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1.
J Card Fail ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39332476

RESUMO

BACKGROUND: AHA/ACC/HFSA recently added SGLT2i in addition to RAASi, Beta-blockers and MRAs to form the 4 pillars of Guideline-directed Medical Therapy (GDMT) for management of Heart Failure with reduced ejection fraction (HFrEF). Despite strong evidence suggesting improved outcomes with inpatient initiation of GDMT at target doses, significant lag has been noted in prescription practices. OBJECTIVES: To study GDMT prescription rates in patients with HFrEF at the time of hospital discharge and evaluate its association with various patient characteristics and all-cause readmission rates. METHODS: We used a modified version of Heart Failure Collaboratory (HFC) score to characterize patients into 2 groups (those with HFC score <3 and HFC score ≥3) and to examine various socio-economic and biomedical factors affecting GDMT prescription practices. RESULTS: Out of the eligible patients, the prescription rates for Beta-blockers was 77.9%, RAASi was 70.3%, and MRAs was 41%. Furthermore, Prescription rates for Sacubitril/Valsartan was 27.7% and SGLT2i was 17%. Only 1% of patients had HFC score 9 (drugs from all 4 classes at target doses). Patients of black ethnicity, those admitted on teaching service and those with HfrEF as the primary cause of admission were more likely to have HFC ≥ 3 at discharge. HFC ≥ 3 was associated with lower rates of 1-month all cause readmissions. CONCLUSION: Consistent with the prior research, our data shows significant gaps in prescription of GDMT in HFrEF. Further implementation research should be done to improve GDMT prescription during inpatient stay.

2.
J Surg Res ; 302: 302-316, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39121798

RESUMO

INTRODUCTION: Although lobectomy has been the treatment of choice for early-stage non-small cell lung cancer (NSCLC), sub-lobar resection (i.e., segmentectomy or wedge resection) has emerged as an alternative over time due to its ability to preserve additional lung function. This meta-analysis explores the survival outcomes of sub-lobar resection versus lobectomy in patients with stage I NSCLC (tumor size: ≤2 cm). MATERIAL AND METHODS: We conducted a systematic search of PubMed, EMBASE, and the Cochrane Library from inception up to July 28, 2023. The hazard ratios and odds ratios for overall survival (OS), disease-free survival (DFS), and mortality were calculated using the random effects model. RESULTS: A total of 27 studies, comprising 10,449 patients, were included. Sub-lobar resection demonstrated comparable OS and DFS to that of lobectomy. Similarly, there was no significant risk of mortality associated with any of the groups. However, the subgroup analysis according to patient selection (intentional, compromised, not specified, and both [intentional and compromised]) showed that the patients in the compromised subgroup had a poor DFS with sub-lobar resection as compared to lobectomy (hazard ratio: 1.52, confidence interval: 1.14-2.02, P = 0.004). Additionally, there was no significant difference in OS, DFS, or overall mortality in the results stratified by surgical procedure or patient selection. CONCLUSIONS: The patients with stage I NSCLC who underwent sub-lobar resection showed a significantly worse DFS and OS in the "compromised group." However, there was no overall significant difference in OS, DFS, or mortality in the sub-lobar resection group as compared to lobectomy.

3.
Neurol Sci ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269572

RESUMO

BACKGROUD: Multiple Sclerosis (MS) is a complex and chronic autoimmune disease that affects the central nervous system. Inflammation and demyelination characterize it, which results in a range of neurological impairments. The increasing worldwide occurrence of MS, affecting an estimated 2.8 million individuals in 2020, highlights the urgent requirement for further research to tackle the significant impact it has on individuals and healthcare systems globally. OBJECTIVE: In this study, we wanted to explore the complex function of the endoplasmic reticulum (ER) in the origin, development, and resolution of MS, emphasizing its importance in neuroinflammatory illnesses. The ER has become a central focus in comprehending the pathogenesis of MS. Upon reviewing the literature, we observed a lack of thorough analysis that explores the involvement of endoplasmic reticulum stress in multiple sclerosis. Thus, we aimed through this research to examine the correlations between ER stress and its influence on immunological dysregulation, demyelination, and neurodegeneration in MS. FINDINGS: Based on the latest clinical trials, we suggested theories that explore possible biomarkers linked to ER stress and the unfolded protein response. Identifying molecules that are suggestive of early stages of illness and can serve as prognostic tools for improving our understanding of the heterogeneity of MS and offering novel approaches for managing the disease. Finally, through our comprehensive search, we wanted to offer a plan for future research, suggesting new and creative methods for managing MS and encouraging the creation of specific treatments that aim to reduce the impact of MS on individuals worldwide.

4.
Medicina (Kaunas) ; 60(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39064515

RESUMO

Background and Objectives: Acinetobacter baumannii (A. baumannii), particularly carbapenem-resistant A. baumannii (CRAB), represents a grave concern in healthcare settings and is associated with high mortality. This study aimed to conduct molecular, mutational, and phylogenetic analyses of specific genes in CRAB and evaluate the synergistic effects of selected antimicrobial combinations. Materials and Methods: Phenotypic characterization was performed on six CRAB strains by using the Modified Hodge Test (MHT) and IMP-EDTA Double-Disc Synergy Test (IMP-EDTA DDST). Carbapenemase- and metallo-beta-lactamase-encoding genes were amplified by using Polymerase Chain Reaction. Phylogenetic analysis using the MEGA 11 tool was used to determine the evolutionary relatedness of these genes. Mutational analysis was performed by using I-Mutant, MUPro, and PHD-SNP bioinformatics tools to predict mutations in the carbapenemase-encoding genes. Microdilution checkerboard titration assessed the synergistic effects of antimicrobial combinations (azithromycin-meropenem, rifampicin-meropenem, meropenem-colistin, and azithromycin-colistin) on these CRAB isolates. Results: The phenotypic characterization of six CRAB isolates revealed positive results for MHT and IMP-EDTA DDST. The molecular characterization revealed that carbapenemase- and MBL-encoding genes were present in all isolates with varying frequencies, including blaOXA-51 (100%) and blaIMP (0%). The sequence analysis revealed high evolutionary relatedness to sequences in the NCBI database. The mutational analysis identified 16 mutations, of which 1 mutation (P116L) in the blaOXA-58 gene predicted a change in the protein product, potentially contributing to carbapenem resistance. The checkerboard titration method did not reveal any synergism among the tested antimicrobial combinations against CRAB. Conclusion: This study's findings underscore the significant challenges posed by CRAB isolates harboring multiple resistant genes in treatment. This highlights the urgent need for novel antimicrobial agents, a crucial step towards reducing mortality rates not only in Pakistan but also globally.


Assuntos
Acinetobacter baumannii , Antibacterianos , Carbapenêmicos , Testes de Sensibilidade Microbiana , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Testes de Sensibilidade Microbiana/métodos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases/genética , Infecções por Acinetobacter/tratamento farmacológico , Proteínas de Bactérias/genética , Quimioterapia Combinada/métodos , Filogenia
5.
Mol Biol Rep ; 50(9): 7381-7392, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37450076

RESUMO

BACKGROUND: Alkaline-salt is one of the abiotic stresses that slows plant growth and developmental processes and threatens crop yield. Long non-coding RNAs (lncRNAs) are endogenous RNA found in plants that engage in a variety of cellular functions and stress responses. METHOD: lncRNAs act as competing endogenous RNAs (ceRNA) and constitute a new set of gene control. The precise regulatory mechanism by which lncRNAs function as ceRNAs in response to alkaline-salt stress remains unclear. We identified alkaline-salt responsive lncRNAs using transcriptome-wide analysis of two varieties including alkaline-salt tolerant [WD20342 (WD)] and alkaline-salt sensitive [Caidao (CD)] rice cultivar under control and alkaline-salt stress treated [WD20342 (WDT, and Caidao (CDT)] conditions. RESULTS: Investigating the competitive relationships between mRNAs and lncRNAs, we next built a ceRNA network involving lncRNAs based on the ceRNA hypothesis. Expression profiles revealed that a total of 65, 34, and 1549 differentially expressed (DE) lncRNAs, miRNAs, and mRNAs were identified in alkaline-salt tolerant WD (Control) vs. WDT (Treated). Similarly, 75 DE-lncRNAs, 34 DE-miRNAs, and 1725 DE-mRNAs (including up-regulated and down-regulated) were identified in alkaline-salt sensitive CD (Control) vs. CDT (Treated), respectively. An alkaline-salt stress ceRNA network discovered 321 lncRNA-miRNA-mRNA triplets in CD and CDT, with 32 lncRNAs, 121 miRNAs, and 111 mRNAs. Likewise, 217 lncRNA-miRNA-mRNA triplets in WD and WDT revealed the NONOSAT000455-osa_miR5809b-LOC_Os11g01210 triplet with the highest degree as a hub node with the most significant positive correlation in alkaline-salt stress response. CONCLUSION: The results of our investigation indicate that osa-miR5809b is dysregulated and plays a part in regulating the defense response of rice against alkaline-salt stress. Our study highlights the regulatory functions of lncRNAs acting as ceRNAs in the mechanisms underlying alkaline-salt resistance in rice.


Assuntos
MicroRNAs , Oryza , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Oryza/genética , Oryza/metabolismo , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Salino/genética , RNA Mensageiro/genética
6.
Physiol Plant ; 174(3): e13696, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35502736

RESUMO

Globally, rice is being consumed as a main staple food and faces different kinds of biotic and abiotic stresses such drought, salinity, and pest attacks. Through the cytokinin signaling, Type-B authentic response regulators (ARR-Bs) respond positively towards the environmental stimuli. ARR-Bs are involved in abiotic stress tolerance and plant development but their molecular mechanisms in fragrant rice are still not fully explored. The current study showed the genome-wide characterization of OsARR-B genes under alkaline salt stress. Results showed that in total, 24 OsARR-B genes were found and divided into four subgroups on the basis of a phylogenetic analysis. These genes were located on all rice chromosomes except 8 and 10. Analysis of gene duplications, gene structure, cis-elements, protein-protein interactions, and miRNA were performed. Gene ontology analysis showed that OsARR-B genes are involved in plant development through the regulation of molecular functions, biological processes, and cellular components. Furthermore, 117 and 192 RNA editing sites were detected in chloroplast and mitochondrial genes, respectively, encoding proteins of OsARR-B. In chloroplast and mitochondrial genes, six and nine types of amino acid changes, respectively, were caused by RNA editing, showing that RNA editing has a role in the alkaline salt stress tolerance in fragrant rice. We also used a comparative transcriptome approach to study the gene expression changes in alkaline tolerant and susceptible genotypes. Under alkaline salt stress, OsARR-B5, OsARR-B7, OsARR-B9, OsARR-B10, OsARR-B16, OsARR-B22, and OsARR-B23 showed higher transcript levels in alkaline salt tolerant genotypes as compared to susceptible ones. Quantitative RT-PCR showed upregulation of gene expression in the alkaline tolerant genotypes under alkaline stress. Our study explored the gene expression profiling and RESs of two rice contrasting genotypes, which will help to understand the molecular mechanisms of alkaline salt tolerance in fragrant rice.


Assuntos
Oryza , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Genes Reguladores , Oryza/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Salino/genética , Tolerância ao Sal/genética , Estresse Fisiológico/genética
7.
Waste Manag Res ; 40(6): 676-684, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34362279

RESUMO

Food wastage is a global concern with high economic, social and environmental impacts. Pakistan, a developing country, is also significantly affected by the adverse impacts of food wastage. For overcoming this problem, the transition from a Linear to a Circular Economy (CE) for the management of food wastage can serve as a viable strategy. However, there are barriers of political, technical and cultural nature, which are impediments in the path of this transition. This study aims to identify and prioritize these barriers in order of their significance. This research study evaluated and ranked these barriers using a Fuzzy Multi-Criteria Decision Making (MCDM) technique, the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). A total of 15 barriers were analyzed, and the 'complicated intrinsic nature of CE', 'misleading information about shelf-life leading to waste rather than distribution', 'the poor economic viability of start-ups with CE model', 'corporate and organizational hesitance to change/innovate' and 'technological backwardness of farmers/growers on the agricultural production side' were ranked as the most significant hurdles. The novelty of this study lies in its application. This study is unique as it has focused on developing countries and proposed policy recommendations for the transition towards a CE. In light of the above-mentioned results, this study provides policy recommendations for public and private sector policymakers that would facilitate the food industry in shifting towards the CE model.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Países em Desenvolvimento , Alimentos , Modelos Econômicos
8.
Entropy (Basel) ; 20(4)2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33265381

RESUMO

The convolution neural network (CNN) has achieved state-of-the-art performance in many computer vision applications e.g., classification, recognition, detection, etc. However, the global optimization of CNN training is still a problem. Fast classification and training play a key role in the development of the CNN. We hypothesize that the smoother and optimized the training of a CNN goes, the more efficient the end result becomes. Therefore, in this paper, we implement a modified resilient backpropagation (MRPROP) algorithm to improve the convergence and efficiency of CNN training. Particularly, a tolerant band is introduced to avoid network overtraining, which is incorporated with the global best concept for weight updating criteria to allow the training algorithm of the CNN to optimize its weights more swiftly and precisely. For comparison, we present and analyze four different training algorithms for CNN along with MRPROP, i.e., resilient backpropagation (RPROP), Levenberg-Marquardt (LM), conjugate gradient (CG), and gradient descent with momentum (GDM). Experimental results showcase the merit of the proposed approach on a public face and skin dataset.

9.
Sensors (Basel) ; 16(9)2016 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-27598167

RESUMO

Due to the recent development in the field of Wireless Sensor Networks (WSNs), the Wireless Body Area Networks (WBANs) have become a major area of interest for the developers and researchers. Human body exhibits postural mobility due to which distance variation occurs and the status of connections amongst sensors change time to time. One of the major requirements of WBAN is to prolong the network lifetime without compromising on other performance measures, i.e., delay, throughput and bandwidth efficiency. Node prioritization is one of the possible solutions to obtain optimum performance in WBAN. IEEE 802.15.6 CSMA/CA standard splits the nodes with different user priorities based on Contention Window (CW) size. Smaller CW size is assigned to higher priority nodes. This standard helps to reduce delay, however, it is not energy efficient. In this paper, we propose a hybrid node prioritization scheme based on IEEE 802.15.6 CSMA/CA to reduce energy consumption and maximize network lifetime. In this scheme, optimum performance is achieved by node prioritization based on CW size as well as power in respective user priority. Our proposed scheme reduces the average back off time for channel access due to CW based prioritization. Additionally, power based prioritization for a respective user priority helps to minimize required number of retransmissions. Furthermore, we also compare our scheme with IEEE 802.15.6 CSMA/CA standard (CW assisted node prioritization) and power assisted node prioritization under postural mobility in WBAN. Mathematical expressions are derived to determine the accurate analytical model for throughput, delay, bandwidth efficiency, energy consumption and life time for each node prioritization scheme. With the intention of analytical model validation, we have performed the simulations in OMNET++/MIXIM framework. Analytical and simulation results show that our proposed hybrid node prioritization scheme outperforms other node prioritization schemes in terms of average network delay, average throughput, average bandwidth efficiency and network lifetime.

10.
Am J Cardiovasc Drugs ; 24(5): 641-650, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38913274

RESUMO

BACKGROUND: Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels. METHODS: A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I2 index. The risk of bias was assessed using Cochrane's RoB 2 tool. This review has been registered with PROSPERO (CRD42023471020). RESULTS: A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = - 63.78, 95% CI - 65.88 to - 61.68, p value < 0.00001, I2 = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, p value < 0.00001, I2 = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, p value < 0.00001, I2 = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB 2 tool. CONCLUSIONS: Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations. REGISTRATION: PROSPERO identifier number CRD42023471020.


Assuntos
Anticorpos Monoclonais Humanizados , LDL-Colesterol , Hipercolesterolemia , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , China , LDL-Colesterol/sangue , População do Leste Asiático , Hipercolesterolemia/tratamento farmacológico , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Curr Probl Cardiol ; 49(1 Pt C): 102186, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37907186

RESUMO

Current pharmacological regimen is unable to improve adverse outcomes such as mortality post hospitalization for Acutely Decompensated Heart Failure (ADHF) patients. Ongoing research is directed towards managing ADHF patients with Cardiac Autonomic Nervous System (CANS) excitatory interventions having long-term prognosis benefits. Recently, a novel treatment coined as Cardiac Pulmonary Nerve Stimulation (CPNS) has reproducibly shown increased inotropy with no change in heart rate. However, there are some potential limitations associated with the neurostimulation of the parasympathetic component of the CANS plexus. The INOVATE-HF trial involved the vagus nerve only. The early termination of the INOVATE-HF trial gave valuable insights into the cardio-protective effect of simultaneously stimulating the sympathetic and parasympathetic components of the CANS plexus done in CPNS. It is essential to individualize the treatment protocol keeping in mind patient selection. Ongoing trials assessing the efficacy and safety of the CPNS technique in ADHF patients shall set the tone for such innovative techniques in times to come.


Assuntos
Insuficiência Cardíaca , Coração , Humanos , Coração/inervação , Sistema Nervoso Autônomo , Prognóstico , Seleção de Pacientes
12.
Clin Genitourin Cancer ; 22(2): 483-490.e5, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38296679

RESUMO

Castration resistant prostate cancer (CRPC) is a challenging subset of prostate cancer associated with an extensive metastatic profile and high mortality. Ketoconazole is a nonselective steroid 17α-hydroxylase/17,20 lyase (CYP17A1) inhibitor and is employed as a second line treatment option for CRPC with an established efficacy profile in patients. The aim of this study is to assess the efficacy of ketoconazole containing regimens for CRPC in terms of prostate specific antigen (PSA) decline rate using a systematic review and meta-analysis. In this review, an electronic search was carried out on PubMed, Cochrane CENTRAL, Scopus, and Google Scholar to find relevant literature. Random effects model was used to assess pooled PSA decline rate and 95% CIs. Publication bias was assessed using the funnel plot symmetry and one-tailed Egger's and Begg's test. In all cases, P-value <.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023466536. A total of 483 articles were retrieved after database searching, out of which 23 studies (having a total of 1315 patients) were included in the review based on prespecified criteria. The PSA decline rate was reported in the 14 observational studies (having 964 patients) and 9 experimental studies (having 351 patients). Pooled results revealed that 48.6% (95% CI 43.1-54.2; P-value <.001; I2 = 73.24%) of participants achieved more than 50% decline in PSA (602/1315 participants). Sensitivity analysis using the leave-one-out method revealed no substantial change in pooled effect estimates; (Risk Ratio) RR 47.2% to RR 49.8% demonstrating the robustness of our results. There was no evidence of publication bias as assessed from the funnel plot symmetry. Ketoconazole containing regimens have shown moderate efficacy in high risk CRPC patients as demonstrated by the pooled results. Hence, a ketoconazole based chemotherapy can be added to patients' regimen if there is a persistent rise in PSA levels after androgen deprivation therapy.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Cetoconazol/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios/uso terapêutico
13.
J Gastrointest Cancer ; 55(2): 559-571, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38315331

RESUMO

BACKGROUND: The relative success of cisplatin-based chemotherapy regimens for PDAC in clinical trials warrants a review of the literature to assess the cumulative results. This study aims to assess the efficacy of cisplatin-containing regimens for PDAC in terms of survival and response outcomes using a systematic review and proportional meta-analysis. METHODS: In this study, an electronic search was conducted on PubMed, Cochrane Library, Scopus, and Google Scholar to find relevant literature. The random effects model was used to assess pooled overall response rate, stable disease rate, progressive disease rate, 1-year overall survival rate, and their 95% CIs. Publication bias was assessed using funnel plot symmetry and the one-tailed Eggers' test. In all cases, p-value < 0.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023459243. RESULTS: A total of 34 studies consisting of 1599 patients were included in this review. All the included studies were of good quality. In total, 906 patients were male, and the median age of the patients was 58-69 years. Overall, 599 patients had cancer of the pancreatic head, 139 had cancer of the pancreatic body, and 102 patients had cancer of the pancreatic tail. The pooled risk ratios (RRs) revealed an overall response rate of 19.2% (95% CI, 14.6-24.2%), a stable disease rate of 42.3% (95% CI, 36.6-48.8), a 1-year overall survival rate of 40% (95% CI, 34.3-45.8), and progressive disease rate of 24.7% (95% CI, 18.8-31.2). Commonly reported adverse events were anemia, thrombocytopenia, abdominal adverse events, neutropenia, fatigue, leukopenia, alopecia, anorexia, mucositis, stomatitis, and hepatobiliary adverse events. CONCLUSION: Cisplatin-containing regimens have shown moderate efficacy with significant improvement in overall survival at 1 year, stable disease rate, and progressive disease rate; however, only a small percentage of patients achieved an overall response rate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Cisplatino , Neoplasias Pancreáticas , Humanos , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/mortalidade , Masculino , Taxa de Sobrevida , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso
14.
Am J Clin Oncol ; 47(8): 399-408, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38907598

RESUMO

OBJECTIVE: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period. METHODS: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). RESULTS: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR: 0.59, 95% CI: 0.45-0.76, P <0.0001, I2 =90%) and >36 months (HR: 0.66, 95% CI: 0.55-0.80, P <0.0001, I2 =80%), and an overall survival benefit for <36 months (HR: 0.87, 95% CI: 0.78-0.98, P =0.02, I2 =0%) but not for >36 months (HR: 0.98, 95% CI: 0.89-1.09, P =0.77, I2 =30%). There was no difference in deaths between intervention and control groups <36 months (RR: 0.95, 95% CI: 0.86-1.04, P =0.26, I2 =10%) or >36 months (RR: 1.02, 95% CI: 0.97-1.06, P =0.50, I2 =0%). Bevacizumab reduced disease progression <36 months (RR: 0.82, 95% CI: 0.72-0.92, P =0.0008, I2 =82%) but not at >36 months (RR: 0.83, 95% CI: 0.58-1.19, P =0.30, I2 =94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. CONCLUSION: Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Ovarianas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Seguimentos , Intervalo Livre de Progressão
15.
Case Rep Oncol ; 16(1): 1253-1258, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915994

RESUMO

Introduction: Esophageal adenocarcinoma (EAC) manifests in the glandular cells present in the lining of the esophagus and usually forms in the distal portion of the esophagus. The metastasis of EAC has been reported to occur in surrounding lymphovascular structures, the liver, brain, and bones. Case Presentation: We present the rare case of a 52-year-old Hispanic male with EAC metastasis to the pericardium and lungs. The patient presented with shortness of breath off and on for the last 6 weeks without any usually reported symptoms of EAC like chest pain, vomiting, or chronic cough. Respiratory examinations of this patient were significant for bilateral bronchial breathing and coarse crackles. The patient had been given numerous courses of oral antibiotics over the previous weeks with the provisional diagnosis of atypical pneumonia. Cardiac tamponade pathophysiology was also observed in this patient, for which a pericardial window was created to relieve the patient's symptoms. A final diagnosis of EAC with an unusual metastasis in the lungs and pericardium was made based on radiological and pathological findings. The patient chose palliative care instead of curative care because of the advanced stage of this cancer. The patient received cancer diagnosis counseling and was sent to hospice care for further management. Conclusion: The metastasis of EAC to the pericardium and lungs instead of usual sites constitutes an important prognostic factor in the overall survival of patients.

16.
Ann Med Surg (Lond) ; 85(6): 2884-2895, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37363463

RESUMO

Aseptic stem loosening after total hip arthroplasty surgery is the commonest complication, whether stem is cemented or uncemented. The aseptic cemented stem loosening has been a challenging problem over the years and a leading cause for revision since the inception of total hip arthroplasty. The objective of systematic review and meta-analysis was to determine the impact of cementing technique on aseptic stem loosening in total hip arthroplasty. Methods: Cochrane, CINAHL, Embase, Google scholar, Medline, PubMed were searched in 13 December 2020. Two independent investigators extracted the data and a third investigator's involvement was reached on consensus. A total of 37 studies of revision rate due to aseptic loosening were reviewed by using fixed/random effects size and were grouped by cementing technique and studies' characteristics. The data were analyzed through Meta-Essentials and RStudio. Results: In revision total hip arthroplasty, retained femoral components revisions rate due to aseptic loosening were recorded in 37 studies involving 6167 cases. Aseptic loosening rate collectively was 5.8% (CI 95%, 0.03-0.08) and mean follow-up of study was 12.5 years. The average follow-up period, mean age at index revision surgery and percentage of aseptic loosening were insignificantly associated with revision rate (P≥0.05), in meta-regression univariant analyses. Conclusion: This investigative analysis showed that there is a minimal difference between results of cementing techniques of total hip arthroplasty in femoral components in long-term follow-ups, and usually have a low risk of failure.

17.
Environ Sci Pollut Res Int ; 29(4): 5736-5761, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34424462

RESUMO

"How does a firm's bankruptcy affect its regional environment?" is an open empirical question that has received little attention in the literature. We hypothesize that because enterprises provide funds to protect their regional environment, their default risk negatively impacts that environment. We analyze the impact of corporate default risk on environmental deterioration in the international setting to answer this question. Using a firm-level corporate default risk quarterly data from 2013q1 to 2020q4, we find that corporate default risk is positively associated with CO2 emissions and decomposed components. These findings are reliable in low-income and highly uncertain countries but weak in countries having more market competition. We also find that the negative impact of corporate default risk on the environment is more robust in countries with more population density and fewer forest area thresholds. Finally, using the instrumental variable approach, we provide preliminary evidence that firm-level political risk (for US and Canadian firms only) increases corporate default risk, leading to a degrading environment. Our findings are robust to alternative measurements of a firm's default risk and environmental deterioration. Our research will help environmental authorities to consider corporate default risk as a determinant when formulating environmental-related strategies.


Assuntos
Organizações , Canadá , Incerteza
18.
Front Genet ; 13: 912251, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860467

RESUMO

Receptor-like protein kinase 1 (RPK1) genes play crucial roles in plant growth and development processes, root architecture, and abiotic stress regulation. A comprehensive study of the RPK1 gene family has not been reported in bread wheat (Triticum aestivum). Here, we reported the genome-wide identification, characterization, and expression patterns of the RPK1 gene family in wheat. Results confirmed 15 TaRPK1 genes, classified mainly into three sub-clades based on a phylogenetic tree. The TaRPK1 genes were mapped on chromosomes 1-3 in the respective A, B, and D genomes. Gene structure, motif conservation, collinearity prediction, and synteny analysis were carried out systematically. A Gene ontology study revealed that TaRPK1 genes play a vital role during molecular and biological processes. We also identified 18 putative miRNAs targeting TaRPK1 genes, suggesting their roles in growth, development, and stress responses. Cis-Regulatory elements interpreted the presence of light-related elements, hormone responsiveness, and abiotic stress-related motifs in the promoter regions. The SWISS_MODEL predicted the successful models of TaRPK1 proteins with at least 30% identity to the template, a widely accepted threshold for successful modeling. In silico expression analysis in different tissues and stages suggested that TaRPK1 genes exhibited the highest expression in root tissues. Moreover, qRT-PCR further validated the higher expression of TaRPK1 genes in roots of drought-tolerant varieties compared to the drought-susceptible variety. Collectively, the present study renders valuable information on the functioning of TaRPK1 genes in wheat that will be useful in further functional validation of these genes in future studies.

19.
Front Plant Sci ; 13: 960641, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092421

RESUMO

Rice (Oryza sativa L.) is considered as a staple food for more than half of the global population, and sustaining productivity under a scarcity of resources is challenging to meet the future food demands of the inflating global population. The aerobic rice system can be considered as a transformational replacement for traditional rice, but the widespread adaptation of this innovative approach has been challenged due to higher losses of nitrogen (N) and reduced N-use efficiency (NUE). For normal growth and developmental processes in crop plants, N is required in higher amounts. N is a mineral nutrient and an important constituent of amino acids, nucleic acids, and many photosynthetic metabolites, and hence is essential for normal plant growth and metabolism. Excessive application of N fertilizers improves aerobic rice growth and yield, but compromises economic and environmental sustainability. Irregular and uncontrolled use of N fertilizers have elevated several environmental issues linked to higher N losses in the form of nitrous oxide (N2O), ammonia (NH3), and nitrate (NO3 -), thereby threatening environmental sustainability due to higher warming potential, ozone depletion capacities, and abilities to eutrophicate the water resources. Hence, enhancing NUE in aerobic rice has become an urgent need for the development of a sustainable production system. This article was designed to investigate the major challenge of low NUE and evaluate recent advances in pathways of the N cycle under the aerobic rice system, and thereby suggest the agronomic management approaches to improve NUE. The major objective of this review is about optimizing the application of N inputs while sustaining rice productivity and ensuring environmental safety. This review elaborates that different soil conditions significantly shift the N dynamics via changes in major pathways of the N cycle and comprehensively reviews the facts why N losses are high under the aerobic rice system, which factors hinder in attaining high NUE, and how it can become an eco-efficient production system through agronomic managements. Moreover, it explores the interactive mechanisms of how proper management of N cycle pathways can be accomplished via optimized N fertilizer amendments. Meanwhile, this study suggests several agricultural and agronomic approaches, such as site-specific N management, integrated nutrient management (INM), and incorporation of N fertilizers with enhanced use efficiency that may interactively improve the NUE and thereby plant N uptake in the aerobic rice system. Additionally, resource conservation practices, such as plant residue management, green manuring, improved genetic breeding, and precision farming, are essential to enhance NUE. Deep insights into the recent advances in the pathways of the N cycle under the aerobic rice system necessarily suggest the incorporation of the suggested agronomic adjustments to reduce N losses and enhance NUE while sustaining rice productivity and environmental safety. Future research on N dynamics is encouraged under the aerobic rice system focusing on the interactive evaluation of shifts among activities and diversity in microbial communities, NUE, and plant demands while applying N management measures, which is necessary for its widespread adaptation in face of the projected climate change and scarcity of resources.

20.
Ann Med Surg (Lond) ; 84: 104931, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36536712

RESUMO

Background: Fibromyalgia syndrome (FMS) is an umbrella term for chronic pain syndrome, associated with tenderness, fatigue, reduced pain thresholds, and paresthesia in the limbs. The field of medicine places doctors in constant work-related stress, sleep deprivation, and depression, thus increasing their vulnerability to developing FMS. This study aims to evaluate the prevalence and severity of FM (fibromyalgia) among physicians in a tertiary care hospital setting. Methods: The cross-sectional study was performed at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from December 2019 to December 2020.243 physicians of either gender, and from all the departments being house officers, medical officers, and post-graduate trainees were included & divided into 3 age groups from 20 to more than 45 years. Widespread Pain Index (WPI) equal to or more than 7 and Symptom Severity Score (SSS) equal to or more than 5 OR WPI = 3 to 6 and SSS equal to or more than 9 were required, according to the modified American College of Rheumatology preliminary diagnostic criteria 2016 for fibromyalgia diagnosis. Data was analyzed using SPSS 25. Results: Among a total of 243 participants, FMS was diagnosed in 69 (28.40%) individuals. The predominant FMS population was the youngest age group 20-35 (56 = 81.16%). Increased BMI, increasing pain score category, gender, and comorbidities are significantly associated with FMS (p ≤ 0.05). Whereas, advancing age is insignificantly linked with FMS (p > 0.05). Conclusions: The prevalence of fibromyalgia was found to be high among doctors working in stressful hospital settings, particularly among the youngest ones.

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