Belatacept-based immunosuppression does not confer increased risk of BK polyomavirus-DNAemia relative to tacrolimus-based immunosuppression.

BACKGROUND: The effect of belatacept on BK polyomavirus (BKPyV) control remains largely unknown. METHODS: This is a propensity matched retrospective cohort study in adult kidney transplant recipients (KTR) transplanted between 2016-2020 who received a belatacept- versus tacrolimus-based immunosuppression regimen. A continuous time multi-state Markov model was used to evaluate BKPyV replication dynamics (BKPyV-dyn). Three BKPyV-dyn states were defined: BKPyV-dyn1 (viral load <3 log10), BKPyV-dyn2 (viral load ≥ 3 log10 and ≤4 log10), and BKPyV-dyn3 (viral load >4 log10). RESULTS: Two hundred eighty KTR on belatacept- and 280 KTR on tacrolimus-based regimens were compared. The probability of transitioning between BKPyV-dyn states and time spent in each state in both groups was comparable. Total duration in BKPyV-dyn-1 was 632.1 days (95% CI 612.1, 648.5) for belatacept versus 615.2 days (95% CI 592.5, 635.8) for tacrolimus, BKPyV-dyn-2 was 49.2 days (95% CI 41.3, 58.4) for belatacept versus 55.6 days (95% CI 46.5, 66.8) for tacrolimus, and BKPyV-dyn-3 was 48.7 days (95% CI 37.1, 363.1) for belatacept versus 59.2 days (95% CI 45.8, 73.5) for tacrolimus. BKPyV associated nephropathy (PyVAN) occurred in 3.9% in belatacept- and 3.9% tacrolimus-treated KRT (P > .9). CONCLUSIONS: Compared with tacrolimus-based immunosuppression, belatacept based immunosuppression was not associated with increased risk of BKPyV-DNAemia or nephropathy.

Acetazolamide and Hydrochlorothiazide Followed by Furosemide Versus Furosemide and Hydrochlorothiazide Followed by Furosemide for the Treatment of Adults With Nephrotic Edema: A Randomized Trial.

BACKGROUND: Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum doses of loop diuretics. This condition can be treated with loop diuretics and thiazides. However, animal studies show that the simultaneous downregulation of pendrin with acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide generates significant diuresis, and furosemide administration following a pendrin inhibitor potentiates furosemide's diuretic effect. Therefore, we performed this study to compare the efficacy of acetazolamide and hydrochlorothiazide followed by furosemide versus furosemide and hydrochlorothiazide followed by furosemide for treatment of refractory nephrotic edema. STUDY DESIGN: Randomized, double-blind, 2-arm, parallel trial. SETTING & PARTICIPANTS: 20 patients with refractory nephrotic edema despite treatment with 80mg of furosemide daily and creatinine clearance > 60mL/min. INTERVENTION: Patients were randomly assigned to 2 groups: group 1 (n=10) received 250mg of acetazolamide and 50mg of hydrochlorothiazide daily and group 2 (n=10) received 40mg of furosemide and 50mg of hydrochlorothiazide daily for 1 week in phase 1. In phase 2, both groups received 40mg of furosemide daily for 2 weeks. OUTCOMES: The primary outcome was absolute change in weight before and at the end of each phase. MEASUREMENTS: Weight and 24-hour urine volume at baseline and the end of each phase. RESULTS: The mean weight decrease was of significantly larger magnitude in group 1 compared with group 2 at the end of phase 1 (-1.4±0.52 [SD] vs -0.65±0.41kg; P=0.001) and phase 2 (-1.6±0.84 vs -0.5±0.47kg; P=0.005). The increase in 24-hour urine volume was also significantly higher in group 1 at the end of phase 2. LIMITATIONS: Small sample size, short follow-up duration, and lack of serum bicarbonate and chloride measurement. CONCLUSIONS: Acetazolamide and hydrochlorothiazide followed by furosemide is more effective than furosemide and hydrochlorothiazide followed by furosemide for the treatment of refractory nephrotic edema.

Nutritional Deficiencies and Sarcopenia in Heart Failure: A Therapeutic Opportunity to Reduce Hospitalization and Death.

There is an expanding prevalence pool of heart failure (HF) due to the increasing prevalence of survivors of myocardial infarction, diabetes, hypertension, chronic kidney disease, and obesity. There is increasing interest in the role of nutrition in all forms of HF, given observations concerning micro- and macronutrient deficiencies, loss of lean body mass or sarcopenia, and their relationships with hospitalization and death. This review examines the relationships among loss of lean body mass, macro- and micronutrient intake, and the natural history of HF, particularly in the elderly, in whom the risks for all-cause rehospitalization, infection, falls, and mortality are increased. These risks are potentially modifiable through strategies that improve nutrition in this vulnerable population.

Effect of levamisole supplementation on tetanus vaccination response rates in haemodialysis patients: a randomized double-blind placebo-controlled trial.

Levamisole as an immunomodulator drug has been demonstrated to improve the immune response to hepatitis B virus vaccination in haemodialysis patients. The aim of this randomized double-blind placebo-controlled trial was to evaluate the effect of levamisole supplementation on tetanus-diphtheria (Td) vaccine response rates in haemodialysis patients. Forty haemodialysis patients who had not received tetanus vaccination in a year before investigation and had unprotective anti-tetanus immunoglobulin G (IgG) levels (<0.1 international unit/mL) were enrolled and randomized into two equal groups to receive one dose of intramuscular Td vaccine supplemented with either levamisole (100 mg) or placebo daily, for 6 days before and 6 days after vaccination. The anti-tetanus IgG levels were measured 1 and 6 months after vaccination. One month post-vaccination, four patients were excluded from the levamisole group and two from the placebo group because of either death or renal transplantation. At 1 month, 13 out of 16 (81%) patients in the levamisole group as compared with six out of 18 (33%) patients in the placebo group developed protective anti-tetanus IgG levels (relative risk = 2.44, 95% confidence interval (CI) = 1.21, 4.88). From 1 to 6 months post-vaccination, one more patient in the levamisole group and two more patients in the placebo group were excluded because of renal transplantation. At 6 months, 11 out of 15 (73%) patients in the levamisole group as compared with four out of 16 (25%) patients in the placebo group still had protective anti-tetanus IgG levels (relative risk = 2.93, 95% CI = 1.19, 7.23). Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients.

Aberrant left main bile duct draining directly into the cystic duct or gallbladder: an unreported anatomical variation and cause of bile duct injury during laparoscopic cholecystectomy.

Despite recent advances, iatrogenic bile duct injury remains one of the most common complications of laparoscopic cholecystectomy. Aberrant biliary tract anatomy is one of the major risk factors for iatrogenic bile duct injury. In this case report, for the first time, we report a case of aberrant left main bile duct draining directly into the cystic duct or gallbladder that presented with bile duct injury after laparoscopic cholecystectomy. We hope that the diagnostic and management approach used in this case will help physicians to identify and manage their patients should they face such a rare anatomy.

Mucinous cystic neoplasm of pancreas in a male patient: a case report and review of the literature.

Mucinous cystic neoplasms (MCNs) are among the most common primary cystic neoplasms of pancreas. These lesions usually occur in body and tail of the pancreas and are characterized by the presence of ovarian type stroma in the pathological evaluation. Mucinous cystic neoplasms have significant malignant potential; therefore, their diagnosis and resection is of utmost importance. Mucinous cystic neoplasms typically occur in women. Only a few cases have been previously reported in male patients. In this case report, we present a 48-year-old man who was referred to our center due to an incidentally found cystic lesion in the tail of the pancreas that was increasing in size in serial evaluation. The patient underwent open distal pancreatectomy. The pathology showed mucinous cystic neoplasm with characteristic ovarian type stroma and positive staining for estrogen and progesterone receptors. This case report shows that mucinous cystic neoplasms can occur in men and should be considered in differential diagnosis of cystic pancreatic lesions in this population.

Portal-endocrine and gastric-exocrine drainage technique of pancreas transplantation provides an easy access for evaluation of pancreatic allograft dysfunction: six-year experience at a single center.

BACKGROUND: The aim of this study is to report our six-year experience with portal-endocrine and gastric-exocrine drainage technique of pancreatic transplantation, which was first developed and implemented at our center in 2007. METHODS: In this study, the outcomes of all patients at our center who had pancreas transplantation with portal-endocrine and gastric-exocrine drainage technique were evaluated. RESULTS: From October 2007 to November 2013, 38 patients had pancreas transplantation with this technique - 31 simultaneous kidney pancreas and seven pancreas alone. Median duration of follow-up was 3.8 years. One-, three-, and five-year patient and graft survival rates were 94%, 87%, 70% and 83%, 65%, 49%, respectively. For pancreas allograft dysfunction evaluation, 51 upper endoscopies were performed in 14 patients; donor duodenal biopsies were successfully obtained in 45 (88%). We detected nine episodes of acute rejection (eight patients) and seven episodes of cytomegalovirus (CMV) duodenitis (six patients). No patient developed any complication due to upper endoscopy. CONCLUSIONS: Portal-endocrine and gastric-exocrine drainage technique of pancreas transplantation provides lifelong easy access to the transplanted duodenum for evaluation of pancreatic allograft dysfunction.

Selenium supplementation improves the nutritional status of hemodialysis patients: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Malnutrition is highly prevalent in hemodialysis (HD) patients. These patients have high levels of oxidative stress and inflammation which can subsequently induce malnutrition. Selenium levels have been found to be decreased in HD patients. As selenium deficiency leads to oxidative stress and inflammatory response, the aim of this study was to evaluate the effects of selenium supplementation on oxidative and inflammatory markers and the nutritional status of HD patients. METHODS: In this randomized double-blind placebo-controlled trial, 80 patients on stable HD for at least 3 months without any acute illness or active infections were randomly allocated to two equal groups to receive one selenium (200 µg) or placebo capsule daily for 12 weeks. Serum levels of lipoproteins, malondialdehyde (MDA), interleukin-6 (IL-6), high-sensitivity C-reactive protein (HSCRP), homocysteine, ferritin and transferrin as well as the subjective global assessment (SGA) score, malnutrition-inflammation score (MIS) and hemoglobin (Hb) levels were measured at the baseline and at the end of the treatment phase. The primary outcome was a change in the nutritional status measured by the SGA score from the baseline towards the end of the treatment phase of the study. RESULTS: The SGA score and MIS decreased significantly in the selenium group compared to the placebo group (P < 0.001 for both). Moreover, serum levels of MDA decreased significantly in the selenium group compared with increasing levels in the placebo group (P < 0.001). Selenium supplementation also hindered an increase in IL-6 levels compared with the placebo group (P = 0.016). There were no significant differences between the selenium and placebo groups in terms of changes in serum levels of lipoproteins, HSCRP, homocysteine, ferritin and transferrin or Hb levels. CONCLUSIONS: This study shows that selenium may be an effective complementary supplement for reducing the severity of malnutrition in HD patients through alleviating oxidative stress and inflammation.

Epidermoid cyst arising from an intrapancreatic accessory spleen: a case report and a review of the literature.

Accessory spleen is estimated to occur in 1 in 10 people in the general population, usually in the tail of the pancreas. Epidermoid cysts arising from ectopic spleen tissue in the tail of the pancreas are a benign and extremely rare pathology. Only 27 cases with such pathology have been reported in the English literature. Differentiating this pathology from other pancreatic pathologies, especially in the presence of a history of recent cancer, is almost impossible. In this article, we report a 36-year-old African-American woman with a history of colon cancer and hemicolectomy who was incidentally found to have a cystic lesion in the tail of her pancreas during surveillance abdominal imaging. After a distal pancreatectomy, the lesion was diagnosed to be an epidermoid cyst in an intrapancreatic accessory spleen. This is the first report of such pathology in a patient with a recent history of cancer. We propose that this pathology be considered as a differential diagnosis when assessing patients with cystic lesions in their pancreas, even when they have a history of previous malignancies.

Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic patients with overt nephropathy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: A large proportion of patients with type 2 diabetes mellitus have diabetic nephropathy. Despite current therapies including renin-angiotensin system inhibitors, diabetic nephropathy progresses to end-stage renal disease in most of these patients. Therefore, there is an urgent need to find new treatments for such patients. The aim of this study was to evaluate the efficacy of silymarin, an herbal drug with antioxidant and anti-inflammatory properties, in preventing the progression of diabetic nephropathy. STUDY DESIGN: Randomized, double-blind, placebo-controlled, 2-arm parallel trial. SETTING & PARTICIPANTS: 60 patients with type 2 diabetes with macroalbuminuria (urinary albumin excretion >300 mg/24 h) despite treatment with the maximum dose of a renin-angiotensin system inhibitor for more than 6 months and estimated glomerular filtration rate >30 mL/min/1.73 m(2). INTERVENTION: Patients were randomly assigned to 2 equal groups to receive three 140-mg tablets of silymarin or 3 tablets of placebo daily for 3 months. OUTCOMES: The primary outcome was absolute change in urinary albumin-creatinine ratio (UACR) from baseline to the end of the treatment phase. MEASUREMENTS: UACR and urinary and serum levels of TNF-α (tumor necrosis factor α; an inflammatory marker), malondialdehyde (MDA; an oxidative stress marker), and TGFß (transforming growth factor ß; a marker of fibrosis) at baseline and the end of the treatment phase. RESULTS: Although UACR decreased in both groups, this decrement was significantly higher in the silymarin compared with the placebo group; mean difference in change in UACR between the 2 groups was -347 (95% CI, -690 to -4) mg/g. Urinary levels of TNF-α and urinary and serum levels of MDA also decreased significantly in the silymarin compared with the placebo group. LIMITATIONS: Small sample size and short duration of the treatment phase. CONCLUSIONS: Silymarin reduces urinary excretion of albumin, TNF-α, and MDA in patients with diabetic nephropathy and may be considered as a novel addition to the anti-diabetic nephropathy armamentarium.

Racial Differences in Medication Utilization for Secondary Prevention of Cardiovascular Disease in Kidney Transplant Recipients: A Post Hoc Analysis of the FAVORIT Trial Cohort.

Rationale & Objective: Black kidney transplant recipients have higher prevalences of cardiovascular disease (CVD) risk factors and less intensive risk factor control than White kidney transplant recipients. Our objective was to evaluate racial disparities in receipt of statins and aspirin for secondary CVD prevention among kidney transplant recipients in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial. Study Design: Cohort study. Setting & Participants: FAVORIT participants of White, Black, and Other races from the United States and Canada with a history of CVD at study entry or who experienced a nonfatal CVD event during follow-up. Predictor: Race. Outcome: Receipt of statins and aspirin for secondary CVD prevention. Analytical Approach: We used parametric (Weibull), proportional-hazards, interval-censored survival models to evaluate the independent association of race with receipt of statins and aspirin for secondary CVD prevention. Results: Of the 4,110 kidney transplant recipients enrolled in FAVORIT trial, 978 met the inclusion criteria (78% White, 17% Black, and 6% Other race). Compared with the White race, Black and Other races were associated with lower hazards of receiving statins (Black race: adjusted HR, 0.76 [95% CI, 0.60-0.97]; Other race: adjusted HR, 0.87 [95% CI, 0.60-1.27]) and aspirin (Black race: adjusted HR, 0.85 [95% CI, 0.67-1.08]; Other race: adjusted HR, 0.63 [95% CI, 0.43-0.94]). Limitations: Lack of granular information on potential indications or contraindications for aspirin or statin use for secondary CVD prevention. Conclusions: Post hoc findings from the FAVORIT trial demonstrated that Black race was associated with a lower likelihood of receiving statins and Other race was associated with a lower likelihood of receiving aspirin for secondary CVD prevention. This represents a potential target to improve CVD care in non-White kidney transplant recipients.

Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications.

BACKGROUND: Uremic pruritus (UP) is still a common tormenting symptom among patients on hemodialysis (HD). The pathogenesis of UP is complex and not fully clarified. Some preliminary studies indicate that UP is a systemic inflammatory disease with a deranged balance of T helper (TH) cell differentiation toward TH1 predominance. The aim of this study was to further elucidate the potential contribution of TH1 cytokines to the pathogenesis of UP. METHODS: In this study, 112 HD patients were screened for UP. After meeting the required criteria, 31 HD patients with UP were included in the study as case group and 30 age- and sex-matched HD patients without UP were enrolled as controls. The serum levels of interleukin (IL)-2 and interferon-γ (as TH1 cytokines), IL-4 (as a TH-2 cytokine), high-sensitive C-reactive protein (as an inflammatory marker), parathyroid hormone, calcium, phosphate, albumin and ferritin were measured in all patients. Moreover, blood variables including hemoglobin and mean corpuscular volume were also determined. The correlations of measured factors with UP severity were determined as well. RESULTS: Except for the serum levels of IL-2, which were significantly higher in HD patients with itch versus those without it [0.544 ± 0.126 (U/mL) versus 0.318 ± 0.145 (U/mL); P < 0.0001], no statistically significant difference was observed in the levels of each of the above-mentioned factors between the two groups. Additionally, no correlation was detected between the levels of measured factors and UP severity. CONCLUSIONS: The results of our study, for the first time, point to the potential important role of IL-2 in UP and further support the notion of TH1 overactivity in its pathogenesis. Our study paves the way for further studies focusing on the contribution of IL-2 to the UP, such as the experimental use of anti-IL-2 receptor antibodies.

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: The Kidney Failure Risk Equation (KFRE) is a simple widely validated prediction model using age, sex, estimated glomerular filtration rate, and urinary albumin-creatinine ratio to predict the risk for end-stage kidney disease. Data are limited for its applicability to kidney transplant recipients. STUDY DESIGN: Validation study of the KFRE as a post hoc analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial. SETTING & PARTICIPANTS: Adult kidney transplant recipients with functioning kidney allografts at least 6 months posttransplantation from 30 centers in the United States, Canada, and Brazil. Participants with estimated glomerular filtration rates < 60 mL/min/1.73 m2 at study entry were included. PREDICTOR: 2- and 5-year kidney failure risk predicted by the KFRE using variables at study entry. OUTCOME: Graft loss, defined by initiation of dialysis. ANALYTICAL APPROACH: Discrimination of the KFRE was assessed using C statistics; calibration was assessed by plotting predicted risk against observed cumulative incidence of graft loss. RESULTS: 2,889 participants were included. Within 2 years, 98 participants developed graft loss, 107 participants died with a functioning graft, and 129 participants were lost to follow-up, and by 5 years, 252 had developed graft loss, 265 died with a functioning graft, and 1,543 were lost to follow-up. The KFRE demonstrated accurate calibration and discrimination (C statistic, 0.85 [95% CI, 0.81-0.88] at 2 years and 0.81 [95% CI, 0.78-0.84] at 5 years); performance was similar regardless of donor type (living vs deceased) and graft vintage, with the noted exception of poorer calibration for graft vintage less than 2 years. LIMITATIONS: Unavailable cause of graft loss. CONCLUSIONS: The KFRE accurately predicted the risk for graft loss among adult kidney transplant recipients with graft vintage longer than 2 years and may be a useful prognostic tool for nephrologists caring for kidney transplant recipients.

Wound myiasis in a patient with squamous cell carcinoma.

A 60-year-old, otherwise healthy, male farmer presented to our Dermatology Department with a large ulcer on his lower right leg. The lesion had started as a small papule 6 months before, which became eroded and transformed into a rather rapidly progressive ulcer. On careful inspection, numerous larvae were found moving within the wound. The larvae were analyzed and found to be Lucilia sericata (the green bottle blowfly). The lesion was diagnosed histopathologically as squamous cell carcinoma. The myiasis was treated by submerging the wound in a dilute permanganate potassium solution.