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1.
World J Clin Pediatr ; 13(1): 87713, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38596436

RESUMO

BACKGROUND: Maintenance rates of exclusive breastfeeding (EBF) worldwide are low, thus, one of the objectives of the summary of policies on breastfeeding (BF) in world nutrition goals for 2025 are that at least 50% of infants under six months of age receive EBF that year. The Objective of this study is to document the rates of EBF in children born in San Ignacio University Hospital (HUSI) and identify factors associated with maintenance. AIM: To document the percentages of EBF in those that were born at HUSI and identify factors associated to their maintenance. METHODS: This is a study of cases and controls in an analytic, retrospective cohort that took children born alive between January 2016 and January 2019 at HUSI located in the city of Bogotá, Colombia. RESULTS: Receiving information about BF at HUSI was able to maintain EBF up until 4 mo (OR = 1.65; 95%CI: 1.02-2.66). The presence of gynecologic and obstetric comorbidities (OR = 0.32; 95%CI: 0.12-0.83), having mastitis (OR = 0.56; 95%CI: 0.33-0.94), and receiving information from mass media (OR = 0.52; 95%CI: 0.31-0.84) are factors associated with not maintaining EBF. CONCLUSION: Receiving education at a Women- and Child-Friendly Institution was the only significant factor to achieve EBF until 4 mo, with a frequency greater than the one reported in the country, which matches multiple studies where counseling and individualized support on BF achieve this purpose. Knowledge about BF and early detection of obstetric/gynecologic complications must be strengthened among the healthcare staff in charge of mothers during post-partum. Additionally, strategies must be promoted to continue BF such as creating milk banks with the objective of increasing BF rates even when mothers return to work.

2.
J Invertebr Pathol ; 204: 108081, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38458349

RESUMO

Epizootics of the entomopathogenic fungus Metarhizium rileyi regulate lepidopteran populations in soybean, cotton, and peanut agroecosystems to the point that insecticide applications could be unnecessary. However, the contribution and how different strains operate during the epizootic are unknown. Several unanswered questions remain: 1. How many genotypes of M. rileyi are present during an epizootic? 2. Which genotype is the most common among them? 3. Are the genotypes involved in annual epizootics at the same location the same? Therefore, the development of molecular markers to accurately identify these genotypes is very important to answer these questions. SSR primers were designed by prospecting in silico to discriminate genotypes and infer the genetic diversity of M. rileyi isolates from the collection kept at Embrapa Soybean. We tested 13 SSR markers on 136 isolates to identify 43 clones and 12 different genetic clusters, with genetic diversity ranging from Hs = 0.15 (cluster I) to Hs = 0.41 (cluster IV) and an average diversity of 0.24. No clusters were categorically distinguished based on hosts or geographical origin using Bayesian clustering analysis. Nonetheless, some clusters comprised most of the isolates with a common geographic origin; for example, cluster VIII was mainly composed of isolates from Central-western Brazil, cluster II from Southern Brazil, and cluster XII from Quincy, Northern Florida, in the United States. Underrepresented regions (few isolates) from Pacific Island nations of Japan, the Philippines, and Indonesia (specifically from Java) were placed into clusters IX and X. Although the analyzed isolates displayed evidence of clonal structure, the genetic diversity indices suggest a potential for the species to adapt to different environmental conditions.

3.
J Nucl Med ; 65(4): 520-526, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38485270

RESUMO

Radiation pneumonitis (RP) that develops early (i.e., within 3 mo) (RPEarly) after completion of concurrent chemoradiation (cCRT) leads to treatment discontinuation and poorer survival for patients with stage III non-small cell lung cancer. Since no RPEarly risk model exists, we explored whether published RP models and pretreatment 18F-FDG PET/CT-derived features predict RPEarly Methods: One hundred sixty patients with stage III non-small cell lung cancer treated with cCRT and consolidative immunotherapy were analyzed for RPEarly Three published RP models that included the mean lung dose (MLD) and patient characteristics were examined. Pretreatment 18F-FDG PET/CT normal-lung SUV featured included the following: 10th percentile of SUV (SUVP10), 90th percentile of SUV (SUVP90), SUVmax, SUVmean, minimum SUV, and SD. Associations between models/features and RPEarly were assessed using area under the receiver-operating characteristic curve (AUC), P values, and the Hosmer-Lemeshow test (pHL). The cohort was randomly split, with similar RPEarly rates, into a 70%/30% derivation/internal validation subset. Results: Twenty (13%) patients developed RPEarly Predictors for RPEarly were MLD alone (AUC, 0.72; P = 0.02; pHL, 0.87), SUVP10, SUVP90, and SUVmean (AUC, 0.70-0.74; P = 0.003-0.006; pHL, 0.67-0.70). The combined MLD and SUVP90 model generalized in the validation subset and was deemed the final RPEarly model (RPEarly risk = 1/[1+e(- x )]; x = -6.08 + [0.17 × MLD] + [1.63 × SUVP90]). The final model refitted in the 160 patients indicated improvement over the published MLD-alone model (AUC, 0.77 vs. 0.72; P = 0.0001 vs. 0.02; pHL, 0.65 vs. 0.87). Conclusion: Patients at risk for RPEarly can be detected with high certainty by combining the normal lung's MLD and pretreatment 18F-FDG PET/CT SUVP90 This refined model can be used to identify patients at an elevated risk for premature immunotherapy discontinuation due to RPEarly and could allow for interventions to improve treatment outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonite por Radiação , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pneumonite por Radiação/diagnóstico por imagem , Pneumonite por Radiação/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18/uso terapêutico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Pulmão , Imunoterapia , Estudos Retrospectivos
4.
Microorganisms ; 12(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38543658

RESUMO

Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%; p < 0.001) and one year mortality (57.1% vs. 27.6%; p < 0.001) than operated patients. The main reason for surgical rejection was high surgical risk (57.1%) and the highest mortality when the cause were severe neurological conditions (76%). When the endocarditis team took the decision not to operate (25.5% of the patients), in-hospital (7%) and one-year mortality (17%) were low. In-hospital mortality associated with each surgical indication was 67% in heart failure, 53% in uncontrolled infection and 45% in prevention of embolisms (p < 0.001). Heart failure (OR: 2.26 CI95%: 1.29-3.96; p = 0.005), Staphylococcus aureus (OR: 3.17; CI95%: 1.72-5.86; p < 0.001) and persistent infection (OR: 5.07 CI95%: 2.85-9.03) are the independent risk factors of in-hospital mortality. One third of the patients with left-sided IE and formal surgical indication are rejected for surgery. In-hospital mortality is very high, especially when heart failure is the indication for surgery and when severe neurological conditions the reason for rejection. Short term prognosis of patients rejected by a specialized endocarditis team is favorable.

5.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38521440

RESUMO

INTRODUCTION AND OBJECTIVES: Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. METHODS: From 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. RESULTS: The prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. CONCLUSIONS: Valvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

7.
J Sci Med Sport ; 27(4): 234-242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395699

RESUMO

OBJECTIVES: To examine the effectiveness of different exercise-based interventions to mitigate the risk of anterior cruciate ligament injury in football players, and to determine which is the most appropriate for them, specifically for female football players. DESIGN: Four databases were accessed in July 2023 using the keywords football, soccer, athletic injuries, anterior cruciate ligament, knee injuries, injury prevention, exercise-based programme, and risk factor. METHODS: Randomised controlled trials that evaluated any exercise-based injury prevention intervention compared with a control group on the prevention of anterior cruciate ligament injury in football players were included. RESULTS: Eleven studies were included. Data were presented as logarithm hazard ratio, credible intervals and standard deviation. FIFA 11+ was the most effective in reducing anterior cruciate ligament injury risk in football players (logarithm hazard ratio = -1.23 [95% credible intervals: -2.20, -0.35]; SD = 0.47), followed by the Knäkontroll programme (logarithm hazard ratio = -0.76 [95% credible intervals: -1.60, -0.03]; standard deviation = 0.42). For females, only Knäkontroll had a significant impact on reducing the risk of anterior cruciate ligament injury (logarithm hazard ratio = -0.62 [95% credible intervals: -1.71, 0.62]; standard deviation = 0.58). CONCLUSIONS: Our results support the use of FIFA 11+ and Knäkontroll to mitigate injury incidence at overall level. However, the effectiveness of these interventions changed when adjusting for females. Knäkontroll is postulated as the programme with the greatest preventive nature, although these results should be interpreted with caution due to the lack of the sample.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos em Atletas , Futebol , Humanos , Feminino , Lesões do Ligamento Cruzado Anterior/prevenção & controle , Lesões do Ligamento Cruzado Anterior/epidemiologia , Futebol/lesões , Metanálise em Rede , Traumatismos em Atletas/prevenção & controle , Terapia por Exercício/métodos
8.
Curr Aging Sci ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38317476

RESUMO

BACKGROUND: Elderly people have multiple comorbidities that often require treatment with multiple medications. Having strategies to lessen the risks associated with pharmacological interactions and potentially inadequate prescribing (PIP) is of major importance. The STOPP- START criteria are useful in identifying PIP along with other tools, such as LASA (look alike/sound alike) drugs and high-risk medications (HRM). OBJECTIVE: We aimed to clinically and sociodemographically characterize the population with PIP according to the STOPP-START criteria in hospitalized elderly patients over 6 months in a third-level hospital in Colombia, South America. We also aimed to calculate the prevalence of PIP, LASA drugs and HRM and to identify other problems related with medication. Finally, we proposed an algorithm for the identification of PIP in this population. METHODS AND MATERIALS: This was a descriptive, cross-sectional study in hospitalized patients older than 60 years during the first semester of 2021 to identify PIP according to STOPP- START criteria. An analysis of clinical and sociodemographic variables was conducted, as well as the construction of an algorithm to identify PIP in the elderly in a semiautomated way. Data were collected and analyzed using the software SPSS 2021, using descriptive statistics and measures of central tendency. RESULTS: The prevalence of PIP in the study population was 25%. Furthermore, 60% of patients had one problem related to medication, and 27% used at least one LASA drug or HRM. CONCLUSION: This study allows one to characterize, for the first time, the Colombian population prone to PIP, as well as the construction of an algorithm that identifies PIP in a semiautomated way.

9.
BMJ ; 384: e075847, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355154

RESUMO

OBJECTIVE: To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions. DESIGN: Systematic review and network meta-analysis. METHODS: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Bayesian arm based, multilevel network meta-analyses were performed for the primary analyses. Quality of the evidence for each arm was graded using the confidence in network meta-analysis (CINeMA) online tool. DATA SOURCES: Cochrane Library, Medline, Embase, SPORTDiscus, and PsycINFO databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any randomised trial with exercise arms for participants meeting clinical cut-offs for major depression. RESULTS: 218 unique studies with a total of 495 arms and 14 170 participants were included. Compared with active controls (eg, usual care, placebo tablet), moderate reductions in depression were found for walking or jogging (n=1210, κ=51, Hedges' g -0.62, 95% credible interval -0.80 to -0.45), yoga (n=1047, κ=33, g -0.55, -0.73 to -0.36), strength training (n=643, κ=22, g -0.49, -0.69 to -0.29), mixed aerobic exercises (n=1286, κ=51, g -0.43, -0.61 to -0.24), and tai chi or qigong (n=343, κ=12, g -0.42, -0.65 to -0.21). The effects of exercise were proportional to the intensity prescribed. Strength training and yoga appeared to be the most acceptable modalities. Results appeared robust to publication bias, but only one study met the Cochrane criteria for low risk of bias. As a result, confidence in accordance with CINeMA was low for walking or jogging and very low for other treatments. CONCLUSIONS: Exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other exercises, particularly when intense. Yoga and strength training were well tolerated compared with other treatments. Exercise appeared equally effective for people with and without comorbidities and with different baseline levels of depression. To mitigate expectancy effects, future studies could aim to blind participants and staff. These forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018118040.


Assuntos
Depressão , Transtorno Depressivo Maior , Humanos , Metanálise em Rede , Depressão/terapia , Transtorno Depressivo Maior/terapia , Teorema de Bayes , Exercício Físico , Antidepressivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Nano Lett ; 24(6): 1944-1950, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305174

RESUMO

Metal nanoparticles can photosensitize two-dimensional metal oxides, facilitating their electrical connection to devices and enhancing their abilities in catalysis and sensing. In this study, we investigated how individual silver nanoparticles interact with two-dimensional tin oxide and antimony-doped indium oxide using electron energy loss spectroscopy (EELS). The measurement of the spectral line width of the longitudinal plasmon resonance of the nanoparticles in absence and presence of 2D materials allowed us to quantify the contribution of chemical interface damping to the line width. Our analysis reveals that a stronger interaction (damping) occurs with 2D antimony-doped indium oxide due to its highly homogeneous surface. The results of this study offer new insight into the interaction between metal nanoparticles and 2D materials.

11.
Ann Thorac Surg ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38316378

RESUMO

BACKGROUND: Despite surgical resection, long-term survival of patients with resectable non-small cell lung cancer (NSCLC) remains poor. Adjuvant chemotherapy, the standard of care for locally advanced NSCLC, provides a marginal 5.4% benefit in survival. Immune checkpoint inhibitors (ICIs) have shown a significant survival benefit in some patients with advanced NSCLC and are being evaluated for perioperative use in resectable NSCLC. METHODS: We conducted a literature search using the PubMed online database to identify clinical trials of immunotherapy in resectable NSCLC and studies analyzing biomarkers and immune priming strategies. RESULTS: Building on previous phase I and II trials, randomized phase III trials have shown efficacy of neoadjuvant nivolumab, perioperative pembrolizumab, adjuvant atezolizumab, and adjuvant pembrolizumab in the treatment of NSCLC with improvement of event-free/disease-free survival of 24% to 42%, leading to United States Food and Drug Administration approval of these drugs in the treatment of resectable NSCLC. Three additional phase III trials have also recently reported the use of immunotherapy both before and after surgery, with pathologic complete response rates of 17% to 25%, significantly better than chemotherapy alone. Perioperative ICI therapy has comparable perioperative morbidity to chemotherapy alone and does not impair surgical outcomes. CONCLUSIONS: Perioperative immunotherapy, in combination with chemotherapy, is safe and improves outcomes in patients with resectable NSCLC. Questions regarding patient selection, the need for adjuvant ICI therapy after neoadjuvant chemoimmunotherapy, and the duration of perioperative immunotherapy remain to be answered by future trials.

12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38311023

RESUMO

INTRODUCTION AND OBJECTIVES: Our aim was to describe the contemporary epidemiological profile of infective endocarditis (IE) in Spain, and to evaluate variations in IE incidence, characteristics, and outcomes among the different Spanish regions (autonomous communities [AC]). METHODS: We conducted a retrospective, population-based study, using data obtained from national in-patient hospital activity of all patients discharged with a diagnosis of IE from hospitals included in the Spanish National Health System, from January 2016 to December 2019. Differences in the IE profile between the 17 Spanish AC were analyzed. RESULTS: A total of 9008 hospitalization episodes were identified during the study period. Standardized incidence of IE was 5.77 (95%CI, 5.12-6.41) cases per 100 000 population. Regarding predisposing conditions, 26.8% of episodes occurred in prosthetic valve carriers, 36.8% had some kind of valve heart disease, and 10.6% had a cardiac implantable electronic device. Significant differences were found between AC in terms of incidence, predisposing conditions, and microbiological profile. Cardiac surgery was performed in 19.3% of episodes in the total cohort, and in 33.4% of the episodes treated in high-volume referral centers, with wide variations among AC. Overall in-hospital mortality was 27.2%. Risk-adjusted mortality rates also varied significantly among regions. CONCLUSIONS: We found wide heterogeneity among Spanish AC in terms of incidence rates and the clinical and microbiological characteristics of IE episodes. The proportion of patients undergoing surgery was low and in-hospital mortality rates were high, with wide differences among regions. The development of regional networks with referral centers for IE could facilitate early surgery and improve outcomes.

13.
Lancet Healthy Longev ; 5(2): e108-e119, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38310891

RESUMO

BACKGROUND: Physical behaviours (ie, physical activity and sedentary behaviour) might have a role in the development of sarcopenia, although the evidence is unclear. We aimed to explore the association of total and intensity-specific levels of physical activity and sedentary behaviour with sarcopenia and its components (ie, muscle mass, muscle strength, and physical performance) in older adults. METHODS: We conducted a systematic review and meta-analysis and searched MEDLINE (via PubMed), Scopus, and Web of Science from inception to July 26, 2022, for peer-reviewed, observational studies or baseline data from randomised clinical trials conducted in older adults (ie, individual age ≥60 years or mean age ≥65 years) and published in English that reported on the association of physical activity or sedentary behaviour or both with sarcopenia (or its determinants: muscle mass or strength, and physical performance). Physical activity and sedentary behaviour were measured by any method. The main outcome was sarcopenia, which could be diagnosed by any means. Estimates were extracted and pooled using Bayesian meta-analytic models and publication bias was assessed using the Egger's test. This study is registered with PROSPERO, CRD42022315865. FINDINGS: We identified 15 766 records, of which 124 studies (230 174 older adults; 121 301 [52·7%] were female and 108 873 [47·3%] were male) were included in the systematic review. 86 studies were subsequently included in the meta-analysis. Higher levels of total physical activity were inversely associated with sarcopenia both cross-sectionally (21 studies, n=59 572; odds ratio 0·49, 95% credible interval 0·37-0·62) and longitudinally (four studies, n=7545; 0·51, 0·27-0·94). A protective association was also identified for moderate-to-vigorous physical activity in cross-sectional research (five studies, n=6787; 0·85, 0·71-0·99), whereas no association was identified for the remaining physical behaviours (ie, steps, light physical activity, or sedentary behaviour). INTERPRETATION: Total and moderate-to-vigorous physical activity are inversely associated with sarcopenia. These findings might support the importance of moderate-to-vigorous, rather than light, intensity physical activity-based interventions to prevent sarcopenia. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.


Assuntos
Sarcopenia , Masculino , Humanos , Feminino , Idoso , Sarcopenia/epidemiologia , Estudos Transversais , Teorema de Bayes , Força Muscular/fisiologia
14.
bioRxiv ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38352610

RESUMO

The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter smoothing out rapid changes. However, hemodynamic responses (their shape and timing) are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of fMRI signals, or the ability of fMRI to preserve fast information, should also vary substantially across the cortex. In this work we investigated how local differences in hemodynamic response timing impact the temporal specificity of fMRI. We conducted our research using ultra-high field (7T) fMRI at high spatiotemporal resolution, using the primary visual cortex (V1) as a model area for investigation. We used visual stimuli oscillating at slow and fast frequencies to probe the temporal specificity of individual voxels. As expected, we identified substantial variability in temporal specificity, with some voxels preserving their responses to fast neural activity more effectively than others. We investigated which voxels had the highest temporal specificity and related those to anatomical and vascular features of V1. We found that low temporal specificity is only weakly explained by the presence of large veins or cerebral cortical depth. Notably, however, temporal specificity depended strongly on a voxel's position along the anterior-posterior anatomical axis of V1, with voxels within the calcarine sulcus being capable of preserving close to 25% of their amplitude as the frequency of stimulation increased from 0.05-Hz to 0.20-Hz, and voxels nearest to the occipital pole preserving less than 18%. These results indicate that detection biases in high-resolution fMRI will depend on the anatomical and vascular features of the area being imaged, and that these biases will differ depending on the timing of the underlying neuronal activity. Importantly, this spatial heterogeneity of temporal specificity suggests that it could be exploited to achieve higher specificity in some locations, and that tailored data analysis strategies may help improve the detection and interpretation of fast fMRI responses.

15.
EMBO J ; 43(5): 666-694, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38279026

RESUMO

The efficacy of current antimitotic cancer drugs is limited by toxicity in highly proliferative healthy tissues. A cancer-specific dependency on the microtubule motor protein KIF18A therefore makes it an attractive therapeutic target. Not all cancers require KIF18A, however, and the determinants underlying this distinction remain unclear. Here, we show that KIF18A inhibition drives a modest and widespread increase in spindle assembly checkpoint (SAC) signaling from kinetochores which can result in lethal mitotic delays. Whether cells arrest in mitosis depends on the robustness of the metaphase-to-anaphase transition, and cells predisposed with weak basal anaphase-promoting complex/cyclosome (APC/C) activity and/or persistent SAC signaling through metaphase are uniquely sensitive to KIF18A inhibition. KIF18A-dependent cancer cells exhibit hallmarks of this SAC:APC/C imbalance, including a long metaphase-to-anaphase transition, and slow mitosis overall. Together, our data reveal vulnerabilities in the cell division apparatus of cancer cells that can be exploited for therapeutic benefit.


Assuntos
Ciclossomo-Complexo Promotor de Anáfase , Neoplasias , Humanos , Ciclossomo-Complexo Promotor de Anáfase/genética , Dineínas , Cinesinas/genética , Cinetocoros , Mitose , Neoplasias/genética
16.
Adv Radiat Oncol ; 9(1): 101284, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38260213

RESUMO

Purpose: Data are limited on radiation-induced lung toxicities (RILT) after multiple courses of lung stereotactic body radiation therapy (SBRT). We herein analyze a large cohort of patients to explore the clinical and dosimetric risk factors associated with RILT in such settings. Methods and Materials: A single institutional database of patients treated with multiple courses of lung SBRT between January 2014 and December 2019 was analyzed. Grade 2 or higher (G2+) RILT after the last course of SBRT was the primary endpoint. Composite plans were generated with advanced algorithms including deformable registration and equivalent dose adjustment. Logistic regression analyses were performed to examine correlations between patient or treatment factors including dosimetry and G2+ RILT. Risk stratification of patients and lung constraints based on acceptable normal tissue complication probability were calculated based on risk factors identified. Results: Among 110 eligible patients (56 female and 54 male), there were 64 synchronous (58.2%; defined as 2 courses of SBRT delivered within 30 days) and 46 metachronous (41.8%) courses of SBRT. The composite median lung V20, lung V5, and mean lung dose were 9.9% (interquartile range [IQR], 7.3%-12.4%), 32.2% (IQR, 25.5%-40.1%), and 7.0 Gy (IQR, 5.5 Gy-8.6 Gy), respectively. With a median follow-up of 21.1 months, 30 patients (27.3%) experienced G2+ RILT. Five patients (4.5%) developed G3 RILT, and 1 patient (0.9%) developed G4 RILT, and no patients developed G5 RILT. On multivariable regression analysis, female sex (odds ratio [OR], 4.35; 95% CI, 1.49%-14.3%; P = .01), synchronous SBRT (OR, 8.78; 95% CI, 2.27%-47.8%; P = .004), prior G2+ RILT (OR, 29.8; 95% CI, 2.93%-437%; P = .007) and higher composite lung V20 (OR, 1.18; 95% CI, 1.02%-1.38%; P = .030) were associated with significantly higher likelihood of G2+ RILT. Conclusions: Our data suggest an acceptable incidence of G2+ RILT after multiple courses of lung SBRT. Female sex, synchronous SBRT, prior G2+ RILT, and higher composite lung V20 may be risk factors for G2+ RILT.

17.
JCO Oncol Pract ; 20(4): 525-537, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38252900

RESUMO

PURPOSE: Hispanic and Latinx people in the United States are the fastest-growing ethnic group. However, previous studies in non-small-cell lung cancer (NSCLC) often analyze these diverse communities in aggregate. We aimed to identify differences in NSCLC stage at diagnosis in the US population, focusing on disaggregated Hispanic/Latinx individuals. METHODS: Data from the National Cancer Database from 2004 to 2018 identified patients with primary NSCLC. Individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression adjusting for age, facility type, income, educational attainment, comorbidity index, insurance, and year of diagnosis was used to create adjusted odds ratios (aORs), with higher odds representing diagnosis at later-stage NSCLC. RESULTS: Of 1,565,159 patients with NSCLC, 46,616 were Hispanic/Latinx (3.0%). When analyzed in the setting of race and ethnicity, Hispanic patients were more likely to be diagnosed with metastatic disease compared with non-Hispanic White (NHW) patients: 47.0% for Hispanic Black, 46.0% Hispanic White, and 44.3% of Hispanic other patients versus 39.1% of non-Hispanic White patients (P < .001 for all). By country of origin, 51.4% of Mexican, 41.7% of Puerto Rican, 44.6% of Cuban, 50.8% of South or Central American, 48.4% of Dominican, and 45.6% of other Hispanic patients were diagnosed with metastatic disease, compared with 39.1% of NHWs. Conversely, 20.2% of Mexican, 26.9% of Puerto Rican, 24.2% of Cuban, 22.5% of South or Central American, 23.7% of Dominican, and 24.5% of other Hispanic patients were diagnosed with stage I disease, compared with 30.0% of NHWs. All Hispanic groups were more likely to present with later-stage NSCLC than NHW patients (greatest odds for Mexican patients, aOR, 1.44; P < .001). CONCLUSION: Hispanic/Latinx patients with non-small-cell lung cancer were more likely to be diagnosed with advanced disease compared with NHWs. Disparities persisted upon disaggregation by both race and country of origin, with over half of Mexican patients with metastatic disease at diagnosis. Disparities among Hispanic/Latinx groups by race and by country of origin highlight the shortcomings of treating these groups as a monolith and underscore the need for disaggregated research and targeted interventions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estados Unidos/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Hispânico ou Latino , México
18.
Diabetes Care ; 47(2): 295-303, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241499

RESUMO

BACKGROUND: The optimal dose or type of physical activity to control glycosylated hemoglobin (HbA1c) in people with diabetes remains unknown. Current guidelines do not include consideration of baseline HbA1c for activity prescription. PURPOSE: To examine the dose-response relationship between physical activity and HbA1c (%) in individuals with type 2 diabetes. DATA SOURCES: A systematic search was performed in Embase, MEDLINE, Scopus, CINAHL, SPORTDiscus, and Web of Science. STUDY SELECTION: We included trials that involved participants diagnosed with type 2 diabetes that included any type of physical activity as intervention. DATA EXTRACTION: Pre- and postintervention HbA1c data, population and interventions characteristics, and descriptive statistics were collected to calculate change scores for each study arm. DATA SYNTHESIS: We used Bayesian random-effects meta-analyses to summarize high-quality evidence from 126 studies (6,718 participants). The optimal physical activity dose was 1,100 MET min/week, resulting in HbA1c reductions, ranging from -1.02% to -0.66% in severe uncontrolled diabetes, from -0.64% to -0.49% in uncontrolled diabetes, from -0.47% to -0.40% in controlled diabetes, and from -0.38% to -0.24% in prediabetes. LIMITATIONS: The time required to achieve these HbA1c reductions could not be estimated due to the heterogeneity between interventions' duration and protocols and the interpersonal variability of this outcome. CONCLUSIONS: The result of this meta-analysis provide key information about the optimal weekly dose of physical activity for people with diabetes with consideration of baseline HbA1c level, and the effectiveness of different types of active interventions. These results enable clinicians to prescribe tailored physical activity programs for this population.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Hemoglobinas Glicadas , Controle Glicêmico , Teorema de Bayes , Exercício Físico
19.
Am J Clin Oncol ; 47(2): 49-55, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38011024

RESUMO

BACKGROUND: Cancer cachexia is a syndrome of unintentional weight loss resulting in progressive functional impairment. Knowledge of radiation therapy utilization in patients with cancer cachexia is limited. We evaluated the use of curative and palliative-intent radiation for the management of patients with non-small cell lung cancer (NSCLC) with cachexia to determine whether tumor-directed therapy affected cachexia-associated outcomes. METHODS: Using an Institutional Tumor Registry, we evaluated all patients with stages of NSCLC treated at a tertiary care system from 2006 to 2013. We adopted the international consensus definition for cachexia, with staging designated by the registry and positron emission tomography. Radiotherapy delivery and intent were retrospectively assessed. RESULTS: In total, 1330 patients with NSCLC were analyzed. Curative-intent radiotherapy was utilized equally between patients with cachexia and non-cachexia with stages I to III NSCLC. Conversely, significantly more patients with stage IV disease and cachexia received palliative radiotherapy versus those without (74% vs 63%, P = 0.006). Cachexia-associated survival was unchanged irrespective of tumor-directed radiation therapy with curative or palliative intent. In fact, pretreatment cachexia was associated with reduced survival for patients with stage III NSCLC receiving curative-intent radiotherapy (median survival = 23.9 vs 15.0 mo, P = 0.009). Finally, multivariate analysis identified pretreatment cachexia as an independent variable associated with worsened survival (hazard ratio = 1.31, CI: 1.14,1.52). CONCLUSION: Patients with advanced NSCLC with cachexia received more palliative-intent radiation than those without weight loss. Tumor-directed therapy in either a curative or palliative approach failed to alter cachexia patient survival across all stages of the disease. These findings offer critical information on the appropriate utilization of radiation in the management of patients with NSCLC with cachexia.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Caquexia/etiologia , Caquexia/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Redução de Peso
20.
J Clin Epidemiol ; 165: 111213, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37949198

RESUMO

OBJECTIVES: To explore the impact of using different data standardization and scale-specific re-expression methods (i.e., processes to convert standardized data into scale-specific units) in meta-analyses using standardized mean differences (SMDs). STUDY DESIGN AND SETTING: We used data assessed by the Short Physical Performance Battery and the Barthel Index from a meta-analysis of randomized controlled trials which synthesized evidence of physical activity effectiveness on the functional capacity of hospitalized older adults. We standardized the data using study-specific pooled standard deviations (SDs), an internal, and an external SD references. Bayesian meta-analyses were performed for each method to compare the posterior distributions of the meta-analysis parameters. Posterior estimates were re-expressed into scale-specific units applying different methods established in the Cochrane guidelines. RESULTS: Meta-analysis estimates depend on the used standardization method. Analyses including data standardized using the largest SD reference presented lower estimates with less uncertainty in both scales. The method applied for re-expressing SMDs into scale-specific units impacted in their posterior clinical interpretation. The most similar results across models were obtained when using the same SD reference to standardize and re-express data. CONCLUSION: Different data standardization methods yielded different meta-analysis estimates on the SMD scale. To avoid the introduction of bias, the use of a single scale-specific SD reference to standardize data is recommended and instead of study-specific pooled sample SDs. Meta-analysis software packages may therefore change their default methods to allow this method by a single scale-specific SD. To re-express the SMDs into scale-specific units, we suggest the application of the same SD reference that was used for data standardization.


Assuntos
Exercício Físico , Humanos , Idoso , Teorema de Bayes , Viés
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