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1.
Cancer Med ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786866

RESUMO

BACKGROUND: There is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India. MATERIALS AND METHODS: This was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients. RESULTS: A total of 200 COVID-19 infection episodes were analysed of which 109 (54.5%) were patients with cancer and 91 (45.5%) were patients without cancer. The median age was 43 (interquartile range [IQR]:32-57), 51 (IQR: 33-62) and 38 (IQR: 31.5-49.3) years; of whole cohort, cancer and non-cancer patients, respectively. Comparison of outcomes showed that oxygen requirement (31.2% [95% CI: 22.6-40.7] vs. 17.6% [95% CI: 10.4-26.9]; p = 0.03), median time to discharge (11 days [IQR: 6.75-16] vs. 6 days [IQR: 3-9.75]; p < 0.001) and mortality (10.0% [95% CI: 5.2-17.3] vs. 1.1% [95% CI: 0.03-5.9]; p = 0.017) were significantly higher in patients with cancer. In univariable analysis, factors associated with higher mortality in the whole cohort included diagnosis of cancer (10.1% vs. 1.1%; p = 0.027; odds ratio [OR]: 7.04), age ≥60 (17.4% vs. 2.6%; p = 0.001; OR: 7.38), oxygen requirement (22% vs. 0.6%; p < 0.001; OR: 29.01), chest infiltrates (19.2% vs. 1.4%; p < 0.001; OR: 22.65), baseline absolute lymphocyte count <1 × 109 /L (10.8% vs. 1.9%; p = 0.023; OR:5.1), C-reactive protein >1 mg% (12.8% vs. 0%; p = 0.027; OR: 24.69), serum procalcitonin >0.05 ng/ml (22.65% vs. 0%; p = 0.004; OR: 4.49) and interleukin-6 >6 pg/ml (10.8% vs. 1.3%; p = 0.036; OR: 3.08). In multivariable logistic regression, factors significantly associated with mortality were oxygen requirement (p = 0.005; OR: 13.11) and high baseline procalcitonin level (p = 0.014; OR: 37.6). CONCLUSION: Cancer patients with COVID-19 have higher mortality and require longer hospital stay. High procalcitonin levels and oxygen requirement during admission are other factors that affect outcomes adversely.

2.
Int J Cancer ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751432

RESUMO

The real-world data on short-course of ICI use is sparse and merits exploration. A multi-centric observational study on the safety and efficacy of ICI in oncology patients between August 2014 to October 2020 involving 1011 patients across 13 centers in India. The median age was 59 (min 16- max 98) years with male preponderance (77.9%). The predominant cohort received short-course ICI therapy; the median number of cycles were 5 (95% CI 1 - 27) and median duration of therapy was 3 (95% CI 0.5 - 13) months. ICI were used commonly in second and third line setting in our study (66.4%, n=671). Objective response rate (ORR) (complete or partial response) was documented in 254 (25.1%) of the patients, 202 (20.0%) had stable disease and 374 (37.0%) had progressive disease. The clinical benefit rate was present in 456 (45.1%). Among the patients whom ICI was stopped (n=906), the most common reason for cessation of ICI was disease progression (616, 68.0%) followed by logistic reasons like financial constraints (234, 25.82%). With a median follow up of 14.1 (95%CI 12.9-15.3) months, there were 616 events of progression and 443 events of death and the median progression free survival and overall survival were 6.4 (95%CI 5.5-7.3) and 13.6 (95%CI 11.6-15.7) months respectively in the overall cohort. Among the immune related adverse events (irAEs), autoimmune pneumonitis (29, 3.8%) and thyroiditis (24, 2.4%) were common. Real-world multicentric Indian data predominantly with short-course ICI therapy, has comparable efficacy/safety to international literature with standard ICI therapy. This article is protected by copyright. All rights reserved.

4.
Shock ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34738957

RESUMO

BACKGROUND: Recent studies have demonstrated that alterations in mitochondrial dynamics can impact innate immune function. However, the upstream mechanisms which link mitochondrial dynamics to innate immune phenotypes have not been completely elucidated. This study asks if δPKC-mediated phosphorylation of Drp1, a key driver of mitochondrial fission, impacts macrophage pro-inflammatory response following bacterial-derived lipopolysaccharide (LPS) stimulation. METHODS: Using RAW 264.7 cells, bone marrow-derived macrophages from C57BL/6J mice, as well as human monocyte-derived macrophages, we first characterized changes in δPKC-mediated phosphorylation of Drp1 following LPS stimulation. Next, using rationally-designed peptides that inhibit δPKC activation (δV1-1) and δPKC-Drp1 interaction (ψDrp1), we determined whether δPKC-mediated phosphorylation of Drp1 impacts LPS-induced changes in mitochondrial morphology, mitochondrial function, and inflammatory response. RESULTS: Our results demonstrated that δPKC-dependent Drp1 activation is associated with increased mitochondrial fission, impaired cellular respiration, and increased mitochondrial reactive oxygen species in LPS-treated macrophages. This is reversed using a rationally-designed peptide which selectively inhibits δPKC phosphorylation of Drp1 (ψDrp1). Interestingly, limiting excessive mitochondrial fission using ψDrp1 reduced LPS-triggered pro-inflammatory response, including a decrease in NF-κB nuclear localization, decreased iNOS induction, and a reduction in pro-inflammatory cytokines (IL-1ß, TNFα, IL-6). CONCLUSION: These data suggest that inhibiting Drp1 phosphorylation by δPKC abates the excessive mitochondrial fragmentation and mitochondrial dysfunction that is seen following LPS treatment. Furthermore, these data suggest that limiting δPKC-dependent Drp1 activation decreases the pro-inflammatory response following LPS treatment. Altogether, δPKC-dependent Drp1 phosphorylation might be an upstream mechanistic link between alterations in mitochondrial dynamics and innate immune phenotypes, and may have therapeutic potential.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34620626

RESUMO

BACKGROUND: Gallstone disease has been associated with colorectal cancer and some form of polyps, although the findings are inconclusive. It remains unknown whether gallstone disease influences the initiation of colorectal cancer. METHODS: We prospectively assessed the association of gallstone disease with risk of colorectal cancer precursors, including conventional adenomas and serrated polyps, in the Nurses' Health Study (1992-2012), the Nurses' Health Study II (1991-2011), and the Health Professionals Follow-up Study (1992-2012). Gallstone diseases were assessed using biennial follow-up questionnaires. Self-reported polyp diagnosis was confirmed by review of medical records. Logistic regression models were used to calculate the ORs with adjustment for smoking and other potential confounders. RESULTS: Among participants who had undergone a total of 323,832 endoscopies, 16.5% had gallstone disease and 11.3% received cholecystectomy. We documented 1,724, 1,212, and 1,943 cases of conventional adenomas and 1,470, 1,090, and 1,643 serrated polyps in patients with gallstones, cholecystectomy, and either of them, respectively. The OR for adenomas was 1.00 [95% confidence interval (CI): 0.95-1.06] for gallstones, 0.99 (95% CI: 0.93-1.06) for cholecystectomy, and 1.00 (95% CI: 0.95-1.05) for either exposure. The corresponding ORs for serrated polyps were 0.98 (95% CI: 0.92-1.04), 0.99 (95% CI: 0.93-1.06), and 0.97(95% CI: 0.92-1.03), respectively. CONCLUSIONS: Gallstone disease is not associated with colorectal polyps. IMPACT: Patients with gallstones appear to have similar risk of colorectal polyps compared with those without and may therefore follow average-risk colorectal cancer screening guidelines.

6.
Ecancermedicalscience ; 15: 1274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567259

RESUMO

Background: A significant proportion of non-small cell lung cancer (NSCLC) patients present with poor performance status (PS) at baseline are almost always excluded from the clinical trials leading to availability of only limited data in this subgroup. Patients and methods: This was an observational single institutional study. The eligibility criteria for inclusion were a histologic or cytologic diagnosis of advanced NSCLC and Eastern Cooperative Oncology Group PS 3 or 4. All patients coming between June 2015 and December 2018 were evaluated for inclusion in this study. Results: A total of 245 patients were enrolled in the study. The median age of the patients was 63 years (range 25-89), 142 (58%) were male, 196 (80%) had adenocarcinoma histology and 192 (78.4%) has PS 3 while rest (21.6%) had PS 4. Out of 245 patients, 192 (78.4%) received oral tyrosine kinase inhibitors (TKI) and supportive care, 45 (18.4%) received supportive care alone, while 8 (3.2%) patients received chemotherapy along with supportive care. Median overall survival (OS) was 3 months (95% CI: 1.8-4.2) in patients who received oral TKI versus 1 month (1.0-2.9) in patients who received supportive care alone (log-rank p = 0.013). The median OS for epidermal growth factor receptor (EGFR) mutant patients who received oral TKI was 12 months (95% CI: 7.7-16.3), while it was 3 months (95% CI: 1.5-4.5) for patients who were EGFR wild-type and received TKI on compassionate basis (HR = 0.50; 95% CI: 0.32-0.77; p = 0.001). Conclusions: The use of oral TKI on a compassionate basis led to improvement in survival in the overall cohort of the patients; this was principally driven by EGFR-mutated patients.

7.
Front Oncol ; 11: 710585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568037

RESUMO

Background: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs). Patients and Methods: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST). Results: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort. Conclusions: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

8.
South Asian J Cancer ; 10(2): 92-96, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34568222

RESUMO

Introduction TFE Translocation renal cell carcinoma (TRCC) represents 1 to 5% of all cases of renal cell carcinoma, with the highest frequency among children and young adults. Management of these tumors is not very well defined in literature. Although in pediatric age group it has favorable prognosis, in adults it has an aggressive nature, with poor outcome. This is a retrospective analysis of treatment outcome in adult patient 18 years or above treated at our hospital between January 2013 and November 2018. Material and Methods Clinical and pathological data of 26 patients from a single institution diagnosed with TRCC between January 2013 and November 2018 were retrospectively reviewed. All cases of TRCC were confirmed with immunohistochemistry or fluorescence in situ hybridization. We analyzed our data of patients treated with surgery only or who progressed after surgery and treated with systemic therapy or who presented with upfront unresectable or metastatic disease treated with systemic therapy with respect to event-free survival (EFS) and overall survival (OS). Results Between January 2013 and November 2018, 26 adult patients who were treated at our center were eligible for this analysis as per our criteria. Out of 26 patients, 25 patients had radical surgery after evaluation and 1 had metastatic disease who was started on systemic therapy. Out 25 patients who were treated with radical surgery, 16 patients progressed and they were started on systemic therapy except for 1 patient who defaulted. Median time to start systemic therapy among patient treated with curative nephrectomy was 13 months. Median EFS and median OS among overall population were 22 and 30 months, respectively. Among 16 patients who were treated with systemic therapy, median EFS to first-line therapy was 8 months and to second-line therapy was 2.5 months. Median OS was 17 months in patients treated with systemic therapy. Conclusion TRCC is rare in adult population but carries significant risk of disease progression even after initial curative treatment with potential response to targeted therapy for short duration.

9.
Gut ; 70(11): 2096-2104, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34489306

RESUMO

OBJECTIVE: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation. DESIGN: We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively. RESULTS: Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation. CONCLUSIONS: A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.


Assuntos
COVID-19/etiologia , Dieta/efeitos adversos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Inquéritos sobre Dietas , Dieta Saudável , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
10.
Histopathology ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586682

RESUMO

AIMS: The recent changes in the American Joint Commission on Cancer-8th edition (AJCC-8E) pT2 and pT3 tumor definitions for penile cancer need robust validation studies. A recent study redefined and modified the pT2 and pT3 stages incorporating the histopathological variables (tumor grade, lymphovascular invasion, perineural invasion) similar to that used in the current AJCC-8E pT1 stage tumor subclassification. In this study, we validate and compare this proposed staging with the AJCC staging systems, on an external dataset. METHODS AND RESULTS: The dataset from a previously published study was obtained. pT2 and pT3 stages were reconstructed as per AJCC 7th edition (AJCC-7E), AJCC-8E, and the proposed staging. The staging systems were correlated with nodal metastasis, disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS). All systems were compared using receiver operating characteristics (ROC) curves. A total of 281 cases formed the study cohort. AJCC-8E (p=0.031) and the proposed staging (p=0.003) correlated with nodal metastasis on adjusted analysis, the latter with a better strength of association (AJCC-8E, γ= -.471, proposed, γ= -.625). On adjusted analysis, all the staging systems had a significant correlation with DFS, while only AJCC-8E and the proposed staging correlated with CSS and OS. On ROC curve analysis, the proposed staging had the highest area under the curve and was the only staging system to statistically correlate with all the outcome variables. CONCLUSIONS: The proposed staging for pT2/pT3 tumor stages in penile cancer may improve the prognostic and predictive ability.

11.
Cardiovasc Res ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469519

RESUMO

AIMS: Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. METHODS AND RESULTS: We used a proteomic platform to measure 71 cardiovascular biomarkers among 5,032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rate (FDR Q-value) <0.05.Growth differentiation factor-15 (GDF15; also known as macrophage inhibitory cytokine-1 [MIC1])) was associated with increased risk of incident cancer (hazards ratio [HR] per 1 standard deviation increment 1.31, 95% CI 1.17-1.47), incident gastrointestinal cancer (HR 1.85, 95% CI 1.37-2.50), incident colorectal cancer (HR 1.94, 95% CI 1.29-2.91) and cancer-related death (HR 2.15, 95% CI 1.72-2.70). Stromal cell-derived factor-1 (SFD1) showed an inverse association with cancer-related death (HR 0.75, 95% CI 0.65-0.86). Fibroblast growth factor-23 (FGF23) showed an association with colorectal cancer (HR 1.55, 95% CI 1.20-2.00), and granulin (GRN) was associated with hematologic cancer (HR 1.61, 95% CI 1.30-1.99). Other circulating biomarkers of inflammation, immune activation, metabolism, and fibrosis showed suggestive associations with future cancer diagnosis. CONCLUSION: We observed several significant associations between circulating CVD biomarkers and cancer, supporting the idea that shared biological pathways underlie both diseases. Further investigations of specific mechanisms that lead to both CVD and cancer are warranted. TRANSLATIONAL PERSPECTIVE: In our prospective cohort study, baseline levels of biomarkers previously associated with CVD were found to be associated with future development of cancer. In particular, GDF15 was associated with increased risk of cancer incidence and mortality, including gastrointestinal and colorectal cancers; SDF1 was inversely associated with cancer-related death, and FGF23 and GRN were associated with increased risk of colorectal and hematologic cancers, respectively. Other biomarkers of inflammation, immune activation, metabolism, and fibrosis showed suggestive associations. These results suggest potential shared biological pathways that underlie both development of cancer and CVD.

12.
Immunol Cell Biol ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582592

RESUMO

Recent studies have highlighted multiple immune perturbations related to severe acute respiratory syndrome coronavirus 2 infection-associated respiratory disease [coronavirus disease 2019 (COVID-19)]. Some of them were associated with immunopathogenesis of severe COVID-19. However, reports on immunological indicators of severe COVID-19 in the early phase of infection in patients with comorbidities such as cancer are scarce. We prospectively studied about 200 immune response parameters, including a comprehensive immune-cell profile, inflammatory cytokines and other parameters, in 95 patients with COVID-19 (37 cancer patients without active disease and intensive chemo/immunotherapy, 58 patients without cancer) and 21 healthy donors. Of 95 patients, 41 had severe disease, and the remaining 54 were categorized as having a nonsevere disease. We evaluated the association of immune response parameters with severe COVID-19. By principal component analysis, three immune signatures defining characteristic immune responses in COVID-19 patients were found. Immune cell perturbations, in particular, decreased levels of circulating dendritic cells (DCs) along with reduced levels of CD4 T-cell subsets such as regulatory T cells (Tregs ), type 1 T helper (Th1) and Th9; additionally, relative expansion of effector natural killer (NK) cells were significantly associated with severe COVID-19. Compared with patients without cancer, the levels of terminal effector CD4 T cells, Tregs , Th9, effector NK cells, B cells, intermediate-type monocytes and myeloid DCs were significantly lower in cancer patients with mild and severe COVID-19. We concluded that severely depleted circulating myeloid DCs and helper T subsets in the initial phase of infection were strongly associated with severe COVID-19 independent of age, type of comorbidity and other parameters. Thus, our study describes the early immune response associated with severe COVID-19 in cancer patients without intensive chemo/immunotherapy.

13.
Indian J Urol ; 37(3): 226-233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465951

RESUMO

Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for muscle invasive bladder cancer (MIBC). The role of neoadjuvant and adjuvant therapy has evolved over the last 3-4 decades, and neoadjuvant chemotherapy (NACT) has now become the standard recommended treatment. However, there are many nuances to this and the utilization of chemotherapy has not been universal. The optimum chemotherapy regimen is still debated. Adjuvant radiation has a role in high-risk patients although not established and immunotherapy has shown promising results. We reviewed the evidence on NACT and adjuvant chemotherapy (ACT) regimens, NACT versus ACT, and the role of adjuvant radiotherapy and immunotherapy in MIBC.

14.
Prostate ; 81(15): 1225-1234, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34469602

RESUMO

OBJECTIVE: The aim of present study was to determine and compare the overall response rates, progression-free survival (PFS), overall survival (OS), and clinical toxicity of the combination of 177Lu-PSMA-617 radioligand therapy (PRLT) and abiraterone acetate (AA) versus 177Lu-PSMA-617 PRLT as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) patients. MATERIALS AND METHODS: The mCRPC patients who received at least one cycle of 177 Lu-PSMA-617 PRLT with or without AA therapy, were included and analyzed in the present study. The patients were divided into two major groups. Group 1 received only 177 Lu-PSMA PRLT and Group 2 received combined 177 Lu-PSMA PRLT + AA therapy. Therapeutic dose of 177 Lu-PSMA-617 PRLT was 4.4-5.55 GBq per patient per cycle administered at intervals of 10-12 weeks in both groups. The Group 2 patients additionally received a dose of 1000 mg of AA once daily and 5 mg of prednisone twice daily. Treatment response in two groups was evaluated under four broad categories (a) symptomatic, (b) biochemical (serum prostate-specific antigen level), (c) objective molecular imaging (68 Ga-PSMA-11 and 18 F-FDG PET/CT), and (d) objective anatomical imaging (computed tomography). For assessing treatment response, patients in two groups were categorized into responders (complete response [CR], partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]). The Kaplan-Meier product-limit method was used to calculate PFS and OS following first 177 Lu-PSMA PRLT in the two groups. Univariate analysis was used to compare the patients' characteristics in two groups using a χ2 or Fisher exact test. The Kaplan-Meier curves of PFS and OS between two groups were compared by using the log-rank test (p < 0.05 significant). RESULTS: A total of 58 mCRPC patients (Group 1, 38 patients and Group 2, 20 patients) were included in this study analysis. The clinical and demographic characteristics of these patients (age, Gleason score, FDG avid disease, metastatic disease burden, and average number of 177 Lu-PSMA PRLT cycles) in two groups were compared and found to be similar (p > 0.05). Post-treatment, symptomatic, biochemical, molecular, and anatomic imaging responders were found in 22 patients (58%) and 17 patients (85%), 22 patients (58%) and 16 patients (80%), 19 patients (54%) and 14 patients (78%), and 19 patients (54%) and 14 patients (78%) in Group 1 and Group 2, respectively. The median PFS of 7 months and median OS of 8 months were documented in Group 1, whereas median PFS was not reached and median OS of 16 months registered in Group 2. Transient hematological toxicity of Grades 1 and 2 was found in total seven patients (five patients in Group 1 and two patients in Group 2). On comparison of the treatment outcome between two groups, significant p value was found for symptomatic responders (58% in Group 1 vs. 85% in Group 2), median PFS (7 months in Group 1 vs. not reached in Group 2), and median OS (8 months in Group 1 vs. 16 months in Group 2), with better outcome in Group 2 patients for these variables. CONCLUSION: In the present study, the combination of 177 Lu-PSMA-617 PRLT and AA therapy showed significant improvement in mCRPC patients' symptomatic response, PFS, and OS as compared to 177 Lu-PSMA-617 PRLT monotherapy.

15.
Oral Oncol ; 122: 105517, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34560383

RESUMO

INTRODUCTION: The addition of Nimotuzumab to radical chemoradiation (CRT) improved outcomes in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing radical CRT in a phase 3 randomized trial. The current study focuses on the quality of life (QoL) of patients in this trial. METHODS: In this phase III randomized trial, patients with newly diagnosed, nonmetastatic, stage III/IV LAHNSCC of the oral cavity, oropharynx, hypopharynx, or larynx were randomized to receive cisplatin 30 mg/m2 or cisplatin 30 mg/m2 with nimotuzumab once a week with curative radiotherapy. The primary end point of the trial was PFS. The aim of the current study was to compare the QoL between the two arms. QoL was assessed using the EORTC QLQ-C30 (v3.0) and HN-35 (v1.0). The linear mixed-effects model was used for longitudinal analysis of QoL. RESULTS: 536 patients were randomized in this trial (268 in each arm) and 423 patients were included for QoL analysis. There was a significant change in the global health status QoL scores over time (p = 0.0016) with no difference between the two arms (p = 0.396). On longitudinal analysis there was a significant difference in the QoL scores in most of the function & symptom scales over time, but there was no significant difference in these scores between the two arms. QoL scores for most symptom scales worsened during treatment and improved thereafter in both arms. CONCLUSION: The addition of nimotuzumab to cisplatin based chemoradiation in LAHNSCC improved PFS, LRC and DFS without negatively impacting QoL.

16.
Oral Oncol ; 122: 105522, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34571463

RESUMO

BACKGROUND: Weight loss during chemotherapy and its impact on the cancer outcomes have been invariably reported in the literature. We also did a post-hoc analysis of a randomized phase III trial to see the same. MATERIALS AND METHODS: The database of a recently published randomized study comparing cisplatin-radiation with nimotuzumab cisplatin-radiation was used for this analysis. Week-wise weight loss during the course of treatment was noted. The impact of severe weight loss (grade 2-3) on progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) was studied using the Kaplan Meier method. Binary logistic regression analysis was used to see the effect of various factors. RESULTS: Out of a total of 536 patients, weight loss was captured in 524. Out of these 524 patients, any degree of weight loss was seen in 293 (55.91%) patients. Grade 1 weight loss was noted in 192 (36.6%) patients, grade 2 in 96 (18.3%) and grade 3 in 5 (1%) patients. The 2-year PFS was 53% and 57.1% in severe and non-severe weight loss groups respectively (p-value = 0.36). The 2-year LRC was 60% in patients with severe weight loss, while it was 63.5% in those with non-severe weight loss (p-value = 0.47). The 2-year OS was 59.3% versus 62.2% in severe and non-severe weight loss cohorts respectively (p-value = 0.21). None of the factors was found to be associated with severe weight loss. CONCLUSION: Severe weight loss was uncommon in our patients. Weight loss during treatment was not associated with poor survival outcomes.

17.
Dig Dis Sci ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403030

RESUMO

BACKGROUND: Higher body mass index (BMI) is associated with increased risk of colorectal cancer. How genetically predicted BMI may be associated with colorectal cancer precursors is unknown. AIMS: Our objective was to quantify the association of genetically predicted and measured BMI with risk of colorectal cancer precursors. METHODS: We evaluated the association of genetically predicted and measured BMI with risk of conventional adenomas, serrated polyps, and synchronous polyps among 27,426 participants who had undergone at least one lower gastrointestinal endoscopy in the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study. Genetic risk score was derived from 97 BMI-related single nucleotide polymorphisms. Multivariable logistic regression evaluated each polyp subtype compared to non-polyps. RESULTS: For conventional adenomas, the OR per 2-kg/m2 increase was 1.03 (95% CI, 1.01-1.04) for measured BMI and 0.98 (95% CI, 0.88-1.10) for genetically predicted BMI; for serrated polyps, the OR was 1.06 (95% CI, 1.04-1.08) and 1.04 (95% CI, 0.90-1.20), respectively; for synchronous polyps, the OR was 1.10 (95% CI, 1.07-1.13) and 1.09 (95% CI, 0.89-1.34), respectively. Genetically predicted BMI was associated with synchronous polyps in women (OR = 1.37, 95% CI: 1.05-1.79). CONCLUSION: Genetically predicted BMI was not associated with colorectal cancer precursor lesions. The confidence intervals were wide and encompassed those for measured BMI, indicating that null findings may be due to insufficient power.

18.
J Genet Eng Biotechnol ; 19(1): 121, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34406518

RESUMO

BACKGROUND: Canine circovirus is a deadly pathogen of dogs and causes vasculitis and hemorrhagic enteritis. It causes lethal gastroenteritis in pigs, fox, and dogs. Canine circovirus genome contains two main (and opposite) transcription units which encode two open reading frames (ORFs), a replicase-associated protein (Rep) and the capsid (Cap) protein. The replicase protein and capsid protein consist of 303 amino acids and 270 amino acids respectively. Several immuno-informatics methods such as epitope screening, molecular docking, and molecular-dynamics simulations were used to craft peptide-based vaccine construct against canine circovirus. RESULTS: The vaccine construct was designed by joining the selected epitopes with adjuvants by suitable linker. The cloning and expression of the vaccine construct was also performed using in silico methods. Screening of epitopes was conducted by NetMHC server that uses ANN (Artificial neural networking) algorithm. These methods are fast and cost-effective for screening epitopes that can interact with dog leukocyte antigens (DLA) and initiate an immune response. Overall, 5 epitopes, YQHLPPFRF, YIRAKWINW, ALYRRLTLI, HLQGFVNLK, and GTMNFVARR, were selected and used to design a vaccine construct. The molecular docking and molecular dynamics simulation studies show that these epitopes can bind with DLA molecules with stability. The codon adaptation and in silico cloning studies show that the vaccine can be expressed by Escherichia coli K12 strain. CONCLUSION: The results suggest that the vaccine construct can be useful in preventing the dogs from canine circovirus infections. However, the results need further validation by performing other in vitro and in vivo experiments.

19.
Indian J Nucl Med ; 36(2): 229-230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34385806

RESUMO

Testicular metastases from solid tumors is a rare entity. We describe one such case where a patient on treatment for prostate cancer presented with a right scrotal swelling. For restaging, whole-body 68-gallium prostate-specific membrane antigen positron emission tomography/computed tomography (PET/CT) was performed. Fused PET/CT images demonstrated intense uptake in the testicular lesion. Unique anatomic and functional information provided by hybrid PET/CT helped in reliably establishing the testicular mass as the site of metastases from prostate cancer, which had a major impact on patient management.

20.
J Surg Educ ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34384730

RESUMO

BACKGROUND: The Surgical Council on Resident Education's (SCORE) structured educational curriculum for general surgery residents uses a 2-year repeating cycle of modules and quizzes called "This Week in SCORE" (TWIS) to organize and sequence the curricular content on the SCORE portal. The purpose of this study was to evaluate the impact of using the SCORE content and TWIS curriculum on American Board of Surgery In-Training Examination (ABSITE) performance. To date, no multi-institutional studies have examined this effect. METHODS: Eight residency programs participated, including university and community-based programs. SCORE usage overall, TWIS usage, and ABSITE percentile scores (adjusted for post-graduate year [PGY]) were analyzed for the academic years 2017 to 2020. SCORE usage was defined as number of SCORE logins annually per resident with "low usage" ≤10 times and "high usage" >10 times. TWIS usage was defined as "low usage" (no TWIS quizzes done) or "high usage" (≥1 TWIS quiz per year). RESULTS: Four hundred and twenty-eight trainees were evaluated. Trainees with high SCORE and TWIS usage consistently achieved a higher ABSITE percentile score. This difference was maintained in subgroup analysis by PGY with the greatest impact in PGY-1 and PGY-2 levels. CONCLUSIONS: Utilization of multiple aspects of SCORE content appears to have a significant positive impact on ABSITE performance across all levels of postgraduate training. This multi-institutional study of a large number of users is the first to demonstrate that increased usage of SCORE content appears to be a predictor of ABSITE performance success.

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