Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks.

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.

Comparative Anti-Platelet Profiling Reveals a Potent Anti-Aggregatory Effect of CD34+ Progenitor Cell-Derived Late-Outgrowth Endothelial Cells in vitro.

BACKGROUND/AIMS: Platelets affect endothelial progenitor cell (EPC) functionality, inducing their differentiation into mature endothelial cells. However, it remains to be established whether EPCs can influence platelet functionality. METHODS: Mononuclear proangiogenic cells (MPCs) and early outgrowth cells (EOCs) were prepared from peripheral blood mononuclear cells, whereas late-outgrowth endothelial cells (OECs) were prepared from cord blood CD34+ cells. The effect of the above cells and their supernatants on washed platelet aggregation was studied. The effect of OECs and their supernatant on the adenosine diphosphate (ADP)-induced magnitude of platelet integrin receptor αIIbß3 activation and on P-selectin membrane expression was investigated. The levels of nitric oxide (NO) and prostacyclin (PGI2) that were secreted from EOCs, OECs, and human umbilical vein endothelial cells (HUVECs) were also assessed. RESULTS: Among all progenitors, OECs and their supernatant exhibited the most potent inhibitory activity towards platelet aggregation. Furthermore, OECs and their supernatant, but not CD34+ cells, reduced αIIbß3 activation and P-selectin membrane expression. Finally, OECs secreted higher NO and PGI2 levels than EOCs did. CONCLUSION: The anti-platelet effect of EPCs depends highly on the degree of their endothelial phenotype, with OECs expressing the highest potency. Therefore, the induction of OEC generation and the enhancement of their functionality in vivo could be a new approach for the treatment of patients at a high thrombotic risk.

Autoimmune pancreatitis versus pancreatic cancer: a comprehensive review with emphasis on differential diagnosis.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis with a discrete pathophysiology, occasional diagnostic radiological findings, and characteristic histological features. Its etiology and pathogenesis are still under investigation, especially during the last decade. Another aspect of interest is the attempt to establish specific criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer, entities that are frequently indistinguishable. DATA SOURCES: An extensive search of the PubMed database was performed with emphasis on articles about the differential diagnosis between autoimmune pancreatitis and pancreatic cancer up to the present. RESULTS: The most interesting outcome of recent research is the theory that autoimmune pancreatitis and its various extra-pancreatic manifestations represent a systemic fibro-inflammatory process called IgG4-related systemic disease. The diagnostic criteria proposed by the Japanese Pancreatic Society, the more expanded HISORt criteria, the new definitions of histological types, and the new guidelines of the International Association of Pancreatology help to establish the diagnosis of the disease types. CONCLUSION: The valuable help of the proposed criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer may lead to avoidance of pointless surgical treatments and increased patient morbidity.

The Effect of Platelet-Rich Plasma on Endothelial Progenitor Cell Functionality.

Platelets mediate circulating endothelial progenitor cell (EPC) recruitment and maturation, participating in vascular repair, however the underlying mechanism(s) remain unclear. We investigated the effect of platelet-rich plasma (PRP) on the functionality of CD34+-derived late-outgrowth endothelial cells (OECs) in culture. Confluent OECs were coincubated with PRP under platelet aggregation (with adenosine diphosphate; ADP) and nonaggregation conditions, in the presence/absence of the reversible P2Y12 platelet receptor antagonist ticagrelor. Outgrowth endothelial cell activation was evaluated by determining prostacyclin (PGI2) and monocyte chemoattractant protein-1 (MCP-1) release and intercellular adhesion molecule-1 (ICAM-1) membrane expression. Similar experiments were performed using human umbilical vein endothelial cells (HUVECs). Platelet-rich plasma increased ICAM-1 expression and PGI2 and MCP-1 secretion compared with autologous platelet-poor plasma, whereas ADP-aggregated platelets in PRP did not exhibit any effect. Platelet-rich plasma pretreated with ticagrelor prior to activation with ADP increased all markers to a similar extent as PRP. Similar results were obtained using HUVECs. In conclusion, PRP induces OEC activation, a phenomenon not observed when platelets are aggregated with ADP. Platelet inhibition with ticagrelor restores the PRP capability to activate OECs. Since EPC activation is important for endothelial regeneration and angiogenesis, we suggest that agents inhibiting platelet aggregation, such as ticagrelor, may promote platelet-EPC interaction and EPC function.

Alopecia associated with birth injury.

BACKGROUND: Alopecia after birth-related caput succedaneum is an extremely rare complication. CASE: The case of a child with permanent alopecia due to birth-related caput succedaneum is presented. After delivery with vacuum extraction, caput succedaneum at the left occipitoparietal region of the neonate's head was noted, which subsided within a week, leaving a circular necrotic crust and finally a circular bald area. At age 4, the child was referred at a tertiary center for the management of alopecia. Treatment initially consisted of the expansion of the hair-bearing skin adjacent to the bald area, which was excised at a second stage and covered with the expanded skin. A pleasing esthetic result was achieved. CONCLUSION: Neonatal alopecia is a rare birth-associated complication. Premature rupture of the membranes, prolonged second stage of the labor, and prolonged vacuum extraction time may be important features in the pathogenesis of this complication. In case of permanent alopecia, excellent esthetic results can be achieved with the use of reconstructive plastic surgery techniques.

Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease.

BACKGROUND: Minimising placebo response is essential for drug development. AIM: To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates. RESULTS: In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics. CONCLUSIONS: Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.

A severe case of xanthogranulomatous cholecystitis along with a review of CT indications for nonoperative management including percutaneous drainage.

BACKGROUND: Xanthogranulomatous cholecystitis is a rare but severe presentation of cholecystitis characterized by extensive inflammation of the gallbladder wall with characteristic histopathological features. Frequently, the inflammatory mass resembles gallbladder cancer macroscopically, which further complicates therapeutic decisions. CASE PRESENTATION: We report a case of xathogranulomatous cholecystitis with characteristic computed tomography findings, which was managed by percutaneous drainage of the gallbladder, giving the opportunity for a delayed elective cholocystectomy with an excellent postoperative outcome. DISCUSSION: Recent studies give emphasis on certain criteria for the differential diagnosis of xanthogranulomatous cholecystitis against carcinoma. Characteristic computed tomography features are usually sufficient to establish the diagnosis with safety and decide a nonoperative management of the disease in the acute phase. Percutaneous gallbladder drainage is regarded as a safe and an efficient method for the initial treatment of severe cases.