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Urothelial carcinoma with osteoclast-like giant cells: An expanded immunohistochemical and molecular profile
No full textOBJECTIVE: Osteoclast-rich undifferentiated carcinoma of the urinary tract, herein referred to as urothelial carcinoma with osteoclast-like giant cells (UCOGC), is a rare tumor currently classified under the poorly differentiated urothelial carcinoma subtype. This study aimed to evaluate the clinicopathologic, immunophenotypic, and molecular features of UCOGC to better characterize its origin and support its classification as a unique subtype.
METHODS: There were 14 UCOGCs studied with immunohistochemistry/in situ hybridization and compared to urothelial carcinomas with trophoblastic differentiation (n = 6) and giant cell urothelial carcinomas (n = 5). Markers were assessed in mononuclear (MN) and giant cell (GC) components. Next-generation sequencing was performed on 4 UCOGCs.
RESULTS: The MN cells of UCOGC demonstrated high expression of CD68, CD163, SATB2, cathepsin K, and CSF1 in situ hybridization (ISH), with moderate staining for GATA3, p63, and PU.1 and low staining for pankeratin. The GCs showed high CD68, PU.1, and cathepsin K expression but low CD163, SATB2, and CSF1 ISH, with no staining for urothelial markers or pankeratin. Both MN and GC were negative for H3.G34W and HCG. Next-generation sequencing revealed mutations consistent with conventional urothelial carcinomas.
CONCLUSIONS: The distinct biphasic morphology, characteristic immunophenotype, and molecular findings of UCOGC suggest it is of urothelial origin, and we believe it justifies its classification as a unique subtype rather than under poorly differentiated urothelial carcinoma
Fenestrated/branched endovascular aortic repair after failed endovascular aortic repair has similar perioperative outcomes to primary repairs
No full textOBJECTIVE: To evaluate the outcomes of fenestrated-branched endovascular aneurysm repair (FB-EVAR) in patients undergoing reintervention for failed EVAR compared with those undergoing primary FB-EVAR.
METHODS: Patients undergoing FB-EVAR between 2014 and 2024 were identified in the Vascular Quality Initiative database. Patients were then divided into two groups, those undergoing FB-EVAR after failed EVAR and those undergoing primary FB-EVAR. Baseline characteristics, operative details, and outcomes were compared between groups. Primary outcomes included mortality, reintervention, and endoleak (EL) (type I/III) rates. Secondary outcomes included perioperative complications. Kaplan-Meier survival analysis and Cox regression were used to evaluate 1-year outcomes.
RESULTS: A total of 2067 patients were included in this study; 386 (18.6%) underwent FB-EVAR after failed EVAR, and 1681 (81.4%) underwent primary FB-EVAR. In the failed EVAR group, perioperative mortality (3.1% vs 4%; P = .934) and rates of type I/III endoleaks (6.5% vs 8.6%; P = .164) were comparable with that of no prior EVAR. At the 12-month follow-up, mortality rates remained similar (17.2% vs 15.8%; P = .265), However, patients with prior EVAR had a significantly higher reintervention rates (hazard ratio, 1.60; 95% confidence interval, 1.10-2.35; P = .015), despite similar mortality and EL rates.
CONCLUSIONS: FB-EVAR is a safe and effective reintervention strategy after failed EVAR, achieving similar mortality and EL outcomes compared with primary FB-EVAR. However, the significantly higher reintervention rates in patients with prior EVAR may be related to the increased complexity this population
The WOLVERINE Technique: Wire Landmark-Guided Orientation Controlled Leaflet-Resection to Prevent Left-Ventricular Outflow-Tract Obstruction Using Endoscopic-Scissors in TMVR Procedures
No full textExploring Vitiligo History and Mental Health Burden Among People Within EU5 Countries: Findings from the Global VALIANT Study
No full textINTRODUCTION: Vitiligo is a chronic autoimmune disease characterized by destruction of pigment-producing melanocytes in the skin. This study explores the patient and treatment history of vitiligo and associated mental health burden in EU5 countries.
METHODS: The cross-sectional global Vitiligo and Life Impact Among International Communities (VALIANT) study recruited people with vitiligo via an online panel and surveyed them regarding clinical characteristics, vitiligo treatment, quality of life (QoL), and mental health.
RESULTS: A total of 1151 patients were surveyed in EU5 countries (France, n = 250; Germany, n = 250; Italy, n = 200; Spain, n = 200; UK, n = 251). Half of patients (50.3%) reported a family history of vitiligo, with highest rates in France (66.4%) and Germany (58.8%). Many patients experienced flares during periods of stress (65.1%) or itching before/during a flare (61.5%), with highest rates in Germany (78.4%/78.8%, respectively; P \u3c 0.01 vs all). German patients used the greatest mean number of vitiligo treatments (6.5; P \u3c 0.0001 vs all), and French patients reported the highest rates of current non-treatment (20.8%; P \u3c 0.05 vs Germany). Half of patients (53.9%) reported frequently hiding their vitiligo lesions, with highest rates in Germany (60.4%) and France (58.4%; both P \u3c 0.05 vs Italy/Spain). German and French patients also reported highest disease burden (P \u3c 0.05 vs Italy/Spain/UK). Over half (58.3%) of patients reported diagnosed mental health conditions (anxiety [26.5%]; depression [23.4%]). Rates of moderate to severe depressive symptoms were highest in Germany (64.8%; P \u3c 0.05 vs all).
CONCLUSION: Among EU5 countries, patients from Germany and France generally reported higher burden than those from Italy, Spain, or the UK, although the impact of vitiligo on these patients cannot be discounted. Patients reported flares during periods of stress and great impact of vitiligo on their QoL and mental health. There is continued need for improved management strategies for patients with vitiligo, including the reduction of QoL and mental health burden
Anti-Anaerobic Antibiotics, Gut Microbiota, and Sepsis-associated Acute Kidney Injury
No full textRATIONALE: Acute kidney injury (AKI) is a common complication of sepsis. Anti-anaerobic antibiotics, which deplete gut commensal bacteria, are common in the initial management of sepsis. Recent studies have reported an association between anti-anaerobic antibiotics and mortality, but the mechanisms underlying this relationship remain unknown.
OBJECTIVE: To determine whether anti-anaerobic antibiotics and gut microbiome disruption increase patient susceptibility to sepsis-associated AKI.
METHODS: We identified a cohort of patients with sepsis and performed four complementary analyses: 1) comparing AKI incidence among patients who did and did not receive early anti-anaerobic antibiotics, 2-3) two instrumental variable analyses using the 2015-16 piperacillin-tazobactam shortage to determine the effect of anti-anaerobic antibiotics on the onset and resolution of AKI, and 4) a matched case-control study comparing gut microbiota in septic patients who did and did not develop AKI. We then modeled sepsis in genetically-identical but microbially-heterogenous mice and compared creatinine elevation with gut microbiota.
MEASUREMENTS AND MAIN RESULTS: In a retrospective cohort study (N=12,776), early exposure to anti-anaerobic antibiotics was independently associated with a 61% increased risk of sepsis-associated AKI (95% CI-37%-92%). In instrumental variable analyses of AKI onset (N=3,036) and resolution (N=2,177), treatment with anti-anaerobic antibiotics (piperacillin-tazobactam) was associated with an increased hazard of AKI onset (HR-1.65, 95% CI-1.18-2.30) and decreased AKI resolution (HR-0.74, 95% CI-0.61-0.88). In a matched case-control study of gut microbiota in 372 patients with sepsis, increased gut bacterial density and enrichment with Enterobacteriaceae and Lachnospiraceae spp. predicted subsequent AKI onset. In a murine model of sepsis (N=53), creatinine elevation was strongly associated with vendor and gut community composition (P\u3c 0.001 for all), with relative abundance of Lachnospiraceae spp. explaining 18% of variation in serum creatinine.
CONCLUSIONS: Anti-anaerobic antibiotics are associated with increased risk of AKI in sepsis, potentially via modulation of the gut microbiome
Hepatitis C-Everything a Primary Care Physician Needs to Know About Diagnosis, Management, and Follow-Up
No full textHepatitis C virus (HCV) infection is a major public health concern, with more than 58 million people chronically infected worldwide. The management of HCV, once the domain of specialists only, has been revolutionized by the advent of direct-acting antiviral therapies. To reduce the burden of HCV in the United States (US), emphasis is now being placed on the involvement of primary care physicians in the management of HCV patients. Inclusion of more primary care providers in the HCV diagnosis and treatment initiatives can assist in achieving the goal of HCV elimination, especially in the medically underserved areas. To actively engage in the management of HCV, primary care providers must understand its epidemiology, risk factors, natural history, current treatment regimen, and potential complications. This manuscript reviews these key areas, along with presenting the cost-effectiveness of treatment and evidence-based guidelines for follow-up care in adults with chronic HCV infection who have undergone HCV treatment. Equipped with this foundational knowledge about HCV management, primary care physicians can play a vital role in eliminating HCV
Cystic Duct Stenting Versus Other Treatment Modalities for the Management of Acute Cholecystitis in Patients with Decompensated Cirrhosis
No full textBACKGROUND AND AIMS: The incidence of cholecystitis and cholelithiasis is higher in patients with cirrhosis. Decompensated liver disease places them at higher risk for morbidity and mortality from cholecystectomy, and many providers prefer non-surgical approaches. We compared cystic duct stenting (CDS) to other modalities mainly percutaneous cholecystostomy (PC), cholecystectomy, and medical management.
METHODOLOGY: We performed a retrospective cohort study. After obtaining IRB approval, we gathered records of all patients at our health care system who had acute cholecystitis on presentation and an underlying diagnosis of cirrhosis with MELD-Na ≥ 15 from 2015 to 2022. Outcomes included 30-day mortality, 60-day mortality, 1-year mortality, 30-day readmission, and worsening liver disease as characterized by increasing MELD-Na by ≥ 3 or new onset ascites or encephalopathy following management.
RESULTS: 67 patients met our inclusion criteria. 19 patients had CDS and were compared to 48 patients managed by other modalities, i.e., cholecystectomy (n = 12), PC (n = 17) and medical management (n = 19). There was no difference in demographics, etiology of cirrhosis, or mean MELD-Na between the two groups. We noticed a significant difference in the protective effect of CDS on one-month readmission rate and liver function with RR of 0.56 (0.4-0.9, P = 0.038) and RR 0.49 (CI 0.3-0.8, P = 0.01), respectively. The only complication in the cystic duct stent group was one case of pancreatitis (5.2%).
CONCLUSION: For patients with decompensated cirrhosis who present with acute cholecystitis, CDS via ERCP prevents readmissions and further decompensation of liver disease when compared to other treatment modalities
Radiologic and surgical peritoneal cancer index in patients with low grade serous ovarian carcinoma
No full textBACKGROUND: Peritoneal cancer index (PCI) is a numerical score that quantifies tumor extent in colorectal cancers. More recently it has been applied to ovarian cancers. However, the prognostic value of PCI in patients with low grade serous ovarian carcinoma (LGSOC) is not well characterized. We investigated whether pre-operative CT imaging could predict intraoperative disease extent and outcomes in LGSOC patients using PCI. We also investigated the association between PCI scores and cytoreduction outcomes.
METHODS: Advanced stage LGSOC who had undergone preoperative CT imaging, cytoreductive surgery, and follow-up in the study timeframe were included. PCI was calculated based on the Sugarbaker method (Harmon & Sugarbaker, 2005). A blinded radiologist calculated CT-PCI scores. Surgical PCI was calculated retrospectively from operative reports. The relationship between CT-PCI and surgical PCI was determined using univariate linear regression. Surgical and survival outcomes were assessed.
RESULTS: For 21 patients (median age at cancer diagnosis = 58 years old, interquartile range (IQR) = 54-69), mean CT-PCI was 13 (SD: 8). Mean surgical PCI was 12 (SD: 7). CT-PCI significantly predicted surgical PCI (beta-coefficient = 0.59, p-value = 0.001). CT-PCI overestimated surgical PCI in 71 % of patients. Neither CT-PCI nor surgical PCI were significantly associated with optimal cytoreduction, though a trend was observed toward higher PCI scores in patients who were sub-optimally cytoreduced.
CONCLUSION: CT-PCI significantly predicts surgical PCI in a small, retrospective cohort of patients with LGSOC. CT-PCI may be useful to estimate surgical PCI and possibly cytoreductive outcome in LGSOC. However, CT-PCI can overestimate surgical PCI and should not be used to preclude LGSOC patients from a cytoreduction attempt
DCE-MRI Tumor Vascular Parameters in Two Preclinical Patient-Derived Orthotopic Xenograft Models of Glioblastoma
No full textTwo preclinical patient-derived orthotopic xenograft (PDOX) models of glioblastoma (GBM) were characterized using measures of tumor physiology. Plasma volume fraction (v(p)), blood-to-tissue forward volumetric transfer constant (K(trans)), and interstitial volume fraction (v(e)) were estimated via dynamic contrast-enhanced (DCE) MRI. Tumor blood flow (TBF) was estimated via continuous arterial spin-labeling and apparent diffusion coefficient of water (ADC) via spin-echo diffusion-weighted imaging. Tumor distribution volume at the tumor rim (V(D)) and peritumoral flux (Flux) were also estimated. Two neurosphere cell lines, taken from a primary human GBM (HF3016) and its recurrence (HF3177), were used in 15 immune-compromised athymic rats (n = 7 for HF3016; n = 8 for HF3177). When the tumors grew to about 3-4 mm in diameter, DCE-MRI data were acquired in a 7T magnet using a low molecular weight gadolinium-chelate contrast agent. DCE data were analyzed voxel-by-voxel using Patlak, extended Patlak, and Logan graphical methods. A data-driven model selection approach was applied to segment the tumor region, and regions of interest (ROIs) based on that segmentation were selected in the imaging slice having the largest tumor cross section. Summary ROI statistics of vascular measures were produced. The parameter estimates K(trans), v(e), v(p), V(D), ADC, TBF, and growth rates between the two models varied slightly, but the differences were not statistically significant (p \u3e 0.05; t-tests). Flux estimates were found to be strongly correlated with V(D) values at the tumor rim in both tumor models (R(2) = 0.84 and 0.91 for HF3016 and HF3177, respectively). These data report physiological properties of untreated GBM models that are representative of human disease both geno- and pheno-typically. Imaging biomarkers of vascular function in GBMs may aid in testing novel antiglioma therapies using these and other similar PDOX models for longitudinal, minimally invasive evaluations of treatment effects
Outcomes after arthroscopically assisted lower trapezius transfer for irreparable posterosuperior rotator cuff tears
No full textBACKGROUND: The preferred surgical management for massive irreparable posterosuperior rotator cuff tears remains undecided. Treatment options include primary partial repair with allograft augmentation, balloon spacer, tendon transfers, and reverse total shoulder arthroplasty (rTSA). For younger and more active patients where rTSA is not preferred, tendon transfers may be an appropriate option. This study evaluates the outcomes of patients who underwent an arthroscopically assisted lower trapezius tendon transfer (AaLTT) for irreparable posterosuperior rotator cuff tears.
METHODS: A total of 54 patients (42 male and 12 female) with an average age of 59 years (range: 36-76 years) were evaluated. All patients were treated with an AaLTT as treatment for a massive irreparable posterosuperior rotator cuff tear and had a minimum follow-up of 12 months. Pre- and postoperative American Shoulder and Elbow Surgeons (ASES) scores, visual analog scale (VAS), and range of motion (ROM) were compared to evaluate improvement in ROM and function after the procedure.
RESULTS: At a minimum follow-up of 12 months, patients demonstrated a significant improvement in forward flexion (average 20°, P value \u3c .0001) and external rotation ROM (average 10°, P value \u3c .0001). A preoperative external rotation lag sign was reversed in 36 of 38 (94.7%) patients. There were significant improvements in postoperative ROM and patient-reported outcome measurement scores (ASES and VAS) with a median improvement of 53 points for the ASES score and a median improvement of 4 points on the VAS. There is no literature describing the minimal clinically important difference for VAS and ASES change after AaLTT. However, our values do exceed the minimal clinically important difference cited in prior reports for arthroscopic rotator cuff repair of 27.13 and 2.37 for ASES and VAS, respectively.
CONCLUSION: This study demonstrates that AaLTTs with allograft augmentation for irreparable rotator cuff tears provide patients with a significant improvement in ROM, specifically forward flexion and external rotation, as well as patient-reported outcome measures. Future studies should focus on follow-up beyond 12 months as well as creating standardization of surgical technique in order to improve procedure adoption