Citations

Background: Breast cancer is the most common cancer that causes death among women worldwide. In Ethiopia, though there has not been an adequate study, the incidence of new cases of breast cancer is currently increasing and has become one of the most common cancer types, causing high rates of morbidity and mortality. Mutation in the BRCA1 gene in 5832insC regions has been demonstrated as the most common genetic factor that increases the occurrence of breast cancer. Thus, this study aimed to detect the frequency of 5832insC gene polymorphism in the BRCA1 gene and its associated risk factors among breast cancer-positive patients visiting the study sites. Materials and Methods: A cross-sectional study was conducted on 100 blood samples of females with breast cancer. Following genomic DNA isolation, PCR amplification was done using specific primer pairs for 5832insC BRCA1 regions. The amplified products were digested with restriction enzymes (HinfI) to detect 5382insC polymorphism. Results: Based on the findings of this study, family history was the only variable that had a significant association (P = 0.001) with 5382insC mutation in the BRCA1 gene. On the other hand, alcohol consumption (P = 0.542), age (P = 0.376), and residence zone (P = 0.856) of the participant did not show any association for this mutation. The total frequency of 5382insC BRCA1 gene mutations in the study participants was found to be 6%. Conclusion: The present study confirmed that 5382insC was the potential BRCA1 alterations that have been encountered in most breast cancer patients in the study area. The use of molecular techniques for early breast cancer detection is highly recommended to improve treatment efficiency and minimize the rate of mortality.

Background/Objectives: GaBHA syndrome (gastric bypass hyperammonemia) is an emerging new syndrome primarily in women who had prior Roux-en-Y gastric bypass surgery (RYGB) and then developed non-cirrhotic hyperammonemia with a high case–fatality ratio. Genetic and nutritional deficiencies have been implicated in the pathogenesis of this clinical condition, but none has been proven. We present an illustrative case and do a scoping review of the current literature in 58 patients with this diagnosis. Methods: A retrospective scoping literature review was utilized to identify patients who fulfilled 1. RYGB surgery, and 2. Hyperammonemic encephalopathy following the PRISMA extended checklist. We searched PubMed, MedLine, SCOPUS, and Web of Science databases. Results: We described the classic presenting symptoms and laboratory findings of this syndrome. We confirmed the female predominance (93%) and the high case–fatality ratio (32%). We then presented a novel hypothesis contending that arginine deficiency ultimately leads to a functional deficiency of the ornithine transcarbamolyase (OTC) enzyme, leading to the non-cirrhotic life-threatening hyperammonemia. Our hypothesis may also explain the high incidence of hypoglycemia found in these patients as we found in our search. Our proposed hypothesis may also be relevant to the occurrence of hyperammonemia in some solid organ transplant recipients. Conclusions: GaBHA syndrome is emerging as an important potential adverse outcome after RYGB surgery. It has a female predominance and a high case–fatality ratio. Arginine deficiency may explain the emergence of a functional OTC deficiency, which then leads to the severe hyperammonemia, and may also explain the frequent occurrence of hypo-glycemia in these patients.

Sindbis virus (SINV), a prototype of the Alphavirus genus (family Togaviridae), is a globally distributed arbovirus causing febrile rash and debilitating arthritis in humans. Viral structural proteins—capsid (C), E1, and E2—are fundamental to the virion’s architecture, mediating all stages from assembly to host cell entry and pathogenesis, thus representing critical targets for study. This review consolidates the historical and current understanding of SINV structural biology, tracing progress from early microscopy to recent high-resolution cryo-electron microscopy (cryo-EM) and X-ray crystallography. We detail the virion’s precise T = 4 icosahedral architecture, composed of a nucleocapsid core and an outer glycoprotein shell. Key functional roles tied to protein structure are examined: the capsid’s dual capacity as a serine protease and an RNA-packaging scaffold that interacts with the E2 cytoplasmic tail; the E1 glycoprotein’s function as a class II fusion protein driving membrane fusion; and the E2 glycoprotein’s primary role in receptor binding, which dictates cellular tropism and serves as the main antigenic target. Furthermore, we connect these molecular structures to viral evolution and disease, analyzing how genetic variation among SINV genotypes, particularly in the E2 gene, influences host adaptation, immune evasion, and the clinical expression of arthritogenic and neurovirulent disease. In conclusion, the wealth of structural data on SINV offers a powerful paradigm for understanding alphavirus biology. However, critical gaps persist, including the high-resolution visualization of dynamic conformational states during viral entry and the specific molecular determinants of chronic disease. Addressing these challenges through integrative structural and functional studies is paramount. Such knowledge will be indispensable for the rational design of next-generation antiviral therapies and broadly protective vaccines against the ongoing threat posed by SINV and related pathogenic alphaviruses.

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). Results: 268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts ( p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p > 0.05). Conclusions: Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.

Abstract Aim The aim of this review was to synthesise qualitative research evidence on factors influencing the implementation of patient reported outcome measures (PROMs) in surgical population. Methods The following databases were searched: MEDLINE, Embase, Emcare, Allied and Complementary Medicine, Global Health, Health and Psychosocial Instruments, Health Management Information Consortium, APA PsycInfo, PubMed and Web of Science. Searches were carried out between 21st and 23rd February 2024. “Best fit” framework analysis was selected for evidence synthesis, necessitating two systematic reviews. The “Models review” focused on relevant theory, framework or conceptual model relating to implementation of PROMs. The “Primary research review” focused on studies describing factors affecting the implementation of PROMs. Case reports, editorial, reviews, meta-analysis, protocols, or studies, conducted in non-surgical or paediatric population, were excluded. Results 3,714 studies were identified in the Models review, of which 7 underwent full-text review and 2 were included in the analysis. Two relevant implementation frameworks were identified: the Theoretical Domains Framework (TDF) and the Consolidated Framework for Implementation Research. TDF was selected as a priori framework for the coding of evidence. Primary research review identified 1,293 studies, of which 50 underwent full-text review and 18 were included in the analysis. Extracted data were coded against TDF, revealing multiple patient-, clinician- and provider-factors affecting the implementation of PROMs, including: beliefs about consequences and capabilities, environmental context and resources, knowledge, skills, social influences, decision processes, emotional and identity factors. Conclusions Successful implementation of PROMs into routine surgical practice requires careful consideration of patient-, clinician- and provider-factors.

Abstract Bispecific T-cell engagers (TCEs) targeting B-cell maturation antigen (BCMA) and CD3, induce deep hematologic responses in ∼60% of heavily pretreated patients with multiple myeloma (MM). We and others found that high tumor burden leads to resistance to TCE and novel strategies are urgently needed to improve responses in this setting. Ikaros degraders, including immunomodulatory drugs (IMiDs) and cereblon E3 ligase modulatory drugs (CELMoDs), represent logical partners for TCEs due to their direct anti-MM effects and additional immune-stimulatory activity; however, it is unclear how to optimally combine them with TCEs. Taking advantage of the immunocompetent IMiD-sensitive Vk∗MYChCRBN murine model of MM, we optimized strategies to overcome primary resistance to BCMA-TCEs and achieve sustained remission, while maintaining a manageable safety profile. The addition of anti–programmed cell death protein 1 (PD1) and pomalidomide reduced the T-cell exhaustion that occurs in response to TCEs in high tumor burden settings. This allowed for a higher degree of T-cell activation and significant improvement in response rates but also increased risk of lethal cytokine release syndrome (CRS). To moderate the response and prevent CRS, we evaluated Ikaros degraders and dexamethasone (DEX) with step-up–dosed TCEs. Pretreatment with iberdomide and DEX reshaped the bone marrow T-cell compartment, promoted infiltration of naïve T cells, and generated 100% response rates and the longest survival in subjects with high tumor burden. This was accompanied by more favorable T-cell profiling, with limited expansion of regulatory T cells and exhaustion. Overall, administering a TCE after DEX and iberdomide treatments provided deeper and more durable responses with a reduced risk of CRS.

Objective Preparation for a career in plastic and reconstructive surgery (PRS) begins long before the residency application process. Given the challenging nature of matching into integrated PRS, the expectations for competitive applicants, including research productivity and networking at conferences, incur significant expenses. Our study is the first to detail the comprehensive costs of pursuing PRS, highlighting many hidden expenses that precede the application process. Design and Setting A branched logic survey was created to inquire about respondents' demographics, personal finances, expenses related to education and research, and opinions on the comprehensive costs of pursuing PRS. Qualitative and quantitative data were collected and analyzed using descriptive statistics. Participants The survey was distributed to PRS residency applicants in the 2023–2024 cycle and to senior members of a virtual PRS research group. The survey achieved a 28.9% response rate. Results Most respondents were fourth-year medical students (57.3%) and attended a school without a home integrated residency program (42.7%). Of students who pursued a research year (37.1%), 40.7% were unpaid, and 53.3% reported living expenses exceeding their income. Most attended more than 5 PRS conferences (29.9%), corresponding to a median total cost of $2000 to $3000. Fourth-year students typically participated in 3 away rotations (40.0%) at a cost of $6000 to $9000. The financial burden of pursuing a career in PRS, including PRS-related extracurricular activities and application-associated costs, is estimated to be $33,400–$45,479. Nearly all respondents (96.6%) believed this cost was too high or excessively high; however, 93.3% determined that it was probably or definitely worth a career in PRS. Conclusions The lofty costs associated with pursuing PRS are unsustainable for many. Additional efforts should be made to reduce financial barriers for PRS applicants. Ensuring funding to all students pursuing a research year, diversifying scholarships for conference attendance and away rotations, increasing loan forgiveness opportunities, and expanding use of lower-cost application options such as the Plastic Surgery Common Application are potential solutions to offset the cost of pursuing PRS.

Worldwide, more than 4 million patients with end-stage kidney disease require hemodialysis through an arteriovenous fistula (AVF). AVFs fail because of venous neointimal hyperplasia (VNH) resulting in venous stenosis formation. A phase 1 randomized trial in patients undergoing upper extremity AVF placement was performed to evaluate the safety and efficacy of autologous adipose–derived mesenchymal stem cells (MSCs) in improving AVF function. The mechanism of action by which MSCs exert their beneficial effects was investigated using AVFs created in mice and pigs treated with allogenic MSCs and xenotransplant using patient MSCs in CD1- Foxn1nu mice. At a median follow-up of 42 months, patients with MSC-treated AVFs had reduced time to maturation with an increase in the vein diameter compared with controls. AVFs treated with allogenic MSCs in mice and pigs had an increase in M2- and M1-like macrophages with a decrease in VNH. Transcriptomic analysis of AVFs treated with allogenic MSCs in mouse and MSC xenotransplants of patients with successful AVFs showed decreased peroxisome proliferator–activated receptor gamma ( Ppar γ) and leptin receptor ( Lepr ) and increased latent transforming growth factor–beta–binding protein 2 ( Ltbp2 ). PPARγ was reduced in CD68 (+) cells from successful AVFs and allogenic MSC-treated mouse AVFs. Venous stenosis and VNH formation were mitigated in AVFs of mice with Ppar γ ablation in immune cells. Conditioned medium from MSCs of responders versus nonresponders had decreased proinflammatory genes, senescence-associated proteins, and monocyte-to-macrophage differentiation induced by phorbol 12-myristate-13-acetate. Periadventitial delivery of MSCs to AVFs promoted positive vascular remodeling through decreased inflammatory responses.