Lumen-apposing metal stents provide early and late clinical benefits for the management of benign gastrointestinal strictures: Is there a role for definitive therapy?

Objectives: This study aimed to characterize the clinical outcomes, safety, and efficacy of lumen-apposing metal stents (LAMS) in treating benign gastrointestinal strictures. Methods: A single-center retrospective review of all patients who underwent LAMS placement for benign strictures from June 2017 to July 2023. Primary outcomes were technical success, early clinical success, late clinical success (LCS), and sustained post-LAMS clinical success (SPLCS). Secondary outcomes included stent dwell time, stenosis changes, adverse events, reintervention rates, and symptomatology evaluation. Results: Thirty-five patients underwent placement of 42 LAMS (74% female, mean age: 54.2 ± 11.7 years). Anastomotic strictures accounted for 64% of cases (N = 27, 45% at the gastrojejunal anastomosis). The median STD was 91.0 days (interquartile range [IQR]: 55.0-132.0). Technical success was obtained in all cases. Early clinical successand LCS were achieved in 80% of cases overall. SPLCS was achieved in 45% (n = 15) of cases. The overall reintervention rate was 63%, with a median time to reintervention being 50.5 days (IQR: 24-105). adverse events occurred in 28% (n = 12) overall, with a 24% migration rate (n = 10). Follow-up was completed in 83% of cases with a median duration of 629 days (range: 192.0-1297.0). Overall symptom improvement occurred in 79% (n = 27) during indwelling LAMS versus 58% and 56% at 30- and 60-days post-removal, respectively. Conclusions: LAMS for benign gastrointestinal strictures are associated with high technical and early clinical success/LCS rates, positive quality-of-life metrics, and a tolerable adverse event rate. Overall, recurrence of symptoms and high reintervention rates post-LAMS removal reinforce the difficulty in managing benign gastrointestinal strictures but also argue for LAMS as a definitive therapy in select cases.

Solitary Giant Primary Gastric Plasmacytoma Mimicking Gastric Adenocarcinoma In Situ.

A solitary extraosseous plasmacytoma is a rare type of plasma cell neoplasm. Its occurrence in the stomach is particularly unusual and can easily be mistaken for more common types of tumors. We describe a case involving a solitary extraosseous plasmacytoma in a patient who experienced weight loss as the sole symptom. Initially, the condition was misdiagnosed as gastric adenocarcinoma based on endoscopic biopsy results, leading to a gastrectomy after neoadjuvant chemotherapy. Subsequent examination of the pathological specimen revealed the presence of plasma cell neoplasia alongside a gastric adenocarcinoma in situ.

MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution.

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution.

Evaluating serum free light chain ratio as a biomarker in multiple myeloma.

Not available.

Nodular Scleroderma: Characterization of a Distinct Clinical Phenotype.

Nodular scleroderma is a rare variant of systemic sclerosis (SSc) characterized by fleshy, indurated nodules commonly distributed over the upper and lower extremities and in the trunk. Most scientific publications of the nodular and keloid variants of scleroderma use the terms interchangeably. However, nodular scleroderma has been recently differentiated from keloid forms. Although few cases of isolated local involvement have been reported, nodular scleroderma more commonly presents in conjunction with other manifestations of SSc. We performed a review of all cases of nodular scleroderma reported in the literature to characterize their clinical features. This review indicated that Nodular Scleroderma is usually associated with a Diffuse SSc phenotype and develops during the early progressive skin involvement. Patients with the Nodular Scleroderma phenotype display antinuclear antibodies with speckled or nucleolar patterns, a low frequency of positive SSc-specific antibodies, and typical SSc multiorgan involvement. However, a very low frequency of pulmonary hypertension was found in these patients. Although immunosuppressive or antifibrotic treatment may improve skin thickening and organ involvement, the characteristic nodules are refractory to treatment with these agents. This is the first review, to our knowledge, characterizing the nodular phenotype in patients with SSc.

Managing the Bariatric Surgery Patient: Presurgery and Postsurgery Considerations.

Obesity has extensive health repercussions, and bariatric surgery remains a viable solution to address this issue. This article focuses on the preoperative and postoperative management strategies required to achieve successful and durable outcomes in bariatric surgery patients. Preoperative assessment includes appropriate patient selection, psychosocial evaluation, nutritional analysis, and behavioral/medical counseling. Postoperative assessment includes immediate perioperative care, diet transition, nutritional needs management, and handling of complications associated with bariatric surgery.

Intragastric Balloons: Practical Considerations.

Obesity is escalating, projected to affect 17.5% of adults globally and afflict 400 million children by 2035. Managing this intricate and chronic condition demands personalized, multidisciplinary approaches. While dietary changes, lifestyle modifications, and medications yield short-term results, long-term outcomes are often poor, with bariatric surgery standing out as the most effective option. However, only a small fraction undergoes surgery due to various barriers. Intragastric balloon (IGB) emerges as a minimally invasive alternative, approved by major regulatory bodies. This review adresses the pivotal role of IGB in obesity management, delving into its history and technological evolution.

Development and Evaluation of the Biological Activities of a Plain Mucoadhesive Hydrogel as a Potential Vehicle for Oral Mucosal Drug Delivery.

This study aimed to develop HGs based on cationic guar gum (CGG), polyethylene glycol (PEG), propylene glycol (PG), and citric acid (CA) using a 2k factorial experimental design to optimize their properties. HGs were characterized through FTIR and Raman spectroscopy, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The biological activities of HGs were determined by evaluating their mucoadhesive capacity and antibacterial activity in vitro, whereas their toxicity was analyzed using Artemia salina nauplii as an in vivo model. Results revealed that HGs were successfully optimized for their viscosity, pH, and sensory properties, and it was observed that varying concentrations of PEG-75 did not influence them. Through SEM analyses, it was noted that increased levels of PEG-75 resulted in HGs with distinct porosity and textures, whereas FTIR and Raman spectroscopy exhibited representative peaks of the raw materials used during the synthesis process. TGA studies indicated the thermal stability of HGs, as they presented degradation patterns at 100 and 300 °C. The synthesized HGs exhibited similar mucoadhesion kinetic profiles, demonstrating a displacement factor at an equilibrium of 0.57 mm/mg at 5 min. The antibacterial activity of HGs was appraised as poor against Gram-positive and Gram-negative bacteria due to their MIC90 values (>500 µg/mL). Regarding A. salina, treatment with HGs neither decreased their viability nor induced morphological changes. The obtained results suggest the suitability of CGG/PEG HGs for oral mucosa drug delivery and expand the knowledge about their mucoadhesive capacity, antibacterial potential, and in vivo biocompatibility.

Fungal Diversity in an Undisturbed Andean Páramo Soil in Quimsacocha (Ecuador).

The Andean Páramo is an environment known for its high biodiversity; however, due to its remote location and difficult access, it is still relatively poorly studied. The aim of this work was to explore the fungal biodiversity of Ecuadorian Páramo soils in the undisturbed natural reserve of Quimsacocha through ITS metabarconding with an MiSeq platform. This analysis revealed the presence of 370 fungal Amplicon Sequence Variants (ASVs), mainly composed by Ascomycota, Mortierellomycota and Basidiomycota. The biodiversity had a great variability among the 19 samples, but the soil humidity proved to be a significant driver of diversity in the relatively dry environment of Páramo. Some of most abundant fungal genera have important relationships with plant roots. This work represents the first glimpse into the complex biodiversity of soil fungi in this understudied area, and further studies will be needed to better understand the fungal biodiversity in this region, together with the development of necessary measures of environmental protection.

Post-Pandemic Maternity Care Planning for Vaccination: A Qualitative Study of the Experiences of Women, Partners, Health Care Professionals, and Policy Makers in the United Kingdom.

Maternal vaccination during pregnancy, in general and against COVID-19 infection, offers protection to both mother and baby, but uptake remains suboptimal. This study aimed to explore the perceptions regarding COVID-19 vaccination in pregnancy, particularly for marginalised populations and those living with social or medical complexity. A total of 96 semi-structured in-depth interviews were conducted with 40 women, 15 partners, 21 HCPs, and 20 policy makers, across all four nations of the United Kingdom (UK), discussing their lived experience of utilising, delivering, or developing policy for COVID-19 vaccination in pregnancy during the pandemic. Three themes were derived: (1) historical and social context, (2) communication of information and guidance, and (3) appraisal and action. Together these captured the participants' legacy of mistrust in drugs during pregnancy; prior positive experiences; concerns about missing information, conflicting information, or false information about COVID-19 vaccines; and confusing guidance for pregnant women. The final theme describes the participants' behaviour and actions undertaken consequent to their experiences and the available information. The findings suggest efforts to improve COVID-19 vaccination in pregnancy may be best focused on personalised communication of information. A trusting relationship and prior positive experiences with other vaccines, both in and outside of pregnancy, positively influenced perceptions of COVID-19 vaccination.

Oceanographical-driven dispersal and environmental variation explain genetic structure in an upwelling coastal ecosystem.

The seascape comprises multiple environmental variables that interact with species biology to determine patterns of spatial genetic variation. The environment imposes spatially variable selective forces together with homogenizing and diverging drivers that facilitate or restrict dispersal, which is a complex, time-dependent process. Understanding how the seascape influences spatial patterns of genetic variation remains elusive, particularly in coastal upwelling systems. Here, we combine genome-wide SNP data, Lagrangian larval dispersal simulated over a hydrodynamic model, and ocean environmental information to quantify the relative contribution of ocean circulation and environmental heterogeneity as drivers of the spatial genetic structure of two congeneric intertidal limpets, Scurria scurra and S. araucana, along the central coast of Chile. We find that a genetic break observed in both limpet species coincides with a break in connectivity shown by the Lagrangian dispersal, suggesting that mean ocean circulation is an important seascape feature, in particular for S. scurra. For S. araucana, environmental variation appears as a better predictor of genetic structure than ocean circulation. Overall, our study shows broad patterns of seascape forcing on genetic diversity and contributes to our understanding of the complex ecological and evolutionary interactions along coastal upwelling systems.

Conspiratorial thinking in a 50-state survey of American adults.

Background: While the NIMH Research Domain Criteria framework stresses understanding how neuropsychiatric phenotypes vary across populations, little is known outside of small clinical cohorts about conspiratorial thoughts as an aspect of cognition. Methods: We conducted a 50-state non-probability internet survey conducted in 6 waves between October 6, 2022 and January 29, 2024, with respondents age 18 and older. Respondents completed the American Conspiratorial Thinking Scale (ACTS) and the 9-item Patient Health Questionnaire (PHQ-9). Survey-weighted regression models were used to examine sociodemographic and clinical associations with ACTS score, and associations with vaccination status. Results: Across the 6 survey waves, there were 123,781 unique individuals. After reweighting, a total of 78.6% of respondents somewhat or strongly agreed with at least one conspiratorial idea; 19.0% agreed with all four of them. More conspiratorial thoughts were reported among those age 25 - 54, males, individuals who finished high school but did not start or complete college, those with household income between $25,000 and $50,000 per year, and those who reside in rural areas, as well as those with greater levels of depressive symptoms. Endorsing more conspiratorial thoughts was associated with a significantly lower likelihood of being vaccinated against COVID-19. Discussion: A substantial proportion of US adults endorsed at least some conspiratorial thinking, which varied widely across population subgroups. The extent of correlation with non-vaccination suggests the importance of considering such thinking in designing public health strategies.

Haploidentical Stem Cell Transplantation With TCR αß+/CD19+ Depletion in Children With Nonmalignant Hematologic Disorders: Outcomes From a Referral Center in Peru.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with TCR αß+/CD19+ cell depletion is a promising therapeutic alternative for children with nonmalignant hematologic disorders, especially in low-income countries where finding a compatible donor is challenging. The use of this transplantation approach for nonmalignant hematologic disorders has not been previously described in the Peruvian pediatric population. METHODS: We present the outcomes of children under 19 with nonmalignant hematologic disorders who underwent haplo-HSCT with TCR αß+/CD19+ cell depletion between 2018-2022 at a referral center in Lima, Peru. Survival probabilities and cumulative incidence functions were calculated using the Kaplan-Meier method. RESULTS: A total of 17 children aged between 1 to 18.6 years (median = 9.7 years) were included. The follow-up period ranged from 10 days to 66.20 months, with a median of 4.34 months. The probability of overall survival, event-free survival, and failure-free survival was 33.70%, 31.40%, and 68.8%, respectively. The incidence rate of graft failure was 49.80%, while the mortality rate not associated with graft failure was 18.8%. The incidence rate of acute graft-versus-host disease (GvHD) was 25.60%, and the incidence rate of viral infections was 59.40%. CONCLUSIONS: The high incidence rates of graft failure and viral infections suggest that these factors may negatively impact the survival of children with nonmalignant hematologic disorders who undergo haplo-HSCT with TCR αß+/CD19+ cell depletion. Therefore, optimizing the current conditioning regimens and ensuring timely access to first, second, and third-line antivirals is crucial to improve the survival of these patients.

Phytotherapeutic potential of Artemisia ludoviciana and Cordia boissieri extracts against the dermatophyte Microsporum canis.

Introduction: Microsporum canis is a dermatophyte that mainly affects dogs and cats. However, it can be transmitted to humans by direct contact. This makes it one of the most frequent causative agents of dermatophytosis in humans, reflecting the frequent human close relationships with pets. Conventional treatment relies on antifungal pharmacological agents. However, errors in application have led to the occurrence of fungal resistance and toxic effects. Consequently, new therapeutic alternatives are needed for M. canis infections. Plant extracts have been explored as phytotherapeutics for the treatment of dermatophyte infections, which prompted an attempt to apply extracts of the ethnopharmacologically important plants Artemisia ludoviciana and Cordia boissieri. Material and Methods: Methanolic extracts of these two plants were obtained using a Soxhlet method and were characterised by phytochemical screening. Extracts were evaluated against a M. canis commercial strain (ATCC-11621) using the microdilution method described in the Clinical and Laboratory Standards Institute protocol M38-A, determining its minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC). Subsequently, these concentrations were tested in a human keratinocyte human cell line. Results: Artemisia ludoviciana and C. boissieri extracts showed MIC values of 2,500 and 1,250 µg/mL, and MFC values of 5,000 and 2,500 µg/mL against M. canis, respectively. These extracts did not inhibit HaCaT cell proliferation in vitro. Conclusion: The evaluated extracts showed potential for the treatment of M. canis fungal infections. However, further studies on their phytochemical characterisation, purification, clinical safety and formulation are required.

Mechanisms behind the high mortality rate in chronic Chagas cardiomyopathy: Unmasking a three-headed monster.

Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC), the most severe form of target organ involvement in Chagas disease, is characterized by a complex pathophysiology and a unique phenotype that differentiates it from other cardiomyopathies, highlighting its worse prognosis compared to other aetiologies of heart failure. The three pathophysiological mechanisms with the largest impact on this differential mortality include rapidly progressive heart failure, a high incidence of stroke, and a high burden of ventricular arrhythmias. However, despite significant advances in understanding the unique molecular circuits underlying these mechanisms, the new knowledge acquired has not been efficiently translated into specific diagnostic and therapeutic approaches for this unique cardiomyopathy. The lack of dedicated clinical trials and the limited CCC-specific risk stratification tools available are evidence of this reality. This review aims to provide an updated perspective of the evidence and pathophysiological mechanisms associated with the higher mortality observed in CCC compared to other cardiomyopathies and highlight opportunities in the diagnostic and therapeutic approaches of the disease.

Assessing abundance-suitability models to prioritize conservation areas for the dwarf caimans in South America.

Species-environment relationships have been extensively explored through species distribution models (SDM) and species abundance models (SAM), which have become key components to understand the spatial ecology and population dynamics directed at biodiversity conservation. Nonetheless, within the internal structure of species' ranges, habitat suitability and species abundance do not always show similar patterns, and using information derived from either SDM or SAM could be incomplete and mislead conservation efforts. We gauged support for the abundance-suitability relationship and used the combined information to prioritize the conservation of South American dwarf caimans (Paleosuchus palpebrosus and P. trigonatus). We used 7 environmental predictor sets (surface water, human impact, topography, precipitation, temperature, dynamic habitat indices, soil temperature), 2 regressions methods (Generalized Linear Models-GLM, Generalized Additive Models-GAM), and 4 parametric distributions (Binomial, Poisson, Negative binomial, Gamma) to develop distribution and abundance models. We used the best predictive models to define four categories (low, medium, high, very high) to plan species conservation. The best distribution and abundance models for both Paleosuchus species included a combination of all predictor sets, except for the best abundance model for P. trigonatus which incorporated only temperature, precipitation, surface water, human impact, and topography. We found non-consistent and low explanatory power of environmental suitability to predict abundance which aligns with previous studies relating SDM-SAM. We extracted the most relevant information from each optimal SDM and SAM and created a consensus model (2,790,583 km2) that we categorized as low (39.6%), medium (42.7%), high (14.9%), and very high (2.8%) conservation priorities. We identified 279,338 km2 where conservation must be critically prioritized and only 29% of these areas are under protection. We concluded that optimal models from correlative methods can be used to provide a systematic prioritization scheme to promote conservation and as surrogates to generate insights for quantifying ecological patterns.

House-roof Neoumbilicoplasty: Six-step Procedure for a Natural Navel.

Background: The umbilicus significantly contributes to abdominal aesthetics, with its reconstruction often necessary after certain procedures like umbilical herniorrhaphy, laparotomies, and abdominoplasty. Neoumbilicoplasty techniques have evolved, addressing various issues through approaches like skin and cartilage grafts, and local flaps. We are reporting our technique for neoumbilicoplasty. Methods: This study describes a novel neoumbilicoplasty technique implemented in 90 patients (88 women, two men) who underwent lipoabdominoplasty between February 2021 and June 2023. Exclusion criteria included procedures unrelated to neoumbilicoplasty. Surgical steps involved precise marking, dissection, and suturing to create a natural umbilical hood. Patient satisfaction was measured using the Global Aesthetic Improvement Scale. Results: The mean age was 37.7 years, with pre- and postoperative anatomics of 24.9 kg per m² and 24.2 kg per m², respectively. The average surgery duration was 84 minutes. No major complications occurred, but minor complications included dehiscence (6%), granuloma (5%), superficial infection (2%), bruising (1%), seroma (1%), and flattening (8%). Most complications were resolved with minor interventions. Patient satisfaction was high, with 96% of patients and the surgeon expressing significant satisfaction. Conclusions: House-roof neoumbilicoplasty is an innovative technique designed to effectively restore abdominal aesthetics through straightforward steps and timing, combined with high-definition lipoabdominoplasty.

Heterogeneous response of estimated insulin sensitivity indices to metformin in young individuals with type 1 diabetes and different phenotypes.

AIMS: This study aimed to investigate whether the response to adding metformin to insulin in young adults with type 1 diabetes (T1D) differs according to weight phenotype and insulin sensitivity index. METHODS: A prospective pilot study was conducted over 26 weeks in which insulin plus metformin (2 g/day) was administered to 35 individuals, ranging from normal weight (NW) to overweight (OW) to obese (OB) T1D individuals, to correlate insulin sensitivity indices and other clinical variables. RESULTS: At the end of the follow-up period, all groups showed an increase in the eGDR (NW: 7.37 vs 8.16, p = 0.002; OW: 7.28 vs 8.24, p < 0.001; OB: 6.33 vs 7.52 p < 0.001). KITT and SEARCH SCORE improved only in the OB group (2.15 vs 3.14, p < 0.001 and 5.26 vs 5.72, p = 0.007, respectively). Furthermore, HbA1c and BMI were significantly greater in the OB group (- 0.62%, p < 0.001; - 1.12 kg/m2, p = 0.031, respectively). Regression analysis revealed that the serum levels of triglycerides and uric acid were significantly (0.059, p = 0.013; 0.076, p = 0.001) associated with insulin sensitivity indices. CONCLUSIONS: The study showed that eGDR improved independently of basal weight after metformin treatment. However, the KITT and SEARCH indices improved only in the obese group. Triglycerides and uric acid are associated with insulin sensitivity indices. These results highlight the heterogeneity of the mechanisms underlying insulin resistance and its response to metformin in individuals with T1D.