INFLA-score: A new diagnostic paradigm to identify pericarditis.

BACKGROUND: Diagnosis of pericarditis may be challenging because not all patients meet the conventional criteria. An overlooked diagnosis implies a longer course of symptoms and an increased risk of recurrences. C-reactive protein (CRP), widely used as an inflammation marker, has some limitations. This study aimed to assess the usefulness and prognostic value of INFLA-score, a validated index assessing low-grade inflammation, in the definite diagnosis of pericarditis. METHODS: Patients with suspected pericarditis were included. The INFLA-score was computed based on white blood cells and platelet count, neutrophil-to-lymphocyte ratio, and CRP, ranging from -16 to +16. An INFLA-score > 0 was considered positive for the presence of pericardial inflammation. The primary end point was the association of INFLA-score with diagnosis of pericarditis according to conventional criteria. The recurrence of pericarditis at 6 months was the secondary end point. RESULTS: A total of 202 patients were included, aged 47 ± 17 years, and 57% were females. Among 72 (36%) patients with a diagnosis of pericarditis, an INFLA-score > 0 was observed in 86% (vs. 36%, p < 0.001), abnormal CRP in 42% (vs. 10%, p < 0.001), pericardial effusion in 44% (vs. 19%, p < 0.001), abnormal electrocardiogram in 56% (vs. 24%, p < 0.001), and rubs in 5% (vs. 0.1%, p = 0.072). INFLA-score > 0 had the strongest predictive value for the diagnosis of pericarditis (hazard ratio 8.48, 95% confidence interval [CI] 3.39-21.21), with 86% sensitivity and 64% specificity, as opposed to CRP (hazard ratio 1.72, non-significant 95% CI 0.69-4.29). Recurrent pericarditis at 6 months was more frequent in patients with a positive INFLA-score (37% vs. 8%, p < 0.001, rate ratio 4.15, 95% CI 2.81-6.12). In patients with normal CRP, INFLA-score-confirmed ongoing inflammation in 78% of the cases. Compared with the conventional criteria, the INFLA-score had the highest accuracy (area under the curve = 0.82). Different cutoffs were valuable to rule out (INFLA-score > 0, sensitivity 86%, and negative likelihood ratio 0.22) or rule in (INFLA-score ≥ 10, specificity 97%, and positive likelihood ratio 13) the diagnosis. CONCLUSIONS: The INFLA-score is a useful diagnostic tool to assess the probability of pericarditis, with a strong prognostic value for further recurrences, outperforming CRP.

Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND AND AIMS: Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia. METHODS: PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867). RESULTS: Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy. CONCLUSIONS: The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.

Severe gastrointestinal injury associated with SARS-CoV-2 infection: Thrombosis or Inflammation?: A retrospective case series study.

OBJECTIVES: Acute gastrointestinal injury (AGI) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a low incidence of complications in patients admitted to the intensive care unit (ICU). Pathophysiological knowledge related to AGI is limited, as few studies have been published on this topic. Therefore, this study was carried out to identify the clinical and histopathological features of patients with SARS-CoV-2 infection and grade IV AGI. METHODS: This is a retrospective case study of fifteen patients with SARS-CoV-2 infection and grade IV AGI who underwent emergency surgery. RESULTS: This study revealed a mortality rate of 62.5%. The most frequent gastrointestinal symptoms were abdominal distension (100%) and increased gastric residual volume (93.3%). Distended bowel loops on plain abdominal radiography (90%) and intestinal pneumatosis on computed tomography (50%) were the most frequent imaging findings. Surgical exploration revealed intestinal ischemia (66.6%) and necrosis (46.6%), and histopathology showed ischemic and liquefactive necrosis with mixed inflammatory involvement and absence of thrombosis as the cause of AGI. CONCLUSIONS: AGI associated with severe SARS-CoV-2 infection has a high mortality rate and poses a diagnostic challenge in the ICU. The complex pathophysiology and histopathological findings indicate an associated inflammatory phenomenon as the main alteration in the absence of thrombosis, as per the intestinal biopsies of the cases studied. Further clinical studies are required to gain a better understanding of this pathology.

Genome of a novel Sediminibacterium discovered in association with two species of freshwater cyanobacteria from streams in Southern California.

Here, we report the discovery of a novel Sediminibacterium sequenced from laboratory cultures of freshwater stream cyanobacteria from sites in Southern California, grown in BG11 medium. Our genome-wide analyses reveal a highly contiguous and complete genome (97% BUSCO) that is placed within sediminibacterial clades in phylogenomic analyses. Functional annotation indicates the presence of genes that could be involved in mutualistic/commensal relationship with associated cyanobacterial hosts.

Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS.

Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin's endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system.

Clinical practice guidelines for the management of community-acquired pneumonia: A critical appraisal using the AGREE II instrument.

OBJECTIVE: The aim of this study was to appraise the methodological quality of published clinical practice guidelines (CPGs) of community-acquired pneumonia (CAP) using AGREE II instrument for further enhancing the CAP CPG development. METHODS: We performed a systematic review of published CPGs on CAP from January 2007 to May 2019. All reviewers independently assessed each CPG using the AGREE II instrument. A standardised score was calculated for each of the six domains. RESULTS: Our search strategy identified 4125 citations but just 18 met our inclusion criteria. Agreement among reviewers was very good: 0.98. The domains that scored better were: "scope and purpose" and "clarity and presentation". Those that scored worse were "editorial independence", and "applicability". According to the AGREE II evaluation for each Guideline, the NICE, IDSA, BTS, SWAB, Korea, Consensur II, Colombian and Peruvian CPGs were the only recommended with no further modifications. In addition, ERS and SEPAR CPGs were recommended with modifications, with lower scores regarding the editorial independence and applicability. CONCLUSION: In conclusion, published CPGs for CAP management vary in quality with a need to improve the methodological and applicability rigour. This could be achieved following the standards for guidelines development and a better emphasis on how to apply CPGs recommendations in clinical practice.

Spatiotemporal distribution of chondroitin sulfate proteoglycans after optic nerve injury in rodents.

The accumulation of chondroitin sulfate proteoglycans (CSPGs) in the glial scar following acute damage to the central nervous system (CNS) limits the regeneration of injured axons. Given the rich diversity of CSPG core proteins and patterns of GAG sulfation, identifying the composition of these CSPGs is essential for understanding their roles in injury and repair. Differential expression of core proteins and sulfation patterns have been characterized in the brain and spinal cord of mice and rats, but a comprehensive study of these changes following optic nerve injury has not yet been performed. Here, we show that the composition of CSPGs in the optic nerve and retina following optic nerve crush (ONC) in mice and rats exhibits an increase in aggrecan, brevican, phosphacan, neurocan and versican, similar to changes following spinal cord injury. We also observe an increase in inhibitory 4-sulfated (4S) GAG chains, which suggests that the persistence of CSPGs in the glial scar opposes the growth of CNS axons, thereby contributing to the failure of regeneration and recovery of function.

Usefulness of sputum gram stain for etiologic diagnosis in community-acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: Implementation of sputum Gram stain in the initial assessment of community-acquired pneumonia (CAP) patients is still controversial. We performed a systematic review and meta-analysis to investigate the usefulness of sputum Gram stain for defining the etiologic diagnosis of CAP in adult patients. METHODS: We systematically searched the Medline, Embase, Science Direct, Scopus and LILACS databases for full-text articles. Relevant studies were reviewed by at least three investigators who extracted the data, pooled them using a random effects model, and carried out quality assessment. For each bacterium (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Gram-negative bacilli), pooled sensitivity, specificity, positive and negative likelihood ratios were reported. RESULTS: After a review of 3539 abstracts, 20 articles were included in the present meta-analysis. The studies included yielded 5619 patients with CAP. Pooled sensitivity and pooled specificity of sputum Gram stain were 0.59 (95% CI, 0.56-0.62) and 0.87 (95% CI, 0.86-0.89) respectively for S. pneumoniae, 0.78 (95% CI, 0.72-0.84) and 0.96 (95% CI, 0.94-0.97) for H. influenzae, 0.72 (95% CI, 0.53-0.87) and 0.97 (95% CI, 0.95-0.99) for S. aureus, and 0.64 (95% CI, 0.49-0.77) and 0.99 (95% CI, 0.97-0.99) for Gram-negative bacilli. CONCLUSION: Sputum Gram stain test is sensitive and highly specific for identifying the main causative pathogens in adult patients with CAP. TRIAL REGISTRATION: This study has been registered at PROSPERO International prospective register of systematic reviews under registration no. CRD42015015337 .