scholarly journals A234 CLINICAL, ENDOSCOPIC AND HISTOLOGICAL IMPROVEMENT IN COMMON VARIABLE IMMUNODEFICIENCY DISEASE ASSOCIATED ENTEROPATHY WITH VEDOLIZUMAB

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 110-112
Author(s):  
H Akhtar ◽  
B Markandey ◽  
C Ma ◽  
T Nguyen ◽  
V Jairath
Keyword(s):  
Villous Atrophy ◽  
Safety Data ◽  
Case Series ◽  
Pneumococcal Vaccination ◽  
Humoral Response ◽  
Lymph Node Excision ◽  
Increased Risk ◽  
Histological Improvement ◽  
Recurrent Sinus ◽  
Common Variable

Abstract Background Common variable immune deficiency (CVID) can be associated with autoimmune manifestations including enteric inflammation and diarrhea. Systemic immunosuppression used in patients with inflammatory bowel disease (IBD) may be associated with increased risk of infection in CVID. Aims We report a patient with CVID associated intestinal enteropathy who underwent clinical, endoscopic and histological improvement after treatment with vedolizumab (IgG1 monoclonal antibody to α4β7 integrin), as well as a concurrent systematic review (SR) of the literature. Methods Case report and systematic literature review. We searched EMBASE, Medline, Cochrane CENTRAL, clinialtrials.gov, and the International Clinical Trials Registry Platform without language restriction using key words to identify patients with CVID associated enteropathy treated with vedolizumab. Clinical, endoscopic and histological outcomes were extracted and safety data. Results A 32-year-old male presented with weight loss, anemia and hypoalbuminemia on a background of chronic diarrhea and recurrent sinus infections. Serology and genetic testing was not consistent with celiac disease. Pan-endoscopy showed complete villous atrophy in the duodenum and biopsies showed and intraepithelial lymphocytosis (IEL) in the duodenum and terminal ileum. CT abdomen showed pan-enteritis with extensive mesenteric lymphadenopathy which were reactive on lymph node excision, as well as bronchiectasis. Pneumococcal vaccination challenge to assess humoral response confirmed CVID. After suboptimal response with steroids and mercaptopurine, treatment was initiated with vedolizumab 300mg IV at weeks 0, 2, and 6, then 8 weekly. This led to normalization of stool frequency, weight gain as well as endoscopic and histological resolution within 6 months of treatment. The SR yielded 101 studies of which 3 case series were identified reporting a total of 7 patients with CVID. In 5 cases there was clinical improvement, 4 reported endoscopic improvement and 3 patients had histologic improvement. No safety concerns associated with vedolizumab were reported. Conclusions Vedolizumab, a selective leucocyte inhibitor to the gut, was able to induce either clinical, endoscopic or histological improvement in 8 published cases in the worldwide literature. Prospective studies are needed to determine whether this treatment could be included in the therapeutic armamentarium for this orphan indication. Funding Agencies None

scholarly journals Increased Risk of Systemic Lupus Erythematosus in 29,000 Patients with Biopsy-verified Celiac Disease

2012 ◽  
Vol 39 (10) ◽  
pp. 1964-1970 ◽  
Author(s):  
JONAS F. LUDVIGSSON ◽  
ALBERTO RUBIO-TAPIA ◽  
VAIDEHI CHOWDHARY ◽  
JOSEPH A. MURRAY ◽  
JULIA F. SIMARD
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Celiac Disease ◽  
General Population ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Villous Atrophy ◽  
Case Series ◽  
Excess Risk ◽  
Systemic Lupus ◽  
Increased Risk

Objective.To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking.Methods.We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden’s 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register. SLE was defined as having at least 2 records of SLE in the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR) for SLE.Results.During followup, 54 individuals with CD had an incident SLE. This corresponded to an HR of 3.49 (95% CI 2.48−4.90), with an absolute risk of 17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of followup, the HR for SLE was 2.54 (95% CI 1.57−4.10). While SLE was predominantly female, we found similar risk estimates in men and women. When we restricted our outcome to individuals who also had a dispensation for a medication used in SLE, the HR was 2.43 (95% CI 1.22−4.87). The HR for having 2 records of SLE diagnoses, out of which at least 1 had occurred in a department of rheumatology, nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97−4.17).Conclusion.Individuals with CD were at a 3-fold increased risk of SLE compared to the general population. Although this excess risk remained more than 5 years after CD diagnosis, absolute risks were low.

Dental Implant Placement in Patients with a History of Medications Related to Osteonecrosis of the Jaws: A Systematic Review

2020 ◽  
Author(s):  
Judd Sher ◽  
Kate Kirkham-Ali ◽  
Denny Luo ◽  
Catherine Miller ◽  
Dileep Sharma
Keyword(s):  
Systematic Review ◽  
At Risk ◽  
Drug Therapy ◽  
Dental Implant ◽  
Case Series ◽  
Cochrane Central Register ◽  
Bisphosphonate Treatment ◽  
Implant Placement ◽  
Increased Risk ◽  
History Of

The present systematic review evaluates the safety of placing dental implants in patients with a history of antiresorptive or antiangiogenic drug therapy. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and OpenGrey databases were used to search for clinical studies (English only) to July 16, 2019. Study quality was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using a modified Newcastle-Ottawa scale and the Joanna Briggs Institute critical appraisal checklist for case series. A broad search strategy resulted in the identification of 7542 studies. There were 28 studies reporting on bisphosphonates (5 cohort, 6 case control, and 17 case series) and one study reporting on denosumab (case series) that met the inclusion criteria and were included in the qualitative synthesis. The quality assessment revealed an overall moderate quality of evidence among the studies. Results demonstrated that patients with a history of bisphosphonate treatment for osteoporosis are not at increased risk of implant failure in terms of osseointegration. However, all patients with a history of bisphosphonate treatment, whether taken orally for osteoporosis or intravenously for malignancy, appear to be at risk of ‘implant surgery-triggered’ MRONJ. In contrast, the risk of MRONJ in patients treated with denosumab for osteoporosis was found to be negligible. In conclusion, general and specialist dentists should exercise caution when planning dental implant therapy in patients with a history of bisphosphonate and denosumab drug therapy. Importantly, all patients with a history of bisphosphonates are at risk of MRONJ, necessitating this to be included in the informed consent obtained prior to implant placement. The James Cook University College of Medicine and Dentistry Honours program and the Australian Dental Research Foundation Colin Cormie Grant were the primary sources of funding for this systematic review.

DEVELOPMENT OF THE MONITORING (CONTROL) PROGRAM OF THE SAFETY OF NUCLEAR POWER PLANTS

2020 ◽  
Vol 2020 (2) ◽  
pp. 50-56
Author(s):  
Mariya Berberova ◽  
Vladislav Chuenko ◽  
Oleg Zolotarev ◽  
Olga Trefilova ◽  
Maksim Grudev ◽  
...  
Keyword(s):  
Nuclear Power ◽  
Power Plants ◽  
Nuclear Power Plants ◽  
Radiation Risk ◽  
Safety Data ◽  
Control Program ◽  
Data Sheet ◽  
Risk Assessments ◽  
Safety Data Sheet ◽  
Increased Risk

Nuclear power plants (NPP), being complex technological systems, represent a source of increased risk, in particular, a specific risk of radiation exposure. Obtaining quantitative assessments of radiation risk is critical for risk reduction and accident prevention. Existing methods for assessing radiation risk do not take into account the influence of external factors, such as population composition, geographical features, anthropogenic environmental changes, etc.[1]. Since 1997, in connection with changes in the norms and rules in the field of the use of atomic energy, it became necessary to perform a probabilistic safety analysis (PSA) at all nuclear power plants in Russia. Subsequently, a standard safety data sheet for a hazardous facility was developed. To fill out the second section of the safety data sheet, it is necessary to carry out a risk assessment of the objects in question. From this moment on, risk assessments were performed for all power units of all operating nuclear power plants in Russia. Today, in our country there are 14 nuclear power plants. On average, there are 3 power units per nuclear power plant. In order to systematize and centralize data on NPP risk assessments, it became necessary to develop a program for monitoring NPP safety. The aim of the work is to develop a monitoring (control) program for ensuring the safety of nuclear power plants, using modern technologies to systematize and group data on nuclear safety data sheets, as well as organize quick access to information.

scholarly journals Death Rate Due to COVID-19 in Alzheimer’s Disease and Frontotemporal Dementia

2020 ◽  
Vol 78 (2) ◽  
pp. 537-541
Author(s):  
Jordi A. Matias-Guiu ◽  
Vanesa Pytel ◽  
Jorge Matías-Guiu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Death Rate ◽  
Case Series ◽  
Care Homes ◽  
Relevant Factor ◽  
Increased Risk ◽  
Care Facilities ◽  
Probability Of Death

We aimed to evaluate the frequency and mortality of COVID-19 in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We conducted an observational case series. We enrolled 204 patients, 15.2% of whom were diagnosed with COVID-19, and 41.9% of patients with the infection died. Patients with AD were older than patients with FTD (80.36±8.77 versus 72.00±8.35 years old) and had a higher prevalence of arterial hypertension (55.8% versus 26.3%). COVID-19 occurred in 7.3% of patients living at home, but 72.0% of those living at care homes. Living in care facilities and diagnosis of AD were independently associated with a higher probability of death. We found that living in care homes is the most relevant factor for an increased risk of COVID-19 infection and death, with AD patients exhibiting a higher risk than those with FTD.

scholarly journals NCMP-17. MISMATCH REPAIR MUTATIONS AND THE CENTRAL NERVOUS SYSTEM: A CASE SERIES OF GERMLINE MUTATIONS AND CNS MALIGNANCY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii126-ii126
Author(s):  
Amber Ruiz ◽  
Jerome Graber
Keyword(s):  
Treatment Response ◽  
Mismatch Repair ◽  
Case Series ◽  
Germline Mutations ◽  
Molecular Characteristics ◽  
Loss Of Function ◽  
Dna Mismatch ◽  
Mutational Burden ◽  
Increased Risk ◽  
Tumor Mutational Burden

Abstract Our understanding of genetic predispositions for malignancy is continually evolving. One family of germline mutations well described in the literature is that of the DNA mismatch repair mechanism (MMR). Lynch syndrome (LS) is due to a loss of function mutation of several MMR genes- MSH2, MLH1, MSH6, and PMS2. Germline MMR mutations lead to microsatellite instability and loss of genomic integrity resulting in an increased risk for various cancers (colorectal, genitourinary, etc). LS may be as common as 1 in 400 people and some MMR mutations have been associated with gliomas. There is a paucity of information regarding frequency of glioma subtypes as well as tumor genetic and molecular characteristics which have important clinical implications. We describe a case series of 6 individuals with germline MMR mutations and brain tumors. Those with MSH2 and PMS2 mutations (n=3) developed glioblastomas at a mean age at diagnosis of 48 years. These tumors expressed MGMT hyper-methylation and high tumor mutational burden. Only one had IDH-1 mutation. Those with MLH1 mutations (n=3), did not develop gliomas. This raises the question of differential glioma subtype development based on MMR gene. It also highlights the possibility of Lynch-associated gliomas having more favorable treatment response due to MGMT methylation and potential response to immunotherapy based on high tumor mutational burden. Though the sample size is small, there appears to be a preponderance of women compared to men (5:1 respectively). Larger studies are needed to verify CNS involvement in germline MMR mutations. In doing so, we hope to identify factors that may influence clinical management and lead to a better understanding of treatment response and disease prognosis.

scholarly journals Case series: Breast and ovarian cancer syndrome

2016 ◽  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca Mutation ◽  
Family Members ◽  
Case Series ◽  
Second Primary ◽  
Time Interval ◽  
Breast And Ovarian Cancer ◽  
Ovarian Carcinomas ◽  
Increased Risk

Aims and Objectives: To report a series of cases with breast and ovarian carcinomas either in same patient or in a family and identifying the importance of BRCA 1,2 genetic testing in such individuals. Materials and Methods: The medical records of breast and ovarian cancer patients operated over past 3 years at a single institute were reviewed retrospectively and their clinical profile, family history, final pathological reports and follow up data was collected. Results: 8 patients were found to have breast and ovarian malignancies, out of which 3 had synchronous breast and ovarian cancers, 4 had metachronous and 1 patient with ovarian cancer had history of breast cancer in family. Median age of presentation to the hospital was 47 years and median time interval in metachronous disease patients was 5.5 years. Conclusion: About 5% of people who have breast cancer and about 10% of women who have ovarian cancer have HBOC, caused by germline mutation in BRCA1, 2 gene. These individuals have increased risk of developing breast cancer at younger age, TNBC, or developing a second primary in breast or ovary plus an overall risk of breast/ovarian/prostate/pancreatic malignancies in other family members due to inheritable mutation. Identification of BRCA mutation in such individuals can help family members to undergo genetic counseling and follow different screening and prevention guidelines from general population thus reducing the cancer risks.

scholarly journals Immunometabolic Status of COVID-19 Cancer Patients

2020 ◽  
Vol 100 (4) ◽  
pp. 1839-1850
Author(s):  
A. Sica ◽  
M. P. Colombo ◽  
A. Trama ◽  
L. Horn ◽  
M. C. Garassino ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Macrophage Activation ◽  
Viral Infections ◽  
Immune Cell ◽  
Case Series ◽  
The United States ◽  
Alternative Activation ◽  
Nad Metabolism ◽  
Increased Risk

Cancer patients appear to be more likely to be diagnosed with coronavirus disease 2019 (COVID-19). This is supported by the understanding of immunometabolic pathways that intersect patients with infection and cancer. However, data derived by case series and retrospective studies do not offer a coherent interpretation, since data from China suggest an increased risk of COVID-19, while data from the United States and Italy show a prevalence of COVID-19 in cancer patients comparable with the general population. Noteworthy, cancer and COVID-19 exploit distinct patterns of macrophage activation that promote disease progression in the most severe forms. In particular, the alternative activation of M2-polarized macrophages plays a crucial role in cancer progression. In contrast, the macrophage-activation syndrome appears as the source of M1-related cytokine storm in severe COVID-19 disease, thus indicating macrophages as a source of distinct inflammatory states in the two diseases, nonetheless as a common therapeutic target. New evidence indicates that NAMPT/NAD metabolism can direct both innate immune cell effector functions and the homeostatic robustness, in both cancer and infection. Moreover, a bidirectional relationship exists between the metabolism of NAD and the protective role that angiotensin converting enzyme 2, the COVID-19 receptor, can play against hyperinflammation. Within this immunometabolic framework, the review considers possible interference mechanisms that viral infections and tumors elicit on therapies and provides an overview for the management of patients with cancer affected by COVID-19, particularly for the balance of risk and benefit when planning normally routine cancer treatments and follow-up appointments.

scholarly journals Exposure therapy for PTSD during pregnancy: a feasibility, acceptability, and case series study of Narrative Exposure Therapy (NET)

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Natalie R. Stevens ◽  
Michelle L. Miller ◽  
Christina Soibatian ◽  
Caitlin Otwell ◽  
Anne K. Rufa ◽  
...  
Keyword(s):  
Mental Health Treatment ◽  
Exposure Therapy ◽  
Case Series ◽  
Perinatal Outcomes ◽  
Post Treatment ◽  
Depression Symptoms ◽  
Narrative Exposure Therapy ◽  
Ptsd Treatment ◽  
Case Series Study ◽  
Increased Risk

Abstract Background Prenatal posttraumatic stress disorder (PTSD) is a significant complication of pregnancy linked to increased risk of adverse perinatal outcomes. Although 1 in 5 pregnant trauma-exposed individuals have PTSD, most PTSD treatment trials exclude participants who are pregnant, and none focus on treatment specifically during pregnancy. Moreover, access to mental health treatment is particularly challenging in low-resource settings with high rates of trauma. This study examined implementation of Narrative Exposure Therapy (NET), a short-term evidence-based PTSD treatment, in an urban prenatal care setting. Partial telehealth delivery was used to increase accessibility. Study aims were to examine (a) feasibility, (b) acceptability, and (c) case-based treatment outcomes associated with NET participation. Method Eight pregnant participants (median age = 27, median gestational week in pregnancy = 22.5) received up to six sessions of NET with partial telehealth delivery. PTSD and depression symptoms were assessed at pre-treatment intake (T1), at each session (T2), and 1-week post-treatment (T3). A multiple case study approach was used to examine recruitment and engagement, retention, treatment completion, treatment barriers, use of telehealth, participants’ experiences of treatment, and PTSD and depression symptoms. Results Nine of the 16 participants (56%) who were invited to participate engaged in treatment, and one dropped out after the first session. Eight participants completed the minimum “dose” of 4 NET sessions (N = 8/9, 89%). Seven participants gave the highest ratings of treatment acceptability. The most frequently reported barriers to treatment were competing priorities of work and caring for other children. Pre-post treatment symptom measures revealed clinically meaningful change in PTSD severity for nearly all participants (7/8, 88%). Conclusions Results suggest that a brief exposure therapy PTSD treatment can be successfully implemented during pregnancy, suggesting promising results for conducting a larger-scale investigation. Trial registration ClinicalTrials.gov, NCT04525469. Registered 20 August 2020–Retrospectively registered, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=View&listmode=Edit&uid=U00058T2&ts=3&sid=S000A59A&cx=-w1vnvn

The Association Between Immunodeficiency and the Development of Autoimmune Disease

1996 ◽  
Vol 10 (1) ◽  
pp. 57-61 ◽  
Author(s):  
J.W. Sleasman
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Iga Deficiency ◽  
Selective Iga Deficiency ◽  
Increased Risk ◽  
High Incidence ◽  
Autoimmune Cytopenias ◽  
The Complement System ◽  
Common Variable

There is a paradoxical relationship between immunodeficiency diseases and autoimmunity. While not all individuals with immunodeficiency develop autoimmunity, nor are all individuals with autoimmunity immunodeficient, defects within certain components of the immune system carry a high risk for the development of autoimmune disease. Inherited deficiencies of the complement system have a high incidence of systemic lupus erythematosus (SLE), glomerulonephritis, and vasculitis. Carrier mothers of children with chronic granulomatous disease, an X-linked defect of phagocytosis, often develop discoid lupus. Several antibody deficiencies are associated with autoimmune disease. Autoimmune cytopenias are commonly observed in individuals with selective IgA deficiency and common variable immune deficiency. Polyarticular arthritis can be seen in children with X-linked agammaglobulinemia. Combined cellular and antibody deficiencies, such as Wiskott-Aldrich syndrome, carry an increased risk for juvenile rheumatoid arthritis and autoimmune hemolytic anemia. Several hypothetical mechanisms have been proposed to explain the associations between autoimmunity and immunodeficiency. Immunologic defects may result in a failure to exclude microbial antigens, resulting in chronic immunologic activation and autoimmune symptoms. There may be shared genetic factors, such as common HLA alleles, which predispose an individual to both autoimmunity and immunodeficiency. Defects within one component of the immune system may alter the way a pathogen induces an immune response and lead to an inflammatory response directed at self-antigens. An understanding of the immunologic defects that contribute to the development of autoimmunity will provide an insight into the pathogenesis of the autoimmune process.

Sign in / Sign up

Export Citation Format

Share Document