Helicobacter Pylori as a Risk Factor for Post Infectious Irritable Bowel Syndrome

Backgrounds: Helicobacter Pylori is a common pathogen leading cause of peptic ulcer disease. Several studies linked Helicobacter Pylori infection and the development of irritable bowel syndrome. Aims: We investigated the effectiveness of standard triple therapy and the association between H.Pylori infection and the development of post infectious irritable bowel syndrome. Materials and methods: Prospective analytical study was conducted and we appointed 200 H.Pylori positive patients, they consented and subjected to structured questionnaire and received standard triple therapy (14 days course of proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole). After three months all patients re-evaluated regarding their symptoms and tested for eradication. Additionally we evaluated the association between H.Pylori infection and irritable bowel syndrome

Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress

Background: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention. Objectives: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC “Triple Pill,” three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. Design: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130–160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety. Results: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024. Conclusion: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.

Inflammation and Intracellular Exposure of Dolutegravir, Darunavir, Tenofovir and Emtricitabine in People living with HIV

Background: Antiretroviral therapy reduces systemic inflammation and immune activation, but not to levels like HIV-negative. Limited drug penetration within tissues has been argued as potential mechanism of persistent inflammation. Data on the role of inflammation on plasma/intracellular (IC) pharmacokinetics (PK) of ARV drugs through to downregulation/expression of cytochrome P450 3A/membrane transport proteins are limited. Aim of this study was to investigate the correlation between inflammation markers and plasma/IC PK of different ARVs regimen in HIV-positive patients. Methods: We included in the study ART-treated HIV+ pts switching to 3 different ARV regimens: 1) DTG-based dual-therapy plus boosted-PIs, 2) DTG-based triple-therapy without PIs, 3) DRV/c-based triple-therapy. Plasma and IC ARV drugs concentration means at the end of dosing interval (T0), IM on samples concomitantly with ARV PK determination: sCD14, CRP, IL-6 and LPS were analysed. Results: 60 samples from pts included in the switching study were used for measuring plasma and IC concentrations of HIV drugs. No significative differences between CRP, sCD14, IL-6 and LPS values in 3 arms of therapy were observed. Significant correlation was observed between tenofovir plasma concentrations and sCD14 (p<0.001), DRV plasma concentration and sCD14 (p=0,07) and DRV IC/plasma ratio and Log10 IL-6 concentrations (p=0.04). Furthermore, in 24 pts on DTG-TT, we observed a negative trend between DTG IC concentrations and sCD14 (p=0.09). Conclusions: Our preliminary data support the hypothesis of lower IC concentrations of DRV and DTG in pts with higher plasma IM, suggesting an interplay between HIV drug penetration and persistent inflammation in cART-treated HIV-positive patients.

High Plus Low Dose Radiation Strategy in Combination with TIGIT and PD1 Blockade to Promote Systemic Antitumor Responses

Tumors deploy various immune-evasion mechanisms that create a suppressive environment and render effector T-cells exhausted and inactive. Therefore, a rational utilization of checkpoint inhibitors may alleviate exhaustion and may partially restore antitumor functions. However, in high-tumor-burden models, the checkpoint blockade fails to maintain optimal efficacy, and other interventions are necessary to overcome the inhibitory tumor stroma. One such strategy is the use of radiotherapy to reset the tumor microenvironment and maximize systemic antitumor outcomes. In this study, we propose the use of anti-PD1 and anti-TIGIT checkpoint inhibitors in conjunction with our novel RadScopal technique to battle highly metastatic lung adenocarcinoma tumors, bilaterally established in 129Sv/Ev mice, to mimic high-tumor-burden settings. The RadScopal approach is comprised of high-dose radiation directed at primary tumors with low-dose radiation delivered to secondary tumors to improve the outcomes of systemic immunotherapy. Indeed, the triple therapy with RadScopal + anti-TIGIT + anti-PD1 was able to prolong the survival of treated mice and halted the growth of both primary and secondary tumors. Lung metastasis counts were also significantly reduced. In addition, the low-dose radiation component reduced TIGIT receptor (PVR) expression by tumor-associated macrophages and dendritic cells in secondary tumors. Finally, low-dose radiation within triple therapy decreased the percentages of TIGIT+ exhausted T-cells and TIGIT+ regulatory T-cells. Together, our translational approach provides a new treatment alternative for cases refractory to other checkpoints and may bring immunotherapy into a new realm of systemic disease control.

An Overview of Combination Treatment with Citicoline in Dementia

Introduction: The present article reports an overview of the studies about combination treatment with citicoline of Alzheimer’s (AD) and mixed dementia (MD). Methods: A Medline search was carried out by using the keywords Alzheimer’s dementia, mixed dementia, older people, treatment with citicoline, memantine, and acetylcholinesterase inhibitors (AchEIs). Results: Six studies were found to match the combination treatment of citicoline with AcheIs and/or memantine. The CITIRIVAD and CITICHOLINAGE studies were the first to report the potential benefits of adding citicoline to acetylcholinesterase inhibitors (AchEIs). Then, we added citicoline to memantine in the CITIMEM study, and finally, we demonstrated benefits in terms of delay in cognitive worsening with the triple therapy (citicoline + AchEIs + memantine). Other authors also reinforced our hypothesis through two further studies. Conclusions: Open, prospective studies are advised to confirm the utility of combination therapy with citicoline for the treatment of AD and MD.

Systemic Triple Therapy in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Ready for Prime Time or Still to Be Explored?

For decades, mono androgen deprivation therapy (ADT) has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published within the last seven years demonstrating a significant survival advantage by combination treatment with standard ADT plus docetaxel or androgen receptor-axis-targeted therapy (ARAT) compared to ADT monotherapy. As a result, overall survival can be prolonged by at least 18 months. Recently published congress data of the PEACE-1 study suggests that in the future, triple therapy might be the new gold standard. In addition to this study, which has shown that triple treatment with standard ADT plus docetaxel plus abiraterone is superior to standard ADT plus docetaxel, several other phase III triple therapy studies are currently ongoing. The different modes of action that are investigated reach from AR-targeting over mitotic inhibition and immunotherapy to PARP and AKT inhibition. In this review we will explore if triple therapy has the potential to be the new standard for mHSPC treatment in the near future.

Eradication of Helicobacter Pylori with Triple Therapy Comprising Probiotic & Proton Pump Inhibitor

Objectives: The current clinical trial compared the effects of conventional triple therapy and probiotic (Lactobacillus reuteri) plus omeprazole combination in peptic ulcer patients. The secondary objectives included estimating the effects of these regimens on safety and tolerability. Study Design: Randomized clinical trial Abode and Period of Study: This was a six month research study conducted at the National Medical Centre, Karachi, Pakistan in October 2020 – March 2021. Materials & Methods: A total of 100 patients were recruited, had baseline positive stool antigen test. All the participants were separated into dual groups: conventional triple remedy (group A1) and probiotic with omeprazole combination (group B1). The study's primary endpoint was stool antigen assay and secondary included change in Hb, LFTs and renal function test. Results: The primary endpoints for combination therapy led to significantly greater reductions in positive stool antigen assay than triple therapy. This means that combination therapy is far better than triple therapy. The stool antigen test showed 56.5% positive and 43.5% negative in group A1 while in group B1 34.8% positive while 65.2% negative after treatment were seen with statistically significant difference (p=0.036). Insignificant findings were observed for level of Hb, LFTs and renal function test between both groups during the entire study. Conclusion: This is the first randomized clinical trial in peptic ulcer patients of Pakistan treated with probiotic plus omeprazole combination. Combination therapy was generally well-tolerated and effective in eradicating the Helicobacter pylori after initiation of therapy.