Synthesis, Characterization and Antimicrobial Studies of Some Novel 1,3,4-Thiadiazolium-2-thiolate Derivatives

In this study, ten new 5-substituted-3-[4,6-di(morpholine-4-yl)-1,3,5-triazine 2-yl]-1,3,5-thiadiazolium-2-thiolate 6(a–j) were prepared via a five step procedure from the starting material 1,3,5-triazine (1). Structures of all synthesized compounds were confirmed by spectral data and elemental analyses. Newly synthesized compounds were tested for their antibacterial and antifungal activities against some important bacterial and fungal species. Some of the compounds were found to be moderately active against the tested organisms.Keywords: Thiadiazol, s-triazine, Mesoionic, NMR spectroscopy, IR spectroscop

Home Parenteral Nutrition in Patients with Advanced Cancer: A Systematic Review and Meta-Analysis

The use of home parenteral nutrition (HPN) in patients with incurable cancer remains controversial with significant variation worldwide. We aimed to systematically evaluate the literature from 1960 to 2018 examining the use of HPN in advanced cancer patients for all intestinal failure indications and assess the potential benefits/burdens of HPN in this cohort of patients. The primary end point was survival and secondary end points were quality of life and nutritional/performance status. Meta-analysis was performed with a random effects model, where suitable. Of 493 studies retrieved, 22 met the quality inclusion criteria. Studies were mainly conducted in Western countries (Italy, USA, Canada, Germany), including a total of 3564 patients (mean age 57.8 years). Mean duration for HPN was 5.0 mo. Mean overall survival was 7.3 mo. Patients with improved performance status survived for longer on HPN. Quality of life was sparsely reported though there was no observed negative impact of PN. HPN-related complications were reported in eight studies only and were mainly catheter-related blood stream infections. In conclusion, HPN is used for several indications in advanced cancer, though there is significant heterogeneity of results. Disparities in geographical distribution of the studies may reflect variation in accessing HPN

Hypophosphataemia after intravenous iron therapy with ferric carboxymaltose—Real world experience from a tertiary centre in the UK

Background: Iron deficiency is the most common global cause of anaemia. Intravenous (IV) iron is used to correct iron deficiency anaemia (IDA) where oral iron cannot be used. Despite being effective, certain IV iron formulations cause significant hypophosphataemia. However, current knowledge on the clinical consequences of IV iron‐induced hypophosphataemia is broadly anecdotal or limited to isolated case reports. / Aims: To retrospectively examine the incidence and potential clinical consequences of hypophosphataemia post‐IV ferric carboxymaltose (FCM) in hospitalised patients with IDA (mixed aetiology). / Methods: Data were collected for 162 patients, who received a total of 169 FCM courses during a 2‐year audit period. Outcomes included incidence of moderate/severe hypophosphataemia (serum phosphate <0.65 mmol/L) ≤90 days post‐FCM, changes in alkaline phosphatase, need for phosphate replacement, and length of hospital stay. / Results: The incidence of moderate/severe hypophosphataemia post‐FCM was 33.7%; within this group the rate of severe hypophosphataemia (serum phosphate ≤0.32 mmol/L) was 8.8%. Moderate/severe hypophosphataemia persisted, with 35% of patients having a serum phosphate of <0.65 mmol/L for ≤90 days at the last measurement after IV FCM. Intervention with IV phosphate—an average of 4.4 infusions per person—was required in 29.8% of cases with moderate/severe hypophosphataemia. FCM‐induced moderate/severe hypophosphataemia was associated with a significantly longer hospital stay (P < 0.0035). / Conclusions: Moderate/severe hypophosphataemia is a frequent adverse drug reaction with FCM. In our study, FCM‐induced moderate/severe hypophosphataemia was also persistent, often required treatment, and was associated with longer hospital stay

Enteral Nutrition in Adult Crohn’s Disease: Toward a Paradigm Shift

Medical and surgical treatments for Crohn’s disease are associated with toxic effects. Medical therapy aims for mucosal healing and is achievable with biologics, immunosuppressive therapy, and specialised enteral nutrition, but not with corticosteroids. Sustained remission remains a therapeutic challenge. Enteral nutrition, containing macro- and micro-nutrients, is nutritionally complete, and is provided in powder or liquid form. Enteral nutrition is a low-risk and minimally invasive therapy. It is well-established and recommended as first line induction therapy in paediatric Crohn’s disease with remission rates of up to 80%. Other than in Japan, enteral nutrition is not routinely used in the adult population among Western countries, mainly due to unpalatable formulations which lead to poor compliance. This study aims to offer a comprehensive review of available enteral nutrition formulations and the literature supporting the use and mechanisms of action of enteral nutrition in adult Crohn’s disease patients, in order to support clinicians in real world decision-making when offering/accepting treatment. The mechanisms of actions of enteral feed, including their impact on the gut microbiome, were explored. Barriers to the use of enteral nutrition, such as compliance and the route of administration, were considered. All available enteral preparations have been comprehensively described as a practical guide for clinical use. Likewise, guidelines are reported and discussed

Clinical and Nutritional Care Pathways of Patients with Malignant Bowel Obstruction: A Retrospective Analysis in a Tertiary UK Center

We describe a retrospective cohort study of patients with malignant bowel obstruction to examine their nutritional care pathways between 1.1.16 and 31.12.16 with readmissions until 31.12.17. Data were analyzed by comparing patients who were referred (R) and not referred (NR) for PN. We identified 72 patients with 117 MBO admissions (mean ± SD age:63.1 ± 13.1yrs, 79% female). 24/72 patients were in R group. Predominant primary malignancies were gynaecological and lower-gastrointestinal cancers (76%). 83% patients had metastases (61% sub-diaphragmatically). All patients were at high-risk of malnutrition and baseline mean weight loss was 7%. Discussion of PN at multidisciplinary team meeting (MDT) (22% vs.5%, P = 0.02) and dietetic contact (94% vs. 41%, P < 0.0001) were more likely to occur in the R group. In 13/69 MBO admissions in NR group, reasons for non-referral were unclear. Median baseline and follow-up weight was similar (55–55.8 kg). Overall survival was 4.7 (1.4–15.2)months, with no differences by referral groups. We compared a sub-sample of patients who ‘may have’ required PN (n = 10) vs. those discharged on home PN (n = 10) and found greater survival in the HPN group (323vs.91 day, P < 0.01). Our findings highlight disparity in care pathways suggesting that nutritional care should be integrated into clinical management discussion(s) at MDT to ensure equal access to nutritional services

Performance Status, Prognostic Scoring and Parenteral Nutrition Requirements Predict Survival in Patients with Advanced Cancer Receiving Home Parenteral Nutrition

We describe a cohort of Home Parenteral Nutrition (HPN) patients with advanced cancer in order to identify factors affecting prognosis. Demographic, anthropometric, biochemical and medical factors, Karnofsky Performance Status (KPS), Glasgow Prognostic Score (GPS), and PN requirements were recorded. Univariate and multivariate analyses were performed including Kaplan–Meier curves, Cox Regression, and correlation analyses. In total, 107 HPN patients (68 women, 39 men, mean age 57 yr) with advanced cancer were identified. The main indications for HPN were bowel obstruction (74.3%) and high output ostomies (14.3%). Cancer cachexia was present in 87.1% of patients. The hazard ratio (HR) for upper gastrointestinal and “other” cancers vs. gynaecological malignancy was 1.75 (p = 0.077) and 2.11 (p = 0.05), respectively. KPS score, GPS, PN volume, and PN potassium levels significantly predicted survival (HRKPS ≥50 vs 0.05). Most patients passed away in their homes or hospice (77.9%). Performance status, prognostic scoring, and PN requirements may predict survival in patients with advanced cancer receiving HPN

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)