Extensive Cervico-Thoraco-Abdominal Attacks of Angioedema: CT Diagnosis in Two Unusual Cases

Angioedema (AE) classically manifests as an acute transient swelling of extra-visceral spaces, subcutaneous and submucosal tissues. Sometimes it may be a life-threatening condition. The causes are numerous, and the common denominator is an increased vascular permeability allowing diffusion or extravasation of fluid from the vascular bed to the interstitial space. The severity of AE is related to the cause, body location, and extension. We hereby report two very unusual cases characterized by a massive attack of AE from the left cervical area to the pelvis through the length of the mediastinum and axial posterior retroperitoneum. The diagnosis was established by CT. The first case was found related to drug intake, and the second appeared idiopathic

SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodiumfalciparum

Over the last decade, several protein kinases inhibitors have reached the market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. The functions of the majority of protein kinases of Plasmodium falciparum, the parasitic protist responsible for the most virulent form of human malaria, remain unknown. Here we present a thorough characterisation of PfTKL3 (PF13_0258), an enzyme that belongs to the tyrosine kinase-like kinase (TKL) group. We demonstrate by reverse genetics that PfTKL3 is essential for asexual parasite proliferation in human erythrocytes. PfTKL3 is expressed in both asexual and gametocytes stages, and in the latter the protein co-localises with cytoskeleton microtubules. Recombinant PfTKL3 displays in vitro autophosphorylation activity and is able to phosphorylate exogenous substrates, and both activities are dramatically dependent on the presence of an N-terminal “sterile α-motif” domain. This study identifies PfTKL3 as a validated drug target amenable to high-throughput screening

Comparative Genomics of the Odorant-Binding and Chemosensory Protein Gene Families across the Arthropoda: Origin and Evolutionary History of the Chemosensory System

Chemoreception is a biological process essential for the survival of animals, as it allows the recognition of important volatile cues for the detection of food, egg-laying substrates, mates, or predators, among other purposes. Furthermore, its role in pheromone detection may contribute to evolutionary processes, such as reproductive isolation and speciation. This key role in several vital biological processes makes chemoreception a particularly interesting system for studying the role of natural selection in molecular adaptation. Two major gene families are involved in the perireceptor events of the chemosensory system: the odorant-binding protein (OBP) and chemosensory protein (CSP) families. Here, we have conducted an exhaustive comparative genomic analysis of these gene families in 20 Arthropoda species. We show that the evolution of the OBP and CSP gene families is highly dynamic, with a high number of gains and losses of genes, pseudogenes, and independent origins of subfamilies. Taken together, our data clearly support the birth-and-death model for the evolution of these gene families with an overall high gene turnover rate. Moreover, we show that the genome organization of the two families is significantly more clustered than expected by chance and, more important, that this pattern appears to be actively maintained across the Drosophila phylogeny. Finally, we suggest the homologous nature of the OBP and CSP gene families, dating back their most recent common ancestor after the terrestrialization of Arthropoda (380--450 Ma) and we propose a scenario for the origin and diversification of these families

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Case report: Ectopic ACTH secretion due to a metastatic atypical lung carcinoid tumor. From diagnosis to treatment.

A 71-year-old woman was admitted in our department for asthenia and biological and clinical suspicion of Cushing Syndrome (CS). She had a remarkable history as she suffered from post-vaccinal poliomyelitis at the age of three with residual paresis of her left arm and leg. She never smoked or drank alcohol. Since one month, she complained of progressive asthenia and edema (especially of the face), centripetal obesity, severe proximal muscle weakness and spontaneous ecchymosis. Depressive symptoms were reported by her relatives. She denied taking exogenous steroids. [...

Complete Remission in a TEMPI Syndrome Treated with a Daratumumab, Lenalidomide, and Dexamethasone-Based Regimen: A Case Report

Introduction: TEMPI syndrome is a rare and acquired condition which is characterized by five classical features: telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. The classical treatment is based on bortezomib which can achieve variable responses. Relapse or refractory disease may occur, so other treatment strategies can be proposed. Case Presentation: We describe the case of a 54-year-old male followed for a refractory TEMPI syndrome who achieved complete remission after a second-line therapy composed of daratumumab-, lenalidomide-, and dexamethasone-based regimen (DLd). He achieved a complete remission with dramatic improvement of his renal function, restitution of a normal blood oxygen, and disappearance of polycythemia. Conclusion: This case highlights the effectiveness of an association of DLd to treat refractory TEMPI syndrome. We also provide arguments for an association between TEMPI syndrome and monoclonal gammopathy of renal significance

Complete Remission in a TEMPI Syndrome Treated with a Daratumumab, Lenalidomide, and Dexamethasone-Based Regimen: A Case Report.

TEMPI syndrome is a rare and acquired condition which is characterized by five classical features: telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. The classical treatment is based on bortezomib which can achieve variable responses. Relapse or refractory disease may occur, so other treatment strategies can be proposed. We describe the case of a 54-year-old male followed for a refractory TEMPI syndrome who achieved complete remission after a second-line therapy composed of daratumumab-, lenalidomide-, and dexamethasone-based regimen (DLd). He achieved a complete remission with dramatic improvement of his renal function, restitution of a normal blood oxygen, and disappearance of polycythemia. This case highlights the effectiveness of an association of DLd to treat refractory TEMPI syndrome. We also provide arguments for an association between TEMPI syndrome and monoclonal gammopathy of renal significance