Juan F. Gallegos-Orozco

Adverse Effects of Testosterone Therapy in Adult Men: A Systematic Review and Meta-Analysis

CONTEXT The risks of testosterone therapy in men remain poorly understood. OBJECTIVE The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. DATA SOURCES We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. STUDY SELECTION Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. DATA EXTRACTION Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. DATA SYNTHESIS The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes. CONCLUSIONS The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.

Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C.

It is unclear whether the current antiviral treatment for chronic hepatitis C virus (HCV) infection results in complete elimination of the virus, or whether small quantities of virus persist. Our study group comprised 17 patients with chronic HCV who had sustained virological response (SVR) after interferon/ribavirin treatment. Serum and peripheral blood mononuclear cells were collected 2 to 3 times at 3‐ to 6‐month intervals starting 40 to 109 months (mean, 64.2 ± 18.5 months) after the end of therapy. In addition, lymphocyte and macrophage cultures were established at each point. In 11 patients, frozen liver tissue samples were available from follow‐up biopsies performed 41 to 98 months (mean, 63.6 ± 16.7 months) after therapy. Presence of HCV RNA was determined by sensitive reverse‐transcriptase polymerase chain reaction, and concentration of positive and negative strands was determined by a novel quantitative real‐time reverse transcriptase polymerase chain reaction. Only 2 of 17 patients remained consistently HCV RNA negative in all analyzed compartments. HCV RNA was detected in macrophages from 11 patients (65%) and in lymphocytes from 7 patients (41%). Viral sequences were also detected in 3 of 11 livers and in sera from 4 patients. Viral replicative forms were found in lymphocytes from 2 and in macrophages from 4 patients. In conclusion, our results suggest that in patients with SVR after therapy, small quantities of HCV RNA may persist in liver or macrophages and lymphocytes for up to 9 years. This continuous viral presence could result in persistence of humoral and cellular immunity for many years after therapy and could present a potential risk for infection reactivation. (HEPATOLOGY 2005;41:106–114.)

Chronic Constipation in the Elderly

Constipation is one of the most frequent gastrointestinal disorders encountered in clinical practice in Western societies. Its prevalence increases with age and is more frequently reported in female patients. Chronic constipation has been associated with considerable impairment in quality of life, can result in large individual healthcare costs, and represents a burden to healthcare delivery systems. This review will focus on the definition, epidemiology, diagnostic approach, and non-pharmacologic as well as pharmacologic management of chronic constipation in the elderly, including an overview of new medications currently under clinical investigation.

Natural History of Post-Liver Transplantation Hepatitis C: A Review of Factors That May Influence Its Course

Our aim was to assess long‐term survival in patients transplanted for HCV‐related end‐stage liver disease (ESLD) and evaluate potentially modifiable predictors of survival. We performed a retrospective analysis of adult liver transplants (LT) at our institution for HCV‐related ESLD since the programs inception. Pertinent demographic, clinical, and biochemical information was retrieved from electronic medical records and histological data from 990 per‐protocol liver biopsies were collected. Three hundred eighty LT were performed at our institution during the study period, 206 patients were transplanted for HCV‐related ESLD; 6 died within 30 days of transplantation and were not included. The remaining 200 recipients (DDLT 168 LDLT 32) constituted the evaluable population. The demographics were as follows: 150 males, median age 53 years; median donor age 39 years; hepatocellular carcinoma (HCC) in 26%. Overall 1‐, 5‐, and 7‐year survival: 95%, 81%, and 79%; median survival 43 months, mortality 15%. Significant HCV recurrence (HAI ≥6 and/or fibrosis ≥2) was present in 49%, “early recurrence” (within 1 year of LT) in 30.5% and biopsy‐proven acute rejection was present in 27%. Factors with a significant negative impact on patient survival included: fibrosis stage ≥2 at 12‐month biopsy, advanced donor age, history of HCC and early acute rejection. Survival was similar regardless of the donor type (DDLT vs. LDLT). Early and aggressive HCV recurrence has a very heavy toll on patient survival. Prompt recognition and treatment of “rapid fibrosers” may impart benefit. As has been described before, avoidance of rejection and selection of young donors for HCV‐positive recipients will also improve survival in this population. On the basis of our findings, LDLT is a good option for HCV‐positive recipients. Liver Transpl 15:1872–1881, 2009.

Health-related quality of life and depression in patients with chronic hepatitis C

BACKGROUND Hepatitis C is a major cause of liver disease worldwide. It has been associated with decreased health-related quality of life (HRQL) and psychiatric symptoms. Our aim was to assess HRQL, depression, and illness understanding in patients with chronic hepatitis C without previous interferon therapy. METHODS Consecutive patients attending a referral center were enrolled. HRQL was measured using SF-36 questionnaire, depression with Zung self-rating depression scale, and illness understanding with self-applied knowledge test. RESULTS Of 157 patients enrolled, 112 were female (71%) and 45 male (29%). Ninety-seven patients (61.8%) had cirrhosis. HRQL was significantly decreased in chronic hepatitis C patients compared to historical normal controls in all eight domains of the SF-36 (p < 0.001). In hepatitis C cirrhotic patients, HRQL was significantly lower among Child-Pugh class B and C subjects in domains reflecting physical health (p <0.05). Ninety-two patients (58.6%) had depression that resulted in lower HRQL when compared to nondepressed patients (p <0.05). One hundred fourteen patients (72.6%) had poor illness understanding of hepatitis C. These subjects had significantly lower HRQL scores in six of eight SF-36 domains when compared to patients with better understanding of the disease (p <0.05). CONCLUSIONS Chronic hepatitis C patients attending a tertiary-referral center had significant decrease in HRQL associated with depression (58.6%) and poor illness understanding (72.6%). Educational programs and their impact on HRQL need to be addressed in detail, particularly for the pre-treatment scenario.

Adult Height in Patients with Congenital Adrenal Hyperplasia: A Systematic Review and Metaanalysis

CONTEXT Treatment for patients with congenital adrenal hyperplasia (CAH) may affect the final height of these patients. OBJECTIVE Our objective was to determine the distribution of achieved height in patients with classic CAH diagnosed at infancy or early childhood and treated with glucocorticoids. DATA SOURCES We searched MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, and Scopus through September 2008; the reference sections of included studies; and expert files. STUDY SELECTION Eligible studies included patients diagnosed with CAH before age 5 and followed to final height. DATA EXTRACTION Reviewers working in duplicate independently extracted data on study characteristics and outcomes and determined each studys risk of bias. DATA SYNTHESIS The sd score (SDS) for final height and corrected height (defined as final height SDS - midparental height SDS) were estimated from each study and pooled using random-effects metaanalysis. The I(2) statistic was used to assess inconsistency in results across studies. RESULTS We found 35 eligible studies, most of which were retrospective single-cohort studies. The final height SDS achieved by CAH patients was -1.38 (-1.56 to -1.20; I(2) = 90.2%), and the corrected height SDS was -1.03 (-1.20 to -0.86; I(2) = 63.1%). This was not significantly associated with age at diagnosis, gender, type and dose of steroid, and age of onset of puberty. Mineralocorticoid users had a better height outcome in comparison with the nonusers (P = 0.02). CONCLUSION Evidence derived from observational studies suggests that the final height of CAH patients treated with glucocorticoids is lower than the population norm and is lower than expected given parental height.

Outcomes of surgical treatment for nonfunctioning pituitary adenomas: a systematic review and meta-analysis

Background  Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta‐analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision.

Outcomes of surgical treatment for nonfunctioning pituitary adenomas

Background  Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta‐analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision.

Prenatal dexamethasone use for the prevention of virilization in pregnancies at risk for classical congenital adrenal hyperplasia because of 21‐hydroxylase (CYP21A2) deficiency: a systematic review and meta‐analyses

Context  Prenatal treatment with dexamethasone to prevent virilization in pregnancies at risk for classical congenital adrenal hyperplasia (CAH) remains controversial.

Evidence for viral persistence in patients who test positive for anti-hepatitis C virus antibodies and have normal alanine aminotransferase levels.

It is unclear whether patients who test positive for anti-hepatitis C virus (HCV) antibodies and have normal alanine aminotransferase (ALT) levels remain infected with the virus. Eleven patients who tested positive for anti-HCV antibodies, had persistently normal ALT levels, and tested negative for HCV RNA by commercial test were studied. Serum and peripheral blood mononuclear cells (PBMCs) were collected 2-3 times at 3-6-month intervals, and PBMCs were cultured with phytohemagglutinin and pokeweed mitogen. HCV RNA was detected in serum samples from 6 (55%) and in PBMCs from 11 (100%) patients. Our results suggest that, in asymptomatic patients who test positive for anti-HCV antibodies, small quantities of HCV RNA commonly persist, even in patients who test negative for HCV RNA in serum by commercial tests.