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1.
N Engl J Med ; 384(13): 1191-1203, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789008

RESUMO

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. METHODS: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. RESULTS: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group. CONCLUSIONS: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Junção Esofagogástrica , Inibidores de Checkpoint Imunológico/uso terapêutico , Nivolumabe/uso terapêutico , Adenocarcinoma/imunologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Nivolumabe/efeitos adversos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia
2.
Ann Surg Oncol ; 31(1): 488-498, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37782415

RESUMO

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Características da Vizinhança
3.
Ann Surg Oncol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138773

RESUMO

Social media has become omnipresent in society, especially given that it enables the rapid and widespread communication of news, events, and information. Social media platforms have become increasingly used by numerous surgical societies to promote meetings and surgical journals to increase the visibility of published content. In September 2020, Annals of Surgical Oncology (ASO) established its Social Media Committee (SMC), which has worked to steadily increase the visibility of published content on social media platforms, namely X (formerly known as Twitter). The purpose of this review is to highlight the 10 ASO original articles with the most engagement on X, based on total number of mentions, since the founding of the SMC. These articles encompass a wide variety of topics from various oncologic disciplines including hepatopancreatobiliary, breast, and gynecologic surgery.

4.
J Surg Res ; 299: 269-281, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788463

RESUMO

INTRODUCTION: Colon cancer (CC) is one of the most common cancers among South Asian Americans (SAAs). The objective of this study was to measure differences in risk-adjusted survival among SAAs with CC compared to non-Hispanic Whites (NHWs) using a representative national dataset from the United States. METHODS: A retrospective analysis of patients with CC in the National Cancer Database (2004-2020) was performed. Differences in presentation, management, median overall survival (OS), three-year survival, and five-year survival between SAAs and NHWs were compared. Kaplan-Meier analysis and multivariable Cox regression were used to assess differences in survival outcomes, adjusting for demographics, presentation, and treatments received. RESULTS: Data from 2873 SAA and 639,488 NHW patients with CC were analyzed. SAAs were younger at diagnosis (62.2 versus 69.5 y, P < 0.001), higher stage (stage III [29.0% versus 26.2%, P = 0.001] or Stage IV [21.4% versus 20.0%, P = 0.001]), and experienced delays to first treatment (SAA 5.9% versus 4.9%, P = 0.003). SAAs with CC had higher OS (median not achieved versus 68.1 mo for NHWs), three-year survival (76.3% versus 63.4%), and five-year survival (69.1% versus 52.9%). On multivariable Cox regression, SAAs with CC had a lower risk of death across all stages (hazard ratio: 0.64, P < 0.001). CONCLUSIONS: In this national study, SAA patients with CC presented earlier in life with more advanced disease, and a higher proportion experienced treatment delay compared to NHW patients. Despite these differences, SAAs had better adjusted OS than NHW, warranting further exploration of tumor biology and socioeconomic determinants of cancer outcomes in SAAs.


Assuntos
Asiático , Neoplasias do Colo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Asiático/estatística & dados numéricos , Neoplasias do Colo/etnologia , Neoplasias do Colo/mortalidade , Estudos Transversais , Bases de Dados Factuais , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Estudos Retrospectivos , Estados Unidos/epidemiologia , Brancos/estatística & dados numéricos , Análise de Sobrevida
5.
J Surg Oncol ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39165230

RESUMO

BACKGROUND: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival. METHODS: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS. RESULTS: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04). CONCLUSIONS: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.

6.
J Surg Oncol ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082628

RESUMO

BACKGROUND AND OBJECTIVES: Pancreaticoduodenectomy (PD), the only surgical option for right-sided pancreatic ductal adenocarcinoma (PDAC), carries significant morbidity. Not all patients may be deriving a survival benefit from this operation. We sought to identify the rate of futile PD and its associated factors in a large national cohort. METHODS: We performed a retrospective analysis using the National Cancer Database (2004-2020), including all patients who underwent PD for non-metastatic PDAC. The primary outcome was operative futility, which was defined as death within 12 months of diagnosis despite PD. Multivariable regression was used to identify factors associated with futility. We performed a subgroup analysis on patients who received neoadjuvant systemic therapy. RESULTS: Data from 66 326 patients were analyzed, and 16 772 (25.3%) underwent PD that met criteria for futility. Macroscopically positive margins (odds ratio [OR]: 2.87; 95% confidence interval [CI]: 2.36-3.48), poor tumor differentiation (OR: 2.44; 95% CI: 2.25-2.65), and N2 nodal stage (OR: 2.09; 95% CI: 1.98-2.20) were associated with the greatest odds of futility. Meanwhile, receipt of any systemic therapy (OR: 0.33; 95% CI: 0.31-0.34), receipt of any radiation (OR: 0.60; 95% CI: 0.57-0.63), and receipt of neoadjuvant systemic therapy (OR: 0.62; 95% CI: 0.57-0.66) were associated with the lowest odds of futility. In the neoadjuvant subgroup, a longer diagnosis-to-surgery interval was associated with lower odds of futility. CONCLUSION: PD was futile in about one quarter of patients. Futility was associated with higher age and worse tumor biology. Receipt of neoadjuvant therapy resulted in fewer futile operations.

7.
World J Surg ; 48(8): 1829-1839, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38844403

RESUMO

BACKGROUND: Despite a glaring need and proven efficacy, prospective surgical registries are lacking in low- and middle-income countries. The objective of this study was to design and implement a comprehensive prospective perioperative registry in a low-income country. METHODS: This study was conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia. Design of the registry occurred from June 2021 to May 2022 and pilot implementation from May 2022 to May 2023. All patients undergoing elective or emergent general surgery were included. Following one year, operability and fidelity of the registry were analyzed by assessing capture rate, incidence of missing data, and accuracy. RESULTS: A total of 67 variables were included in the registry including demographics, preoperative, operative, post-operative, and 30-day data. Of 440 eligible patients, 226 (51.4%) were successfully captured. Overall incidence of missing data and accuracy was 5.4% and 90.2% respectively. Post pilot modifications enhanced capture rate to 70.5% and further optimized data collection processes. CONCLUSION: The establishment of a low-cost electronic prospective perioperative registry in a low-income country represents a significant step forward in enhancing surgical care in under-resourced settings. The initial success of this registry highlights the feasibility of such endeavors when strong partnerships and local context are at the center of implementation. Continuous efforts to refine this registry are ongoing, which will ultimately lead to enhanced surgical quality, research output, and expansion to other sites.


Assuntos
Melhoria de Qualidade , Sistema de Registros , Etiópia , Humanos , Estudos Prospectivos , Feminino , Masculino , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/normas , Adulto , Pessoa de Meia-Idade , Países em Desenvolvimento , Projetos Piloto , Assistência Perioperatória/normas
8.
J Pak Med Assoc ; 74(3 (Supple-3)): S87-S92, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39262068

RESUMO

Guidelines for low- and middle-income countries (LMICs) are needed in complex, multidisciplinary areas such as oncology, requiring mobilising considerable resources and specialists for coordinated care. Neuro-oncology guidelines have been primarily established in countries where technological advancements and robust care pathways facilitate broad resource utilisation. In contrast, LMICs require complex and region-specific interventions to provide equitable care. The present opinion paper is a culmination of our own centre's experience collaborating and developing loco-regional guidelines for brain tumour care, keeping in mind LMIC experiences and expertise available. We intend for the process and methodology to apply to a broader audience of other LMIC authors and clinicians collaborating with LMIC institutions to develop guidelines and clinical recommendations.


Assuntos
Neoplasias Encefálicas , Países em Desenvolvimento , Oncologia , Guias de Prática Clínica como Assunto , Humanos , Neoplasias Encefálicas/terapia , Oncologia/normas , Neurologia/normas
9.
Lancet Oncol ; 24(12): e472-e518, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37924819

RESUMO

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.


Assuntos
Neoplasias , Cirurgiões , Humanos , Neoplasias/cirurgia , Saúde Global , Política de Saúde
10.
J Surg Res ; 290: 188-196, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37269802

RESUMO

INTRODUCTION: Systematic collection and analysis of surgical outcomes data is a cornerstone of surgical quality improvement. Unfortunately, there remains a dearth of surgical outcomes data from low- and middle-income countries (LMICs). To improve surgical outcomes in LMICs, it is essential to have the ability to collect, analyze, and report risk-adjusted postoperative morbidity and mortality data. This study aimed to review the barriers and challenges to developing perioperative registries in LMIC settings. METHODS: We conducted a scoping review of all published literature on barriers to conducting surgical outcomes research in LMICs using PubMed, Embase, Scopus, and GoogleScholar. Keywords included 'surgery', 'outcomes research', 'registries', 'barriers', and synonymous Medical Subject Headings derivatives. Articles found were subsequently reference-mined. All relevant original research and reviews published between 2000 and 2021 were included. The performance of routine information system management framework was used to organize identified barriers into technical, organizational, or behavioral factors. RESULTS: Twelve articles were identified in our search. Ten articles focused specifically on the creation, success, and obstacles faced during the implementation of trauma registries. Technical factors reported by 50% of the articles included limited access to a digital platform for data entry, lack of standardization of forms, and complexity of said forms. 91.7% articles mentioned organizational factors, including the availability of resources, financial constraints, human resources, and lack of consistent electricity. Behavioral factors highlighted by 66.6% of the studies included lack of team commitment, job constraints, and clinical burden, which contributed to poor compliance and dwindling data collection over time. CONCLUSIONS: There is a paucity of published literature on barriers to developing and maintaining perioperative registries in LMICs. There is an immediate need to study and understand barriers and facilitators to the continuous collection of surgical outcomes in LMICs.


Assuntos
Países em Desenvolvimento , Cirurgia Geral , Resultado do Tratamento , Humanos , Sistema de Registros
11.
J Surg Oncol ; 127(4): 678-687, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36519668

RESUMO

BACKGROUND: Colorectal cancer (CRC) often recurs in the peritoneum, although the pattern of peritoneal recurrence (PR) has received less attention. We sought to describe the presentation and risk factors for PR following CRC resection. METHODS: We performed a cohort study of patients undergoing resection of Stage I-III CRC from 2006 to 2007 using merged data from a Commission on Cancer Special Study and the National Cancer Database. We estimated the timing, method of detection, and risk factors for isolated PR. RESULTS: Here, 8991 patients were included and isolate PR occurred in 77 (0.9%) patients. The median time to PR was 16.2 months (intrquartile range = 9.3-28.0 months) and most patients were identified via new symptoms (36.4%). Pathologic factors associated with increased odds of PR included higher T stage (T3 vs. T2, odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.5-15.7), N stage (N1 vs. N0, OR = 2.00, CI = 1.1-3.7), and signet ring (OR = 8.2, CI = 3.0-22.3) or mucinous histology (OR = 2.6, CI = 1.5-4.7). CONCLUSIONS: The majority of PR was detected within 18 months and few were identified by surveillance. Advanced T/N stage and signet ring/mucinous histology were associated with increased odds of PR.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma de Células em Anel de Sinete , Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Estudos de Coortes , Peritônio/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/patologia , Carcinoma de Células em Anel de Sinete/patologia , Adenocarcinoma Mucinoso/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
12.
J Surg Oncol ; 128(2): 280-288, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37073788

RESUMO

BACKGROUND: Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC). METHODS: We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score. RESULTS: A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration. CONCLUSIONS: Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Nomogramas , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Pancreáticas
13.
J Thromb Thrombolysis ; 55(2): 376-381, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36454476

RESUMO

BACKGROUND: Postoperative venous thromboembolism (VTE) is associated with significant morbidity. Evidence from other surgical specialties demonstrate inadequate use of extended VTE prophylaxis following cancer surgery. While guidelines recommend extended VTE prophylaxis for patients undergoing surgery for colorectal cancer (CRC), it is unknown to what extent colon and rectal surgeons adhere to these recommendations. METHODS: An 18-question online survey was distributed to all surgeon members of the American Society of Colon and Rectal Surgeons (ASCRS). The survey was designed to capture knowledge, attitudes, and practices regarding ASCRS VTE prevention guidelines. Questions were also designed to elucidate barriers to adopting these guidelines. RESULTS: The survey was distributed to 2,316 ASCRS-member surgeons and there were 201 complete responses (8.7% response rate). Most respondents (136/201, 68%) reported that they were familiar with ASCRS VTE prevention guidelines and used them to guide their practice. Extended VTE prophylaxis was reported to be routinely prescribed by the majority of surgeons following CRC resection (109/201, 54%), with an additional 27% reporting selective prescribing (55/201). The most frequently reported reasons for not prescribing extended VTE chemoprophylaxis following CRC resection included patient compliance and insurance/copay issues. CONCLUSION: Most ASCRS-member surgeon respondents reported that they are familiar with ASCRS VTE prevention guidelines, though only 54% surgeons reported routinely prescribing extended VTE prophylaxis following CRC surgery. Patient compliance and insurance issues were identified as the most common barriers. Targeted interventions at the surgeon, patient, and payer level are required to increase the use of extended VTE prophylaxis following CRC resection.


Assuntos
Cirurgia Colorretal , Cirurgiões , Tromboembolia Venosa , Humanos , Estados Unidos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/tratamento farmacológico , Cirurgia Colorretal/efeitos adversos , Anticoagulantes/uso terapêutico , Inquéritos e Questionários , Colo/cirurgia , Complicações Pós-Operatórias/prevenção & controle
14.
New Phytol ; 234(1): 122-136, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34716593

RESUMO

Shoot branching is regulated by multiple signals. Previous studies have indicated that sucrose may promote shoot branching through suppressing the inhibitory effect of the hormone strigolactone (SL). However, the molecular mechanisms underlying this effect are unknown. Here, we used molecular and genetic tools to identify the molecular targets underlying the antagonistic interaction between sucrose and SL. We showed that sucrose antagonizes the suppressive action of SL on tillering in rice and on the degradation of D53, a major target of SL signalling. Sucrose inhibits the gene expression of D3, the orthologue of the Arabidopsis F-box MAX2 required for SL signalling. Overexpression of D3 antagonizes sucrose inhibition of D53 degradation and enables the SL inhibition of tillering under high sucrose. Sucrose prevents SL-induced degradation of D14, the SL receptor involved in D53 degradation. In contrast to D3, D14 overexpression enhances D53 protein levels and sucrose-induced tillering, even in the presence of SL. Our results show that sucrose inhibits SL response by affecting key components of SL signalling and, together with previous studies reporting the inhibition of SL synthesis by nitrate and phosphate, demonstrate the central role played by SLs in the regulation of plant architecture by nutrients.


Assuntos
Arabidopsis , Oryza , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Lactonas/metabolismo , Lactonas/farmacologia , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sacarose/metabolismo , Sacarose/farmacologia
15.
Plant Physiol ; 185(4): 1722-1744, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33793928

RESUMO

Moderate leaf rolling is beneficial for leaf erectness and compact plant architecture. However, our understanding regarding the molecular mechanisms of leaf rolling is still limited. Here, we characterized a semi-dominant rice (Oryza sativa L.) mutant upward rolled leaf 1 (Url1) showing adaxially rolled leaves due to a decrease in the number and size of bulliform cells. Map-based cloning revealed that URL1 encodes the homeodomain-leucine zipper (HD-Zip) IV family member RICE OUTERMOST CELL-SPECIFIC 8 (ROC8). A single-base substitution in one of the two conserved complementary motifs unique to the 3'-untranslated region of this family enhanced URL1 mRNA stability and abundance in the Url1 mutant. URL1 (UPWARD ROLLED LEAF1) contains an ethylene-responsive element binding factor-associated amphiphilic repression motif and functions as a transcriptional repressor via interaction with the TOPLESS co-repressor OsTPL2. Rather than homodimerizing, URL1 heterodimerizes with another HD-ZIP IV member ROC5. URL1 could bind directly to the promoter and suppress the expression of abaxially curled leaf 1 (ACL1), a positive regulator of bulliform cell development. Knockout of OsTPL2 or ROC5 or overexpression of ACL1 in the Url1 mutant partially suppressed the leaf-rolling phenotype. Our results reveal a regulatory network whereby a transcriptional repression complex composed of URL1, ROC5, and the transcriptional corepressor TPL2 suppresses the expression of the ACL1 gene, thus modulating bulliform cell development and leaf rolling in rice.


Assuntos
Oryza/citologia , Oryza/crescimento & desenvolvimento , Oryza/genética , Folhas de Planta/citologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/genética , Fatores de Transcrição/metabolismo , Proliferação de Células/genética , Proliferação de Células/fisiologia , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Mutação , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo
16.
Plant Physiol ; 186(1): 497-518, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33591317

RESUMO

Leaf morphology influences photosynthesis, transpiration, and ultimately crop yield. However, the molecular mechanism of leaf development is still not fully understood. Here, we identified and characterized the narrow leaf21 (nal21) mutant in rice (Oryza sativa), showing a significant reduction in leaf width, leaf length and plant height, and increased tiller number. Microscopic observation revealed defects in the vascular system and reduced epidermal cell size and number in the nal21 leaf blade. Map-based cloning revealed that NAL21 encodes a ribosomal small subunit protein RPS3A. Ribosome-targeting antibiotics resistance assay and ribosome profiling showed a significant reduction in the free 40S ribosome subunit in the nal21 mutant. The nal21 mutant showed aberrant auxin responses in which multiple auxin response factors (ARFs) harboring upstream open-reading frames (uORFs) in their 5'-untranslated region were repressed at the translational level. The WUSCHEL-related homeobox 3A (OsWOX3A) gene, a key transcription factor involved in leaf blade lateral outgrowth, is also under the translational regulation by RPS3A. Transformation with modified OsARF11, OsARF16, and OsWOX3A genomic DNA (gDNA) lacking uORFs rescued the narrow leaf phenotype of nal21 to a better extent than transformation with their native gDNA, implying that RPS3A could regulate translation of ARFs and WOX3A through uORFs. Our results demonstrate that proper translational regulation of key factors involved in leaf development is essential to maintain normal leaf morphology.


Assuntos
Oryza/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas Ribossômicas/genética , Oryza/crescimento & desenvolvimento , Folhas de Planta/genética , Proteínas de Plantas/metabolismo , Proteínas Ribossômicas/metabolismo
17.
Ann Surg Oncol ; 29(11): 6606-6614, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35672624

RESUMO

BACKGROUND: Patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) are frequently admitted to the intensive care unit (ICU) for mitigation of potential complications, although ICU length of stay (LOS) is a significant driver of cost. This study asked whether a fiscal argument could be made for the selective avoidance of ICU admission after CRS/HIPEC. METHODS: Prospective data for select low-risk patients (e.g., lower peritoneal cancer index [PCI]) admitted to the intermediate care unit (IMC) instead of the ICU after CRS/HIPEC were matched with a historic cohort routinely admitted to the ICU. Cohort comparisons and the impact of the intervention on cost were assessed. RESULTS: The study matched 81 CRS/HIPEC procedures to form a cohort of 49 pre- and 15 post-intervention procedures for patients with similar disease burdens (mean PCI, 8 ± 6.7 vs. 7 ± 5.1). The pre-intervention patients stayed a median of 1 day longer in the ICU (1 day [IQR, 1-1 day] vs. 0 days [IQR, 0-0 days]) and had a longer LOS (8 days [IQR, 7-11 days] vs. 6 days [IQR, 5.5-9 days]). Complications and complication severity did not differ statistically. The median total hospital cost was lower after intervention ($30,845 [IQR, $30,181-$37,725] vs. $41,477 [IQR, $33,303-$51,838]), driven by decreased indirect fixed cost ($8984 [IQR, $8643-$11,286] vs. $14,314 [IQR, $12,206-$18,266]). In a weighted multiple variable linear regression analysis, the intervention was associated with a savings of $2208.68 per patient. CONCLUSIONS: Selective admission to the IMC after CRS/HIPEC was associated with $2208.68 in savings per patient without added risk. In this era of cost-conscious practice of medicine, these data highlight an opportunity to decrease cost by more than 5% for patients undergoing CRS/HIPEC.


Assuntos
Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Cuidados Críticos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/terapia , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
18.
Support Care Cancer ; 30(4): 3419-3427, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997315

RESUMO

INTRODUCTION: Cancer patients' sources of distress are often unaddressed, and patient-reported distress data could be utilized to identify those with unmet and impending care needs. We explored the association between moderate/severe distress and healthcare utilization in a large sample of non-small cell lung cancer (NSCLC) and non-colorectal gastrointestinal cancer patients. METHODS AND MATERIALS: Adult patients treated between July 2013 and March 2019. Data from the NCCN Distress Thermometer (DT) and the accompanying "Problem List" were extracted from the EHR. A DT score of ≥ 4 indicates "actionable distress." Statistical analysis was performed using descriptive analysis for patient characteristics, clinical outcomes, and sources of distress. Generalized linear mixed models were fit to determine the relationship between distress and healthcare utilization (hospitalization, emergency department (ED) visit, or both). RESULTS: The ten most frequently reported problems were from the Physical and Emotional domains of the Problem List. Distress was mostly related to physical symptoms (pain, fatigue) and emotional issues (worry, fears, sadness, nervousness). Patients with actionable distress generally reported more problems across all their visits. Actionable distress was associated with higher odds of the composite outcome measure of hospitalization or visiting the ED, within both the next 3 months (OR = 1.37; 95% CI = 1.19, 1.58; p < 0.001) and 6 months (OR = 1.19; 95% CI = 1.03, 1.37; p = 0.019). CONCLUSION: Patients with significant distress had marked utilization of ED and inpatient services. DT scores are a source of untapped data in the EHR that can highlight patients in need of intervention, including palliative care and cancer support services.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias , Carcinoma Pulmonar de Células não Pequenas/complicações , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , Neoplasias/psicologia , Cuidados Paliativos/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia
19.
Genomics ; 113(1 Pt 2): 1029-1043, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33157261

RESUMO

Rice is an important cereal crop that serves as staple food for more than half of the world population. Abiotic stresses resulting from changing climatic conditions are continuously threating its yield and production. Genes in APETALA-2 (AP2) family encode transcriptional regulators implicated during regulation of developmental processes and abiotic stress responses but their identification and characterization in indica rice was still missing. In this context, twenty-six genes distributed among eleven chromosomes in Indica rice encoding AP2 transcription-factor subfamily were identified and their diverse haplotypes were studied. Phylogenetic analysis of OsAP2 TF family-members grouped them into three clades indicating conservation of clades among cereals. Segmental duplications were observed to be principal route of evolution, supporting the higher positive selection-pressure, which were estimated to be originated about 10.57 to 56.72 million years ago (MYA). Conserved domain analysis and intron-exon distribution pattern of identified OsAP2s revealed their exclusive distribution among the specific clades of the phylogenetic tree. Moreover, the members of osa-miR172 family were also identified potentially targeting four OsAP2 genes. The real-time quantitative expression profiling of OsAP2s under heat stress conditions in contrasting indica rice genotypes revealed the differential expression pattern of OsAP2s (6 genes up-regulated and 4 genes down-regulated) in stress- and genotype-dependent manner. These findings unveiled the evolutionary pathways of AP2-TF in rice, and can help the functional characterization under developmental and stress responses.


Assuntos
Evolução Molecular , Resposta ao Choque Térmico , Oryza/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , MicroRNAs/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Seleção Genética , Fatores de Transcrição/metabolismo
20.
J Pak Med Assoc ; 72(Suppl 4)(11): S16-S24, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36591623

RESUMO

OBJECTIVE: To identify populations at risk for lost to follow-up while undergoing management of brain tumours in a low-resource setting. Methods: A retrospective study was conducted at the neurosurgical centre on patients presenting with a brain tumour from January 1, 2019, to December 31, 2019. Data on demographic characteristics, surgical characteristics, treatment, and outcomes such as mortality status, were collected by manual chart review. LTFU was defined as patients discontinuing clinical follow-up at the institute of surgical consultation within two years from the initial visit. Univariate (odds ratio) and multivariate (b-coefficient) logistic regression were used to determine factors' significance for LTFU. RESULTS: From a total of 2750 patients from 32 centres, 1140 (41.4%) were LTFU during the study period. Of these 1140 LTFU patients, 156 (13.7%) were LTFU without any intervention, 984 (86.3%) were LTFU after the primary surgery, and 872 (76.5%) patients were LTFU without any adjuvant treatment. On univariate analysis annual hospital case volume (p< 0.001), older age group (15-39 years (p=0.037) and ?40 years (p= 0.016)), and non-surgical treatment (p<=0.026) correlated with a higher risk of LTFU. Belonging to the middle-class cohort was correlated with a better chance of follow up (p=0.001). Multivariate analysis demonstrated that larger centres had the largest b-coefficient of 1.53 (95% CI= 1.3-1.8, p< 0.001). CONCLUSIONS: Our study demonstrated that almost half of patients diagnosed with brain tumours were LTFU within two years of diagnosis. Larger centres, non-surgical treatment, and older age seem to be associated with higher LTFU. Identifying vulnerable populations will allow the need-based provision of care and follow-up to improve health outcomes.


Assuntos
Neoplasias Encefálicas , Infecções por HIV , Humanos , Idoso , Estudos Retrospectivos , Perda de Seguimento , Paquistão/epidemiologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Infecções por HIV/tratamento farmacológico , Seguimentos , Fatores de Risco
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