Spontaneous Retroperitoneal Hemorrhage in a Patient with Acquired Cystic Kidney Disease

Spontaneous retroperitoneal hemorrhage (SRH) is a rare emergency. It is usually encountered in patients on hemodialysis and is associated with high rate of morbidity and mortality. This is a case from the emergency department. The patient had unstable vitals with SRH following dialysis. Immediate exploration and nephrectomy using transverse lateral lumbotomy incision were done. Patients on hemodialysis are at a risk of SRH and frequent surveillance is recommended. Acquired cystic kidney disease (ACKD) can develop in hemodialysis patients and put them at risk for bleeding. Transverse lateral lumbotomy may be a safe option for direct access to the kidney in emergency kidney surger

Un processus d'admission aux programmes de médecine basé sur la localisation géographique n'influence pas les résultats académiques avant l'externat ni ceux à l'examen menant à l’obtention du permis d'exercice

Background: Students are selected for admission to the Northern Ontario School of Medicine University (NOSM U) MD degree program using criteria aiming to maximize access of persons thought most likely to practice in the region, including use of a geographic context score (GCS) which ranks those with lived experience in northern Ontario and/or rurality most highly. This study investigates the effect of this admissions process upon medical school academic performance.  Methods: We used a retrospective cohort design combined with multiple linear regression analysis to investigate the relationship between admission scores and performance on pre-clerkship courses, and the Medical Council of Canada Qualifying Exam Part 1 (MCCQE1). The GCS did not significantly explain performance variance on any pre-clerkship course, nor on the MCCQE1, while the undergraduate Grade Point Average correlated with most assessment scores.  The number of prior undergraduate biomedical courses predicted science and clinical skills performance, particularly in Year 1, but not with MCCQE1 scores. Performance on Year 2 courses, particularly foundational sciences and clinical skills, significantly predicted MCCQE1 scores. Results: Our data suggest that admission geographic context scoring is unrelated to future academic performance. Further, students with fewer prior undergraduate biomedical courses may benefit from increased support and/or a modified program during the early years. Contexte : La sélection étudiants à l'École de médecine du Nord de l'Ontario est fondée sur des critères visant à faciliter l’admission de candidats qu’on estime susceptibles de pratiquer dans la région. Un de ces critères est le score de contexte géographique (SCG) qui classe au premier rang les personnes ayant déjà vécu dans le Nord de l'Ontario ou en milieu rural. Cette étude examine l'effet de ce processus d'admission sur les résultats académiques des étudiants en médecine. Méthodes : Nous avons utilisé un modèle de cohorte rétrospective et une analyse par régression linéaire multiple pour étudier la relation entre les scores d'admission et les résultats obtenus aux cours avant l’externat et à l'examen d'aptitude du Conseil médical du Canada (EACMC), partie 1. Le SCG n'explique pas de manière significative la variance des résultats dans les cours pré-cliniques, ni à l'EACMC1, tandis que la moyenne pondérée cumulative au premier cycle est en corrélation avec la plupart des scores d'évaluation. Le nombre de cours en sciences biomédicales suivis dans un programme de premier cycle ont permis de prédire les résultats en sciences et en compétences cliniques, en particulier en première année, mais pas les résultats à l'EACMC1. Les résultats aux cours de deuxième année, en particulier de sciences fondamentales et de compétences cliniques, ont permis de prédire de manière significative les résultats à l'EACMC1. Résultats : Nos données portent à croire que le score de contexte géographique au moment de l'admission est sans lien avec les résultats académiques subséquents. En outre, les étudiants ayant suivi moins de cours en sciences biomédicales au premier cycle pourraient bénéficier d’un soutien plus important ou d'un programme adapté au cours des premières années

Successful Surgical Management of Locally Advanced Renal Cell Carcinoma Invading Spleen and Pancreas

Over the last two decades, the treatment of metastatic RCC has changed significantly, and the role of surgery is being debated. A 50-year-old man presented with pain in his left loin. An ultrasound, followed by a CT scan, revealed a 17.5 cm left renal mass invading the left suprarenal gland, spleen, and pancreatic tail. Radical nephrectomy through chevron incision under epidural block with general anesthesia was performed. The entire mass was removed en bloc. The estimated blood loss was 300 mL, and no blood transfusions were performed. The operation took approximately 2 h. Histological examination revealed clear cell renal carcinoma with extension into the spleen, pancreatic tail, and diaphragmatic fibers with negative resection margin. The patient discharged after a 3-day uneventful hospital stay. Aggressive surgical removal of a locally invasive renal cell carcinoma is feasible and should be considered in patients with good performance status and no or minimal distant metastases

Bilateral Single-Stage Nephrectomy for Synchronous Bilateral Renal Cell Carcinoma

Bilateral synchronous renal cell carcinoma (RCC) is uncommonly encountered. Debate exists among urologists in managing these cases in a single surgery versus staged surgeries. We aim to report our experience in managing encountered cases using single-stage surgeries. Retrospective collection of cases with pathologically confirmed RCC that had single-stage bilateral renal surgery over the past 2 years. Three cases were identified. Patients were managed using bilateral transverse lateral lumbotomy. All patients did not have intraoperative or postoperative complications. Kidney function stayed stable after surgery. Single-stage bilateral renal surgery is a safe procedure. Bilateral transverse lateral lumbotomy allows for a fast and safe surgery with minimal complications. There is a possible histological dis-concordance in bilateral synchronous RCC

Partial Nephrectomy for T1b/T2 Renal Mass: An Added Shift from Radical Nephrectomy

The aim of our study was to show our short-term experience in managing large renal masses (cT1b/T2) through partial nephrectomy (PN) over the last 3 years. Retrospective data collection for all patients managed by PN for renal masses larger than 4 cm over the last 3 years. Epidemiological data were collected. Surgical data including surgical and ischemic times as well as intra and postoperative complications were collected. Pre- and postoperative estimated glomerular filtration rate (eGFR) data were collected and correlated as well as postoperative complications and recurrence. We could identify 47 patients managed by PN for radiologically confirmed >4 cm renal masses. The mean age of the patients was 55.7 ± 13.4, including 29 males and 18 females. Masses were T1b and T2 in 40 and 7 patients, respectively. The mean tumor size was 6.2 ± 1.5 cm. Using renal nephrometry score; 8, 28, and 11 had low, moderate, and high complexity, respectively. Renal cell carcinoma (RCC) was identified in 42 patients. Five patients out of 42 cancerous cases (12%) had pathological T3 RCC. The mean preoperative and postoperative eGFR were 89.09 ± 12.41 and 88.50 ± 10.50, respectively (P 0.2). The median follow-up was 14 months and within that short time, no patient had evidence for cancer recurrence. PN for large renal masses is safe in experienced hands and should be attempted in a higher percentage of patients, regardless of the tumor complexity. No cancer recurrence or deterioration of renal function was observed within our short-term follow-up

Predation effects on mean time to extinction under demographic stochasticity

Methods for predicting the probability and timing of a species' extinction are typically based on a combination of theoretical models and empirical data, and focus on single species population dynamics. Of course, species also interact with each other, forming more or less complex networks of interactions. Models to assess extinction risk often lack explicit incorporation of these interspecific interactions. We study a birth and death process in which the death rate includes an effect from predation. This predation rate is included via a general nonlinear expression for the functional response of predation to prey density. We investigate the effects of the foraging parameters (e.g. attack rate and handling time) on the mean time to extinction. Mean time to extinction varies by orders of magnitude when we alter the foraging parameters, even when we exclude the effects of these parameters on the equilibrium population size. In particular we observe an exponential dependence of the mean time to extinction on handling time. These findings clearly show that accounting for the nature of interspecific interactions is likely to be critically important when estimating extinction risk.Comment: 11 pages, 4 figures; Typos removed. For further discussion about the paper go to http://purl.org/net/extinctio

History of infantile BCG immunization did not predict lamina propria invasion and/or high-grade in patients with non-muscle invasive bladder cancer

Objective: To evaluate the utility of infantile BCG vaccination history in predicting stage and grade of tumours in non-muscle invasive bladder cancer (NMIBC). Materials and methods: We retrospectively analyzed data from patients from a single center who were diagnosed with new NMIBC and underwent transurethral resection of bladder tumour (TURBT) between 2017 and 2022. We assessed BCG immunization status with various demographics and comorbidities, as well as tumour recurrence, progression, stage, and grade. Results: A total of 188 patients met the inclusion criteria for our study. The mean age of patients at the time of diagnosis was significantly lower in those that had been immunized with BCG (71 ± 9) than those who had not (77 ± 10) (p < 0.0001). History of BCG immunization did not correlate with sex, history of diabetes mellitus (DM), prior history of intravesical BCG treatment, and tumour recurrence, progression, stage, and grade. Conclusions: History of infantile BCG vaccination did not correlate with the depth of invasion and/or the grade in patients with non-muscle invasive bladder cancer. Patients that received infantile BCG vaccination were significantly younger at the time of diagnosis of NMIBC

A trematode parasite derived growth factor binds and exerts influences on host immune functions via host cytokine receptor complexes

The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allow- ing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF) superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL)-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory recep- tor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is depen- dent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs) in their evasion of antibody- dependent cell cytotoxicity (ADCC) by reducing the NO response of macrophages—again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for damp- ened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow for a reduced effector response targetingjuvenile parasites which we demonstrate extends to an abrogation of the ADCC response. Thus suggesting that FhTLM is a stage specific evasion molecule that utilises host cytokine receptors. These findings are the first to clearly demonstrate the interaction of a helminth cytokine with a host receptor complex resulting in immune modifications that facilitate the non-protective chronic immune response which is characteristic of F. hepatica infection

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial