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1,567 result(s) for "Ahmed, Shahid"
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Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management
Background: Obesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity. Methods: A literature search using PubMed and Google Scholar was performed and the keywords ‘obesity’ and cancer’ were used. The search was limited to research papers published in English prior to September 2022 and focused on studies that investigated epidemiology, the pathogenesis of cancer, cancer incidence and the risk of recurrence, and the management of obesity. Results: About 4–8% of all cancers are attributed to obesity. Obesity is a risk factor for several major cancers, including post-menopausal breast, colorectal, endometrial, kidney, esophageal, pancreatic, liver, and gallbladder cancer. Excess body fat results in an approximately 17% increased risk of cancer-specific mortality. The relationship between obesity and the risk associated with the development of cancer and its recurrence is not fully understood and involves altered fatty acid metabolism, extracellular matrix remodeling, the secretion of adipokines and anabolic and sex hormones, immune dysregulation, and chronic inflammation. Obesity may also increase treatment-related adverse effects and influence treatment decisions regarding specific types of cancer therapy. Structured exercise in combination with dietary support and behavior therapy are effective interventions. Treatment with glucagon-like peptide-1 analogues and bariatric surgery result in more rapid weight loss and can be considered in selected cancer survivors. Conclusions: Obesity increases cancer risk and mortality. Weight-reducing strategies in obesity-associated cancers are important interventions as a key component of cancer care. Future studies are warranted to further elucidate the complex relationship between obesity and cancer with the identification of targets for effective interventions.
Neural network-based adaptive global sliding mode MPPT controller design for stand-alone photovoltaic systems
The increasing energy demand and the target to reduce environmental pollution make it essential to use efficient and environment-friendly renewable energy systems. One of these systems is the Photovoltaic (PV) system which generates energy subject to variation in environmental conditions such as temperature and solar radiations. In the presence of these variations, it is necessary to extract the maximum power via the maximum power point tracking (MPPT) controller. This paper presents a nonlinear generalized global sliding mode controller (GGSMC) to harvest maximum power from a PV array using a DC-DC buck-boost converter. A feed-forward neural network (FFNN) is used to provide a reference voltage. A GGSMC is designed to track the FFNN generated reference subject to varying temperature and sunlight. The proposed control strategy, along with a modified sliding mode control, eliminates the reaching phase so that the sliding mode exists throughout the time. The system response observes no chattering and harmonic distortions. Finally, the simulation results using MATLAB/Simulink environment demonstrate the effectiveness, accuracy, and rapid tracking of the proposed control strategy. The results are compared with standard results of the nonlinear backstepping controller under abrupt changes in environmental conditions for further validation.
Diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome in patients with cancer: A multicentre study
•This retrospective cohort study evaluated 33 consecutive hospitalized adult patients with an active cancer and diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS).•Patients with active cancer and DKA/HSS were relatively older and most had an advanced cancer. In about one-third cancer patients, DKA or HHS was the presenting manifestation of new onset diabetes.•Overall, 30 % patients died. Administration of a systemic cancer treatment within 30 days of admission was associated with an odd ratio of hospital mortality of 3.0 (0.62–14.8).•It is important to recognize DKA and HHS early in symptomatic cancer patients undergoing treatment to promptly initiate appropriate care and avoid inferior outcomes. Diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. However, limited data about DKA and HHS are available in patients with cancer. The current study aimed to determine characteristics and outcomes of patients with cancer who were admitted with DKA/HHS in a mid-size Canadian city. Consecutive adult patients with an active cancer who were admitted with DKA or HHS from January 2008 to December 2020 in the city of Saskatoon, Saskatchewan, Canada were retrospectively evaluated. A univariate logistic regression analysis was performed to examine the correlation of various clinical variables with hospital mortality. During the study period 6,555 patients with diabetes and cancer were admitted in one of the three tertiary care hospitals. Among them 33 (0.5 %) eligible patients with DKA or HHS with a median age of 60 years (range 36–94 years) were identified. In 36 % of patients, DKA or HHS was the presenting manifestation of newly diagnosed diabetes. Of all patients, 66 % developed DKA and 73 % had an advanced cancer. Overall, 52 % patients received a systemic cancer therapy prior to the admission, and 41 % received steroids. Ten (42 %) of 24 patients with an advanced cancer died, compared to none of the nine patients with an early-stage cancer (p = 0.032). No clinical factors significantly correlated with hospital mortality. Although DKA or HHS is uncommon in patients with diabetes and cancer, it is the manifestation of undiagnosed diabetes in about one-third of patients with cancer. It has been associated with high hospital mortality in patients with advanced cancer. [Display omitted]
An increase in splenic volume after first-line immunotherapy is associated with worse PFS in patients with metastatic renal cell carcinoma
Abstract Importance Reliable prognostic markers for immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC) remain limited. Objective To examine the impact of splenic volume change after ICI initiation on progression-free survival (PFS) and overall survival (OS) in patients with mRCC. Design A retrospective cohort study reviewing data from 2015 to 2023. Setting The Emory Kidney Cancer database (single-center academic instution). Participants Patients with mRCC who underwent first-line ICI treatment and had available abdominal imaging 30 days before and 60-120 days after ICI initiation. A total of 109 patients met inclusion criteria. Exposure Splenic volume change calculated as a percentage difference between baseline and follow-up imaging (median 2.8 months post-initiation) using a standardized formula, grouped into ≥10% increase and <10% increase. Main Outcomes and Measures Differences in OS and PFS assessed using Kaplan–Meier curves and multivariable Cox hazards regression models. Results A total of 109 patients met inclusion criteria. Median follow-up time was 25.2 months (IQR 11.2-41.5), during which there were 47 mortality events. Patients with a splenic volume increase ≥ 10% at a median 2.8 months after ICI initiation had worse 2-year PFS (28.5% vs 50.4%, P = .022) but not OS (69.4% vs 77.8%, P = .853) compared to patients with a < 10% increase in splenic volume. On multivariable analysis, a splenic volume increase ≥ 10% was independently associated with worse PFS (2.33 [95% CI 1.37-3.96], P = .002). Conclusions and Relevance In patients with mRCC, a splenic volume increase ≥ 10% at a median of 2.8 months following ICI initiation is independently associated with worse survival compared to an < 10% increase. Monitoring splenic volume changes may serve as a cost-effective radiographic prognostic marker to guide treatment sequencing. Graphical Abstract Graphical Abstract
Current status of immunotherapy in metastatic colorectal cancer
BackgroundImmunotherapy focuses on selectively enhancing the host’s immune response against malignant disease. It has been investigated as an important treatment modality against malignant disease for many years, but until recently its use was mostly limited to a few cancers. The advent of new immunemodulating agents in the recent past has changed the landscape for management of many solid tumors. Currently, immunotherapy offers a valuable, and in many cases, a more effective alternate to the conventional cytotoxic therapy. Colorectal cancer is a leading cause of cancer-related death. Despite progress in systemic therapy, most patients with metastatic colorectal cancer die of their disease. There is an unmet need for more effective treatments for patients with metastatic colorectal cancer. The current data support that colorectal tumors are immunoresponsive and a subset of patients with advanced disease achieve long term benefit with immunotherapy.ObjectivesThis review aims to provide the current status of immunotherapy in patients with metastatic colorectal cancer.MethodsWe researched sources published in the English language between January 2000 and August 2018 and listed within the PubMed database using combinations of the key words and reviewed the proceedings of international cancer conferences and current guidelines made by major cancer societies.ResultsIn this review, we summarize the current status of research on immunotherapy in metastatic colorectal cancer and discuss various treatment modalities including checkpoint inhibitors, cancer vaccines, adoptive cell transfer, oncolytic virus therapy, and various other agents that are under investigation with a special emphasis on immune checkpoint inhibitors. Since the toxicity profile of immunotherapy is very different from conventional cytotoxic agents and could involve any organ system, we briefly review common adverse effects and their management.
Stakeholders’ perspectives on barriers to and facilitators of school-based HPV vaccination in the context of COVID-19 pandemic-related disruption: a qualitative mixed methods study
Despite successfully implementing the Human Papilloma Virus Vaccine (HPVV) program, Saskatchewan (SK) struggled to improve HPVV uptake rates. This suboptimal uptake of HPVV with a status quo of HPV-linked cervical cancer incidence rate is mainly because HPVV's impact on cancer prevention has not been realized adequately by vaccine providers and receivers. Further exploration of determinants of HPVV uptake is required to uncover high-resolution quality improvement targets for investment and situate contextually appropriate policies to improve its uptake. The study undertook a qualitative inquiry into understanding stakeholders' perspectives on HPVV experience through school-based programmes. It collected data through semi-structured initial interviews (N = 16) and follow-up interviews (N = 10) from across Saskatchewan's four Integrated Service Areas. Document analysis was conducted on all publicly available documents that included information on HPVV from January 2015 to July 2023. Thematic analysis of the data identified that inadequate information, awareness and education about HPV infection and HPVV among several groups, especially, parents, youth and school staff, was the main barrier to optimal HPVV uptake. Vaccine-related logistics, including the technical and text-heavy vaccine information sheet, understaffing, and time constraints, were other important factors that impeded HPVV uptake. A person-centred approach could educate parents in multiple dimensions.
CD40 agonist improves the therapeutic efficacy of irreversible electroporation ablation for metastatic melanoma by promoting unexpected CD8+CD103+ cDC1 and TRM cell responses
Background Melanoma is one of the deadliest forms of skin cancer. Irreversible electroporation (IRE) is an innovative, non-thermal ablation technology for treating irresectable solid cancers. However, most IRE treatments are incapable of cancer eradication and only temporarily prolong patient survival. Methods In this study, we developed a novel IRE + Combo treatment regimen that combines IRE-ablation with Combo-adjuvant [CpG, anti-PD-L1 antibody (PD-L1-Ab) and CD40-agonist] and investigated its anti-tumor immunity in a mouse BL6-10 OVA (BL OVA ) melanoma model. Results We demonstrated that inclusion of the CD40-agonist in the IRE + Combo treatment regimen promoted a more robust CD8 + T cell response (6.89%) when compared with IRE + CpG/PD-L1-Ab (2.67%) or IRE alone (0.21%) treatments, leading to eradication of subcutaneous BL OVA melanoma in 5/8 of BL OVA -bearing mice and simultaneous elimination of lung melanoma metastases. Addition of CD40-agonist to the IRE + Combo treatment regimen also induced a higher frequency (17.1%) of CD8 + CD103 + conventional type-1 dendritic cells (cDC1s) with up-regulated expression of CD54, CD80, MHC II, Bcl-xL and 41BBL in tumor-drainage lymph nodes (TDLNs) relative to the control IRE + CpG/PD-L1-Ab (12.1%) and IRE alone (9.0%) treatment groups. We also show that CD40-agonist stimulated a higher frequency of CD103 + TCF1 + tissue-resident memory T (T RM ) cells (32.1%) in TDLNs when compared with the two control (15.3% and 6.7%) treatment groups, and that these T RM cells exhibited enhanced mitochondrial content and greater relative expression of the effector cytokines IFN-γ and TNF-α and the transcriptional regulators TRAF1, p38-MAPK and PGC-1α. Conclusion Taken together, this study establishes that the CD40-agonist greatly potentiates the efficacy of IRE-ablation for metastatic melanoma by promoting unexpected CD8 + CD103 + cDC1 and CD103 + TCF1 + T RM cell responses and suggests the importance of targeting CD40-signaling to improve the efficacy of cancer IRE-ablation therapy.
Early discontinuation of adjuvant chemotherapy in patients with early-stage pancreatic cancer correlates with inferior survival: A multicenter population-based cohort study
The current study aimed to determine the association between timing and completion of adjuvant chemotherapy and outcomes in real-world patients with early-stage pancreatic cancer. In this multi-center cohort study patients with early-stage pancreatic cancer who were diagnosed from 2007-2017 and underwent complete resection in the province of Saskatchewan were examined. Cox proportional multivariate analyses were performed for correlation with recurrence and survival. Of 168 patients, 71 eligible patients with median age of 69 years and M:F of 37:34 were identified. Median time to the start of adjuvant therapy from surgery was 73 days. Of all patients, 49 (69%) patients completed adjuvant chemotherapy and 22 (31%) required early treatment discontinuation. Median recurrence-free survival of patients who completed treatment was 22 months (95%CI:15.8-28.2) vs. 9 months (3.3-14.7) if treatment was discontinued early (P<0.001). Median overall survival of those who completed treatment was 33 (17.5-48.5) vs. 16 months (17.5-48.5) with early treatment discontinuation (P<0.001). In the multivariate analysis, treatment discontinuation was significantly correlated with recurrent disease, hazard ratio (HR), 2.57 (1.41-4.68), P = 0.002 and inferior survival, HR, 2.55 (1.39-4.68), P = 0.003. No correlation between treatment timing and survival was noted. Early discontinuation but not the timing of adjuvant chemotherapy correlates with inferior outcomes.
Static and dynamic RCA analysis of India and China in world economy
This study is an attempt to examine similarities and differences in the patterns of revealed comparative advantage (RCA) of India and China in the global market at different levels of classification. The study analyses whether RCAs of these economies have undergone any structural shift/change or whether the pattern of specialization in these economies is competitive or complementary in the world market. The study reveals that India holds a comparative advantage in 9 out of 16 product groups of Harmonized System (HS) classification, 41 out of 97 HS chapters at HS 2‐digit level, and 2377 out of 4163 traded commodities at HS 6‐digit level, while China holds a comparative advantage in 6 out of 16 HS product groups, 45 out of 97 HS chapters at HS 2‐digit level, and 2075 out of 4381 traded commodities at HS 6‐digit level in 2018. Major findings suggest that both the countries have been performing well and broadly maintained their comparative advantage, especially since 2000. A comparative analysis of India and China reveals a small structural change in RCA over time in both economies at disaggregated levels. The study highlights that India and China neither have a competitive nor a complementary relationship in the global market. These findings reflect a scope of independent expansion of the economies of both India and China, without hurting mutual interest in the global market. It may be inferred from the results that mutual cooperation will enhance the competitiveness of both economies and contributes to global economic progress.