Ovarian teratoma associated Anti-N-methyl-D-aspartate receptor encephalitis: a difficult diagnosis with a favorable prognosis

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently described auto-immune and paraneoplastic encephalitis with prominent neuropsychiatric manifestations affecting young adults with ovarian teratoma. The availability of a novel assay to measure these antibodies might suggest an etiology for this potentially life-threatening disease, which if early recognized can be treated promptly with surgery with chances of a good clinical outcome. Reported prognostic indicators for a good outcome depend on the presence of a tumor, prompt treatment and no admission to an intensive care unit. However, due to the rarity and unawareness of this disease, the diagnosis may be delayed as primary psychiatric disorders, and infective encephalitis is taken more into consideration and ruled out first. Here we report a case of anti-NMDAR encephalitis in a 22-year-old female prompted by an ovarian teratoma with a gradual and complete resolution of symptoms after surgical excision of the teratoma and immunomodulating therapies

Clinical Presentation of Psoriasis

SUMMARY Psoriasis is a chronic, inflammatory disease affecting 1-3% of the world's population. Joints can be affected in up to 30% of patients. About one third of patients have either severe or moderate (involving more than 10% of body surface area) disease. Patients affected with extensive psoriasis have an impaired quality of life. Psoriasis has a large spectrum of clinical features and evolution, so no complete agreement on the classification of the clinical variants exists. Plaque psoriasis is the commonest form (more than 80% of affected patients). The course of plaque psoriasis varies. Spontaneous resolution is possible, but rarely occurs. Plaques tend to remain static or slowly enlarge. Flexural (inverse, intertriginous) psoriasis manifests with lesions thinner than those of plaque form with no or minimal scaling, and is localized in the skin folds. Guttate (eruptive) psoriasis has frequently a sudden onset and frequently appears abruptly after a bacterial or viral febrile episode of inflammation of the upper ways. Pustular and erythrodermic psoriasis are the most severe clinical variants. In the diffuse pustular form recurrent episodes of fever occur, followed by new outbreaks of pustules. Erythrodermic psoriasis corresponds to the generalized form of the disease. The entire skin is bright red and is covered by superficial scales. Fatigue, myalgia, shortness of breath, fever and chills may also occur. In sebopsoriasis (seborrheic dermatitis + psoriasis) the lesions tend to occur at the same sites as seborrheic dermatitis; greasy scales predominate, but silvery scales can be found in some areas. Nail psoriasis shows various features: nail pits; oil spots; subungual hyperkeratosis; onycholysis. Rare forms include psoriasis circinata, lip psoriasis and oral psoriasis. Differential diagnosis includes many other dermatological conditions. Key words: Psoriasis, nail, quality of lif

Ovarian teratoma associated Anti-N-methyl-D-aspartate receptor encephalitis: a difficult diagnosis with a favorable prognosis

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently described auto-immune and paraneoplastic encephalitis with prominent neuropsychiatric manifestations affecting young adults with ovarian teratoma. The availability of a novel assay to measure these antibodies might suggest an etiology for this potentially life-threatening disease, which if early recognized can be treated promptly with surgery with chances of a good clinical outcome. Reported prognostic indicators for a good outcome depend on the presence of a tumor, prompt treatment and no admission to an intensive care unit. However, due to the rarity and unawareness of this disease, the diagnosis may be delayed as primary psychiatric disorders, and infective encephalitis is taken more into consideration and ruled out first. Here we report a case of anti-NMDAR encephalitis in a 22-year-old female prompted by an ovarian teratoma with a gradual and complete resolution of symptoms after surgical excision of the teratoma and immunomodulating therapies

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Immunomodulatory mechanisms of action of calcitriol in psoriasis

Background: Calcitriol is well known for its therapeutic efficacy in psoriasis, but its mechanism of action is still unclear. In this study, we tried to elucidate the precise mechanism of calcitriol for its therapeutic efficacy in psoriasis. Materials and Methods: Proliferation and apoptosis studies were done to determine the effect of calcitriol on normal human epidermal keratinocytes (NHEKs) and T lymphocytes. To elucidate the effect of Calcitriol on relevant chemokines and epidermal proteins of psoriasis, real-time polymerase chain reaction were done on the modified reconstructed human epidermis (RHE) an in vitro model of psoriasis. All experiments were done in triplicate. Results were expressed as mean ± standard error of mean. Results and Conclusions: In vitro, Calcitriol showed significant inhibition of NHEKs and T lymphocyte proliferation by inducing apoptosis of these cells. Moreover, in an in vitro model of psoriasis (RHE), Calcitriol significantly inhibited relevant gene expression of chemokines (Interleukin-8, Regulated upon Activation Normal T-cell Expressed and Secreted [RANTES]) and psoriasin (S100A7). Here, we observed that Calcitriol inhibits critical pathological events associated with the inflammatory-proliferative cascades of psoriasis. Calcitriol induced apoptosis of NHEKs and T lymphocytes as well as inhibited gene expression of relevant chemokines and epidermal proteins in the in vitro model of psoriasis

Folate Insufficiency Due to Celiac Disease in a 49-Year-Old Woman of Southeast Asian-Indian Ethnicity.

The clinical presentation of celiac disease has evolved from chronic diarrhea and malnutrition to mild nutrient insufficiencies. Recently diagnosed adults with celiac disease should be assessed for micronutrient deficiencies because early institution of a gluten-free diet (GFD) prevents morbidity and reduces the incidence of gastrointestinal malignant neoplasms and osteoporosis. In this report, we present the case of a 49-year-old woman of Southeast Asian-Indian descent living in the United States who had folate insufficiency, as manifested by low serum and red blood cell (RBC) folate levels. Further investigation, including serologic testing and intestinal biopsy, confirmed a diagnosis of celiac disease and other nutrient deficiencies. Managing the condition of this patient with folate supplements and implementation of a recommended GFD reversed the folate insufficiency. In conclusion, when serum and/or RBC levels are low in a person of Southeast Asian-Indian descent living in a country with folate fortification of the grain supply, such as the United States, the medical team needs to look for an organic cause, as in our patient, to diagnose and manage celiac disease early and, hopefully, forestall complications

Leukoerythroblastosis in a Sickle Cell Patient With Pregnancy: An Interesting Peripheral Blood Smear Finding.

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shaken the entire world. The social, health and financial impacts of this pandemic are beyond words. We have learnt a lot about this new disease in a short period of time, but still a long road to go to fully determine its pathogenic effect. The primary target of this virus is angiotensin-converting enzyme 2 (ACE2) receptor, which is prevalent in endothelial cells throughout the body. Immunocompromised patients such as patients with sickle cell disease are more vulnerable to severe respiratory infections, including infection with SARS-CoV-2. In addition, sickle cell disease patients are prone to vaso-occlusive crisis, and theoretically SARS-CoV-2 can worsen the situation as it also can cause endothelial dysfunction and thrombosis. Herein, we are sharing an interesting peripheral blood smear finding of an asymptomatic 31-year-old multigravida pregnant female with a history of sickle cell disease and found to have a positive COVID-19 polymerase chain reaction (PCR) test during her third trimester of pregnancy at a routine clinic visit. Two weeks after the initial positive test, she developed nausea, vomiting, constipation and a pain crisis affecting her extremities while her COVID-19 PCR test was still positive. She was hemodynamically stable, and lab workup revealed chronic anemia, leukocytosis with neutrophilia and lymphopenia. Morphologic examination of the peripheral blood smear showed a marked leukoerythroblastosis: rare myeloblasts, sickle cells, markedly abundant nucleated red blood cells (RBCs), metamyelocytes, and many large and giant platelets were seen. In this context, her previous peripheral blood smears (prior to positive COVID-19 test) did not show leukoerythroblastosis. She was managed conservatively with hydration and pain control and delivered at 36 weeks via cesarean section due to pre-term labor and intrauterine growth retardation. The unusual finding of leukoerythroblastosis in a pregnant sickle cell disease patient with an asymptomatic COVID-19 infection indicates further studies to determine its effect on hematopoietic system and elucidate its clinical significance

Cross talk between neuroregulatory molecule and monocyte: nerve growth factor activates the inflammasome.

BACKGROUND:Increasing evidence points to a role for the extra-neuronal nerve growth factor (NGF) in acquired immune responses. However, very little information is available about its role and underlying mechanism in innate immunity. The role of innate immunity in autoimmune diseases is becoming increasingly important. In this study, we explored the contribution of pleiotropic NGF in the innate immune response along with its underlying molecular mechanism with respect to IL-1β secretion. METHODS:Human monocytes, null and NLRP3 deficient THP-1 cell lines were used for this purpose. We determined the effect of NGF on secretion of IL-1β at the protein and mRNA levels. To determine the underlying molecular mechanism, the effect of NGF on NLRP1/NLRP3 inflammasomes and its downstream key protein, activated caspase-1, were evaluated by ELISA, immunoflorescence, flow cytometry, and real-time PCR. RESULTS:In human monocytes and null THP-1 cell line, NGF significantly upregulates IL-1β at protein and mRNA levels in a caspase-1 dependent manner through its receptor, TrkA. Furthermore, we observed that NGF induces caspase-1 activation through NLRP1/NLRP3 inflammasomes, and it is dependent on the master transcription factor, NF-κB. CONCLUSIONS:To best of our knowledge, this is the first report shedding light on the mechanistic aspect of a neuroregulatory molecule, NGF, in innate immune response, and thus enriches our understanding regarding its pathogenic role in inflammation. These observations add further evidence in favor of anti-NGF therapy in autoimmune diseases and also unlock a new area of research about the role of NGF in IL-1β mediated diseases