Echidna Splenule: A Case Study of Continuous Splenogonadal Fusion.

Splenogonadal fusion (SGF) is a rare congenital anomaly of an aberrant accessory spleen-gonad connection. We present a rare case of continuous splenogonadal fusion in a full-term male with a left undescended testis, multiple congenital limb anomalies, and syndromic facies. Diagnostic laparoscopy revealed the "Echidna Splenule," a snake-like intraperitoneal splenule coursing from the spleen along the left paracolic region and engulfing an atrophic intra-abdominal testis preventing spontaneous descent and distally herniating into the left open internal inguinal ring. The atrophic testis and Echidna Splenule were resected. Splenogonadal fusion should be considered in children with left undescended testis and concomitant limb and facial anomalies.

Malpractice Litigation in Iatrogenic Ureteral Injury: a Legal Database Review.

OBJECTIVE: To examine the factors associated with iatrogenic ureteral injury litigation and outcomes. METHODS: The Westlaw legal database was queried for all iatrogenic ureteral injury cases. Variables extracted included available clinical factors, method of settlement, and litigation outcomes. Linear regression analysis was conducted to examine factors associated with award amount. RESULTS: A total of 522 cases from 1961 to 2019 were included in the study. The most common specialty named was gynecology (353/512, 68.9%), followed by urology (89/512, 17.4%). The most common claim was intraoperative negligence (474/522 cases, 90.8%). Fifty two cases were settled or arbitrated and 470 went to trial. Settlement or arbitration was more likely in cases involving institution-only defendant (15.4% vs 7.3%, P< .01), academic institution (19.7% vs 7.1%, P < .01), and patient death (42.9% vs 10.7%; P < .001). Of cases that went to trial, the verdict favored the defendant in 339/470 cases (72.1%). The median award was $552,822.96 (interquartile range 187,007-1,063,603). Duration of temporary drainage ($5050/day, P = .02), delayed repair (P = .03), claim of inadequate workup (P = .03), and claim of failure to supervise trainee (P < .001) were significantly associated with increasing award amount. CONCLUSION: The majority of ureteral injury litigation ruled in favor of the defendant. However, when awarded, the amount was substantial and correlated with drainage duration, delayed repair, claim of inadequate workup, and failure to supervise trainee. These findings highlight factors perceived to be associated with significant distress and reflect trends in medicolegal decision-making.

Comparative Postoperative Outcomes of Rezum Prostate Ablation in Patients with Large Versus Small Glands.

Introduction: Rezum water vapor thermal ablation is a new minimally invasive technique used to treat benign prostatic hyperplasia. Major advantages include minimal anesthesia and recovery time, low rate of sexual side effects, and durable clinical improvement. However, data are lacking regarding use of Rezum in prostate glands >80 cc. Here we seek to examine the clinical outcomes of men with large prostate glands following Rezum. Patients and Methods: We retrospectively reviewed patients who underwent Rezum therapy at our institution since July 2017. Three-month postoperative outcomes were analyzed, including American Urological Association symptom score (AUASS), peak flow, and postvoid residual (PVR). Complications, including hematuria and urinary tract infections, were also assessed. All statistical analyses were conducted using RStudio 1.2.1335. Results: One hundred eighty-two patients undergoing Rezum were identified, of whom 25.8% had prostate volume >80 cc. Mean gland volume in this group was 119 cc and 55.3% were catheter dependent. Following Rezum, statistically significant improvement was seen in AUASS from 22 to 13.4 (p = 0.04) and PVR from 305 to 149 cc (0.05). Statistically significant improvement was seen in peak flow rate from 7.7 to 12.7 mL/second (p = 0.002). In a subset of catheter-dependent patients, the postoperative catheter-free rate was 83% for men with glands >80 cc, which was comparable with 88% in the smaller gland group. Postoperative complication rate was not significantly different between large or small glands. Conclusions: In our experience, Rezum is efficacious in patients with glands >80 cc. Patients experience symptomatic and objective improvement in voiding parameters that is comparable with patients with glands smaller than 80 cc. Among catheter-dependent patients with glands >80 cc, over 80% are catheter free after Rezum. Our experience supports the consideration of Rezum in patients with prostate glands >80 cc; further studies are warranted to confirm long-term outcomes.

Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals.

PURPOSE: In adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection. METHODS: Forty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6 kg/m2; median age 57, range 50-69 years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors. RESULTS: In regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2 = 0.23; ß = 0.03; p = 0.044) and higher radius cortical BMD (R2 = 0.43; ß = 8.4; p = 0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2 = 0.38; ß = 0.96; p = 0.050), higher radius trabecular number (R2 = 0.31; ß = 0.01; p = 0.026), lower tibia and radius trabecular separation (tibia: R2 = 0.30; ß = -0.003; p = 0.038; radius: R2 = 0.35; ß = -0.003; p = 0.021), and higher radius bone stiffness (R2 = 0.45; ß = 0.38; p = 0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2 = 0.44; ß = 4.06; p = 0.036), higher tibia bone stiffness (R2 = 0.46; ß = 3.06; p = 0.050), and higher tibia estimated failure load (R2 = 0.46; ß = 0.17; p = 0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2 = 0.39; ß = -41.2; p = 0.042), lower radius trabecular number (R2 = 0.34; ß = -0.44; p = 0.009) and greater radius trabecular separation (R2 = 0.42; ß = 0.16; p = 0.002), while TDF use without a PI was not associated with reduced bone quality. CONCLUSIONS: In adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.

Health Changes in Low Income Men Transitioning from a State Funded Prostate Cancer Program to Comprehensive Insurance.

PURPOSE: We evaluated the effect of transitioning from a prostate cancer specific treatment program to comprehensive insurance under the ACA (Patient Protection and Affordable Care Act) on the physical, mental and prostate cancer related health of poor, previously uninsured men. MATERIALS AND METHODS: We assessed general and prostate cancer specific health related quality of life using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and the UCLA PCI (Prostate Cancer Index) at 3 time points in 24 men who transitioned to comprehensive insurance as the insured group relative to 39 who remained in the prostate cancer program as the control group. We used mixed effects models controlling for treatment and patient factors to measure health differences between the groups during the transition period. RESULTS: Demographics, prostate cancer treatment patterns, and mental, physical and general health were similar before transition in the control and insured groups. After transition men who gained insurance coverage reported significantly worse physical health than men who remained in the prostate cancer program (p = 0.0038). After adjustment in the mixed effects model physical health remained worse in men who gained insurance (p = 0.0036). Mental health and prostate cancer related quality of life did not differ with time between the groups. CONCLUSIONS: Compared to controls who remained in the state funded prostate cancer treatment program for poor, uninsured men, newly insured men reported worse physical health after transitioning to ACA coverage. Providers and policy makers may draw important lessons from understanding the mechanisms of this paradoxical worsening in physical health after gaining insurance. These results inform the development of disease specific models of care in the broader health insurance context.

Developing an Algorithm for Optimizing Care of Elderly Patients With Glioblastoma.

BACKGROUND: Elderly patients with glioblastoma have an especially poor prognosis; optimizing their medical and surgical care remains of paramount importance. OBJECTIVE: To investigate patient and treatment characteristics of elderly vs nonelderly patients and develop an algorithm to predict elderly patients' survival. METHODS: Retrospective analysis of 554 patients (mean age = 60.8; 42.0% female) undergoing first glioblastoma resection or biopsy at our institution (2005-2011). RESULTS: Of the 554 patients, 218 (39%) were elderly (≥65 yr). Compared with nonelderly, elderly patients were more likely to receive biopsy only (26% vs 16%), have ≥1 medical comorbidity (40% vs 20%), and develop postresection morbidity (eg, seizure, delirium; 25% vs 14%), and were less likely to receive temozolomide (TMZ) (78% vs 90%) and gross total resection (31% vs 45%). To predict benefit of resection in elderly patients (n = 161), we identified 5 factors known in the preoperative period that predicted survival in a multivariate analysis. We then assigned points to each (1 point: Charlson comorbidity score >0, subtotal resection, tumor >3 cm; 2 points: preoperative weakness, Charlson comorbidity score >1, tumor >5 cm, age >75 yr; 4 points: age >85 yr). Having 3 to 5 points (n = 78, 56%) was associated with decreased survival compared to 0 to 2 points (n = 41, 29%, 8.5 vs 16.9 mo; P = .001) and increased survival compared to 6 to 9 points (n = 20, 14%, 8.5 vs 4.5 mo; P < .001). Patients with 6 to 9 points did not survive significantly longer than elderly patients receiving biopsy only (n = 57, 4.5 vs 2.7 mo; P = .58). CONCLUSION: Further optimization of the medical and surgical care of elderly glioblastoma patients may be achieved by providing more beneficial therapies while avoiding unnecessary resection in those not likely to receive benefit from this intervention.

Improved Survival with Decreased Wait Time to Surgery in Glioblastoma Patients Presenting with Seizure.

BACKGROUND: Preoperative seizure is reported to confer favorable prognosis in glioblastoma patients, but studies to date have not investigated how broadly applicable seizure is as a prognostic factor. OBJECTIVE: To investigate if prompter surgical intervention affects the relationship between preoperative seizure and prognosis in glioblastoma patients, focusing on the development of tumor growth and/or additional preoperative symptoms after seizure. METHODS: Retrospective analysis of 443 patients (mean age = 60.2; 60% male) undergoing first glioblastoma resection at our institution (2005-2011). RESULTS: Preoperative seizure(s) occurred in 28% of patients (n = 124), of which 63 (51%) had only seizure at presentation. Patients experiencing seizure as their only preoperative symptom ("seizure-only"; n = 45) survived over twice as long as patients who presented with seizure and then later developed additional preoperative symptoms (n = 18; "other symptoms postseizure"; 26.8 vs 10.2 months, P < .001) and patients without preoperative seizure ("no seizure"; 26.8 vs 13.1 months, P < .001). Multivariate stepwise analysis revealed preoperative seizures only (hazard ratio 0.54 [0.37-0.75]; P < .001) to be independently associated with increased survival. Longer wait time from presentation (ie, diagnostic magnetic resonance imaging) to surgery was a risk factor for developing additional symptoms. Eleven "other symptoms postseizure" patients (69%) vs 6 of the "seizure-only" patients (15%) had wait times >45 days (P < .001). CONCLUSION: Seizure as the only preoperative symptom independently improved survival, however, when patients developed additional preoperative symptoms, typically due to surgical delay, no prognostic benefit was observed. Prompt diagnosis and neurosurgical intervention is warranted in patients with seizures without other preoperative symptoms to preserve their favorable prognosis.

GLUT3 upregulation promotes metabolic reprogramming associated with antiangiogenic therapy resistance.

Clinical trials revealed limited response duration of glioblastomas to VEGF-neutralizing antibody bevacizumab. Thriving in the devascularized microenvironment occurring after antiangiogenic therapy requires tumor cell adaptation to decreased glucose, with 50% less glucose identified in bevacizumab-treated xenografts. Compared with bevacizumab-responsive xenograft cells, resistant cells exhibited increased glucose uptake, glycolysis, 13C NMR pyruvate to lactate conversion, and survival in low glucose. Glucose transporter 3 (GLUT3) was upregulated in bevacizumab-resistant versus sensitive xenografts and patient specimens in a HIF-1α-dependent manner. Resistant versus sensitive cell mitochondria in oxidative phosphorylation-selective conditions produced less ATP. Despite unchanged mitochondrial numbers, normoxic resistant cells had lower mitochondrial membrane potential than sensitive cells, confirming poorer mitochondrial health, but avoided the mitochondrial dysfunction of hypoxic sensitive cells. Thin-layer chromatography revealed increased triglycerides in bevacizumab-resistant versus sensitive xenografts, a change driven by mitochondrial stress. A glycogen synthase kinase-3ß inhibitor suppressing GLUT3 transcription caused greater cell death in bevacizumab-resistant than -responsive cells. Overexpressing GLUT3 in tumor cells recapitulated bevacizumab-resistant cell features: survival and proliferation in low glucose, increased glycolysis, impaired oxidative phosphorylation, and rapid in vivo proliferation only slowed by bevacizumab to that of untreated bevacizumab-responsive tumors. Targeting GLUT3 or the increased glycolysis reliance in resistant tumors could unlock the potential of antiangiogenic treatments.

Novel approaches in genetic characterization and targeted therapy for brain metastases.

Metastases to the brain are a common complication of various cancers and are associated with poor prognosis. Management of these patients requires a multidisciplinary approach including whole-brain radiation therapy, stereotactic radiosurgery, surgical resection, chemotherapy, and supportive treatment. Because of recent technological advancements in genomics, our understanding of the genetics of brain metastases is rapidly advancing. This has led to the discovery of many potential genetic therapeutic targets in metastatic brain lesions. One of the limitations to systemic therapies is their limited ability to cross the blood brain barrier, necessitating the urgency to develop clinical trials to evaluate efficacy. A description of these genetic mutations, targeted therapies, and associated clinical trials in brain metastases from lung cancers, breast cancers, and melanoma is outlined in this review.