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PURPOSE: Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently. METHODS: A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN). RESULTS: The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2 months. The median age was 67 years. The median margin SRS dose was 19 Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95). CONCLUSION: The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Encefálicas/patologiaRESUMO
Brain metastases (BMs) represent the most common intracranial tumors in adults, and most commonly originate from lung, followed by breast, melanoma, kidney, and colorectal cancer. Management of BM is individualized based on the size and number of brain metastases, the extent of extracranial disease, the primary tumor subtype, neurological symptoms, and prior lines of therapy. Until recently, treatment strategies were limited to local therapies, like surgical resection and radiotherapy, the latter in the form of whole-brain radiotherapy or stereotactic radiosurgery. The next generation of local strategies includes laser interstitial thermal therapy, magnetic hyperthermic therapy, post-resection brachytherapy, and focused ultrasound. New targeted therapies and immunotherapies with documented intracranial activity have transformed clinical outcomes. Novel systemic therapies with intracranial utility include new anaplastic lymphoma kinase inhibitors like brigatinib and ensartinib; selective "rearranged during transfection" inhibitors like selpercatinib and pralsetinib; B-raf proto-oncogene inhibitors like encorafenib and vemurafenib; Kirsten rat sarcoma viral oncogene inhibitors like sotorasib and adagrasib; ROS1 gene rearrangement (ROS1) inhibitors, anti-neurotrophic tyrosine receptor kinase agents like larotrectinib and entrectinib; anti-human epidermal growth factor receptor 2/epidermal growth factor receptor exon 20 agent like poziotinib; and antibody-drug conjugates like trastuzumab-emtansine and trastuzumab-deruxtecan. This review highlights the modern multidisciplinary management of BM, emphasizing the integration of systemic and local therapies.
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Neoplasias Encefálicas , Proteínas Proto-Oncogênicas , Adulto , Humanos , Proteínas Proto-Oncogênicas/uso terapêutico , Trastuzumab/uso terapêutico , Vemurafenib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Encefálicas/genéticaRESUMO
BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the two most common malignant neoplasms of the liver. The objective of this study was to assess outcomes of surgical approaches to liver ablation comparing laparoscopic versus percutaneous microwave ablation (MWA), and MWA versus radiofrequency ablation (RFA) in patients with HCC or CRLM lesions smaller than 5 cm. METHODS: A systematic review was conducted across seven databases, including PubMed, Embase, and Cochrane, to identify all comparative studies between 1937 and 2021. Two independent reviewers screened for eligibility, extracted data for selected studies, and assessed study bias using the modified Newcastle Ottawa Scale. Random effects meta-analyses were subsequently performed on all available comparative data. RESULTS: From 1066 records screened, 11 studies were deemed relevant to the study and warranted inclusion. Eight of the 11 studies were at high or uncertain risk for bias. Our meta-analyses of two studies revealed that laparoscopic MW ablation had significantly higher complication rates compared to a percutaneous approach (risk ratio = 4.66; 95% confidence interval = [1.23, 17.22]), but otherwise similar incomplete ablation rates, local recurrence, and oncologic outcomes. The remaining nine studies demonstrated similar efficacy of MWA and RFA, as measured by incomplete ablation, complication rates, local/regional recurrence, and oncologic outcomes, for both HCC and CRLM lesions less than 5 cm (p > 0.05 for all outcomes). There was no statistical subgroup interaction in the analysis of tumors < 3 cm. CONCLUSION: The available comparative evidence regarding both laparoscopic versus percutaneous MWA and MWA versus RFA is limited, evident by the few studies that suffer from high/uncertain risk of bias. Additional high-quality randomized trials or statistically matched cohort studies with sufficient granularity of patient variables, institutional experience, and physician specialty/training will be useful in informing clinical decision making for the ablative treatment of HCC or CRLM.
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Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Colorretais , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Neoplasias Hepáticas/secundário , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Micro-Ondas/uso terapêutico , Resultado do Tratamento , Neoplasias Colorretais/cirurgiaRESUMO
BACKGROUND: Colorectal liver metastases (CRLM) occur in roughly half of patients with colorectal cancer. Minimally invasive surgery (MIS) has become an increasingly acceptable and utilized technique for resection in these patients, but there is a lack of specific guidelines on the use of MIS hepatectomy in this setting. A multidisciplinary expert panel was convened to develop evidence-based recommendations regarding the decision between MIS and open techniques for the resection of CRLM. METHODS: Systematic review was conducted for two key questions (KQ) regarding the use of MIS versus open surgery for the resection of isolated liver metastases from colon and rectal cancer. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Additionally, the panel developed recommendations for future research. RESULTS: The panel addressed two KQs, which pertained to staged or simultaneous resection of resectable colon or rectal metastases. The panel made conditional recommendations for the use of MIS hepatectomy for both staged and simultaneous resection when deemed safe, feasible, and oncologically effective by the surgeon based on the individual patient characteristics. These recommendations were based on low and very low certainty of evidence. CONCLUSIONS: These evidence-based recommendations should provide guidance regarding surgical decision-making in the treatment of CRLM and highlight the importance of individual considerations of each case. Pursuing the identified research needs may help further refine the evidence and improve future versions of guidelines for the use of MIS techniques in the treatment of CRLM.
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Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Hepatectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Retais/cirurgiaRESUMO
BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.
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Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Colorretais , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/cirurgia , Micro-Ondas/uso terapêutico , Ablação por Cateter/métodos , Resultado do Tratamento , Ablação por Radiofrequência/métodos , Neoplasias Colorretais/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: While surgical resection has a demonstrated utility for patients with colorectal liver metastases (CRLM), it is unclear whether minimally invasive surgery (MIS) or an open approach should be used. This review sought to assess the efficacy and safety of MIS versus open hepatectomy for isolated, resectable CRLM when performed separately from (Key Question (KQ) 1) or simultaneously with (KQ2) the resection of the primary tumor. METHODS: PubMed, Embase, Google Scholar, Cochrane CENTRAL, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov databases were searched to identify both randomized controlled trials (RCTs) and non-randomized comparative studies published during January 2000-September 2020. Two independent reviewers screened literature for eligibility, extracted data from included studies, and assessed internal validity using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed using risk ratios (RR) and mean differences (MD). RESULTS: From 2304 publications, 35 studies were included for meta-analysis. For staged resections, three RCTs and 20 observational studies were included. Data from RCTs indicated MIS having similar disease-free survival (DFS) at 1-year (RR 1.03, 95%CI 0.70-1.50), overall survival (OS) at 5-years (RR 1.04, 95%CI 0.84-1.28), fewer complications of Clavien-Dindo Grade III (RR 0.62, 95%CI 0.38-1.00), and shorter hospital length of stay (LOS) (MD -6.6 days, 95%CI -10.2, -3.0). For simultaneous resections, 12 observational studies were included. There was no evidence of a difference between MIS and the open group for DFS-1-year, OS-5-year, complications, R0 resections, blood transfusions, along with lower blood loss (MD -177.35 mL, 95%CI -273.17, -81.53) and shorter LOS (MD -3.0 days, 95%CI -3.82, -2.17). CONCLUSIONS: Current evidence regarding the optimal approach for CRLM resection demonstrates similar oncologic outcomes between MIS and open techniques, however MIS hepatectomy had a shorter LOS, lower blood loss and complication rate, for both staged and simultaneous resections.
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Neoplasias Colorretais , Laparoscopia , Neoplasias Hepáticas , Humanos , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias Colorretais/patologia , Laparoscopia/métodosRESUMO
INTRODUCTION: The COVID-19 pandemic has resulted in a significant burden on healthcare systems causing disruption to the medical and surgical training of doctors globally. AIMS AND OBJECTIVES: This is the first international survey assessing the perceived impact of the COVID-19 pandemic on the training of doctors of all grades and specialties. METHODS: An online global survey was disseminated using Survey Monkey® between 4th August 2020 and 17th November 2020. A global network of collaborators facilitated participant recruitment. Data were collated anonymously with informed consent and analysed using univariate and adjusted multivariable analyses. RESULTS: Seven hundred and forty-three doctors of median age 27 (IQR: 25-30) were included with the majority (56.8%, n = 422) being male. Two-thirds of doctors were in a training post (66.5%, n = 494), 52.9% (n = 393) in a surgical specialty and 53.0% (n = 394) in low- and middle-income countries. Sixty-nine point two percent (n = 514) reported an overall perceived negative impact of the COVID-19 pandemic on their training. A significant decline was noted amongst non-virtual teaching methods such as face-to-face lectures, tutorials, ward-based teaching, theatre sessions, conferences, simulation sessions and morbidity and mortality meetings (P ≤ .05). Low or middle-income country doctors' training was associated with perceived inadequate supervision while performing invasive procedures under general, local or regional anaesthetic. (P ≤ .05). CONCLUSION: In addition to the detrimental impact of the COVID-19 pandemic on healthcare infrastructure, this international survey reports a widespread perceived overall negative impact on medical and surgical doctors' training globally. Ongoing adaptation and innovation will be required to enhance the approach to doctors' training and learning in order to ultimately improve patient care.
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COVID-19 , Médicos , Humanos , Masculino , Pandemias , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as "first" of their country or color or other achievement. All of them are included as outstanding-in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life's work, they chose service, often of the most neglected-those with pain, trauma, and disability. These women inspire and point the way to a time when the term "women leaders" as an exception is unnecessary.-Katharine J. Drummond, MD, on behalf of this month's topic editors.
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Neurocirurgia , Feminino , Humanos , Procedimentos NeurocirúrgicosRESUMO
Biliary endoprostheses are increasingly being utilised across both the developing and developed world, due to growing access to endoscopic biliary stenting. Stent migration, a well-documented complication of this minimally invasive procedure, occurs in up to 10% of cases post-insertion, sometimes leading to catastrophic complications. While distal migration frequently leads to spontaneous passage of the stent, proximal migration can result in a variety of problems. We here describe a rare case of transhepatic intraperitoneal migration of a double-pigtail, plastic stent and present a comprehensive review of literature.
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BACKGROUND & OBJECTIVES: Chikungunya (CHIK) re-emerged in India in 2006 after a gap of three decades. In Uttar Pradesh (UP), <100 confirmed cases per million were reported during this outbreak. Based on an upsurge of CHIK cases at UP, this retrospective study was conducted to investigate clinical and serological profile of CHIK cases in UP. METHODS: A retrospective study was done on all clinically suspected CHIK cases that had been tested by ELISA for anti-CHIK virus IgM antibodies from September 2012 to December 2017. Based on clinical features, a subset of patients had earlier been tested serologically for dengue and Japanese encephalitis (JE). RESULTS: Of the 3240 cases enrolled, 771 (23.8%) were seropositive. Patients had a range of clinical manifestations with seropositivity highest in those exhibiting arthralgia with fever (40%), followed by fever of unknown origin (FUO) (22%), encephalitis (13%) and fever with rash (12%). Cases (total, seropositive) increased over 20-fold in 2016 (1389, 412) and 2017 (1619, 341), compared to 2012-2015. Nearly a third of dengue serology-positive cases and a fifth of JE serology-positive cases were co-positive for CHIKV. INTERPRETATION & CONCLUSIONS: Archival data from 2006-2011 and data from this study (2012-2017) indicated that UP experienced first CHIK outbreak in the decade in 2016, as part of a large-scale upsurge across northern India. CHIK should be considered as a differential diagnosis in patients presenting with fever of unknown origin or fever with rash or acute encephalitis, in addition to classical arthralgia.
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Febre de Chikungunya , Vírus Chikungunya , Anticorpos Antivirais , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Surtos de Doenças , Humanos , Índia/epidemiologia , Estudos RetrospectivosRESUMO
How to cite this article: Ozair A, Agrawal A, Siddiqui SS. Training and Delivery of Critical Care Medicine in India: Concerns Revealed by COVID-19 Pandemic. Indian J Crit Care Med 2020;24(4):285-286.
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BACKGROUND AND AIMS: Following spinal anesthesia (SA), patient discharge is often delayed due to postoperative urinary retention (POUR), the incidence of which varies widely. The present study of bupivacaine versus ropivacaine in equianalgesic doses was taken to explore the correlation between time to void urine and time for complete functional recovery. MATERIAL AND METHODS: In this double-blinded study fifty adult patients were assigned to two groups (bupivacaine/ropivacaine) according to alternate case allocation for receiving SA for lower abdominal, perineal, and lower limb surgeries, lasting less than 2 h. Statistical analysis was conducted using an intention-to-treat approach, using Mann-Whitney test for nonparametric data. Primary outcome data could not be obtained for 14 out of the 50 patients due to perioperative bladder catheterization. No patients were lost to follow-up. RESULTS: Both the bupivacaine and ropivacaine groups were comparable in terms of ability to void (8.0 ± 2.3 vs. 7.0 ± 1.2 h; P > 0.05), modified Bromage scale after 4 h of SA (1.8 ± 1.3 vs. 2.6 ± 0.9 grade; P > 0.05), time to complete ambulation (6.7 ± 1.4 vs. 6.1 ± 1.0 h; P > 0.05), and time to negative Romberg test (6.1 ± 1.4 vs. 5.6 ± 0.9 h; P > 0.05), respectively. Strong positive correlations (r = 0.7-0.9) were found between time to void urine and time for complete ambulation. CONCLUSIONS: Time to void urine and recovery of motor functions were found comparable statistically when bupivacaine and ropivacaine were used in the doses of 12.5 and 18.75 mg, respectively, for SA. However, group ropivacaine required lesser time to void and no patient developed POUR. Time to void urine was more than the time for ambulation. This may indicate a need for "selective spinal anesthesia" or adjuvant combination technique to accelerate the resolution of a block for ambulatory surgery.
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BACKGROUND: Patients in low- and middle-income countries (LMICs) have substantial treatment abandonment and non-adherence with outpatient oral medications. This work sought to investigate outcomes of postoperative discitis treated with debridement and a novel technique focused on reducing outpatient antibiotic requirement in an LMIC setting. METHODS: This study, conducted and reported following STROBE guidelines, reviewed outcomes of all patients with postoperative discitis who had been debrided by 1 neurosurgeon in a resource-limited setting during 2008-2020. Patients had undergone single-level L4-L5 or L5-S1 discectomy elsewhere, later developing magnetic resonance imaging-confirmed discitis. After non-response or deterioration following intravenous antibiotics, patients underwent early debridement, followed by in-patient antibiotic instillation into disc space for 2 weeks via drain. Study outcomes were modified Kirkaldy-Willis Grade, Japan Orthopaedic Association (JOA) score, and visual analog scale (VAS) score, all assessed at 1 year. RESULTS: Twelve patients were included, 10 male and 2 female, with median age of 46 (IQR 3.5) years. Debridement was done after median 82.5 (IQR 35) days and took median time of 105 (IQR 17.5) minutes. VAS scores (mean ± SD) decreased from 9.25 ± 0.75 preoperatively to 0.67 ± 0.89 1 year postoperatively (mean difference 8.58, 95% CI 8.01-9.15, P < 0.001). JOA scores (mean ± SD) improved from 4.5 ± 2.94 to 26.42 ± 1.31 1 year postoperatively (mean difference 21.92, 95% CI 20.57-23.26, P < 0.001). Kirkaldy-Willis grade was excellent in 6 (50%) patients, good in 5 (41.7%), and fair in 1 (8.3%). Patients became ambulatory within 2 weeks, with no major complications during 4.15 (IQR 3.45) years of median follow-up. CONCLUSIONS: In LMICs, patients with medically refractory postoperative discitis potentially have good outcomes after debridement plus 2-week local antibiotic instillation.
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Discite , Humanos , Masculino , Feminino , Pré-Escolar , Discite/tratamento farmacológico , Discite/cirurgia , Vértebras Lombares/cirurgia , Antibacterianos/uso terapêutico , Desbridamento/métodos , Região de Recursos Limitados , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Lacrosse, a sport of increasing popularity, is played with netted sticks and a firm rubber ball propelled at speeds frequently reaching over 100 miles/hour. While lacrosse injuries have been previously described, little published literature exists on lacrosse balls causing pulmonary contusion. We present a case of a 17-year-old male lacrosse player athlete who suffered a lacrosse ball strike to the left posterolateral chest, leading to a clinical presentation of local bruising, shortness of breath, and hemoptysis. Despite delayed arrival to the emergency room, where imaging revealed pulmonary contusion, multidisciplinary supportive management led to favorable clinical outcome with no residual effect on athletic ability and quality of life. Although pulmonary contusion may be a rare injury in the setting of thoracic trauma from lacrosse ball strikes, prompt evaluation and a high index of suspicion can rule out more life-threatening processes and ensure an excellent clinical prognosis.
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BACKGROUND: Frontal craniotomies for a medial subfrontal approach necessitate crossing the frontal sinus. Large superior extensions of the frontal sinus into frontal bone can result in mucosal retention in a free craniotomy bone flap, leading to a delayed mucocele with significant associated morbidity. The authors describe an "open-window" craniectomy technique that permits mucosal removal under direct vision and maintains the inner table on the bone flap's inferior side, helping to seal off the sinus opening with a pericranial flap. OBSERVATIONS: An illustrative case involving a medial right frontal craniotomy for a third ventricle mass in a patient with a large superior extension of the frontal sinus into frontal bone is presented. After creating a free frontal bone flap, the inner table was drilled out to the margins of the frontal sinus cavity and any remaining mucosa was cleared. A portion of the inner table above the bone flap's inferior margin was left in place, resembling an open window when viewed from the inner table side. The remaining anterior and posterior wall of the flap inferiorly provided a matched surface for the opening into the remaining frontal sinus, which was covered by pericranium. Long-term follow-up indicated no major complications or delayed mucocele. LESSONS: The open-window craniectomy technique can be considered for frontal sinus violations in patients with large superior frontal bone extension.
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Novel tissue-agnostic therapeutics targeting driver mutations in tumor cells have been recently approved by FDA, driven by basket trials that have demonstrated their efficacy and safety across diverse tumor histology. However, the relative rarity of primary brain tumors (PBTs) has limited their representation in early trials of tissue-agnostic medications. Thus, consensus continues to evolve regarding utility of tissue-agnostic medications in routine practice for PBTs, a diverse group of neoplasms characterized by limited treatment options and unfavorable prognoses. We describe current and potential impact of tissue-agnostic approvals on management of PBTs. We discuss data from clinical trials for PBTs regarding tissue-agnostic targets, including BRAFV600E, neurotrophic tyrosine receptor kinase (NTRK) fusions, microsatellite instability-high (MSI-High), mismatch repair deficiency (dMMR), and high tumor mutational burden (TMB-H), in context of challenges in managing PBTs. Described are additional tissue-agnostic targets that hold promise for benefiting patients with PBTs, including RET fusion, fibroblast growth factor receptor (FGFR), ERBB2/HER2, and KRASG12C, and TP53Y220C.
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Neoplasias Encefálicas , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Humanos , Mutação , Neoplasias Colorretais/genética , Prognóstico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genéticaRESUMO
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.
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Educação Médica , Médicos , Humanos , Pessoal de Saúde , ÍndiaRESUMO
Introduction: Sex differences in glioblastoma (GBM) have been observed in incidence, genetic and epigenetic alterations, and immune response. These differences have extended to the methylation of the MGMT promoter, which critically impacts temozolomide resistance. However, the association between sex, MGMT methylation, and survival is poorly understood, which this study sought to evaluate. Methods: A retrospective cohort study was conducted and reported following STROBE guidelines, based on adults with newly diagnosed GBM who received their first surgical intervention at Cleveland Clinic (Ohio, USA) between 2012 and 2018. Kaplan-Meier and multivariable Cox proportional hazards models were used to analyze the association between sex and MGMT promoter methylation status on overall survival (OS). MGMT was defined as methylated if the mean of CpG 1-5 ≥ 12. Propensity score matching was performed on a subset of patients to evaluate the effect of individual CpG site methylation. Results: A total of 464 patients had documented MGMT methylation status with a mean age of 63.4 (range 19-93) years. A total of 170 (36.6%) were female, and 133 (28.7%) received gross total resection as a first intervention. A total of 42.5% were MGMT methylated, with females more often having MGMT methylation than males (52.1% vs. 37.4%, p = 0.004). In univariable analysis, OS was significantly longer for MGMT promoter methylated than un-methylated groups for females (2 yr: 36.8% vs. 11.1%; median: 18.7 vs. 9.5 months; p = 0.001) but not for males (2 yr: 24.3% vs. 12.2%; median: 12.4 vs. 11.3 months; p = 0.22, p for MGMT-sex interaction = 0.02). In multivariable analysis, MGMT un-methylated versus methylated promoter females (2.07; 95% CI, 1.45-2.95; p < 0.0001) and males (1.51; 95% CI, 1.14-2.00; p = 0.004) had worse OS. Within the MGMT promoter methylated group, males had significantly worse OS than females (1.42; 95% CI: 1.01-1.99; p = 0.04). Amongst patients with data on MGMT CpG promoter site methylation values (n = 304), the median (IQR) of CpG mean methylation was 3.0% (2.0, 30.5). Females had greater mean CpG methylation than males (11.0 vs. 3.0, p < 0.002) and higher per-site CpG methylation with a significant difference at CPG 1, 2, and 4 (p < 0.008). After propensity score matching, females maintained a significant survival benefit (18.7 vs. 10.0 months, p = 0.004) compared to males (13.0 vs. 13.6 months, p = 0.76), and the pattern of difference was significant (P for CpG-sex interaction = 0.03). Conclusions: In this study, females had higher mean and individual CpG site methylation and received a greater PFS and OS benefit by MGMT methylation that was not seen in males despite equal degrees of CpG methylation.