Hypothermia associated with clobazam use in adult epilepsy

AbstractClobazam, a 1,5-benzodiazepine FDA-approved in 2011, is commonly used to treat anxiety and epilepsy. It has not been associated with hypothermia until very recently, in a case report involving two pediatric patients. Here, we report the first case of hypothermia development in an adult patient with epilepsy associated with clobazam use. A couple months after starting clobazam, the patient started developing episodes of hypothermia every several weeks, with temperatures ranging from 90°F–95°F. Normothermia was achieved with Bair Hugger therapy. Thyroid-stimulating hormone and cortisol levels were normal, and there was no evidence of infection in most instances. After 11 total episodes of hypothermia over a year of clobazam use, the drug was discontinued. It has now been 7months after discontinuation, and the patient has not experienced any more episodes of hypothermia. Early recognition of the link between clobazam and hypothermia may prevent avoidable Emergency Department visits and hospitalizations

Letter: faecal microbiota transplantation for irritable bowel syndrome

his article is linked to Lahtinen et al papers. To view these articles, visit https://doi.org/10.1111/apt.15810 and https://doi.org/10.1111/apt.15875

Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts

The gut microbiota is a reservoir for antimicrobial resistance genes (ARGs). With current sequencing methods, it is difficult to assign ARGs to their microbial hosts, particularly if these ARGs are located on plasmids. Metagenomic chromosome conformation capture approaches (meta3C and Hi-C) have recently been developed to link bacterial genes to phylogenetic markers, thus potentially allowing the assignment of ARGs to their hosts on a microbiome-wide scale. Here, we generated a meta3C dataset of a human stool sample and used previously published meta3C and Hi-C datasets to investigate bacterial hosts of ARGs in the human gut microbiome. Sequence reads mapping to repetitive elements were found to cause problematic noise in, and may importantly skew interpretation of, meta3C and Hi-C data. We provide a strategy to improve the signal-to-noise ratio by discarding reads that map to insertion sequence elements and to the end of contigs. We also show the importance of using spike-in controls to quantify whether the cross-linking step in meta3C and Hi-C protocols has been successful. After filtering to remove artefactual links, 87 ARGs were assigned to their bacterial hosts across all datasets, including 27 ARGs in the meta3C dataset we generated. We show that commensal gut bacteria are an important reservoir for ARGs, with genes coding for aminoglycoside and tetracycline resistance being widespread in anaerobic commensals of the human gut

Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection.

BACKGROUND: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. METHODS: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. FINDINGS: Clinical response was 83·9% (95% CI 76·0%-90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%-89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. INTERPRETATION: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments

The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease

The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD. With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD. This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD

Electrical cortical stimulation can impair production of the alphabet without impairing counting

Neurosurgery has the potential to cure patients with drug-resistant focal epilepsy, but carries the risk of permanent language impairment when surgery involves the dominant hemisphere of the brain. This risk can be estimated and minimized using electrical stimulation mapping (ESM), which uses cognitive and linguistic tasks during cortical ESM to differentiate "eloquent" and "resectable" areas in the brain. One such task, counting, is often used to screen and characterize language during ESM in patients whose language abilities are limited. Here we report a patient with drug-resistant epilepsy arising from the language-dominant hemisphere using fMRI. Our patient experienced loss of the ability to recite or write the alphabet, but not to count, during ESM of the dominant left posterior superior temporal gyrus. This selective impairment extended to both spoken and written production. We suggest the need for caution when using counting as a sole means to screen language function and as a method of testing low functioning patients using ESM

Optimising triage of urgent referrals for suspected IBD: results from the Birmingham IBD inception study

Objective: Diagnostic delays in inflammatory bowel disease (IBD) result in adverse outcomes. We report a bespoke diagnostic pathway to assess how best to combine clinical history and faecal calprotectin (FCP) for early diagnosis and efficient resource utilisation. Methods: A rapid-access pathway was implemented for suspected IBD patients referred outside urgent ‘two-week wait’ criteria. Patients were triaged using symptoms and FCP. A 13-point symptom history was taken prediagnosis and clinical indices, including repeat FCP, collected prospectively. Results: Of 767 patients (January 2021–August 2023), 423 were diagnosed with IBD (208 Crohn’s disease (CD), 215 ulcerative colitis (UC)). Most common symptoms in CD were abdominal pain (84%), looser stools (84%) and fatigue (79%) and in UC per-rectal bleeding (94%), urgency (82%) and looser stools (81%). Strongest IBD predictors were blood mixed with stools (CD OR 4.38; 95% CI 2.40–7.98, UC OR 33.68; 15.47–73.33) and weight loss (CD OR 3.39; 2.14–5.38, UC OR 2.33; 1.37–4.00). Repeat FCP testing showed reduction from baseline in non-IBD. Both measurements >100 µg/g (area under the curve (AUC) 0.800) and >200 µg/g (AUC 0.834) collectively predicted IBD. However, a second value ≥220 µg/g considered alone, regardless of the first result, was more accurate (Youden’s index 0.735, AUC 0.923). Modelling symptoms with FCP increased AUC to 0.947. Conclusion: Serial FCP measurement prevents unnecessary colonoscopy. Two FCPs >200 µg/g could stream patients direct to colonoscopy, with two >100 µg/g prompting clinic review. A second result ≥220 µg/g was more accurate than dual-result thresholds. Coupling home FCP testing with key symptoms may form the basis of effective self-referral pathways

Blood urea nitrogen as an early predictor of severity in acute pancreatitis

Background: Acute pancreatitis presents as acute abdominal pain and is usually associated with raised pancreatic enzyme levels in the blood or urine. Aims and objectives of the study was to evaluate the role of serial BUN measurement as an early prognostic marker of acute pancreatitis.Methods: From each patient detailed history was taken, general and systemic examination were done and relevant investigations were conducted. BUN was repeated after 24 hours and the change in the level of BUN was noted. Imaging in the form of CT after 72 hours of admission were performed in each patient. The severity of acute pancreatitis was gauged by modified CTSI and the same was compared to the change in BUN values over first 24 hours of admission.Results: Mean BUN values at ‘0’ hour in severe acute pancreatitis and non-severe acute pancreatitis were 31.91±6.79 and 15.44±5.95 mg/dl, respectively. The difference between the two groups was statistically significant with p value of <0.001. Similarly, the difference in BUN values at ‘24’ hours between the two groups was statistically significant. BUN value ≥23 mg/dl at ‘0’ hour was found to be the optimal cut off for determining the severity of pancreatitis with sensitivity of 91.3%. BUN ≥25 mg/dl at 24 hours was found to be the optimal cut-off for determining the severity of acute pancreatitis with sensitivity of 95.7%.Conclusions: BUN as a single marker for acute pancreatitis can be useful as it is easy to perform and cheap marker to predict severity without the need for complex calculations.

Synergistic effect p-phenylenediamine and n,n diphenylthiourea on the electrochemical corrosion behaviour of mild steel in dilute acid media

Electrochemical studies of the synergistic effect of p-phenylenediamine and n,n diphenylthiourea (TPD) as corrosion inhibitor of mild steel in dilute sulphuric and hydrochloric acid through weight loss and potentiodynamic polarization at ambient temperature were performed. Experimental results showed the excellent performance of TPD with an optimal inhibition efficiency of 88.18 and 93.88 %in sulphuric and 87.42 and 87.15 %in hydrochloric acid from both tests at all concentration studied. Polarization studies show the compound to be a mixed-type inhibitor. Adsorption of deanol on the steel surface was observed to obey the Langmuir and Frumkin isotherm models. X-ray diffractometry confirmed the absence of corrosion products and complexes. Optical microscopy confirmed the selective inhibition property of TPD to be through chemical adsorption on the steel surfac

Systemic aminoglycosides are trafficked via endolymph into cochlear hair cells

Aminoglycoside antibiotics rapidly enter and kill cochlear hair cells via apical mechanoelectrical transduction (MET) channels in vitro. In vivo, it remains unknown whether systemically-administered aminoglycosides cross the blood-labyrinth barrier into endolymph and enter hair cells. Here we show, for the first time, that systemic aminoglycosides are trafficked across the blood-endolymph barrier and preferentially enter hair cells across their apical membranes. This trafficking route is predominant compared to uptake via hair cell basolateral membranes during perilymph infusion