Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014-2021. The utility of the previously defined total SIPAT cut-off (<21 [excellent/good candidates] vs ≥21 [minimally acceptable/high risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT score and LT waitlisting outcomes. Youden's J statistic was used to identify the optimal SIPAT cut-off for MASLD patients. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had SIPAT score ≥21. Patients with SIPAT score ≥21 had higher hemoglobin A1c compared to patients with lower psychosocial risk (median (IQR): 7.8 (6.0-9.7) vs 6.6 (5.8, 7.9); p=0.04). There were no other differences in metabolic comorbidities between SIPAT groups. Increasing SIPAT score was associated with decreased odds of listing (OR: 0.82 per five-point increase; p=0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cut-off in this population, resulting in an adjusted OR for listing of 0.53 vs SIPAT <12 (p=0.001). In this large cohort of MASLD patients evaluated for LT, few patients met the previously defined high SIPAT cut-off for transplant suitability. Nevertheless, increasing SIPAT score was associated with waitlist outcome. Our suggested SIPAT cut-off of ≥12 for MASLD patients warrants further external validation using data from other centers.

Radiofrequency ablation for the management of pancreatic mass lesions.

PURPOSE OF REVIEW: Patients with pancreatic tumors may have limited treatment options. Pancreatic tumor ablation is a novel and emerging treatment modality which can now be performed using endoscopic ultrasound (EUS) guidance. This modality is well suited to guide energy delivery for radiofrequency ablation (RFA) and microwave ablation. These approaches provide minimally invasive, nonsurgical methods for delivering energy to ablate pancreatic tumors in situ . This review summarizes the current data and safety profile for ablation in managing pancreatic cancer and pancreatic neuroendocrine tumors. RECENT FINDINGS: RFA uses thermal energy to induce cell death by coagulative necrosis and protein denaturation. Studies have reported increased overall survival in patients with pancreatic tumors treated with EUS-guided RFA in a multimodality systemic approach and when used in palliative surgeries. Radiofrequency ablation may have corollary benefits in inducing an immune-modulatory effect. Tumor marker carbohydrate antigen 19-9 has been reported to decrease in response to RFA. Microwave ablation is an emerging modality. SUMMARY: RFA utilizes focal thermal energy to induce cell death. RFA has been applied through open, laparoscopic, and radiographic modalities. EUS-guided approaches are now allowing RFA and microwave ablation to be performed for pancreatic tumors in situ .

The impact of screening for social risks on OBGYN patients and providers: A systematic review of current evidence and key gaps.

BACKGROUND: Increasingly, policymakers and professional organizations support screening for social assets and risks during clinical care. Scant evidence exists on how screening impacts patients, providers, or health systems. OBJECTIVE: To systematically review published literature for evidence of the clinical utility of screening for social determinants of health in clinical obstetric and gynecologic (OBGYN) care. SEARCH STRATEGY: We systematically searched Pubmed (March 2022, 5,302 identified) and identified additional articles using hand sorting (searching articles citing key articles (273 identified) and through bibliography review (20 identified)). SELECTION CRITERIA: We included all articles that measured a quantitative outcome of systematic social determinants of health (SDOH) screening in an OBGYN clinical setting. Each identified citation was reviewed by two independent reviewers at both the title/abstract and full text stages. DATA COLLECTION AND ANALYSIS: We identified 19 articles for inclusion and present the results using narrative synthesis. MAIN RESULTS: The majority of articles reported on SDOH screening during prenatal care (16/19) and the most common SDOH was intimate partner violence (13/19 studies). Overall, patients had favorable attitudes towards SDOH screening (in 8/9 articles measuring attitudes), and referrals were common following positive screening (range 5.3%-63.6%). Only two articles presented data on the effects of SDOH screening on clinicians and none on health systems. Three articles present data on resolution of social needs, with inconsistent results. CONCLUSIONS: Limited evidence exists on the benefits of SDOH screening in OBGYN clinical settings. Innovative studies leveraging existing data collection are needed to expand and improve SDOH screening.

A Descriptive Study of Maternal Vaccination Uptake, Attitudes, and Beliefs in Pregnancy Among Persons Delivering at an Urban Safety Net Hospital.

Objective: To estimate uptake of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), and COVID-19 vaccines during pregnancy and describe vaccine attitudes and beliefs among predominantly racial and ethnic minority individuals delivering at a publicly funded hospital. Methods: We collected survey and electronic medical record data for English-speaking postpartum individuals who delivered a live-born infant from July 7, 2022, through August 21, 2022, and agreed to participate in our study. The 58-item survey included questions about general vaccine attitudes and beliefs as well as vaccine-specific questions. We calculated rates of influenza, Tdap, and COVID-19 vaccinations and compared distributions of survey responses by number (no vaccines, one vaccine, or two or three of the recommended vaccines) and type of vaccines received during pregnancy. Results: Of the 231 eligible individuals, 125 (54.1%) agreed to participate. Rates of influenza, Tdap, and COVID-19 vaccination were 18.4%, 48.0%, and 5.6% respectively. A total of 61 (48.8%) did not receive any recommended vaccines during pregnancy, 40 (32.0%) received one vaccine, and 24 (19.0%) received two or three vaccines. Approximately 66.1% of the no vaccine group, 81.6% of the one vaccine group, and 87.5% of the two or three vaccine group strongly agreed or agreed that they trusted the vaccine information provided by their obstetrician or midwife. While most (>69.2%) agreed that the vaccine-preventable diseases were dangerous for pregnant women, only 24.0%, 29.3%, and 40.3% agreed that they were worried about getting influenza, whooping cough, or COVID-19, respectively, while pregnant. Discussion: Vaccine uptake in our population was low and may be due, in part, to low perceived susceptibility to vaccine-preventable diseases. Obstetricians and midwives were trusted sources of vaccine information, suggesting that enhanced communication strategies could be critical for addressing maternal vaccine hesitancy, particularly in communities of color justifiably affected by medical mistrust.

Caspase-11-mediated enteric neuronal pyroptosis underlies Western diet-induced colonic dysmotility.

Enteric neuronal degeneration, as seen in inflammatory bowel disease, obesity, and diabetes, can lead to gastrointestinal dysmotility. Pyroptosis is a novel form of programmed cell death but little is known about its role in enteric neuronal degeneration. We observed higher levels of cleaved caspase-1, a marker of pyroptosis, in myenteric ganglia of overweight and obese human subjects compared with normal-weight subjects. Western diet-fed (WD-fed) mice exhibited increased myenteric neuronal pyroptosis, delayed colonic transit, and impaired electric field stimulation-induced colonic relaxation responses. WD increased TLR4 expression and cleaved caspase-1 in myenteric nitrergic neurons. Overactivation of nitrergic neuronal NF-κB signaling resulted in increased pyroptosis and delayed colonic motility. In caspase-11-deficient mice, WD did not induce nitrergic myenteric neuronal pyroptosis and colonic dysmotility. To understand the contributions of saturated fatty acids and bacterial products to the steps leading to enteric neurodegeneration, we performed in vitro experiments using mouse enteric neurons. Palmitate and lipopolysaccharide (LPS) increased nitrergic, but not cholinergic, enteric neuronal pyroptosis. LPS gained entry to the cytosol in the presence of palmitate, activating caspase-11 and gasdermin D, leading to pyroptosis. These results support a role of the caspase-11-mediated pyroptotic pathway in WD-induced myenteric nitrergic neuronal degeneration and colonic dysmotility, providing important therapeutic targets for enteric neuropathy.

Mitochondrial DNA evolution in the Anaxyrus boreas species group.

The Anaxyrus boreas species group currently comprises four species in western North America including the broadly distributed A. boreas, and three localized species, Anaxyrus nelsoni, Anaxyrusexsul and Anaxyrus canorus. Phylogenetic analyses of the mtDNA 12S rDNA, cytochrome oxidase I, control region, and restriction sites data, identified three major haplotype clades. The Northwest clade (NW) includes both subspecies of A. boreas and divergent minor clades in the middle Rocky Mountains, coastal, and central regions of the west and Pacific Northwest. The Southwest (SW) clade includes A. exsul, A. nelsoni, and minor clades in southern California. Anaxyrus canorus, previously identified as paraphyletic, has populations in both the NW and SW major clades. The Eastern major clade (E) includes three divergent lineages from southern Utah, the southern Rocky Mountains, and north of the Great Basin at the border of Utah and Nevada. These results identify new genetic variation in the eastern portion of the toad's range and are consistent with previous regional studies from the west coast. Low levels of control region sequence divergence between major clades (2.2-4.7% uncorrected pair-wise distances) are consistent with Pleistocene divergence and suggest that the phylogeographic history of the group was heavily influenced by dynamic Pleistocene glacial and climatic changes, and especially pluvial changes, in western North America. Results reported here may impact conservation plans in that the current taxonomy does not reflect the diversity in the group.

Widespread phenotypic hypervariation in the enigmatic anchialine shrimp Barbouria cubensis (Decapoda: Barbouriidae).

Classification and evolutionary relationships among anchialine shrimp from the family Barbouriidae Christoffersen, 1987, has long been a topic of debate amongst crustacean taxonomists. To date, no study has examined morphological or molecular variation among populations of these enigmatic shrimp. The present study documents and analyzes patterns of widespread morphological variation within populations of Barbouria cubensis von Martens, 1872, from anchialine pools on three Bahamian islands. Such extensive morphological variation confounds identification using classic taxonomical methods. Phenotypic variation is by no means a new topic, but studies of decapods are typically limited to isolated individuals or few morphological characters. Moreover, past studies of B. cubensis do not report extensive morphological variation, however we find that upwards of 90% of individuals are affected. Anomalous phenotypes are described in 54 morphological characters with no detectable pattern associated with geographic distribution. The term phenotypic hypervariation (PhyV) is used to describe morphological variation that greatly deviates from any previous taxonomic descriptions.  Analysis of partial sequences of the 16S and COI mitochondrial genes confirm the identity of morphologically variable specimens as B. cubensis without population structure across the tropical western Atlantic. A test for cryptic diversity within B. cubensis suggests PhyV is not correlated with cryptic diversity. Morphological variation at this scale likely depends on recent changes either to their environment or genetic diversity.

Natural History of Pediatric Low-Grade Glioma Disease - First Multi-State Model Analysis.

Background: Pediatric low-grade glioma [PLGG] is often a chronic progressive disease requiring multiple treatments, i.e. surgery, chemotherapy and irradiation. The multi-state model [MSM] allows an extended analysis of disease-states, that patients may undergo, incorporating competing risks over the course of time. Purpose: We studied disease-state-probabilities of the German SIOP-LGG 2004 cohort from the initial state "diagnosis" to the final state "death". Transient "disease-states" incorporated successive surgical and non-surgical treatments. We evaluated clinical risk factors for highly progressive disease requiring multiple interventions and death. Results: We identified 22 states within 1587 patients (median follow-up 6.3 years). For robust statistical calculation, we reduced the model to 7 states and eventually to three levels of disease-progressiveness: non, low and highly progressive. Five years after diagnosis state-probabilities were: 0.11 no therapy, 0.49 one and 0.11 two or more surgeries only, 0.19 one and 0.06 two or more non-surgical interventions with or without prior surgery. At this time point higher probability for highly progressive disease was found in infants (0.30), supratentorial-midline location (0.17) and diffuse astrocytoma WHO-grade II (0.12). Neurofibromatosis type-1 patients were most likely not to be treated (0.36) or to have received only non-surgical therapy (0.45). Two years after diagnosis 3-year predictions for highly progressive disease and death increased with the number of interventions patients underwent in the first 2 years after diagnosis. Conclusion: In this first MSM analysis we delineated a refined description of PLGG disease course over time, identifying three levels of progressiveness. Growth behavior in the first two years predicted future progressiveness and death.

Motor function in survivors of pediatric acute lymphoblastic leukemia treated with chemotherapy-only.

BACKGROUND: Up to 43% of survivors of pediatric acute lymphoblastic leukemia (ALL) may exhibit fine-motor problems. Information on manual dexterity in this cohort is still limited. OBJECTIVES: We tested survivors of childhood ALL treated with chemotherapy-only for fine-motor function in terms of drawing and handwriting abilities using a Digitizing Tablet (DT) with three tasks for drawing and handwriting of varying complexity, for ataxia using the International Cooperative Ataxia Rating Scale (ICARS), and for tremor and hand-eye coordination using the Nine Hole Steadiness Tester (NHST). RESULTS: We examined a cohort of non-irradiated survivors (n = 31) after a median time of 3.5 years after end of therapy. In all tasks of the DT the cohort demonstrated significant (p < 0.05) impairment of speed, automation, and variability in at least two tasks and significantly more pressure. Impaired speed (SPV) inversely correlated with lag time since end of therapy. Dexterity performance of six survivors (19%) lay below the 5th percentile. No survivor exhibited ataxia, tremor, or impaired hand-steadiness. CONCLUSION: Despite the absence of gross ataxia, tremor, and impaired hand-eye coordination, we nevertheless detected significant fine-motor impairment in a relevant number of survivors of childhood ALL. Prospective studies are needed to reveal the pathophysiological underpinnings and genetic risk factors for development of such deficits due to ALL and its treatment.