Pre-operative anaemia, intra-operative hepcidin concentration and acute kidney injury after cardiac surgery: a retrospective observational study.

Acute kidney after cardiac surgery is more common in anaemic patients, whereas haemolysis during cardiopulmonary bypass may lead to iron-induced renal injury. Hepcidin promotes iron sequestration by macrophages: hepcidin concentration is reduced by anaemia and increased by inflammation. We analysed the associations in 525 patients between pre-operative anaemia (haemoglobin < 130 g.l-1 in men and < 120 g.l-1 in women), intra-operative hepcidin concentration and acute kidney injury (dialysis or > 26.4 µmol.l-1 or > 50% creatinine increase during the first two days after cardiac surgery. Rates of pre-operative anaemia and postoperative kidney injury were 109/525 (21%) and 36/525 (7%), respectively. The median (IQR [range]) intra-operative hepcidin concentration was 20 (10-33 [0-125]) µg.l-1 and was lower in anaemic patients than those who were not: 15 (4-28 [0-125]) µg.l-1 vs. 21 (12-33 [0-125]) µg.l-1 , respectively, p = 0.002. Four variables were independently associated with postoperative kidney injury, for which the beta-coefficients (SE) were: minutes on cardiopulmonary bypass, 0.016 (0.004), p < 0.001; intra-operative hepcidin concentration, 0.032 (0.008), p < 0.001; pre-operative anaemia, 1.97 (0.56), p < 0.001; and Cleveland clinic risk score, 0.88 (0.35), p = 0.005. Contrary to generally increased rates of kidney injury in patients with higher hepcidin concentrations, rates of kidney injury in anaemic patients were lower in patients with higher hepcidin concentrations, beta-coefficient (SE) -0.037 (0.01), p = 0.007. In cardiac surgical patients the rate of postoperative acute kidney injury predicted by the Cleveland risk score might be adjusted for pre-operative anaemia and intra-operative cardiopulmonary bypass time and hepcidin concentration. Pre-operative correction of anaemia, reduction in intra-operative bypass time and modification of iron homeostasis and hepcidin concentration might reduce acute kidney injury.

Vascular content, tone, integrity, and haemodynamics for guiding fluid therapy: a conceptual approach.

BACKGROUND: Despite many clinical trials and investigative efforts to determine appropriate therapeutic intervention(s) for shock, this topic remains controversial. The use of i.v. fluid has represented the cornerstone for the treatment of hypoperfusion for two centuries. METHODS: As a part of International Acute Dialysis Quality Initiative XII Fluids Workgroup meeting, we sought to incorporate recent advances in our understanding of vascular biology into a more comprehensive yet accessible approach to the patient with hypoperfusion. In this workgroup, we attempted to develop a framework that incorporates key aspects of the vasculature into a diagnostic approach. RESULTS: The four main components of our proposal involve the assessment of the blood flow (BF), vascular content (vC), the vascular barrier (vB), and vascular tone (vT). Any significant perturbation in any of these domains can lead to hypoperfusion at both the macro- and micro-circulatory level. We have termed the BF, vC, vB, and vT diagnostic approach the vascular component (VC) approach. CONCLUSIONS: The VC approach to hypoperfusion has potential advantages to the current diagnostic system. This approach also has the distinct advantage that it can be used to assess the systemic, regional, and micro-vasculature, thereby harmonizing the approach to clinical vascular diagnostics across these levels. The VC approach will need to be tested prospectively to determine if this system can in fact improve outcomes in patients who suffer from hypoperfusion.

The role of early and sufficient isolated venovenous ultrafiltration in heart failure patients with pulmonary and systemic congestion.

Hypervolemia, present in at least 70% of patients with decompensated heart failure, results in renal dysfunction due to increased renal venous pressure, impaired renal autoregulation, and decreased renal blood flow that are associated with increased morbidity and mortality. Loop diuretics, widely used in congested patients, result in the production of hypotonic urine and neurohormonal activation. In contrast, ultrafiltration (UF) removes isotonic fluid without increasing renin secretion by the macula densa. Simplified devices that permit us to perform UF with peripheral venous access, adjustable blood flows, and small extracorporeal blood volumes make this therapy feasible at most hospitals and in less acute care settings. Conflicting results on the effects of UF in heart failure patients underscore the challenges of patient selection and choice of fluid removal rates. Unfavorable outcomes in patients undergoing UF in the midst of cardiorenal syndrome type 1 are in contrast with the sustained benefits of UF initiated before unsuccessful use of high-dose intravenous (IV) diuretics. UF rates should be based on a precise knowledge of the degree of hypervolemia and careful assessment of blood volume changes, so that extracellular fluid gradually refills the intravascular space and volume depletion is avoided. Poor outcomes are likely to occur if fluid removal rates are not tailored to individual patients' clinical characteristics. A large trial is ongoing to determine if a strategy of early UF, initiated before renal function is worsened by other therapies, is superior to IV diuretics in reducing 90-day heart-failure-related hospitalizations in patients with pulmonary and systemic congestion.

Emergent cardiopulmonary bypass during cesarean delivery. A case report.

Successful management of Cesarean Delivery complicated by emergent CPB and AVR requires meticulous multidisciplinary planning. This case also represents the volatility that can arise from severe aortic regurgitation during pregnancy.

Evolving practices in the management of acute kidney injury in the ICU (Intensive Care Unit).

Acute kidney injury (AKI) is a life-threatening illness whose mortality has remained high since the introduction of hemodialysis three decades ago. Current therapeutic options have been limited to dialytic support because there are no approved pharmacologics for the treatment of AKI. Previous clinical trials have focused on drugs and interventions that increase renal perfusion. These approaches have not been fruitful to date. However, early goal-directed therapy (EGDT) appears to improve renal and overall outcomes. The mechanism whereby EGDT improves outcomes appears to be related to decreased levels of proinflammatory cytokines and apoptosis. Inflammation and AKI are intimately related in preclinical studies. This relationship has been recently confirmed in clinical studies as well. Elevated concentrations of plasma IL-6 predict AKI in patients with sepsis, acute respiratory distress syndrome (ARDS), and hospital-acquired pneumonia. We postulate that inflammation causes AKI. This hypothesis could explain why clinical interventions focused on improving renal perfusion alone have not been effective. If inflammation causes AKI, than therapeutic interventions that decrease inflammation should improve renal outcome. Lung-protective strategies in patients with ARDS increase survival and decrease levels of proinflammatory cytokines. As expected, these decreased levels of proinflammatory cytokines as a result of implementing a lung-protective strategy are associated with improved renal outcome. Mounting evidence supports the hypothesis that inflammation is an important causal component of AKI. Interventions that safely decrease inflammation should be integrated in good clinical practice in order to maximize benefit. In the future, interventions and drugs targeted at inflammation may prove to be robust agents for the treatment of AKI.

The furosemide stress test for prediction of worsening acute kidney injury in critically ill patients: A multicenter, prospective, observational study.

PURPOSE: To validate the furosemide stress test (FST) for predicting the progression of acute kidney injury (AKI). MATERIALS AND METHODS: We performed a multicenter, prospective, observational study in patients with stage I or II AKI. The FST (1 mg/kg for loop diuretic naïve patients and 1.5 mg/kg in patients previously exposed to loop diuretics) was administered. Subsequent urinary flow rate (UFR) recorded and predictive ability of urinary output was measured by the area under the curve receiver operatic characteristics (AuROC). Primary outcome was progression to Stage III AKI. Secondary outcomes included in-hospital mortality and adverse events. RESULTS: We studied 92 critically ill patients. 23 patients progressed to stage III AKI and had significantly lower UFR (p < 0.0001). The UFR during the first 2 h was most predictive of progression to stage III AKI (AuROC = 0.87), with an ideal cut-off of less than 200mls, with a sensitivity of 73.9% and specificity of 90.0%. CONCLUSION: In ICU patients without severe CKD with mild AKI, a UFR of less than 200mls in the first 2 h after an FST is predictive of progression to stage III AKI. Future studies should focus on incorporating a FST as part of a clinical decision tool for further management of critically ill patients with AKI.

Endothelium-derived relaxing factor is important in mediating the high output state in chronic severe anemia.

OBJECTIVES: We evaluated the endothelial and vascular smooth muscle function in patients with chronic severe anemia to determine whether increased basal nitric oxide levels contribute to the systemic vasodilation and high cardiac output seen in these patients. BACKGROUND: Patients with chronic severe anemia have a high output state due to a low systemic vascular resistance. However, the cause of the low vascular resistance is unclear. Because hemoglobin is a potent inhibitor of endothelium-derived relaxing factor, we postulated that in chronic severe anemia, low circulating hemoglobin results in reduced inhibition of endothelium-derived relaxing factor. The basal endothelium-derived relaxing factor activity therefore increases, and this contributes significantly to the low systemic vascular resistance and the hyperdynamic state seen in this condition. METHODS: Hemodynamic variables and forearm blood flow (using plethysmography) were measured in eight patients with chronic severe anemia before (hematocrit 16 +/- 2% [mean +/- SD]) and within 24 h of red blood cell transfusion (n = 6, hematocrit 30 +/- 1%) and in six control subjects. The effect on baseline blood flow of blocking endothelium-derived relaxing factor activity with NG-monomethyl-L-arginine was investigated. In addition, the effects of both endothelium-dependent and endothelium-independent vasodilators on forearm blood flow were tested. RESULTS: Baseline forearm blood flow was markedly increased in untreated patients (6.5 +/- 1.2 ml/min per 100 ml) compared with that in control subjects (2.8 +/- 0.7 ml/min per 100 ml, p < 0.0001, 95% confidence interval [CI] for difference -5 to -2.5). Red blood cell transfusion significantly reduced blood flow in the anemic patients to 3.5 +/- 1.1 ml/min per 100 ml (p < 0.001, 95% CI for difference -4.9 to -1.9), which was not significantly different from that in control subjects; increased systemic vascular resistance (796 +/- 141 to 1,230 +/- 151 dynes.s.cm-5, p < 0.001); and decreased cardiac output (4.9 +/- 0.6 to 3.5 +/- 0.5 liters/min per m2, p < 0.001). NG-monomethyl-L-arginine (16 mumol/min), a specific inhibitor of endothelium-derived relaxing factor, reduced forearm blood flow by an equal amount (p = 0.9, 95% CI for difference -0.7 to 0.8) in control subjects (0.98 +/- 0.39 ml/min) and treated patients (1.03 +/- 0.8 ml/min) but caused a threefold greater decrease in flow (2.9 +/- 0.9 ml/min) in untreated patients (p = 0.0003, 95% CI for difference between untreated patients and control subjects 1.1 to 2.7). These findings suggest increased basal endothelium-derived relaxing factor activity in patients with anemia. Stimulated forearm blood flows (both endothelium dependent and endothelium independent) were similar in all groups, confirming normal endothelial and smooth-muscle function. CONCLUSIONS: These findings support the hypothesis that enhanced basal endothelium-derived relaxing factor activity makes an important contribution to the low systemic vascular resistance in chronic severe anemia.

Needle free injection technology: A complete insight.

Needle free injection technology (NFIT)is an extremely broad concept which include a wide range of drug delivery systems that drive drugs through the skin using any of the forces as Lorentz, Shock waves, pressure by gas or electrophoresis which propels the drug through the skin, virtually nullifying the use of hypodermic needle. This technology is not only touted to be beneficial for the pharma industry but developing world too find it highly useful in mass immunization programmes, bypassing the chances of needle stick injuries and avoiding other complications including those arising due to multiple use of single needle. The NFIT devices can be classified based on their working, type of load, mechanism of drug delivery and site of delivery. To administer a stable, safe and an effective dose through NFIT, the sterility, shelf life and viscosity of drug are the main components which should be taken care of. Technically superior needle-free injection systems are able to administer highly viscous drug products which cannot be administered by traditional needle and syringe systems, further adding to the usefulness of the technology. NFIT devices can be manufactured in a variety of ways; however the widely employed procedure to manufacture it is by injection molding technique. There are many variants of this technology which are being marketed, such as Bioject(®) ZetaJetTM, Vitajet 3, Tev-Tropin(®) and so on. Larger investment has been made in developing this technology with several devices already being available in the market post FDA clearance and a great market worldwide.

Hemodialysis central venous catheter tip fracture with embolization into the pulmonary artery.

We describe the first reported case of spontaneous hemodialysis catheter fracture and embolization. We also include a summary of similar cases not previously reported in the literature that appear in the Food and Drug Administration records as medical equipment malfunctions. Our patient presented with a cough and was initially treated for presumptive pneumonia. A chest radiograph indicated that the tip of the catheter had fractured and migrated into a distal branch of the pulmonary artery. The catheter was replaced, but the tip could not be retrieved because of its peripheral location. Possible causes and consequences of this underreported complication are discussed.

Levels of arsenic in Indian opium eaters.

Intake of opium is very common in India. The contraband material is generally contaminated with arsenic. Most often opium eaters present with neuropathy and hepatomegaly. Arsenic was estimated in serum, urine, nails and hair of opium eaters with and without neuropathy. Arsenic was also estimated in various opium samples. Arsenic was significantly higher in serum, urine, nails and hair of opium addicts when compared to controls. The opium samples analysed showed varyingly high amounts of arsenic.

Levels of arsenic in alcohol-related liver disease.

Increased levels of arsenic were found in serum and urine and in hair and nails of patients suffering from alcohol-related liver disease (ALD). Various surveys were conducted in different places to find the cause for high arsenic in ALD. It was found that patients were consuming 'home made brew' which was contaminated with arsenic.

Zinc nutritional status modifies renal osteodystrophy in uremic rats.

BACKGROUND: Previous studies from our laboratories suggested that zinc depletion reduces the circulating level of 1,25-dihydroxycholecalciferol (1,25(OH)2D, calcitriol) in calcium- and phosphorus-depleted rats with normal renal function, and rats with uremia. Since calcitriol synthesis is in part dependent on renal function, we studied levels of circulating vitamin D metabolites, PTH response, mineral balance and bone histomorphometry in animals with different zinc nutritional and renal functional status. METHODS: Fifty-eight male Sprague-Dawley rats were pair-fed zinc-replete (+) or -deplete (-) diets for two weeks. Thereafter, half of each paired group underwent nephrectomy (N), while half had sham (S) operations. Animals were observed for eight weeks after surgery. External mineral balances of zinc, calcium, phosphate and magnesium were determined before surgery, and 1, 2 and 7 weeks after surgery. Plasma creatinine, zinc, calcium, phosphorus, magnesium, 25-hydroxycholecalciferol, calcitriol and PTH were determined at sacrifice. Static and dynamic bone histomorphometry was determined by standard techniques. RESULTS: After an 8-week observation period, zinc-depleted animals had lower plasma zinc levels, and nephrectomized animals had lower creatinine clearances than respective controls at sacrifice. Plasma calcium and phosphorus concentrations were similar in all four groups at sacrifice. Plasma magnesium concentrations were similar in groups with renal insufficiency, regardless of zinc nutritional status. Plasma 25-hydroxycholecalciferol and calcitriol levels were similar in all groups. There was no difference between mean PTH concentration in sham-operated animals, regardless of zinc nutritional status. Although nephrectomized groups' PTH levels were increased compared to S controls, PTH levels were increased in +Zn/N animals compared to the -Zn/N group. Zinc-deplete groups had consistent negative net zinc balance, however, there was no consistent effect of nephrectomy on external calcium, phosphorus, or magnesium balance, when nephrectomized groups of different zinc nutritional status were compared. Nephrectomized animals had histomorphometric changes indicative of higher bone turnover and abnormal mineralization. Zinc deficiency was associated with less evidence of increased parathyroid hormone activity on bone in nephrectomized rats. CONCLUSIONS: Zinc depletion limits the increase in plasma PTH concentration and the expression of secondary hyperparathyroid bone disease during the development of renal insufficiency in the renal ablation model of uremia in rats. The mechanism underlying this effect is unknown, but may involve a direct effect of zinc on the synthesis, release, metabolic clearance, and/or action of PTH on the cellular level, on the interrelationship of calcitriol and PTH, or a direct effect of zinc on bone mineral metabolism. These data highlight the potential relevance of zinc nutritional status to mineral metabolism in patients with chronic renal insufficiency and end-stage renal disease.

Endoscopic techniques in the diagnosis of upper gastrointestinal tract malignancies. A comparison.

OBJECTIVE: To perform a comparative evaluation of various endoscopic techniques in the diagnosis of upper gastrointestinal tract malignancies. STUDY DESIGN: Thirty cases of suspected malignancy involving the upper gastrointestinal tract were studied. In all 30 cases, four endoscopic cytology techniques (brushing before biopsy, brushing after biopsy, fine needle aspiration cytology [FNAC] and suction cytology) were evaluated and correlated with histology by forceps biopsy. All the cytologic techniques were used and forceps biopsy carried out in a single sitting, but the forceps biopsy was repeated in 4 of 30 cases. RESULTS: The respective positive yields of brushing before biopsy, brushing after biopsy, FNAC, suction cytology and forceps biopsy were 80.0%, 86.6%, 83.3%, 76.6% and 90.0%. When two cytologic techniques were combined, 100% accuracy was obtained by brushing after biopsy and FNAC and brushing before biopsy and suction cytology. CONCLUSION: Brushing cytology is a sensitive diagnostic test, and the combined use of biopsy and brushing offers the highest probability of identifying malignancy.

Prognostic significance of transient type II second degree atrioventricular block induced during exercise testing.

During exercise testing a 70 years old male developed Type II second degree AV block which reverted in recovery period. On follow up 3 months later, he developed symptomatic 2: 1 atrioventricular block and required permanent pacemaker implantation.

Indolent gastric carcinoma.

A 55 year old woman presenting with epigastric pain and dyspeptic symptoms was diagnosed to have gastric carcinoma on endoscopic biopsy independently on two occasions. She was subsequently asymptomatic without any specific therapy till she developed gastric outlet obstruction and weight loss four years later. Histology of the resected specimen revealed an adenocarcinoma infiltrating the serosa without any evidence of metastasis.

Esophageal candidiasis following omeprazole therapy: a report of two cases.

Esophageal candidiasis was diagnosed at endoscopy in two patients receiving omeprazole therapy. There was no clinical evidence of immunosuppression or any obstructive lesion in the esophagus. There was prompt response of oral ketoconazole. These cases suggest that marked acid reduction may predispose to esophageal candidial infection.

Serum pepsinogen levels in patients with gastro-duodenal lesions.

Serum pepsinogen (SP) levels were studied in 100 patients with gastroduodenal lesions, and 100 healthy volunteers. SP levels were significantly elevated in patients with duodenal ulcer (DU) and duodenitis compared to the controls. SP values above 150 ug Tyr/ml/24 hr were highly suggestive of duodenal ulcer disease. Age and sex of patients and controls did not influence SP levels. The mean values of SP in North India were found to be lower in both normal and DU subjects compared to the west.

Jaundice in Plasmodium falciparum.

Thirty-two patients of smear positive Plasmodium falciparum malaria having jaundice were analysed retrospectively. Majority of the cases were in the age group of 31-40 years. Serum bilirubin levels ranged from 2 mg to 40 mg%. Fourteen (42.6%) had serum bilirubin above 10 mg%. Conjugated bilirubinaemia was found in twenty one patients (65.5%), unconjugated in 4 (12.5%) while 7 patients (21.8%) had a mixed pattern. Serum transaminases were high in 21.8% patients. Twenty five patients (78%) had associated azotaemia, 11(34.3%) had intravascular haemolysis and 3(9.3%) had possible cerebral malaria. Hepatosplenomegaly was seen in all the 32 patients. Mortality was 21% but none died of hepatic encephalopathy. Histologically the most consistent finding in liver biopsies was reticulo-endothelial cell hyperplasia. Pigmentation in kupffer cells, fatty change, sinusoidal and portal infiltration and cholestasis were the other features seen.

Ascitic fluid cholesterol in differential diagnosis of ascites.

Cholesterol was estimated in ascitic fluid of 89 patients (29 malignant and 60 non-malignant ascites). Mean ascitic cholesterol level was significantly higher in malignant ascites (89.52 mg/dl) as compared to non-malignant ascites (29.93 mg/dl). At a cut off value of 48 mg/dl, the sensitivity, specificity, positive and negative predictive value and overall diagnostic accuracy for diagnosing malignant ascites is 96.5%, 96.6%, 93.3%, 98.3% and 96.6% respectively. Ascitic fluid cholesterol estimation is an easy and reliable test for differentiating malignant ascites from non-malignant ascites.