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1.
JACC Adv ; 3(5): 100927, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38939627

RESUMO

Background: Persistent left ventricular hypertrophy after transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), due to their favorable effects on ventricular remodeling, have been hypothesized to improve outcomes post-TAVR, yet there are no recommendations regarding their use. Objectives: This study aimed to compare the outcomes of patients receiving ACEIs/ARBs with those not receiving ACEIs/ARBs after TAVR. Methods: We performed a literature search on PubMed and Cochrane Library until June 14, 2023, and included all studies comparing clinical outcomes between patients given ACEIs/ARBs and those not given ACEIs/ARBs after TAVR. All-cause mortality was the primary outcome. We used a random effects model with appropriate corrections to calculate relative risk (RR) and CIs, with all analyses carried out using R v4.0.3. Results: We included ten studies on the use of ACEIs/ARBs post-TAVR. Patients on ACEIs/ARBs had lower risk of all-cause mortality (RR: 0.74, 95% CI: 0.65-0.86, I2 = 62%, chi-square P < 0.01), cardiovascular mortality (RR: 0.70, 95% CI: 0.56-0.88, I2 = 0%, chi-square P = 0.54), and new-onset atrial fibrillation (RR: 0.71, 95% CI: 0.52-0.96, I2 = 0%, chi-square P = 0.59). Patients on ACEIs/ARBs had a similar risk of myocardial infarction, heart failure, stroke, new permanent pacemaker implantation, acute kidney injury, major bleeding, vascular complications, aortic regurgitation, and mitral regurgitation. Conclusions: We found that patients receiving ACEIs/ARBs had a lower risk of all-cause mortality, cardiovascular mortality, and new-onset atrial fibrillation. Risk of other outcomes was similar to patients not receiving ACEIs/ARBs. Randomized clinical trials are needed to explore the benefits of ACEIs/ARBs post-TAVR, so that definitive guidelines can be developed.

2.
Curr Probl Cardiol ; 49(9): 102693, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38852909

RESUMO

INTRODUCTION: Cardiology conferences represent a major avenue for learning, career advancement, and professional networking. Yet, costs of attending these conferences represent a major barrier, particularly for trainees and participants from low-middle-income countries (LMICs). Our study aimed to analyze the registration fees of major cardiology conferences worldwide. METHODS: We included conferences organized by international cardiovascular societies and those representing global regions. We did not include individual national or institutional conferences due to inability to systematically identify them. We collected 2024 registration fees from official conference websites, taking 2023 or 2022 fees if unavailable, and categorized them according to career stage and society membership status. Where specified, we chose 'early-bird' fees. All fees were converted to US dollars according to currency exchange rates per the International Monetary Fund on December 4, 2023, or if unavailable, per the last reported US Treasury Data. Other data collected included host country, virtual option availability, and LMIC discounts. RESULTS: 30 (65.2 %) conferences provided discounts for medical students, regardless of membership status, while 1 (2.2 %) provided discounts only for student-members. 36 (78.2 %) conferences offered discounts for residents/fellows, while 2 (4.3 %) offered discounts only for resident/fellow-members. Median fees for students and residents/fellows with membership were $255 and $287 (in US dollars), respectively while median fees for non-members were $303.5 and $397, respectively. 31 (67.4 %) conferences provided discounts for staff- members. Median fees for staff were $701 and $800 for members and non-members, respectively. Only 12 (26.1 %) conferences mentioned a virtual component, with 11 offering discounted registration compared with in-person rates. 7 (15.2 %) conferences had special in-person fees for LMIC-based registrants. 5 offered the same discounted rate regardless of training stage, while 2 offered additional discounts for trainees. CONCLUSION: We found that conference registration costs were substantial, including for trainees, with only a minority of conferences providing discounted rates for LMICs. Professional societies must reduce registration costs, potentially by implementing a tiered system based on training stage and country of origin. Further, to augment LMIC participation, dedicated scholarships and mentorship programs for LMIC-based registrants are needed.


Assuntos
Cardiologia , Congressos como Assunto , Humanos , Cardiologia/educação , Cardiologia/economia , Honorários e Preços , Sociedades Médicas , Países em Desenvolvimento
3.
South Asian J Cancer ; 13(1): 33-37, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38721108

RESUMO

Dr. Vikram GotaCovid-19 has led to significant mortality worldwide, with an increased risk in cancer patients. Vaccination provides significant protection against the infection. The study focuses on the immunogenicity and effectiveness of ChAdOx1 nCoV-19 vaccine in cancer patients within a real-world setting. Blood samples for measuring Covid antibody titers against the receptor binding domain were collected according to a convenient sparse sampling strategy in a real-world setting, with the days of the collection coinciding with their hospital appointment. The antibody titers between different groups were analyzed descriptively. A total of 56 patients were enrolled in the study. There was no apparent effect in antibody titers between patients with solid tumors and hematological malignancies (mean ± standard deviation [SD]: 36.80 ± 41.18 vs. 52.02 ± 26.27), among patients who were undergoing chemotherapy, immunotherapy, or local therapy (mean ± SD: 42.50 ± 44.46 vs. 50.06 ± 51.39 vs. 28.70 ± 25.03), and in patients with up to 90 days and more than 90 days' interval between their last treatment and date of vaccination (mean ± SD: 38.96 ± 42.66 vs. 40.51 ± 38.65). Additionally, there were only 2/56 patients with breakthrough infection, which points out the effectiveness of this vaccine in cancer patients. The ChAdOx1 nCoV-19 vaccine has activity in cancer regardless of the tumor type, type of treatment, or time from the last treatment.

4.
Indian Heart J ; 76(2): 113-117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38537883

RESUMO

OBJECTIVE: Despite the development of dedicated, two-stent strategies, including the double kissing (DK) crush technique, the ideal technique for coronary artery bifurcation stenting has not been identified. We aimed to compare and determine the absolute risk difference (ARD) of the DK crush technique alone versus provisional stenting approaches for coronary bifurcation lesions, using the Bayesian technique. METHOD: We queried PubMed/MEDLINE to identify randomized controlled trials (RCTs) that compared DK crush technique with provisional stenting for bifurcation lesions, published till January 2023. We used Bayesian methods to calculate the ARD and 95% credible interval (CrI). RESULTS: We included three RCTs, with 916 patients, in the final analysis. The ARD of cardiac death was centered at -0.01 (95% CrI: -0.04 to 0.02; Tau: 0.02, 85% probability of ARD of DK crush vs. provisional stenting <0). ARD for myocardial infarction was centered at -0.03 (95%CrI: -0.9 to 0.03; Tau: 0.05, 87% probability of ARD of DK crush vs. provisional stenting <0). ARD for stent thrombosis was centered at 0.00 (95% CrI: -0.04 to 0.03, Tau: 0.03, 51% probability of ARD for DK crush vs. provisional stenting <0). Finally, ARD for target lesion revascularization was centered at -0.05 (95% CrI: -0.08 to -0.03, Tau: 0.02, 99.97% probability of ARD for DK crush vs. provisional stenting <0). CONCLUSIONS: Bayesian analysis demonstrated a lower probability of cardiac death, myocardial infarction and target lesion revascularization, with DK crush compared with provisional stenting techniques, and a minimal probability of difference in stent thrombosis.


Assuntos
Teorema de Bayes , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/diagnóstico , Intervenção Coronária Percutânea/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Stents Farmacológicos , Angiografia Coronária , Stents
5.
Med Educ Online ; 29(1): 2302232, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38194431

RESUMO

India has been historically challenged by an insufficient and heterogeneously clustered distribution of healthcare infrastructure. While resource-limited healthcare settings, such as major parts of India, require multidisciplinary approaches for improvement, one key approach is the recruitment and training of a healthcare workforce representative of its population. This requires overcoming barriers to equity and representation in Indian medical education that are multi-faceted, historical, and rooted in inequality. However, literature is lacking regarding the financial or economic barriers, and their implications on equity and representation in the Indian allopathic physician workforce, which this review sought to describe. Keyword-based searches were carried out in PubMed, Google Scholar, and Scopus in order to identify relevant literature published till November 2023. This state-of-the-art narrative review describes the existing multi-pronged economic barriers, recent and forthcoming changes deepening these barriers, and how these may limit opportunities for having a diverse workforce. Three sets of major economic barriers exist to becoming a specialized medical practitioner in India - resources required to get selected into an Indian medical school, resources required to pursue medical school, and resources required to get a residency position. The resources in this endeavor have historically included substantial efforts, finances, and privilege, but rising barriers in the medical education system have worsened the state of inequity. Preparation costs for medical school and residency entrance tests have risen steadily, which may be further exacerbated by recent major policy changes regarding licensing and residency selection. Additionally, considerable increases in direct and indirect costs of medical education have recently occurred. Urgent action in these areas may help the Indian population get access to a diverse and representative healthcare workforce and also help alleviate the shortage of primary care physicians in the country. Discussed are the reasons for rural healthcare disparities in India and potential solutions related to medical education.


Assuntos
Educação Médica , Médicos , Humanos , Pessoal de Saúde , Índia
6.
Lung India ; 41(1): 67-70, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38160462

RESUMO

Pneumonia remains the top most killer of under-five Indian children. Pneumonia in children is usually caused by viral or bacterial infections. However, there are some unusual causes of pneumonia that merit consideration when pneumonia is recurrent or persistent.

7.
J Chem Phys ; 159(24)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38156635

RESUMO

We demonstrate an approach to two-dimensional electronic spectroscopy (2DES) that combines the benefits of shot-to-shot detection at high-repetition rates with the simplicity of a broadband white light continuum input and conventional optical elements to generate phase-locked pump pulse pairs. We demonstrate this through mutual synchronization between the laser repetition rate, the acousto-optical deflector, the pump delay stage, and the CCD line camera, which allows for rapid scanning of pump optical delay synchronously with the laser repetition rate, while the delay stage is moved at a constant velocity. The resulting shot-to-shot detection scheme is repetition rate scalable and only limited by the CCD line rate and the maximum stage velocity. Using this approach, we demonstrate the measurement of an averaged 2DES absorptive spectrum in as much as 1.2 s of continuous sample exposure per 2D spectrum. We achieve a signal-to-noise ratio of 6.8 for optical densities down to 0.05 with 11.6 s of averaging at 100 kHz laser repetition rate. Combining rapid scanning of mechanical delay lines with shot-to-shot detection as demonstrated here provides a viable alternative to acousto-optic pulse shaping approaches that is repetition-rate scalable, has comparable throughput and sensitivity, and minimizes sample exposure per 2D spectrum with promising micro-spectroscopy applications.

8.
Cureus ; 15(9): e45997, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37900493

RESUMO

Gitelman syndrome (GS) is a rare renal tubulopathy, classically characterized by renal salt wasting and metabolic alkalosis. It is usually an incidental diagnosis, being asymptomatic or with mild symptoms. GS manifesting with acute flaccid paralysis is extremely uncommon. We report a case of GS that mimicked Guillain-Barré syndrome (GBS), manifesting with acute hypokalemic paralysis. A middle-aged male with no known comorbidities presented to our center with paresthesias of all four limbs for one month and progressive, asymmetric limb weakness over the past eight days. Neurological examination revealed hypotonia, global areflexia, and power ranging from 3/5 to 4/5 in all four limbs, leading to our initial clinical diagnosis of GBS. Our patient's laboratory panel revealed hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalcemia, characteristic of GS. Additionally, he had significantly elevated creatine phosphokinase, suggestive of rhabdomyolysis. Further urine studies revealed renal potassium wasting, confirming the diagnosis of GS. Whole exome genome sequencing for common causative genes and workup for autoimmune disease were both negative. With gradual electrolyte correction, the patient rapidly improved symptomatically. Our case highlights an uncommon initial presentation of GS and emphasizes the need for more literature on its manifestations from the Indian subcontinent.

9.
J Glob Infect Dis ; 15(3): 121-123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37800087

RESUMO

Delftia acidovorans (D. acidovorans) is an aerobic, nonfermentative Gram-negative bacillus infrequently isolated from clinical specimens. The pathogenicity and clinical significance of the organism has not been ascertained due to uncommon clinical isolation and suspected low virulence. The organism has been reported to be inherently resistant to aminoglycoside group of drugs which remain as a widely used first-line drug of choice for febrile neutropenic patients. Hereby, we report a case of D. acidovorans-associated pleural effusion in a patient of metastatic adenocarcinoma diagnosed and treated timely and successfully with appropriate antibiotics.

10.
Cureus ; 15(8): e43285, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37692704

RESUMO

Tracheal duplication cysts (TDCs) are congenital malformations that are rarely diagnosed in adulthood. The authors present a case of a 43-year-old female with no known comorbidities with a two-year history of chest and upper abdominal pain. Her previous imaging on an outpatient basis was suggestive of an esophageal duplication cyst, and she was lost to follow-up until the current admission. She gave a past surgical history of video-assisted thoracoscopic surgery for a "cyst" excision, with the relevant details unavailable. On examination, the findings were unremarkable. Repeat imaging was suggestive of an esophageal duplication cyst with no change in dimensions. She underwent a right-sided elective thoracotomy and cyst excision. Intraoperatively, a smooth globular mass was visualized next to the esophagus below the level of the carina. The biopsy revealed a TDC. The patient had an uneventful postoperative period and was asymptomatic on follow-up after three months. TDCs pose a diagnostic challenge as they can only be diagnosed by imaging and histopathology. However, when the imaging is atypical, histopathology clinches the diagnosis. Complete surgical excision is recommended for symptomatic patients after ruling out malignancy. Recurrence of the lesion must be considered in patients such as ours. Our case emphasizes the consideration of TDCs in the differential diagnosis and advocates the importance of complete surgical resection to prevent a recurrence.

12.
Cureus ; 15(6): e41191, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37525783

RESUMO

Dropped head syndrome (DHS) is characterized by neck extensor muscle weakness, which may be isolated or secondary to another neurologic diagnosis. DHS, due to lysosomal storage disorders, has not been reported in the literature. We present a 21-year-old male who had complaints of slowly worsening difficulty swallowing for the past eight years, along with difficulty keeping his head erect. His past medical history was significant for apical hypertrophic cardiomyopathy (HCM), and he had a history of sudden cardiac death in his immediate family. Clinical examination was significant only for neck extensor muscle weakness. His laboratory investigations were unremarkable, save for a significantly elevated creatine kinase (CK). Finally, whole exome sequencing identified a hemizygous stop gain variant in the lysosome-associated membrane protein 2 (LAMP-2) gene, pointing to a diagnosis of Danon disease (DD). DD is a rare, X-linked, inherited disease, due to a defect in the LAMP-2 gene that disrupts lysosomal autophagy. It is characterized by a triad of HCM, skeletal myopathy, and intellectual disability. Males typically suffer a more severe phenotype, and the cardiac disease drives its prognosis. Management involves regular cardiac monitoring, with appropriate physical therapy for myopathy and multidisciplinary treatment for intellectual disability. We suggest that DD be considered in the differential diagnosis for patients with HCM and elevated CK.

13.
Artigo em Inglês | MEDLINE | ID: mdl-37360886

RESUMO

SARS coronavirus (SARS-CoV-2) since the year 2020 has been affecting people of all age groups involving all systems possible. The effect of COVID-19 on hematological system has been commonly seen in the form of cytopenia, prothrombotic states, or disorders of coagulation, but it has been rarely implicated as a causal factor for hemolytic anemia in children. We present a 12-year-old male child who presented in congestive cardiac failure due to severe hemolytic anemia caused by SARS-CoV-2, with hemoglobin falling to a nadir of 1.8 g/dL. Child was diagnosed as a case of autoimmune hemolytic anemia and managed with supportive management and long-term steroids. This case highlights one of the lesser known effects of the virus, causing severe hemolysis and the role of steroids in its treatment.

14.
J Lab Physicians ; 15(2): 264-268, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37323610

RESUMO

Objective Radiotherapy (RT) and chemotherapy (CT) are important treatment options in patients with head and neck cancers. A common complication of this is microbial colonization or infection of mucosal surfaces. These infections may commonly be due to bacteria or yeasts. Salivary proteins with their buffering activity and immunoglobulin, especially immunoglobulin A (IgA), protect oral tissue, mucosal surfaces, and teeth from various microorganisms. This study characterizes the common microorganisms encountered and evaluates the role of salivary IgA in predicting microbial infections in this group of patients with mucositis. Methods A total of 150 adult head and neck cancer patients on CTRT were evaluated at baseline and at the end of 3 and 6 weeks, respectively. Oral swabs collected from buccal mucosa were processed in the microbiology laboratory for the presence of microorganisms. Saliva was processed for IgA level estimation on Siemens Dimension Automated biochemistry analyzer. Results Pseudomonas aeruginosa and Klebsiella pneumonia e were the most common organisms found in our patients, followed by Escherichia coli and group A beta-hemolytic Streptococci . A significant increase ( p = 0.0203) in the incidence of bacterial infection was observed in post-CTRT patients (61%) compared to pre-CTRT patients (49.33%). There was significant increase in levels of salivary IgA ( p = 0.003) in patients with bacterial and fungal infection ( n = 135/267) when compared to those in samples showing no growth ( n = 66/183). Conclusion A significant increase in the incidence of bacterial infection in post-CTRT patients was observed in this study. This study also indicated that postoperative head and neck cancer patients with oral mucositis that developed an infection were associated with high salivary IgA levels, and it may serve as a surrogate biomarker of infection in these patients.

15.
Cureus ; 15(4): e37069, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37153278

RESUMO

Supratentorial strokes causing ipsilateral hemiparesis (ILH) are rare. We report a middle-aged male with multiple atherosclerotic risk factors, who had previously suffered a right-hemispheric stroke that caused left hemiplegia. Subsequently, he presented with worsening left-sided hemiplegia, with imaging revealing a left-hemispheric stroke. Diffusion tensor tract imaging showed crossed motor tracts, with disruption of the left-sided pyramidal tract. During his stay, he developed right hemiplegia due to the expansion of the same left-hemispheric infarct. Potential mechanisms for ILH in a stroke include injury to reorganized tracts following an initial insult and congenitally uncrossed motor tracts. In our patient, after his first stroke, the left hemisphere likely assumed greater ipsilateral motor control, causing ILH after the recent stroke. Our case adds to the literature on this interesting phenomenon and provides further insight into post-stroke recovery.

16.
J Educ Health Promot ; 12: 19, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37034846

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the number one cause of death in India. Atherosclerosis begins in the second decade of life; thus, preventive efforts beginning in adolescence are crucial. Yet, there are no national or regional school-based educational programs in India for the prevention of CVD. We aimed to assess the impact of a simple educational intervention on the awareness regarding CVD among school-going adolescents in a rural area of Bengaluru. MATERIALS AND METHODS: This study was conducted using a convenience sample of school-going adolescents of classes 8, 9, and 10 in three schools in a rural area of Anekal subdistrict, Bengaluru, with a sample size of 170. A standardized, validated questionnaire testing CVD awareness was administered, followed by a simple lecture with audio-visual aids on key aspects of CVD. Three weeks later, the same questionnaire was administered to the same students. The results were then analyzed using appropriate descriptive (mean, percentage) and inferential analyses (Chi-square, paired t-test). RESULTS: The mean (SD) age was 14.5 (1.0) years, and 54% (n = 100) were boys. 75% (139) belonged to privately funded schools. 23% (43) belonged to class 8, 37% (69) to class 9, and 40% (74) to class 10. The mean (SD) total score on baseline assessment was 27.4 (9.3) out of 100, with girls and students of private schools scoring higher. The mean (SD) post-test total score was 48.5 (15.7), with significant increases in all domains of awareness, and in all categories of students. DISCUSSION: Awareness regarding CVD among adolescents from rural Bengaluru was poor, highlighting the need for educational interventions to aid preventive efforts. A simple educational intervention resulted in significant improvements in CVD awareness, even after 3 weeks.

17.
Drug Metab Pers Ther ; 38(3): 227-236, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37098129

RESUMO

OBJECTIVES: This real-world study was conducted to assess the adverse effects following immunization (AEFI) and immunogenicity of ChAdO×1 nCoV-19 vaccine in terms of neutralising antibody titers and to study the effects of covariates such as age, sex, comorbidities and prior COVID status on these outcomes. Also, the effectiveness of the vaccine based on interval between the two doses was also investigated. METHODS: A total of 512 participants (M/F=274/238) aged 35(18-87) years comprising a mixed population of healthcare workers, other frontline workers and general public were enrolled between March and May 2021. Records for adverse events if any were collected telephonically by following up with participants up to 6 months post first dose and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5. Blood samples for measuring antibody titers against the receptor binding domain (RBD) were collected serially using a convenient sampling strategy up to 6 months after the first dose. Data on breakthrough COVID infection was collected telephonically till December 2021. RESULTS: Incidence of local reactions was higher after first dose at 33.4 % (171/512) compared to those after second dose at 12.9 % (66/512). Commonest side effect observed was injection site pain after the first (87.1 %; 149/171) and second (87.9 %; 56/66) dose respectively. Among systemic reactions, fever was the most common manifestation followed by myalgia and headache. Female sex (p<0⸱001) and age less than 60 years (p<0⸱001) had significantly higher predilection for systemic toxicities. Age ≤60 years (p=0.024) and prior-COVID (p<0.001) were found to be significantly associated with higher antibody titers, however, no association was found between these variables and breakthrough COVID infection. Longer spacing between the doses (≥6 weeks) was found to offer better protection against breakthrough infection compared to a spacing of 4 weeks. All breakthroughs were mild-moderate in severity, not requiring hospitalization. CONCLUSIONS: The ChAdOx1 nCov-19 vaccine is apparently safe and effective against SARS-CoV-2 virus infection. Prior COVID infection and younger age group achieve higher antibody titers, but no additional protection. Delaying the second dose up to at least 6 weeks is more effective compared to shorter spacing between doses.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Feminino , ChAdOx1 nCoV-19 , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Índia/epidemiologia , Infecções Irruptivas
18.
Med J Armed Forces India ; 79(2): 238-240, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969110

RESUMO

Combined saposin deficiency (OMIM #611721), an exceedingly rare lysosomal storage disorder, is caused by a mutation in the gene PSAP. This gene encodes a protein, prosaposin, that cleaves into four constituent proteins, each of which has a role as a cofactor for the enzymes whose deficiency results in Krabbe disease, metachromatic leukodystrophy, Gaucher disease, and Farber disease, respectively. Intact prosaposin itself is essential for neuronal survival. The typical manifestation of combined saposin deficiency is of severe neurological features in the neonatal period, hepatosplenomegaly, thrombocytopenia, and early death. We report, to the best of our knowledge, the first Indian case with these clinical manifestations and confirmation by genetic and enzymatic testing.

19.
Cancers (Basel) ; 15(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36831683

RESUMO

Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I-IV (now 1-4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas. The review also highlights potential diagnostic and/or therapeutic targets in associated cellular biomolecules, structures, and processes. Targeting of MGMT promoter methylation, TET-hTDG-BER pathway, association of G-CIMP with key gene mutations, PARP inhibition, IDH and 2-HG-associated processes, TERT mutation and ARL9-associated pathways, DNA Methyltransferase (DNMT) inhibition, Histone Deacetylase (HDAC) inhibition, BET inhibition, CpG site DNA methylation signatures, along with others, present exciting avenues for translational research. This review also summarizes the current clinical trial landscape associated with the therapeutic utility of epigenetics in low-grade gliomas. Much of the evidence currently remains restricted to preclinical studies, warranting further investigation to demonstrate true clinical utility.

20.
JMIR Med Educ ; 9: e37069, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607718

RESUMO

The United States Medical Licensing Examination (USMLE) Step 1, arguably the most significant assessment in the USMLE examination series, changed from a 3-digit score to a pass/fail outcome in January 2022. Given the rapidly evolving body of literature on this subject, this paper aims to provide a comprehensive review of the historical context and impact of this change on various stakeholders involved in residency selection. For this, relevant keyword-based searches were performed in PubMed, Google Scholar, and Scopus to identify relevant literature. Given the unique history of USMLE Step 1 in the US residency selection process and the score's correlation with future performance in board-certifying examinations in different specialties, this scoring change is predicted to significantly impact US Doctor of Medicine students, US Doctor of Osteopathic Medicine students, international medical graduates, and residency program directors, among others. The significance and the rationale of the pass/fail change along with the implications for both residency applicants and educators are also summarized in this paper. Although medical programs, academic institutions, and residency organizing bodies across the United States have swiftly stepped up to ensure a seamless transition and have attempted to ensure equity for all, the conversion process carries considerable uncertainty for residency applicants. For educators, the increasing number of applications conflicts with holistic application screening, leading to the expected greater use of objective measures, with USMLE Step 2 Clinical Knowledge likely becoming the preferred screening tool in lieu of Step 1.

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