Circulating tumor cells shed large extracellular vesicles in capillary-sized bifurcations.

Circulating tumor cells (CTCs) and their clusters are the drivers of metastasis, but their interactions with capillary beds are poorly understood. Using microfluidic models mimicking human capillary bifurcations, we observed cell size- and bifurcation-dependent shedding of nuclei-free fragments by patient CTCs, CTC-derived explant cells and numerous cancer cell lines. Shedding reduced cell sizes up to 61%, facilitating their transit through bifurcations. We demonstrated that shed fragments were a novel class of large extracellular vesicles (LEVs), whose proteome was associated with immune-related and signaling pathways. LEVs were internalized by endothelial and immune cells, disrupted endothelial barrier integrity and polarized monocytes into M2 tumor-promoting macrophages. Cumulatively, these findings suggest that CTCs shed LEVs in capillary beds that drive key processes involved in the formation of pre-metastatic niches.

Molecular Heterogeneity in Leiomyosarcoma and Implications for Personalised Medicine.

OPINION STATEMENT: Leiomyosarcoma (LMS) is one of the more common subtypes of soft tissue sarcomas (STS), accounting for about 20% of cases. Differences in anatomical location, risk of recurrence and histomorphological variants contribute to the substantial clinical heterogeneity in survival outcomes and therapy responses observed in patients. There is therefore a need to move away from the current one-size-fits-all treatment approach towards a personalised strategy tailored for individual patients. Over the past decade, tissue profiling studies have revealed key genomic features and an additional layer of molecular heterogeneity among patients, with potential utility for optimal risk stratification and biomarker-matched therapies. Furthermore, recent studies investigating intratumour heterogeneity and tumour evolution patterns in LMS suggest some key features that may need to be taken into consideration when designing treatment strategies and clinical trials. Moving forward, national and international collaborative efforts to aggregate expertise, data, resources and tools are needed to achieve a step change in improving patient survival outcomes in this disease of unmet need.

A Rare Finding of Incidental Intracholecystic Papillary Neoplasm Following Acute Cholecystitis Management.

Intracholecystic papillary neoplasm (ICPN) is a grossly visible, mass-forming, noninvasive epithelial neoplasm arising from the mucosa and projecting into the lumen of the gallbladder. ICPN is a lesser-known tumor of the gallbladder lining, which although has a better prognosis compared to gallbladder adenocarcinoma carries the potential for metastatic transformation with spread to other organs. ICPN is found incidentally on imaging or during postop histological evaluation. However, we present a unique case of ICPN that was incidentally diagnosed in a 72-year-old Eastern European woman following cholecystectomy for acute cholecystitis and was missed on preoperative imaging. Follow-up protocols of ICPN are poorly understood and vastly underreported. We discuss this patient's findings in light of current literary evidence available on ICPN and outline future directions for better clinical understanding. We also highlight the need for screening guidelines in light of known risk factors to better understand the natural history of the disease to prevent malignant transformation into invasive gallbladder carcinoma.

Keloid Development After Fine Needle Aspiration of the Thyroid: A Rare Case and Review of Management Strategies.

Keloids are pathological scars characterized by abnormal proliferation of tissue as a result of cutaneous injury. There is a high prevalence of keloid development in certain ethnicities. Individuals from African, Hispanic, and Asian backgrounds have a higher likelihood of developing keloids when compared to Caucasians. Keloids are known to lack spontaneous regression and have a high rate of recurrence after removal, thereby causing a cosmetic problem that affects people physically and emotionally. Keloids commonly occur after burns, tattoos, piercings, and deep wounds; however, in rare cases, they may develop after minimally invasive procedures. This case describes the experience of a 48-year-old African American male who underwent a thyroid fine needle aspiration biopsy and subsequently developed a keloid in the neck region. This report aims to explore this unique occurrence, highlight the interplay between epidemiology, race, and genetics in influencing the development of keloids, and review the management strategies for neck keloids.

Small Bowel Obstruction Secondary to Laparoscopic Adjustable Gastric Band Connecting Tube Intertwinement Within the Mesentery: A Case Report.

Laparoscopic adjustable gastric banding (LAGB) is a technique used for the surgical management of morbid obesity. This report illustrates the case of a 46-year-old African American woman who presented with a rare case of small bowel obstruction (SBO) two years post-LAGB placement. SBO, in this case, was a result of LAGB connecting tube intertwinement within the mesentery, accompanied by adhesions. The patient was diagnosed clinically and radiologically by computed tomography (CT) scan, which showed high-grade SBO. Initially, an exploratory laparoscopy was conducted, which soon transformed into an exploratory laparotomy when the cause of obstruction was seen to be the intertwinement of the connecting tube of the gastric band with the mesentery. With the rise of bariatric procedures to combat the epidemic of obesity in American society, this rare complication secondary to one of the most widely performed procedures beckons the attention of bariatric surgeons, emergency personnel, and device manufacturers.

First Line of Defense: The Vital Role of Family Medicine Physicians in Preventing Acute Mesenteric Ischemia in High-Risk Patients.

Acute mesenteric ischemia (AMI) is a life-threatening condition with a high mortality rate despite surgical interventions. Morbidity and mortality are especially high in those with risk factors, which include diabetes mellitus (DM), hypertension (HTN), coronary artery disease, recent myocardial infarction, and rheumatic autoimmune diseases, among others. We present the case of a 70-year-old Caucasian woman diagnosed with AMI. The patient presented acutely to the emergency department after nine episodes of vomiting and was admitted to the surgical floor the same day for an emergent exploratory laparotomy. She presented acutely with an atypical presentation and without any progressive symptoms, despite various comorbidities. This patient was classified as "very high risk", but she had not been on any medications or monitored for any of her comorbidities. We highlight the essential and multifaceted role of family medicine physicians, also known as primary care physicians (PCPs), in the prevention of bowel ischemia and recommend the use of routine outpatient monitoring with clinical examination, blood testing, and imaging. These, along with a high index of suspicion, have clinical utility in preventing hospitalization, surgical intervention (bowel resection), and other serious sequelae of AMI. Timely detection, management, and specialist referrals from a family medicine physician can lower the overall burden on healthcare resources and personnel.

End-Stage Renal Disease in a 29-Year-Old Male With Aneurysmal Arteriovenous Fistulas Status Post-Right-Kidney Transplant: A Case Report.

The occurrence of renal failure is higher among African Americans in comparison to individuals of other descents, indicating a disproportionate representation. Chronic kidney disease (CKD) poses a significant healthcare burden that disproportionately affects low-income and minority communities. There are various factors that drive the progression and deterioration of CKD to its advanced stages. These factors include genetic predispositions, socioeconomic status, barriers to medical care, and the patients' own health beliefs and behaviors which impact their screening, risk factor control, and adherence to treatment. Earlier detection and management of hypertension can slow or halt the progression of CKD. This case report is on a case of a 29-year-old African American male with end-stage renal disease (ESRD) status-post right renal transplant. At 21 years old, the patient was diagnosed with benign essential hypertension which progressed from CKD to ESRD. Furthermore, at the age of 23 years old, he was requiring right renal transplants. We aim to shed light on the underlying predispositions that put this young patient at risk for CKD and related comorbidities. Lastly, to highlight dialysis-related complications from the treatment of ESRD and the impact of chronic illness on this patient's overall health.

Persistent Postoperative Delirium Following Laparoscopic Cholecystectomy.

Gallstones are the primary cause of symptomatic gallbladder disease and lead to a significant portion of hospitalizations related to gastrointestinal diseases. The gold standard treatment for gallbladder disease continues to be cholecystectomy, which is commonly done laparoscopically, and improves patients' quality of life. With any surgical intervention there are inherent risks, and in the setting of severe illness, the risk of potential complications increases immensely. Postoperative altered mental status, namely, delirium, may occur in the elderly and a high index of suspicion is required to recognize the clinical signs for swift diagnosis and management. This case involves a 61-year-old male who underwent laparoscopic cholecystectomy and developed persistent delirium during the hospital course. This report aims to explore the multiple risk factors that lead to postoperative delirium and review the diagnostic and therapeutic strategies utilized in managing this patient.

Atypical Presentation of Diverticulitis in a Young Hispanic Male: A Case Report.

Diverticulitis is a significant contributor to the number of hospital admissions and healthcare costs in Western societies. The authors present the case of an otherwise healthy 33-year-old Hispanic male presenting to the emergency department with complaints of abdominal pain, pneumaturia, and hematochezia. The patient had no underlying risk factors, substantial prior medical history, or typical symptoms of diverticulitis. He was diagnosed with acute diverticulitis with a presumed colovesical fistula. The unique clinical presentation and the intraoperative findings are discussed. The objective of this case report is to make clinicians aware of atypical presentations of acute diverticulitis and guide the appropriate diagnostic workup for young Hispanic males presenting to the emergency departments with complaints of abdominal pain.

The prognostic capability of inflammatory proteins in predicting peripheral artery disease related adverse events.

Background: Levels of inflammatory proteins and their prognostic potential have been inadequately studied in patients with peripheral artery disease (PAD). In this study, we quantified and assessed the ability of inflammatory proteins in predicting PAD-related adverse events. Methods: In this prospective case-control study, blood samples were collected from patients without PAD (n = 202) and patients with PAD (n = 275). The PAD cohort was stratified by disease severity based on ankle brachial index (ABI): mild (n = 49), moderate (n = 164), and severe (n = 62). Patients were followed for 2 years. Plasma concentrations of 5 inflammatory proteins were measured: Alpha-2-Macroglobulin (A2M), Fetuin A, Alpha-1-Acid Glycoprotein (AGP), Serum Amyloid P component (SAP), and Adipsin. The primary outcome of our study was major adverse limb event (MALE), defined as the need for vascular intervention (open or endovascular revascularization) or major amputation. The secondary outcome was worsening PAD status, defined as a drop in ABI greater than or equal to 0.15 over the study period. Multivariable logistic regression was performed to assess the prognostic value of inflammatory proteins in predicting MALE, adjusting for confounding variables. Results: Compared to patients without PAD, three inflammatory proteins were differentially expressed in patients with PAD (AGP, Fetuin A, and SAP). The primary outcome (MALE) and secondary outcome (worsening PAD) status were noted in 69 (25%) and 60 (22%) patients, respectively. PAD-related adverse events occurred more frequently in severe PAD patients. Based on our data, the inflammatory protein AGP was the most reliable predictor of primary and secondary outcomes. On multivariable analysis, there was a significant association between AGP and MALE in all PAD disease states [mild: adjusted HR 1.13 (95% CI 1.05-1.47), moderate: adjusted HR 1.23 (95% CI 1.16-1.73), severe: adjusted HR 1.37 (95% CI 1.25-1.85)]. High levels of AGP were associated with lower 2-year MALE-free survival in all PAD disease states [mild (64% vs. 100%, p = 0.02), moderate (64% vs. 85%, p = 0.02), severe (55% vs. 88%, p = 0.02), all PAD (62% vs. 88%, p = 0.01)]. Conclusion: Levels of inflammatory protein AGP may help in risk stratifying PAD patients at high risk of MALE and worsening PAD status and subsequently facilitate further vascular evaluation and initiation of aggressive medical/surgical management.

The Clinical Utility of D-Dimer and Prothrombin Fragment (F1+2) for Peripheral Artery Disease: A Prospective Study.

D-dimer and prothrombin fragment (F1+2) levels are elevated in patients with peripheral artery disease (PAD). We examined their prognostic potential in predicting decreasing ABI and major adverse limb events (MALE). A total of 206 patients were recruited from St. Michael's Hospital and followed for two years. Baseline plasma concentrations of D-dimer and F1+2 were recorded. Pearson's correlation was used to assess the correlation between the biomarkers and ABI at year 2. During follow-up, multivariable Cox proportional hazard analysis was performed to investigate their role in predicting decreasing ABI (defined as change in ABI > −0.15) and MALE (defined as the need for arterial intervention or major limb amputation). Cumulative survival was assessed using Kaplan−Meier analysis. Baseline D-dimer and F1+2 levels were elevated in PAD patients (median (IQR) 1.34 (0.80−2.20) for D-dimer and 3.60 (2.30−4.74) for F1+2; p = 0.001) compared to non-PAD controls (median (IQR) 0.69 (0.29−1.20) for D-dimer and 1.84 (1.17−3.09) for F1+2; p = 0.001). Both markers were negatively correlated with ABI at year 2 (r = −0.231 for D-dimer, r = −0.49 for F1+2; p = 0.001). Cox analysis demonstrated F1+2 and D-dimer to be independent predictors of PAD status (HR = 1.27, 95% CI = 1.15−1.54; p = 0.013 for D-dimer and HR = 1.28, 95% CI = 1.14−1.58; p = 0.019 for F1+2). Elevated baseline concentrations of D-dimer and F1+2 were associated with high incidence of decreasing ABI and 1- and 2-year event-free survival (62% and 86%, respectively). Combined analysis of D-dimer and F1+2 provides important prognostic information that facilitates risk stratification for future disease progression and MALE outcomes in patients with PAD.