Triple-drug Therapy Research Articles

Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients.

Amphotericin B (AMPH-B) is used to prevent opportunistic infections associated with immunosuppressive therapy after heart transplantation (HTx), while the blood concentrations of tacrolimus (TAC) are carefully controlled. Although AMPH-B has the potential to inhibit TAC metabolism in in vitro studies, its interaction with clinically used AMPH-B oral suspension has not been investigated. In the present study, we examined whether oral AMPH-B therapy influences the pharmacokinetics of TAC in HTx patients. A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. All patients with HTx enrolled in the study received standard triple-drug immunosuppression therapy including the regular release of TAC, mycophenolate mofetil, and prednisolone as well as prophylactic therapy with AMPH-B oral suspension. Patient characteristics and clinical laboratory data were collected from the electronic medical record system. Blood concentrations of TAC were used for pharmacokinetic analysis. A total of 14 patients were enrolled in the study. There were no statistically significant differences in the variables except for serum creatinine levels and eGFR before and after discontinuation of oral AMPH-B therapy. The dose and trough concentrations of TAC and the area under the time-concentration curve and apparent oral clearance calculated from its concentrations were not influenced by discontinuation of AMPH-B treatment. The prophylactic treatment with AMPH-B oral suspension did not influence the pharmacokinetics of TAC and was demonstrated as a safe and easy method to prevent early post-HTx fungal infection.

Cystic fibrosis: A changing landscape.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder that causes a lifetime of debilitating and life-threatening complications affecting the lungs and other organ systems. Over 1,700 gene mutations that cause this rare disorder have been identified. This article describes the current treatment landscape for adults with CF, including the 2019 FDA approval of a breakthrough triple-drug combination therapy that may significantly improve the quality of life for an estimated 90% of patients with CF.

Abstract #1002634: Efficacy of Hydroxychloroquine as a Fourth Add-On in T2DM Patients who were inadequately Controlled on Triple Drug Therapy

To evaluate the efficacy of hydroxychloroquine 400 mg as a fourth therapeutic agent in type 2 diabetes mellitus (T2DM) patients with poorly controlled blood glucose despite receiving an optimum dose of three oral antidiabetic drugs (OAD).

Abstract #1004069: Effectiveness of Remogliflozin and Vildagliptin Combination in Type 2 Diabetes Mellitus Patients Uncontrolled on Triple Oral Drug Therapy

Abstract #1004069: Effectiveness of Remogliflozin and Vildagliptin Combination in Type 2 Diabetes Mellitus Patients Uncontrolled on Triple Oral Drug Therapy

POS-753 LONG TERM BENEFITS OF PRESERVED GRAFT FUNCTIONS AFTER LATE WITHDRAWAL OF CALCINEURIN INHIBITORS IN LIVE DONOR KIDNEY TRANSPLANT RECIPIENTS.

With the use of calcineurin inhibitors (CNI) and induction therapy , graft survival has reached over 90% at 1 year. Despite short and medium term improvement , long term graft survival has not shown proportionate improvement. There is debate about role of CNI induced nephrotoxicity and long term graft dysfunction and there is no uniformity in renal outcome after CNI minimization or withdrawal 1 year after transplantation, especially in live donor transplants and well matched kidneys. This retrospective data analyses the long term outcome of patient and graft survival after CNI withdrawal from triple drug therapy of CNI, prednisolone and azathioprine /mycophenolate mofetyl (MMF) Twenty two adults (M:F- 16: 6) who had kidney from live donor and no rejections with stable renal function at one year after transplant were evaluated in this retrospective study. 6 recipients for financial reasons opted for CNI withdrawal which was done over 8 weeks. In the transition period prednisolone and azathioprine dose was stepped up. In another 12 patients CNI was withdrawn over 1-2 years post transplantation for gradually rising serum creatinine. In the remaining 4 patients CNI was withdrawn after graft biopsy revealed no evidence of rejection and histological changes suggestive of CNI toxicity,48-140 months( mean 90 +/-40) after transplant.Patients were followed up regularly for estimation of renal functions. Withdrawal of CNI after 12 months and even in late withdrawal did not result in graft rejection and all patients tolerated the intervention well. At time of early withdrawal at 12 months in 6 patients(Group A) serum creatinine ranged from 1.12 –1.6 mg/dl (Mean1.28 +/-0.16) and eGFR of 65.16 +/-12.81ml/mt. In12 patients (Group-B) in whom CNI was withdrawn between12-24 months serum creatinine ranged from 1.3-1.75 mg/dl (mean 1.51+/- 0.15) and eGFR 56.16 +/-7.1 ml/mt. In remaining 4 patients (group 3) who had evidence of toxicity,CNI was withdrawn 48 to140 months after transplant.Their serum creatinine was1.3 -1.75 mg/dl (mean 1.57+/-0.19) and eGFR 47+/-7.63ml/mt. At the end of follow up ranging from 60-348 months (mean 170+/-72 months ) all the patients had well preserved renal functions with their mean GFR of 65, 56 and 47 ml/mt in respective group with serum creatinine1.02 to 5.2 mg/dl (mean 1.86 +/- 0.99) There were 9 deaths after a follow up of 82-300 months (mean 200 +/- 75.2 )months.Three patients had carcinoma tongue of whom one had achieved prolonged remission after therapy but during follow up along with 2others reached ESRD and were initiated on hemodialysis.Cardiovascular events in 3 and infections in other 2 patients accounted for their mortality. Recipients of kidney from live donors with at least 1 haplo match and who did not have rejections in the1st year of transplant had excellent long term graft survival with 2 drugs only without CNI.In selected live donor transplant recipients who do not have rejection in first year calceinurin inhibitors can safely be withdrawn at least one year after transplant which helps in ameliorating CNI induced renal injury and prevents further deterioration of renal functions. In patients with graft dysfunction with histological features of CNI toxicity this beneficial effect of CNI withdrawal can sometimes be seen even many years after transplantation.

Systematic Review: Comparison of triple drug therapy versus double drug therapy for Lymphatic Filariasis

Background: Lymphatic filariasis is a parasitic infection caused by nematodes such as filaria Wuchereria bancrofti, Brugia malayi, and Brugia timori. These parasites can be transmitted through mosquito bites such as several species of mosquitoes, particularly Anopheles, Aedes, Culex, and Mansonia with geographical variations in the dominant vector identity. The main strategy used consists of community-wide mass drug administration (MDA) for the entire population at risk to stop disease transmission and prevent infectious morbidity. WHO recommends the use of annual medication in combination with the triple drug ivermectin therapy. Objective: To compare DEC and albendazole (IDA) versus the two drugs albendazole and diethycarbamazine or albendazole and ivermectin therapy. Methods: The literature search was carried out independently by the researcher using the Sciencedirect, Pubmed, and Cochrane online databases without limiting the type of study or the year of publication. The keywords used in this study were combined with the Boolean operator, namely "AND" namely ((((Lymphatic filariasis) AND (albendazole)) AND (diethylcarbamazine)) AND (ivermectin)) AND (compare). Results: Where triple drug therapy was significantly better in reducing and clearing microfilariae and worm nests in patients with lymphatic filariasis compared to two drug therapy alone. However, side effects occur more frequently in the combination of three therapies. The average side effects were low, such as headaches, joint pain, fatigue, and nausea. Conclusion: although it has relatively low side effects that occur in three drug combinations rather than two drug combination therapy, triple therapy combination therapy is more effective than two drug therapy in treating lymphatic filariasis disease.

Levofloxacin based non-rifampicin anti-tuberculous therapy: An effective alternative in renal transplant recipients in resource limited setting.

Rifampicin is one of the most effective components of anti-tuberculous therapy (ATT). Since rifampicin is a hepatic enzyme (CYP3A4) inducer, in a post-renal transplant recipient, the dose of calcineurin inhibitors needs to be up-regulated and frequently monitored. In resource-limited (low- and lower-middle-income countries) setting this is not always feasible. Therefore, we evaluated a non-rifampicin-based ATT using levofloxacin in kidney transplant recipients. We retrospectively studied the medical records of renal transplant recipients diagnosed with tuberculosis in our institute between 2014 and 2017. After a brief discussion with patients regarding the nature and course of ATT, those who opted for a non-rifampicin based therapy due to financial constraints were included in the study and followed for a minimum of 6 months period after the completion of ATT. Out of the 550 renal transplant recipients, 67 (12.2%) developed tuberculosis after a median period of 24 (1-228) months following transplantation, of them, 64 patients opted for non-rifampicin-based ATT. The mean age was 37.6 years. Only 25% were given anti-thymocyte globulin based induction, while the majority (56; 87.5%) of them were on tacrolimus-based triple-drug maintenance therapy. Extrapulmonary tuberculosis was noted in 33% of cases, while 12 (18.7%) had disseminated disease. The median duration of treatment was 12 months and the cure rate of 93.7% (n = 60) was achieved at the end of therapy. Levofloxacin based ATT appears to be a safe and effective alternative of rifampicin in kidney transplant recipients who cannot afford heightened tacrolimus dosage.

Carotid Artery Surgery to Reduce Long-Term Stroke Rates: Individual Patient Data Meta-Analysis of the Randomised Trials in Asymptomatic Patients

Background: Among patients with severe carotid artery stenosis but no recent symptoms from it, carotid surgery involves hazards, but then reduces long-term stroke rates. Triple-drug therapy (statin, anti-thrombotic, anti-hypertensive) also reduces long-term stroke rates in these asymptomatic patients. Past trials of carotid endarterectomy (CEA) can help assess the proportional reduction by carotid surgery in long-term stroke rates before and since triple-drug therapy became common. Methods: Intention-to-treat analyses used individual data from all 3 properly randomised trials among asymptomatic patients of immediate CEA vs deferral of any CEA until definitely indicated. Analyses of long-term stroke rates, censored at non-stroke death, used Kaplan-Meier life-tables and logrank methods. Findings: 2599 patients were allocated immediate CEA vs 2627 allocated deferral, with 89% vs 7% operated on within 1 year. Non-perioperative stroke rates were halved by allocation to immediate CEA (10-year stroke rate ratio [RR]=0.54, 95%CI 0.46-0.65, p<0.0001; 5.8% vs 11.7% by year 5); for fatal/disabling strokes, RR=0.55 (0.40-0.77, p<0.0001). Proportional reductions depended little on gender, or other patient characteristics. Ipsilateral and contralateral strokes were both reduced. In analyses restricted to strokes occurring on triple-drug therapy, absolute hazards and long-term stroke rates were lower than in the overall findings, but allocation to immediate CEA still halved long-term stroke rates (RR=0.56, 0.41-0.76; p=0.0002; 3.5% vs 7.0% by year 5). Of all CEAs undertaken, 3.1% involved perioperative stroke/death (71/3348; 40 dead/disabled, 31 not). Interpretation: Successful CEA halves long-term stroke rates. Net benefits will depend on surgical risks, long-term stroke rates without surgery, and life expectancy. Trial Registration: The trial is registered with the ISRCTN registry, ISRCTN21144362. Funding: MRC. Declaration of Interest: None to declare.

Clinical effect of the combination therapy of hydroxychloroquine, azithromycin and ivermectin in patients with COVID-19

Background: The ongoing pandemic has highlighted the need for an effective treatment of COVID-19 patients and prevention of SARS-CoV-2 community transmission.Methods: We conducted a prospective observational study on a cohort of 85 COVID-19 patients (80% males, median age 46 years, range 18–80 years). Patients were treated with a triple drug therapy: ivermectin 12 mg once a week, hydroxychloroquine 400 mg twice a day on the first day and 200 mg twice a day for the next 4 days, and azithromycin 500 mg once a day for 5 days. Endpoints were assessed by clinical outcomes, death, negative SARS-CoV-2 RNA-PCR test on the tenth day, and length of the hospital stay.Results: All patients improved except one 70-year-old female, who died on the third day of admission. The clinical outcome was considered good as 95.24% (80/84) of patients presented a negative SARS-CoV-2 RNA-PCR test on the tenth day of admission and 90.48% (76/84) were discharged in stable condition.Conclusions: The response must focus on immediate isolation of COVID-19 patients and their early treatment to prevent irreversible severe respiratory injury. Our study shows the beneficial effect of triple drug therapy in terms of clinical recovery, shorter duration of viral carriage, community spread prevention, and minimal cost of therapy.

Role of spironolactone in patients with resistant hypertension

Treatment-resistant hypertension (RH) is defined as uncontrolled blood pressure (BP) despite use of at least three different antihypertensive agents (including angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, calcium channel blocker, and a diuretic) at their optimal doses. It is important to properly diagnose and treat RH because patients are at high risk of end-organ damage. Activated renin-angiotensin-aldosterone system, increased renal sympathetic nervous system activity (increase sodium and water reabsorption and thus increase in extracellular fluid volume), and increased arterial stiffness become the main reason for hypertension. Therefore, a controlled BP can be achieved by the use of mineralocorticoid receptor blockers as add-on treatment to the first-line triple-drug combination therapy. In this review, we provide evidences from various studies comparing spironolactone treatment with other comparators (diuretics or other mineralocorticoid receptor blockers) or placebo signifying spironolactone is beneficial for controlling BP in patients with RH. Furthermore, there is a greater need to increase the use of mineralocorticoid receptor blocker, spironolactone, as fourth-line medication add-on to three drug therapy in patients with RH.

Progress in the elimination of lymphatic filariasis in the Western Pacific Region: successes and challenges.

The Western Pacific Region is the largest and most diverse region in the world, made up of 37 countries and territories in the Pacific, Oceania and parts of Asia, with a population of more than 1.9 billion people stretching over an area from China and Mongolia in the north to New Zealand in the south. In 1999, 22 countries and territories in the Pacific joined together and launched the Pacific Programme to Eliminate Lymphatic Filariasis. Shortly after, the Global Programme to Eliminate Lymphatic Filariasis was launched in 2000. In 2004, 12 countries in the Asia subregion of the Western Pacific Region and Southeast Asian Region joined and developed the Mekong-Plus Strategic Plan for Elimination of Lymphatic Filariasis. Since then, significant efforts have been made by all endemic countries, with annual mass drug administration (MDA) as a principal strategy, through strong partnership with the WHO and other donors and partners. As a result, by the end of 2019, 10 of 22 endemic countries in the region, including 8 of 16 countries in the Pacific and 2 countries in the Asia subregion, achieved WHO validation for elimination of lymphatic filariasis (LF) as a public health problem. All the other countries are either progressing with post-MDA surveillance or accelerating efforts by adoption of the new triple drug therapy strategy and enhancement of MDA campaigns to tackle persistent transmission. Some 85% of the originally endemic implementation units have stopped MDA and the number of people requiring MDA for LF in the Western Pacific Region was reduced by 72% from 2000 to 2018. This paper reviews the progress, key success factors and remaining challenges and indicates the way forward to achieve LF elimination in the Western Pacific Region.

Oral prophylaxis as an adjunct to systemic H.pylori eradication therapy

Introduction: Helicobacter pylori is the known bacteria, causing multiple gastric disorders. Its prevalence in dental plaque noted by multiple researchers. The presence of helicobacter pylori in dental plaque even after systemic eradication done using triple drug therapy noted by few. Purpose of this study was to establish need of oral prophylaxis as an adjunct to systemic eradication of H.pylori. Materials and Methods: Total of 22 H.pylori positive patients divided in two groups irrespective of gender. 14 patient underwent oral prophylaxis and remaining 8 subjects did not, along with triple drug therapy for systemic eradication of H.pylori. Plaque samples from only posteroior teeth collected and PCR was done for detection of H.pylori strains after 6 months. Results: Statistical significant reduction in prevalence of H.pylori noted in patients undergone oral prophylaxis along with anti-H pylori therapy. Conclusion: Oral prophylaxis has to be considered along with anti-H pylori eradication therapy to prevent dental plaque acting as a reservoir causing reinfection. Keywords: Oral prophylaxis, Helicobacter pylori, Reservoir, Systemic eradication.

A community survey of coverage and adverse events following country-wide triple-drug mass drug administration for lymphatic filariasis elimination, Samoa 2018.

The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administration (MDA) results with two drugs (DEC and albendazole) have been suboptimal, as is the case in Samoa. In August 2018, Samoa was the first country in the world to implement countrywide triple-drug MDA. This paper aims to describe Samoa’s experience with program coverage and adverse events (AEs) in the first round of triple-drug MDA. We conducted a large cross-sectional community survey to assess MDA awareness, reach, compliance, coverage and AEs in September/October 2018, 7–11 weeks after the first round of triple-drug MDA. In our sample of 4420 people aged ≥2 years (2.2% of the population), age-adjusted estimates indicated that 89.0% of the eligible population were offered MDA, 83.9% of the eligible population took MDA (program coverage), and 80.2% of the total population took MDA (epidemiological coverage). Overall, 83.8% (2986/3563) reported that they did not feel unwell at all after taking MDA. Mild AEs (feeling unwell but able to do normal everyday things) were reported by 13.3% (476/3563) and moderate or severe AEs (feeling unwell and being unable to do normal everyday activities such as going to work or school) by 2.9% (103/3563) of participants. This study following the 2018 triple-drug MDA in Samoa demonstrated a high reported program awareness and reach of 90.8% and 89.0%, respectively. Age-adjusted program coverage of 83.9% of the total population showed that MDA was well accepted and well tolerated by the community.

Palliative Medical Management of Inoperable Malignant Bowel Obstruction With "Triple Therapy": Dexamethasone, Octreotide, and Metoclopramide.

Malignant bowel obstruction (MBO) is a complication of advanced malignancy. For inoperable patients, symptoms are often treated using analgesics, anticholinergics, and anti-emetics. There are, however, few published guidelines for the medical management of MBO. To measure the effect of the combination of dexamethasone, octreotide, and metoclopramide ("triple therapy") in patients with MBO, compared to patients who received none of the 3 medications ("no drug therapy"). A retrospective cohort study of patients with MBO admitted in a single-center comprehensive cancer center. Patients who received dexamethasone, octreotide, and metoclopramide during their hospitalization for treatment of inoperable MBO were selected for analysis. Patients were excluded if they received a venting gastric tube. Rate of de-obstruction as well as time to de-obstruction were measured. There were 20 patients identified who received all 3 drugs of interest, and 29 patients identified who received none of the 3 medications. There was no statistically significant difference in rates of de-obstruction between the 2 groups, though there was a non-significant trend toward patients who received triple therapy were more likely to reach de-obstruction, compared to patients who had no drug therapy (95% vs. 83%, p = 0.379); there was no significant difference in adjusted analysis. In patients with inoperable MBO, there was no statistically significant difference in rates of de-obstruction with triple drug therapy compared to patients who received none of the 3 drugs, though the study may not have been powered to detect a difference and further investigation is warranted.

Пациент с гомозиготной семейной гиперхолестеринемией: трудное лечение. Клинический случай

Homozygous familial hypercholesterolemia is a severe genetic disorder characterized by extremely high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C), as well as by rapid atherosclerosis progression in various vascular territories. Objective examination of the affected patients often reveals multiple Achilles tendon xanthomas, xanthomas on the extensor surface of arms, knee joints, etc. The prevalence of such severe inherited hyperlipidemia in many populations is about 1 : 1 000 000, however, the family heterozygous type frequency increase leads to the decrease of this value and to the increase in the affected people number. The paper introduces case report for the patient V.I. aged 16 who was diagnosed with homozygous familial hypercholesterolemia at the age of 12. DNA testing revealed pathogenic mutations in the LDL receptor gene which confirmed the diagnosis. The paper reports the results of the discussed patient treatment using triple-drug combination lipid-lowering therapy with rosuvastatin (40 mg/day), ezetimibe (10 mg/day) and evolocumab (420 mg/day) in the last two years. The total cholesterol level decreased from 20.8 mmol/L (baseline) to 7.3–12.00 mmol/L, and the LDL-C level decreased from 19.9 mmol/L to 4.6–9.9 mmol/L due to therapy, the treatment was well tolerated. During the observation period, a rapid regression of xanthomas on the buttocks, knee and elbow joints, and Achilles tendon was achieved. A series of baseline instrumental tests (2013) revealed severe atherosclerosis of carotid arteries (maximum stenosis up to 50%), and first symptoms of aortic valve stenosis. Another examination in the hospital (2019) revealed slowing the progression of atherosclerosis in the carotid arteries and aorta, however, the arterial hypertension onset required additional prescription of a low dose of enalapril. Exercise testing and Holter ECG monitoring has yet identified no myocardial ischemia. Thus, the timely diagnosis together with long-term triple-drug intensive lipid-lowering therapy make it possible to slow down the atherosclerosis progression in the discussed rare and severe category of patients.

Blood Pressure Control, Left Ventricular Hypertrophy and Treatment Practice Among Hypertensive Patients in Ethiopia.

BackgroundGlobally, hypertension is the most important public health issue and is a increasing health problem in Ethiopia. Blood pressure (BP) control is an ultimate therapeutic goal of hypertensive patients in reducing early complications of hypertension. Hence, this study was sought to examine the magnitude of uncontrolled BP, left ventricular hypertrophy (LVH), and treatment practice. Predictors of uncontrolled BP and LVH were also investigated.MethodsA hospital-based cross-sectional study was conducted among 223 outpatients with hypertension on follow-up at Ayder Comprehensive Specialized Hospital (ACSH). Hypertensive patients with ≥18 years old who had been on follow-up care for at least 3 months were included in the study. Severely ill patients requiring urgent medical care and wheelchair-bound individuals or persons who had difficulty standing steady and pregnant women were excluded. Data were collected using a structured questionnaire and patients’ chart review. Data were entered and analyzed using SPSS version 22.0. To identify predictors, binary logistic regression model analysis was performed. Statistical significance was set at P-value of < 0.05.ResultsThe magnitude of uncontrolled BP (>140/90mmgH) and LVH was found to be 31.4% and 39.5%, respectively. More than half (53%) of participants were on at least two antihypertensive drug combinations of different classes. Uncontrolled BP was significantly associated with poor adherence to salt reduction in meal (Adjusted Odds Ratio (AOR) =8.552, 95% CI: 2.853, 15.638, P<0.001), non-adherence to medications (AOR =2.886, 95% CI: 1.710, 3.935, P<0.001), and taking triple-drug therapy (AOR=7.228, 95% CI: 1.110, 10.57, P=0.039). Presence of LVH was significantly associated with abdominal obesity (AOR= 2.2, 95% CI: 1.399, 4.69, P=0.003), age of ≥60 years (AOR= 2.421, 95% CI: 1.263, 4.639, P=0.008), and uncontrolled BP (AOR= 3.16, 95% CI: 1.208, 5.232, P=0.021).ConclusionIn this study, a significant proportion of patients with uncontrolled BP and LVH were found. Abdominal obesity, older age and uncontrolled blood pressure were predictors of LVH. Therefore, tailored interventions targeting BP control to reduce the magnitude of LVH and other early complications of hypertension deemed to be compulsory.

The Immune Response to Eastern Equine Encephalitis Virus Acquired Through Organ Transplantation.

The human immune response to eastern equine encephalitis virus (EEEV) infection is poorly characterized due to the rarity of infection. We examined the humoral and cellular immune response to EEEV acquired from an infected donor via liver transplantation. Both binding and highly neutralizing antibodies to EEEV as well as a robust EEEV-specific IgG memory B cell response were generated. Despite triple-drug immunosuppressive therapy, a virus-specific CD4+ T cell response, predominated by interferon-γ production, was generated. T cell epitopes on the E2 envelope protein were identified by interferon-γ ELISpot. Although these results are from a single person who acquired EEEV by a non-traditional mechanism, to our knowledge this work represents the first analysis of the human cellular immune response to EEEV.

Arrhythmogenic right ventricular cardiomyopathy in recipients on heart transplant waiting list

Aim. To determine the clinical features of arrhythmogenic right ventricular dysplasia (ARVD) in recipients on heart transplant waiting list (WL) and after a heart transplantation (HTx).Material and methods. From January 2010 to December 2018, we included 192 recipients in heart transplant waiting list (HTx WL) on behalf of Almazov National Medical Research Center. ARVD was diagnosed in 4 subjects (F Marcus et al. criteria, 2010). All 4 patients (female, mean age 46,5 years-old (16-54-year-old)) underwent HTx. Prior to HTx, arrhythmias (atrial fibrillation, atrial flutter) were diagnosed in 3 recipients. In patient №2, pacemaker in VVI mode was implanted due to sick sinus syndrome (SSS) and tachycardia-bradycardia syndrome and others underwent ICD implantation.Results. Survival after HTx was 30,9 (3,9-46,2) months. All recipients were treated with triple-drug immunosuppressive therapy (calcineurin inhibitors, mycophenolic acid, steroids) and induction with Basiliximab. All patients experienced high sensitivity to immunosuppressive therapy (agranulocytosis), and therefore a colony-stimulating factor was administered to all of them. After immunosuppression reduction (Tacrolimus plus Methylprednisolone) agranulocytosis did not recur.Conclusion. ARVD is a rare disease in the structure of end-stage heart failure in recipients in HTx WL. An examination of this pathology is necessary to manage patients on-time with surgical treatment (ICD, HTx). According to our results, causal variants in desmosome genes were determined in 1 from 4 patients and simultaneous presence of two unique genetic variants in the RKR2 gene were found in one. A special feature of post-HTx management was the development of agranulocytosis, which once again underlines the need for a personalized approach to the selection of the immunosuppressive therapy.

Circulating Small Noncoding RNA Biomarkers of Response to Triple Disease-modifying Antirheumatic Drug Therapy in White Women With Early Rheumatoid Arthritis.

To identify small noncoding RNA (sncRNA) serum biomarkers that predict response to triple disease-modifying antirheumatic drug (DMARD) therapy in patients with early rheumatoid arthritis (RA). Early RA patients entered into a treat-to-target management algorithm, with triple DMARD therapy (methotrexate, sulfasalazine, hydroxychloroquine). Patients were assessed following 6 months of therapy and classified as European League Against Rheumatism responders or nonresponders. RNA was isolated from 42 archived serum samples, collected prior to commencement of triple DMARD therapy. Small RNA sequencing was performed and the reads mapped to annotations in a database of human sncRNA. Differential expression analysis was performed, comparing responders (n = 24) and nonresponders (n = 18). Pretreatment levels of 4 sncRNA were significantly increased in nonresponders: chr1. tRNA131-GlyCCC (4.1-fold, adjusted P = 0.01), chr2.tRNA13-AlaCGC (2.2-fold, adjusted P = 0.02), U2-L166 (6.6-fold, adjusted P = 0.02), and piR-35982 (2.4-fold, adjusted P = 0.03). 5S-L612 was the only sncRNA significantly increased in responders (3.3-fold; adjusted P = 0.01). Reads for chr1. tRNA131-GlyCCC and chr2.tRNA13-AlaCGC mapped to the 5' end of each tRNA gene and were truncated at the anticodon loop, consistent with these sncRNA having roles as 5' translation interfering tRNA halves (tiRNA). Pretreatment levels of specific serum sncRNA might facilitate identification of patients more likely to respond to triple DMARD therapy.

Eradication of Helicobacter Pylori Infection Using Triple Drug Therapy: A Hospital Based Observational Study in Sikkim

Introduction: Helicobacter pylori infection is the important cause of various gastrointestinal. Variable resistance to treatment has been reported. This study was conducted to assess eradication rate of h pylori infection using the standard clarithromycin triple therapy. Method: This retrospective observational study was conducted in Central Referral Hospital, Sikkim Manipal Institute of Medical Sciences. 100 consecutive patients in a period of one year from 2016-2017 who were found positive for H pylori infection by rapid urease test (RUT) or histology or both were included in the study.Assessment of the eradication of H pylori was carried out after 8 weeks of treatment using 14 days of clarithromycin containing standard triple regimen. Results: Out of 100 patients,63 were males and 37 were females. Mean age of the patients was 38 years. Overall eradication rate was found to 63% after 8 weeks of treatment. Patients with gastric ulcer disease had worst eradication rate and it was statistically significant.[p=0.0143, OR 4.29(1.33-13.79)] .Out of these patients, eradication rate for H pylori was higher in duodenal ulcer patients than gastric ulcer patients. [p=0.0069, OR 6.5(1.6751-25.7798)].We found eradication rate of 63% in our study similar to these studies.7-10 days of triple therapy containing clarithromycin is reported to have around 90% eradication rate. (6) Of late, 7-10 days triple therapies have shown unacceptably low cure rates. We found eradication rate of 63% in our study similar to these studies. Discussion: Triple therapy, a recommended first-line treatment of H. pylori infection is found to be one of the most effective eradication in Asia and Africa. Seven days administration of a PPI, amoxicillin or metronidazole and clarithromycin is well-tolerated and improves patient’s compliance. 7-10 days of triple therapy containing clarithromycin is reported to have around 90% eradication rate.