Litigation claims in Urology in the UK National Health Service: an analysis of the trends, costs and causes over a 16-year period.

OBJECTIVE: To analyse the litigation trends and the reasons for claims within the specialty of Urology, within the UK National Health Service (NHS), over a 16-year period. MATERIALS AND METHODS: Data were requested from NHS Resolution under the Freedom of Information Act 2000. This included the total number of claims in Urology, the number of these that were successful (settled or closed), and the costs in damages paid out per financial year between 2006 and 2022. A breakdown of the successful claims by their primary cause was also collected. These were coded into the categories: 'non-operative', 'intraoperative', 'postoperative', and 'other'. RESULTS: A total of 4124 litigation claims were made between 2006 and 2022 and 60.9% (2511/4124) of these claims were successful. In all, £145 million (British pounds) was paid out in damages. The number of successful claims increased 2.9-fold from the start to end of this 16-year period, and the costs in damages paid out increased 10-fold. Regarding primary causes for the successful claims, failure or delay in treatment (20.9%, 525/2511), failure or delay in diagnosis (14.5%, 364/2511), and intraoperative problems (9.1%, 229/2511) accounted for the highest proportion. Overall, non-operative causes for successful claims accounted for 73.3% (1840/2511), intraoperative for 20.1% (504/2511), and postoperative for 3.9% (98/2511). CONCLUSIONS: The number of successful urological litigation claims, and their associated costs is rising. The majority are due to non-operative causes, which may be partially explained by NHS waiting lists alongside the effects of the coronavirus disease 2019 (COVID-19) pandemic.

Lemierre's Syndrome in the 21st Century: A Literature Review.

Lemierre's syndrome is a rare, life-threatening complication of an acute oropharyngeal infection. It is generally characterised by pharyngitis secondary to Fusobacterium necrophorum, causing thrombophlebitis of the internal jugular vein and sepsis, with subsequent formation of septic emboli that can rapidly spread to different organ sites. The condition is associated with high mortality if treatment with antibiotics is delayed, and recent evidence suggests that patients are at significant risk of in-hospital morbidity and long-term neurological sequelae. Although it is agreed that antibiotics are the mainstay of treatment, there is currently no consensus on the use of anticoagulation in the condition. This review article aims to summarise our current understanding of Lemierre's syndrome with regard to its definition, epidemiology, microbiology, presentation, diagnosis, and treatment.

Combinatorial encoding of odors in the mosquito antennal lobe.

Among the cues that a mosquito uses to find a host for blood-feeding, the smell of the host plays an important role. Previous studies have shown that host odors contain hundreds of chemical odorants, which are detected by different receptors on the peripheral sensory organs of mosquitoes. But how individual odorants are encoded by downstream neurons in the mosquito brain is not known. We developed an in vivo preparation for patch-clamp electrophysiology to record from projection neurons and local neurons in the antennal lobe of Aedes aegypti. Combining intracellular recordings with dye-fills, morphological reconstructions, and immunohistochemistry, we identify different sub-classes of antennal lobe neurons and their putative interactions. Our recordings show that an odorant can activate multiple neurons innervating different glomeruli, and that the stimulus identity and its behavioral preference are represented in the population activity of the projection neurons. Our results provide a detailed description of the second-order olfactory neurons in the central nervous system of mosquitoes and lay a foundation for understanding the neural basis of their olfactory behaviors.

Role of Positron Emission Tomography/Computed Tomography in Epithelial Ovarian Cancer.

Ovarian cancer (OC) is the most lethal gynecological malignancy with majority of cases diagnosed in advanced stages and associated with high morbidity and mortality. Positron emission tomography/computed tomography (PET/CT) has emerged as an integral part of the management of several nongynecological cancers. We used PubMed search engine using MeSH words "ovarian cancer" and "PET/CT" and reviewed the current status of PET/CT in epithelial OC. Its application related to ovarian tumor including adnexal mass evaluation, baseline staging, as a triaging tool for upfront surgery or neoadjuvant chemotherapy, for response assessment and prognostication, and for relapse detection and treatment planning has been highlighted. we highlight the current guidelines and newer upcoming PET modalities and radiotracers.

Impact of PD1 and PDL1 immunotherapy on non-small cell lung cancer outcomes: a systematic review.

INTRODUCTION: Despite comprising many cancer diagnoses, few treatments are suitable for patients with advanced non-small cell lung cancer (aNSCLC). Trials suggest blockade of programmed death 1 (PD1) or its ligand (PDL1) may be effective for these patients. However, this therapy's impact on outcomes other than survival, and outcomes of patients not in trials, remains largely unknown. Therefore, we compared the effectiveness of PD1 and PDL1 immunotherapy to chemotherapy and placebo across multiple clinical outcomes. METHODS: Six databases were searched on 12-13 October 2019 for randomised controlled trials (RCTs) and observational studies investigating nivolumab, pembrolizumab, atezolizumab or durvalumab. Study selection was performed independently by two reviewers. Data for overall survival, progression-free survival, adverse effects (AEs) and quality of life (QoL) were descriptively and meta-analysed. Factors impacting treatment outcomes, including PDL1 expression, were explored. The similarity between RCT and observational data was assessed. RESULTS: From 5423 search results, 139 full texts and abstracts were included. Immunotherapy was associated with a lower risk of death than both comparators. In RCTs, the incidence of treatment-related AEs was approximately 20% lower among patients using immunotherapy compared with chemotherapy. However, no other consistent benefits were observed. Progression-free survival results were inconsistent. Improvements to QoL varied according to the instrument used; however, QoL was not recorded widely. Survival results were similar between study designs; however, AEs incidence was lower in observational studies. DISCUSSION: Among patients with aNSCLC, immunotherapy improved overall survival and incidence of treatment-related AEs compared with chemotherapy. Benefits to progression-free survival and QoL were less consistent. PROSPERO REGISTRATION NUMBER: CRD42019153345.

Intractable Seizures and Limbic Encephalitis, Unaccounted Complications of Type 1 Diabetes Autoimmunity.

Glutamic acid decarboxylase 65kD autoantibody (GAD65Ab) is frequently detected in patients with refractory epilepsy and stiff person syndrome. In contrast to T1D, the pathological role of GAD65Ab in neurological disorders is still debatable. As a result, the implementation of possible immunotherapy is usually delayed. This report presents 2 cases of GAD65Ab-associated brain autoimmunity and their different management. We present clinical data and discuss management based on available evidence in the reviewed literature. Both cases presented with acute on chronic neurological symptoms and were GAD65Ab positive. Case 1, a 30-year-old man with a history of early-onset type 1 diabetes mellitus at 14 months, followed by cryptogenic temporal epilepsy at 11 years of age, presented with intractable seizures. Case 2, a 48-year-old woman, presented with a history of recurrent severe headaches, cognitive impairment, decreased memory, and behavioral symptoms. GAD65Ab was detected in both patients' sera. Cerebrospinal fluid GAD65Ab was only checked and positive in case 1. Case 2 was diagnosed with limbic encephalitis, treated with immunotherapy, and showed a remarkable clinical improvement. Case 1 with refractory epilepsy failed multiple antiepileptic drugs and responsive-stimulator system treatments. He was finally diagnosed with autoimmune epilepsy. The delay in diagnosis resulted in a lost opportunity for early immunotherapy. In conclusion, autoantibody screening and early initiation of immunotherapy should be considered to manage GAD65Ab-associated neurological disorders.

Comparing Model Performance in Characterizing the PK/PD of the Anti-Myostatin Antibody Domagrozumab.

Modeling and simulation provides quantitative information on target coverage for dose selection. Optimal model selection often relies on fit criteria and is not necessarily mechanistically driven. One such case is discussed where healthy volunteer data of an anti-myostatin monoclonal antibody domagrozumab were used to develop different target-mediated drug disposition models; a quasi-steady state (QSS) rapid binding approximation model, a Michaelis-Menten (MM)-binding kinetics (MM-BK) model, and an MM-indirect response (MM-IDR) model. Whereas the MM-BK model was identified as optimal in fitting the data, with all parameters estimated with high precision, the QSS model also converged but was not able to capture the nonlinear decline. Although the least mechanistic model, MM-IDR, had the lowest objective function value, the MM-BK model was further developed as it provided a reasonable fit and allowed simulations regarding growth differentiation factor-8 target coverage for phase II dose selection with sufficient certainty to allow for testing of the underlying mechanistic assumptions.

Comparative laboratory efficacy of novel botanical extracts against Tribolium castaneum.

BACKGROUND: Citrus sinensis, Allium sativum, Ocimum basilicum, Mentha spicata, Curcuma longa, Carica papaya, Andrographis paniculata, Azadirachta indica, Cymbopogon citratus and Acorus calamus were compared in the form of extracts of chloroform, hexane and aqueous media for their effectiveness in repelling Tribolium castaneum. Filter paper of 9 cm in diameter was cut into halves. Using a micro-pipette, each extract was applied to one half of the filter paper. The volume applied was kept constant at 0.6 mL per 30 cm2 . The filter paper was dried and reattached leaving a 0.5 cm gap between, in a Petri-plate. Ten adults of T. castaneum were introduced and the repellency was observed after 30, 60 and 180 min. RESULTS: The aqueous extract of C. papaya exhibited the highest repellency (82-97%) followed by that of garlic bulbs (aqueous extract) with 86.67% repellency. Further, gunny bags were sprayed separately using bottle sprayers with the two most effective extracts at a constant volume of 42 mL per 575 cm2 . These treated gunny bags were compared with malathion-treated gunny bags in the insect management unit. The observations were taken after 2, 8 and 24 h. Papaya leaf extract-treated gunny bags showed relative repellent activity similar to that of malathion-treated gunny bags after 24 h of treatment. Thus, gas chromatography-mass spectrometry analysis of aqueous extract of papaya leaves was performed. CONCLUSIONS: It can be concluded that extract of papaya leaves containing 2-methoxy-4-vinylphenol (8.47% peak area) can be used as a repellent biopesticide. © 2019 Society of Chemical Industry.

Impact of Personal Alcohol Consumption on Aspects of Medical Student Alcohol-Related Competencies.

AIM: As part of the prevention and management of alcohol-related harms, health professionals need to be competent to assess the level of alcohol use in patients. In this study, we explored how medical students' own alcohol consumption impacts on their familiarity with alcohol brands, strengths and alcohol-related harms. METHODS: As part of a wider study investigating the concept of 'alcohol health literacy', this study combined an anonymous online survey, linked to an electronic alcohol 'brand' recognition game. Participants were medical students in their first clinical year. The survey recorded demographics, self-reported alcohol consumption (using the AUDIT-C), a visual test of relative alcohol concentrations of wine, beer and spirits, and a free-text response asking them to list alcohol-related harms. Participants then completed the brand recognition game recording accuracy and reaction time for identifying alcohol drink brands. RESULTS: One hundred and fifty students participated. There was a significant effect of ethnicity on drinking status, with 48% of non-white participants scoring zero on the AUDIT-C. Students who reported any alcohol consumption were more likely to correctly assess relative alcohol concentrations and were faster and more accurate at recognizing alcohol brands, which was dose dependent. Overall, only 45% correctly recognized relative alcohol strengths of drinks presented. CONCLUSIONS: Among third-year medical students, ability to correctly identify relative strengths of alcoholic drinks is low. As might be expected, students who drink alcohol tend to identify brands and strengths more accurately. This has implications for how best to tailor the delivery of teaching and training about alcohol to ensure similar levels of clinical confidence in dealing with future patients regardless of personal experience.

Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling.

The human adaptive immune system is a very complex network of different types of cells, cytokines, and signaling molecules. This complex network makes it difficult to understand the system level regulations. To properly explain the immune system, it is necessary to explicitly investigate the presence of different feedback and feedforward loops (FFLs) and their crosstalks. Considering that these loops increase the complexity of the system, the mathematical modeling has been proved to be an important tool to explain such complex biological systems. This review focuses on these regulatory loops and discusses their importance on systems modeling of the immune system.

Isolated Polycystic Liver Disease: An Unusual Cause of Recurrent Variceal Bleed.

Isolated polycystic liver disease is a rare disorder. Majority of the patients with isolated polycystic liver disease are asymptomatic with incidental detection of liver cysts on imaging studies done for other purposes. Minority of patients develop symptoms which are mostly secondary to enlarging cysts size and hepatomegaly. Rarely, these patients develop portal hypertension and can present with its clinical manifestations and consequences in the form acute variceal bleeding or recurrent ascites. We present a rare case of 67-year-old female patient with significant history of polycystic liver disease who presented to the hospital with recurrent hematemesis and melena. She underwent esophagogastroduodenoscopy which showed multiple large esophageal varices requiring banding.

Posttransplant Tacrolimus-Induced Diabetic Ketoacidosis: Review of the Literature.

Diabetic ketoacidosis (DKA) in patients receiving tacrolimus as part of their immunosuppressive regimen is a rarely reported adverse event. We report a patient with autosomal dominant polycystic kidney disease (ADPKD) and no known history of diabetes mellitus who presented with DKA, 3 months after kidney transplantation.

ERCP-Related Duodenal Perforation Presenting as Pneumoscrotum.

Duodenal perforation is a rare but life-threatening complication of endoscopic retrograde cholangiopancreatography (ERCP). Duodenal perforation can cause air leak into the extraperitoneal space. In rare instances, the air in the extraperitoneal space could dissect along the fascial planes of the abdomen to reach scrotum, leading to pneumoscrotum. We present the case of a 35-year-old male patient who developed scrotal pain and swelling following ERCP. He was found to have extensive pneumoscrotum, pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema. The patient was diagnosed with retroperitoneal duodenal perforation. He was managed conservatively with close monitoring and supportive care.

Massive Upper and Lower GI Bleed from Simultaneous Primary (AL) Amyloidosis of the Stomach and Transverse Colon in a Patient with Multiple Myeloma.

Symptomatic primary (amyloid light-chain or AL) amyloidosis of the gastrointestinal (GI) tract is very rare. Most of the patients with symptomatic involvement of the GI tract present with altered motility, malabsorption, or bleeding. We report a case of gastric and colonic amyloidosis on anticoagulation presenting with massive upper and lower GI bleeding. A 67-year-old lady known to have multiple myeloma and AL amyloidosis on rivaroxaban presented with massive upper GI bleeding. Esophagogastroduodenoscopy showed a mass lesion (3 × 7 cm) located along the greater curvature in the body/antrum with active bleeding. Mucosal biopsies revealed amyloid deposition. She underwent partial gastrectomy and recovered well after surgery, and was discharged home on rivaroxaban. The patient presented again 4 weeks after discharge with bleeding per rectum, and a colonoscopy revealed a large mass in the proximal transverse colon with active bleeding. Biopsy of the mass showed amyloid deposition. At this point, the patient declined any further intervention. Rivaroxaban was discontinued, the rectal bleeding stopped, and she was discharged home with no further episodes of GI bleed. Amyloidosis of the GI tract presenting with massive GI bleed is extremely rare and is thought to be related to small-vessel fragility due to amyloid infiltration and impaired hemostasis caused by factor X deficiency. Even though GI bleeding with amyloidosis is spontaneous, use of anticoagulation could activate such episodes in these patients. Caution should be exercised with the use of anticoagulation in patients with amyloidosis involving the GI tract, and colonoscopy should be considered in patients with gastric amyloidosis.

The Traumatic Tube: Bleeding Rectal Ulcer Caused by Flexi-Seal Device.

Diarrhea and fecal incontinence are common in critically ill patients and present a challenging problem in patient management. The Flexi-Seal® Fecal Management System is a device to divert the stools away from the patient, thus improving the care to patients with fecal incontinence. There have been only few case reports describing the complications with the use of this device. Here, we present a case of a 77-year-old woman who was admitted due to massive hematochezia while on anticoagulation. She was found to have a large rectal ulcer caused by the Flexi-Seal device, used during the last hospital stay for fecal incontinence. Flexi-Seal device can be effective for the management of incontinence; however, caution should be exercised during handling and pressure from the retention balloon should be relieved periodically.

Celiac Disease Associated with a Benign Granulomatous Mass Demonstrating Self-Regression after Initiation of a Gluten-Free Diet.

Celiac disease is a chronic immune-mediated enteropathy in which dietary gluten induces an inflammatory reaction predominantly in the duodenum. Celiac disease is known to be associated with benign small bowel thickening and reactive lymphadenopathy that often regresses after the institution of a gluten-free diet. A 66-year-old male patient with celiac disease presented with abdominal pain and diarrheal illness. Computerized tomography of the abdomen revealed a duodenal mass. Endoscopic ultrasound-guided fine needle aspiration of the mass revealed bizarre stromal cells which represent a nonspecific tissue reaction to inflammation. This inflammatory mass regressed after the institution of a gluten-free diet. This case report describes a unique presentation of celiac disease in the form of a granulomatous self-regressing mass. Also, this is the first reported case of bizarre stromal cells found in association with celiac disease. In addition to lymphoma and small bowel adenocarcinoma, celiac disease can present with a benign inflammatory mass, which should be serially monitored for resolution with a gluten-free diet.

Unusual Clinical Presentation of Hemobilia with Recurrent Vasovagal Episodes.

Hemobilia is caused by the abnormal connection between a blood vessel and the bile duct, which is usually iatrogenic and caused by hepatobiliary procedures. The classic triad of hemobilia includes biliary colic, obstructive jaundice, and gastrointestinal bleeding. We present the case of an 80-year-old man who had laparoscopic cholecystectomy complicated by hemobilia. He had an unusual presentation of hemobilia in the form of transient vasovagal episodes in addition to abdominal pain and hematochezia.

Recurrent Upper Extremity Thrombosis Associated with Overactivity: A Case of Delayed Diagnosis of Paget-Schroetter Syndrome.

Paget-Schroetter syndrome is thrombosis of the axillary-subclavian vein that is associated with strenuous and repetitive activity of the upper extremities. Overuse of the arm coupled with external compression results in microtrauma in the intima of the subclavian vein, resulting in the activation of the coagulation cascade. Diagnosis is usually made by Doppler ultrasound and the treatment involves thrombolysis, while routine surgical decompression of the thoracic outlet is controversial. In this report, we present a case of a patient who presented with a second episode of spontaneous right upper extremity deep venous thrombosis. The first episode was inadequately treated with oral anticoagulation alone. During the second episode, Paget-Schroetter syndrome was diagnosed, after careful review of his occupational history. He subsequently underwent angioplasty and decompression of thoracic outlet with no recurrence of thrombosis in a 12-month follow-up period.

Alveolar Soft Part Sarcoma with Unusual Cardiac Metastasis: A Case Report and Review of the Literature.

Alveolar soft part sarcoma is a very uncommon soft tissue malignancy which accounts for <1% of soft tissue sarcoma. It is a malignant and highly vascular tumor arising most commonly in the musculature of the lower extremities, with metastasis primarily to the lungs, bones, and brain. Cardiac metastasis is very rare and only 5 cases have been reported in the literature so far. We report a case of a young woman with a history of surgically resected alveolar soft part sarcoma of left thigh who presented with persistent dry cough and was found to have a cardiac mass, which on biopsy proved to be alveolar soft part sarcoma.