Renal hyperparathyroidism- a risk factor in the development of encapsulating peritoneal sclerosis.

Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls. Methods: Linear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients. Results: EPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively. Conclusion: High levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.

Novel Colorimetric and Light Scatter Methods to Identify and Manage Peritoneal Dialysis-Associated Peritonitis at the Point-of-Care.

Introduction: Peritoneal dialysis (PD)-related peritonitis (PDRP) is a common cause of transfer to hemodialysis, patient morbidity, and is a risk factor for mortality. Associated patient anxiety can deter selection of PD for renal replacement therapy. Diagnosis relies on hospital laboratory tests; however, this might be achieved earlier if such information was available at the point-of-care (POC), thereby significantly improving outcomes. The presence of culturable microbes and the concentration of leukocytes in effluent both aid peritonitis diagnosis, as specified in the International Society for Peritoneal Dialysis (ISPD) diagnostic guidelines. Here, we report the development of 2 new methods providing such information in simple POC tests. Methods: One approach uses a tetrazolium-based chemical reporting system, primarily focused on detecting bacterial contamination and associated vancomycin-sensitivity. The second approach uses a novel forward light-scatter device (QuickCheck) to provide an instant quantitative cell count directly from PD patient effluent. Results: The tetrazolium approach detected and correctly distinguished laboratory isolates, taking 10 hours to provide non-quantitative results. We compared the technical performance of the light scatter leukocyte counting approach with spectrophotometry, hemocytometer counting and flow cytometry (Sysmex) using patient effluent samples. QuickCheck had high accuracy (94%) and was the most precise (coefficient of variation <4%), showing minimal bias, overall performing similarly to flow cytometry. Conclusion: These complementary new approaches provide a simple means to obtain information to assist diagnosis at the POC. The first provides antibiotic sensitivity following 10 hours incubation, whereas the second optical approach (QuickCheck), provides instant accurate total leukocyte count.

Congenital myopathy presenting as recurrent pneumonia with lung collapse and pulmonary artery hypertension.

A boy presented with cough, breathlessness for 1 month, fever for 1 week with similar previous episodes without hospitalisation. He had generalised muscle wasting, acute chronic malnutrition and required immediate ventilation. Provisional diagnosis of recurrent pneumonia with failure to thrive was made. As serial chest X-rays showed recurrent lung collapse, congenital lung anomalies were ruled out. 2D-echocardiography showed pulmonary arterial hypertension. Workup for congenital immunodeficiency and cystic fibrosis was negative. There was no improvement in muscle mass despite total parenteral nutrition. He was noticed to have myopathic facies. History was reviewed when the mother reported reduced fetal movements in this pregnancy. The patient had low voice amplitude. Creatine kinase levels were normal. Muscle biopsy followed by whole exome sequencing identified frameshift duplication NM_020451.3(SELENON):c.249_250dupGG (p.Asp84Glyfs*17), thus, confirming diagnosis of SEPN1-related congenital myopathy (CM) with fibre-type disproportion. Respiratory system involvement was distracter, emphasising consideration of CM while evaluating persistent lung collapse with muscle wasting.

Osteomyelitis variolosa: Forgotten complication of an eradicated disease.

BACKGROUND: Orthopedic manifestations and sequelae of small pox disease are largely forgotten. Presening features in the modern era are not only the classical deformities but also includes precocious arthritis, pathological fractures and joint instability. OBJECTIVES: To conduct a thorough and systematic review of the literature for all articles reporting osteomyelitis variolosa and its sequelae post eradication and to present an additional case as an illustration. STUDY DESIGN: Systematic review and case report. METHOD: ology: PubMed, EMBASE and Google Scholar databases were searched for relevant articles using different combinations of the keywords till 20th June 2017. All articles reporting cases of osteomyelitis variolosa following small pox eradication were included. Pearling of the bibliographies of selected articles was conducted to locate articles missed by the primary database search. Data from these reports were collected on pre-defined forms and the results were analysed. RESULTS: A total of 8 cases have been reported in the literature so far post-eradication of small pox and all cases are from India. These cases have predominant involvement of elbow followed by hands, feet and ankle. Characteristic clinical signs in the present era are secondary arthritis, pathological fractures, joint instability and some cases even have incidental presentation.The diagnosis is further confirmed by plain radiographs which show pathognomonic features of this condition. Rate of missed/misdiagnosis is very high due to rarity of this condition. All cases in the published literature were managed conservatively except those presenting with pathological fracture. CONCLUSIONS: The purpose of this study is to remind clinicians of an easily recognised sequelae of an eradicated disease and make them aware of its complications.

Longitudinal Trends in Quality of Life and Physical Function in Frail Older Dialysis Patients: A Comparison of Assisted Peritoneal Dialysis and In-Center Hemodialysis.

BACKGROUND: In-center hemodialysis (HD) has been the standard treatment for older dialysis patients, but reports suggest an associated decline in physical and cognitive function. Cross-sectional data suggest that assisted peritoneal dialysis (aPD), an alternative treatment, is associated with quality of life (QoL) outcomes that are comparable to in-center HD. We compared longitudinal changes in QoL between modalities. METHODS: We enrolled 106 aPD patients, matched with 100 HD patients from 20 renal centers in England and Northern Ireland. Patients were assessed quarterly for 2 years using the Hospital Anxiety and Depression Scale (HADS), SF-12 physical and mental scores, symptom score, Illness Intrusiveness Rating Scale (IIRS), Barthel's score, and the Renal Treatment Satisfaction Questionnaire (RTSQ). Mixed model analysis was used to assess the impact of dialysis modality on these outcomes during follow-up. P values were adjusted for multiple significance testing. RESULTS: Multivariate analysis showed no difference in any of the outcome measures between aPD and HD. Longitudinal trends in outcomes were also not significantly different. Higher age at baseline was associated with lower IIRS and RTSQ scores during follow-up. One-hundred and twenty-five (60.6%) patients dropped out of the study: 59 (28.6%) died, 61 (29.6%) withdrew during follow-up, and 5 (2.5%) were transplanted. CONCLUSIONS: Quality of life outcomes in frail older aPD patients were equivalent to those receiving in-center HD. Assisted PD is thus a valid alternative to HD for older people with end-stage kidney disease (ESKD) wishing to dialyze at home.

Thumb Opposition Recovery Following Surgery for Severe Carpal Tunnel Syndrome: A Clinical, Radiological, and Electrophysiological Pilot Study.

PURPOSE: To objectively assess recovery of thumb opposition in patients with carpal tunnel syndrome (CTS) after open carpal tunnel release and to evaluate electrophysiological and magnetic resonance (MR) neurography findings as predictors of thumb opposition recovery. METHODS: A total of 22 patients with severe CTS and thenar atrophy were included in this study. A detailed clinical, electrophysiological, and MR neurography evaluation was done both before and after surgery at 6 months to assess thumb opposition recovery. RESULTS: The median duration of symptoms was 12 months (interquartile range, 12-20 months). The compound muscle action potential of the abductor pollisis brevis (CMAP-APB) also showed statistically significant improvement of 0.5 + 0.2 mV after surgery. Tip-tip pulp pinch strength increased from 1.2 ± 0.4 to 2.0 ± 0.4 kg at 6-month follow-up, lateral pulp pinch strength increased from 1.9 ± 0.6 to 2.8 ± 0.9 kg at 6-month follow-up, and 3-point pulp pinch also improved from 1.9 ± 0.5 to 2.8 ± 0.9 at final follow-up. On MR neurogram, the proportion of patients with abnormal median nerve morphology decreased from 81.8% to 68.2%, abnormal thenar branch morphology decreased from 63.6% to 36.4% and denervation edema deceased from 59.1% to 13.6%. CONCLUSIONS: Patients suffering from severe CTS with thenar atrophy and detectable CMAP-APB showed promising improvement following open carpal tunnel release. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Isolation, Identification, and Characterization of an Unknown Impurity in Lovastatin EP.

An unknown impurity in the fermentation-based drug substance lovastatin at 0.52 RRT was observed invariably in all batches when analyzed by HPLC as per the PhEur monograph. This impurity was isolated from the impurity-enriched sample using reversed-phase preparative HPLC and characterized by using spectroscopic (PMR, CMR, MASS, and UV) techniques as the structurally-related compound Monacolin-X, having the molecular formula C24H34O6 and the chemical name 2-methyl-3-oxobutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester.

Outcomes of peritoneal dialysis patients and switching to hemodialysis: a competing risks analysis.

BACKGROUND: We performed a review of a large incident peritoneal dialysis cohort to establish the impact of current practice and that of switching to hemodialysis. METHODS: Patients starting peritoneal dialysis between 2004 and 2010 were included and clinical data at start of dialysis recorded. Competing risk analysis and Cox proportional hazards model with time-varying covariate (technique failure) were used. RESULTS: Of 286 patients (median age 57 years) followed for a median of 24.2 months, 76 were transplanted and 102 died. Outcome probabilities at 3 and 5 years respectively were 0.69 and 0.53 for patient survival (or transplantation) and 0.33 and 0.42 for technique failure. Peritonitis caused technique failure in 42%, but ultrafiltration failure accounted only for 6.3%. Davies comorbidity grade, creatinine and obesity (but not residual renal function or age) predicted technique failure. Due to peritonitis deaths, technique failure was an independent predictor of death hazard. When successful switch to hemodialysis (surviving more than 60 days after technique failure) and its timing were analyzed, no adverse impact on survival in adjusted analysis was found. However, hemodialysis via central venous line was associated with an elevated death hazard as compared to staying on peritoneal dialysis, or hemodialysis through a fistula (adjusted analysis hazard ratio 1.97 (1.02 - 3.80)). CONCLUSIONS: Once the patients survive the first 60 days after technique failure, the switch to hemodialysis does not adversely affect patient outcomes. The nature of vascular access has a significant impact on outcome after peritoneal dialysis failure.

Value of Indian Diabetes Risk Score among Medical Students and Its Correlation with Fasting Plasma Glucose, Blood Pressure and Lipid Profile.

INTRODUCTION: The Indian Diabetes Risk Score is a tool which was devised by the Madras Diabetes Research Foundation to screen people for the risk of developing Diabetes mellitus; it comprises of the family history, the abdominal circumference, age and the physical activity. AIM OF THE STUDY: This study was aimed at finding out whether the Indian Diabetes Risk Score (MDRF) correlated with the blood sugar levels, the lipid profile and the blood pressure readings of medical students. METHODS: Seventy five female and 75 male students who signed the informed consent were selected for the study. Their IDRS was calculated by using a validated questionnaire which involved the family history, the abdominal circumference, age and the details of the physical activity. All of them had their blood pressure, fasting plasma glucose and lipid profiles measured. RESULTS: There were 101 students with an IDRS of <30, 42 students with a moderate IDRS (30-50) and 7 who had a high IDRS of ≥60. The fasting plasma glucose was significantly correlated with the IDRS (P=0.001, r = 0.472), with a mean FPG of 84 ± 3.63mg/dl in the low risk groups, of 88 ± 4.93mg/dl in the moderate risk groups and of 94 ± 6.50mg/dl in the high risk groups. The total cholesterol value was r = 0.420 (P= 0.001), the total triglycerides value was r = 0.373 (P=0.001), the LDL cholesterol value was r = 0.578 (P=0.001) and the VLDL value was r = 0.566 (P=0.001), which positively correlated with the risk score and the HDL value r = -0.480 (P=0.001) correlated negatively with the risk score. There was no correlation between the IDRS and the blood pressure. CONCLUSION: Our study showed that nearly 40% of the medical students had a moderate to a high IDRS. The IDRS significantly correlated with the fasting plasma glucose and with all the components of the lipid profile. The IDRS did not correlate with the blood pressure readings.

Developing an assisted automated peritoneal dialysis (aAPD) service-a single-centre experience.

There is an ongoing increase in the number of elderly or frail patients requiring renal replacement therapy. Assisted automated peritoneal dialysis (aAPD) is one treatment option for this patient group and is becoming increasingly recognized as a distinct dialysis modality. In this article, we review the current status of aAPD and its evolution across Europe, describing the differences in service provision. We also report our experience locally of outcomes on our aAPD population over the last 4 years. We found that aAPD is a viable dialysis modality in the frail and elderly with limited lifespan, and complications of peritoneal dialysis are perhaps lower than would be expected in this population. This form of therapy also avoids the disruption to life which results from hospital-based dialysis.

Dialysis treatment is an independent risk factor for foot ulceration in patients with diabetes and stage 4 or 5 chronic kidney disease.

OBJECTIVE: To determine whether dialysis treatment is an independent risk factor for foot ulceration in patients with diabetes and renal impairment. RESEARCH DESIGN AND METHODS: We performed a cross-sectional study of consecutive patients with diabetes and stage 4 or 5 chronic kidney disease (CKD) attending clinics in Manchester (U.K.). Patients were classified as either receiving dialysis therapy (dialysis) or not (no dialysis). Foot assessment included diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD), prior foot ulceration and amputation, and foot self-care. Risk factors for prevalent foot ulceration were assessed by logistic regression. RESULTS: We studied 326 patients with diabetes and CKD (mean age 64 years; 61% male; 78% type 2 diabetes; 11% prevalent foot ulceration). Compared with no dialysis patients, dialysis patients had a higher prevalence of DPN (79 vs. 65%), PAD (64 vs. 43%), prior amputations (15 vs. 6.4%), prior foot ulceration (32 vs. 20%), and prevalent foot ulceration (21 vs. 5%, all P < 0.05). In univariate analyses, foot ulceration was related to wearing bespoke footwear (odds ratio 5.6 [95% CI 2.5-13]) dialysis treatment (5.1 [2.3-11]), prior foot ulceration (4.8 [2.3-9.8], PAD (2.8 [1.3-6.0], and years of diabetes (1.0 [1.0-1.1], all P < 0.01). In multivariate logistic regression, only dialysis treatment (4.2 [1.7-10], P = 0.002) and prior foot ulceration (3.1 [1.3-7.1], P = 0.008) were associated with prevalent foot ulceration. CONCLUSIONS: Dialysis treatment was independently associated with foot ulceration. Guidelines should highlight dialysis as an important risk factor for foot ulceration requiring intensive foot care.

High levels of foot ulceration and amputation risk in a multiracial cohort of diabetic patients on dialysis therapy.

OBJECTIVE: To evaluate the prevalence of lower-limb complications in a multiracial cohort of patients with diabetes receiving dialysis. RESEARCH DESIGN AND METHODS: This work was a cross-sectional study of lower-limb complications in dialysis-treated patients with diabetes in the U.K. and U.S. RESULTS: We studied 466 patients (139 U.K.; 327 U.S.). The prevalence of lower-limb complications was high (foot ulcers 12%, neuropathy 79%, peripheral arterial disease 57%, history of foot ulceration 34%, and prior amputation 18%), with no significant ethnic variation, except that foot ulcers were more common in whites than in patients of African descent (P = 0.013). Ninety-five percent of patients were at high risk of lower-limb complications. Prior amputation was related to foot ulcer history, peripheral arterial disease, and hemodialysis modality in multivariable analysis. Prevalent ulceration showed independent associations with foot ulcer history and peripheral arterial disease, but not with ethnicity. CONCLUSIONS: All patients with diabetes receiving dialysis are at high risk of lower-limb complications independent of ethnic background.

Decrease in infections with the introduction of mupirocin cream at the peritoneal dialysis catheter exit site.

UNLABELLED: Staphylococcus aureus associated peritonitis and catheter exit site infections (ESI) are an important cause of hospitalization and catheter loss in the patients undergoing chronic peritoneal dialysis (PD). We aimed to determine the potential effectiveness of the application of mupirocin cream at the catheter exit site in preventing exit site infection and peritonitis. METHODS: This prospective historically controlled study was done in a total of 86 patients who entered our PD program from April 1999 to January 2001. They were instructed to apply Mupirocin cream 2% to the exit site daily or on alternate days. The patients were not screened to determine whether they were staphylococcus aureus carriers. One hundred and thirteen patients on PD prior to April 1999 acted as historical controls. Both groups were followed prospectively for a period of 22 months. RESULTS: In the study group application of mupirocin lead to a significant reduction in the incidence rate of both exit site infections overall (0.43 vs. 0.09; p<0.0001) and ESI due staphylococcus aureus (0.14 vs. 0.02; p=0.004) amounting to a relative reduction of 79% and 85% respectively. Although the overall incidence of peritonitis did not change (0.28 vs. 0.26; p=0.7) there was a significant reduction in peritonitis caused by staphylococcus aureus (0.07 vs. 0; p=0.01) Although only one catheter required removal in the mupirocin group as against 5 in the control group, this was not statistically significant. CONCLUSIONS: Mupirocin application at the exit site significantly lowers the incidence of ESI and peritonitis caused by staphylococcus aureus without any significant side effects.

Synthesis and cytotoxic activity of 3-O-acyl/3-hydrazine /2-bromo/20,29-dibromo betulinic acid derivatives.

A series of 3-O-acyl, 3-hydrazine, 2-bromo, and 20,29-dibromo betulinic acid derivatives (1-27) have been synthesized and screened for in vitro cytotoxic activity on human cancer cell lines MOLT-4, JurkatE6.1, CEM.CM3, BRISTOL8, U937, DU145, PA-1, A549, and L132. A number of compounds have shown ED(50)<1 microg/mL against the cancer cell lines tested and have shown better cytotoxicity than betulinic acid. Compounds 13, 19, 20, 23, and 27 were the best derivatives and were selected as lead molecules for further development. The structure-activity relationship has been described.

Synthesis of 3-O-acyl/3-benzylidene/3-hydrazone/3-hydrazine/17-carboxyacryloyl ester derivatives of betulinic acid as anti-angiogenic agents.

New 3-O-acyl, 3-benzylidene, 3-hydrazone, 3-hydrazine, 17-carboxyacryloyl ester derivatives of betulinic acid (2-6, 8-11, 13, 17, 18, 21, and 22) were synthesized and evaluated in vitro for anti-angiogenic activity on endothelial cell cytotoxicity, specificity, and tube-formation ability. All derivatives reported here showed IC(50)<4 microg/mL. Compounds 3, 9, 10, 17, 21, and 22 have shown better cytotoxicity (IC(50)<1.2 microg/mL) than betulinic acid (1) and improved endothelial cell specificity (ECS>10) in some cases. Compounds 10, 17, and 18 have shown 20%, 32%, and 48% reduction in TLS, respectively, and were found better than betulinic acid (1). We have shown that 20,29-dihydrobetulinic acid derivatives have better anti-angiogenic activity as compared to betulinic acid or its other derivatives.

Betulinic acid and its derivatives as anti-angiogenic agents.

Betulinic acid (1) significantly caused cytotoxicity to endothelial cell line ECV304 (IC(50) 1.26+/-0.44 microg/mL) in a 5-day MTT assay. Novel and more potent derivatives of betulinic acid (2, 4, 6-8) have been synthesized with IC(50) less than 0.4 microg/mL. The endothelial cell specificity against human tumor cell lines DU145, L132, A549, and PA-1 were determined. Further betulinic acid (1) inhibited TLS formation of ECV304 cells on Matrigel(TM) by 5.5% while its derivatives caused an inhibition of 13.1-49.2%.