The effect of warm ischemic time on renal function and injury in the isolated hemoperfused kidney

BACKGROUND: The precise effect of warm ischemia on renal allograft function remains unclear and leads to variable warm ischemic time (WIT) limits advocated by transplant programs. This study aims to investigate the relationship between WIT, renal ischemia reperfusion injury, and graft function using a hemoperfused kidney model. METHODS: Porcine kidneys were perfused with normothermic blood on an isolated organ perfusion system. Kidneys were divided into four groups (n=6) and subjected to 7, 15, 25, and 40 min WIT. Physiological parameters were measured throughout the 6 hr perfusion period. Serum, tissue, and urine samples were analyzed for histological and biochemical markers of ischemia reperfusion injury. RESULTS: Creatinine clearance, urine output, renal hemodynamics, and oxygen consumption deteriorated proportionally with increasing WIT. A significant increase in plasma carbonyl levels during perfusion was seen after 25 and 40 min WIT only. Plasma 8-isoprostane levels were higher after 40 min WIT (2.5+/-1.6) vs. 7, 15, and 25 min WIT (0.65+/-0.43, 0.25+/-0.12, and 0.62+/-0.21, respectively; P<0.05). A negative correlation was shown between urine output and plasma carbonyls (r=-0.415, P<0.05) and between 8-isoprostane levels and creatinine clearance (r=-0.649, P<0.005). Caspase-3 activity was significantly higher after 7 min WIT compared with the other groups, correlating positively with creatinine clearance, urine output, and renal blood flow. CONCLUSION: The isolated organ perfusion system successfully delineated a clear WIT-dependent variation in renal function which correlated accurately with oxidative injury markers. This model may represent a clinically applicable tool for assessing graft viability.     

Prevention and treatment of hypotension during Caesarean delivery

Regional anesthesia for Caesarean delivery is often accompanied by a reduction in maternal blood pressure. Maternal hypotension may lead to a reduction in uteroplacental blood flow with consecutive fetal acidosis. In order to avoid reductions in uteroplacental blood flow, tremendous research has been performed, showing that the avoidance of aortocaval compression, compression of the lower extremities, and prehydration with colloids are effective in reducing maternal hypotension. Further means include the recent introduction of low dose spinal anesthesia with a combination of small amounts of local anesthetics and opioids. Nevertheless, maternal hypotension is not always preventable and the use of vasopressors is still frequently required. Although ephedrine has been considered the vasopressor of choice over the last decades, current studies show that fetal acidosis is less frequently encountered with the use of phenylephrine, which should thus be considered as a first-line agent.     

The HIV care cascade: models,measures and moving forward

Introduction

This article seeks to identify where delays occur along the adult HIV care cascade (“the cascade”), to improve understanding of what constitutes “delay” at each stage of the cascade and how this can be measured across a range of settings and to inform service delivery efforts. Current metrics are reviewed, measures informed by global guidelines are suggested and areas for further clarification are underscored.

Discussion

Questions remain on how best to evaluate late entry into each stage of the cascade. The delayed uptake of HIV testing may be more consistently measured once rapid CD4 testing is administered at the time of HIV testing. For late enrolment, preliminary research has begun to determine how different time intervals for linking to HIV care affect individual health. Regarding treatment, since 2013, the World Health Organization (WHO) and UNAIDS recommend treatment initiation when CD4 <500 cells/mm³; these guidelines provide a useful albeit evolving threshold to define late treatment initiation. Finally, WHO guidelines for high-, low- and middle-income countries also could be used to standardize measures for achieving viral suppression.

Conclusions

There is no “one size fits all” model as the provision of services may differ based on a range of factors. Nonetheless, measures informed by global guidelines are needed to more consistently evaluate the scope of and factors associated with delays to each stage of the cascade. Doing so will help identify how practitioners can best deliver services and facilitate access to and continued engagement in care.     

Current determinants of 30-day and 3-month mortality in over 2000 aortic valve replacements: Impact of routine laboratory parameters.

OBJECTIVE: Haematological and biochemical measurements are performed routinely before surgery to exclude organ malfunction and blood cell and coagulation abnormalities. We aimed to test routinely obtained laboratory data as factors predicting operative risk. METHODS: Between 1996 and 2003, 2198 patients underwent aortic valve replacement (AVR) (908 of them with concomitant CABG) in our institute. The mean age of the study population was 69+/-11 years (range 13-91, 43% female). Clinical and laboratory parameters based on the consolidated data mart set were evaluated by multiple logistic regression analysis. RESULTS: The overall operative mortality (within 30 days) was 3.8% and the mortality after 3 months was 5.9%. In addition to clinical characteristics, the following laboratory values were identified as independent predictors of 30-day mortality: fasting blood glucose, antithrombine III, partial thromboplastine time and creatinine kinase. As independent predictors of 3-month mortality, the following laboratory values were indentified: fasting blood glucose, serum creatinine, antithrombine III, partial thromboplastine time, lactate dehydrogenase, sodium concentration and serum proteins. The discriminative power of the models increased if laboratory parameters were included in addition to preoperative clinical characteristics (from 0.75 to 0.79 and from 0.75 to 0.78 for 30-day and 3-month mortality, respectively). The discriminative power using the logistic EuroScore was lower (0.71 and 0.7, for 30-day and 3-month mortality, respectively). CONCLUSIONS: Laboratory parameters as objective markers for organ function and nutritional status are useful data for the prediction of 30-day and 3-month mortality after aortic valve replacement. Using modern methods of information technology, these valuable data which are stored electronically in most hospitals, can be used efficiently for research and quality control.     

Fear of hypoglycemia,a game changer during physical activity in type 1 diabetes mellitus patients

Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus (T1DM). Fear of hypoglycemia (FoH) is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity (e.g., cardiometabolic health, improved body composition, cardiovascular fitness, quality of life). Technological advances, improved insulin regimens, and a better understanding of the physiology of various types of exercise could help ameliorate FoH. This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.     

Isolated main pancreatic duct injuries spectrum and management

BACKGROUND: We present our experience with the rare injury of isolated major pancreatic duct disruption. METHODS: From 1997 to 2003, 3 females and 13 males whose age ranged from 4 to 46 years were identified. Stabs caused 2 and blunt trauma 14 injuries. Nine presented acutely. Delay occurred in 7 patients, 6 with pseudocysts and 1 with infected pancreatic necrosis. RESULTS: Nine cases were managed in the acute phase: 6 by splenic-preserving distal pancreatectomy and 2 by distal pancreatico-enteric anastomosis; 1 was drained. A small pseudocyst and transient pancreatic fistula were the only complications. The 6 cases with pseudocysts were managed endoscopically. Five were stented and 1 was drained without stent. Four had resolution. Two had stent cyst migration. One required a pancreaticojejunostomy and another distal pancreatectomy. One patient died of infected pancreatic necrosis. Long-term outcome could not be assessed. CONCLUSION: In the acute situation, resection or distal pancreatico-enteric anastomoses are attainable with low morbidity. Endoscopic pseudocyst management options are feasible, with good short-term resolution. Giant cysts may be better managed operatively.     

Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation

Experimental mouse models of bacterial skin infections that have been described show that pathogenic microorganisms can readily invade the epidermis and dermis to produce localized infections. We used an epicutaneous mouse skin infection model to determine how the level of barrier disruption by tape‐stripping correlates with persistence of Staphylococcus aureus skin colonization, concomitant induction of cutaneous inflammation and infection. Furthermore, we investigated how murine skin responds to S. aureus colonization in a physiologic setting by analysing proinflammatory cytokines and antimicrobial peptides in mouse skin. We show that previous cutaneous damage allows skin inflammation to develop and favours S. aureus persistence leading to cutaneous colonization, suggesting an interdependence of cutaneous bacteria and skin. Our study suggests that skin barrier defects favour S. aureus skin colonization, which is associated with profound cutaneous inflammation.     

Effect of intravitreal injections and volume changes on intraocular pressure: clinical results and biomechanical model

PURPOSE: Intravitreal injections are used extensively to treat retinal diseases. Performing an intravitreal injection increases intraocular volume by the amount of fluid brought into the eye. Whether this influences intraocular pressure (IOP) was investigated here. METHODS: A biomechanical model relying on 3-dimensional elasticity theory was developed to determine the short-term effect of volume changes on IOP. We calculated the effect for intravitreal injections of 0.1 ml in myopic, emmetropic and hyperopic eyes. Our calculations were compared with IOP measurements obtained immediately after intravitreal injection of 4 mg triamcinolone in 0.1 ml solution (IVTA) in 22 patients. Shortly after the measurement had been taken, IOP was reduced by paracentesis. RESULTS: Immediately after IVTA, measured IOP was elevated by a mean of 40.6 +/- 12.1 mmHg compared with initial pressure (p < 0.001). Measured and calculated IOP were comparable. Eyes with shorter axial length had higher IOP immediately after the injection (p < 0.05). CONCLUSIONS: The effect of injected volumes on IOP can be calculated with a biomechanical model. Our results show that paracentesis might be recommended when injecting 0.1 ml of a substance to avoid a short-term increase in IOP. As intravitreal injections are mostly applied in diseases that are due to vascular compromise, it might be prudent not to impair perfusion in those eyes, even for short periods of time.     

Pseudotumoral pulmonary cryptococcosis in association with Cushing's syndrome

Opportunistic infections in endogenous Cushing's syndrome are associated with severe cortisol excess and carry a high mortality. Pulmonary cryptococcosis is one of these opportunistic infections and can mimic a lung neoplasm, therefore making its diagnosis difficult. We report a case of a young male with ACTH-dependent Cushing's syndrome and severe hypercortisolism. The patient achieved cure after the transfenoidal surgery, but developed a febrile state. A chest computed tomography showed a pulmonary nodule that did not change in serial chest radiographs. Diagnosis of tuberculosis, fungal and bacterial infections were inconclusive, so the hypothesis of lung neoplasm became more probable. The necropsy, however, disclosed a pseudotumoral cryptococcosis. Opportunistic infections, like Cryptococcus neoformans, should be considered in patients with Cushing's syndrome and a pulmonary infiltrate.     

Comorbidity in young patients with juvenile systemic lupus erythematosus: how can we improve management?

Clinical Rheumatology -