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PURPOSE: We present a methodically devised protocol for conducting a systematic review and meta-analysis aimed at ascertaining the prevalence of BReast CAncer gene (BRCA) mutations in breast and ovarian cancer (BOC) among women in India. The review will include cross-sectional, cohort, case-series, and registry-based studies focusing on females clinically diagnosed with any stage of BOC, tested for BRCA germline mutation and undergone any form of treatment. METHODS: A Cochrane literature search will be carried out to identify all the published and unpublished articles available in English from 2010 till date across various electronic databases including PubMed, Psych Info, SCI, Cochrane Central, Embase, Scopus, IND Med and Google Scholar. A step-by-step process will be followed to select all the relevant studies for final inclusion using Rayyan software. The selection process of the review will be reported based on Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA) checklist. The protocol has been registered in PROSPERO (ID: CRD42023463452). Joanna Briggs Institute Critical Appraisal Checklist will be used to evaluate the methodological quality of the included studies. The outcome measure will be the prevalence of BRCA1/2 gene mutation in this population. Meta-analysis will be performed to report the pooled prevalence along with 95% confidence interval. DISCUSSION: The results of this review study will provide valuable insights for clinicians, and policy makers, enabling them to formulate guidelines that underscore the importance of screening for BRCA mutations in cases of BOC.
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Neoplasias da Mama , Neoplasias Ovarianas , Revisões Sistemáticas como Assunto , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Mutação em Linhagem Germinativa , Índia/epidemiologia , Metanálise como Assunto , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/epidemiologia , PrevalênciaRESUMO
ABSTRACT: Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.
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Neoplasias do Sistema Nervoso Central , Humanos , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Linfoma de Células T/patologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/mortalidade , Prognóstico , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Fatores de Risco , Recidiva , Células Matadoras Naturais , Adulto JovemRESUMO
BACKGROUND: The rapid urbanization of Kenya has led to an increase in the growth of informal settlements. There are challenges with access to maternal, newborn, and child health (MNCH) services and higher maternal mortality rates in settlements. The Kuboresha Afya Mitaani (KAM) study aimed to improve access to MNCH services. We evaluate one component of the KAM study, PROMPTS (Promoting Mothers through Pregnancy and Postpartum), an innovative digital health intervention aimed at improving MNCH outcomes. PROMPTS is a two-way AI-enabled SMS-based platform that sends messages to pregnant and postnatal mothers based on pregnancy stage, and connects mothers with a clinical help desk to respond and refer urgent cases in minutes. METHODS: PROMPTS was rolled out in informal settlements in Mathare and Kawangware in Nairobi County. The study adopted a pre-post intervention design, comparing baseline and endline population outcomes (1,416 participants, Baseline = 678, Endline = 738). To further explore PROMPTS's effect, outcomes were compared between endline participants enrolled and not enrolled in PROMPTS (738 participants). Outcomes related to antenatal (ANC) and postnatal (PNC) service uptake and knowledge were assessed using univariate and multivariate linear and logistic regression. RESULTS: Between baseline and enldine, mothers were 1.85 times more likely to report their babies and 1.88 times more likely to report themselves being checked by a provider post-delivery. There were improvements in moms and babies receiving care on time. 45% of the 738 endline participants were enrolled in the PROMPTS program, with 87% of these participants sending at least one message to the system. Enrolled mothers were 2.28 times more likely to report completing four or more ANC visits relative to unenrolled mothers. Similarly, enrolled mothers were 4.20 times more likely to report their babies and 1.52 times more likely to report themselves being checked by a provider post-delivery compared to unenrolled mothers. CONCLUSIONS: This research demonstrates that a digital health tool can be used to improve care-seeking and knowledge levels among pregnant and postnatal women in informal settlements. Additional research is needed to refine and target solutions amongst those that were less likely to enroll in PROMPTS and to further drive improved MNCH outcomes amongst this population.
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Saúde Digital , Serviços de Saúde Materna , Lactente , Recém-Nascido , Criança , Feminino , Gravidez , Humanos , Saúde do Lactente , Quênia , Mães , Período Pós-Parto , Cuidado Pré-NatalRESUMO
BRAF mutations are associated with a small number of hematologic malignancies, including hairy cell leukemia and histiocytic disorders. In addition, BRAF mutations have also been detected in low frequency in other B-cell lymphomas, such as chronic lymphocytic leukemia and diffuse large B-cell lymphoma, but never in mantle cell lymphoma (MCL). We present a case of a 69-year-old female with classic MCL harboring a BRAFN581S mutation. To our knowledge, this is the first reported case of any BRAF mutation in MCL.
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Diffuse large B-cell lymphoma (DLBCL) and angioimmunoblastic T-cell lymphoma (AITL) are two subtypes of non-Hodgkin lymphoma (NHL). The simultaneous occurrence of DLBCL and AITL in a composite lymphoma is very rare, and there are no established treatment regimens. We present the case of an 85-year-old male admitted to the intensive care unit with distributive shock, lymphocytosis, and lymphadenopathy, who was subsequently diagnosed with composite AITL and DLBCL, and treated with brentuximab vedotin (BV) and rituximab. To our knowledge, this is the first case of composite lymphoma presenting with distributive shock and treated with BV and rituximab, with successful resolution of shock.
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PURPOSE: With the advent of taxanes and targeted agents in neoadjuvant chemotherapy (NACT) for breast cancer, the rates for pathologic complete response (pCR) have been steadily increasing. Surgery in these women serves as a biopsy to confirm or negate a pCR. METHODS: All newly diagnosed patients with nonmetastatic breast cancer, planned for NACT, were screened. Eligible patients with a complete or near-complete response to NACT as seen on a mammogram and ultrasound (US) were recruited. A magnetic resonance imaging was performed for these patients for documentation. US-guided core biopsies of the tumor bed (Core Bx) using a 14G needle was performed (minimum four in number), and the results were compared with the final histopathology report after surgery for standard performance parameters. RESULTS: This study recruited 65 women of whom 94% were node-positive, and 60% were hormone receptor-negative. The pCR rate was 41.5% and 53.8% for the whole cohort and the hormone receptor-negative subgroup, respectively. The false-negative rate (FNR) for Core Bx was 42.1% (95% CI, 26.3 to 59.2), with a negative predictive value of 59.0% (95% CI, 42.1 to 74.4). Among the hormone receptor-negative tumors, the FNR was 44.4% (95% CI, 21.5 to 69.2) with a negative predictive value of 70.4% (95% CI, 49.8 to 86.2). CONCLUSION: The Complete Responders in the Breast study results suggest that ultrasound-guided 14G core needle biopsy of the tumor bed may not be a reliable predictor of pCR in the breast. These results highlight the importance of further research into the omission of surgery in the breast after chemotherapy. This study is registered with Clinical Trials Registry of India (CTRI/2018/01/011122).
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Mama/diagnóstico por imagem , Mama/cirurgia , Mama/patologia , Mamografia , Biópsia , Hormônios/uso terapêuticoAssuntos
Neoplasias da Mama , Mastectomia Segmentar , Humanos , Feminino , Mastectomia , Neoplasias da Mama/cirurgiaRESUMO
BACKGROUND: The choice between nonmyeloablative chemotherapy (NMA-C) or autologous hematopoietic cell transplantation (autoHCT) as consolidation in primary central nervous system lymphoma (PCNSL), and timing of autoHCT differs among centers. We aimed to clarify these points. METHODS: We retrospectively analyzed PCNSL adult patients who received consolidation in CR1 or underwent autoHCT during their treatment course. Cohort A included those who underwent autoHCT in CR1, cohort B included those who underwent NMA-C in CR1, and cohort C included patients who underwent autoHCT in CR2+. We compared cohorts A and B, and cohorts A and C. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), treatment-related mortality (TRM) and cumulative incidence of relapse (CIR). RESULTS: 36 patients were included in cohort A, 30 in cohort B, and 14 in cohort C. The 5-year OS for cohorts A vs B and vs C were 90.7% vs 62.8% (P = .045) and vs 77.9% (P = .32), respectively. The 5-year PFS from diagnosis for cohorts A vs B was 87.8% vs 37.3% (P < .001). The 5-year PFS from autoHCT for cohorts A vs C was 87.6% vs 58.4% (P = .023). The 5-year TRM and CIR in cohorts A vs B was 9.4% vs 9.5% (P = .674), and 2.9% vs 53.2% (P < .001), respectively. The 5-year TRM and CIR in cohorts A vs C from the time of autoHCT was 9.5% vs 22.1% (P = .188), and 2.9% vs 19.5% (P = .104), respectively. CONCLUSION: Despite the limitations, thiotepa-based autoHCT in CR1 appears to improve outcomes in eligible patients with PCNSL.
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Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Linfoma , Adulto , Humanos , Sistema Nervoso Central/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Tiotepa/uso terapêutico , Transplante AutólogoRESUMO
Although sentinel lymph node biopsy (SLNB) has become a standard of care for management of axilla in breast cancer patients, the technique of SLNB is still not well defined. Unlike radioactive sulfur colloid which requires nuclear medicine facilities, methylene blue dye is readily available. The purpose of this study is to validate the use of methylene blue dye alone for SLNB in early breast cancer patients. 60 patients of early breast cancer were randomized to receive either methylene blue alone (Group A-30 patients) or a combination of both methylene blue and radioactive colloid (Group B-30 patients) for detection of sentinel lymph nodes. Sentinel lymph node biopsy was done followed by complete axillary dissection in all patients. In both Groups A and B, sentinel node was identified in all 30 patients, giving identification rate of 100%. In group A, sentinel node was the only positive node in 1 patient, with a false-positive rate of 14.2%. The negative predictive value was 91.3%. The sensitivity of the procedure in predicting further axillary disease was 75% with a specificity of 95.45%. The overall accuracy was 90%. In group B, sentinel node was the only positive node in 2 cases, giving a false-positive rate of 28.7%. The negative predictive value was 95.65%. The sensitivity of the procedure in predicting further axillary disease was 83.33% with a specificity of 91.67%. The overall accuracy was 90%. Although the false-negative rate was slightly higher with methylene blue alone than that using combination (8.6%-4.3%), it was statistically insignificant. Similarly the sensitivity (75%-83.33%), specificity (95.45-91.67%), and negative predictive value (91.3%-95.67%) were also comparable between groups A and B, respectively. Negative predictive value and false-negative rates are comparable, whether blue dye is used alone or a combination of blue dye and radioactive colloid is used. Sentinel lymph node biopsy with blue dye alone is reliable and can be put to clinical practice more widely, even if nuclear medicine facilities are not available in resource constrained centers, so as to reduce long-term morbidity of axillary dissection, with similar oncological outcomes.
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Bleeding is a known complication of sickle cell disease (SCD) and includes hemorrhagic stroke, hematuria, and vitreous hemorrhage. However, the incidence of bleeding events in patients with SCD has not been well described. We present a retrospective, population-based study examining the cumulative incidence of bleeding in 6423 patients with SCD from 1991 to 2014. We also studied risk factors associated with bleeding and the effects of bleeding on mortality, using Cox proportional hazards regression models. We used California emergency department and hospitalization databases to identify patients with SCD with intracranial hemorrhage, gastrointestinal (GI) bleeding, hemophthalmos, gross hematuria, epistaxis, menorrhagia, and other bleeding events. The cumulative incidence of any first bleeding event at age 40 years was 21% (95% confidence interval [CI], 19.8%-22.3%), increasing with age to 41% by age 60 years (95% CI, 38.8%-43.1%). The majority of bleeding events were GI (41.6%), particularly from the upper GI tract. A higher bleeding risk was associated with increased frequency of hospitalization (hazard ratio [HR], 2.16; 95% CI, 1.93-2.42), venous thromboembolism 180 days before bleeding event (HR, 4.24; 95% CI, 2.86-6.28), osteonecrosis of the femoral head (HR, 1.25; 95% CI, 1.08-1.46), and ischemic stroke (HR, 1.65; 95% CI, 1.20-2.26). Bleeding was also associated with a twofold increased risk for death (HR, 2.09; 95% CI, 1.82-2.41) adjusted for other SCD-related complications. Our novel finding of a high incidence of bleeding in patients with SCD, particularly from the upper GI tract, suggests that patients with SCD may be predisposed to bleeding, with possible etiologies including increased use of nonsteroidal anti-inflammatory drugs, mucosal infarction from vascular occlusion by sickled red blood cells, and increased stress ulceration from frequent hospitalization.
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Anemia Falciforme , Tromboembolia Venosa , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Feminino , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Incidência , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Young women form a unique cohort in breast cancer, with evidence suggesting a later stage at presentation with more aggressive cancers. We aimed at evaluating the prognostic significance of young age and the impact of stage and molecular subtypes on survival. We conducted an audit of a prospectively maintained database at our institute between 2010 and 2014. All women with available receptor status and documented follow-up were included. The young breast cancer (YBC) cohort comprised 103 women and 230 women constituted the comparator arm (45-55 years). The median follow-up was 4 years. The YBC had a higher incidence of hormone negative tumors (61.1% vs. 46.3%, p = 0.012, significant [S]); however, both groups were similar in their stage at presentation. On classification into luminal subtypes, triple negative breast cancer was more common in the YBC cohort (50.5% vs. 29.6%, p = 0.001, S). The 5-year disease-free survival (DFS) was significantly worse in the YBC cohort (70.3% vs. 78%, p = 0.03, S). This detriment appeared to be significantly more in women presenting with operable breast cancer (77.2% vs. 82.6%, p = 0.012, S). Among the Luminal subtypes, there was no significant difference in the DFS between the two groups. Young age is a negative prognostic factor among women presenting with breast cancer. Further studies are required to evaluate whether any specific stage or molecular sub-type is particularly vulnerable to a poor outcome despite treatment.
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Neoplasias da Mama/terapia , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Background: Obesity is associated with an increased risk of bladder cancer recurrence. This study investigated the role of adipose tissue in bladder cancer progression. Methods: Gene expression profiling was performed on adipose tissues collected from normal weight (n=5), overweight (n=11), and obese (n=10) patients with invasive bladder cancer, and adipose stromal cells (ASCs) were obtained from two normal weight, two overweight, and two obese patients. Conditioned media (CM) was characterized and evaluated for its effects on the proliferation, migration, and invasive potential of T24 bladder cancer cells. Results: Expression profiling demonstrated depot-specific or body mass index-specific differences. Increased T24 cell migration was observed using CM harvested from all ASCs. ASC CM from an obese patient significantly increased T24 cell migration and invasion compared to ASC CM collected from normal weight and overweight patients. We identified abundant expression of CXCL1, PAI1, IL6, CX3CL1, and CCL2 in all CM. Exogenous treatment of T24 cells with PAI1, IL6, and CXCL1 enhanced migration. Depletion of CXCL1, PAI1, and IL6 in an obese patient ASC CM abrogated T24 migration. Conclusion: Factors secreted by adipose tissue influence the migration of bladder tumor cells and could play an active role in tumor progression.
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Tecido Adiposo/metabolismo , Índice de Massa Corporal , Movimento Celular , Quimiocinas/metabolismo , Citocinas/metabolismo , Neoplasias da Bexiga Urinária/patologia , Adipócitos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Células Cultivadas , Meios de Cultivo Condicionados , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Obesidade/metabolismo , Sobrepeso/metabolismo , TranscriptomaAssuntos
Hipertensão/complicações , Hipertensão/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Endotelina-1/metabolismo , Feminino , Humanos , Isquemia/patologia , Neovascularização Patológica , Estresse Oxidativo , Placenta/irrigação sanguínea , Placenta/patologia , Período Pós-Parto , Gravidez , Sistema Renina-AngiotensinaRESUMO
BACKGROUND: Text message (short message service, SMS) reminders and incentives are two demand-side interventions that have been shown to improve health care-seeking behaviors by targeting participant characteristics such as forgetfulness, lack of knowledge, and transport costs. Applying these interventions to routine pediatric immunizations may improve vaccination coverage and timeliness. OBJECTIVE: The Mobile Solutions for Immunization (M-SIMU) trial aims to determine if text message reminders, either with or without mobile phone-based incentives, sent to infant's parents can improve immunization coverage and timeliness of routine pediatric vaccines in rural western Kenya. METHODS: This is a four-arm, cluster, randomized controlled trial. Villages are randomized to one of four study arms prior to enrollment of participants. The study arms are: (1) no intervention (a general health-related text message will be texted to this group at the time of enrollment), (2) text message reminders only, (3) text message reminders and a 75 Kenyan Shilling (KES) incentive, or (4) text message reminders and a KES200 incentive. Participants assigned to study arms 2-4 will receive two text message reminders; sent 3 days before and one day before the scheduled immunization visit at 6, 10, and 14 weeks for polio and pentavalent (containing diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b antigens) type b antigens) vaccines, and at 9 months for measles vaccine. Participants in incentive arms will, in addition to text message reminders as above, receive mobile phone-based incentives after each timely vaccination, where timely is defined as vaccination within 2 weeks of the scheduled date for each of the four routine expanded program immunization (EPI) vaccination visits. Mother-infant pairs will be followed to 12 months of age where the primary outcome, a fully immunized child, will be ascertained. A fully immunized child is defined as a child receiving vaccines for bacille Calmette-Guerin, three doses of pentavalent and polio, and measles by 12 months of age. General estimating equation (GEE) models that account for clustering will be employed for primary outcome analyses. RESULTS: Enrollment was completed in October 2014. Twelve month follow-up visits to ascertain immunization status from the maternal and child health booklet were completed in February 2016. CONCLUSIONS: This is one of the first studies to examine the effect of text message reminders on immunization coverage and timeliness in a lower income country and is the first study to assess the effect of mobile money-based incentives to improve immunization coverage. TRIAL REGISTRATION: Clinicaltrials.gov NCT01878435; https://clinicaltrials.gov/ct2/show/NCT01878435 (Archived by WebCite at http://www.webcitation.org/6hQlwGYJR).
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Cell-to-cell communication in plants includes the selective trafficking of transcription factors and other signals through plasmodesmata. The KNOTTED1 (KN1) homeobox (KNOX) family transcription factors, which use this pathway, are essential for stem cell establishment and/or maintenance. Here we show that KN1 trafficking requires the chaperonin complex, which belongs to a group of cytosolic chaperones that fold specific substrate proteins. Genetic and physical interaction data show a functional relevance for chaperonins in KNOX family-dependent stem cell maintenance. Furthermore, tissue-specific complementation assays indicate a mechanistic basis for chaperonin function during the posttranslocational refolding process. Our study shows that chaperonins are essential for the cell-to-cell trafficking of a subset of mobile transcription factors and demonstrates the importance of chaperonin-dependent protein trafficking for plant stem cell function.