Severe Rhabdomyolysis in Glucose-6-Phosphate Dehydrogenase Deficiency.

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is an X-linked genetic disorder associated with intravascular hemolysis. Rhabdomyolysis with myoglobinuria in a patient with G6PD deficiency is a very rare manifestation, in fact, to the best of our knowledge, only a few case reports have been published in the literature to date. Herein, we report an unusual presentation of a 33-year-old male with G6PD deficiency with multiple episodes of severe rhabdomyolysis with no significant concurrent hemolysis. This case supports the hypothesis that rhabdomyolysis may be a rare manifestation of G6PD deficiency, though the exact causation still remains unclear.

Re-Educating Residents About Non-Invasive Colorectal Cancer Screening: An Approach to Improving Colon Cancer Screening Compliance.

BACKGROUND: Colorectal cancer is the third leading cause of cancer death; therefore early detection by screening is beneficial. Residents at a clinic in NJ, USA were not offering other forms of colon cancer screening when patients refused colonoscopy, which lead to the creation of the quality improvement project. METHODS: Residents practicing at the clinic were given an anonymous survey determining which method of colon cancer screening they used and which alternative method they offered when patients refused the original method. The residents were educated about all methods of colon cancer screening and the residents were resurveyed. RESULTS: A total of 64% of residents offered less invasive testing when colonoscopy was refused. Six months after education, 95% of residents offered less invasive testing when colonoscopy was refused. CONCLUSIONS: Early detection and removal of polyps by colonoscopy reduce the risk of cancer development. Colonoscopy is the gold standard for colon cancer screening; however other less invasive modalities are approved. This quality improvement project lead to offering the fecal immunochemical test or fecal occult blood test once patients refused colonoscopy at the clinic, increasing the number of patients receiving colorectal cancer screening, and thus providing better medical care.

Clinical Resolution of Osmotic Demyelination Syndrome following Overcorrection of Severe Hyponatremia.

Osmotic Demyelination Syndrome (ODS) occurs after rapid overcorrection of severe chronic hyponatremia usually in those with a predisposition such as chronic alcoholism, malnutrition, or liver disease. Rarely, do patients make a full recovery. We report a case of ODS secondary to overcorrection of severe hyponatremia with pathognomonic clinical and radiologic signs making a complete neurological recovery. A detailed course of events, review of literature, and optimal and aggressive management strategies are discussed. There is some controversy in the literature regarding the prognosis of these patients. Our aim here is to show that, with aggressive therapy and long-term care, recovery is possible in these patients.

Severe Metabolic Acidemia in a Patient with Aleukemic Leukemia.

Malignancy associated lactic acidosis is a rare metabolic complication that may accompany various types of malignancies. To date, most cases that have been reported are associated with hematologic malignancies (lymphoma and leukemia). Many theories have been proposed to explain the pathophysiology of lactic acidosis in malignancies. We are reporting an unusual case of a 62-year-old female who presented with a complaint of generalized weakness. Patient was found to have pancytopenia and metabolic acidosis with an anion gap secondary to lactic acid in addition to non-anion gap acidosis (NAGA). The lactic acidosis resolved only after initiation of chemotherapy as she was diagnosed with B-cell acute lymphoblastic leukemia. Our patient also had a coexistent Renal Tubular Acidosis (RTA) with large kidneys. The kidney size also decreased with chemotherapy. Our case is unique as evidenced by aleukemic leukemia combined with anion gap acidosis and non-anion gap acidosis. Lactic acidosis has many different causes; although rare, hematologic malignancies should be included in the differential diagnosis regardless of cell counts or tumor burden.

Infective Endocarditis in Hemodialysis Patients.

BACKGROUND AND AIM OF THE STUDY: Infective endocarditis (IE) is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The study aim was to evaluate the demographic, clinical, microbiological and inpatient mortality data of IE in hemodialysis patients. METHODS: Data were analyzed for all IE patients admitted to the authors' 800-bed tertiary care hospital between January 2001 and December 2014. These data included demographics, comorbidities, clinical and microbiological characteristics, echocardiographic findings, complications, outcomes, and in-patient mortality. RESULTS: A total of 296 patients, including 52 on hemodialysis, was admitted with a diagnosis of IE. The median age of patients with ESRD (28 females, 24 males) was 55.9 ± 15.47 years. The prevalences of comorbidities such as hypertension (80%) and diabetes mellitus (46%) were significantly higher in ESRD patients, whereas other comorbidities were similarly distributed in both groups. The mitral valve was the most commonly involved (55.8%), followed by aortic (21.7%), tricuspid (21.2%) and pulmonary (1.9%) valves. Staphylococcus aureus was the most common organism (40%), followed by Enterococcus sp. (13.7%), Gram-negative staphylococci (13.7%), coagulase-negative staphylococci (11.5%), and Streptococcus sp. (5.7%). Polymicrobes were found in 11.5% of patients and cultures were negative in 19%. The mean ejection fraction in these patients was 42 ± 4.19% and the mean area of vegetation was 63.5 ± 40 mm2. The in-hospital course of 11 patients was complicated by embolic events, while three patients had acute heart failure and one patient had heart block secondary to IE. A total of four patients (7.7%) died during the index hospitalization. CONCLUSIONS: IE in patients receiving chronic hemodialysis is a very frequent occurrence. Its diagnosis is complex and its presence should be considered in all hemodialysis patients with bacteremia. In the present study the etiology was shown to be multifactorial, with the mitral valve being the most commonly involved and S. aureus the most common organism.

Adenomatous Colon Polyps in Diabetes: Increased Prevalence in Patients with Chronic Kidney Disease and Its Association with Parathyroid Hormone.

Previous studies have shown a higher prevalence of malignancy in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). The purpose of this study was to investigate the prevalence of adenomatous colon polyps (ACP) as they occur in subjects with DM and coexisting CKD. This is a retrospective cohort study of patients with DM (n=565) who had undergone colonoscopy between 2000-2010. The cohort was further bifurcated into those with CKD (n=296) and those with normal renal function (n=269). Presence or absence of ACP was measured in both groups. Concentrations of serum parathyroid hormone (PTH), Calcium (Ca), and phosphorous (P) were recorded for the CKD group. The levels of these variables in patients with ACP (n=171) were compared with the levels from those without ACP (n=175). Nonparametric statistical methods were applied with statistical significance suggested by p<0.05 (two-sided). The presence of CKD in this cohort demonstrated a significant association with ACP (OR: 2.96; 95% CI: 2.02 to 4.34; p<0.0001). We did not detect a statistically significant difference in P or Ca between the groups. There was, however, a statistically significant difference in PTH; for the group with ACP, PTH: 387.7±351.3 ng/L vs. 172.2±196.7 ng/L; p<0.0001. This data suggests that CKD is associated with ACP in subjects with DM and those with ACP exhibit higher PTH levels when compared to those without ACP.

Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of literature.

Recently, cancer therapies have been supplemented by vascular endothelial growth factor (VEGF) inhibitors as anti-angiogenic agents. However, kidney-related adverse reactions associated with these agents clinically manifest as hypertension and proteinuria, the most severe form being thrombotic microangiopathy (TMA). We present the spectrum of pathological features in VEGF inhibitor-associated kidney disease. Clinicopathological findings of kidney disease were retrospectively studied in 5 cancer patients treated with anti-VEGF agents. Although 4 cases received bevacizumab (anti-VEGF-A), one was given sorafenib (small molecule tyrosine kinase inhibitor affecting VEGF-R2). All patients presented with acute kidney injury, hypertension, and/or proteinuria. All kidney biopsies showed recent and chronic endothelial injury of varying severity and vascular sclerosis, including 2 with typical active features of TMA. Furthermore, acute tubular injury with focal necrosis was seen in all cases. While administration of VEGF inhibitor was discontinued in 4 cases, it was resumed for 5 more doses, following steroid therapy in 1 case. Cessation of VEGF inhibitor therapy was successful in reversing anemia and led to improvement of hypertension and proteinuria in 4 of the 5 cases. One case with TMA progressed to end-stage renal disease. A range of renal pathologic lesions secondary to endothelial injury are noted often accompanied by acute tubular damage following anti-VEGF therapy, the most severe being TMA. While most of the clinical manifestations are reversible with discontinuation of therapy, the role of other nephrotoxic chemotherapeutic agents in enhancing renal injury including severe TMA and other host factors with possible poor outcome should be considered.

Collapsing glomerulopathy superimposed on diabetic nephropathy: insights into etiology of an under-recognized, severe pattern of glomerular injury.

BACKGROUND: Collapsing glomerulopathy (CG) represents severe podocyte injury with massive proteinuria, rapid progression and relative resistance to therapy. It is associated with multiple etiologies, including obliterative arteriopathy in transplants. However, its association with diabetic nephropathy (DN) has not been reported. METHODS: Renal biopsies performed in diabetic patients for either increasing proteinuria or deteriorating renal function, or both, were retrospectively reviewed. The clinicopathologic features and immunohistochemical staining of podocytes were analyzed. RESULTS: Of 534 patients with DN, 26 human immunodeficiency virus (HIV)-negative patients were found to have CG superimposed on DN (5% DN cases). At the time of biopsy, their mean serum creatinine was 3.8 mg/dL and proteinuria was 9.8 g/24 h. Renal biopsy showed CG in 2-30% (mean 16% of glomeruli), with segmental (2%) and global (33%) glomerulosclerosis. DN classification was Class IV-12, III-8, IIb-4 and IIa-2. Vascular sclerosis was moderate (44%) and severe (56%). Extensive arteriolar hyalinosis with >50% luminal stenosis was seen in 85% of cases. Markers of podocyte differentiation were lost, consistent with other types of CG. Cytokeratin was focally positive in 70% and VEGF overexpressed in 43%. Follow-up on 17 patients: 13 developed end-stage renal disease (ESRD) in 7 months from the time of biopsy. The development to ESRD in these patients was more rapid than diabetic controls without CG (P=0.005). The remaining four, 5-24 months follow-up, had an increase in creatinine with stable proteinuria. CONCLUSIONS: CG contributes to an increased level or new onset of proteinuria in DN which may be intractable. CG in DN with advanced vascular hyalinosis is presumably due to ischemic podocyte injury and is of prognostic significance.

Phase IIa study of the immunogenicity and safety of the novel Staphylococcus aureus vaccine V710 in adults with end-stage renal disease receiving hemodialysis.

Bacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses against Staphylococcus aureus in patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conserved S. aureus surface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase II immunogenicity study, 206 chronic hemodialysis patients between the ages of 18 and 80 years old were randomized to receive 60 µg V710 (with or without adjuvant), 90 µg V710 (with adjuvant), or a placebo in various combinations on days 1, 28, and 180. All 201 vaccinated patients were to be followed through day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 V710 doses on days 1 and 28 would have a ≥2.5 geometric mean fold rise (GMFR) in anti-IsdB IgG titers over the baseline 28 days after the second vaccination (day 56). At day 56, all three groups receiving 2 doses of V710 achieved a ≥2.5 GMFR in anti-IsdB antibodies compared to the baseline (P values of <0.001 for all 3 groups), satisfying the primary immunogenicity hypothesis. None of the 33 reported serious adverse experiences were considered vaccine related by the investigators. V710 induced sustained antibody responses for at least 1 year postvaccination in patients on chronic hemodialysis.

Pulmonary gas exchange during hemodialysis: a comparison of subjects with and without COPD on bicarbonate hemodialysis.

Little is known about the effect of hemodialysis (HD) on gas exchange in subjects with chronic obstructive pulmonary disease (COPD). The purpose of this study was to examine blood gases and pH in COPD patients undergoing HD with bicarbonate dialysate. We studied thirteen subjects with COPD and thirteen controls (CON). All were dialyzed for 4 hrs against a bicarbonate HD solution. Blood gases, pH and HCO(3) (-) were initially analyzed (t(0)) and, during HD, at 30 min (t(0.5)), 1 hr (t(1)) and 4 hrs (t(4)). At t(0), a statistically significant difference was observed for PO(2) (CON: 84.7±3.60, COPD: 72.19±4.92; p<0.001). For the first hr, PO(2) decreased, and at t(1), oxygen was required for 6 COPD subjects. By t(4), there was no significant difference in PO(2) between groups. The alveolar-arterial gradient (ΔA-a) remained different between groups (P<0.001, all times), with increasing ΔA-a for both groups up to t(1) and decreasing over the remaining 3 hr. For both groups, at t(4), ΔA-a was higher than at t(0) (p<0.001). For PCO(2), both groups demonstrated increases from t(0) to t(1) (p=0.0004), with COPD having PCO(2) higher than CON at t(0.5) and t(1) (p<0.05 for both); by t(4), PCO(2) levels decreased to nearly the same as at t(0). Over the 4 hr treatment, HCO(3) (-) and pH increased significantly for both groups; however no significant difference was observed between COPD and CON. Markedly increased ΔA-a is observed during HD in some COPD patients. COPD patients retain more CO(2). However, the effect of HCO(3) (-) leads to mild metabolic alkalosis at t(4).

Chronic kidney disease as a risk factor for Clostridium difficile infection.

INTRODUCTION: Clostridium difficile-associated diarrhoea (CDAD) is the most common cause of nosocomial diarrhoea in the USA. In this study, we sought to determine the association between chronic kidney disease (CKD) and CDAD. METHODS: A case-control study was designed to determine the association between CKD and CDAD in an urban hospital. Over a 2-year period, all patients diagnosed with CDAD (n = 188) were included as cases and the prevalence of CKD was calculated. Age- and sex-matched patients without CDAD were considered as controls with a ratio of 2:1 controls to cases. The prevalence of different stages of advanced CKD (stages 3-5) was determined and compared between groups. Also the calculated odds ratios (OR) were adjusted for multiple possible confounding variables using logistic regression analysis. RESULTS: There was no significant difference in prevalence of advanced CKD between cases and controls (OR = 1.38, 95% confidence intervals (CI) = 0.90-2.12, P = 0.1365). The association between CKD and CDAD remained insignificant in subjects with CKD stages 3-5 who were not on dialysis (OR = 1.07, 95% CI = 0.65-1.77), P = 0.7970). However, the group with end-stage renal disease on dialysis showed a significant association (OR = 2.60, 95% CI = 1.25-5.41, P = 0.0165). Controlling for antibiotics as a possible confounding variable, yielded an OR that was not statistically significant (OR = 2.05, 95% CI = 0.94-4.47, P = 0.07), but still showing a trend towards increased risk. CONCLUSION: End-stage renal disease may increase the risk of acquiring CDAD through unknown mechanisms. This suggests implementing better surveillance strategies for these patients and eliminating the known risk factors for CDAD.