Citations

Background Although micro‐ and nanoplastics are an emerging risk factor for the development of cardiovascular diseases, the association of marine microplastic levels (MMLs) with the burden of cardiometabolic diseases at a population level remains unexplored. We investigated the relationship between the mean microplastic concentration in ocean water within 200 nautical miles of the US coastline and the prevalence of type 2 diabetes, coronary artery disease, and stroke in nearby counties. Methods Microplastic concentration data within 200 nautical miles of the US coastline were geospatially analyzed to calculate mean MMLs. The coastal counties were stratified into 4 categories based on MMLs in the adjacent ocean water body: low, medium, high, or very high. The Behavioral Risk Factor Surveillance System 2019 to 2020 survey data were used to identify the prevalence of type 2 diabetes, coronary artery disease, and stroke in these counties. Univariate and population‐weighted multivariate quasi‐Poisson regression, adjusted for county‐level confounding variables, was used to evaluate the unadjusted and adjusted associations between disease prevalence and MMLs. Results The mean age of the population was 43±6 years. After adjusting for age, sex, physician access, and socioenvironmental vulnerabilities at the county level, counties with very high MMLs exhibited an 18%, 7%, and 9% higher adjusted prevalence of type 2 diabetes, coronary artery disease, and stroke, respectively, compared with those with low levels. Conclusion Marine microplastic levels were significantly associated with the prevalence of cardiometabolic diseases in coastal counties. Comprehensive studies at an individual level are needed to further investigate the health impacts of microplastic pollution.

Objective: We comparatively analyzed the longitudinal outcomes of conversion to open procedure, laparoscopic subtotal cholecystectomy (CCY), and laparoscopic cholecystostomy tube placement. Background: Severe cholecystitis often causes dense inflammation that distorts the hepatocystic anatomy and can make safe dissection during CCY challenging. However, controversy exists regarding the optimal bailout procedure in such situations. Methods: The New York and Florida State all-claims databases were queried for patients who underwent laparoscopic CCY for acute cholecystitis from 2012 to 2021. Hierarchical logistic regression models were used to obtain adjusted estimates, with fixed effects assigned to patient-level variables and random effects assigned to hospital identifiers to adjust for intraclass correlation. Results: Of 384,948 laparoscopic CCYs performed, 5448 (1.4%) were not completed laparoscopically; 1370 underwent conversion to open procedure, 2646 underwent laparoscopic subtotal CCY, and 1432 underwent laparoscopic cholecystostomy tube placement. The conversion to open rate decreased from 0.6% in 2012 to 0.3% in 2021, while the laparoscopic subtotal CCY rate increased from 0.2% in 2012 to 1.4% in 2021. The 1-year bile duct injury (BDI) rate was highest for the conversion to open group (4.4%), followed by the laparoscopic subtotal CCY (0.8%) and laparoscopic cholecystostomy tube groups (0.3%, P<0.001). On adjusted analyses with the conversion to open group as the control, laparoscopic subtotal CCY (OR: 0.17, P<0.001) and laparoscopic cholecystostomy tube were associated with lower BDI rates (OR: 0.08, P<0.001, Figure). The 1-year postoperative endoscopic biliary intervention rate was lowest for the conversion to open group (4.2%), followed by the laparoscopic subtotal CCY (8.4%) and the laparoscopic cholecystostomy tube groups (8.8%, P<0.001). The completion CCY rates for the laparoscopic subtotal CCY and laparoscopic cholecystostomy tube groups were 2.1% and 23.4%, respectively. Among completion CCYs, the open rates were 56.4% in the laparoscopic subtotal CCY group versus 24.5% in the laparoscopic cholecystostomy tube group (P<0.001). Conclusions: In patients with severe cholecystitis requiring a bailout procedure, the BDI rate was highest after conversion to open procedure. Laparoscopic subtotal CCY and laparoscopic cholecystostomy tube were associated with lower BDI rates at the cost of higher postoperative endoscopic biliary intervention rates. Completion CCYs were required in 2.1% and 23.4% of patients who underwent laparoscopic subtotal CCY and laparoscopic cholecystostomy tube placement, respectively, of which the former group’s CCY was more likely to require an open operation.

Aims Testicular sex cord‐stromal tumours (TSCSTs) are relatively rare, accounting for ~5% of all testicular neoplasms. They were historically classified into Leydig cell tumour, Sertoli cell tumour, granulosa cell tumour, and unclassified sex cord‐stromal tumour. More recently, classification was expanded to incorporate additional histologic types, including some associated with inherited cancer predisposition syndromes. However, the classification of TSCSTs still relies entirely on morphology, with some tumour types being defined based on their resemblance to ovarian counterparts. In recent years, molecular studies have identified drivers and genomic alterations associated with aggressive behaviour and progression; however, these findings have not yet impacted classification and management. Methods and results Under sponsorship of the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS), a group of genitourinary pathologists was assembled in 2023 with the aim of assessing how to use these new data to improve the classification and management of TSCSTs. Conclusions This paper summarizes the recommendations derived from the consensus activities and the first meeting of the te sticular s ex cord‐ s tromal t umour (TESST) group (held at Johns Hopkins Hospital, Baltimore, USA, 3/23/2024).

Abstract Objective This study was undertaken to evaluate the response to second treatments for infantile epileptic spasms syndrome (IESS). Methods Infants aged 2–24 months with IESS were prospectively enrolled in the National Infantile Spasms Cohort study at 21 pediatric epilepsy centers in the United States from 2012 to 2018. We analyzed data from infants who initially received standard treatment (hormonal therapy [adrenocorticotropic hormone, high‐dose prednisolone] or vigabatrin), had continued or recurring epileptic spasms, and received a second treatment. We excluded those with tuberous sclerosis. Treatment groups included hormonal therapy followed by vigabatrin (reference), hormonal‐to‐hormonal, hormonal‐to‐nonstandard, vigabatrin‐to‐hormonal, and vigabatrin‐to‐nonstandard. Nonstandard treatments included other antiseizure medications and dietary therapy. Treatment groups were tested for differences in 3‐month clinical remission using a binary logistic regression to estimate odds ratios (ORs). Results There were 153 infants with IESS who received second treatments. The highest rates of 3‐month remission were among infants in the hormonal‐to‐vigabatrin (22/65, 34%) and vigabatrin‐to‐hormonal (9/26, 35%) groups, followed by vigabatrin‐to‐nonstandard (3/10, 30%), hormonal‐to‐hormonal (4/22, 18%), and hormonal‐to‐nonstandard (1/30, 3.3%). Compared to the hormonal‐to‐vigabatrin group (reference), fewer infants had remission in the hormonal‐to‐nonstandard group (OR = .07, 95% confidence interval [CI] = .01–.53), and there was a trend toward fewer infants in the hormonal‐to‐hormonal group (OR = .43, 95% CI = .13–1.4, p = .17). Following initial hormonal treatment, the number needed to treat was three infants for one additional infant to have remission when treated with vigabatrin compared to nonstandard therapy as the second treatment. Significance This updated analysis with an expanded sample size provided power for additional subgroup analysis. Overall response rates were low, and at best only one third had remission after second treatment. Results support a clinical strategy of switching mechanism of action when selecting a second medication for epileptic spasms (i.e., use vigabatrin after hormonal therapy, or hormonal therapy after vigabatrin). Our findings also support the use of standard over nonstandard therapies.

Activation of oncogenes, such as through mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS), triggers profound disruptions in cellular homeostasis that set off a cascade of stress responses. These responses enable cells to cope with the array of challenges encountered during tumorigenesis by activating defense mechanisms that promote adaptation and survival. Key components of this oncogenic stress response include heat shock proteins, the ubiquitin-proteasome system, autophagy, nuclear factor erythroid 2-related factor 2–antioxidant response element signaling, DNA damage response proteins, p53, redox-regulating proteins, and stress granules. This review concentrates on KRAS-driven oncogenic transformation, as KRAS mutations are among the most common in human cancers, accounting for over 90% of pancreatic ductal adenocarcinoma cases, around 30% of lung cancers, and approximately 50% of colorectal cancers. We examine the intricate molecular interplay between oncogenic stress and the associated cellular defense mechanisms, emphasizing the key molecular events that follow KRAS activation. Importantly, the very pathways that allow cancer cells to adapt to oncogenic stress also offer novel therapeutic opportunities. By selectively targeting pivotal regulators within these stress response pathways, we can potentially disrupt the survival mechanisms of cancer cells. This strategy not only promises to enhance the effectiveness of existing treatments but also paves the way for the development of innovative therapies designed to combat tumor progression. In essence, exploiting oncogenic stress responses represents an original and promising therapeutic approach in the fight against cancer.

AbstractINTRODUCTIONGiven the close interactions between the retina and the brain, retinal amyloid imaging may serve as a diagnostic and prognostic tool for Alzheimer's disease and related dementias. This retrospective study investigated multivariable associations between retinal perivascular amyloid and cognitive domains.METHODSIntegrated analysis of retinal perivascular amyloid imaging, neuropsychological assessment, and brain magnetic resonance imaging in adults with and without cognitive impairment (N = 26; mean age: 65 ± 7 years; 50% female). Correlations between perivascular amyloid plaque burden and cognitive domains were evaluated with linear regression and interactions with hippocampal volumetry were explored.RESULTSHigher perivascular and periarteriolar amyloid plaque count in the secondary small and tertiary branches were associated with poorer verbal and visual memory in this cohort (p = 0.005–0.009). Higher perivascular amyloid burden interacted with hippocampal atrophy to worsen visual memory (p = 0.033).DISCUSSIONRetinal perivascular amyloid may serve as a non‐invasive marker for cognitive impairment and may shed insight into pathological changes in the brain.Highlights In vivo retinal perivascular amyloid plaque counts are associated with poorer memory. Retinal perivascular amyloid interacted with hippocampal atrophy to worsen memory. Retinal amyloid imaging is a potential biomarker for neurodegenerative diseases.

Importance Bilateral vocal cord paralysis is a challenging problem to manage in adults, and a known complication of thyroid surgery which is more common in resource-limited settings. Posterior graft laryngotracheal reconstruction is a management option that has not been studied in this population or setting. Objective To report the surgical outcomes of posterior graft laryngotracheal reconstruction for bilateral vocal cord paralysis in a resource-limited setting, and to evaluate the efficacy of a hybrid system for teaching this technique in Kenya. Design Retrospective cohort study. Setting Tertiary public referral hospital, Eldoret, Kenya Participants Adults >18 years with tracheostomy dependence secondary to bilateral vocal cord paralysis after thyroid surgery or other iatrogenesis. The hybrid training program included Kenyan surgeons and surgical trainees. Intervention or Exposures Posterior graft laryngotracheal reconstruction and hybrid training system included didactic lectures, simulation-based training, case discussion and planning, and live cases. Main Outcomes Measures One-year airway outcomes measured by achievement of tracheostomy decannulation, and self-reported surgeon knowledge and skill acquisition. Results Ten patients met criteria and were included in the analysis, with mean age 42 years (range 30-62 years) and had been tracheostomy dependent for an average of 6 years (range 1-12 years). Seven (70%) had open reconstruction, and 3 (30%) had endoscopic reconstruction. All were decannulated and remained tracheostomy-free at 1 year. Three surgeons and 7 trainees participated in the hybrid teaching methods. All reported increased comfort in laryngotracheal reconstruction, with all 3 surgeons reporting comfort performing the surgeries independently. Conclusion Posterior graft laryngotracheal reconstruction shows promise as a potential method of treating bilateral vocal cord paralysis and achieving decannulation in a resource-limited setting. Relevance The methods reported in this study lend themselves to replication and expansion to other similar settings. The authors plan to replicate this work in other centers in East Africa.

PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.

Although innovation in cancer treatment has improved cure rates and survival, the costs have escalated beyond societies' ability to pay. Cancer care costs in the United States are expected to rise to 245 billion by 2030. In this health policy session, we focused on three cost-containment strategies, and their potential impact on cancer care delivery. Site Neutrality: Curbing the Cost of Cancer Care, but at What Risk? , explores legislation that would introduce payment parity across differing sites of care: elimination of facility fees in hospital owned practices and shift of billing for oncology infusions away from hospital owned practices. Unintended consequences could reduce access to care for vulnerable populations, shift costs to patients, and reduce safety. Post-Pandemic Digital Health Reimbursement: Impact on Access to Care , explores how the emergency waivers, licensure flexibilities, and parity reimbursement necessitated by COVID-19 shepherded innovation that outpaced the regulatory framework needed for long-term sustainability. Today, telehealth services, hospital at home, remote patient monitoring, and decentralized clinical trial enrollment face reintroduction of regulatory and payment barriers. Will we live to see efficacy-based pricing for cancer drugs? Learning from international models , explores how lack of drug price negotiation has led to higher prices in the United States compared with Canada and Europe. Comparative clinical effectiveness pricing systems compare the value of each drug to standard treatments. Comparative cost-effectiveness programs look at the incremental cost per additional unit of health gained above the standard of care. The United States could learn from these approaches used in comparable countries.