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ESMO Open Jun 2024Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a...
BACKGROUND
Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.
PATIENTS AND METHODS
Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients with ovarian cancer treated at the highest dose level. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1.
RESULTS
Our study included 49 patients. Maximum tolerated dose was not reached, but higher rates of adverse events were observed at higher dose levels. There were no treatment-related deaths. The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (n = 31; 63%), increased alanine aminotransferase (n = 26; 53%), decreased neutrophil count (n = 26; 53%), and decreased white blood cell count (n = 26; 53%). Most adverse events were either grade 1 or 2. In the 44 patients with evaluable disease, 12 (27%) had stable disease as the best overall response, including three patients with prolonged stable disease, and 4 patients (9%) achieved a partial response.
CONCLUSIONS
The combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors.
Topics: Humans; Paclitaxel; Female; Middle Aged; Aged; Neoplasms; Male; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Taxoids; Maximum Tolerated Dose; Syk Kinase
PubMed: 38914452
DOI: 10.1016/j.esmoop.2024.103486 -
PLoS Neglected Tropical Diseases Jun 2024Due to limited diagnostic capacity and availability of point-of-care tests, diagnosis of Clade I mpox in the geographical regions most affected is usually on clinical...
BACKGROUND
Due to limited diagnostic capacity and availability of point-of-care tests, diagnosis of Clade I mpox in the geographical regions most affected is usually on clinical grounds. This may be complicated due to the similarity between mpox and varicella (chickenpox) lesions. Visual assessment of lesions is also used for determining clinical progress and to assess patient outcomes in clinical trials. However, there has been no investigation into whether clinicians can (i) identify Clade I mpox compared to other viral lesions (ii) differentiate between Clade I mpox lesion stages.
METHODOLOGY/PRINCIPLE FINDINGS
The objective of this study was to evaluate inter-rater reliability and agreement between clinicians assessing lesions in patients with Clade I mpox. We presented experienced clinicians with 17 images of Clade I mpox or varicella and asked them to independently indicate the most likely diagnosis-mpox or varicella-and to categorise the lesions according to their stage. When selecting the most likely diagnosis, accuracy varied across all images, the inter-rater reliability was poor (κ = 0.223; z = 10.1) and agreement was moderate (Po = 68%). When categorising lesions according to their type, if a single lesion type was present in the image, inter-rater reliability was moderate (κ = 0.671, z = 40.6) and agreement was good (Po = 78%), but when multiple lesion types were shown in an image, both inter-rater reliability (κ = 0.153, z = 10.5) and agreement (Po = 29%) decreased substantially.
CONCLUSIONS
This study demonstrates that there are presently limitations in using visual assessment to diagnose Clade I mpox and evaluate lesion stage and treatment outcomes, which have an impact on clinical practice, public health and clinical trials. More robust indicators and tools are required to inform clinical, public-health, and research priorities, but these must be implementable in countries affected by mpox.
PubMed: 38913721
DOI: 10.1371/journal.pntd.0012087 -
PloS One 2024Asylum seekers, migrants, and refugees from African countries may have significant health needs, resulting in economic implications for receiving countries around the... (Review)
Review
BACKGROUND
Asylum seekers, migrants, and refugees from African countries may have significant health needs, resulting in economic implications for receiving countries around the world. The risk of mental illness is higher in these communities because of factors like violence, deprivation, and post-immigration challenges.
OBJECTIVE
The purpose of this study was to examine the literature to determine the prevalence, predictors, and economic impacts of mental health (MH) disorders among asylum seekers, migrants, and refugees from African countries.
DESIGN AND METHODS
In this scoping review, we followed the guidelines from PRISMA and CoCoPop. A modified version of the Appraisal Tool for Cross-Sectional Studies (AXIS) was used to assess study quality for cross-sectional studies, while an appraisal list was used for qualitative studies based on the Critical Appraisal Skills Programme (CASP). Inclusion criteria included peer-reviewed articles published in English, and articles based on official reports from credible institutions and organizations. Among the exclusion criteria were publications that were not peer reviewed or had not been sourced by credible sources, publications that did not meet the study topic or language criteria, mixed populations (including Africans and non-Africans), and research abstracts, reviews, news articles, commentary on study protocols, case reports, letters, and guidelines.
DATA SOURCES
A systematic search was carried out in Medline (via PubMed), EMBASE, APA PsycINFO, Web of Science and EBSCO, to identify relevant articles that were published between 1 January 2000 and 31 January 2024.
RESULTS
A total of 38 studies met the inclusion criteria, including 22 from African countries and three qualitative studies. In terms of number of countries contributing, Uganda was the largest (n = 7), followed by Italy (n = 4). The most studied conditions, using multiple diagnostic tools, were Post-Traumatic Stress Disorder (PTSD, n = 19) and depression (n = 17). These studies all revealed elevated rates of mental health disorders among these groups, and these were related to migration, refugee-related factors, and traumatic events. Most of these groups are dominated by young males. There is, however, a prominent presence of minors and women who have suffered a variety of forms of violence, in particular sexual violence. Furthermore, mental illnesses, such as PTSD and depression, are not only persistent, but can also be transmitted to children. In accordance with our inclusion criteria, our review found only one study that examined the economic impact of MH disorders in these groups, leaving a significant knowledge gap. According to this randomized controlled trial, intervention to reduce psychological impairment can help young people stay in school, improve their quality-adjusted life year (QALY), and earn an incremental cost-effectiveness ratio (ICER) of $7260 for each QALY gained.
CONCLUSION
Asylum seekers, migrants, and refugees from African countries are likely to experience MH needs, according to this scoping review. As well as posing persistent challenges, these disorders can also be transmissible to offspring. In addition to longitudinal studies of these groups, economic impact studies of mental illnesses are necessary.
Topics: Humans; Refugees; Africa; Prevalence; Mental Disorders; Transients and Migrants; Mental Health; Female; Male; Cost of Illness; Stress Disorders, Post-Traumatic
PubMed: 38913631
DOI: 10.1371/journal.pone.0305495 -
BJS Open May 2024The potential benefits of robotic-assisted compared with laparoscopic surgery for locally advanced cancer have not been sufficiently proven by prospective studies. One...
BACKGROUND
The potential benefits of robotic-assisted compared with laparoscopic surgery for locally advanced cancer have not been sufficiently proven by prospective studies. One factor is speculated to be the lack of strict surgeon criteria. The aim of this study was to assess outcomes for robotic surgery in patients with locally advanced rectal cancer with strict surgeon experience criteria.
METHODS
A criterion was set requiring surgeons to have performed more than 40 robotically assisted operations for rectal cancer. Between March 2020 and May 2022, patients with rectal cancer (distance from the anal verge of 12 cm or less, cT2-T4a, cN0-N3, cM0, or cT1-T4a, cN1-N3, cM0) were registered. The primary endpoint was the rate positive circumferential resection margin (CRM) from the pathological specimen. Secondary endpoints were surgical outcomes, pathological results, postoperative complications, and longterm outcomes.
RESULTS
Of the 321 registered patients, 303 were analysed, excluding 18 that were ineligible. At diagnosis: stage I (n = 68), stage II (n = 84) and stage III (n = 151). Neoadjuvant therapy was used in 56 patients. There were no conversions to open surgery. The median console time to rectal resection was 170 min, and the median blood loss was 5 ml. Fourteen patients had a positive CRM (4.6%). Grade III-IV postoperative complications were observed in 13 patients (4.3%).
CONCLUSION
Robotic-assisted surgery is feasible for locally advanced rectal cancer when strict surgeon criteria are used.
Topics: Humans; Rectal Neoplasms; Robotic Surgical Procedures; Male; Female; Middle Aged; Aged; Prospective Studies; Feasibility Studies; Margins of Excision; Adult; Postoperative Complications; Treatment Outcome; Aged, 80 and over; Neoplasm Staging; Laparoscopy; Neoadjuvant Therapy; Operative Time
PubMed: 38913419
DOI: 10.1093/bjsopen/zrae048 -
Journal of Medical Internet Research Jun 2024Photographs from medical case reports published in academic journals have previously been found in online image search results. This means that patient photographs... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Photographs from medical case reports published in academic journals have previously been found in online image search results. This means that patient photographs circulate beyond the original journal website and can be freely accessed online. While this raises ethical and legal concerns, no systematic study has documented how often this occurs.
OBJECTIVE
The aim of this cross-sectional study was to provide systematic evidence that patient photographs from case reports published in medical journals appear in Google Images search results. Research questions included the following: (1) what percentage of patient medical photographs published in case reports were found in Google Images search results? (2) what was the relationship between open access publication status and image availability? and (3) did the odds of finding patient photographs on third-party websites differ between searches conducted in 2020 and 2022?
METHODS
The main outcome measure assessed whether at least 1 photograph from each case report was found on Google Images when using a structured search. Secondary outcome variables included the image source and the availability of images on third-party websites over time. The characteristics of medical images were described using summary statistics. The association between the source of full-text availability and image availability on Google Images was tested using logistic regressions. Finally, we examined the trend of finding patient photographs using generalized estimating equations.
RESULTS
From a random sample of 585 case reports indexed in PubMed, 186 contained patient photographs, for a total of 598 distinct images. For 142 (76.3%) out of 186 case reports, at least 1 photograph was found in Google Images search results. A total of 18.3% (110/598) of photographs included eye, face, or full body, including 10.9% (65/598) that could potentially identify the patient. The odds of finding an image from the case report online were higher if the full-text paper was available on ResearchGate (odds ratio [OR] 9.16, 95% CI 2.71-31.02), PubMed Central (OR 7.90, 95% CI 2.33-26.77), or Google Scholar (OR 6.07, 95% CI 2.77-13.29) than if the full-text was available solely through an open access journal (OR 5.33, 95% CI 2.31-12.28). However, all factors contributed to an increased risk of locating patient images online. Compared with the search in 2020, patient photographs were less likely to be found on third-party websites based on the 2022 search results (OR 0.61, 95% Cl 0.43-0.87).
CONCLUSIONS
A high proportion of medical photographs from case reports was found on Google Images, raising ethical concerns with policy and practice implications. Journal publishers and corporations such as Google are best positioned to develop an effective remedy. Until then, it is crucial that patients are adequately informed about the potential risks and benefits of providing consent for clinicians to publish their images in medical journals.
Topics: Cross-Sectional Studies; Humans; Photography; Internet
PubMed: 38913416
DOI: 10.2196/55352 -
JAMA Network Open Jun 2024Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. (Randomized Controlled Trial)
Randomized Controlled Trial
Intravascular Imaging and Angiography Guidance in Complex Percutaneous Coronary Intervention Among Patients With Diabetes: A Secondary Analysis of a Randomized Clinical Trial.
IMPORTANCE
Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes.
OBJECTIVE
To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes.
DESIGN, SETTING, AND PARTICIPANTS
This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024.
INTERVENTIONS
Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone.
MAIN OUTCOMES AND MEASURES
The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization.
RESULTS
Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02).
CONCLUSIONS AND RELEVANCE
In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03381872.
Topics: Humans; Percutaneous Coronary Intervention; Male; Female; Aged; Middle Aged; Coronary Angiography; Diabetes Mellitus; Republic of Korea; Coronary Artery Disease; Treatment Outcome
PubMed: 38913377
DOI: 10.1001/jamanetworkopen.2024.17613 -
Frontiers in Oncology 2024Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative...
BACKGROUND
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression.
METHODS
We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone.
RESULTS
Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1-76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6-26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3-94.8%] compared to 21.1% [95% CI 12.2-31.7%] for patients with non-tailored treatment.
CONCLUSIONS
Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.
PubMed: 38912058
DOI: 10.3389/fonc.2024.1408664 -
Frontiers in Immunology 2024The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current... (Review)
Review
The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field.
Topics: Humans; Thyroid Neoplasms; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Animals; T-Lymphocytes; Clinical Trials as Topic; Treatment Outcome
PubMed: 38911868
DOI: 10.3389/fimmu.2024.1411300 -
HRB Open Research 2023Improved Pregnancy Outcomes via Early Detection (IMPROvED) is a multi-centre, European phase IIa clinical study. The primary aim of IMPROvED is to enable the assessment...
BACKGROUND
Improved Pregnancy Outcomes via Early Detection (IMPROvED) is a multi-centre, European phase IIa clinical study. The primary aim of IMPROvED is to enable the assessment and refinement of innovative prototype preeclampsia risk assessment tests based on emerging biomarker technologies. Here we describe IMPROvED's profile and invite researchers to collaborate.
METHODS
A total of 4,038 low-risk nulliparous singleton pregnancies were recruited from maternity units in Ireland (N=1,501), United Kingdom (N=1,108), The Netherlands (N=810), and Sweden (N=619) between November 2013 to August 2017. Participants were interviewed by a research midwife at ~11 weeks (optional visit), ~15 weeks, ~20 weeks, ~34 weeks' gestation (optional visit), and postpartum (within 72-hours following delivery).
FINDINGS TO DATE
Clinical data included information on maternal sociodemographic, medical history, and lifestyle factors collected at ~15 weeks' gestation, and maternal measurements, collected at each study visit. Biobank samples included blood, urine, and hair collected at each study visit throughout pregnancy in all units plus umbilical cord/blood samples collected at birth in Ireland and Sweden. A total of 74.0% (N=2,922) had an uncomplicated pregnancy, 3.1% (N=122) developed preeclampsia, 3.6% (N=143) had a spontaneous preterm birth, and 10.5% (N=416) had a small for gestational age baby. We evaluated a panel of metabolite biomarkers and a panel of protein biomarkers at 15 weeks and 20 weeks' gestation for preeclampsia risk assessment. Their translation into tests with clinical application, as conducted by commercial entities, was hampered by technical issues and changes in test requirements. Work on the panel of proteins was abandoned, while work on the use of metabolite biomarkers for preeclampsia risk assessment is ongoing.
FUTURE PLANS
In accordance with the original goals of the IMPROvED study, the data and biobank are now available for international collaboration to conduct high quality research into the cause and prevention of adverse pregnancy outcomes.
PubMed: 38911611
DOI: 10.12688/hrbopenres.13812.2 -
Frontiers in Neurology 2024Evidence on the activity of patisiran therapy in specific subgroups of patients with hereditary transthyretin amyloidosis variant (ATTRv) is still scarce. This...
OBJECTIVES
Evidence on the activity of patisiran therapy in specific subgroups of patients with hereditary transthyretin amyloidosis variant (ATTRv) is still scarce. This prospective real-world study was designed to provide the first in-depth clinical data on the effectiveness of patisiran in patients with ATTRv reporting the p.Ile88Leu variant, the most widespread variant in the Emilia-Romagna regional area, which has been less represented in previous clinical trials.
PATIENTS AND METHODS
This prospective study evaluated all the patients with genetically proven ATTRv (p.Ile88Leu) and polyneuropathy treated with patisiran in the Emilia-Romagna referral centers for ATTRv (Institute of Neurological Sciences in Bologna and Division of Neurology in Rimini) from March 2021 to April 2023. All subjects underwent clinical and neurological evaluations at baseline and after 9-12 months of treatment.
RESULTS
A total of 22 patients were included in the study; the median age was 73 years (IQR: 9), the age at diagnosis was 72 years (IQR: 10), and the disease duration was 1.6 years (IQR: 2.3). We observed stability of all considered neurological and cardiological parameters at 9-12 months after the beginning of patisiran treatment.
CONCLUSION
Our findings support the clinical data regarding the effectiveness of patisiran in stabilizing the disease course and extend this activity to the subset of patients with the p.Ile88Leu variant.
PubMed: 38911588
DOI: 10.3389/fneur.2024.1415851