Metabolic theories of Whipple disease

Whipple disease is a rare, infectious, disease first described from a single case by Whipple in 1907. As well as characterising the clinical and pathological features of the condition, Whipple made two suggestions regarding its aetiology. These were either than the disease was caused by an infectious agent, or that it was of metabolic origin. As the disease is now thought to be caused by infection with the bacterium Tropheryma whipplei, historical reviews of the history of the disease typically mention only the first of these suggestions. In this paper, we therefore revisit Whipple’s other theory. We argue that a diverse and often successful research programme was developed around this mechanism of disease causation which gave rise to many useful findings on the condition. In the later parts of this article, we then turn to discuss the surprising neglect of this period of Whipple disease research in the current literature, and conclude by offering a brief reconstruction of this early history suitable for use in a technical context

072 Five-year outcome of patients with bifurcation lesions treated with provisional side branch T-stenting using drug-eluting stents

BackgroundCoronary bifurcation lesions remain a challenge, as lower success rates and higher reintervention rates persist in this lesion subset. The ideal strategy to treat such lesions is still debated and data regarding long-term efficacy and safety of drug-eluting stents in this setting are sparse.ObjectivesWe sought to determine the long-term efficacy and safety of a provisional side branch T-stenting (PTS) strategy for bifurcation lesions in an unselected population.Methods477 consecutive Pts were treated for bifurcation lesions with DES (Paclitaxel or Sirolimus-eluting stents) between 2003 and 2005. Data were entered prospectively into a single-center registry. The PTS strategy was employed in 92%, with a side-branch stent in 28% and final kissing balloon inflation in 95%. Five-year follow-up, at a median of 61 months, is available for 93.5% of patients.ResultsAngiographic success was achieved in 99%, with 2.5% in-hospital major adverse cardiac events (MACE, defined as any cardiac death, early reintervention, Q – or non-Q-wave MI or target vessel revascularisation). The cumulative rate of MACE was 10.7% at 1 year, 13.6% at 2 years and 19.7% at 5 years, including target vessel revascularisation rates of 6.9%, 8.9% and 13%, and cardiac death rates of 3%, 3.7% and 6.7%, respectively. Ischaemia-driven target lesion revascularisation at 5 years is 7.3%. The cumulative rate of definite or probable stent thrombosis at long-term is 3.1%, most cases occurring within the first year (2.5%). The need for reintervention in the long-term was not predicted by any procedural variable, and not significantly related to the use of 1 or 2 stents or to the type of stent deployed.ConclusionsA PTS strategy with first generation drug-eluting stents, was applicable to over 90% of real-world patients with bifurcation lesions with a target lesion revascularisation < 10% at 5 years. The rate of very-late stent thrombosis in this complex lesion subset remains low

Manejo de pacientes con trauma craneoencefálico en el servicio de emergencia del Hospital Regional Escuela Ernesto Sequeira Blanco en el 2018

El presente estudio sobre trauma Cráneo encefálico tiene como objetivo valorar el manejo adecuado inicial bajo conocimientos validados, siendo este fundamental, para disminuir la morbimortalidad de esta entidad, pero: ¿Cuál es el manejo que se aplica en el Hospital Regional Ernesto Sequeira Blanco? La respuesta a esta incógnita se encuentra en el trabajo presente donde se realizó revisión de casos con un total de 50 Pacientes, entre los resultados significativos abarcan revisión primaria en un cumplimiento de un 50 % del total de casos, necesidad de mejorar calidad de la revisión secundaria ejecutándose un examen físico completo apenas en un 64%, estandarizar implementación de métodos complementarios realizándose en menos del 50 % los estudios pertinentes y limitaciones en el manejo farmacológico con uso excesivo de corticoides y antibióticos en un 30 y 34 % respectivamente

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

The predictive value of the high school grade point average and a select group of standardized tests for junior college achievement

The purpose of this investigation was to evaluate the high school grade point average and a select group of standardized tests, administered on both the high school and junior college levels, to ascertain their usefulness in predicting academic achievement in a specified group of courses taken on the junior college level; and to determine if a combination of tests and the high school grade point average would yield higher predictive validities than the high school grade point average alone.Education, College o

Altered sensory innervation and pain hypersensitivity in a model of young painful arthritic joints: short- and long-term effects

Abstract Background Early life experience can cause long-term alterations in the nociceptive processes underlying chronic pain, but the consequences of early life arthritic joint inflammation upon the sensory innervation of the joint is not known. Here, we measure pain sensitivity and sensory innervation in a young, juvenile and adult rodent model of arthritic joints and test the consequences of joint inflammation in young animals upon adult arthritic pain and joint innervation. Methods Unilateral ankle joint injections of complete Freund’s adjuvant (CFA) (6−20 µl) were performed in young, postnatal day (P)8, adolescent (P21) and adult (P40) rats. A separate cohort of animals were injected at P8, and again at P40. Hindpaw mechanical sensitivity was assessed using von Frey monofilaments (vF) for 10 days. Nerve fibres were counted in sections through the ankle joint immunostained for calcitonin gene-related peptide (CGRP) and neurofilament 200 kDa (NF200). Results Ankle joint CFA injection increased capsular width at all ages. Significant mechanical pain hypersensitivity and increased number of joint CGRP + ve sensory fibres occurred in adolescent and adult, but not young, rats. Despite the lack of acute reaction, joint inflammation at a young age resulted in significantly increased pain hypersensitivity and CGRP+ fibre counts when the rats were re-inflamed as adults. Conclusions Joint inflammation increases the sensory nociceptive innervation and induces acute pain hypersensitivity in juvenile and adult, but not in young rats. However, early life joint inflammation ‘primes’ the joint such that adult inflammatory pain behaviour and nociceptive nerve endings in the joint are significantly increased. Early life joint inflammation may be an important factor in the generation and maintenance of chronic arthritic pain. </jats:sec