SEPN1-Related Myopathy: The Importance of Diagnosis and Challenges to Management of CMD in Resource Poor Settings.
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ABSTRACT:
SUBMITTER: Gajam S
PROVIDER: S-EPMC8965955 | biostudies-literature | 2021 Nov-Dec
REPOSITORIES: biostudies-literature
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SEPN1-Related Myopathy: The Importance of Diagnosis and Challenges to Management of CMD in Resource Poor Settings.
Gajam Siddhartha S Maganthi Madhuri M Mathew Ann Agnes AA Rath Suman S
Annals of Indian Academy of Neurology 20210305 6
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Project description:IntroductionGlomerular diseases are the leading drivers of nondiabetic chronic kidney disease disability-adjusted life years in resource-limited countries. Proper diagnosis and treatment relies on resources including kidney biopsy, ancillary testing, and access to evidence-based therapies.MethodsWe conducted a cross-sectional internet-based survey cascaded through society mailing lists among nephrologists in countries of Asia, Africa, and Eastern Europe. We collected the data on respondent demographics, their ability to perform and appropriately interpret a kidney biopsy, and their access to complementary investigations and treatment practices.ResultsA total of 298 kidney care specialists from 33 countries (53.3% from Asia and 44.6% from Africa; 64% from academic or university hospitals) participated in the survey. Of these specialists, 85% performed kidney biopsy. About 61% of the respondents could not obtain a kidney biopsy in more than 50% of patients with suspected glomerular disease. About 43% of the respondents from Africa had access to only light microscopy. Overall, the inability to undertake and fully evaluate a biopsy and perform ancillary investigations were more profound in Africa than in Asia. Overall, 59% of participants reported that more than 75% of their patients meet the cost of diagnosis and treatment by out-of-pocket payments. Empirical use of immunosuppression was higher in Africa than in Asia. The main barriers for diagnosis and treatment included delayed presentation, incomplete diagnostic work-up, and high cost of treatment.ConclusionMajor system-level barriers impede the implementation of guideline-driven approaches for diagnosis and treatment of patients with glomerular disease in resource-limited countries.
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Project description:BackgroundOn a global scale, cases of placenta accreta spectrum are often just identified during cesarean delivery because they are missed during antenatal care screening. Routine operating teams not trained in the management of placenta accreta spectrum are faced with difficult surgical situations and have to make decisions that may define the clinical outcomes. Although there are general recommendations for the intraoperative management of placenta accreta spectrum, no studies have described the clinical reality of unexpected placenta accreta spectrum cases in resource-poor settings.ObjectiveThis study aimed to describe the maternal outcomes of previously undiagnosed placenta accreta spectrum managed in resource-poor settings in Colombia and Indonesia.Study designThis was a retrospective case series of women with histologically confirmed placenta accreta spectrum treated in 2 placenta accreta spectrum centers after referral from remote resource-poor hospitals. Clinical outcomes were analyzed according to the initial type of management: (1) no cesarean delivery; (2) placenta left in situ after cesarean delivery; (3) partial removal of the placenta after cesarean delivery; and (4) post-cesarean hysterectomy. In addition, we evaluated the use of telemedicine by comparing the outcomes of women in hospitals that used the support of the placenta accreta spectrum center during the initial surgery.ResultsA total of 29 women who were initially managed in Colombia (n=2) and Indonesia (n=27) were included. The lowest volume of blood loss and the lowest frequency of complications were in women who underwent deferred cesarean delivery (n=5; 17.2%) and in those who had a delayed placental delivery (n=5; 20.7%). Five maternal deaths (14%) occurred in the group that did not receive telehelp, and 4 women died of irreversible shock because of uncontrolled bleeding.ConclusionPreviously undiagnosed placenta accreta spectrum in resource-poor hospitals was associated with a high risk of maternal mortality. Open-close abdominal surgery or leaving the placenta in situ seem to be the best choices for unexpected placenta accreta spectrum management in resource-poor settings. Telemedicine with a placenta accreta spectrum center may improve prognosis.
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Project description:Posterior reversible encephalopathy syndrome (PRES) is a rare clinical syndrome that has been observed in different age groups, including pediatric patients. Identified triggers of PRES in both children and adults have included immunosuppressive and cytotoxic agents, organ transplantation, severe sepsis, blood transfusion, or evidence of human immunodeficiency virus-1 (HIV-1). Its clinical and radiological courses have been reported as mostly benign and reversible over days to weeks. Computed tomography (CT) scans are helpful in diagnosis, but magnetic resonance imaging (MRI) remains the gold standard. Unfortunately, because of the prohibitive costs of such medical equipment, diagnosis remains a challenge in developing countries. There is a dearth of information about pediatric PRES in resource-poor settings. This narrative aims to draw attention to the possible existence of PRES in children and to identify factors responsible for the difficulty in making the diagnosis. This review will hopefully increase awareness of PRES among pediatricians in order to make early diagnosis and institute appropriate management of this condition.
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Project description: Not available
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Project description:BackgroundNeurocysticercosis (NCC) is the most common cause of acquired epilepsy in Taenia solium endemic areas, primarily situated in low-income countries. Diagnosis is largely based upon the "Del Brutto diagnostic criteria" using the definitive/probable/no NCC diagnosis approach. Neuroimaging and specific T. solium cysticercosis antibody detection results are at the mainstay of this diagnosis, while antigen detection in serum has never been included. This study aimed at evaluating the addition of antigen detection as a major diagnostic criterion, especially in areas where neuroimaging is absent.MethodsThe B158/B60 monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating cysticercus antigen was carried out retrospectively on serum samples collected during a hospital-based study from 83 people with epilepsy (PWE) in an endemic area.ResultsThe addition of antigen results as a major criterion allowed the correct diagnosis of definitive NCC in 10 out of 17 patients as opposed to 0/17 without antigen results in the absence of neuroimaging. A sensitivity of 100% and a specificity of 84% were determined for the diagnosis of active NCC using antigen ELISA. While the use of a higher cutoff improves the specificity of the test to 96%, it decreases its sensitivity to 83%.ConclusionsIn areas where neuroimaging is absent, NCC diagnosis according to the existing criteria is problematic. Taking into account its limitations for diagnosis of inactive NCC, antigen detection can be of added value for diagnosing NCC in PWE by supporting diagnostic and treatment decisions. Therefore, we recommend a revision of the "Del Brutto diagnostic criteria" for use in resource poor areas and suggest the inclusion of serum antigen detection as a major criterion.
| S-EPMC3475663 | biostudies-literature
Project description:Reducing childhood mortality in resource-poor regions depends on effective interventions to decrease neonatal mortality from severe infection, which contributes up to a half of all neonatal deaths. There are key differences in resource-poor, compared to resource-rich, countries in terms of diagnosis, supportive care and treatment. In resource-poor settings, diagnosis is based on identifying clinical syndromes from international guidelines; microbiological investigations are restricted to a few research facilities. Low levels of staffing and equipment limit the provision of basic supportive care, and most facilities cannot provide respiratory support. Empiric antibiotic treatment guidelines are based on few aetiological and antimicrobial susceptibility data. Research on improving health care systems to provide effective supportive care, and implementation of simple pragmatic interventions, such as low-cost respiratory support, are essential, together with improved surveillance to monitor emerging drug resistance and treatment failures. Reductions in mortality will also be achieved through prevention of infection; including emerging vaccination and anti-sepsis strategies.
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Project description:GNE myopathy, previously known as hereditary inclusion body myopathy (HIBM), or Nonaka myopathy, is a rare autosomal recessive muscle disease characterized by progressive skeletal muscle atrophy. It has an estimated prevalence of 1 to 9:1,000,000. GNE myopathy is caused by mutations in the GNE gene which encodes the rate-limiting enzyme of sialic acid biosynthesis. The pathophysiology of the disease is not entirely understood, but hyposialylation of muscle glycans is thought to play an essential role. The typical presentation is bilateral foot drop caused by weakness of the anterior tibialis muscles with onset in early adulthood. The disease slowly progresses over the next decades to involve skeletal muscles throughout the body, with relative sparing of the quadriceps until late stages of the disease. The diagnosis of GNE myopathy should be considered in young adults presenting with bilateral foot drop. Histopathologic findings on muscle biopsies include fiber size variation, atrophic fibers, lack of inflammation, and the characteristic "rimmed" vacuoles on modified Gomori trichome staining. The diagnosis is confirmed by the presence of pathogenic (mostly missense) mutations in both alleles of the GNE gene. Although there is no approved therapy for this disease, preclinical and clinical studies of several potential therapies are underway, including substrate replacement and gene therapy-based strategies. However, developing therapies for GNE myopathy is complicated by several factors, including the rare incidence of disease, limited preclinical models, lack of reliable biomarkers, and slow disease progression.
| S-EPMC6277305 | biostudies-literature
Project description:ObjectiveThe study aimed to compare the usefulness of two staining methods for imprint cytology for diagnosis of Helicobacter pylori infection. Gastric biopsy specimens (from dyspeptic patients attending routine upper gastrointestinal endoscopy) were placed on glass slides to obtain imprints. The imprints were stained with Toluidine blue and Giemsa stains separately and observed under ×400 magnification using a light microscope. Imprinted biopsies were sectioned and stained with H & E stain and Giemsa stain for histological analysis. Diagnosis of H. pylori infection in both imprint and histological sections were confirmed by a consultant pathologist. The sensitivity, specificity, positive predictive value and negative predictive value of each stain were calculated and benchmarked against histological diagnosis.ResultsOf the 55 dyspeptic patients enrolled in the study, 5 were positive for H. pylori by Toluidine blue stain and 4 by Giemsa stain. The sensitivity of Toluidine blue stain (57.1%) was higher than Giemsa stain (42.9%) while the specificity of both stains was equal (97.9%). Giemsa stain gave a better discrimination for identification of H. pylori bacteria among the mucosal background. Imprint cytology is a rapid, simple and cost effective diagnosis method that can supplement histological diagnosis.
| S-EPMC6048746 | biostudies-literature
Project description:Mutations in SEPN1 result in a spectrum of early-onset muscle disorders referred to as SEPN1-related myopathy. The SEPN1 gene encodes selenoprotein N (SelN), which contains the amino acid selenocysteine (Sec). Incorporation of Sec occurs due to redefinition of a UGA codon during translation. Efficient insertion requires a Sec insertion sequence (SECIS) in the 3'UTR and, for at least a subset of selenoprotein genes, a Sec redefinition element (SRE) located adjacent to the UGA codon. We report the effect of three novel and one previously reported point mutation in the SelN SRE element on Sec insertion efficiency. Notably, the previously reported mutation c.1397G>A (p.R466Q), which weakens the secondary structure of the SRE element, reduces Sec insertion efficiency and SelN RNA levels. Muscle from patients with this mutation have negligible levels of SelN protein. This data highlights the importance of the SRE element during SelN expression and illustrates a novel molecular mechanism by which point mutations may lead to SEPN1-related myopathy.
| S-EPMC2909032 | biostudies-literature
Project description:IntroductionAcute kidney injury (AKI) is prevalent in low- and middle-income countries (LMIC) and is associated with significant morbidity and mortality, particularly among hospitalized patients. Successful strategies for the prevention and management of AKI in these countries are dependent on the capacity of primary care centers to provide optimal initial management of patients at risk for this disorder.MethodsFrom December 2018 to February 2019, using mixed methods, we assessed hospital capacity and the knowledge of clinicians relevant to the prevention, diagnosis, and management of AKI in Rwanda. A checklist based on Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and clinical vignette-based assessment tool were used to assess hospital capacity and provider knowledge base, respectively. Data were analyzed using stata 13 with findings reported as simple frequencies or means with standard deviation. Multivariate analysis was used to assess factors associated with a higher knowledge score among clinicians.ResultsTen hospitals and 193 health care providers from sites throughout Rwanda participated in the survey. Surveyed hospitals were equipped with basic general medical equipment but were deficient in diagnostic tools and medical supplies that would allow the diagnosis and nondialytic management of AKI. Although 20% of the hospitals could offer hemodialysis services, peritoneal dialysis services were nonexistent. With regard to knowledge base, the health care providers demonstrated significant deficiencies in the diagnosis and management of AKI. The mean knowledge score for all health providers was 6.3 (±1.5) of a maximum of 11, with a mean (±SD) score for doctors, nurses, and midwives of 6.3 ± 2.05, 6.4 ± 1.3, and 6.08 ± 1.2, respectively. On multivariate analysis, the length of clinical experience and age of the respondents were significantly associated with participants' knowledge score.ConclusionThis study documents significant barriers to providing optimal management of AKI in primary health care settings in Rwanda, a resource-limited setting. These include lack of specialized medical personnel, significant knowledge gaps among primary health care providers, suboptimal diagnostic capacity, and limited treatment options for detection and management of AKI.
| S-EPMC7336002 | biostudies-literature