Role of NLRP3 inflammasome in diabetes and COVID-19 role of NLRP3 inflammasome in the pathogenesis and treatment of COVID-19 and diabetes NLRP3 inflammasome in diabetes and COVID-19 intervention.

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A "cytokine storm", i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients.

Diagnostic ambiguity of aseptic necrobiosis of a uterine fibroid in a term pregnancy: a case report.

BACKGROUND: Uterine fibroids are the most common uterine tumours in females of reproductive age. During pregnancy, uterine fibroids may be complicated by aseptic necrobiosis. We herein report an ambiguous clinical presentation of uterine fibroids in pregnancy and discuss the diagnostic challenges encountered in our resource-constraint setting. CASE PRESENTATION: A term pregnant Cameroonian woman was admitted to our maternity unit with clinical findings suggestive of a strangulated umbilical hernia. She underwent an emergency caesarean section which fortuitously revealed aseptic necrobiosis of a uterine fibroid, managed within the same surgical intervention by myomectomy. Her post-operative course was uneventful. CONCLUSION: The authors highlight the need for a high index of suspicion by healthcare providers, as well as the need for a multidisciplinary approach for a favourable maternal and foetal outcome.

Necrotizing meningoencephalitis caused by Sarcocystis falcatula in bare-faced ibis (Phimosus infuscatus).

The infection by S. falcatula is commonly associated with respiratory disease in captive psittacine birds, with a few case reports of this protozoan causing encephalitis in wild birds. We describe the clinical, pathological, and molecular aspects of an infection by S. falcatula in a bare-faced ibis (Phimosus infuscatus). Clinically, wing paralysis and mild motor incoordination were observed. At necropsy, the telencephalic cortex showed multifocal to coalescing yellowish soft areas. Histologically, multifocal to coalescent nonsuppurative necrotizing meningoencephalitis of telencephalic cortex, cerebellum, and brainstem was observed. Necrotic areas showed multiple protozoan organism characteristics of Sarcocystis sp. schizonts in the cytoplasm of endothelial cells or lying free in the neuropil. Partial genetic sequences of the gene encoding cytochrome b (CYTB), the gene encoding the beta subunit of RNA polymerase (RPOB) and the first internal transcribed spacer (ITS-1) from Sarcocystis sp. schizonts revealed that the parasite had ITS-1 sequences that were 100% identical to the homologous alleles from Sarcocystis sp. shed by Didelphis albiventris in Brazil. RPOB and CYTB sequences were 100% identical to homologous of S. falcatula available in Genbank. Thus, this is the first report of necrotizing meningoencephalitis caused by S. falcatula in bare-faced ibis (P. infuscatus).

[Cutaneous granulomatosis]. / Granulomatoses cutanées.

Granulomatous skin diseases represent a large group of reactive dermatoses occurring in response to different stimuli and whose skin biopsy is characterized by a granulomatous inflammatory infiltrate. By their very heterogeneous clinical presentation, it seems difficult to distinguish them and make their diagnosis. Clinically, it may be useful to separate localized forms of disseminated forms of cutaneous granulomatosis, although this distinction is often artificial. We will discuss here the main forms of localized and disseminated cutaneous granulomatosis, and, in light of recent literature data, mention different therapeutic options in each case.

Cutaneous necrobiotic conditions associated with rheumatoid arthritis: important extra-articular involvement.

Rheumatoid arthritis (RA) presents with various skin conditions as extra-articular manifestations. Rheumatoid nodule is the representative specific skin lesion, histologically exhibiting central necrosis (necrobiosis) surrounded by palisaded macrophages, and being further perivascularly infiltrated with inflammatory cells in the outer regions. Also, there are several skin lesions which histologically show necrobiotic conditions with altered connective tissue degeneration. Necrobiosis may be closely associated with the pathogenesis of RA, i.e., collagen degeneration, recruitment of activated neutrophils, production of various cytokines, and vascular injury. On the other hand, rheumatoid nodule is suggested to develop during therapies with certain drugs such as methotrexate and biologics. These findings may be a clue to understanding the pathomechanisms of rheumatoid nodules. This paper describes several necrobiotic conditions associated with RA, and also discusses the possible pathogenesis and differential diagnosis of rheumatoid nodules. Necrobiosis is the major pathologic condition of cutaneous involvement associated with RA.

Palisaded neutrophilic and granulomatous dermatitis in association with subcutaneous nodular and systemic sarcoidosis.

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare entity that has been clearly defined neither clinically nor histopathologically. PNGD has been associated with some immune-mediated disorders such as rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, Behçet's disease, as well as with lymphoproliferative conditions, bacterial endocarditis, sarcoidosis, and various drugs. We present a 44-year-old Caucasian woman with roundish erythematous-livid plaque and erythematous papules on the left calf that were present for three months. Histopathology of plaque lesion showed palisading neutrophilic and granulomatous dermatitis. Subsequently, she developed a firm and tender nodule on the right calf. Histopathology of the nodule showed typical naked sarcoid granulomas in the dermis and subcutis. Additionally, the patient developed non-tender subcutaneous nodules on the cheeks, submandibular region and left breast with normal overlying skin, which were histopathologically diagnosed as sarcoid granuloma. Red eyes and lower visual acuity on the right eye were diagnosed as anterior uveitis. Therefore, systemic sarcoidosis was established. This is a case of PNGD described in an adult patient with sarcoidosis with cutaneous, breast, eye and lung involvement established by clinical, radiographic, laboratory, and histopathologic criteria.

[Role of medical treatment for symptomatic leiomyoma management in premenopausal women]. / Place des traitements médicaux : indication, durée, efficacité, chez la femme porteuse de fibromes utérins symptomatiques en période d'activité génitale.

The most frequent symptom with leiomyoma is menometrorrhagia. However, it can be responsible of pelvic pain, dysmenorrhea or urinary and digestive compression when it is particularly voluminous. These recommandations were made in order to review medical management of fibroids. If no therapy is able to have them disappear, various drugs may reduce their related symptoms. Tranexamic acid, non-steroidal anti-inflammatory drugs and high dose of oestrogen may be useful in the management of acute hemorrhagic disorders. Progestin, such as lynestrenol induces small reduction in leiomyoma volume and moderate increase in hemoglobin level before surgery. Pregnane and nor-pregnane may improve menstrual bleeding in short or mild delays. The use of Gonadotropin Releasing Hormone (GnRH) agonists can reduce menstrual bleeding with hemoglobin recovery. Add-back therapy using tibolone seems interesting since secondary effects encountered with GnRH agonists may be reduced. Levonorgestrel-releasing intrauterine system is proven to reduce increased menstrual bleeding and restore hemoglobin level. Aminoglutethimide and fadrozole have been underevaluated to conclude when letrozole seems as efficient as GnRH agonists to reduce leiomyoma volume and provide less hot flushes. Anastrozol is associated with reduction in leiomyomata volume, pain and menstrual bleeding. Mifepristone reduces the size of uterine leiomyomata, improves symptomatology, but could be associated with development of endometrial hyperplasia. SPRM evaluated in females have shown to improve leiomyoma related symptomatology. Danazol could be useful to reduce leiomyoma related symptoms in short terms. Tamoxifen and raloxifen show modest overall benefit. Because of insufficient data concerning fulvestrant, pirfenidone or interferon, their prescription cannot be recommended in patients with leiomyomata.