External validation of a modified model of Acute Physiology and Chronic Health Evaluation (APACHE) II for orthotopic liver transplant patients

INTRODUCTION: The purpose of the study was to validate the newly derived postoperative orthotopic liver transplantation (OLTX)-specific diagnostic weight for the Acute Physiology and Chronic Health Evaluation (APACHE) II mortality prediction system in independent databases. METHODS: Medical records of 174 liver transplantation patients admitted postoperatively to the adult intensive care units at King Fahad National Guard Hospital and the University of Wisconsin were reviewed, and data on age, sex, the underlying liver disease, APACHE II scores and the hospital outcome were collected. Predicted mortality was calculated using: 1) the original APACHE II diagnostic weight of postoperative other gastrointestinal surgery and 2) the newly derived OLTX-specific diagnostic category weight. Standardized mortality ratio and 95% confidence intervals were calculated. Calibration was evaluated with the Hosmer–Lemeshow goodness-of-fit C-statistic. Discrimination was tested by 2 × 2 classification matrices and by computing the areas under the receiver operating characteristic curves. Patient characteristics and outcome data were compared between the two hospitals. RESULTS: APACHE II significantly overestimated mortality when the original diagnostic weight was used, but provided a closer estimate of mortality with the OTLX-specific diagnostic weight. The C-statistic analysis showed better calibration for the new approach; discrimination was also improved. The performances of the prediction systems were similar in the two hospitals. The new model provided more accurate estimates of hospital mortality in each hospital. DISCUSSION: APACHE II provided an accurate estimate of mortality in liver transplant patients when the OLTX-specific diagnostic weight was used. With the new model, APACHE II can be used as a valid mortality prediction system in this group of patients

Prevalence of Bleeding Symptoms among Adolescents and Young Adults in the Capital City of Saudi Arabia

Background. Bleeding disorders vary in prevalence. While some are rare, some can be common in both sexes. Most bleeding disorders manifest as chronic bleeding tendencies or as an increase in bleeding during surgical procedures or trauma. The consequences of bleeding can be as simple as iron deficiency or catastrophic, resulting in severe morbidity and mortality. Bleeding disorders typically affect both sexes except hemophilia A and B, which mainly affects males. Method. We conducted a questionnaire-based survey among adolescents and young adults (1901 [49%] boys, 1980 [51%] girls) in Riyadh city regarding bleeding symptoms. Of these, 1849 (47.6%) responded “Yes/Positive” for at least one question about the bleeding symptoms. Results. The most common bleeding symptom was epistaxis (19.7% of the sample population) detected in Phase I of the study. A tandem survey was conducted among 525 adolescents who had responded “Yes/Positive” to any one of the questions inquiring about bleeding symptoms. Conclusion. In this study, we report for the first time the prevalence of bleeding symptoms in a representative sample of Saudi adolescents and young adults

Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population