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1.
J Hosp Infect ; 145: 59-64, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38141666

RESUMO

BACKGROUND: Mandatory mask-wearing policies were one of several measures employed to reduce hospital-acquired SARS-CoV-2 infection throughout the pandemic. Many nations have removed healthcare mask mandates, but there remains a risk of new SARS-CoV-2 variants or epidemics of other respiratory viruses. AIM: To demonstrate the impact of removing the healthcare mask mandate. METHODS: SARS-CoV-2 infections were analysed in a large teaching hospital for 40 weeks in 2022 using a controlled interrupted time-series design. The intervention was the removal of a staff/visitor surgical mask-wearing policy for the most wards at week 26 (intervention group) with a subset of specific wards retaining the mask policy (control group). The hospital-acquired SARS-CoV-2 infection rate was adjusted by the underlying community infection rate. FINDINGS: In the context of a surge in SARS-CoV-2 infection, removal of the mask mandate for staff/visitors was not associated with a statistically significant change in the rate of nosocomial SARS-CoV-2 infection in the intervention group (incidence rate ratio: 1.105; 95% confidence interval: 0.523-2.334; P = 0.79) and there was no post-intervention trend (1.013; 0.932-1.100; P = 0.76) to suggest a delayed effect. The control group also showed no immediate or delayed change in infection rate. CONCLUSION: No evidence was found that removal of a staff/visitor mask-wearing policy had a significant effect on the rate of hospital-acquired SARS-CoV-2 infection. This does not demonstrate that masks were ineffective through the pandemic, but provides some objective evidence to justify the removal of healthcare mask mandates once there was widespread immunity and reduced disease severity.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Pandemias/prevenção & controle , Máscaras , Hospitais
2.
Oral Oncol ; 147: 106587, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37925894

RESUMO

BACKGROUND: In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC. MATERIALS AND METHODS: Patients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3-6 months of previous platinum-containing definitive therapy for locally advanced disease. Patients were randomly assigned (1:1) to pembrolizumab 200 mg Q3W or investigator's choice of standards of care (SOC): methotrexate, docetaxel, or cetuximab. Outcomes included OS, PFS, ORR, and DOR. The data cutoff was May 15, 2017. RESULTS: There were 125 patients (pembrolizumab, 53; SOC, 72) in the recurrent-only subgroup, 204 in the recurrent-metastatic subgroup (pembrolizumab, 108; SOC, 96), and 166 in the metastatic-only subgroup (pembrolizumab, 86; SOC, 80). The hazard ratio (95% CI) for death for pembrolizumab versus SOC was 0.83 (0.55-1.25) in the recurrent-only, 0.78 (0.58-1.06) in the recurrent-metastatic, and 0.74 (0.52-1.05) in the metastatic-only subgroups. PFS was similar between treatment arms in all subgroups. ORR was 22.6% for pembrolizumab versus 16.7% for SOC in the recurrent-only, 10.2% versus 6.3% in the recurrent-metastatic, and 15.1% versus 8.8% in the metastatic-only subgroups. DOR was numerically longer with pembrolizumab in all subgroups. CONCLUSION: Pembrolizumab provided numerically longer OS and durable responses in all subgroups compared with SOC, suggesting that patients with previously treated R/M HNSCC benefit from pembrolizumab regardless of recurrence pattern.


Assuntos
Neoplasias de Cabeça e Pescoço , Metotrexato , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Cetuximab/uso terapêutico , Docetaxel/uso terapêutico , Platina/uso terapêutico , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
J Hosp Infect ; 141: 88-98, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37678435

RESUMO

This is a report on an outbreak of Panton-Valentine leucocidin-producing meticillin-resistant Staphylococcus aureus (PVL-MRSA) in an intensive care unit (ICU) during the COVID-19 pandemic that affected seven patients and a member of staff. Six patients were infected over a period of ten months on ICU by the same strain of PVL-MRSA, and a historic case identified outside of the ICU. All cases were linked to a healthcare worker (HCW) who was colonized with the organism. Failed topical decolonization therapy, without systemic antibiotic therapy, resulted in ongoing transmission and one preventable acquisition of PVL-MRSA. The outbreak identifies the support that may be needed for HCWs implicated in outbreaks. It also demonstrates the role of whole-genome sequencing in identifying dispersed and historic cases related to the outbreak, which in turn aids decision-making in outbreak management and HCW support. This report also includes a review of literature of PVL-MRSA-associated outbreaks in healthcare and highlights the need for review of current national guidance in the management of HCWs' decolonization regimen and return-to-work recommendations in such outbreaks.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Meticilina , Leucocidinas/genética , Pandemias/prevenção & controle , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Exotoxinas/genética , Surtos de Doenças/prevenção & controle , Staphylococcus aureus , Pessoal de Saúde
4.
Malar J ; 22(1): 45, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36747302

RESUMO

BACKGROUND: Compared to 2017, India achieved a significant reduction in malaria cases in 2020. Madhya Pradesh (MP) is a tribal dominated state of India with history of high malaria burden in some districts. District Mandla of MP state showed a considerable decline in malaria cases between 2000 and 2013, except in 2007. Subsequently, a resurgence of malaria cases was observed during 2014 and 2015. The Malaria Elimination Demonstration Project (MEDP) was launched in 2017 in Mandla with the goal to achieve zero indigenous malaria cases. This project used: (1) active surveillance and case management using T4 (Track fever, Test fever, Treat patient, and Track patient); (2) vector control using indoor residual sprays and long-lasting insecticidal nets; (3) information education communication and behaviour change communication; and (4) regular monitoring and evaluation with an emphasis on operational and management accountability. This study has investigated malaria prevalence trends from 2008 to 2020, and has predicted trends for the next 5 years for Mandla and its bordering districts. METHODS: The malaria prevalence data of the district Mandla for the period of January 2008 to August 2017 was obtained from District Malaria Office (DMO) Mandla and data for the period of September 2017 to December 2020 was taken from MEDP data repository. Further, the malaria prevalence data for the period of January 2008 to December 2020 was collected from DMOs of the neighbouring districts of Mandla. A univariate time series and forecast analysis was performed using seasonal autoregressive integrated moving average model. FINDINGS: Malaria prevalence in Mandla showed a sharp decline [- 87% (95% CI - 90%, - 84%)] from 2017 to 2020. The malaria forecast for Mandla predicts zero cases in the next 5 years (2021-2025), provided current interventions are sustained. By contrast, the model has forecasted a risk of resurgence of malaria in other districts in MP (Balaghat, Dindori, Jabalpur, Seoni, and Kawardha) that were not the part of MEDP. CONCLUSION: The interventions deployed as part of MEDP have resulted in a sustainable zero indigenous malaria cases in Mandla. Use of similar strategies in neighbouring and other malaria-endemic districts in India could achieve similar results. However, without adding extra cost to the existing intervention, sincere efforts are needed to sustain these interventions and their impact using accountability framework, data transparency, and programme ownership from state to district level.


Assuntos
Malária , Humanos , Fatores de Tempo , Malária/epidemiologia , Malária/prevenção & controle , Índia/epidemiologia , Projetos de Pesquisa , Administração de Caso
5.
Malar J ; 22(1): 62, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810077

RESUMO

BACKGROUND: Global malaria cases rose by 14 million, and deaths by 69,000, in 2020. In India, a 46% decline has been reported between 2020 and 2019. In 2017, the Malaria Elimination Demonstration Project conducted a needs-assessment of the Accredited Social Health Activists (ASHAs) of Mandla district. This survey revealed the inadequate level of knowledge in malaria diagnosis and treatment. Subsequently, a training programme was launched for enhancing malaria-related knowledge of ASHAs. The present study was conducted in 2021 to evaluate the impact of training on malaria-related knowledge and practices of ASHAs in Mandla. This assessment was also done in two adjoining districts: Balaghat and Dindori. METHODS: A cross-sectional survey using a structured questionnaire was administered to ASHAs to measure their knowledge and practices related to malaria etiology, prevention, diagnosis, and treatment. A comparison of information collected from these three districts was performed using simple descriptive statistics, comparison of means and multivariate logistic regression analysis. RESULTS: Significant improvement was noted amongst ASHAs of district Mandla between 2017 (baseline) and 2021 (endline) in knowledge related to malaria transmission, preventive measures, adherence to the national drug policy, diagnosis using rapid diagnostic tests, and identification of age group-specific, colour-coded artemisinin combination therapy blister packs (p < 0.05). The multivariate logistic regression analysis revealed that odds of Mandla baseline was 0.39, 0.48, 0.34, and 0.07 times lower for malaria-related knowledge on disease etiology, prevention, diagnosis, and treatment, respectively (p < 0.001). Further, participants in districts Balaghat and Dindori showed significantly lower odds for knowledge (p < 0.001) and treatment practices (p < 0.01) compared to Mandla endline. Education, attended training, having a malaria learner's guide, and minimum 10 years' work experience were potential predictors for good treatment practices. CONCLUSION: The findings of the study unequivocally establishes significant improvement in overall malaria-related knowledge and practices of ASHAs in Mandla as a result of periodic training and capacity building efforts. The study suggests that learnings from Mandla district could be helpful in improving level of knowledge and practices among frontline health workers.


Assuntos
Malária , Humanos , Estudos Transversais , Índia , Agentes Comunitários de Saúde , Inquéritos e Questionários
6.
Int J Radiat Oncol Biol Phys ; 116(1): 50-59, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36720317

RESUMO

PURPOSE: Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at greater risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs affect patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). We aimed to analyze the effect of residing in an FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. METHODS AND MATERIALS: This is a retrospective study of 573 patients with locally advanced NSCLC consecutively treated from January 2000 to January 2020. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence. Cox regression with forward model selection was used for multivariate analysis. RESULTS: Thirty-two percent of patients resided in an FPA (n = 183) and were more likely to self-identify as Black (P < .0001), single (P < .001), <60 years of age (P = .001), and uninsured (P < .0001), with a lower median income (P < .001). Patients in FPAs also had lower mean pre-chemoradiation (CRT) albumin (P = .002), lower pre-CRT body mass index (BMI) (P = .026), and were less likely to receive trimodality therapy (P ≤ .001) compared with patients not living in FPAs. There was no difference in OS or freedom from recurrence between the 2 cohorts. However, in patients with a normal BMI, either pre-CRT (median OS, 18.4 vs 25.0 months; P = .005) or after CRT (15.1 vs 28.1 months, P = .002), residing in an FPA resulted in an OS detriment. CONCLUSIONS: We demonstrated a clear socioeconomic divide in our patient population with stage III NSCLC, where residing in FPAs was associated with less-aggressive therapy and an OS detriment for patients with a normal-weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Índice de Massa Corporal , Estudos Retrospectivos , Estudos Prospectivos , Quimiorradioterapia/métodos , Estadiamento de Neoplasias
7.
RSC Adv ; 12(3): 1352-1360, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35425173

RESUMO

The need for replacing conventional sources of energy with renewable ones has been on a swift rise since the last couple of decades. In this context, the progress in third-generation solar cells has taken a good leap in the last couple of years with increasing prospects of high efficiency, stability, and lifetime. Quite recently, a new form of carbon has been discovered accidentally in the form of carbon quantum dots (C QD), which is being pursued actively owing to its chemical stability and luminescent properties. In the current work, we report highly luminescent C QD prepared via a simple hydrothermal route. Transmission electron microscopy revealed an average particle size of 3.4 nm. The prepared C QD were used in a co-sensitized solar cell, where an improvement in the device characteristics was observed. The enhancement in the device characteristics is supported by impedance and electron life-time analysis. Further, the time-dependent analysis of the current and voltage revealed the functioning of the solar cell in real-time condition.

8.
NPJ Precis Oncol ; 6(1): 13, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35233056

RESUMO

The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting.

9.
Lung Cancer ; 163: 7-13, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34890832

RESUMO

OBJECTIVES: To better understand genetic determinants of response to ceritinib, an exploratory analysis was conducted using tumor biopsies from anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients treated with ceritinib at doses of ≥ 300 mg in the ASCEND-1 study. METHODS: ASCEND-1 was an open-label, multicentre, phase 1, dose-escalation and expansion study of ceritinib (fasted) in ALK inhibitor (ALKi)-naïve or ALKi-pretreated patients with locally advanced or metastatic ALK + NSCLC. Biopsies were assayed by next-generation sequencing (NGS) using a Foundation Medicine panel targeting 295 genes. Somatic alterations were correlated with clinical outcome (cut-off 14-Apr-2014). A total of 285 ALK + NSCLC patients were treated with ceritinib at doses ≥ 300 mg. RESULTS: NGS data were generated for 85 pts (ALKi-pretreated [n = 54]; ALKi-naïve [n = 31]), 57 were collected from patients before exposure to any ALKi. NGS did not detect ALK rearrangement in 14 of 85 patients; several of these ALK NGS negative cases harbored alternative drivers, e.g. EGFR mutation. Of the 71 biopsies with NGS confirmed ALK rearrangement, the most frequently detected rearrangements were EML4-ALK variant 1 (V1) and EML4-ALK V3 (36.6% [26/71] and 32.4% [23/71] respectively). Eight (six crizotinib-pretreated and two pretreated with crizotinib followed by alectinib) of the 21 ALKi-pretreated patients carried a point mutation of the ALK TKD, and had the biopsy collected between 1 and 14 days before ceritinib; with the exception of one patient with a G1202R point mutation, all patients derived clinical benefit from ceritinib treatment. Of the 14 ALKi-naïve patients, ceritinib was effective in almost all patients, including a patient carrying a concomitant ERBB4 and HGF amplification. CONCLUSIONS: This exploratory analysis highlights the potential role of NGS in improving our understanding of response and resistance to ceritinib. It also illustrates that ceritinib is active against almost all ALK resistance mutations found in ALKi-pretreated patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01283516. Registered January 26, 2011, https://clinicaltrials.gov/ct2/show/NCT01283516.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas , Receptores Proteína Tirosina Quinases/genética , Sulfonas
10.
Vaccine ; 39(44): 6470-6476, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34538521

RESUMO

BACKGROUND: The pre-existing partner network created in India for the delivery of polio vaccines was initially used to eradicate polio and later on embedded in the health systems network to promote routine immunization and other health interventions efficiently. The experience from this network offered lessons for strengthening the health care systems and provided a well-established network that could be utilized for other vaccine initiatives. It has also been established that successful partnerships between a broad range of stakeholders provide support, strengthen the health system, and accelerate vaccine innovation, introduction, access, logistics, and communication support. However, beyond polio eradication, there have not been too many documented success stories of vaccine introduction, which could be replicated in other new vaccine introductions and allied health initiatives. The authors have reviewed the successful and time-bound introduction of rotavirus vaccine (RVV) in India in the present article. METHODS: The review was conducted based on a partnership framework which analysed multiple factors-partnership prerequisites, partnership model, partnership process, and partnership performance, thereby providing a comprehensive insight into the successful utilization of partnership networks for rotavirus vaccine introduction under the Universal Immunization Program in India. RESULTS & CONCLUSION: The review also highlights the role of a lead agency in creating a fertile ground for lush, efficient, and effective partnerships amongst different stakeholders. The already existing RVV partnership framework reviewed by the authors can be successfully utilized for future new vaccine introductions.


Assuntos
Poliomielite , Vacinas contra Rotavirus , Humanos , Programas de Imunização , Índia , Estudos Retrospectivos , Vacinação
11.
Sci Rep ; 10(1): 19296, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168847

RESUMO

Strategies that interfere with the binding of the receptor programmed cell death protein-1 (PD-1) to programmed death ligand-1 (PD-L1) have shown marked efficacy against many advanced cancers, including those that are negative for PD-L1. Precisely why patients with PD-L1 negative tumors respond to PD-1/PD-L1 checkpoint inhibition remains unclear. Here, we show that platelet-derived PD-L1 regulates the growth of PD-L1 negative tumors and that interference with platelet binding to PD-L1 negative cancer cells promotes T cell-induced cancer cytotoxicity. These results suggest that the successful outcomes of PD-L1 based therapies in patients with PD-L1 negative tumors may be explained, in part, by the presence of intra-tumoral platelets. Altogether, our findings demonstrate the impact of non-cancer/non-immune cell sources of PD-L1 in the tumor microenvironment in the promotion of cancer cell immune evasion. Our study also provides a compelling rationale for future testing of PD-L1 checkpoint inhibitor therapies in combination with antiplatelet agents, in patients with PD-L1 negative tumors.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/metabolismo , Neoplasias/imunologia , Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Plaquetas/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Sistema Imunitário , Imuno-Histoquímica , Células Jurkat , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Pessoa de Meia-Idade , Ativação Plaquetária , Inibidores da Agregação Plaquetária/farmacologia , Estudos Retrospectivos , Linfócitos T/citologia , Microambiente Tumoral
12.
Radiat Prot Dosimetry ; 188(2): 162-173, 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31820784

RESUMO

The un-attached part of radon (222Rn) progeny is one of the imperative variables for the definitive evaluation of the effective dose from the radon exposure perspective, and it might fluctuate enormously in various ecological conditions. Therefore, estimate dispersion of 222Rn/220Rn progeny, un-attached part and aerosol concentration was estimated in an indoor domain of Jammu and Kashmir State, India utilizing progeny deposition based sensors. Distinctive sorts of residence were picked up for this exploratory examination and maximum 222Rn and thoron (220Rn) descendants concentration was found in working environments or workplaces when contrasted from other abodes because of low ventilation rate. The average evaluated portions of an unattached for 222Rn and 220Rn are 0.29 and 0.26 and in addition, observed to be most extreme in work environments. The age-dependent dose has furthermore been determined utilizing attached and un-attached 222Rn/220Rn progeny concentrations. The dose to trachea-bronchial region and aerosol concentrations has additionally been estimated.


Assuntos
Poluentes Radioativos do Ar , Poluição do Ar em Ambientes Fechados , Monitoramento de Radiação , Radônio , Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Habitação , Índia , Radônio/análise , Produtos de Decaimento de Radônio/análise
13.
JNMA J Nepal Med Assoc ; 54(202): 88-90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27935931

RESUMO

Caesarean scar pregnancy is one of the rarest forms of ectopic pregnancy. Transvaginal ultrasound and color flow Doppler provides a high diagnostic accuracy. A delay in diagnosis and treatment can lead to uterine rupture, major hemorrhage, hysterectomy and serious maternal morbidity and mortality. Early diagnosis can offer treatment options of avoiding uterine rupture and hemorrhage, thus preserving the uterus and future fertility. Primary health care provider should know about this rare entity, because if diagnosed timely, and referral to specialized centre is done without delay will definitely save maternal morbidity and mortality. Management plan should be individualized. Termination of pregnancy is the treatment of choice in the first trimester. Expectant treatment has a poor prognosis because of risk of rupture. In this case report we aim to discuss the associated diagnostic dilemma, most appropriate methods of diagnosis and management, with their implications in clinical practice.


Assuntos
Cesárea/efeitos adversos , Cicatriz/complicações , Gravidez Ectópica/diagnóstico por imagem , Aborto Terapêutico , Diagnóstico Precoce , Feminino , Humanos , Histerectomia , Gravidez , Gravidez Ectópica/etiologia , Gravidez Ectópica/cirurgia , Hemorragia Uterina/prevenção & controle , Ruptura Uterina/prevenção & controle
14.
Ann Oncol ; 27(9): 1706-12, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27217541

RESUMO

BACKGROUND: Despite aggressive multimodal therapy, locally advanced and/or metastatic penile squamous cell carcinoma (SqCC) is associated with significant morbidity and mortality, indicating a need for new therapeutic options. Given the emerging clinical utility of immunotherapeutics, we sought to assess the incidence and potential clinical significance of PD-L1 expression in penile SqCC. PATIENTS AND METHODS: Using an anti-PD-L1 primary antibody (clone 5H1), immunohistochemistry was carried out on whole tumor sections from 37 patients with penile SqCC treated at our institution between 2005 and 2013. PD-L1-positive tumors were defined as those with membranous staining in ≥5% of tumor cells. Association between PD-L1 expression and clinicopathologic parameters was examined using Fisher's exact test. Correlation between PD-L1 expression in primary tumors and matched metastases was assessed using the Spearman rank correlation coefficient (ρ). The difference in cancer-specific mortality between PD-L1-positive and -negative groups was examined using the log-rank test. RESULTS: Twenty-three (62.2%) of 37 primary tumors were positive for PD-L1 expression, and there was strong positive correlation of PD-L1 expression in primary and metastatic samples (ρ = 0.72; 0.032 < P < 0.036). Primary tumor PD-L1 expression was significantly associated with usual type histology (P = 0.040) and regional lymph node metastasis (P = 0.024), as well as decreased cancer-specific survival (P = 0.011). CONCLUSIONS: The majority of primary penile SqCC tumors express PD-L1, which is associated with high-risk clinicopathologic features and poor clinical outcome. These data provide a rational basis for further investigation of anti-PD-1 and anti-PD-L1 immunotherapeutics in patients with advanced penile SqCC.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Penianas/genética , Idoso , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunoterapia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Penianas/imunologia , Neoplasias Penianas/patologia , Neoplasias Penianas/terapia , Fatores de Risco
15.
Prostate Cancer Prostatic Dis ; 19(3): 292-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27215611

RESUMO

BACKGROUND: There has been a recent proposal to change the grading system of prostate cancer into a five-tier grade grouping system. The prognostic impact of this has been demonstrated in regards only to biochemical recurrence-free survival (bRFS) with short follow-up (3 years). METHODS: Between 1990 and 2013, 847 consecutive men were treated with definitive external beam radiation therapy at a single academic center. To validate the new grade grouping system, bRFS, distant metastases-free survival (DMFS) and prostate cancer-specific survival (PCSS) were calculated. Adjusted Kaplan-Meier and multivariable Cox regression analyses were performed to assess the independent impact of the new grade grouping system. Discriminatory analyses were performed to compare the commonly used three-tier Gleason score system (6, 7 and 8-10) to the new system. RESULTS: The median follow-up of our cohort was 88 months. The 5-grade groups independently validated differing risks of bRFS (group 1 as reference; adjusted hazard ratio (aHR) 1.35, 2.16, 1.79 and 3.84 for groups 2-5, respectively). Furthermore, a clear stratification was demonstrated for DMFS (aHR 2.03, 3.18, 3.62 and 13.77 for groups 2-5, respectively) and PCSS (aHR 3.00, 5.32, 6.02 and 39.02 for groups 2-5, respectively). The 5-grade group system had improved prognostic discrimination for all end points compared with the commonly used three-tiered system (that is, Gleason score 6, 7 and 8-10). CONCLUSIONS: In a large independent radiotherapy cohort with long-term follow-up, we have validated the bRFS benefit of the proposed five-tier grade grouping system. Furthermore, we have demonstrated that the system is highly prognostic for DMFS and PCSS. Grade group 5 had markedly worse outcomes for all end points, and future work is necessary to improve outcomes in these patients.


Assuntos
Gradação de Tumores/métodos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/normas , Prognóstico , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Resultado do Tratamento
16.
Radiat Prot Dosimetry ; 171(2): 217-222, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27032782

RESUMO

In the present investigation, radon concentration and heavy metal analysis were carried out in drinking water samples in Jammu district, Jammu & Kashmir, India. The radon concentration was measured by using RAD-7, portable alpha particle detector. The values of radon concentration in drinking water samples were also compared within the safe limit recommended by different health agencies. The total annual effective dose ranged from 53.04 to 197.29 µSv y-1 The annual effective dose from few locations from the studied area was found to be greater than the safe limit (100 µSv y-1) suggested by World Health Organisation (WHO) and EU Council. Heavy metal concentration was determined by atomic absorption spectrophotometer. A total of eight elements were analysed, viz. arsenic, mercury, zinc, iron, copper, chromium, manganese and cadmium. Heavy metals are considered to be the major pollutants of water sources. The results were compared with the limits of WHO, EU and Indian organisations. The trace metal analysis is not on the exceeding side of the permissible limit in all the samples.


Assuntos
Água Potável/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Doses de Radiação , Radônio/análise , Poluentes Químicos da Água/análise , Geografia , Água Subterrânea/análise , Índia , Temperatura , Oligoelementos/análise , Poluentes Químicos da Água/normas , Abastecimento de Água
17.
Radiat Prot Dosimetry ; 171(2): 208-211, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27036531

RESUMO

Radon is the most important source of natural radiation and is responsible for approximately half of the received dose from all sources. Most of this dose is from inhalation of the radon progeny, especially in closed atmospheres. Concentration of radon (222Rn) and thoron (220Rn) in the different villages of Jalandhar and Kapurthala district of Punjab has been calculated by pinhole cup dosemeters and RAD7. On an average, it has been observed from the study that the values of all the parameters calculated are higher in case of active monitoring than the passive monitoring. The calculated equilibrium equivalent 222Rn concentration (EECRn) and equilibrium equivalent 220Rn concentration (EECTh) fluctuate in the range from 5.58 to 34.29 and from 0.35 to 2.7 Bq m-3 as estimated by active technique, respectively. Similarly, the observed mean value of the potential alpha energy concentration of 222Rn (PAECRn) and 220Rn (PAECTh) is 4.55 and 4.34 mWL, respectively. The dose rate to the soft tissues and lung from indoor 222Rn varies from 0.06 to 0.38 and from 0.50 to 3.05 nGy h-1, respectively. The total annual effective dose for the residents of the study area is less than 10 mSv.


Assuntos
Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento de Radiação/métodos , Radiometria/métodos , Produtos de Decaimento de Radônio/análise , Radônio/análise , Partículas alfa , Atmosfera , Habitação , Índia
18.
Indian J Surg ; 77(Suppl 1): 190-2, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25972693

RESUMO

Amoebiasis is an infection with the parasitic intestinal protozoan Entamoeba histolytica (E. histolytica). Most infections are usually asymptomatic, but the disease spectrum can range from dysentery to extraintestinal infections, including liver abscesses. The management of a 68-year-old male with amoeboma, a rare manifestation of intestinal amoebiasis, is described along with a review of literature.

19.
Anaesthesia ; 69(7): 669-77, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24917333

RESUMO

Guidelines outlining recommended actions are difficult to implement in the stressful, time-pressured situation of an airway emergency. Cognitive aids such as posters and algorithms improve performance during some anaesthetic emergencies; however, their effects on team behaviours have not been determined. In this study, 64 participants were randomly assigned into control (no cognitive aid) and intervention (cognitive aid provided) groups before a simulated 'can't intubate, can't oxygenate' scenario. Video analysis was undertaken of the non-technical skills and technical performance during the scenarios. All categories had higher Anaesthetists' Non-Technical Skills (ANTS) scores when a cognitive aid was supplied (mean (SD) total ANTS score 10.4 (3.1) vs. 13.2 (2.4), p < 0.001). The number of times the cognitive aid was used was associated with higher ANTS scores (ρ = 0.383, p = 0.002). A trend towards the establishment of an infraglottic airway within 3 min was also noted (control group 55.3% vs. intervention 76.9%, p = 0.076). Non-technical skills are improved when a cognitive aid is present during airway emergencies.


Assuntos
Manuseio das Vias Aéreas/métodos , Obstrução das Vias Respiratórias/terapia , Competência Clínica/estatística & dados numéricos , Serviços Médicos de Emergência/métodos , Capacitação em Serviço/métodos , Pôsteres como Assunto , Análise de Variância , Humanos , Intubação Intratraqueal , Manequins , Estudos Prospectivos
20.
Ann Oncol ; 25(7): 1410-1416, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24799460

RESUMO

BACKGROUND: The purpose of this article was to study the association of human papillomavirus (HPV) with clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Archival baseline tumor specimens were obtained from patients treated on two clinical trials in recurrent or metastatic SCCHN: E1395, a phase III trial of cisplatin and paclitaxel versus cisplatin and 5-fluorouracil, and E3301, a phase II trial of irinotecan and docetaxel. HPV DNA was detected by in situ hybridization (ISH) with a wide-spectrum probe. p16 status was evaluated by immunohistochemistry. Clinical outcomes of interest were objective response, progression-free survival (PFS) and overall survival (OS). RESULTS: We analyzed 64 patients for HPV ISH and 65 for p16. Eleven tumors (17%) were HPV+, 12 (18%) were p16+, whereas 52 (80%) were both HPV- and p16-. The objective response rate was 55% for HPV-positive versus 19% for HPV-negative (P = 0.022), and 50% for p16-positive versus 19% for p16-negative (P = 0.057). The median survival was 12.9 versus 6.7 months for HPV-positive versus HPV-negative patients (P = 0.014), and 11.9 versus 6.7 months for p16-positive versus p16-negative patients (P = 0.027). After adjusting for other covariates, hazard ratio for OS was 2.69 (P = 0.048) and 2.17 (P = 0.10), favoring HPV-positive and p16-positive patients, respectively. The other unfavorable risk factor for OS was loss of ≥5% weight in previous 6 months (P = 0.0021 and 0.023 for HPV and p16 models, respectively). CONCLUSION: HPV is a favorable prognostic factor in recurrent or metastatic SCCHN that should be considered in the design of clinical trials in this setting. CLINICAL TRIAL IDENTIFIER: NCT01487733 Clinicaltrials.gov.


Assuntos
Alphapapillomavirus/isolamento & purificação , Neoplasias de Cabeça e Pescoço/virologia , Metástase Neoplásica , Adulto , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus/patogenicidade , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva
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