isolates (100%), exceeding that of other approved β-lactam/β-lactamase inhibitor combinations (0%–24% susceptible), cefiderocol (76%), cefiderocol-xeruborbactam (86%) and cefepime-taniborbactam (81%). Conclusions While currently approved β-lactam agents retained activity against many DTR P. aeruginosa isolates, their performance was markedly compromised in the presence of carbapenemases, with the notable exceptions of cefepime-zidebactam and cefiderocol. Investigational β-lactam/β-lactamase inhibitor combinations exhibited consistently robust activity across resistance phenotypes, including carbapenemase-producing isolates, representing promising options for DTR P. aeruginosa infections.

Abstract We report an eightfold increase in sulbactam-durlobactam MICs in a carbapenem-resistant Acinetobacter baumannii cerebrospinal fluid isolate recovered after 14 days of sulbactam-durlobactam plus meropenem therapy. Treatment-emergent mutations in the AdeFGH efflux system were identified, accompanied by a 166-fold increase in adeG expression. Efflux pump inhibition restored sulbactam-durlobactam susceptibility.

The NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Breast Cancer focuses on the recommendations for the management of recurrent or stage IV (M1) metastatic breast cancer. It summarizes the treatment strategies stratified by tumor biology, including hormone receptor status and HER2 expression, as well as clinical factors such as prior therapy and disease-free interval. Throughout all treatment lines, supportive care, quality of life preservation, toxicity minimization, and clinical trial participation are emphasized as integral components of patient care.

Importance Opioid prescribing has decreased in the US for more than a decade. However, less is known about how prescribing trends differ by prescriber specialty and separately for short-term and long-term opioid prescribing for which the indications, clinical decision-making, and potential for harm vary substantially. Objective To characterize opioid analgesic prescribing trends in the US between January 1, 2010, and December 31, 2024, by prescriber specialty, analyzing short-term and long-term opioid use episodes separately. Design, Setting, and Participants This cross-sectional study used administrative claims data for commercially insured and Medicare Advantage patients (aged ≥65 years and <65 years with long-term disability) with at least 90 days of enrollment in medical and prescription coverage. Statistical analysis was performed from May 2025 to September 2025. Main Outcomes and Measures Prescribing volume, daily dose, and prescription duration. Results The study identified 110 288 218 opioid fills by 14 959 612 patients during the 15-year study period. Among opioid fills, 59.4% were attributed to female patients; the median (IQR) age at opioid fill was 61 (50-71) years. From 2010 to 2024, decreases in opioid prescribing were greater for long-term than short-term opioid use episodes (eg, commercial cohort: 81.3% reduction [from 33.2 fills per 100-person years in 2010 to 6.2 in 2024] and 74.6% reduction [from 36.2 fills per 100-person years in 2010 to 9.2 in 2024]), respectively. The proportion of all opioid fills written by primary care clinicians decreased (eg, Medicare Advantage with disability cohort: from 52.2% to 47.2%), whereas those written by pain medicine specialists increased (eg, Medicare Advantage with disability cohort: from 17.1% to 25.7%). Distinct trends for short-term and long-term opioid use episodes were observed in prescription characteristics, such as daily dose and duration. Conclusions and Relevance In this cross-sectional study of opioid prescribing trends in the US between 2010 and 2024, decreases in prescribing were greatest in long-term opioid use episodes, and prescribing was increasingly concentrated among pain medicine specialists. These findings suggest the need to balance reductions in opioid prescribing with provision of nonopioid pain treatments and raise concerns about access to care for patients taking opioids for chronic pain management.

Abstract Background Alzheimer’s disease (AD) is clinicopathologically heterogeneous. A proportion of patients living with AD present clinically at a younger onset of cognitive symptoms before 65 years old and/or non-amnestic clinical syndromes. Neuropathologically, corticolimbic distribution of neurofibrillary tangle pathology occurs on a continuum with some cases having greater cortical tau pathology relative to limbic regions and others with relatively restricted accumulation in limbic structures. These patterns of corticolimbic tangle distribution are associated with clinical presentation and age at onset. This study sought to examine protein expression differences across the spectrum of clinicopathologic heterogeneity using the NULISA targeted proteomics platform. Methods A series of thirteen neuropathologically diagnosed AD cases from Mayo Clinic prospectively followed research studies were selected to reflect heterogeneity of clinical syndromes and corticolimbic distribution of tangle pathology. Frozen postmortem brain tissue samples were isolated from inferior parietal cortex and homogenized in RIPA buffer for analysis using Alamar Biosciences’ NULISA CNS disease 120 panel. Applying a conservative detection threshold of 75% level of detection for the novel application of NULISA in human brain, we evaluated levels of 69 of 129 protein targets across samples. We examined associations between age at onset cognitive symptoms and corticolimbic distribution of tangles (CLix) separately with individual protein targets using linear regression analysis. Results AD cases with a younger age at onset had higher measured levels of ubiquitin, while older age was associated with higher levels of total tau, CRH, and NPTX2. Investigations of corticolimbic heterogeneity revealed AD cases with lower CLix score (i.e., cortical predominant distribution of tau) had higher measured p-tau181, p-tau231, ubiquitin, and p62. AD cases with higher CLix (i.e., relative cortical sparing) had higher levels of total tau, CRH, NPTX2, MDH1, and HBA1. Brain-derived total tau consistently showed a stronger association in both models. Conclusion This work demonstrates the utility of postmortem proteomics for investigating biomarkers associated with AD clinicopathologic heterogeneity. We observed proteomic differences in synapse integrity, tau post-translational modification, and ubiquitination associated with age at symptomatic onset and corticolimbic distribution of tangle pathology.

Abstract Objective This study was undertaken to provide an overview of the research landscape and evaluate the impact of lifestyle modifications on seizure reduction and quality of life in people with epilepsy receiving standard medical treatment. Methods Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines, we conducted a systematic review of major databases (Medline, Embase, American Psychological Association PsycInfo, Cochrane Library, and Web of Science) through November 2025. After screening 5151 articles, 118 studies met inclusion criteria: prospective trials reporting seizure frequency in adults or mixed populations with epilepsy. Four epilepsy‐trained reviewers independently assessed studies. A random‐effects meta‐analysis was performed on studies reporting ≥50% seizure reduction or data allowing its calculation. Short‐term response was defined as the earliest postintervention time point, and long‐term response as the final reported time point. Results The 118 studies covered diet ( n = 33), supplements ( n = 20), biofeedback ( n = 14), psychosocial/behavioral therapy ( n = 13), yoga/meditation/mindfulness ( n = 8), music therapy ( n = 7), and others. Fifty‐two (44%) included control groups, whereas 91 (77%) reported statistical analysis of seizure frequency. Among those, 68% showed significant seizure reduction. Quality of life was assessed in 31 studies, 68% reporting improvement. Seventy‐one studies (60%) were included in the meta‐analysis. Overall, the ≥50% seizure reduction response rate was 44% for short‐term outcomes (95% confidence interval [CI] = 38%–50%) and 50% for long‐term outcomes (95% CI = 44%–56%). Dietary interventions had the largest evidence base ( n = 33), with short‐ and long‐term response rates of 40% and 51%, respectively. Meditation/yoga/mindfulness had the highest response rate (62% short term, 79% long term), whereas exercise and supplements had the lowest (30%–35%). Significance Lifestyle modifications may offer beneficial, adjunctive effects on seizure control. However, the current evidence is limited by variability in study design and quality. Larger, well‐designed trials with standardized outcomes are needed to clarify how these interventions can complement epilepsy treatment. This systematic review and meta‐analysis serves as a foundation for future research to better define the role of lifestyle interventions in epilepsy care.

Scattered tubular-like cells (STCs) are dedifferentiated renal tubular cells that repair other damaged kidney cells. This study shows that renovascular disease (RVD) induces site-specific 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications in DNA associated with transcriptional changes and impaired proliferative capacity of swine STCs, which could be mitigated in RVD-STCs treated with an epigenetic modulator. Therefore, our observations may contribute to the development of novel approaches to preserve the reparative capacity of STCs in individuals with RVD.

Premature ventricular contractions (PVCs) are common arrhythmia encountered in patients with and without structural heart disease. Although often benign and asymptomatic, they may also cause palpitations, exercise intolerance, presyncope, and reduced quality of life, and in some patients can contribute to PVC-induced cardiomyopathy or trigger malignant ventricular arrhythmias. Their clinical significance depends on symptom burden, PVC frequency, ventricular function, and the presence of underlying myocardial disease. Diagnostic evaluation includes electrocardiography, ambulatory rhythm monitoring, echocardiography, exercise testing, and cardiac magnetic resonance imaging for tissue characterization and risk stratification. Management ranges from reassurance and lifestyle modification to pharmacologic therapy and catheter ablation. Beta-blockers and nondihydropyridine calcium channel blockers remain common first-line options, whereas antiarrhythmic drugs may be considered in carefully selected patients. Catheter ablation is an effective treatment for symptomatic PVCs, high PVC burden, and PVC-induced cardiomyopathy, with high procedural success rates and favorable effects on arrhythmic burden and ventricular function. Novel approaches, including electrocardiographic imaging-guided planning, pulsed field ablation, stereotactic radioablation, neuromodulation, and renal denervation, may further expand future therapeutic options. This review summarizes the pathophysiology, clinical implications, diagnostic evaluation, and contemporary management of PVCs, with emphasis on medical therapy, catheter ablation, and emerging treatments.

Introduction Hospital readmissions in the US place a considerable burden on patients and their caregivers. Our study will investigate whether spiritual intervention during a patient’s hospital stay contributes to lower rates of readmissions 30 days after hospital discharge. Methods Two hundred patients receiving palliative care will be randomized into control (n = 100) and intervention groups (n = 100). The control group will receive a standard spiritual support visit, while the intervention group will receive a spiritual intervention consisting of active listening, compassionate presence, assessment of post-discharge resources, and a supportive phone call 5 to 7 days after discharge. The primary outcome will be hospital readmission within 30 days of discharge. Board-certified chaplains will be allowed to use their individual skillsets but within the standardized ACA spiritual care model. Training chaplains to assess patients in the same way will help with this discrepancy as the same form will be used. Discussion We hypothesize that patients who receive spiritual intervention with a supportive phone call will experience fewer hospital readmissions. Spiritual intervention will instill.confidence in those patients at risk of readmission by assuring them that the hospital staff remain concerned about their well-being even after discharge.