A Case of Meningococcal and HSV-2 Meningitis in a Patient Being Treated with Ustekinumab for Pityriasis Rubra Pilaris

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous dermatosis affecting both adults and children. Six subtypes of PRP have been described. Recently, the management of PRP with biologic immunosuppressive agents regularly used in psoriasis has been supported by several case reports and series. Ustekinumab is an anti-IL12/23 IgG1 kappa human monoclonal antibody. It has been approved for the treatment of Crohn’s disease, plaque psoriasis, psoriatic arthritis and ulcerative colitis. It has also been reported to be effective as an off-label treatment for PRP. Current data are equivocal regarding infectious disease risk with ustekinumab administration. We describe a case of meningococcal and HSV-2 infection of the central nervous system in a patient being treated with ustekinumab for PRP

Procedural confidence in hospital based practitioners: implications for the training and practice of doctors at all grades

<p>Abstract</p> <p>Background</p> <p>Medical doctors routinely undertake a number of practical procedures and these should be performed competently. The UK Postgraduate Medical Education and Training Board (PMETB) curriculum lists the procedures trainees should be competent in. We aimed to describe medical practitioner's confidence in their procedural skills, and to define which practical procedures are important in current medical practice.</p> <p>Methods</p> <p>A cross sectional observational study was performed measuring procedural confidence in 181 hospital practitioners at all grades from 2 centres in East Anglia, England.</p> <p>Results</p> <p>Both trainees and consultants provide significant service provision. SpR level doctors perform the widest range and the highest median number of procedures per year. Most consultants perform few if any procedures, however some perform a narrow range at high volume. Cumulative confidence for the procedures tested peaks in the SpR grade. Five key procedures (central line insertion, lumbar puncture, pleural aspiration, ascitic aspiration, and intercostal drain insertion) are the most commonly performed, are seen as important generic skills, and correspond to the total number of procedures for which confidence can be maintained. Key determinants of confidence are gender, number of procedures performed in the previous year and total number of procedures performed.</p> <p>Conclusion</p> <p>The highest volume of service requirement is for six procedures. The procedural confidence is dependent upon gender, number of procedures performed in the previous year and total number of procedures performed. This has implications for those designing the training curriculum and with regards the move to shorten the duration of training.</p

Sources and processes that control the submicron organic aerosol composition in an urban Mediterranean environment (Athens): a high temporal-resolution chemical composition measurement study

Submicron aerosol chemical composition was studied during a year-long period (26 July 2016–31 July 2017) and two wintertime intensive campaigns (18 December 2013–21 February 2014 and 23 December 2015–17 February 2016), at a central site in Athens, Greece, using an Aerosol Chemical Speciation Monitor (ACSM). Concurrent measurements included a particle-into-liquid sampler (PILS-IC), a scanning mobility particle sizer (SMPS), an AE-33 Aethalometer, and ion chromatography analysis on 24 or 12&thinsp;h filter samples. The aim of the study was to characterize the seasonal variability of the main submicron aerosol constituents and decipher the sources of organic aerosol (OA). Organics were found to contribute almost half of the submicron mass, with 30&thinsp;min resolution concentrations during wintertime reaching up to 200&thinsp;µg&thinsp;m−3. During winter (all three campaigns combined), primary sources contributed about 33&thinsp;% of the organic fraction, and comprised biomass burning (10&thinsp;%), fossil fuel combustion (13&thinsp;%), and cooking (10&thinsp;%), while the remaining 67&thinsp;% was attributed to secondary aerosol. The semi-volatile component of the oxidized organic aerosol (SV-OOA; 22&thinsp;%) was found to be clearly linked to combustion sources, in particular biomass burning; part of the very oxidized, low-volatility component (LV-OOA; 44&thinsp;%) could also be attributed to the oxidation of emissions from these primary combustion sources. These results, based on the combined contribution of biomass burning organic aerosol (BBOA) and SV-OOA, indicate the importance of increased biomass burning in the urban environment of Athens as a result of the economic recession. During summer, when concentrations of fine aerosols are considerably lower, more than 80&thinsp;% of the organic fraction is attributed to secondary aerosol (SV-OOA 31&thinsp;% and LV-OOA 53&thinsp;%). In contrast to winter, SV-OOA appears to result from a well-mixed type of aerosol that is linked to fast photochemical processes and the oxidation of primary traffic and biogenic emissions. Finally, LV-OOA presents a more regional character in summer, owing to the oxidation of OA over the period of a few days.</p

CRISPR-enhanced human adipocyte \u27browning\u27 as cell therapy for metabolic disease [preprint]

Obesity and type 2 diabetes (T2D) are associated with poor tissue responses to insulin [1,2], disturbances in glucose and lipid fluxes [3-5] and comorbidities including steatohepatitis [6] and cardiovascular disease [7,8]. Despite extensive efforts at prevention and treatment [9,10], diabetes afflicts over 400 million people worldwide [11]. Whole body metabolism is regulated by adipose tissue depots [12-14], which include both lipid-storing white adipocytes and less abundant \u27brown\u27 and \u27brite/beige\u27 adipocytes that express thermogenic uncoupling protein UCP1 and secrete factors favorable to metabolic health [15-18]. Application of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing [19,20] to enhance \u27browning\u27 of white adipose tissue is an attractive therapeutic approach to T2D. However, the problems of cell-selective delivery, immunogenicity of CRISPR reagents and long term stability of the modified adipocytes are formidable. To overcome these issues, we developed methods that deliver complexes of SpyCas9 protein and sgRNA ex vivo to disrupt the thermogenesis suppressor gene NRIP1 [21,22] with near 100% efficiency in human or mouse adipocytes. NRIP1 gene disruption at discrete loci strongly ablated NRIP1 protein and upregulated expression of UCP1 and beneficial secreted factors, while residual Cas9 protein and sgRNA were rapidly degraded. Implantation of the CRISPR-enhanced human or mouse brown-like adipocytes into high fat diet fed mice decreased adiposity and liver triglycerides while enhancing glucose tolerance compared to mice implanted with unmodified adipocytes. These findings advance a therapeutic strategy to improve metabolic homeostasis through CRISPR-based genetic modification of human adipocytes without exposure of the recipient to immunogenic Cas9 or delivery vectors

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study

© 2022 The Authors. Published by Taylor & Francis. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1080/16078454.2022.2082725Objectives There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. Methods The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2–5) and high grade (≥G3) infections. Results In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2–8), 23.4% of patients experienced ≥1 any grade (G2–5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16–75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response (<PR) (p = 0.048) are independent predictors of ≥ G3 infections. Conclusion Our study described initial results of infection burden during IsaPomDex treatment. We recommend close monitoring particularly in elderly patients with co-morbidities, the effective use of an-infective prophylaxis, as well as optimal vaccination strategies, to limit infections

Post-Doc Talks

Moderator: Dr. Mary Ellen Lane, Dean, Graduate School of Biomedical Sciences and Professor, Neurobiology Presenters: Sneha Shah, Program in Molecular Medicine (Joel Richter lab): “FMRP loss alters the epigenetic landscape and alternative splicing of mRNAs in Fragile X Syndrome” Emmanouela Tsagkaraki, Program in Molecular Medicine (Mike Czech lab): “CRISPR RNP-enhanced adipocyte \u27browning\u27 as cell therapy for metabolic disease” Khursheed Wani, Laboratory of Comparative Immunology (Javier Irazoqui lab): “NHR-49/PAARα and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase

Is In-Vivo laparoscopic simulation learning a step forward in the Undergraduate Surgical Education?

Background Essentials Skills in the Management of Surgical Cases – ESMSC is an International Combined Applied Surgical Science and Wet Lab course addressed at the Undergraduate level. Laparoscopic Skills is a fundamental element of Surgical Education and various Simulation-Based Learning (SBL) models have been endorsed. This study aims to explore if there is any significant difference in delegates&apos; performance depending on whether they completed In Vivo module prior to the equivalent in the laparoscopic simulator. Materials and methods 37 Medical Students from various EU countries were divided in 2 groups, and both completed the “Fundamentals in Laparoscopic Surgery” module in the Dry-lab Laparoscopic Simulator as well as the same module “In Vivo” on a swine model. Group A (18 students, 48.6%) completed the “Fundamentals in Laparoscopic Surgery - FLS” module prior to the “In Vivo”, whereas group B completed the “In Vivo” module first. Direct Observation of Procedural Skills (DOPS) were used to assess delegates&apos; performance. Results The mean DOPS scores for the “FLS” and “In Vivo” models were 2.27 ± 0.902 and 2.03 ± 0.833, respectively, and the delegates&apos; performance was not statistically significantly different between them (p = 0.128). There was no statistically significant difference in the scores among different gender, year of study, school and handedness groups. The alteration in the sequence between Dry-lab “FLS” and “In Vivo” modules did not affect the performance in neither the “FLS” nor the “In Vivo” models. Conclusions The inexpensive, but low-fidelity “FLS” model could serve an equal alternative Simulation-Based Learning model for the early undergraduate training. Our study demonstrated that high fidelity In Vivo simulation for laparoscopic skills does not affect significantly the improvement in the delegates&apos; performance at the undergraduate level. Further studies should be conducted to identify at which stage of training should high fidelity simulation be introduced. © 2017 The Author

The Role of Anxiety in Simulation-Based Dexterity and Overall Performance: Does It Really Matter?

Background: Essential Skills in the Management of Surgical Cases (ESMSC) is an international undergraduate surgical masterclass which combines ex vivo, dry lab and high fidelity in vivo simulation-based learning (SBL). It consists of 32 stations of skills-based learning, including open reduction internal fixation (ORIF) of fractures. Current literature suggests early involvement in skills-based learning at the undergraduate level is vital. Aims: To compare students&apos; dexterity and skills-based performance with demographic and educational background parameters. Methods: 112 medical students from European Union countries including the United Kingdom, Germany, Greece, Cyprus, Germany, and Bulgaria were selected from a competitive pool of candidates to attend the course. Students undertook ORIF in an ex vivo swine model, and in a simulated fracture on a bamboo rod. Skills-based performance was assessed by two consultant surgeons with validated direct observation of procedural skills (DOPS) forms. Anxiety was self-assessed using the Westside Anxiety Scale prior to the ORIF stations. Dexterity was measured with the O&apos;Connor tweezer dexterity test. Results: Female students had significantly higher dexterity scores (median difference 7, p =.003). Right-handed students achieved higher dexterity than left-handed students (median difference 7, p =.043). There was no difference in students&apos; performance across different medical schools, and across year groups (p &lt;.05 for any correlation). Self-reported anxiety was not correlated with high fidelity skills-based performance (r = 0.032, p =.74). Conclusion: Anxiety does not seem to play a significant role in Simulation Skills-Based learning. Undergraduate surgical curricula should incorporate SBL-based modules to enhance practical skills learning and motivate future orthopedic surgeons. © 2017, Copyright © 2017 Taylor &amp; Francis Group, LLC

Introducing In Vivo Dissection Modules for Undergraduate Level Trainees: What Is the Actual Benefit and How Could We Make It More Efficient?

Essential Skills in the Management of Surgical Cases (ESMSC) is an international wet lab simulation course aimed at undergraduate students. It combines basic science workshops, case-based lectures and ex vivo skills modules, as well as in vivo dissections using a swine model. This study aims to evaluate the effectiveness of high-fidelity In Vivo Simulation-Based Learning for undergraduate level trainees. Also our goal was to compare the skill-based performance of final year students vs. more junior-level ones. Forty undergraduate delegates at clinical rotation level (male = 28, female = 12, mean age = 23.12, 22–24, SD = 0.69) attended this 2-day course in Athens. N = 1 (2.5 %) was year 3, N = 4 (10 %) were year 4, N = 23 (57.5 %) were year 5 and N = 12 (30 %) were year 6. N = 30 (75 %) came from Hellenic universities, N = 8 (20 %) from the UK and N = 2 (5 %) from Germany. N = 20 (50 %) attended the in vivo dissections module first, and then the ex vivo one (type A rotation), whereas N = 20 followed the reverse training sequence with the ex vivo dissection first, followed by the in vivo one (type B rotation). The mean global rating scores for type A rotation were better in both the in vivo by 0.10 (2.40 vs. 2.30) and ex vivo modules by 0.15 (2.85 vs. 2.70), though it did not reach statistical significance (p &gt; 0.05). Furthermore, the mean improvement of performance, in the laparoscopic skills station for the type A rotation, was better compared to type B by 0.351 (2.00 vs. 1.65, p = 0.003). Year 6 students performed better in the laparoscopic station (2.00 vs. 1.75, p = 0.059), whereas years 3, 4 and 5 performed better in the in vivo (2.42 vs. 2.16, p = 0.157) as well as the ex vivo dissections (2.78 vs. 2.75, p = 0.832), though none of those comparisons reached statistical significance. Delegates seemed to appreciate and enjoy the in vivo dissections as reflected in the feedback (8.67/10, min = 6 and max = 10, SD = 1.79). Although medical students seem to appreciate in vivo dissections modules, currently, further evidence is needed to support their recommendation in the undergraduate level. Surgical skills should be part of the undergraduate curriculum to improve final year students’ performance in the theatre. © 2016, Association of Surgeons of India