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Frontiers in Oncology 2024Regorafenib improves overall survival (OS) of patients with advanced progressive gastrointestinal stromal tumors (GISTs) after standard chemotherapy in phase III trials...
BACKGROUND
Regorafenib improves overall survival (OS) of patients with advanced progressive gastrointestinal stromal tumors (GISTs) after standard chemotherapy in phase III trials in the 3rd-line setting. This large-scale, prospective observational study evaluated the safety and effectiveness of regorafenib in Japanese patients with GIST in a real-world clinical setting.
METHODS
Patients with GIST received oral regorafenib at a maximum daily dose of 160 mg for weeks 1-3 of each 4-week cycle (dose could be modified at investigator's discretion). The primary objective was to assess safety, particularly significant adverse drug reactions (ADRs), as well as the frequency of occurrence of ADRs, hand and foot syndrome (HFS), discontinuation of treatment due to disease progression and adverse events. A Cox proportional hazards model was used to evaluate associations between OS or time to treatment failure (TTF) and baseline characteristics or HFS.
RESULTS
Between August 2013 and March 2021, 143 evaluable patients were enrolled. ADRs occurred in 90.2% of patients and led to treatment discontinuation in 28.3%. The most frequent ADRs were HFS, hypertension, and liver injury. The overall response rate was 11.3% and disease control rate 56.5% (RECIST) based on investigators' assessments. Median OS was 17.4 months (95% CI 14.24-23.68). Median TTF was 5.3 (95% CI 4.0-6.5) months. Improved OS and TTF responses occurred in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1.
CONCLUSION
The outcomes in this real-world study were consistent with those seen in clinical trials. No new safety concerns were identified.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov, identifier NCT01933958.
PubMed: 38952554
DOI: 10.3389/fonc.2024.1412144 -
Frontiers in Oncology 2024Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly...
BACKGROUND
Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity.
METHODS
We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering , , , , , , , , but not ) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]).
RESULTS
Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in and 1.8% in . Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in , or were identified in 3.9% of cases, while mutations in were found in 2.1%. No mutations were detected, nor were TMB high or MSI cases.
CONCLUSION
We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives.
PubMed: 38952553
DOI: 10.3389/fonc.2024.1372947 -
Pakistan Journal of Medical Sciences Jul 2024Chronic kidney disease (CKD) patients are at high risk of heart failure (HF) and both share similar risk factors, including diabetes and elevated blood Pressure (B.P)....
OBJECTIVE
Chronic kidney disease (CKD) patients are at high risk of heart failure (HF) and both share similar risk factors, including diabetes and elevated blood Pressure (B.P). Aim of this study was to determine the impact of sacubitril/valsartan on the quality of life (QOL) and ejection fraction (EF) of patients with HF with and without CKD.
METHODS
Single center (Doctors Hospital Lahore), observational study with longitudinal follow up, on 104 HF patients from July 2019 to July 2020. HF was diagnosed on both clinical and echo parameters. New York Heart Association Class II-IV, EF less than or equal to 40% HF with reduced EF and stage three CKD patients were included. Sacubitril/Valsartan was prescribed at a starting daily dose of 50mg and then up titrated to 400mg. Patients were followed up with clinical evaluation, QOL assessment, echocardiography and biochemical profile at one, four, eight and 12 months.
RESULTS
Gender, age, and diabetes mellitus between CKD and non-CKD patients were noted to be statistically different, defined as p<0.05. CKD patients' QOL increased from 45.15 to 57.57 from baseline to 12 months (p-value<0.01). Non-CKD patients' QOL increased from 48.07 to 56.25. In CKD patients, EF increased from 27.87% to 29.29% from baseline to 12 months (p-value 0.03) whereas in non-CKD patients EF improved from 29.42% to 31.43%.
CONCLUSION
Sacubitril/ valsartan improves QOL in patients of HF with reduced EF both with and without CKD. Clinical improvement was independent of Left Ventricular EF as measured by QOL. Thus, QOL is a useful tool to assess the drug's beneficial effect.
PubMed: 38952524
DOI: 10.12669/pjms.40.6.7892 -
Journal of Physical Therapy Science Jul 2024[Purpose] This study aimed to determine the characteristics of regional phase angles based on locomotion level among older Japanese females requiring long-term care in a...
[Purpose] This study aimed to determine the characteristics of regional phase angles based on locomotion level among older Japanese females requiring long-term care in a health facility. [Participants and Methods] This was a cross-sectional observational study. The participants included 91 residents (mean age ± standard deviation: 90.2 ± 5.6 years) admitted to an older health facility. Based on their indoor locomotion status, the participants were divided into three groups: group I, able to walk with or without walking aids; group II, able to move in a wheelchair without assistance; and group III, able to move in a wheelchair with assistance. The regional phase angle was measured using a bioimpedance device. [Results] Significant differences were observed in the regional phase angle of the upper limbs between groups I and III and between groups II and III; in that of the lower limbs among all groups; and in that of the trunk between groups I and II and between groups I and III. [Conclusion] The level of locomotion may be explained by the regional phase angles of the lower limbs.
PubMed: 38952460
DOI: 10.1589/jpts.36.392 -
Frontiers in Endocrinology 2024Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable... (Observational Study)
Observational Study
Assessing causal associations of blood counts and biochemical indicators with pulmonary arterial hypertension: a Mendelian randomization study and results from national health and nutrition examination survey 2003-2018.
BACKGROUND
Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH).
METHODS
A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 to verify the relationship.
RESULTS
The MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH.
CONCLUSION
Our study reveals a causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension. These findings offer novel insights into the etiology and pathological mechanisms of PAH, and emphasizes the important value of these markers as potential targets for the prevention and treatment of PAH.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Female; Male; Middle Aged; Biomarkers; Nutrition Surveys; Pulmonary Arterial Hypertension; Adult; Blood Cell Count; Polymorphism, Single Nucleotide; Aged; Bilirubin; Platelet Count
PubMed: 38952391
DOI: 10.3389/fendo.2024.1418835 -
Frontiers in Epidemiology 2024Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however,...
BACKGROUND
Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population.
METHODS AND RESULTS
Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS national registries (Aruba, Dominican Republic, Honduras, and Panama), data on prevalence, phenotypes and demographics. Expanded Disability Status Scale (EDSS), and therapeutic schemes were included. ENHANCE data from 758 patients disclosed 79.8% of Mestizo ethnicity; 72.4% female; median age at onset 31.0 years and 33.2 at diagnosis. The highest incidence rate was from Aruba, 2.3-3.5 × 100,000 inhabitants, and the lowest, 0.07-0.15 × 100,000, from Honduras. Crude prevalence rates per 100,000 inhabitants fluctuated from 27.3 (Aruba) to 1.0 (Honduras). Relapsing MS accounted for 87.4% of cases; EDSS <3.0 determined in 66.6% (mean disease duration: 9.1 years, SD ± 5.0); CSF oligoclonal bands 85.7%, and 87% of subjects hydroxyvitamin D deficient. Common initial therapies were interferon and fingolimod. Switching from interferon to fingolimod was the most common escalation step. The COVID-19 pandemic affected follow-up aspects of these studies.
CONCLUSION
This is the first study providing data on frequencies and clinical characteristics from 8 countries from the Central American and Caribbean region, addressing MS as an emergent epidemiologic disorder. More studies from these areas are encouraged.
PubMed: 38952354
DOI: 10.3389/fepid.2024.1368675 -
Clinical Transplantation Jul 2024We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving... (Observational Study)
Observational Study
BACKGROUND
We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy.
METHODS
A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events.
RESULTS
Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%).
CONCLUSIONS
In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Platelet Aggregation Inhibitors; Anticoagulants; Follow-Up Studies; Heart Transplantation; Prognosis; Blood Transfusion; Risk Factors; Aged; Adult; Dabigatran; Postoperative Complications
PubMed: 38952201
DOI: 10.1111/ctr.15380 -
Neuroepidemiology Jun 2024Knowledge gaps exist about the usefulness and extent of blood tests and nerve conduction studies in the workup of polyneuropathy. We hypothesize that a limited workup...
BACKGROUND
Knowledge gaps exist about the usefulness and extent of blood tests and nerve conduction studies in the workup of polyneuropathy. We hypothesize that a limited workup improves costs spend on diagnostics without loss of diagnostic reliability or disadvantageous effect on treatment choice in many patients with a clinical diagnosis chronic polyneuropathy. We aim to determine which investigations are necessary in the workup of patients with suspected chronic polyneuropathy clinically diagnosed by neurologists in an outpatient clinic and will perform an early health technology assessment.
METHODS
This is a prospective multi-center quality in health care evaluation. We compare two diagnostic strategies, both performed on all participants: the standard care by each patient's neurologist, and the proposed (limited) workup by the study panel members consisting of neurologists with experience in neuromuscular diseases.
RESULTS
The primary outcome is effectiveness of a limited workup expressed as concordance between the patient's neurologist diagnosis and the panel diagnosis. This will be related to differences in costs and impact on treatment or patient management otherwise. Other outcomes are burden/gain for the patient in terms of number of investigations, time to diagnosis, hospital visits, sick-leave, loss of productivity, expenses, experienced quality of care.
CONCLUSION
This multicenter prospective observational study on quality in healthcare will provide improved evidence about the components of a cost-effective workup for patients with chronic polyneuropathy.
PubMed: 38952135
DOI: 10.1159/000539957 -
JMIR Public Health and Surveillance Jun 2024Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI),... (Observational Study)
Observational Study
BACKGROUND
Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI), targeted and rapid interventions can be facilitated that prevent COVID-19 outbreaks without primary reliance on testing.
OBJECTIVE
This study aims to assess the temporal relationship between confirmed SARS-CoV-2 infections and self-reported and health care provider-reported CLI in university and county settings, respectively.
METHODS
We collected aggregated COVID-19 testing and symptom reporting surveillance data from Cornell University (2020-2021) and Tompkins County Health Department (2020-2022). We used negative binomial and linear regression models to correlate confirmed COVID-19 case counts and positive test rates with CLI rate time series, lagged COVID-19 cases or rates, and day of the week as independent variables. Optimal lag periods were identified using Granger causality and likelihood ratio tests.
RESULTS
In modeling undergraduate student cases, the CLI rate (P=.003) and rate of exposure to CLI (P<.001) were significantly correlated with the COVID-19 test positivity rate with no lag in the linear models. At the county level, the health care provider-reported CLI rate was significantly correlated with SARS-CoV-2 test positivity with a 3-day lag in both the linear (P<.001) and negative binomial model (P=.005).
CONCLUSIONS
The real-time correlation between syndromic surveillance and COVID-19 cases on a university campus suggests symptom reporting is a viable alternative or supplement to COVID-19 surveillance testing. At the county level, syndromic surveillance is also a leading indicator of COVID-19 cases, enabling quick action to reduce transmission. Further research should investigate COVID-19 risk using syndromic surveillance in other settings, such as low-resource settings like low- and middle-income countries.
Topics: Humans; COVID-19; Retrospective Studies; Universities; Sentinel Surveillance
PubMed: 38952000
DOI: 10.2196/54551 -
BMC Anesthesiology Jun 2024Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of... (Observational Study)
Observational Study
PURPOSE
Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of children was assessed.
MATERIALS AND METHODS
Children with severe caries who received dental treatment under general anesthesia and deep extubation between January 2017 and June 2023 were included in this study. Data were collected on the following variables: details and time of anesthesia, perioperative vital signs, and incidence of postoperative complications. The incidence of laryngeal spasm (LS) was considered to be the primary observation indicator.
RESULTS
The perioperative data obtained from 195 children undergoing dental treatment was reviewed. The median age was 4.2 years (range: 2.3 to 9.6 years), and the average duration of anesthesia was 2.56 h (range 1 to 4.5 h). During intubation with a videoscope, purulent mucus was found in the pharyngeal cavity of seven children (3.6%); LS occurred in five of them (2.6%), and one child developed a fever (T = 37.8 °C) after discharge. Five children (2.6%) experienced emergence agitation (EA) in the recovery room. Also, 13 children (6.7%) experienced epistaxis; 10 had a mild experience and three had a moderate experience. No cases of airway obstruction (AO) and hypoxemia were recorded. The time to open eyes (TOE) was 16.3 ± 7.2 min. The incidence rate of complications was 23/195 (11.8%). Emergency tracheal reintubation was not required. Patients with mild upper respiratory tract infections showed a significantly higher incidence of complications (P < 0.001).
CONCLUSIONS
Propofol-assisted deep extubation is a suitable technique that can be used for pediatric patients who exhibited non-cooperation in the outpatient setting. Epistaxis represents the most frequently encountered complication. Preoperative upper respiratory tract infection significantly increases the risk of complications. The occurrence of EA was notably lower than reported in other studies.
Topics: Humans; Airway Extubation; Child, Preschool; Retrospective Studies; Propofol; Child; Male; Female; Anesthetics, Intravenous; Anesthesia, General; Postoperative Complications; Laryngismus; Intubation, Intratracheal; Anesthesia, Dental
PubMed: 38951786
DOI: 10.1186/s12871-024-02599-2