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Leukemia Feb 2023High-grade B-cell lymphoma, not otherwise specified (HGBL-NOS) is rare and data focused on these neoplasms is lacking. We studied the clinicopathologic and genetic...
High-grade B-cell lymphoma, not otherwise specified (HGBL-NOS) is rare and data focused on these neoplasms is lacking. We studied the clinicopathologic and genetic features of 136 HGBL-NOS patients and compared them to patients with DLBCL/HGBL-DH (n = 224, defined by 5th Edition WHO) and DLBCL (n = 217). HGBL-NOS patients had clinical features similar to DLBCL/HGBL-DH patients. MYC rearrangement (MYC-R) was present in 43% of HGBL-NOS. With induction regimen similar to DLBCL/HGBL-DH patients, HGBL-NOS patients had a median overall survival (OS) of 28.9 months, similar to DLBCL/HGBL-DH (p = 0.48) but inferior to DLBCL patients (p = 0.03). R-EPOCH induction was associated with improved OS compared with R-CHOP. MYC-R, history of lymphoma, and high IPI were independent adverse prognostic factors in HGBL-NOS patients. Whole transcriptome profiling performed on a subset of HGBL-NOS cases showed a profile more similar to DLBCL/HGBL-DH than to DLBCL; 53% of HGBL-NOS had a DH-like signature (DH-like-Sig) and were enriched for MYC-R. DH-like-Sig+ HGBL-NOS patients had a poorer OS than DH-like-Sig-negative patients (p = 0.04). In conclusion, HGBL-NOS has clinicopathologic features and a gene expression profile more similar to DLBCL/HGBL-DH than to DLBCL. Cases of HGBL-NOS frequently carry MYC-R and have a DH-like-Sig+. R-EPOCH induction in HGBL-NOS appears associated with improved OS compared with standard R-CHOP.
Topics: Humans; Lymphoma, B-Cell; Rituximab; Proto-Oncogene Proteins c-myc; Dermatitis Herpetiformis; Antineoplastic Combined Chemotherapy Protocols; Lymphoma, Large B-Cell, Diffuse; Proto-Oncogene Proteins c-bcl-2; Prognosis
PubMed: 36513804
DOI: 10.1038/s41375-022-01778-9 -
Health Technology Assessment... Oct 2022Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to...
BACKGROUND
Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma.
OBJECTIVES
The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care.
DESIGN
(1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives.
DATA SOURCES
For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE (National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used.
REVIEW METHODS
For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed.
RESULTS
People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents ( = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research.
LIMITATIONS
The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet.
CONCLUSIONS
Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia).
FUTURE WORK
Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42019115506 and CRD42020170766.
FUNDING
This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.
Topics: United States; Adult; Child; Male; Humans; Female; Celiac Disease; Longitudinal Studies; Prospective Studies; Skin Neoplasms; Immunoglobulin A; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 36321689
DOI: 10.3310/ZUCE8371 -
World Journal of Clinical Cases Oct 2022Dedicator of cytokinesis 8 (DOCK 8) deficiency, also known as autosomal recessive hyper immunoglobulin E (IgE) syndrome, is a combined immunodeficiency disease that was...
BACKGROUND
Dedicator of cytokinesis 8 (DOCK 8) deficiency, also known as autosomal recessive hyper immunoglobulin E (IgE) syndrome, is a combined immunodeficiency disease that was first recognized in 2009. It is caused by genetic alterations (mutations or deletions) in the DOCK 8 gene and is characterized by multiple allergies, elevated IgE levels, and susceptibility to viral and bacterial infections. Early diagnosis is critical to optimize the success of stem cell transplantation.
CASE SUMMARY
This study reports the case of a pediatric patient with DOCK 8 deficiency who had negative genetic testing using multiplex primary immunodeficiency (PID) panel and whole-exome sequencing (WES) with a next-generation sequencing method. He presented with chronic diarrhea and was managed as celiac disease based on previous negative workup for immunodeficiency and duodenal biopsy. He developed a generalized vesicular rash which was thought to be dermatitis herpetiformis associated with celiac disease. However, it turned out to be Eczema herpeticum based on positive herpes simplex virus from blood and lesions. The diagnosis was re-evaluated after the child was found to have multiple viral, bacterial, and parasitic co-infections (herpes simplex virus, cytomegalovirus, Epstein-Barr virus, , and ). Re-evaluation with target gene testing with copy number variation (CNV) analysis and Multiplex Ligation Probe Amplification (MLPA) showed a large homozygous deletion in the DOCK 8 gene, confirming the diagnosis of DOCK 8 deficiency.
CONCLUSION
Targeted gene testing with CNV analysis might detect deletions that can be missed by WES for diagnosing patients with PID.
PubMed: 36312485
DOI: 10.12998/wjcc.v10.i29.10735 -
JAAD Case Reports Nov 2022
PubMed: 36267650
DOI: 10.1016/j.jdcr.2022.09.019 -
Cureus Sep 2022Dermatitis herpetiformis (DH) is an auto-inflammatory skin disease that is linked to gluten sensitivity and is related to celiac disease (CD). Psoriasis is an...
Dermatitis herpetiformis (DH) is an auto-inflammatory skin disease that is linked to gluten sensitivity and is related to celiac disease (CD). Psoriasis is an inflammatory skin disorder found to have an association with the celiac disease, according to various genetic and epidemiological studies. We report a 12-year-girl who presented with multiple tense blisters along with red raised, scaly and itchy lesions over her body. She was a known case of psoriasis and was diagnosed as dermatitis herpetiformis in an immunofluorescence study. In this case report, we want to highlight the fact that the co-existence of dermatitis herpetiformis and psoriasis could be more than a mere coincidence. In our patient's previously uncontrolled psoriasis and dermatitis herpetiformis both improved after a gluten-free diet along with systemic therapy.
PubMed: 36258965
DOI: 10.7759/cureus.29218 -
Polski Merkuriusz Lekarski : Organ... Aug 2022Arterial thromboembolic events (ATE) in COVID-19, similarly as venous thromboembolism (VTE), are observed mainly in severely ill patients. ATE include brain, heart,...
UNLABELLED
Arterial thromboembolic events (ATE) in COVID-19, similarly as venous thromboembolism (VTE), are observed mainly in severely ill patients. ATE include brain, heart, aortic, and peripheral ischemic complications which usually aggravate a course of the disease leading to lifethreatening conditions.
A CASE REPORT
The authors describe a case of a 53-year-old male with Duhring disease in the remission period admitted due to severe COVID-19 pneumonia. The patient was treated with ceftriaxone (2000 mg once daily), dexamethasone (8 mg once daily), enoxaparin (60 mg twice daily), baricitinib (4 mg once daily), and remdesivir (200 mg on the first day, followed by 100 mg within 4 consecutive days); he required high flow oxygen therapy. On day 5 of hospitalization, he began to suffer from pain of the right lower extremity; in physical examination the limb was cold with absent femoral, popliteal, and pedal pulses. Urgent computed tomography angiography revealed total occlusion of the right superficial femoral artery (SFA) in the absence of any atherosclerotic plaques in the aorta. The patient was intubated and transferred to department of vascular surgery, where a giant clot was removed from SFA. Unfortunately, the patient outcome was unfavorable due to respiratory failure progression. The authors underline that ATE may occur even in anticoagulated patients and that association of some therapeutic options of COVID-19, like janus kinase (JAK) inhibitors use with an increased risk of ATE, should not be excluded.
Topics: Azetidines; COVID-19; Dermatitis Herpetiformis; Femoral Artery; Humans; Male; Middle Aged; Purines; Pyrazoles; Sulfonamides; COVID-19 Drug Treatment
PubMed: 36086986
DOI: No ID Found -
The American Journal of Dermatopathology Dec 2022
Topics: Humans; Dermatitis Herpetiformis; Immunoglobulin A
PubMed: 36075577
DOI: 10.1097/DAD.0000000000002297 -
Dermatologie (Heidelberg, Germany) Sep 2022Autoimmune bullous diseases (AIBD) comprise a group of organ-specific autoimmune diseases which are characterised by the production of autoantibodies against adhesion... (Review)
Review
Autoimmune bullous diseases (AIBD) comprise a group of organ-specific autoimmune diseases which are characterised by the production of autoantibodies against adhesion molecules and structural proteins of skin and mucosae. Depending on the target protein, AIBD are classified into intraepidermal (pemphigus group) and subepidermal (pemphigoid group, epidermolysis bullosa acquisita, dermatitis herpetiformis) blistering disorders. Depending on the clinical entity, patients can develop blisters, pustules, erosions, and erythema on the skin and mucosae.
Topics: Autoimmune Diseases; Blister; Epidermolysis Bullosa Acquisita; Humans; Mucous Membrane; Pemphigoid, Bullous; Skin Diseases, Vesiculobullous
PubMed: 36006424
DOI: 10.1007/s00105-022-05036-y -
The Journal of Investigative Dermatology Jan 2023
Topics: Humans; Dermatitis Herpetiformis; T-Lymphocytes; Celiac Disease
PubMed: 35961617
DOI: 10.1016/j.jid.2022.07.007