Analysis of gastrointestinal drugs in patients admitted in CCU and ICCU of a tertiary care hospital in Goa, India

Background: Gastrointestinal (GI) diseases are a common problem worldwide. They are frequently encountered in non-critical as well as in critically ill hospitalized patients.Methods: This was a prospective and observational study conducted on patients admitted in CCU and ICCU of Goa Medical College and Hospital. Data was collected from the patients’ case records and was analysed referring to WHO prescribing indicators. Data was represented as Mean±SD, number and frequency.Results: A total of 2250 drugs were prescribed, out of which 376 (16.71%) were gastrointestinal drugs. Most common route of administration was oral 323 (85.90%). Prescription patterns of GI drugs were:  275 (73.14%) from National List of Essential Medicines, 20 (5.31%) as fixed dose combinations and 4 (1.06%) by generic names. Pantoprazole 183 (48.67%) was the most frequently prescribed drug for peptic ulcer in present study.Conclusions: From the findings of this study we noted that among the GI drugs used, those for peptic ulcer were the most commonly prescribed. Also majority were from the essential drug list. But prescribing by generic names was low. Review of drug utilization trends is a necessary aid to formulate and modify existing protocols and guidelines to improve treatment outcomes in a given setting

Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells

Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1?? and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1??, IL-6 and IFN-??. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth.ope

Bone Marrow Derived Mesenchymal Stem Cells Inhibit Inflammation and Preserve Vascular Endothelial Integrity in the Lungs after Hemorrhagic Shock

Hemorrhagic shock (HS) and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs) are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. In this paper, in vitro studies with pulmonary endothelial cells (PECs) reveal that conditioned media (CM) from MSCs and MSC-PEC co-cultures inhibits PEC permeability by preserving adherens junctions (VE-cadherin and β-catenin). Leukocyte adhesion and adhesion molecule expression (VCAM-1 and ICAM-1) are inhibited in PECs treated with CM from MSC-PEC co-cultures. Further support for the modulatory effects of MSCs on pulmonary endothelial function and inflammation is demonstrated in our in vivo studies on HS in the rat. In a rat “fixed volume” model of mild HS, we show that MSCs administered IV potently inhibit systemic levels of inflammatory cytokines and chemokines in the serum of treated animals. In vivo MSCs also inhibit pulmonary endothelial permeability and lung edema with concurrent preservation of the vascular endothelial barrier proteins: VE-cadherin, Claudin-1, and Occludin-1. Leukocyte infiltrates (CD68 and MPO positive cells) are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HS-induced lung injury

Presentation and Outcomes of Infants With Idiopathic Cholestasis: A Multicenter Prospective Study

Objectives: The aim of the study was to determine the frequency and natural history of infantile idiopathic cholestasis (IC) in a large, prospective, multicenter cohort of infants. Methods: We studied 94 cholestatic infants enrolled up to 6 months of age in the NIDDK ChiLDReN (Childhood Liver Disease Research Network) "PROBE" protocol with a final diagnosis of IC; they were followed up to 30 months of age. Results: Male sex (66/94; 70%), preterm birth (22/90 with data; 24% born at 1 mg/dL and/or ALT > 35 U/L; n = 7), and exited healthy (resolved disease per study site report but without documented biochemical resolution; n = 34). Biochemical resolution occurred at median of 9 months of age. GGT was <100 U/L at baseline in 34 of 83 participants (41%). Conclusions: Frequency of IC and of death or liver transplant was less common in this cohort than in previously published cohorts, likely because of recent discovery and diagnosis of genetic etiologies of severe/persistent cholestasis that previously were labeled as idiopathic. Preterm birth and other factors associated with increased vulnerability in neonates are relatively frequent and may contribute to IC. Overall outcome in IC is excellent. Low/normal GGT was common, possibly indicating a role for variants in genes associated with low-GGT cholestasis-this warrants further study

Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response. Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. Clinical trial registered with www.clinicaltrials.gov (NCT01560624)