Limitation of Terminal Serum Creatinine as a Kidney Donor Profile Index Variable in Predicting Long-Term Kidney Transplant Outcomes.

BACKGROUND: Donor final serum creatinine (SCr) is a dynamic variable and is 1 of 10 factors used in calculating kidney donor profile index (KDPI). We hypothesize that deceased-donor kidneys (DDKs) with higher SCr were likely accepted for transplantation if procurement biopsy findings were favorable and with long-term outcomes no worse than kidneys with lower final SCr within a KDPI group. METHODS: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified DDK transplant recipients from 2000 to 2015 who received induction and calcineurin inhibitor/mycophenolate mofetil maintenance. Patients were divided into 4 KDPI groups: 0-20%, 21%-50%, 51%-85%, and >85%. In each KDPI category, long-term outcomes were compared, with the use of Cox models, between patients who received kidneys with final SCr >2 versus ≤2 mg/dL. RESULTS: A total of 59,644 patients were divided into KDPI groups 0-20% (SCr >2 mg/dL, n = 478; SCr ≤2 mg/dL, n = 14,769), 21%-50% (SCr >2 mg/dL, n = 1,592; SCr ≤2 mg/dL, n = 17,762), 51%-85% (SCr >2 mg/dL; n = 1,388, SCr ≤2 mg/dL, n = 18,024), and >85% (SCr >2 mg/dL, n = 349; SCr ≤2 mg/dL, n = 5,282). Adjusted overall graft failure risks (hazard ratio [HR] 0.88, P = .04; HR, 0.86, P = .007) and patient death risks (HR, 0.86, P = .04; HR, 0.84, P = .01) for final SCr >2 versus ≤2 mg/dL groups were lower in KDPI categories 21%-50% and 51%-85%, respectively, with similar death-censored graft failure risks. DISCUSSION: Outcomes of transplanting DDKs with elevated final SCr are no worse than transplanting kidneys with lower final SCr, highlighting the limitation of the single value of final SCr as a variable for calculating KDPI.

Point prevalence & risk factor assessment for hospital-acquired infections in a tertiary care hospital in Pune, India.

BACKGROUND & OBJECTIVES: Hospital-acquired infections (HAIs) are a major challenge to patient safety and have serious public health implications by changing the quality of life of patients and sometimes causing disability or even death. The true burden of HAI remains unknown, particularly in developing countries. The objective of this study was to estimate point prevalence of HAI and study the associated risk factors in a tertiary care hospital in Pune, India. METHODS: A series of four cross-sectional point prevalence surveys were carried out between March and August 2014. Data of each patient admitted were collected using a structured data entry form. Centers for Disease Control and Prevention guidelines were used to identify and diagnose patients with HAI. RESULTS: Overall prevalence of HAI was 3.76 per cent. Surgical Intensive Care Unit (ICU) (25%), medical ICU (20%), burns ward (20%) and paediatric ward (12.17%) were identified to have significant association with HAI. Prolonged hospital stay [odds ratio (OR=2.81), mechanical ventilation (OR=18.57), use of urinary catheter (OR=7.89) and exposure to central air-conditioning (OR=8.59) had higher odds of acquiring HAI (P<0.05). INTERPRETATION & CONCLUSIONS: HAI prevalence showed a progressive reduction over successive rounds of survey. Conscious effort needs to be taken by all concerned to reduce the duration of hospital stay. Use of medical devices should be minimized and used judiciously. Healthcare infection control should be a priority of every healthcare provider. Such surveys should be done in different healthcare settings to plan a response to reducing HAI.

Outcomes of Kidney Transplantation in Patients Exposed to Hepatitis B Virus: Analysis by Phase of Infection.

BACKGROUND: In kidney transplant recipients (KTRs) with hepatitis B virus (HBV) infection, immunosuppression may increase viral replication with increased risk for liver disease progression and HBV-related kidney diseases, factors that could adversely influence graft and patient outcomes. We aimed to analyze the impact of different phases of HBV infection on the outcomes in KTRs. METHODS: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we selected adult KTRs from 2001 to 2011 who received peri-operative antibody induction followed by calcineurin inhibitor/mycophenolate mofetil maintenance with/without steroid. The cohort was divided into 4 groups, based on the presence/absence of hepatitis B surface antigen (HBsAg) and core antibody (HBcAb) at the time of transplantation: group 1: HBsAg+/HBcAb- (acute infection); group 2: HBsAg+/HBcAb+ (developing immune response); group 3; HBsAg-/HBcAb+ (resolving infection); and group 4: HBsAg-/HBcAb- (HBV-naive). Graft and patient survivals were compared among the groups in a multivariate Cox model. RESULTS: Adjusted overall graft (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.10; P = .58) and patient (HR, 0.95; 95% CI, 0.83-1.09; P = .52) survival rates were similar between groups 1 and 2, with inferior death-censored graft survival in group 1 (HR, 0.83; 95% CI, 0.71-0.98; P = .02). Adjusted over all graft (HR, 1.0; 95% CI, 0.90-1.00; P = .46) and patient (HR, 1.03; 95% CI, 0.90-1.10; P = .10) survival rates were similar between groups 3 and 4, and death-censored graft survival trended inferior in group 3 (HR, 0.97; 95% CI, 0.90-1.00; P = .05). CONCLUSIONS: Our analysis supports a practice of delaying kidney transplantation in HBV-infected patients until they develop an immune response and preferably until the infection is cleared.

Human Leukocyte Antigen Mismatch and Steroid Maintenance in Kidney Transplantation.

BACKGROUND: This study aimed to analyze the impact of chronic steroid maintenance (CSM) vs early steroid withdrawal (ESW) in kidney transplant recipients (KTRs) stratified by the level of human leukocyte antigen (HLA) mismatch. METHODS: Adult KTRs between 2001 and 2011 who received antibody induction followed by calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF) maintenance with or without steroid were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database. Using multivariate analysis, graft and patient outcomes were compared for CSM vs ESW in KTRs stratified by HLA mismatch levels separately for depleting and nondepleting antibody-induced patients. RESULTS: Among 43,096 study patients, 26,582 received depleting induction (zero HLA mismatch = 5324 [CSM = 3416; ESW = 1908]; 5-6 HLA mismatch = 21,258 [CSM = 13,739; ESW = 7519]) and 16,514 patients received nondepleting induction (zero HLA mismatch = 4109 [CSM = 3453; ESW = 656]; 5-6 HLA mismatch = 12,405 [CSM = 10,890; ESW = 1515]). Adjusted graft failure risks for CSM vs ESW groups for zero HLA mismatch patients were as follows: HR 1.13, P = .07 (depleting induction); HR 1.30, P = .01 (nondepleting induction). Graft outcomes were similar for CSM vs ESW in 5-6 HLA mismatch groups for both induction types. Adjusted patient death risks were significantly higher for CSM vs ESW with depleting (HR 1.3, P = .003) and nondepleting (HR 1.45, P = .006) induction in zero HLA mismatch patients and only with depleting induction in 5-6 HLA mismatch groups (HR 1.16, P < .001). CONCLUSION: Our study supports the feasibility of ESW regardless of the level of HLA mismatch in KTRs selected for antibody induction and CNI/MMF maintenance.

Kidney allograft survival after acute rejection, the value of follow-up biopsies.

Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss.

Limb salvage surgery in bone tumors: a retrospective study of 50 cases in a single center.

Modular segmental replacement system (MSRS) is one of the options for Limb conservation surgery in bone tumors. The study analyses a single center experience of use of MSRS for limb conservation in cases of primary bone tumors. Retrospective analysis was done for a series of cases of limb salvage procedures done over a five year period. All Patients with bone tumors who underwent limb salvage procedures utilising MSRS prosthesis were included in the study. The patients' record were perused for pre operative staging; neoadjuvant therapy used, if any; surgical procedure done; follow-up for prosthesis related complications and overall survival achieved. Total of 50 cases studied,included 28 males and 22 females . Median age at diagnosis of 28 (10-73) years. Tumor localized in lower limb in 38 patients, and upper limb in 12 patients. Tumors were malignant in 28 patients (56 %) and benign in 22 (44 %). The most common diagnosis was osteosarcoma (21 patients (42 %)) . The median resection length was 15 cm (range 6-25). High grade tumors (grade 2a and 2b) was found in 27 of 29 cases(93.1 %) . 14 patients had prosthesis related complications. The mean follow-up was 5 years (range: 3-7). 42 patients of 50 were alive with the endoprosthesis at the last follow-up. Survival rate of prosthesis is 84 %. The modular segmental-replacement system prosthesis favoured by us in limb sparing surgery for bone tumors results in satisfactory results in terms of tumor control and limb function.

Structurally diverse peroxisome proliferator-activated receptor agonists induce apoptosis in human uro-epithelial cells by a receptor-independent mechanism involving store-operated calcium channels.

OBJECTIVES: Peroxisome proliferator-activated receptors (PPARs) are implicated in epithelial cell proliferation and differentiation, but investigation has been confounded by potential off-target effects of some synthetic PPAR ligands. Our aim was to determine mechanisms underlying the pro-apoptotic effect of synthetic PPAR agonists in normal human bladder uro-epithelial (urothelial) cells and to reconcile this with the role of PPARs in urothelial cytodifferentiation. MATERIALS AND METHODS: Normal human urothelial (NHU) cells were grown as non-immortal lines in vitro and exposed to structurally diverse agonists ciglitazone, troglitazone, rosiglitazone (PPARgamma), ragaglitazar (PPARalpha/gamma), fenofibrate (PPARalpha) and L165041 (PPARbeta/delta). RESULTS: NHU cells underwent apoptosis following acute exposure to ciglitazone, troglitazone or ragaglitazar, but not fenofibrate, L165041 or rosiglitazone, and this was independent of ERK or p38 MAP-kinase activation. Pro-apoptotic agonists induced sustained increases in intracellular calcium, whereas removal of extracellular calcium altered the kinetics of ciglitazone-mediated calcium release from sustained to transient. Cell death was accompanied by plasma-membrane disruption, loss of mitochondrial membrane-potential and caspase-9/caspase-3 activation. PPARgamma-mediated apoptosis was unaffected following pre-treatment with PPARgamma antagonist T0070907 and was strongly attenuated by store-operated calcium channel (SOC) inhibitors 2-APB and SKF-96365. CONCLUSIONS: Our results provide a mechanistic basis for the ability of some PPAR agonists to induce death in NHU cells and demonstrate that apoptosis is mediated via PPAR-independent mechanisms, involving intracellular calcium changes, activation of SOCs and induction of the mitochondrial apoptotic pathway.

The characteristics of rhizosphere microbes associated with plants in arsenic-contaminated soils from cattle dip sites.

Soil microorganisms and plants were studied in samples of arsenic-contaminated soil from two cattle dip sites. The aim was to delineate the parameters that will determine the feasibility of future remediation by growing arsenic-accumulating plants, including the identity and characteristics of some rhizosphere soil microbes. The soil samples contained high total, but low soluble arsenic concentrations which, together with other properties, resembled the previously reported characteristics of dip-site soils from this region of rural Australia. A glasshouse trial demonstrated that dip-site rhizosphere microbes promoted arsenic accumulation by the grass Agrostis tenuis on contaminated dip-site soil without inhibition of growth. The arsenic content of the shoots was increased by 45%. We studied the colonization of roots of dip-site plants by mycorrhizal fungi and tentatively identified six genera of other fungi present in the soil samples. Two plant species growing at the sites, Kikuyu grass (the most abundant plant) and Rainbow fern, exhibited mixed infections of their roots by endomycorrhizal fungi (tentatively identified as Acaulospora and Gigaspora) and by soil-born pathogens. Five rhizosphere bacteria were identified to genus level and we determined the effect of arsenic on their growth. The two most prevalent strains differed greatly in their growth sensitivity to arsenate; Arthrobacter sp. being the most sensitive while Ochrobactrum sp. exhibited exceptional resistance to arsenate. Of the other, less prevalent strains, two were Bacillus spp. and the last, Serratia sp., was the most resistant to arsenite. These findings show the importance of understanding plant-soil microbe interactions for developing future strategies aimed at a phytoremediation-based approach to removing arsenic from soil at dip sites.

Nasal Wegener's and skin sarcoid--a rare combination of two granulomatous diseases.

Wegener's granulomatosis (WG) and sarcoidosis are two distinct granulomatous diseases characterized by multisystem involvement. We report a patient who initially presented with symptoms of limited WG predominantly affecting the nose, followed by a facial rash, which was histologically proven to be due to sarcoidosis. The sequential development of these two diseases in one patient is very rare, and to our knowledge, only one such case has been reported in the last 50 years (Am J Kidney Dis 28:893-898, 1996).

Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis.

Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle, whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study, we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle, and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2X(1), P2X(2), P2X(3), P2X(4), P2X(5), P2X(6), and P2X(7)) and P2Y (P2Y(1), P2Y(2), and P2Y(4)) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X(1) and loss of P2Y(2) receptor staining. Both P2X(3) and P2Y(4) are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X (P2X(2), P2X(1)) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X(1) expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because the urothelial cells appear to have a sensory function in the bladder, it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC.

CSF beta-1 Globulin--a potential marker in differentiating multiple sclerosis and acute disseminated encephalomyelitis: a preliminary study.

The exact diagnosis of demyelinating diseases is an enigma even in the best neurological centres. In the present study, the potential role of differential CSF proteins has been critically evaluated in differentiating multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). Cellulose acetate electrophoresis was carried out on CSF and serum samples of 14 MS patients, 23 ADEM patients and 30 controls. There was no statistically significant difference between serum electrophoresis of controls and MS patients. However, in case of CSF electrophoresis there was a statistically significant decrease in beta-1 fraction in 92.2% of MS patients (p=0.01). A comparison between serum electrophoresis of controls and ADEM patients indicated a statistically significant decrease in serum albumin in 87% patients and an increase of alpha-2 globulin in 73.9%. There was no statistically significant difference between CSF electrophoresis of controls and ADEM patients except for the prealbumin fraction which was raised in 60.9% of patients. No statistically significant difference was seen between the serum electrophoresis of ADEM and MS patients. However, on comparing CSF electrophoresis, it was seen that beta-1 fraction was significantly higher in ADEM patients (p<0.05). The predictive value of beta-1 fraction in differentiating MS and ADEM was then evaluated. The negative predictive value was 100% indicating that all samples with a beta-1 fraction of>6.5% cannot be diagnosed as MS. The significant decrease in beta-1 fraction in MS patients may prove to be an early indicator in differentiating between MS and ADEM patients.

Cyclooxygenase-1 is a marker for a subpopulation of putative nociceptive neurons in rat dorsal root ganglia.

Immunocytochemical and morphometric techniques were used to quantify the distribution of cyclooxygenase (cox)-containing neurons in rat L5 dorsal root ganglia (DRG). Cox-1 immunolabelling was almost exclusively restricted to small diameter DRG neurons (< 1000 microm2), and was extensively colocalized with calcitonin gene-related peptide (CGRP) and isolectin B4 (IB4). Cox-1 was present in 65% and 70% of CGRP- and IB4-labelled neurons, respectively. Cox-1 labelling was also found in neurons expressing the sensory neuron-specific (SNS) Na+ channel. Cox-2 labelling was absent in DRG from normal rats. In the Freund's adjuvant model of monoarthritis, the proportion of cox-1-positive DRG neurons was unchanged and no neurons were found to be labelled for cox-2. In primary tissue culture, cox-1 immunolabelling persisted in vitro for up to 9 days and was present in morphologically identical neurons. The selective expression of cox-1 in peripheral ganglia was confirmed by the small number of nodose ganglion neurons and superior cervical ganglion (SCG) neurons labelled for cox-1. These data suggest that cox-1 is a marker for a subpopulation of putative nociceptive neurons in vitro and in vivo, and suggests that the prostaglandins synthesized by these neurons may be important for nociceptor function. These data may have important implications for the mode and mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs).

Characterization of the binding of two novel glycine site antagonists to cloned NMDA receptors: evidence for two pharmacological classes of antagonists.

The potency of two novel glycine site antagonists, GV150,526A and GV196,771A, was assessed by their ability to inhibit the binding of [(3)H]-MDL105,519 to cell homogenates prepared from mammalian cells transfected with either NR1-1a, NR1-2a, NR1-1a/NR2A, NR1-1a/NR2B, NR1-1a/NR2C or NR1-1a/NR2D NMDA receptor clones. The inhibition constants (K(i)s) for GV150,526A displacement of [(3)H]-MDL105,519 binding to either NR1-1a or NR1-2a expressed alone were not significantly different and were best fit by a one-site binding model. GV150,526A inhibition to NR1-1a/NR2 combinations was best fit by a two-site model with the NR1-1a/NR2C having an approximate 2 - 4 fold lower affinity compared to other NR1-1a/NR2 receptors. The K(i)s for GV196,771A displacement of [(3)H]-MDL105,519 binding to NR1-1a, NR1-2a and all NR1-1a/NR2 combinations was best fit by a two-site binding model. There was no significant difference between the K(i)s for the binding to NR1-1a and NR1-2a; NR1-1a/NR2A receptors had an approximate 4 fold lower affinity for GV196,771A compared to other NR1-1a/NR2 combinations. The K(i)s for both GV150, 526A and GV196,771A for the inhibition of [(3)H]-MDL105,519 binding to membranes prepared from adult rat forebrain were determined and compared to the values obtained for binding to cloned NMDA receptors. The K(i)s for a series of glycine site ligands with diverse chemical structures were also determined for the inhibition of [(3)H]-MDL105,519 binding to NR1-1a/NR2A receptors. L689,560 displayed similar binding characteristics to GV150,526A. It is suggested that glycine site antagonists may be divided into two classes based on their ability to distinguish between NR1 and NR1/NR2 receptors with respect to binding curve characteristics.