Second-Line Antiretroviral Treatment Outcome in HIV-Infected Patients Coinfected with Tuberculosis in Pakistan.

Background: Tuberculosis (TB) coinfection in human immunodeficiency virus- (HIV-) infected patients is considered a risk of antiretroviral therapy (ART) failure. Coadministration of antitubercular therapy (ATT) with ART is another challenge for TB management. Objective: The study was aimed at investigating contributing factors affecting treatment outcomes in HIV-/TB-coinfected patients. Design: Cross-sectional. Setting. Samples were collected from the Pakistan Institute of Medical Sciences Hospital Islamabad. Subject and Methods. Clinicodemographic and immunovirological factors between the two groups were compared. The Student t-test and chi-square test were applied to compare outcome variables, and logistic regression was applied to determine the effect of TB on virological failure (VF). Main Outcome Measures. TB coinfection did not increase VF even in univariate (p = 0.974) and multivariate analysis at 6 and 12 months of 2nd-line ART start. ARV switching was significant (p = 0.033) in TB-coinfected patients. VF was significantly high in ATT-coadministered patients along with a viral load of ≥1000 (p = 0.000). Sample Size and Characteristics. We recruited seventy-four HIV patients on 2nd-line ART; 33 coinfected with TB were followed for at least 12 months. Conclusion: In HIV-/TB-coinfected patients, CD4 count, CD4 gain, and VF remained comparable to HIV patients with no TB infection. ATT significantly affects the treatment outcome, suggesting drug-to-drug interactions. These factors are important to revisit the therapeutic guidelines to maximize the benefit of dual therapy in resource-limited settings.

Case report: Unilateral conduction hearing loss due to central venous occlusion.

Central venous stenosis is a well-known complication in patients with vascular access for hemodialysis. We report two cases involving patients on hemodialysis with arteriovenous fistulas who developed reversible unilateral conductive hearing loss secondary to critical stenosis of central veins draining the arteriovenous dialysis access. A proposed mechanism for the patients' reversible unilateral hearing loss is pterygoid venous plexus congestion leading to decreased Eustachian tube patency. Endovascular therapy was conducted to treat the stenosis and the hearing loss of both patients was returned to near normal after successful central venous angioplasty.

TOTAL LYMPHOCYTE COUNT AS A SUBSTITUTE TO CD4 COUNT IN MANAGEMENT OF HIV INFECTED INDIVIDUALS IN RESOURCE LIMITED SOCIETY.

BACKGROUND: Pakistan is a resource limited society and gold standard parameters to monitor HIV disease activity are very costly. The objective of the study was to evaluate total lymphocyte count (TLC) as a surrogate to CD4 count to monitor disease activity in HIV/AIDS in resource limited society. METHODS: This cross sectional study was carried out at HIV/AIDS treatment centre, Pakistan Institute of Medical Sciences (PIMS), Islamabad. A total of seven hundred and seventy four (774) HIV positive patients were enrolled in this study, and their CD4 count and total lymphocyte count were checked to find any correlation between the two by using Spearman ranked correlation coefficient. Results: The mean CD4 count was (434.30 +/- 269.23), with minimum CD4 count of (9.00), and maximum of (1974.00). The mean total lymphocyte count (TLC) was (6764.0052 +/- 2364.02) with minimum TLC (1200.00) and maximum TLC was (20200.00). Using the Pearson's correlation (r) there was a significant and positive correlation between TLC and CD4 count. (r2=0.127 and p=0.000) at 0.01 level. CONCLUSION: Our study showed a significant positive correlation between CD4 count and total lymphocyte count (TLC), so TLC can be used as a marker of disease activity in HIV infected patients.

Co-existence of thin basement membrane nephropathy with other glomerular pathologies; a single center experience.

BACKGROUND: The co-existence of thin basement membrane nephropathy (TBMN) and another glomerular pathology portends a worse prognosis than TBMN alone. OBJECTIVES: The purpose of our study was to investigate the prevalence of TBMN and associated glomerular pathologies at our institution. PATIENTS AND METHODS: We reviewed all renal biopsies performed at Saint Louis University hospital over a 7-year period. We excluded all post transplant biopsies, and biopsies showing diabetic glomerulopathy, membranoproliferative glomerulopathy, membranous glomerulopathy, and biopsies where no electron microscopy or immunofluorescent studies were done. All other biopsies were included. RESULTS: A total of 634 biopsies were included in the study. The prevalence of TBMN was 47 (7.4%), of whom 17 (36.2%) had TBMN alone. In the remaining 30 (63.8%) patients TBMN was associated with other glomerular pathologies: IgAN 9 (19.1%) and FSGS 9 (19.1%). We found significantly higher prevalence of IgAN in patients with TBMN versus all biopsies (19.1% vs. 7.7%, respectively, P = 0.002). We found significant similarities in biopsy indications for TBMN and IgAN group. CONCLUSIONS: Around two thirds of the cases of TBMN were associated with other glomerular pathologies. The prevalence of IgAN, but not focal segmental glomerulosclerosis, was significantly higher in patients with TBMN as compared to the general renal biopsy specimens.

Acute kidney injury after cardiac surgery: is minocycline protective?

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) after cardiac bypass surgery (CABG) is common and carries a significant association with morbidity and mortality. Since minocycline therapy attenuates kidney injury in animal models of AKI, we tested its effects in patients undergoing CABG. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is a randomized, double-blinded, placebo-controlled, multi-center study. We screened high risk patients who were scheduled to undergo CABG in two medical centers between Jan 2008 and June 2011. 40 patients were randomized and 19 patients in each group completed the study. Minocycline prophylaxis was given twice daily, at least for four doses prior to CABG. Primary outcome was defined as AKI [0.3 mg/dl increase in creatinine (Cr)] within 5 days after surgery. Daily serum Cr for 5 days, various clinical and hemodynamic measures and length of stay were recorded. RESULTS: The two groups had similar baseline and intra-operative characteristics. The primary outcome occurred in 52.6% of patients in the minocycline group as compared to 36.8% of patients in the placebo group (p = 0.51). Peak Cr was 1.6 ± 0.7 vs. 1.5 ± 0.7 mg/dl (p = 0.45) in minocycline and placebo groups, respectively. Death at 30 days occurred in 0 vs. 10.5% in the minocycline and placebo groups, respectively (p = 0.48). There were no differences in post-operative length of stay, and cardiovascular events between the two groups. There was a trend towards lower diastolic pulmonary artery pressure [16.8 ± 4.7 vs. 20.7 ± 6.6 mmHg (p = 0.059)] and central venous pressure [11.8 ± 4.3 vs. 14.6 ± 5.6 mmHg (p = 0.13)] in the minocycline group compared to placebo on the first day after surgery. CONCLUSIONS: Minocycline did not protect against AKI post-CABG.

Anti-retroviral drugs compliance in intravenous and non intravenous drug abusers.

BACKGROUND: Intravenous drug abuse is often associated with poor adherence to anti-retroviral drugs in HIV/AIDS. Very few studies in Pakistan have determined implications of intravenous drug abuse on anti-retroviral drug compliance in HIV/AIDS patients. The objectives of the study were to assess and compare the adherence to anti-retroviral drugs in intravenous drug users (IDUs) and non-intravenous drug users (NIDUs) and to determine various factors influencing the adherence to anti-retroviral (ARV) drugs in HIV positive IDUs in HIV treatment centre Pakistan Institute of Medical Sciences (PIMS), Islamabad. METHODS: This descriptive observational study was carried out at HIV/AIDS treatment and care centre PIMS, Islamabad. A total of 162 HIV positive male (81 IDU and 81 NIDU) were enrolled in this study. They were followed over a period of five years from 2008-2012. ARV drug compliance and anti-tuberculosis treatment (ATT) outcome in IDUs and NIDUs were assessed using standard outcome parameters. RESULTS: Among IDUs Hepatitis C was positive in 63 (77.77%) cases and negative in 18 (22.22%) cases. In NIDUs hepatitis C was positive in 5 (6.17%) and negative in 76 (93.82%) (p=0.000). In IDUs Pulmonary tuberculosis was present in 61 (75.30%) patients and in NIDUs it was present in 52 (64.19%) (p=0.171). Regarding ATT outcome, amongst IDUs 41 (50.61%) lost to follow up, 16 (19.75%) were compliant to treatment and 4 (4.93%) were transferred out. In NIDUs, 2 (2.46%) patients were lost to follow-up, 38 (46.91%) remained compliant to treatment and 6 (7.40%) were transferred out (p=0.000). Regarding end status of ARVs, in IDUs, 48 (59.25%) were lost to follow-up, 1 (1.23%) was defaulter, 16 (19.75%) were compliant to treatment, 8 (9.87%) were transferred out and 8 (9.87%) expired. In NIDUs, 73 (90.12%) were compliant to treatment, 5 (6.17%) expired, 2 (2.46%) were lost to follow-up. CONCLUSIONS: Due to various socioeconomic and clinical factors, compliance to ARVs in IDUs is poorer as compared to NIDUs. The factors recognized are illiteracy, poor socioeconomic status, unemployment and various comorbidities (Hepatitis B, C and Tuberculosis) which are more prevalent in IDUs.

Vitamin D in kidney disease: pathophysiology and the utility of treatment.

CKD is associated with decreased vitamin D metabolites, both the storage form 25(OH)D and the active form 1,25-dihydroxyvitamin D. This contributes to hyperparathyroidism, and increased levels of PTH mobilize minerals from the skeleton and increase the risk for fractures. Treatment with vitamin D sterols efficiently reduces secondary hyperparathyroidism of CKD. Observational studies suggest survival and other potential benefits of vitamin D treatment in the CKD population. These observations need to be verified with controlled prospective trials.

Safety and efficacy of transjugular renal biopsy performed by interventional nephrologists.

Obtaining renal tissue is often critical in the diagnosis and management of patients with renal disease of unknown etiology. Bleeding diathesis, liver disease, and obesity are common contraindications for percutaneous renal biopsy. In high-risk patients, transjugular renal biopsy is believed to be a safe and effective procedure. This study reports the experience of an academic interventional nephrology program with performing transjugular renal biopsy. We performed a retrospective observational study of 23 patients with either acute or chronic kidney disease with contraindications for percutaneous renal biopsy. All transjugular renal biopsies were performed by interventional nephrologists at our university. We studied the efficacy and safety of transjugular renal biopsy in these patients. Twenty out of 23 (87%) of the procedures yielded adequate tissue for pathologic diagnosis. Three (13%) patients required blood transfusions, none required coil embolization or nephrectomy, and there were no deaths. Even though performing transjugular renal biopsy requires considerable technical expertise and must be performed in an interventional radiology suite, it can be safely and effectively performed by well-trained interventional nephrologists to achieve pathological diagnosis.

Vitamin D in kidney disease: pathophysiology and the utility of treatment.

Vitamin D physiology has gained more importance and publicity than any of its counterparts in the water- and fat-soluble vitamin groups combined. This is partly because vitamin D deficiency is still widely prevalent in the developed world and the beneficial effects are thought to extend beyond the regulation of calcium and phosphorus homeostasis alone. Vitamin D deficiency becomes even more important in the various stages of chronic kidney disease (CKD); CKD itself is also on the increase. How vitamin D physiology is altered in CKD and how the various treatment modalities can alter the morbidity and mortality associated with CKD is the topic of discussion for this article.

Infective endocarditis in haemodialysis patients: 16-year experience at one institution.

Objectives. To ascertain the characteristics, outcomes and correlates of mortality in chronic haemodialysis patients with confirmed infective endocarditis (IE). Methods. Patients were identified by computerized discharge diagnosis and chart review of admissions to Saint Louis University hospital from January 1990 through January 2006. Modified Duke Criteria were retrospectively applied to confirm the diagnosis of IE. Survivors and non-survivors were compared to identify clinical correlates of IE mortality. Results. We identified 59 patients with IE who had received dialysis for a mean duration of 52.9 ± 58.0 months prior to IE diagnosis. Dialysis access comprised 28 (47.5%) catheters, 26 (44.1%) arteriovenous grafts, 3 (5.1%) arteriovenous fistulas and 2 (3.4%) life sites. The causative organisms were MRSA in 15 (25%), MSSA 12 (20%), S. Epidermidis 10 (17%), Enterococci 8 (14%), multi-organism 6 (10%), gram negative 2 (3%) and VRE 1 (2%). Valves involved were mitral valve in 37 (63%), aortic valve in 10 (17%), tricuspid valve in 3 (5%) and multiple valves in 8 (13%) cases. Patient mortality was 28.8% (n = 17) during hospitalization, 37.9% (n = 22) at 30 days and 63.1% (n = 36) at 1 year. In multivariable logistic regression, the adjusted odds ratio of in-hospital mortality was 3.6-fold higher in those with IE and arteriovenous grafts (P = 0.04, 95% CI 1.04-12.27) compared to other forms of dialysis access. Conclusion. Mortality of IE remains high, despite the availability of potent antibiotics. Patients with arteriovenous grafts who develop IE may face increased risk for in-hospital mortality, perhaps reflecting difficulty eradicating endovascular infection if a graft is involved.

Frequency of the metabolic syndrome in adult type 2 diabetics presenting to Pakistan Institute of Medical Sciences.

OBJECTIVE: To determine the frequency of metabolic syndrome in both genders, in a limited adult type 2 diabetic population presenting to Pakistan Institute of Medical Sciences, Islamabad. METHODS: This was a cross sectional study conducted in a tertiary care teaching hospital. During the six months of study period, 106 adult type 2 diabetics were examined and evaluated for the presence of metabolic syndrome according to the ATP-III criteria. Asian standards for the waist circumference were used. RESULTS: Out of 106 patients, 91 (85.8%) had metabolic syndrome of whom 95% were females. Abdominal obesity was present in 91% females and 86% males. Low HDL levels were present in all females and 83% males. Seventy eight percent females and 63% males had elevated levels of triglycerides. Hypertension was present in 68% and 73% females and males respectively. CONCLUSION: This study showed a very high prevalence of the metabolic syndrome in type2 diabetic population. Females were more affected than males in all respects.

Changes in serum 25-hydroxyvitamin D and plasma intact PTH levels following treatment with ergocalciferol in patients with CKD.

BACKGROUND: Vitamin D insufficiency and deficiency are very common in patients with chronic kidney disease (CKD). The effect of ergocalciferol administration on serum 25-hydroxyvitamin D and plasma intact parathyroid hormone (PTH) levels in these patients is not known. STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: Patients with CKD stage 3 or 4 who had a serum 25-hydroxyvitamin D level less than 30 ng/mL (<75 nmol/L) and increased plasma intact PTH level were treated with 50,000 IU of ergocalciferol once weekly for 12 weeks and once monthly thereafter for a total of 6 months. Patients were excluded if they had a history of active vitamin D sterol use. OUTCOME & MEASUREMENTS: 25-Hydroxyvitamin D and intact PTH were measured at baseline and follow-up. RESULTS: 66 patients met inclusion criteria. Average age was 70.4 +/- 1.3 (SE) years (range, 40 to 88 years), and 97% were men. There were 44 patients (66%) with CKD stage 3 and 22 patients (33%) with CKD stage 4. After a median follow-up of 6 months, there was a significant increase in 25-hydroxyvitamin D levels from 16.6 +/- 0.7 to 27.2 +/- 1.8 ng/mL (41 +/- 2 to 68 +/- 4 nmol/L; P < 0.05) and a significant decrease in plasma intact PTH levels from 231 +/- 26 to 192 +/- 25 pg/mL (ng/L; P < 0.05). A multivariate logistic regression model showed that an increase in 25-hydroxyvitamin D level greater than 5 ng/mL (>12 nmol/L) is associated with a significant likelihood of a greater than 30% decrease in plasma intact PTH level (odds ratio, 4.5; 95% confidence interval, 1.5 to 15.1; P < 0.05). Although posttreatment 25-hydroxyvitamin D levels were not different between patients with CKD stages 3 and 4, only patients with CKD stage 3 had a significant decrease in plasma intact PTH levels. LIMITATIONS: This is a retrospective study with mostly male patients. CONCLUSIONS: Results show that ergocalciferol administration has a favorable effect on PTH levels if therapy results in an increase in 25-hydroxyvitamin D levels; this effect is more evident in patients with CKD stage 3.

Effect of significant histologic steatosis or steatohepatitis on response to antiviral therapy in patients with chronic hepatitis C.

BACKGROUND & AIMS: Treatment of chronic hepatitis C (CHC) results in an average sustained viral response (SVR) rate of 54%-63%. Most previous studies have not separately reported SVR rates for patients who have CHC and concomitant significant hepatic steatosis (>33%) or histologic evidence of steatohepatitis (SH). The aim of this study was to evaluate SVR in patients with CHC plus steatosis or SH on biopsy examination, compared with a group of controls with CHC and no significant steatosis or SH. METHODS: Our surgical pathology database and clinical files were queried for CHC between 1997 to 2002. Biopsy specimens with both CHC and significant steatosis (>33%) or SH were categorized as group 1. Of the patients treated with antiviral therapy, information on either SVR (hepatitis C virus [HCV] RNA negative at 6 months posttreatment) or lack of SVR (nonresponse as early as 12 weeks into therapy and relapsers) with either interferon (IFN)/ribavirin or pegylated IFN/ribavirin was found in 84 patients. A control group (group 2) of 231 CHC patients was identified by using a 2-year database (January 2000-June 2001) of patients without evidence of greater than 33% steatosis or SH. RESULTS: The overall SVR was 28% in group 1, compared with 44% for group 2 ( P = .001). For HCV genotype 1, the SVR was 23% vs 34% for group 2 ( P = .19). For HCV genotypes 2 and 3, the SVR was 42% vs 78% for groups 1 and 2 ( P = .008), respectively. CONCLUSIONS: Overall SVR for patients with HCV and significant steatosis or SH is considerably lower than for HCV and steatosis less than 33% and no SH.