A Penetrating Neck Injury Resulting in the Complete Transection of the Ipsilateral Common Carotid Artery, Delayed Contralateral Pneumothorax, and Occult Esophageal Injury: A Case Report With a Multidisciplinary Approach to Management.

A 29-year-old male presented with a zone one penetrating neck injury resulting in complete transection of the left carotid sheath and its contents. The proximal common carotid artery and internal jugular vein injuries were successfully managed with vessel ligation without adverse neurological sequelae. The patient also developed a contralateral pneumothorax, which was due to an occult through-and-through esophageal injury at the junction of the cervical and thoracic esophagus. The esophageal injury was successfully managed with surgical repair and wide drainage of the neck and right chest.

Temporal dynamics and genomic programming of plasma cell fates.

Affinity-matured plasma cells (PCs) of varying lifespans are generated through a germinal center (GC) response. The developmental dynamics and genomic programs of antigen-specific PC precursors remain to be elucidated. Using a model antigen, we demonstrate biphasic generation of PC precursors, with those generating long-lived bone marrow PCs preferentially produced in the late phase of GC response. Clonal tracing using scRNA-seq+BCR-seq in spleen and bone marrow compartments, coupled with adoptive transfer experiments, reveal a novel PC transition state that gives rise to functionally competent PC precursors. The latter undergo clonal expansion, dependent on inducible expression of TIGIT. We propose a model for the proliferation and programming of precursors of long-lived PCs, based on extended antigen encounters followed by reduced antigen availability.

Disrupting of family with sequence similarity 105, member A (Fam105a) deteriorates pancreatic ß-cell physiology and insulin secretion in INS-1 cells.

The role of "Family with sequence similarity 105, member A" (FAM105A) in pancreatic ß-cell function in relation to type 2 diabetes mellitus (T2D) is not fully understood. To address this issue, various molecular and functional experiments were conducted on primary human islets and INS-1 cells. RNA-seq expression analysis showed that FAM105A is highly expressed in human islets and its expression is reduced in diabetic islets compared to healthy islets. FAM105A expression correlated negatively with HbA1c levels and body mass index (BMI). Co-expression analysis showed a significant correlation between FAM105A with PDX1, GCK, GLUT1 and INSR, but not the INS gene. Silencing of Fam105a impaired insulin release, content, glucose uptake, and mitochondria ATP content but did not affect cell viability, reactive oxygen species (ROS) or apoptosis levels. Silencing of Fam105a was associated with reduced Pdx1 and Glut2 expression at mRNA and protein levels. RNA-seq analysis of dysregulated genes in Fam105a-silenced cells showed an overall downregulation of gene expression in ß-cells and insulin secretion pathway. Disrupting Pdx1 did not affect Fam105a expression in INS-1 cells. Overall, the results suggest that FAM105A plays an important role in pancreatic ß-cells biology and may be involved in the development of T2D.

Breast Implant Illness: A Cohort Study.

Background Breast implant illness (BII) is a clinical disease defined by a constellation of symptoms that patients experience as a result of their breast implants. This retrospective, cohort study evaluated the benefit of breast implant explantation with total capsulectomy on patients' symptoms. Methodology This is a single-center, single-arm, cohort study utilizing retrospectively collected data. All participants included in this study voluntarily presented to the department of plastic and reconstructive surgery and requested breast implant removal. A total of 229 patients were enrolled in the study over a three-year period from 2018 to 2021. The primary endpoints of the study were to objectively grade the improvement of symptomatology following surgical intervention. The secondary endpoints were to identify co-factors such as age, comorbidities, implant characteristics, the timing of symptoms, and other data that were potentially influenced by or influencers of the breast implant illness. Results The study achieved a total of 549-point decrease in symptom frequencies following surgery. Furthermore, with an average preoperative symptom score of 3.5 (scored 1-5) and a postoperative average of 1.9, the study demonstrated a score reduction of 1.6 across all symptoms. Furthermore, the study was able to eliminate on average 2.8 symptoms of breast implant illness from every patient following explantation. Conclusion Breast implant illness is a true clinical entity that affects an extensive population of patients who have undergone breast augmentation. This study has not only highlighted the extensive morbidity of breast implant illness but has also demonstrated that there is an opportunity to standardize treatment for this disease. These outcomes have proven that a significant reduction in disease severity can be achieved with breast implant explantation and total capsulectomy.

Breast Implant Illness: A Case Series.

Since the advent of breast implants, there has been unprecedented controversy and FDA bands regarding their safety. There has been a demonstrated link with certain types of lymphoma, autoimmune disorders, and systemic illness associated with breast implants. A significant population of women currently pursue bilateral breast implant removal in hopes to alleviate a constellation of symptoms anecdotally known as "breast implant illness". This is not yet an accepted clinical entity due to the lack of sound literature on the subject. Common presenting symptoms include fatigue, anxiety, chronic pain, endocrine, autonomic, and peripheral nervous system dysfunction. Currently, there is no standard of care or guideline for treating women experiencing such symptoms. The current literature regarding breast implant illness has been widely observational and descriptive. With over four million women across the globe with augmented breasts, the potential impact of this research is great. This paper presents three patients believed to be suffering from breast implant illness, who after en-bloc resection, experienced resolution of their symptoms.

Incidental Pathogenic Fibrin-Associated Diffuse Large B-cell Lymphoma Found During Aorto-Biiliac Bypass.

Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is in and of itself a rare entity and is a subset of the Epstein-Barr virus (EBV)-associated lymphoma. Due to its indolent course, FA-DLBCL is generally an incidental finding on histopathological examinations. We present the first reported case of FA-DLBCL found within a native aortic thrombus during an aorto-biiliac bypass. This is a 77-year-old male who was taken to the operative theater for open aorto-biiliac bypass secondary to aortooclusive disease resulting in intermittent claudication and gangrene of the right lower extremity digits. Intraoperatively, suspicious inflammatory changes were noted around the aorta. Pathological evaluation of the thrombus within the aorta noted cells of B-cell lineage with BCL2 and MYC positivity in addition to CD30 and EBV positivity. Postoperatively, the patient's course was complicated by acute tubular necrosis, uremia, dialysis dependence, intubation, and cardiac arrhythmias including cardiac arrest. He was able to recover from these complications, however, he ultimately chose to self-enroll in hospice care. An extensive literature review of over 128 mentions of FA-DLBCL noted a complete paucity of reported cases of FA-DLBCL within a native aorta. The patient's clinical presentation and histopathology without mass-forming lesions lead to the diagnosis of FA-DLBCL. FA-DLBCL is an extremely rare EBV+ lymphoproliferative disorder associated with chronic inflammation (DLBCL-CI). FA-DLBCL is a rare condition without defined uniform treatment. This article serves to highlight the first reported case of FA-DLBCL found within an abdominal aortic thrombus in a native aorta. Given the paucity of literature on this condition, postoperative treatment and long-term outcomes should be the focus of this condition.

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling.

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19.

The FGF-21 genetic variants rs838133 and rs838145 are associated with high salt intake in the Emirati population.

Food predilection is linked to variants in the hepatokine "Fibroblast Growth Factor-21" gene (FGF21); with rs838133 linked to the sweet tooth in Caucasians. The effect of FGF21 variants on food intake is still unclear in other populations. A cohort of 196 healthy Emirati subjects was investigated [age: 30.34 ± 9.75yrs (44.4% males)]. The FGF21 rs838133 and rs838145 were genotyped. The daily intake was calculated based on a 61-item food frequency questionnaire. Multivariate analysis was performed using in house R script that implements two-way unsupervised hierarchical clustering to detect the association of the studied single-nucleotide polymorphisms (SNPs) and related SNPs in linkage disequilibrium, using data from the 1000 genome project. Both SNPs were in Hardy-Weinberg Equilaribium (HWE). BMI positively correlated with age (p = 0.002), but not with caloric intake. Salt intake was significantly higher in subjects homozygous (A: rs838133) and (G:rs838145),(p = 0.03 and 0.01, respectively). An interaction was observed between both SNPs; significantly associated with high salt intake. Using publicly available data, both SNPs fall within a region transmitted in Iberians which has a profile closely similar to Caucasians, but far from Chinese population. In conclusion, the minor alleles of FGF21 rs838145 and rs838133 are associated with high salt intake in Emiratis and may suggest neuro-metabolic link to dietary preference across different populations.

Insulin therapy for pre-hyperglycemic beta-cell endoplasmic reticulum crowding.

Insulin therapy improves ß-cell function in early stages of diabetes by mechanisms that may exceed alleviation of glucotoxicity. In advance type 2 diabetes, hyperglycemia causes ß-cell damage and ultimately ß-cell loss. At such an advanced stage, therapeutic modalities are often inadequate. Growing evidence indicates that in early stages of type-2 diabetes and some types of monogenic diabetes linked with malfunctioning endoplasmic-reticulum (ER), the ß-cell ER fails to process sufficient proinsulin once it becomes overloaded. These changes manifest with ER distention (ER-crowding) and deficiency of secretory granules. We hypothesize that insulin therapy may improves ß-cell function by alleviating ER-crowding. To support this hypothesis, we investigated pre-diabetic ß-cell changes in hProC(A7)Y-CpepGFP transgenic mice that develop prolonged pre-diabetes due to proinsulin dysmaturation and ER-crowding. We attenuated the ß-cell ER proinsulin synthesis with a treat-to-target insulin therapy while avoiding hypoglycemia and weight gain. Alleviation of ER-crowding resulted in temporary improvement in proinsulin maturation, insulin secretion and glucose tolerance. Our observations suggest that alleviation of pre-diabetic ER-crowding using a treat-to-target insulin therapy may improve ß-cell function and may prevent further metabolic deterioration.