Progressive ataxia with oculo-palatal tremor and optic atrophy

The final publication is available at Springer via doi: 10.​1007/​s00415-013-7136-

Coupled plasma filtration adsorption (CPFA) plus continuous veno-venous haemofiltration (CVVH) versus CVVH alone as an adjunctive therapy in the treatment of sepsis

To compare the efficacy of Coupled Plasma Filtration and Adsorption (CPFA) plus Continuous Veno-Venous Haemofiltration (CVVH) versus CVVH alone as an adjunct treatment of sepsis in terms of haemodynamic stability, inotropic requirement and inflammatory mediators. Design and Methods: Prospective randomized controlled trial involving septic patients with/without acute kidney injury (AKI) whom were randomized to receive CPFA + CVVH or CVVH alone. Haemodynamic parameters including inotropic requirements and inflammatory mediators [procalcitonin (PCT) and C reactive protein (CRP)] were measured. Results: Twenty-three patients [CPFA + CVVH (n = 11), CVVH (n = 12)] were enrolled. Haemodynamic stability occurred earlier and sustained in the CPFA + CVVH group with an increase in diastolic blood pressure (p = 0.001 vs. p = 0.226) and mean arterial pressure (p = 0.001 vs. p = 0.575) at the end of treatment with no increment in inotropic requirement. Both groups had a reduction in PCT and CRP (CPFA + CVVH: p = 0.003, p = 0.026 and CVVH: p = 0.008, p = 0.071 respectively). The length of intensive care unit stay, hospital stay and 30 day outcomes were similar between the groups. There was an inverse association between serum albumin and CRP (p = 0.018). Serum albumin positively correlated with systolic blood pressure (p = 0.012) and diastolic blood pressure (p = 0.009). We found a trend between CRP and length of hospital stay (p = 0.056). Patients with a lower PCT at 24 h had a better outcome (survival) than those with a higher PCT (p = 0.045). Conclusion: CPFA is a feasible, albeit expensive adjunctive extracorporeal treatment that may be superior to CVVH alone in the treatment of severe sepsis

C13orf31 (FAMIN) is a central regulator of immunometabolic function.

Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration. FAMIN-dependent FAO controlled inflammasome activation, mitochondrial and NADPH-oxidase-dependent production of reactive oxygen species (ROS), and the bactericidal activity of macrophages. As p.I254V and p.C284R resulted in diminished function and loss of function, respectively, FAMIN determined resilience to endotoxin shock. Thus, we have identified a central regulator of the metabolic function and bioenergetic state of macrophages that is under evolutionary selection and determines the risk of inflammatory and infectious disease.Supported by the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement 260961, the Wellcome Trust (investigator award 106260/Z/14/Z; a PhD fellowship for clinicians; and a Career Re-Entry Fellowship), the Wellcome Trust Sanger Institute, the US National Institutes of Health (5U420D011174 and 5U54HG006348), the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research Cambridge Biomedical Research Centre, the European Crohn’s and Colitis Organisation and the Swedish Medical Research Council and the Olle Engkvist foundation.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ni.353

Predisposing factors, outcomes, and treatment approach to fluid gusher complication during cochlear implant surgery

Our research focused on the fluid gusher complication from cochlear implant surgery. Fluid gusher is one of the most prevalent complications of cochlear implant surgery and occurs when cerebral spinal fluid leaks from the cochleostomy site. The complication occurs with opening the round window. We performed a systematic review of the literature, focusing on overviews of cochlear implant surgery complications. There are many factors contributing to the cause of fluid gushers including, biological sex, age, time of procedure, follow up time, temporal bone abnormalities, and abnormalities of the lateral wall of the internal auditory canal. Fluid gusher puts some patients at a higher risk of developing postoperative meningitis. Treatment includes elevating the patient’s head to reduce intracranial pressure, and packing the cochleostomy/round window. Closing the cochleostomy with temporalis fascia, muscle, connective tissue, or fibrin glue in addition to intravenous 20% mannitol drip was the most frequently reported management approach. We hope continued research will develop a mainstay treatment approach for fluid gusher complications, as there is no standardized treatment protocol currently put in place

Assessment of the impact of race and proxies of socioeconomic status on the prevalence and health outcome of peripartum cardiomyopathy (PPCM) using the “All of Us” Databank

Background: Peripartum Cardiomyopathy (PPCM) is a form of cardiomyopathy occurring during the last month of pregnancy or within months after giving birth in women with previously normal hearts. PPCM is an idiopathic systolic dysfunction that causes a reduced left ventricle ejection fraction. The estimated incidence of PPCM worldwide is 1 diagnosis out of 2,000 live births, and the causes of PPCM remain unknown. A retrospective cohort study conducted at the University of Pennsylvania Health System by Getz et al. showed that black race and socioeconomic proxies (like neighborhood disadvantage index (NDI)) were independently associated with sustained cardiac dysfunction (Getz et al., Am Heart J 2021). This study also showed that from all the components of NDI (education, high rental occupied housing, annual income below poverty line, female headed household, adults unemployed, adults on public assistance), low education and high rental occupied housing were significantly associated with sustained cardiac dysfunction. The central aim of the present project is to assess the effect of socioeconomic proxies (including NDI, lack of access to health care and food insecurity) on the prevalence of sustained cardiac dysfunction from PPCM across the US using the “All of Us” databank. A secondary aim is to test the compliance of the All of Us database capacity to interrogate this potential association. Lastly, we aim to compare the results obtained from the All of Us database with the UK Biobank. Methods: The All of Us databank (Ramirez et al., Patterns 2022; The All of US Research Program, NEJM 2019) will be used to conduct a retrospective cohort study to assess how proxies of socioeconomic status may affect the incidence and prevalence of sustained cardiac dysfunction from PPCM across different ethnicities in the US. The All of Us database focuses on enrolling people in the US from diverse groups that have historically been underrepresented in medical research. Therefore, it includes a more diverse population than the population targeted in the retrospective study conducted at the University of Pennsylvania in which only black women from Philadelphia, PA, were included. To further interrogate the impact that geographic location and population ethnicity may have on the prevalence of sustained cardiac dysfunction from PPCM, the results obtained from the “All of Us” database will be compared against data obtained from the UK Biobank. Expected Results: We expect that the socioeconomic proxies interrogated in this study will have a significant impact on the prevalence of sustained cardiac dysfunction from PPCM. Current knowledge is limited on how socioeconomic status affects sustained cardiac dysfunction resulting from PPCM. Previous studies have been done on populations restricted to small geographic areas and did not analyze factors such as food security, access to care, or disability status. Understanding how these factors affect the incidence and prevalence of sustained cardiac dysfunction from PPCM may be used to improve prevention, early diagnosis, and management of PPCM

A new paradigm for healthcare system using emerging technologies

There are many diseases threatening humans around the globe. Many of them are from the past centuries, and a few are newly discovered. This study has mainly focused on trending technologies such as Artificial Intelligence, Machine Learning, Big Data, Internet of Things that are used to predict diseases in the health sector. This study has collected data from the previously published articles from the reputed publishers using a systematic review approach, and these data were analyzed separately for each technology mentioned above. Studies confirmed that most of the research focused on IoT in the health sector. Furthermore, all the above technologies provide higher accuracy in predicting diseases. But, IoT provides higher accuracy than other emerging technologies for predicting most diseases. A few constraints of the study were the size of the dataset and missing quality qualities. In the end, it is recommended to study the security issues in IoT in the healthcare sector to predict and diagnose diseases

Physical activity monitoring to assess disability progression in multiple sclerosis

Background: Clinical outcome measurement in multiple sclerosis (MS) usually requires a physical visit. Remote activity monitoring (RAM) using wearable technology provides a rational alternative, especially desirable when distance is involved or in a pandemic setting. Objective: To validate RAM in progressive MS using (1) traditional psychometric methods (2) brain atrophy. Methods: 56 people with progressive MS participated in a longitudinal study over 2.5 years. An arm-worn RAM device measured activity over six days, every six months, and incorporated triaxial accelerometry and transcutaneous physiological variable measurement. Five RAM variables were assessed: physical activity duration, step count, active energy expenditure, metabolic equivalents and a composite RAM score incorporating all four variables. Other assessments every six months included EDSS, MSFC, MSIS-29, Chalder Fatigue Scale and Beck’s Depression Inventory. Annualized brain atrophy was measured using SIENA. Results: RAM was tolerated well by people with MS; the device was worn 99.4% of the time. RAM had good convergent and divergent validity and was responsive, especially with respect to step count. Measurement of physical activity over one day was as responsive as six days. The composite RAM score positively correlated with brain volume loss. Conclusion: Remote activity monitoring is a valid and acceptable outcome measure in MS