RESUMO
BACKGROUND: Inborn errors of immunity are mostly monogenic. However, disease phenotype and outcome may be modified by the coexistence of a second gene defect. OBJECTIVE: We sought to identify the genetic basis of the disease in a patient who experienced bleeding episodes, pancytopenia, hepatosplenomegaly, and recurrent pneumonia that resulted in death. METHODS: Genetic analysis was done using next-generation sequencing. Protein expression and phosphorylation were determined by immunoblotting. T-cell proliferation and F-actin levels were studied by flow cytometry. RESULTS: The patient harbored 2 homozygous deletions in STX11 (c.369_370del, c.374_376del; p.V124fs60∗) previously associated with familial hemophagocytic lymphohistiocytosis and a novel homozygous missense variant in SLP76 (c.767C>T; p.T256I) that resulted in an approximately 85% decrease in SLP76 levels and absent T-cell proliferation. The patient's heterozygous family members showed an approximately 50% decrease in SLP76 levels but normal immune function. SLP76-deficient J14 Jurkat cells did not express SLP76 and had decreased extracellular signal-regulated kinase signaling, basal F-actin levels, and polymerization following T-cell receptor stimulation. Reconstitution of J14 cells with T256I mutant SLP76 resulted in low protein expression and abnormal extracellular signal-regulated kinase phosphorylation and F-actin polymerization after T-cell receptor activation compared with normal expression and J14 function when wild-type SLP76 was introduced. CONCLUSIONS: The hypomorphic mutation in SLP76 tones down the hyperinflammation due to STX11 deletion, resulting in a combined immunodeficiency that overshadows the hemophagocytic lymphohistiocytosis phenotype. To our knowledge, this study represents the first report of the opposing effects of 2 gene defects on the disease in a patient with an inborn error of immunity.
Assuntos
Actinas , Linfo-Histiocitose Hemofagocítica , Humanos , MAP Quinases Reguladas por Sinal Extracelular , Linfo-Histiocitose Hemofagocítica/genética , Mutação , Proteínas Qa-SNARE/genética , Receptores de Antígenos de Linfócitos T/genética , Transdução de SinaisRESUMO
BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described. METHODS AND RESULTS: The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis. CONCLUSIONS: While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.
Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Doença da Artéria Coronariana , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Prevalência , Doença da Artéria Coronariana/complicações , Incidência , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/epidemiologia , Neuropatias Amiloides Familiares/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Cardiomiopatias/terapiaRESUMO
Heart failure (HF) etiology, presentation and prognosis differ by sex, with female sex-specific and -predominant risk factors playing important roles. We systematically reviewed the studies cited by the 2017 American College of Cardiology/ American Heart Association/ Heart Failure Society of America Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Female cardiovascular risk factors were broadly categorized as female sex-specific (reproductive, pregnancy, menopausal) and female sex-predominant (depression, anthracycline exposure, autoimmune disease) risk factors. Of the 205 cited articles, only 3 studies (1.6%) reported any female sex-specific cardiovascular risk factor in the data analysis or results sections. Oral contraceptive use (n = 1), menopausal status (n = 2) and hormone replacement therapy (n = 2) were the only female sex-specific cardiovascular risk factors reported. No other female sex-specific or -predominant cardiovascular risk factor was reported by any of the eligible studies. Our work highlights that in addition to the need for proportional representation of women in heart failure clinical studies, inclusion of female sex-specific and -predominant risk factors in data collection and analysis is of paramount importance to guide heart failure care in the female population.
Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , American Heart Association , Doenças Cardiovasculares/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/terapia , Humanos , Masculino , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Cervical cancer is considered the third leading cause of death among women worldwide, and human papillomavirus was identified as a major causative agent for developing cervical cancer. OBJECTIVES: This study aimed to assess the knowledge and attitudes towards cervical cancer prevention among women in Khartoum state, Sudan. DESIGN: A community-based cross-sectional study implemented in Khartoum state, Sudan, from 1 August 2020 to 1 September 2020. METHODS: We conducted a descriptive cross-sectional community-based study using an electronic questionnaire for data collection. Descriptive statistics, frequency, mean, and percentage were computed. RESULTS: The study included 716 female participants with a mean age of 27.6 + 8.7 years. 580 (81.0%) and 229 (32.0%) had heard about cervical cancer and Pap test, respectively. cervical cancer was assumed related to alcohol consumption 109 (15.2%), giving birth to many children 51 (7.1%), ageing 118 (16.5%), and having many sexual partners 335 (46.8%). In addition, 300 (41.9%) attributed cervical cancer to having human papillomavirus infection, 256 (35.6%) to the prolonged use of contraceptives, and 162 (22.6%) to smoking. Knowledge about the best time to be vaccinated against human papillomavirus, 110 (15.4%) stated it is better after marriage. Regression models to predict the effectors on participants' knowledge and attitudes showed a low standard deviation of the estimates with higher values of the adjusted R2 [R: 0.041, 0.017, and 0.006; std: 1.527, 0.417, and 0.426]. This indicates the combined influence of occupation, educational level, family income, and marital status on the participant's knowledge and attitude levels. CONCLUSION: This study revealed that the participant's knowledge and attitudes levels are mainly driven by their occupation, educational level, family income, and marital status altogether. This underscores the need for a countrywide community engagement campaign through health education and raising awareness sessions, and massive social media to sensitize the community and healthcare providers about the risk of cervical cancer and the available prevention and control measures.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Adolescente , Adulto , Criança , Feminino , Humanos , Gravidez , Adulto Jovem , Atitude , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Papillomavirus Humano , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Sudão , Inquéritos e Questionários , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal/efeitos adversosRESUMO
Since the 50 s of the last century, labor charts have been proposed and appraised as a tool to diagnose labor abnormalities and guide decision-making. The partogram, the most widely adopted form of labor charts, has been endorsed by the world health organization (WHO) since 1994. Nevertheless, recent studies and systematic reviews did not support clinical significance of application of the WHO partogram. These results have led to further studies that investigate modifications to the structure of the partogram, or more recently, to reconstruct new labor charts to improve their clinical efficacy. This guideline appraises current evidence on use of labor charts in management of labor specially in low-resource settings.
Assuntos
Trabalho de Parto , Gravidez , Feminino , Humanos , Educação de Pós-Graduação , Oriente MédioRESUMO
BACKGROUND: Unplanned dialysis initiation is common in patients with chronic kidney disease (CKD). OBJECTIVE: To determine common definitions and patient risk factors for unplanned dialysis. DESIGN: Systematic review. SETTING: MEDLINE, EMBASE, and the Cochrane Library were searched from inception to February 2018. PATIENTS: Studies that included incident chronic dialysis patients or patients with CKD that cited a definition or examined risk factors for unplanned dialysis were included. MEASUREMENTS: Definitions and criteria for unplanned dialysis reported across studies. Patient characteristics associated with unplanned dialysis. METHODS: Two reviewers independently extracted data using a standardized data abstraction form and assessed study quality using a modified New Castle Ottawa Scale. RESULTS: From 2797 citations, 48 met eligibility criteria. Reported definitions for unplanned dialysis were variable. Most publications cited dialysis initiation under emergency conditions and/or with a central venous catheter. The association of patient characteristics with unplanned dialysis was reported in 26 studies, 18 were retrospective and 21 included incident dialysis patients. The most common risk factors in univariate analyses were (number of studies) increased age (n = 7), cause of kidney disease (n = 6), presence of cardiovascular disease (n = 7), lower serum hemoglobin (n = 9), lower serum albumin (n = 10), higher serum phosphate (n = 6), higher serum creatinine or lower estimated glomerular filtration rate (eGFR) at dialysis initiation (n = 7), late referral (n = 5), lack of dialysis education (n = 6), and lack of follow-up in a predialysis clinic prior to dialysis initiation (n = 5). A minority of studies performed multivariable analyses (n = 10); the most common risk factors were increased age (n = 4), increased comorbidity score (n = 3), late referral (n = 5), and lower eGFR at dialysis initiation (n = 3). LIMITATIONS: Comparison of results across studies was limited by inconsistent definitions for unplanned dialysis. High-quality data on patient risk factors for unplanned dialysis are lacking. CONCLUSIONS: Well-designed prospective studies to determine modifiable risk factors are needed. The lack of a consensus definition for unplanned dialysis makes research and quality improvement initiatives in this area more challenging.
CONTEXTE: L'initiation non planifiée d'un traitement de dialyse est fréquente chez les patients atteints d'insuffisance rénale chronique (IRC). OBJECTIFS: L'étude visait à définir la dialyse non planifiée et à définir ses facteurs de risques chez les patients. TYPE D'ÉTUDE: Une revue systématique. SOURCES: Les bases de données MEDLINE et EMBASE, de même que la bibliothèque Cochrane ont été consultées, de leur création à février 2018. SUJETS: Les études traitant de patients atteints d'IRC ou dialysés de façon chronique, et qui citaient une définition ou examinaient les facteurs de risques associés à une dialyse non planifiée. MESURES: On a colligé les différentes définitions d'une dialyse non planifiée rapportées dans l'ensemble des études, ainsi que les critères la définissant et les caractéristiques des patients qui y étaient associées. MÉTHODOLOGIE: À l'aide d'un formulaire normalisé d'extraction des données, deux examinateurs ont compilé les données de façon indépendante. La qualité des études a été évaluée avec une échelle de Newcastle-Ottawa modifiée. RÉSULTATS: Des 2 797 études répertoriées, 48 satisfaisaient les critères d'admissibilité. Les définitions d'une dialyse non planifiée variaient d'une étude à l'autre. La plupart des publications mentionnaient une dialyse débutée en situation d'urgence et/ou avec un cathéter veineux central. L'association des caractéristiques des patients à une dialyse non planifiée a été signalée dans 26 études, desquelles 18 constituaient des études rétrospectives et 21 incluaient des patients dialysés incidents. Les facteurs de risque les plus souvent cités dans les analyses univariées étaient (en nombre d'études) : l'âge avancé du patient (n=7), la cause de la néphropathie (n=6), la présence d'une cardiopathie (n=7), de faibles taux d'hémoglobine (n=9) et d'albumine (n=10), un taux élevé de phosphate sérique (n=6), un taux élevé de créatinine sérique ou un faible DFGe à l'amorce de la dialyse (n=7), un aiguillage tardif (n=5), le manque d'information sur la dialyse (n=6), et l'absence de suivi dans une clinique de prédialyse avant l'initiation du traitement (n=5). Seules quelques études avaient procédé à des analyses multivariées (n=10). Dans ces dernières, les facteurs de risques les plus fréquemment cités étaient : l'âge avancé du patient (n=4), un score de comorbidité élevé (n=3), un aiguillage tardif (n=5), et un faible DFGe au moment de l'initiation de la dialyse (n=3). LIMITES: La comparaison des résultats d'une étude à l'autre était difficile en raison d'un manque d'uniformité dans les définitions d'une dialyse non planifiée. On manque de données robustes sur les facteurs de risque menant à une dialyse non planifiée chez les patients. CONCLUSION: On constate un besoin pour des études prospectives bien conçues examinant les facteurs de risque modifiables. L'absence d'une définition consensuelle pour la dialyse non planifiée rend plus difficiles les initiatives de recherche et d'amélioration de la qualité dans ce domaine.
RESUMO
The purpose of this pilot study was to describe the presenting symptoms and its explanation from the patients' perspective of GHQ (General Health Questionnaire) positive cases attending primary care facility/a general practice in semiurban Lahore. Fifteen consecutive attenders were screened with GHQ and 11 GHQ positive cases went on to complete an adapted questionnaire derived from SEMI (Short Explanatory Model Interview). Though there was no consistency in the presenting symptoms of GHQ positive cases on presentation to a general practitioner, all described their problems as intense, less than 2 years on onset and on reflection located its origins in their social worlds. These findings have implications in terms of providing preliminary data for a larger study, perhaps looking at development of psychosocial interventions for treatment of mental distress in our local context as it seems to have its origins in their social worlds.