Newly diagnosed cirrhosis secondary to gastrointestinal bleed due to portal hypertensive colopathy.

Portal hypertensive colopathy (PHC) is a colonic phenomenon commonly causing chronic gastrointestinal bleeding or less commonly a life-threatening acute colonic hemorrhage. An otherwise well, 58-year-old female presents general surgeons a diagnostic dilemma for symptomatic anemia. An interesting case where the rare and elusive PHC was diagnosed on colonoscopy, which led to the diagnosis of liver cirrhosis without evidence of oesophageal varices. Although PHC is most common in patients with cirrhosis, it is likely still underdiagnosed, given the current stepwise treatment approach of these cirrhotic patients often leads to treatment of the PHC alongside PHG without establishing a diagnosis. Instead, this case presents a generalised approach to patients with underlying portal and sinusoidal hypertension due to a variety of causes, and the endoscopic and radiological findings, which lead to their successful diagnosis and medical management of the gastrointestinal bleeding.

Testicular ischemia as a result of an incarcerated inguinal hernia containing omentum: a two-case series.

Acute scrotal pain is a very common presentation to the emergency room. The most important pathology we must exclude is testicular infarction or testicular ischemia. Here we describe two rare cases of acute scrotum where incarcerated inguinal hernias containing omentum resulted in testicular ischemia/infarction. In Case 1, we describe a rare case in an adult where a large, incarcerated hernia containing omentum along with direct trauma to the testicle resulted in testicular infarction. In Case 2, we describe a 2-year-old boy who presented with left scrotal tenderness due to a left inguinal hernia containing omentum resulting in compromised testicular blood flow. Both patients underwent scrotal exploration. This article also explores the possible pathophysiology of how omentum containing hernias may result in an increased risk of testicular ischemia.

A case of spontaneous idiopathic tension pneumoperitoneum successfully managed with bedside pig-tail catheter.

We present a 67-year-old gentleman with a high perioperative mortality and morbidity risk who presented with spontaneous idiopathic tension pneumoperitoneum that was successfully managed with bedside pig-tail catheter insertion. Here we also discuss other potential non-surgical aetiologies of pneumoperitoneum.

Combined flow cytometry and high-throughput image analysis for the study of essential genes in Caenorhabditis elegans.

BACKGROUND: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes has lagged behind because lethal or sterile mutations pose a bottleneck for high-throughput approaches, and a systematic way to analyse genetic interactions of essential genes in multicellular organisms has been lacking. RESULTS: In C. elegans, non-conditional lethal mutations can be maintained in heterozygosity using chromosome balancers, commonly expressing green fluorescent protein (GFP) in the pharynx. However, gene expression or function is typically monitored by the use of fluorescent reporters marked with the same fluorophore, presenting a challenge to sort worm populations of interest, particularly at early larval stages. Here, we develop a sorting strategy capable of selecting homozygous mutants carrying a GFP stress reporter from GFP-balanced animals at the second larval stage. Because sorting is not completely error-free, we develop an automated high-throughput image analysis protocol that identifies and discards animals carrying the chromosome balancer. We demonstrate the experimental usefulness of combining sorting of homozygous lethal mutants and automated image analysis in a functional genomic RNA interference (RNAi) screen for genes that genetically interact with mitochondrial prohibitin (PHB). Lack of PHB results in embryonic lethality, while homozygous PHB deletion mutants develop into sterile adults due to maternal contribution and strongly induce the mitochondrial unfolded protein response (UPRmt). In a chromosome-wide RNAi screen for C. elegans genes having human orthologues, we uncover both known and new PHB genetic interactors affecting the UPRmt and growth. CONCLUSIONS: The method presented here allows the study of balanced lethal mutations in a high-throughput manner. It can be easily adapted depending on the user's requirements and should serve as a useful resource for the C. elegans community for probing new biological aspects of essential nematode genes as well as the generation of more comprehensive genetic networks.

Efficacy and Safety of Intravenous Ferric Carboxymaltose in Geriatric Inpatients at a German Tertiary University Teaching Hospital: A Retrospective Observational Cohort Study of Clinical Practice.

Current iron supplementation practice in geriatric patients is erratic and lacks evidence-based recommendations. Despite potential benefits in this population, intravenous iron supplementation is often withheld due to concerns regarding pharmacy expense, perceived safety issues, and doubts regarding efficacy in elderly patients. This retrospective, observational cohort study aimed to evaluate the safety and efficacy of intravenous ferric carboxymaltose (FCM, Ferinject) in patients aged >75 years with iron deficiency anaemia (IDA). Within a twelve-month data extraction period, the charts of 405 hospitalised patients aged 65-101 years were retrospectively analysed for IDA, defined according to WHO criteria for anaemia (haemoglobin: <13.0 g/dL (m)/<12.0 g/dL (f)) in conjunction with transferrin saturation <20%. Of 128 IDA patients screened, 51 (39.8%) received intravenous iron. 38 patient charts were analysed. Mean cumulative dose of intravenous FCM was 784.4 ± 271.7 mg iron (1-3 infusions). 18 patients (47%) fulfilled treatment response criteria (≥1.0 g/dL increase in haemoglobin between baseline and hospital discharge). AEs were mild/moderate, most commonly transient increases of liver enzymes (n = 5/13.2%). AE incidence was comparable with that observed in patients <75 years. No serious AEs were observed. Ferric carboxymaltose was well tolerated and effective for correction of Hb levels and iron stores in this cohort of IDA patients aged over 75 years.

Prohibitin-mediated lifespan and mitochondrial stress implicate SGK-1, insulin/IGF and mTORC2 in C. elegans.

Lifespan regulation by mitochondrial proteins has been well described, however, the mechanism of this regulation is not fully understood. Amongst the mitochondrial proteins profoundly affecting ageing are prohibitins (PHB-1 and PHB-2). Paradoxically, in C. elegans prohibitin depletion shortens the lifespan of wild type animals while dramatically extending that of metabolically compromised animals, such as daf-2-insulin-receptor mutants. Here we show that amongst the three kinases known to act downstream of daf-2, only loss of function of sgk-1 recapitulates the ageing phenotype observed in daf-2 mutants upon prohibitin depletion. Interestingly, signalling through SGK-1 receives input from an additional pathway, parallel to DAF-2, for the prohibitin-mediated lifespan phenotype. We investigated the effect of prohibitin depletion on the mitochondrial unfolded protein response (UPRmt). Remarkably, the lifespan extension upon prohibitin elimination, of both daf-2 and sgk-1 mutants, is accompanied by suppression of the UPRmt induced by lack of prohibitin. On the contrary, gain of function of SGK-1 results in further shortening of lifespan and a further increase of the UPRmt in prohibitin depleted animals. Moreover, SGK-1 interacts with RICT-1 for the regulation of the UPRmt in a parallel pathway to DAF-2. Interestingly, prohibitin depletion in rict-1 loss of function mutant animals also causes lifespan extension. Finally, we reveal an unprecedented role for mTORC2-SGK-1 in the regulation of mitochodrial homeostasis. Together, these results give further insight into the mechanism of lifespan regulation by mitochondrial function and reveal a cross-talk of mitochondria with two key pathways, Insulin/IGF and mTORC2, for the regulation of ageing and stress response.

An etiologic profile of anemia in 405 geriatric patients.

Background. Anemia is a common condition in the elderly and a significant risk factor for increased morbidity and mortality, reducing not only functional capacity and mobility but also quality of life. Currently, few data are available regarding anemia in hospitalized geriatric patients. Our retrospective study investigated epidemiology and causes of anemia in 405 hospitalized geriatric patients. Methods. Data analysis was performed using laboratory parameters determined during routine hospital admission procedures (hemoglobin, ferritin, transferrin saturation, C-reactive protein, vitamin B12, folic acid, and creatinine) in addition to medical history and demographics. Results. Anemia affected approximately two-thirds of subjects. Of 386 patients with recorded hemoglobin values, 66.3% were anemic according to WHO criteria, mostly (85.1%) in a mild form. Anemia was primarily due to iron deficiency (65%), frequently due to underlying chronic infection (62.1%), or of mixed etiology involving a combination of chronic disease and iron deficiency, with absolute iron deficiency playing a comparatively minor role. Conclusion. Greater awareness of anemia in the elderly is warranted due to its high prevalence and negative effect on outcomes, hospitalization duration, and mortality. Geriatric patients should be routinely screened for anemia and etiological causes of anemia individually assessed to allow timely initiation of appropriate therapy.

Ligation of intersphincteric fistula tract compared with advancement flap for complex anorectal fistulas requiring initial seton drainage.

BACKGROUND: The ligation of intersphincteric fistula tract (LIFT) is a relatively new surgical technique for treating complex anorectal fistulas. METHODS: LIFT was compared with anorectal advancement flap management (ARAF) of complex anorectal fistulas requiring previous seton drainage. Crohn's patients were excluded. Patients with no confirmed recurrent sepsis after 6 months were randomized to day surgery performance of LIFT (25; 17 male) or ARAF (14; 10 male) with removal of the seton. Outcome measures included recurrences, surgical time, complications, hospital readmissions, and fecal incontinence. RESULTS: LIFT was 32.5 minutes shorter than ARAF (P < .001). Complications were similar, with no hospital readmissions. Return to normal activities was 1 week for LIFT patients, 2 weeks for ARAF patients (P = .016). At 19 months there were 3 recurrences (2 in the LIFT group). One ARAF patient had minor incontinence. CONCLUSIONS: The LIFT procedure was simple, safe, shorter, and patients returned to work earlier. All patients had preliminary seton drainage, possibly contributing to the low recurrence rates.

The maintenance of neuromuscular function requires UBC-25 in Caenorhabditis elegans.

Caenorhabditis elegans gene ubc-25 encodes a novel type of an E2 ubiquitin transferase domain (UBCc) protein, which is highly conserved in multicellular animals, but which is not present in the genomes of fungi or plants. To identify the cellular localization of UBC-25 during the development of C. elegans, we used a ubc-25::gfp reporter gene construct. These experiments showed that ubc-25 expression starts during embryogenesis and that it is restricted to neurons and muscle cells in all later stages of development as well as in adult animals. RNA interference with ubc-25 caused late-onset paralysis of most muscular functions such as locomotion, egg laying, and defecation. We therefore propose that ubc-25 in C. elegans is required for the maintenance (homeostasis) of neuromuscular functions by contributing to a tissue specific protein modification pathway, and we speculate that the adult onset phenotype results from the accumulation of target proteins which fail to be degraded.