Association of Single Nucleotide Polymorphisms in the Human Tumor Necrosis Factor-α and Interleukin 1-β Genes in Patients with Pre-eclampsia

Pre-eclampsia is a pregnancy-specific syndrome that may be dangerous especially to the fetus. Different cytokines have been found to be elevated in women with pre-eclampsia and may have possible roles in the development of this disorder. Alleles of the interleukin-l-beta (IL-lβ) and tumor necrosis factor alpha (TNF-α) genes are associated with pr-eeclampsia in several studies in different populations. The aim of the present study was to investigate the relationship between IL-lβ (C+3954T) and TNF-α (G-308A) gene polymorphisms with pre-eclampsia in north east of Iran (Khorasan province).This study included 54 diagnosed patients with pre-eclampsia and 50 normal pregnant women as control group. DNA was extracted from peripheral blood and the polymorphisms were determined by PCR-RFLP method. Data was analyzed using chi-square and Fisher's exact tests.There was significant association between TNF-α (G-308A) genotype and pre-eclampsia (p=0.001) but we did not find any significant association between IL-lβ (C+3954T) genotype and pre-eclampsia (p=0.39).The present study might suggest a role for TNF-α in the development of pre-eclampsia; however, IL-lβ (C+3954T) polymorphism could not be considered as a marker of susceptibility to preeclampsia in our population.     

Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Na?ve Patients with Chronic Hepatitis B

Background/Aims

Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated.

Methods

In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated.

Results

The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ≥6 log₁₀ IU/mL (p=0.032) and detectable serum HBV DNA (≥12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients.

Conclusions

The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents.     

HCV Therapy in 2011: Development of New Treatment Paradigms for Na?ve and Non-Responder Patients

The approval of the first direct-acting antiviral (DAA) drugs for treatment of HCV in 2011 has lead to improved sustained viral response (SVR) rates up to 79% in treatment-na?ve or relapse genotype 1 (G1) patients, and up to 59% for non-responder G1 patients. This review discusses the clinical skills required for the use of direct-acting anti-viral drugs (DAA), the use of genetic tests and HCV RNA assays, resistance-associated variants (RAV), treatment of special populations, and future directions. The results of the pivotal phase 3 trials with both telaprevir and boceprevir are summarized, including the efficacy, safety and tolerability, drug-drug interactions and management of the most common side-effects. Treatment strategies implemented in order to minimize the development of resistance with these first-generation protease inhibitors are explored. The use of these drugs ushers in a new era for the treatment of HCV but should be done with both care and caution.     

Advanced Stage Is the Most Important Prognostic Factor for Survival in Patients with Systemic Acquired Immunodeficiency Syndrome-Related Non-Hodgkin’s Lymphoma Treated with CHOP and Highly Active Antiretroviral Therapy

In the era of highly active antiretroviral therapy (HAART), the prognosis for acquired immunodeficiency syndrome-related lymphomas (ARL) seems to be similar to that for aggressive B-cell lymphomas in human immunodeficiency virus (HIV)-negative patients. This improvement in prognosis might lead to a modification of the classic prognostic factors for ARL. We evaluated the prognostic factors for response and survival in a series of HIV-infected patients with systemic non-Hodgkin's lymphoma (NHL) in the HAART era. Forty patients with systemic NHL treated with a CHOP-based chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) and HAART were studied. The main clinicopathologic and laboratory parameters were recorded in each case. Patients were scheduled to receive cycles of CHOP therapy, and all received granulocyte colony-stimulating factor. In addition, 9 patients received rituximab (375 mg/m2). The complete remission (CR) rate was 62.5% (n = 25). No prognostic factors influencing CR attainment were found. The 5-year disease-free survival (DFS) probability (95% confidence interval [CI]) was 73% (54%-92%). The median overall survival (OS) time was 69.17 months, and the 5-year OS rate (95% CI) was 51% (35%-67%). A disease stage of III to IV was the only parameter with prognostic influence on DFS. The factors influencing OS were an International Prognostic Index >2, an Eastern Cooperative Ecology Group (ECOG) score >2, and a disease stage of III to IV. Patients with an advanced stage had a lower OS probability in a multivariate analysis (odds ratio, 4.24; 95% CI, 1.24- 14.57). Advanced stage was the main prognostic factor predicting survival in ARL treated with CHOP and HAART.     

Antiretroviral therapy for treatment-na?ve patients: A review of recent literature and the updated guidelines

The improved efficacy and safety of antiretroviral agents have fundamentally changed the face of HIV infection. Advances in antiretroviral therapy have dramatically improved the prognosis of HIV infection, which is now on a par with other chronic illnesses. This article addresses the optimal timing of antiretroviral therapy initiation and the optimal drug choices for initial regimens, with a focus on recent data and published guidelines issued by the US Department of Health and Human Services and the International AIDS Society-USA.     

The Effects of Telmisartan and Amlodipine in Treatment-Naïve and Previously Treated Hypertensive Patients: A Subanalysis from a 4 × 4 Factorial Design Study

The subanalysis of a 4 × 4 factorial, 8-week study to evaluate the efficacy and tolerability of telmisartan (T) 40–80 mg/amlodipine (A) 5–10 mg used in treatment-naïve patients (n = 231) and patients previously treated with antihypertensive agents (n = 880). Similar blood pressure (BP) reductions were achieved with T + A, regardless of their pretreatment status. Highest reductions were achieved with T80 + A10 (treatment-naïve ?26.5/?18.2 mm Hg and previously treated ?25.6/?19.9 mm Hg). Most patients (treatment-naïve 72.4% and previously treated 77.6%), including those with added risk, achieved BP goal (<140/90 mm Hg) with T80 + A10. Tolerability was comparable in both groups.

Trial registration: ClinicalTrials.gov identifier: NCT00281580.     

Partial Response to Entecavir and Tenofovir in Na?ve Patients with Chronic Hepatitis B: Clinical Relevance and Management

Entecavir and tenofovir are the currently recommended first line analogues for treatment of na?ve patients with chronic hepatitis B. Despite their overall efficacy and high genetic barrier granting for a low risk of resistance, both regimens will fail to completely suppress HBV DNA at week 48 in 10% of HBeAg-negative and 30% of HBeAg-positive patients. A pre-treatment level >8 log₁₀ IU/mL HBV DNA and poor medication adherence were the most significant predictors of a partial virological response (PVR). While the clinical relevance of PVR is still poorly understood, nucleos(t)ide (NUC)-naive PVR patients who maintained detectable levels of viremia in follow up, were at risk of developing resistance to ETV. Patients with a suboptimal decline of viremia during the first 48?weeks of therapy with ETV and/or a residual viremia >1,000?IU/mL, can be protected by a rescue switch to TDF. Resistance to TDF has not been described so far, yet the long-term risk of PVR in TDF-treated patients remains unclear.     

Tenofovir in the Treatment of Na?ve and Refractory Chronic Hepatitis B: A Single Center Experience in Saudi Arabia

Background/Aims:

Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used in the treatment of chronic hepatitis B (CHB) infection. This study evaluated the efficacy of TDF in achieving undetectable HBV DNA after 48 weeks of treatment in a Saudi cohort of CHB patients.

Patients and Methods:

This retrospective study included patients treated at a tertiary care center in Saudi Arabia from January 2009 to December 2012. Of the 68 eligible patients, 51 were treatment naïve and 17 were treatment-refractory. Twenty-three patients tested positive for HBeAg. The remaining 45 patients were HBeAg-negative.

Results:

The mean HBV DNA viral load decreased from 95 million IU/mL at baseline to 263 IU/mL after 48 weeks of treatment (P < 0.001). Overall, 62% of patients achieved a complete virological response (CVR) and 37% a partial virological response (PVR). Respective CVR and PVR rates according to subgroup were: HBeAg-positive (21.7% and 78.3%) and HBeAg-negative (84.4% and 15.6%). At 48 weeks, HBV DNA was undetectable in 66.7% of treatment-naïve and 53% of treatment-refractory patients (P = 0.3). Seroconversion occurred in 13 (57%) of HBeAg-positive patients. Two (3%) of the HBeAg-negative patients lost HBsAg at follow up. Mean alanine aminotransferase decreased significantly from 134 U/L before treatment to 37 U/L at 48 weeks (P < 0.001). Significant adverse events were not encountered during the study period.

Conclusion:

Forty-eight weeks of treatment with TDF reduced HBV DNA to undetectable levels in more than half of our patients regardless of whether they were treatment-naïve or refractory. HBeAg-negative (vs positive) patients experienced a better response rate.     

Increases in Entamoeba histolytica Antibody–Positive Rates in Human Immunodeficiency Virus–Infected and Noninfected Patients in Japan: A 10-Year Hospital-Based Study of 3,514 Patients

Serological evidence of the epidemiological trends in Entamoeba histolytica infection is scarce, especially in nonendemic countries. We aimed to determine the antibody-positive rates over a 10-year period, and compare the trends between human immunodeficiency virus (HIV)–infected and –noninfected patients. We reviewed 3,514 patients who underwent antibody testing during the study periods, which were divided into five annual categories: 2004–2005, 2006–2007, 2008–2009, 2010–2011, and 2012–2013. Anti-E. histolytica antibody was assessed by indirect immunofluorescence assay. The antibody-positive rate increased yearly from 2004–2005 to 2012–2013 (P < 0.001), although there was no increase in the annual number of antibody tests. This trend was seen among males (18.6–28.3%; P < 0.01), females (5.4–28.2%; P < 0.01), HIV-infected patients (18.4–26.9%; P < 0.001), and non-HIV-infected patients (14.6–36.8%; P < 0.001), and HIV-infected men who have sex with men (19.4–29.1%; P < 0.001). Among antibody-positive patients, there was a significant increase in the proportion of patients with high (≥ 1,600) titers (0.7–12.9%; P < 0.001), whereas this trend was not seen in patients with low (100) or intermediate (200–800) titers (P = 0.282 and 0.409, respectively). This large hospital-based study demonstrated that positive anti-E. histolytica antibody rates increased over 10 years, even though the annual number of antibody tests remained constant. Moreover, this trend was identified in non-high-risk patients (females and non-HIV-infected patients) as well as in high-risk patients. The proportion of patients with high antibody titers significantly increased among the antibody-positive patients.     

High Frequency of Diarrheagenic Escherichia coli in Human Immunodeficiency Virus (HIV) Patients with and without Diarrhea in Lima,Perú

Diarrhea is still a prevalent health issue in HIV patients. Our objective was to characterize the different diarrheagenic E. coli (DEC) groups in stools from adult HIV patients. Cross sectional study: We enrolled HIV-positive and -negative patients with and without diarrhea from a tertiary-care center of Lima, Peru. Clinical data was recorded and a stool sample per patient was cultured. Multiplex PCR was used to detect different DECs. One hundred eighty-four participants were enrolled. The frequency of having at least one DEC was more common in HIV-positive than HIV-negative patients with diarrhea (42% versus 20%, P < 0.05). The enterotoxigenic E. coli (ETEC) was the most common DEC in patients with diarrhea, 13% in HIV patients. The diffusely adherent E. coli (DAEC) was only present in HIV positive patients with diarrhea (10.1%). Different types of DEC are frequent in stools from HIV-positive patients.Since the highly active anti-retroviral treatment (HAART) was introduced for acquired immunodeficiency syndrome (AIDS), the incidence of opportunistic infections has decreased and new pathogens, such as diarrheagenic Escherichia coli (DEC) groups,¹ are now associated with diarrhea in human immunodeficiency virus (HIV) patients. Because antibiotic therapy may be successful in cases where pathogenic bacteria are identified, studies focusing on bacterial diarrhea in AIDS patients are needed. The DECs have been classified into six groups based on specific genes that determine their virulence factors: enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), Shiga toxin producing E. coli (STEC), enteroagregative E. coli (EAEC), enteropathogen E. coli (EPEC), and diffusely adherent E. coli (DAEC).² The role of different DECs in causing diarrhea in HIV-infected people in Latin American countries has not been adequately addressed because most studies have not examined for all currently recognized groups of DECs. Our objective was to characterize the different DECs in stools from adult HIV patients in Lima, Perú.     

Diagnosis of Helicobacter pylori Infection from Antral Biopsies in Pediatric Patients: Is Urease Test that Reliable?

Our objectives were to determine if the urease (CLO) test alone is a reliable diagnostic test for H. pylori gastritis in children and if the density of H. pylori influences the CLO test result. We performed a combined retrospective and prospective study reviewing the results of CLO-test and histology of gastric mucosal biopsy from 67 patients (35 females) with H. pylori gastritis. Two antral biopsies were inoculated on the CLO-test and two processed for histology to grade the severity of gastritis and H. pylori density. The mean age of patients was 11 years (sd ± 4.53). Only 50 patients tested positive for H. pylori on CLO-test, whereas all patients were positive on histology. %The sensitivity of the CLO-test was 75%. There was a significant association between CLO-test positivity and the density of H. pylori organisms on histology (P < 0.01), and with the severity of gastritis (P < 0.001) by the Pearson chi-square test. However, there was no association between the density of H. pylori and severity of gastritis. In conclusion, the CLO-test is not reliable as a sole diagnostic test for H. pylori gastritis in children because of a significant number of false negatives. Histologic examination of gastric mucosal biopsy is superior to the CLO-test in diagnosing H. pylori infection.     

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Na?ve Patients With Type 2 Diabetes

Background:

This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m² and ≤ 45 kg/m².

Method:

Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device.

Results:

Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P < .001) from baseline to study end in patients’ fear of self-injecting, as measured by the mD-FISQ.

Conclusions:

The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable therapy.     

Angiotensin-converting Enzyme Inhibitors in Pediatric Patients with Mitral Valve Regurgitation—Case-control Study and Review of the Literature

Objectives. To investigate the effectiveness of chronic administration of angiotensin-converting enzyme inhibitors in pediatric patients with mitral valve regurgitation. Design, Setting, Patients, Interventions. This was a case-control study of all echocardiograms of patients with moderate-to-severe mitral valve regurgitation, who underwent chronic administration of angiotensin-converting enzyme inhibitors between January 1990 and December 2006 at a single center. Outcome Measures. Echocardiographic parameters (left ventricular end-diastolic diameter, left ventricular posterior wall diameter, interventricular septum diameter, left atrium to aortic root diameter ratio, grade of mitral valve regurgitation, shortening fraction) were analyzed before and during therapy with angiotensin-converting enzyme inhibitors in 12 patients and compared with 12 patients without medications after one month and one year. Results. Twenty-four consecutive pediatric patients (median age of 7 years with a range 1 month–16 years) with moderate-to-severe mitral valve regurgitation were included. Data are given as standard deviation scores (z-scores) derived from body-surface-adjusted normal values. During angiotensin-converting enzyme inhibition left ventricular end-diastolic diameter decreased from mean z-score 2.04 to 1.66 (after 1 month) and to 1.73 (after 1 year), while left ventricular posterior wall diameter decreased from 0.25 to 0.12 (after 1 year), respectively. Shortening fraction, interventricular septum diameter, grade of mitral valve regurgitation, and left atrium to aortic root diameter ratio remained stable. Conclusions. In this case-control study of patients with moderate-to-severe mitral valve regurgitation effectiveness of angiotensin-converting enzyme inhibition on left ventricular dimensions and function after 1 month and 1 year is limited. Reviewing the literature, the lack of long-term follow-up studies with large patient cohorts and controversial study-results in adults require a prospective long-term multicenter follow-up study in pediatric patients.     

Effectiveness of Sofosbuvir,Ribavirin and PEG-IFNα-2a in the Treatment of Naïve Egyptian Patients With Chronic Hepatitis C Virus Genotype 4

Background

Egypt is one of the largest epidemic areas of hepatitis C virus (HCV) in the world. Its prevalent genotype is 4 with a majority of subtype 4a. In 2013, the Food and Drug Administration approved a new direct-acting antiviral drug (sofosbuvir) to treat patients with chronic HCV infection. In Egypt, the patients are already being treated with sofosbuvir in conjunction with ribavirin and pegylated interferon alfa-2a (PEG-IFNα-2a) for 12 weeks since 2015. The present study was planned to explain the efficacy of this treatment regimen against the HCV genotype 4a in Egyptian patients and its pretreatment predictive factors of virological response.

Efficacy of the Combination of Tetracycline, Amoxicillin, and Lansoprazole in the Eradication of Helicobacter pylori in Treatment-Naïve Patients and in Patients Who Are Not Responsive to Clarithromycin-Based Regimens: A Pilot Study

Background/Aims

The aim of this study was to evaluate the eradication rate of a triple therapy regimen that included a proton pump inhibitor, amoxicillin, and tetracycline instead of clarithromycin in treatment-Naïve patients and in patients who did not respond to standard triple therapy.

Methods

This study included 110 patients infected with Helicobacter pylori. Patients in groups A and B were treatment-Naïve, and those in group C were not responsive to previous standard triple therapy. Patients in group A (n=40) received lansoprazole 30 mg b.i.d., amoxicillin 1,000 mg b.i.d., and clarithromycin 500 mg b.i.d. for 14 days. Patients in groups B (n=40) and C (n=30) received lansoprazole 30 mg b.i.d., amoxicillin 1,000 mg b.i.d., and tetracycline 500 mg q.i.d. for 14 days.

Results

In group A, eradication was achieved in 18 (45%) of the 40 patients included in the intention-to-treat (ITT) analysis and in 18 (47.4%) of the 38 patients included in the per-protocol (PP) analysis. In group B, eradication was achieved in 15 (37.5%) of the 40 patients included in the ITT analysis and in 15 (39.3%) of the 38 patients included in the PP analysis. In group C, eradication was achieved in 14 (46.6%) of the 30 patients included in the ITT analysis and in 14 (43.8%) of the 29 patients included in the PP analysis. There was no statistically significant difference among the 3 groups with regard to eradication rates (p>0.05).

Conclusions

Despite the low rate of resistance to tetracycline, the combination of lansoprazole, amoxicillin, and tetracycline instead of clarithromycin is not a good option for the eradication of H. pylori.