Sumoylated HSP-90 Is a Frequent Autosomal-Inherited Target of Paraproteins in Monoclonal Gammopathies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 26-26
Author(s):  
Klaus-Dieter Preuss ◽  
Natalie Fadle ◽  
Evi Regitz ◽  
Michael Pfreundschuh
Keyword(s):  
African American ◽  
Posttranslational Modification ◽  
Conflicts Of Interest ◽  
Family Members ◽  
Significant Proportion ◽  
Carrier State ◽  
Antigenic Stimulation ◽  
Chronic Antigenic Stimulation ◽  
Increased Risk ◽  
Hsp 90

Abstract Background Chronic antigenic stimulation might have a role in the pathogenesis of monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma. We previously identified a group of 11 autoantigenic paraprotein targets (paratargs) of which paratarg-7 is the most frequent, found in ~15 % of all MGUS/MM/Waldenstrom patients. These paratarg autoantigens all have in common to be 1) recognised by patients paraprotein with an extreme high titer (>1:1011), 2) hyperphosphorylated in patients, and 3) their phosphorylation carrier state is autosomal-dominant inherited in patients families. The finding that all these paratargs were permanently hyperphosphorylated in patients in contrast to healthy controls brought up the assumption that abnormal posttranslational modification of autoantigens might be a frequent finding in those patients. Methods A RZPD macroarray representing more than 30.000 different human proteins was subjected to in-vitro posttranslational modification using sumoylation-competent recombinant enzymes followed by screening with paraprotein-containing sera at high dilution (1:107). Immunopositive signals were identified and characterized by DNA sequencing, SDS-PAGE, isoelectric focusing, western blotting and ELISA. Findings Twenty-seven of 226 (11.9%) paraproteins from European, 9/80 (11.2%) from African-American and 9/176 (5.1%) from Japanese patients reacted specifically with the sumoylated heat shock protein-90β isoform-α (HSP90-SUMO). No reactivity was detected in >800 controls. All patients with HSP90-SUMO-binding paraproteins carried HSP90-SUMO. HSP90-SUMO carrier state is autosomal-dominantly inherited and was sown to be caused by the inability of SENP2 to desumoylate HSP90-SUMO. Five of 550 (0.9%) European, 2/100 (2%) African-American and 2/178 (0.8%) Japanese controls carried HSP90-SUMO, resulting in odds ratios of 14.8, 6.2 and 7.4, respectively, of healthy carriers for MGUS/MM/WM. Only, but all MGUS/MM/WM patients who were HSP90-SUMO carriers had HSP90-SUMO-specific paraproteins suggesting that sumoylated HSP-90 is involved in the pathogenesis of MGUS/MM/WM by chronic antigenic stimulation. Demonstration of HSP90-SUMO carriership identifies family members of HSP90-SUMO patients at risk. Interpretation A significant proportion of MGUS/MM/WM are associated with a dominant inheritance of posttranslationally modified autoantigens as shown for members of the paratarg autoantigen family and for HSP90-SUMO, enabling family members at increased risk for MGUS/MMWM to be identified by simple analysis of their peripheral blood. That only patients with MGUS/MM/WM who are carriers of such modified autoantigens have target-specific paraproteins suggests that the posttranslational modification induces auto-immunity and is involved in the pathogenesis of MGUS/MM/WM, for example, by chronic antigenic stimulation. Supported by Deutsche Forschungsgemeinschaft DFG, Deutsche José Carreras Leukämie Stiftung, Wilhelm-Sander-Stiftung, Deutsche Krebshilfe e.V. Disclosures No relevant conflicts of interest to declare.

Hyperphosphorylated Paratarg-7 Is a Frequent Antigenic Target of IgM Paraproteins, Is Dominantly Inherited and Represents a Highly Significant Risk Factor for Monoclonal Gammopathy of Undetermined Significance of the IgM Type (IgM-MGUS) and Waldenstrom's Macroglobulinemia (WM), Allowing for the Identification of Family Members at Risk in Cases of Familial IgM-MGUS and WM.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3935-3935
Author(s):  
Sandra Grass ◽  
Klaus-Dieter Preuss ◽  
Alexandra Wikowicz ◽  
Evangelos Terpos ◽  
Marita Ziepert ◽  
...  
Keyword(s):  
Risk Factor ◽  
Isoelectric Focusing ◽  
Odds Ratio ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Carrier State ◽  
Antigenic Stimulation ◽  
Chronic Antigenic Stimulation ◽  
Phosphatase Treatment ◽  
Increased Risk

Abstract Abstract 3935 Poster Board III-871 Background Antigenic targets of paraproteins in MGUS, multiple Myeloma (MM) and WM might play a role in the pathogenesis of these neoplasms by chronic antigenic stimulation, but very few have been identified, of which most were specific for one individual paraprotein only. In contrast, we recently described paratarg-7, a protein of unknown function which is expressed in all human tissues as the target of 15% of IgA and IgG paraproteins in MGUS and MM (Grass et al.; Lancet Oncology 2009 in press). Methods To determine if and how frequently paratarg-7 functions as the antigenic target of the IgM paraproteins in MGUS/WM, sera from patients with IgM-MGUS/WM were tested for reactivity with recombinant paratarg-7 by ELISA. The specificity of the paraprotein-mediated reaction was demonstrated by absorption studies with recombinant paratarg-7 and by cloning the B-cell receptor from bone marrow cells of patients with a paratarg-7 specific paraprotein. Lysates of peripheral blood from patients and controls were tested by gel electrophoresis and isoelectric focusing before and after phosphatase treatment. Moreover, paratarg-7 cDNA was sequenced to exclude SNPs and mutations. Results The paraproteins of 18 (9 WM and 9 IgM-MGUS) of 161 (11%) sera from patients in Germany, USA and Greece reacted specifically with paratarg-7, proving paratarg-7 as the first antigen identified as a paraprotein target in a significant proportion of patients with IgM-MGUS/WM. Mutations or polymorphisms of paratarg-7 were not found. However, 2D-gelelectrophoresis, isoelectric focusing and phosphatase treatment revealed that paratarg-7 was hyperphosphorylated in all patients with an anti-paratarg-7 specific IgM-paraprotein tested. In contrast, only 4 of 200 (2%) healthy blood donors were carriers of hyperphosphorylated paratarg-7. Thus, carriers of hyperphosphorylated paratarg-7 have a significantly increased risk (odds ratio= 6.5; 95%-CI: 2.1-19.6; p=0.001) for developing IgM-MGUS/MW. Moreover, family analyses of relatives of IgM-MGUS/WM patients with an anti-paratarg-7 specific paraprotein revealed that the hyperphosphorylated state of this protein is inherited as a dominant trait. The results obtained in IgM-MGUS/WM are similar to recent observations made in 252 patients with IgG- or IgA-MGUS/MM where hyperphosphorylated paratarg-7 was also associated with a significantly increased risk of developing IgG- and IgA-MGUS (odds ratio: 7.9; 95% CI, 2.8-22.6; p=0.0001). Conclusions Hyperphosphorylated paratarg-7 is a highly significant risk factor for MGUS, WM and MM, with the highest odds ratio of any risk factor reported to date for these diseases. Hyperphosphorylated paratarg-7 is the first molecularly defined and dominantly inherited risk factor identified for any hematological neoplasm reported to date. The carrier state of hyperphosphorylated paratarg-7 explains cases with familial MGUS, MM and WM and enables the identification of family members of patients at increased risk for MGUS/WM/MM. That only MGUS/WM/MM patients who are carriers of hyperphosphorylated paratarg-7 had a paratarg-7 specific paraprotein suggests that the hyperphosphorylation of paratarg-7 induces auto-immunity and is involved in the pathogenesis of these diseases, e.g. by chronic antigenic stimulation. The identification of paratarg-7 as a frequent antigenic target enables the more detailed analysis of tumor-host interactions in these patients and its role in the pathogenesis of these diseases. Moreover, its dominant inheritance and the identification of familial cases with MGUS/MM/WM and hyperphosphorylated paratarg-7 carrier state facilitate genome-wide screens for the identification of the SNP responsible for hyperphosphorylation of this molecule. Disclosures: No relevant conflicts of interest to declare.

Autoimmune or Chronic Infectious Disease in B-CLL at Diagnosis: Association with Unmutated VH Gene Status and Unfavorable Cytogenetics.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3092-3092
Author(s):  
Katrina Vanura ◽  
Trang Le ◽  
Harald Esterbauer ◽  
Florentin Spaeth ◽  
Edith Porpaczy ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Antigenic Stimulation ◽  
Control Group ◽  
Chronic Stimulation ◽  
Chronic Antigenic Stimulation ◽  
Mutational Status ◽  
Increased Risk ◽  
Group 3 ◽  
Vh Gene ◽  
Vh Genes

Abstract It is well known that chronic stimulation of the immune system (chronic infection, autoimmune disease) confers an increased risk of developing cancer. B-CLL represents an interesting model for the association of chronic antigenic stimulation with neoplastic transformation. We investigated the incidence of pre-existing chronic stimulation in patients with B-CLL at diagnosis. Chronic stimulation (CS) was defined as suffering from autoimmune disease or chronic or recurrent infection. The B-CLL control group consisted of patients without known chronic stimulation or concomitant diseases (non-CS). 187 unselected patients with known VH status diagnosed at our department were included in the study. Baseline characteristics were typical for a representative CLL patient cohort. Median age was 63 ranging from 25 to 83 years. Female:male ratio was 1:1,7. 87% of patients were staged Binet A, 13% Binet B or C. 63% of patients had mutated IgVH genes, 37% had unmutated genes (cut-off ≤ 98%). Normal karyotype was found by FISH in 25.8% of patients, 13q− in 46,1%, 11q− in 21,3%, +12 in 18%, and 17p− in 7,9% of patients. Of these 187 patients, 23,5% had a history of chronic stimulation (10,7% AI, 12,8% Inf). Age and Binet stage were similar between CS and non-CS patients. CS patients included a higher percentage of women (43.3 vs. 33.3%), and a higher percentage of CD38 positive (cut-off = 30%) patients (43,8 vs. 27,9%) compared to the non-CS subgroup, although both not statistically different. CS patients had a significantly higher percentage of unmutated clones (53%) compared to non-CS patients (28%) (p=0,002). Unfavorable cytogenetics (11q−, 17p−, +12) were more pronounced in CS patients compared to the non-CS group (77,8% vs 26,4%). The 4 most frequently used VH genes were 1–69, 3–30, 4–34, and 5–51 for the CS group, and 1–69, 2–5, 3–23, and 3–7 for the non-CS group. VH 1-69, the most frequently used VH gene overall, was unmutated in all CS patients, in non-CS patients several mutated cases were found. Several VH genes (2–26, 2–5, 3–7, 3–9) were exclusively unmutated in CS patients while they were mutated in non-CS patients. Several genes were exclusively used in either CS group (3–13, 3–15, 4–31, 4–39, 4–61, 5–51) or non-CS group (3–64, 3–65, 3–71, 3–74, 4–30, 7–4). They were mutated in most cases. Despite the drawbacks of our study (classification based on patients history and medical records), we provide unique and novel data on the frequency of chronic antigenic stimulation in an unselected cohort of newly diagnosed CLL patients. We noted considerable discrepancies between CS and non-CS patients regarding mutational status and VH gene usage. Our data warrant further evaluation of the role of CS in the development and course of B-CLL.

scholarly journals Sickle Cell Disease (SCD) As a Risk for COVI19 Compared to Those without SCD Among Patients Admitted in a Large Urban Center, As Estimated By PCR Sars-v-2 Positive Vs Negative Testing

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4170-4170
Author(s):  
Tom Adamkiewicz ◽  
Mohamed Mubasher ◽  
Folashade Omole ◽  
Melvin R. Echols ◽  
Jason Payne ◽  
...  
Keyword(s):  
African American ◽  
Respiratory Failure ◽  
Conflicts Of Interest ◽  
Care Facility ◽  
Memorial Hospital ◽  
Beta Thalassemia ◽  
Separate Analysis ◽  
Black African ◽  
Medicine Service ◽  
Increased Risk

Abstract A diagnosis of SCD is considered to be at risk for COVD19. To further define the association between SCD and infection with COVID-19, we estimated risk, by comparing presence or absence of COVID19 infections in individuals with and without SCD admitted concurrently to a large urban health care facility (Grady Memorial Hospital, Atlanta, GA; 960 beds, 5th largest public hospital in the US). Primary outcome was a positive or negative COVID-19 diagnosis as defined bySARS-CoV-2 PCR testing. A patient was considered to be COVID-19 positive if tested positive withSARS-CoV-2 PCR for the first time, anytime during the study period, irrespective of number of tests. A patient was considered to be COVID-19 negative if patient had no positive tests during the study period, and had one or moreSARS-CoV-2 PCR negative tests. For COVID19 positive patients, the admission of theSARS-CoV-2 PCR positive test was included in the analysis. For COVID19 negative patients, the first admission with aSARS-CoV-2 PCR negative test was considered for analysis. For this interim analysis, SCD was defined by ICD10 and registry data. Clinical diagnosis such as obesity and respiratory failure were defined by ICD10 coding. Data was obtained from quarterly centralized Epic EMR data extractions. Analysis of outcome of COVID19 positive vs negatives was stratified in four separate analysis: all admissions, ICU admissions, those with respiratory failure and those who died. Multivariate dichotomous logistic regression analyses modeled binary outcome effect of SCD, adjusted for age (<40 vs. > 40 years), sex at birth (females vs. males) and obesity (SAS version 9.4 was used for statistical analyses and overall significance level was set at 0.05). To ensure population homogeneity analysis was conducted on patient ages 20 to 60 years that were Black/African American and admitted from the Emergency Department for a short stay and/or the medicine service (variable interactions at a p<0.01). The study was approved by the institutional review board and by the hospital research oversight committee. Overall, between 3/23/2020 and 6/30/2020, 23697 patients were admitted once or more to Grady Memorial Hospital with one or more PCR sars-cov-2 test, of these 405 were patients with SCD (1.7%). Of the total, 2566 patients (10.8%) tested positive for COVID-19, and 48 patients with SCD (11.8%) were positive. Of 7041 (29.7%) were part of the study population, 332 (4.7%) where patients with SCD (hemoglobin [hb] SS/Sbeta0 =252, hbSC n=55, hbS beta thalassemia+ or hbS beta thalassemia undetermined n=21). Among patients without SCD, 36.3% were female, (n=2557) and among patients with SCD, 53.6% (n=178). The mean age of patients without SCD was: 51.1 years (standard deviation [std]) +/- 19.5 years), and for those with SCD: 35.0 years (std +/- 12.0 years). Results of univariate and multivariate analysis are presented in the table. In conclusion, in a Black/African American patients admitted from the Emergency Room for observation and/or the internal medicine service, when adjusted for age, gender and obesity, with SCD are at a significant increased risk for admissions with COVID-19 infection in general as well as ICU admission or admission with respiratory failures. Further studies can help articulate the risk associated with SCD as well as its potential interaction with other factors, with attention to confounders. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Associated Malignancies Among Patients and Kin with Waldenstrom's Macroglobulinemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4159-4159
Author(s):  
Christina Hanzis ◽  
Zachary Hunter ◽  
Robert Manning ◽  
Megan Lewicki ◽  
Philip Brodsky ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Family Members ◽  
Skin Melanoma ◽  
Waldenström’S Macroglobulinemia ◽  
Familial Predisposition ◽  
Increased Risk ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Abstract 4159 Waldenstrom's macroglobulinemia (WM) is a B-cell malignancy characterized as an IgM secreting lymphoplasmacytic lymphoma. Familial predisposition is common in WM. Studies to date by us and others have revealed three identifiable clinical subtypes for WM predisposition: * Sporadic; proband has WM, but there is an absence of WM or other B-cell disorders in other family members; * Familial, Mixed B-cell Disorders Subtype; proband has WM, and various B-cell disorders are manifested by other family members. * Familial, WM Only Subtype; proband has WM, and only WM is present in other family members; While these studies suggest a separate genetic predisposition for WM, the correlation of additional cancer risk among all patients with WM and their kin, and well as those sub typed by familial WM predisposition may herald important information for common genetic risks to cancer. We therefore examined the incidence of additional malignancies in 923 consecutive WM patients seen at our Institution, and characterized the frequencies of additional malignancies based on familial subtype and against SEER data. In addition, we also characterized the incidence of solid cancers in kin of WM patients, and sub typed these cancers based on familial WM presentation. Of the 923 patients, 221 (23.9%) patients had at least one additional malignancy to WM. Among these patients, 32 had 2, and 4 (0.43%) had 3 additional malignancies. For 167/221 (75.5%), the associated cancers were diagnosed before WM. The associated malignancies for all patients were as follows: Prostate (n=53; 9.2% of all males); Breast (n=27; 7.7% of all females); Skin (Basal and Squamous; n=61; 6.6%); Skin (Melanoma; n=16; 1.7%); Lung (n=12; 1.3%); Thyroid (n=10; 1.1%); Colorectal (n=7; 0.8%); Bladder (n=8; 0.9%) Other B-cell Malignancies (n=18; 2.0%); Renal (n=6; 0.7%); MDS (n=6; 0.65%); Other (n=11; 1.2%). The incidence of Lung (p=0.002) and Prostate (p=0.07) were higher among WM patients with Familial, Mixed B-cell Disorders Subtype. To avoid potential treatment related impact on additional cancer development, we next adjusted the observed versus expected frequencies based on SEER-17 data. The age adjusted incidence for development of any malignancy among WM patients was 7.6 fold higher when the development of another cancer antedated the diagnosis of WM. Among all WM patients, the incidence of solid cancers among first degree kin were as follows: Prostate (n=98; 10.6%); Breast (n=133; 14.4%); Skin (Basal and Squamous; n=21; 2.3%); Skin (Melanoma; n=21; 2.3%); Lung (n=116; 12.5%); Thyroid (n=9; 1.0%), Colorectal (n=79; 8.6%); Renal (n=8; 0.9%); and Gastric (n=20; 2.2%). The incidence of Breast (p=0.0098), and Skin (Melanoma) (p=0.037) cancers were higher among first degree kin of patients with the Sporadic versus Familial, Mixed B-cell Disorders Subtype. In summary, the above data suggest an increased risk for additional cancers among all WM patients, as well as specific risks for lung and prostate cancer among patients with Familial, Mixed B-cell Disorders Subtype. Moreover, these data also show the association of specific types of solid cancers in first degree kin of WM patients, particularly for WM patients with the Sporadic Subtype. n= Age (Yrs) Gender % Treated Additional Cancers Sporadic 666 60 (29–91) 64% M; 36% F 515 (77%) 163 (24.4%) Familial, Mixed B–cell Disorders 212 58 (36–85) 57% M; 43% F 156 (73%) 50 (23.5%) Familial, WM Only 45 61 (35–89) 56% M; 44% F 35 (77%) 8 (17.7%) Total 923 59 (29–91) 62% M; 38% F 706 (76.4%) 221 (23.9%) Disclosures: No relevant conflicts of interest to declare.

Development of a Splenic Marginal Zone Lymphoma Associated with Active Chronic Visceral Leishmaniasis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5202-5202
Author(s):  
Maja Ølholm Vase ◽  
Ylva Kristina Hellberg ◽  
Carsten Schade Larsen ◽  
Jørgen Eskild Petersen ◽  
Henrik Schaumburg ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Marginal Zone ◽  
Conflicts Of Interest ◽  
Marginal Zone Lymphoma ◽  
Antigenic Stimulation ◽  
Whole Body ◽  
Splenic Marginal Zone Lymphoma ◽  
Antigen Stimulation ◽  
Increased Risk ◽  
Leishmania Amastigotes

Abstract Abstract 5202 We here report the observation of the development of a splenic marginal zone lymphoma (SMZL) after years of active chronic visceral Leishmania (VL) infection, implying a possible pathogenic link between these two conditions, where the neoplastic process is preceded by a prolonged period of chronic antigen stimulation. In 2004, a 60-year old male developed attack-like episodes of septic fever with chills, rigor and subsequent profound fatigue. He had a 4 years previous medical history of severe asthma-like symptoms and hypereosinophilia. A bone marrow (BM) and liver biopsy were inconclusive. A whole-body computed tomography showed a moderately enlarged spleen. No evidence of bacterial, fungal or viral infection was found; the symptoms persisted, although mitigated, with occasional exacerbations over the following 3 years. By 2007 the patient was admitted again and a new BM biopsy was taken, still showing reactive changes. Due to increased splenomegaly, a diagnostic splenectomy was performed. Examination of the spleen revealed a primary splenic marginal zone lymphoma (SMZL). In 2010 the patient was admitted with septicaemia and constitutional symptoms. A BM biopsy showed the presence of numerous Leishmania amastigotes and a retrospective review of all previous biopsies (since 2004) identified Leishmania amastigotes in all of them. In fact, a thorough travel history covering the previous two decades revealed several visits, often twice a year, to the Mediterranean basin, e.g. Greece and Malta, areas endemic for Leishmania infantum (L. infantum). Visceral Leishmaniasis is a frequent opportunistic infection in HIV-infected immunodeficient individuals but uncommon in cancer patients, and only a few cases of VL in patients with already well-established malignant lymphoma have been reported. Chronic antigenic stimulation by microbial pathogens has been proposed as a pathogenetic factor in a variety of marginal zone lymphomas. Tissue specific immune responses toward Leishmania parasites have been shown in rodents, and the spleen is a ‘safe harbor’ for the long-term persistence of visceralizing Leishmania. Sustained antigenic stimulation with upregulation of critical signaling pathways may result in prolonged polyclonal B-cell proliferation, and a subsequent increased risk of malignant transformation. This case is the first to provide evidence for a possible link between chronic antigen stimulation by long-lasting L. infantum infection and the development of a SMZL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation

2021 ◽  
Vol 22 (8) ◽  
pp. 1008-1019 ◽  
Author(s):  
Mohamed S. Abdel-Hakeem ◽  
Sasikanth Manne ◽  
Jean-Christophe Beltra ◽  
Erietta Stelekati ◽  
Zeyu Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Antigenic Stimulation ◽  
Chronic Antigenic Stimulation ◽  
Memory Differentiation

scholarly journals A qualitative study on the multi-level process of resilience development for adults recovering from eating disorders

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Katie Grogan ◽  
Hannah O’Daly ◽  
Jessica Bramham ◽  
Mary Scriven ◽  
Caroline Maher ◽  
...  
Keyword(s):  
Eating Disorders ◽  
Eating Disorder ◽  
Qualitative Study ◽  
Significant Proportion ◽  
Well Being ◽  
Fundamental Aspect ◽  
Increased Risk ◽  
Resilience Process ◽  
Multi Level ◽  
Level Process

Abstract Background Resilience research to date has been criticised for its consideration of resilience as a personal trait instead of a process, and for identifying individual factors related to resilience with no consideration of the ecological context. The overall aim of the current study was to explore the multi-level process through which adults recovering from EDs develop resilience, from the perspectives of clients and clinicians. The objective of this research was to outline the stages involved in the process of developing resilience, which might help to inform families and services in how best to support adults with EDs during their recovery. Method Thirty participants (15 clients; 15 clinicians) took part in semi-structured interviews, and responded to questions relating to factors associated with resilience. Using an inductive approach, data were analysed using reflexive thematic analysis. Results The overarching theme which described the process of developing resilience was ‘Bouncing back to being me’, which involved three stages: ‘Who am I without my ED?’, ‘My eating disorder does not define me’, and ‘I no longer need my eating disorder’. Twenty sub-themes were identified as being involved in this resilience process, thirteen of which required multi-level involvement. Conclusion This qualitative study provided a multi-level resilience framework for adults recovering from eating disorders, that is based on the experiences of adults with eating disorders and their treating clinicians. This framework provided empirical evidence that resilience is an ecological process involving an interaction between internal and external factors occurring between adults with eating disorder and their most immediate environments (i.e. family and social). Plain English summary Anorexia nervosa, bulimia nervosa and binge-eating disorder demonstrate high rates of symptom persistence across time and poor prognosis for a significant proportion of individuals affected by these disorders, including health complications and increased risk of mortality. Many researchers have attempted to explore how to improve recovery outcomes for this population. Eating disorder experts have emphasised the need to focus not only on the weight indicators and eating behaviours that sustain the eating disorder during recovery, but also on the psychological well-being of the person recovering. One way to achieve this is to focus on resilience, which was identified as a fundamental aspect of eating disorder recovery in previous research. This study conceptualises resilience as a dynamic process that is influenced not only at a personal level but also through the environment in which the person lives. This study gathered data from adults with eating disorders and their treating clinicians, to devise a framework for resilience development for adults recovering from eating disorders. The paper discussed ways in which these findings and the framework identified can be easily implemented in clinical practice to facilitate a better understanding of eating disorder resilience and to enhance recovery outcomes.

scholarly journals Exploring Condom Use Behaviors Among African American Adolescent Boys in the Deep South

2021 ◽  
Vol 15 (2) ◽  
pp. 155798832110090
Author(s):  
Jessica Thames Chambliss ◽  
Retta Evans ◽  
Anneliese Bolland ◽  
Martha S. Wingate ◽  
John M. Bolland
Keyword(s):  
African American ◽  
Condom Use ◽  
Sexual Behaviors ◽  
Unplanned Pregnancy ◽  
The United States ◽  
Deep South ◽  
Adolescent Boys ◽  
African American Adolescent ◽  
Factors Associated ◽  
Increased Risk

Risky sexual behaviors among adolescents can increase adverse outcomes including unplanned pregnancy or contraction or transmission of disease. Adolescents who engage in risky sexual activities are at increased risk for adverse health and social outcomes compared to those who do not engage. Despite declines in adolescent pregnancy and birth rates, the diagnosis of sexually transmitted infections (STIs) is steadily increasing among adolescents. Moreover, African American adolescent boys in the United States, specifically in the southeastern region are disproportionally at greater risk for STIs, and STI diagnosis within this population has increased over time, compared to their white counterparts. This study sought to identify factors associated with condom use among adolescent boys in the Deep South. Using data from the Mobile Youth Survey, a longitudinal adolescent community-based survey, this study assessed the relationship between personal, behavioral, and environmental factors and condom use among African American adolescent boys (14–19 years). Younger participants (14–15 and 16–17) were more likely to use a condom during the last sexual intercourse compared to older participants (18–19 years). High positive attachment to boy/girlfriend was associated with increased condom use. The number of sexual partners, age at their first sexual encounter, recent sexual behavior, and having an STI were also associated with increased condom use among participants. The study provides further insights into factors associated with condom use among African American adolescent boys and results can inform the development of sexual health interventions.

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 Why do frail patients with chronic heart failure die and become hospitalised?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Sze ◽  
P Pellicori ◽  
J Zhang ◽  
J Weston ◽  
A.L Clark
Keyword(s):  
Heart Failure ◽  
Cause Of Death ◽  
Hospital Admissions ◽  
Average Length ◽  
Significant Proportion ◽  
Length Of Hospital Stay ◽  
Clinical Frailty Scale ◽  
Frail Patients ◽  
Increased Risk

Abstract Background Frailty is common in patients with heart failure (HF) and is associated with increased morbidity and mortality. A better understanding of the causes of hospitalisations and death in frail patients might help to tailor interventional strategies for these at-risk patients. Purpose We studied the cause of death and hospitalisations in ambulatory patients with HF and frailty. Methods We assessed frailty using the clinical frailty scale (CFS) in consecutive HF patients attending a routine follow-up visit. Those with CFS ≥5 were classified as frail. Mortality and hospitalisations were ascertained from medical records (updated systematically using an NHS electronic database), discharge letters, autopsy reports and death certificates. We studied the primary cause of death and hospitalisations within one year of enrolment. Results 467 patients (67% male, median (IQR) age 76 (69–82) years, median (IQR) NT-proBNP 1156 (469–2463) ng/L) were enrolled. 206 (44%) patients were frail. Frail patients were more likely to not receive or receive suboptimal doses of ACEi/ARB and Beta-blockers; while non-frail patients were more likely to be treated with optimal doses. At 1-year follow up, there were 56 deaths and 322 hospitalisations, of which 46 (82%) and 215 (67%) occurred in frail patients. Frailty was associated with an increased risk of all-cause mortality (HR (95% CI): 4.27 (2.60–7.01)) and combined mortality/ hospitalisation (HR (95% CI): 2.85 (2.14–3.80)), all p<0.001. 57% (n=26) of frail patients died of cardiovascular causes (of which 58% were due to HF progression); although deaths due to non-cardiovascular causes (43%, n=20), especially severe infections, were also common (26%, n=12). (Figure 1) The proportion of frail patients who had non-elective hospital admissions within 1 year was more than double that of non-frail patients (46% (n=96) vs 21% (n=54); p<0.001). Compared to non-frail patients, frail patients had more recurrent (≥2) hospitalisations (28% (n=59) vs 9% (n=24); p<0.001) but median (IQR) average length of hospital stay was not significantly different (frail: 6 (4–11) vs non-frail: 6 (2–12) days, p=0.50). A large proportion of hospitalisations (64%, n=137) in frail patients were due to non-cardiovascular causes (of which 34%, 30% and 20% were due to infections, falls and comorbidities respectively). Of cardiovascular hospitalisations (36%, n=78), the majority were due to decompensated HF (67%, n=46). (Figure 1) Conclusion Frailty is common in patients with HF and is associated with an increased risk of mortality and recurrent hospitalisations. A significant proportion suffered non-cardiovascular deaths and hospitalisations. This implies that interventions targeted at HF alone can only have limited impact on outcomes in frail patients. Figure 1 Funding Acknowledgement Type of funding source: None

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