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1.
J Immunother Cancer ; 12(4)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599660

RESUMO

With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence of immune-related adverse events (irAEs) is on the rise. Dermatologic immune-related adverse events (D-irAEs) are the most common and earliest to manifest, often with important downstream consequences for the patient. Current guidelines lack clarity in terms of diagnostic criteria for D-irAEs. The goal of this project is to better define D-irAE for the purposes of identification, diagnosis, and future study of this important group of diseases.The objectives of this project were to develop consensus guidance for an approach to D-irAEs including disease definitions and severity grading. Knowing that consensus among oncologists, dermatologists, and irAE subspecialists would be critical for usability, we formed a Dermatologic irAE Disease Definition Panel. The panel was composed of 34 experts, including oncologists, dermatologists, a rheumatologist, and an allergist/immunologist from 22 institutions across the USA and internationally. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two virtual meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness, and accuracy on 9-point scales in electronic surveys and provided free text comments. A working group aggregated survey responses and incorporated them into revised definitions. Consensus was based on numeric ratings using the RAND/UCLA Appropriateness Method with prespecified definitions.Following revisions based on panelist feedback, all items received consensus in the second round of ratings. Consensus definitions were achieved for 10 core D-irAE diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover's, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, and ICI-erosive mucocutaneous. A standard evaluation for D-irAE was also found to reach consensus, with disease-specific exceptions detailed when necessary. Each disorder's description includes further details on disease subtypes, symptoms, supportive exam findings, and three levels of diagnostic certainty (definite, probable, and possible).These consensus-driven disease definitions standardize D-irAE classification in a useable framework for multiple disciplines and will be the foundation for future work. Given consensus on their accuracy and usability from a representative panel group, we anticipate that they can be used broadly across clinical and research settings.


Assuntos
Exantema , Oncologistas , Humanos , Consenso , Inibidores de Checkpoint Imunológico/efeitos adversos , Radioimunoterapia
2.
Int Urogynecol J ; 35(1): 3-17, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37796329

RESUMO

INTRODUCTION AND HYPOTHESIS: The aim of the study was to perform a systematic review and meta-analysis of the impact of pregnancy and childbirth (vaginal delivery [VD]) or cesarean section (CS) on the recurrence of pelvic floor disorders in women who had previously undergone pelvic floor reconstructive surgery for pelvic organ prolapse (POP) or stress urinary incontinence (SUI), to facilitate future evidence-based counseling. METHODS: PubMed, Cochrane, Embase, BJOG, Scopus, etc. were screened, from 1990 to date. Inclusion criteria included cohort studies, case-control studies, case series, and case reports that reported on the primary outcome measure of the review. Exclusion criteria included studies on surgical procedures whose outcomes are unlikely to be impacted by pregnancy and childbirth or are obsolete. Meta-analysis was performed using Review Manager 5.3. RESULTS: Seven papers on midurethral slings (MUS; 181 women in both VD and CS groups respectively) and three papers on different hysteropexy techniques (47 and 29 women in the VD and CS groups respectively), were included in the meta-analysis. No difference was seen between the two groups regarding the recurrence of SUI in women who had previously undergone MUS surgery (OR: 1.18 [0.66, 2.09]; Z = 0.56; p = 0.58) or the recurrence of POP following hysteropexy using various apical suspension procedures (OR: 1.81 [0.04, 80.65]; Z = 0.31; p = 0.76). There are insufficient data to support meta-analyses for individual MUS sub-types or hysteropexy procedures. CONCLUSION: Current literature does not demonstrate a protective effect of CS in preventing recurrent SUI in women who had undergone MUS surgery for SUI. When hysteropexy is considered irrespective of the apical suspension procedure employed, the incidence of recurrent POP appears similar after CS and VD.


Assuntos
Prolapso de Órgão Pélvico , Cirurgia Plástica , Incontinência Urinária por Estresse , Feminino , Gravidez , Humanos , Cesárea/efeitos adversos , Diafragma da Pelve/cirurgia , Parto Obstétrico/efeitos adversos , Parto , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/cirurgia , Incontinência Urinária por Estresse/epidemiologia , Prolapso de Órgão Pélvico/cirurgia , Prolapso de Órgão Pélvico/complicações
4.
J Natl Compr Canc Netw ; 21(9): 961-979, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37673108

RESUMO

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.


Assuntos
Mesotelioma Maligno , Mesotelioma , Humanos , Oncologia , Mesotelioma/diagnóstico , Mesotelioma/terapia , Peritônio
5.
J Natl Compr Canc Netw ; 21(4): 340-350, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37015337

RESUMO

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante
6.
N Engl J Med ; 388(9): 813-823, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36856617

RESUMO

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).


Assuntos
Antineoplásicos Imunológicos , Melanoma , Terapia Neoadjuvante , Neoplasias Cutâneas , Humanos , Adjuvantes Imunológicos , Progressão da Doença , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/cirurgia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Quimioterapia Adjuvante
7.
Indian J Ophthalmol ; 70(10): 3569-3574, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36190048

RESUMO

Purpose: This study was done to report intermediate-term outcomes of irrigating goniectomy with trabectome (trabectome) surgery among different types of glaucoma eyes from a single center in India using a cross-sectional, longitudinal, observational study design. Methods: Fifty-three patients (58 eyes) with glaucoma who underwent irrigating goniectomy with trabectome between January 2019 and February 2020 were included. Pre-operative data included age, gender, eye laterality, specific diagnosis, number of anti-glaucoma medications (AGMs), prior glaucoma surgeries, visual acuity, and intraocular pressure (IOP) on medical treatment. Post-operative data included IOP changes during the follow-up till 1-year, number of AGMs, any complications, or additional surgical intervention required. Success was defined as IOP ≤ 21 mmHg and ≥ 20% reduction of IOP from pre-operative IOP with no additional glaucoma surgery. Results: The cohort included 58 eyes (male 53.4% and female 46.6%) ranging from 0.6 to 81 years of age. The average baseline IOP was 23.4 ± 10.2 mmHg and reduced significantly with surgery to 14.1 ± 5.3 mmHg at 1-year follow-up. The AGMs reduced from 2.4 ± 1.4 pre-surgery to 1.6 ± 1.4 at 1-year follow-up. Four eyes required additional glaucoma surgeries for IOP control. The success rate of trabectome with phacoemulsification (88%) was discernibly higher than with trabectome alone (67%). Intra-operatively, significant blood reflux was noticed in 27 eyes, of which only one required tamponading with a viscoelastic agent. Conclusion: This study concludes that irrigating goniectomy with trabectome has good efficacy and safety in both pediatric and adult cases of glaucoma in terms of IOP control, reduction in AGMs, and low incidence of complications in the Indian population.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Trabeculectomia , Adulto , Criança , Estudos Transversais , Feminino , Seguimentos , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Masculino , Estudos Retrospectivos , Resultado do Tratamento
8.
Rev Dev Econ ; 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35942311

RESUMO

Information provision for social welfare via cheap technological media is now a widely available tool used by policymakers. Often, however, an ample supply of information does not translate into high consumption of information due to various frictions in demand, possibly stemming from the pecuniary and non-pecuniary cost of engagement, along with institutional factors. We test this hypothesis in the Indian context using a unique data set comprising 2 million call records of enrolled users of ARMMAN, a Mumbai-based nongovernmental organization that sends timely informational calls to mobile phones of less-privileged pregnant women. The strict lockdown induced by COVID-19 in India was an unexpected shock on engagement with m-Health technology, in terms of both reductions in market wages and increased time availability at home. Using a difference-in-differences design on unique calls tracked at the user-time level with fine-grained time-stamps on calls, we find that during the lockdown period, the call durations increased by 1.53 percentage points. However, technology engagement behavior exhibited demographic heterogeneity increasing relatively after the lockdown for women who had to borrow the phones vis-à-vis phone owners, for those enrolled in direct outreach programs vis-à-vis self-registered women, and for those who belonged to the low-income group vis-à-vis high-income group. These findings are robust with coarsened exact matching and with a placebo test for a 2017-2018 sample. Our results have policy implications around demand-side frictions for technology engagement in developing economies and maternal health.

9.
Front Oncol ; 12: 785350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692764

RESUMO

Purpose/Objectives: The abscopal effect could theoretically be potentiated when combined with immunomodulating drugs through increased antigen production. The optimal dosing and schedule of radiotherapy with immunotherapy are unknown, although they are actively investigated in laboratory and clinical models. Clinical data in patients treated for metastatic disease with both modalities may guide future studies. Materials and Methods: This is a single-institution retrospective review of all patients treated with stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS) and immunomodulating therapy within 6 months before or after SBRT/SRS for metastatic cancer. Clinical and tumor characteristics were recorded, as well as SBRT/SRS details, immunotherapy details, and survival. Log-rank tests on Kaplan-Meier curves for overall survival (OS) that were calculated from the end of SBRT/SRS were used in univariate analysis and Cox proportional hazards regression for multivariate analysis. Results: A total of 125 patients were identified who met the inclusion criteria; 70 received SBRT, and 57 received SRS. Eighty-three patients were treated for non-small cell lung cancer, 7 patients for small cell lung cancer, and 35 patients for other cancers, with the most common one being melanoma. Fifty-three percent of patients received nivolumab, 29% pembrolizumab, 13% atezolizumab, 5% other. Twenty percent received immunotherapy before SBRT/SRS, 39% during SBRT/SRS, 41% after. Eighty-six patients had died by the time of the analysis; the median OS for the whole cohort was 9.7 months. Patients who had completed immunotherapy prior to SBRT/SRS had worse OS than those who received concurrent therapy or immunotherapy after SBRT/SRS, with a difference in median OS of 3.6 months vs. 13.0 months (p = 0.010) that was retained on multivariate analysis (p = 0.011). There was no significant difference in OS between patients receiving SRS vs. SBRT (p = 0.20), sex (p = 0.53), age >62 years (p = 0.76), or lung primary vs. others (p = 0.73) on univariate or multivariate analysis. When comparing before/concurrent to after/concurrent administration, there is a difference in survival with after/concurrent survival of 8.181 months and before survival of 13.010 months, but this was not significant (p = 0.25). Conclusions: OS appears to be worse in patients who complete immunotherapy prior to SBRT/SRS compared to those receiving it concurrently or after. The design of this retrospective review may be prone to lead time bias, although the difference in median survival is longer than the 6-month window before SBRT/SRS and could only account for part of this difference. Further analysis into causes of death and toxicity and prospective studies are needed to confirm the results of this analysis.

10.
J Natl Compr Canc Netw ; 20(5): 497-530, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35545176

RESUMO

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Oncologia , Recidiva Local de Neoplasia
11.
J Natl Compr Canc Netw ; 20(4): 387-405, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35390769

RESUMO

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.


Assuntos
Oncologia , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico
12.
Int Urogynecol J ; 33(2): 173-187, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34977950

RESUMO

INTRODUCTION AND HYPOTHESIS: This narrative review describes the existing epidemiologic literature and identifies gaps regarding pelvic organ prolapse (POP) prevalence, incidence, natural history, and current and future service needs. MATERIALS AND METHODS: A PubMed search identified relevant citations published in 2000 or later. Pre-specified criteria were used to screen titles, abstracts, and manuscripts, including reference sections. Study findings were summarized to define what is known, identify gaps in current knowledge, and suggest priority areas for future research. RESULTS: The reported prevalence of POP varies widely (1-65%) based on whether its presence is ascertained by symptoms (1-31%), pelvic examination (10-50%), or both (20-65%). Most existing population-based surveys do not include physical examination data. White women from higher income countries are overrepresented in the existing literature. Incidence and natural history data are limited and consist mainly of cohorts that follow women after pregnancy or menopause. Given global increases in aging populations in well-resourced countries, the need for POP treatment is anticipated to increase in the coming decades. In lower and middle income countries (LMICs) where demographic trends are different, there is a dearth of information about anticipated POP service needs. CONCLUSION: Future POP incidence, prevalence, and natural history studies should include non-white women from LMICs and should combine pelvic examination data with validated patient-reported outcome measures when feasible. Anticipated future service needs differ globally, with a greater demand for POP treatment services in well-resourced settings where aging populations are prevalent.


Assuntos
Prolapso de Órgão Pélvico , Envelhecimento , Feminino , Humanos , Incidência , Prolapso de Órgão Pélvico/epidemiologia , Prolapso de Órgão Pélvico/terapia , Gravidez , Prevalência , Encaminhamento e Consulta
13.
J Natl Compr Canc Netw ; 20(4): 371-377.e5, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384045

RESUMO

BACKGROUND: Optimal treatment of nonoperative patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. Current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend definitive radiotherapy (RT) with or without sequential chemotherapy and do not include concurrent chemoradiotherapy (chemoRT) as a treatment option. In this study, we identified factors that predict nonadherence to NCCN Guidelines. PATIENTS AND METHODS: Patients who received definitive RT for nonmetastatic, node-negative NSCLC with tumor size of 5 to 7 cm were identified in the National Cancer Database from 2004 through 2016. Patients were evaluated by RT type (stereotactic body RT [SBRT], hypofractionated RT [HFRT], or conventionally fractionated RT [CFRT]) and chemotherapy use (none, sequential, or concurrent with RT). Patients were classified as receiving NCCN-adherent (RT with or without sequential chemotherapy) or NCCN-nonadherent (concurrent chemoRT) treatment. Demographic and clinical factors were assessed with logistic regression modeling. Overall survival was evaluated with Kaplan-Meier, log-rank, and univariable/multivariable Cox proportional hazards regression analyses. RESULTS: Among 2,020 patients in our cohort, 32% received NCCN-nonadherent concurrent chemoRT, whereas others received NCCN-adherent RT alone (51%) or sequential RT and chemotherapy (17%). CFRT was most widely used (64% CFRT vs 22% SBRT vs 14% HFRT). Multivariable analysis revealed multiple factors to be associated with NCCN-nonadherent chemoRT: age ≤70 versus >70 years (odds ratio [OR] , 2.72; P<.001), treatment at a nonacademic facility (OR, 1.65; P<.001), and tumor size 6 to 7 cm versus 5 to 6 cm (OR, 1.27; P=.026). Survival was similar between the NCCN-nonadherent chemoRT and NCCN-adherent groups (hazard ratio, 1.00; P=.992) in multivariable analysis. CONCLUSIONS: A substantial proportion of inoperable patients with large, node-negative NSCLC are not treated according to NCCN Guidelines and receive concurrent chemoRT. Younger patients with larger tumors receiving treatment at nonacademic medical centers were more likely to receive NCCN-nonadherent therapy, but adherence to NCCN Guidelines was not associated with differences in overall survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Idoso , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/patologia , Hipofracionamento da Dose de Radiação , Resultado do Tratamento
16.
Nat Rev Clin Oncol ; 18(5): 313-319, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33723371

RESUMO

Emerging efficacy data have led to the emergency use authorization or approval of COVID-19 vaccines in several countries worldwide. Most trials of COVID-19 vaccines excluded patients with active malignancies, and thus data on the safety, tolerability and efficacy of the vaccines in patients with cancer are currently limited. Given the risk posed by the COVID-19 pandemic, decisions regarding the use of vaccines against COVID-19 in patients participating in trials of investigational anticancer therapies need to be addressed promptly. Patients should not have to choose between enrolling on oncology clinical trials and receiving a COVID-19 vaccine. Clinical trial sponsors, investigators and treating physicians need operational guidance on COVID-19 vaccination for patients with cancer who are currently enrolled or might seek to enrol in clinical trials. Considering the high morbidity and mortality from COVID-19 in patients with cancer, the benefits of vaccination are likely to far outweigh the risks of vaccine-related adverse events. Herein, we provide operational COVID-19 vaccine guidance for patients participating in oncology clinical trials. In our perspective, continued quality oncological care requires that patients with cancer, including those involved in trials, be prioritized for COVID-19 vaccination, which should not affect trial eligibility.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Ensaios Clínicos como Assunto , Neoplasias , Vacinação/normas , Humanos , Neoplasias/terapia , Seleção de Pacientes , SARS-CoV-2
17.
Clin Cancer Res ; 27(11): 3050-3060, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33771853

RESUMO

PURPOSE: As hypoxia can mediate resistance to immunotherapy, we investigated the safety, tolerability, and efficacy of combining evofosfamide, a prodrug that alleviates hypoxia, with ipilimumab, an immune checkpoint inhibitor, in immunologically "cold" cancers, which are intrinsically insensitive to immunotherapy, as well as in "hot/warm" metastatic cancers that are, atypical of such cancers, resistant to immunotherapy. PATIENTS AND METHODS: In a phase I, 3+3 dose-escalation trial (NCT03098160), evofosfamide (400-640 mg/m2) and ipilimumab (3 mg/kg) were administered in four 3-week cycles. The former was administered on days 1 and 8 of cycles 1-2, while the latter was administered on day 8 of cycles 1-4. Response was assessed using immune-related RECIST and retreatment was allowed, if deemed beneficial, after completion of cycle 4 or at progression. RESULTS: Twenty-two patients were enrolled, of whom 21 were evaluable, encompassing castration-resistant prostate cancer (n = 11), pancreatic cancer (n = 7), immunotherapy-resistant melanoma (n = 2), and human papillomavirus-negative head and neck cancer (n = 1). Drug-related hematologic toxicities, rash, fever, nausea, vomiting, and elevation of liver enzymes were observed in > 10% of patients. The most common drug-related grade 3 adverse event was alanine aminotransferase elevation (33.3%). Two patients discontinued ipilimumab and 4 required evofosfamide deescalation due to toxicity. Of 18 patients with measurable disease at baseline, 3 (16.7%) achieved partial response and 12 (66.7%) achieved stable disease. The best responses were observed at 560 mg/m2 evofosfamide. Preexisting immune gene signatures predicted response to therapy, while hypermetabolic tumors predicted progression. Responders also showed improved peripheral T-cell proliferation and increased intratumoral T-cell infiltration into hypoxia. CONCLUSIONS: No new or unexpected safety signals were observed from combining evofosfamide and ipilimumab, and evidence of therapeutic activity was noted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Ipilimumab/administração & dosagem , Melanoma/tratamento farmacológico , Nitroimidazóis/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Mostardas de Fosforamida/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Feminino , Humanos , Ipilimumab/efeitos adversos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Nitroimidazóis/efeitos adversos , Mostardas de Fosforamida/efeitos adversos , Segurança , Resultado do Tratamento
18.
J Minim Access Surg ; 17(2): 159-164, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33723179

RESUMO

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) has been proven to induce significant weight loss and remission of related co-morbidities in patients with morbid obesity. The long-term follow-up data show weight regain or failure to achieve complete remission of type 2 diabetes mellitus (T2DM) in some patients. In this study, we report weight loss patterns and remission of T2DM in patients with morbid obesity during a 5-year follow-up after RYGB. OBJECTIVE: The objective was to evaluate outcomes during the follow-up on excess weight loss (EWL) and remission of T2DM after laparoscopic RYGB among Indian patients. SETTING: The study was conducted in a tertiary care hospital, Kerala, India. MATERIALS AND METHODS: This is a retrospective study in patients who underwent surgery between 2007 and 2010. The patient demographics, pre- and post-operative body mass index (BMI), co-morbidities and EWL were recorded from the medical records. These data were compared between pre-operative and follow-up intervals till 5 years using statistical approaches. RESULTS: The study included 157 patients (91 males and 66 females) having a mean pre-operative BMI of 47.91 ± 7.01 kg/m2. A significant reduction in the BMI was observed at each follow-up point (P < 0.01) till 5 years after the surgery. The mean percentage of EWL increased from 34.57% ± 12.62% to 71.50% ± 15.41% from 3 months to 5 years after the surgery. Twelve per cent (n = 19) of patients achieved normal BMI (<25 mg/kg2) by 3rd year after the surgery. However, the remission of T2DM was achieved in >50% of patients within a year of surgery. During the 5th year, weight regain (1-22 kg) was observed in 36.70% (n = 58) patients, and recurrence of T2DM was observed in two patients. CONCLUSIONS: The long-term durability of RYGB in the study population was satisfactory with significant weight loss and remission of T2DM.

19.
Int Urogynecol J ; 32(3): 653-659, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32949252

RESUMO

INTRODUCTION AND HYPOTHESIS: The objective was to determine age-related changes in measurements of urethral sphincter complex components in asymptomatic nulliparous women. METHODS: Eighty nulliparous women ≥18 years underwent 3D ultrasound of the anterior pelvic compartment in a cross-sectional study. Measurements of the urethral sphincter components (smooth muscle sphincter [SMS] and striated urinary sphincter [SUS]) and urethra including area, length, width, and distance of the SUS and SMS from the urethrovesical junction were obtained. The women were grouped into four age groups: < 30 years (group A), 30 to < 45 (group B), 45 to < 60 (group C), and ≥ 60 years (group D). Age-related differences in the measurements were determined. Inter-rater and intra-rater agreement were performed for 20 nulliparous women. RESULTS: There were 24, 18, 26, and 12 women in groups A, B, C, and D respectively. None of the urethral sphincter complex measurements was significantly associated with age (p > 0.05). No differences were found between the groups for any measurements using one-way ANOVA and multiple comparison pairwise comparison (p > 0.05) other than width of SMS (C > A), urethral length (C > A), and distance of SUS from urethrovesical junction (C > D). Inter-rater and intra-rater agreement were moderate for area, length, and width of SUS (intraclass correlation 0.6) and good (intraclass correlation above 0.8) for the remaining measurements. CONCLUSION: Other than width of SMS, urethral length, and distance of SUS from urethrovesical junction, the dimensions of urethral sphincter complex components, as visualized by 3D endovaginal ultrasound, do not vary with age.


Assuntos
Músculo Liso , Uretra , Adulto , Estudos Transversais , Feminino , Humanos , Paridade , Gravidez , Ultrassonografia , Uretra/diagnóstico por imagem
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