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Frontiers in Oncology 2024Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients...
BACKGROUND
Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated.
METHODS
Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher's exact test were used for correlation analysis.
RESULTS
1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified.
CONCLUSION
1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.
PubMed: 38952544
DOI: 10.3389/fonc.2024.1390820 -
Pakistan Journal of Medical Sciences Jul 2024Task-oriented therapy (TOT) is used to increase the effectiveness of upper extremity (UE) in activity daily living (ADL). This study aimed to investigate the effect of...
OBJECTIVE
Task-oriented therapy (TOT) is used to increase the effectiveness of upper extremity (UE) in activity daily living (ADL). This study aimed to investigate the effect of TOT on the participation and ADLs of stroke patients.
METHODS
Between October 2018 and February 2019, 28 chronic stroke patients were included in the study treated in Kocaeli University Hospital, Department of Physical Medicine and Rehabilitation, Turkey. The performance areas and participation status of the patients in which they experienced limitations were evaluated with the Canadian Occupational Performance Scale (COPM), and their level of independence in ADLs was evaluated with the Modified Frenchay Activity Index (mFAI) and Barthel Index (BI). All patients were included in the occupational therapy (OT) program five days a week for three weeks at Kocaeli University Hospital. Three ADLs in which they had difficulties were studied with 28 patients. Each of the activities was designed specifically for the patient. All assessments were repeated after three weeks of treatment.
RESULTS
A total of 28 patients, 12 females and 16 males, diagnosed with stroke, were included in the study. A statistically significant increase was found in the COPM performance and satisfaction value compared to the pre-treatment value (p<0.001). A statistically significant difference was found between pre- and post-treatment mFAI and BI values (p<0.001).
CONCLUSIONS
Adding task-oriented therapy to the rehabilitation programs of stroke patients will contribute to the improvement of ADL.
PubMed: 38952526
DOI: 10.12669/pjms.40.6.7954 -
Pakistan Journal of Medical Sciences Jul 2024To explore content experts' experiences with item vetting during item bank development at a public sector medical university of Rawalpindi, Pakistan.
OBJECTIVE
To explore content experts' experiences with item vetting during item bank development at a public sector medical university of Rawalpindi, Pakistan.
METHODS
An exploratory study was carried out from December 2022 to February 2023 at a public sector medical college of Rawalpindi. A purposive sampling technique was employed to collect data from all content experts of the study institute who participated in item vetting activity during pre-exam moderation in the university. A pilot-tested semi-structured interview guide was utilized, interviews were audio recorded and later transcribed. Participants' anonymity was ensured. Various quality assurance strategies were employed to ensure the trustworthiness of the findings. Thematic analysis was performed on the transcribed data and themes were finalized by achieving consensus among all authors.
RESULTS
Six themes overarching the fourteen subthemes emerged from the data. Participants expressed a profound sense of satisfaction and valued their experience in refining expertise in constructing multiple-choice questions (MCQs). It was widely acknowledged that such activities not only contribute to the enhancement of item development skills but also improve quality of items.
CONCLUSIONS
The consistent implementation of item vetting routines, in conjunction with diligent adherence to item writing protocols, contributes to quality assurance measures in assessment. Item bank development for fair and transparent assessment ensures production of competent healthcare professionals filtering incompetent ones hence improving health care services in the community.
PubMed: 38952493
DOI: 10.12669/pjms.40.6.8664 -
Orthopaedic Surgery Jul 2024Total hip arthroplasty (THA) remains the primary treatment option for femoral neck fractures in elderly patients. This study aims to explore the risk factors associated...
Development and Validation of a Machine Learning Algorithm to Predict the Risk of Blood Transfusion after Total Hip Replacement in Patients with Femoral Neck Fractures: A Multicenter Retrospective Cohort Study.
OBJECTIVE
Total hip arthroplasty (THA) remains the primary treatment option for femoral neck fractures in elderly patients. This study aims to explore the risk factors associated with allogeneic blood transfusion after surgery and to develop a dynamic prediction model to predict post-operative blood transfusion requirements. This will provide more accurate guidance for perioperative humoral management and rational allocation of medical resources.
METHODS
We retrospectively analyzed data from 829 patients who underwent total hip arthroplasty for femoral neck fractures at three third-class hospitals between January 2017 and August 2023. Patient data from one hospital were used for model development, whereas data from the other two hospitals were used for external validation. Logistic regression analysis was used to screen the characteristic subsets related to blood transfusion. Various machine learning algorithms, including logistic regression, SVA (support vector machine), K-NN (k-nearest neighbors), MLP (multilayer perceptron), naive Bayes, decision tree, random forest, and gradient boosting, were used to process the data and construct prediction models. A 10-fold cross-validation algorithm facilitated the comparison of the predictive performance of the models, resulting in the selection of the best-performing model for the development of an open-source computing program.
RESULTS
BMI (body mass index), surgical duration, IBL (intraoperative blood loss), anticoagulant history, utilization rate of tranexamic acid, Pre-Hb, and Pre-ALB were included in the model as well as independent risk factors. The average area under curve (AUC) values for each model were as follows: logistic regression (0.98); SVA (0.91); k-NN (0.87) MLP, (0.96); naive Bayes (0.97); decision tree (0.87); random forest (0.96); and gradient boosting (0.97). A web calculator based on the best model is available at: (https://nomo99.shinyapps.io/dynnomapp/).
CONCLUSION
Utilizing a computer algorithm, a prediction model with a high discrimination accuracy (AUC > 0.5) was developed. The logistic regression model demonstrated superior differentiation and reliability, thereby successfully passing external validation. The model's strong generalizability and applicability have significant implications for clinicians, aiding in the identification of patients at high risk for postoperative blood transfusion.
PubMed: 38951965
DOI: 10.1111/os.14160 -
Chinese Medicine Jun 2024Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of...
BACKGROUND
Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy.
METHODS
From December 2022 to December 2023, a large-scale screening study was conducted in Fujian, China. Based on traditional Chinese medicine theory, we simultaneously collected tongue images and inquiry information from 1034 participants, considering the potential of these data for PLGC screening. Then, we introduced inquiry information for the first time, forming a multimodality artificial intelligence model to integrate tongue images and inquiry information for pre-endoscopic screening. Moreover, we validated this approach in another independent external validation cohort, comprising 143 participants from the China-Japan Friendship Hospital.
RESULTS
A multimodality artificial intelligence-assisted pre-endoscopic screening model based on tongue images and inquiry information (AITonguequiry) was constructed, adopting a hierarchical prediction strategy, achieving tailored endoscopic recommendations. Validation analysis revealed that the area under the curve (AUC) values of AITonguequiry were 0.74 for overall PLGC (95% confidence interval (CI) 0.71-0.76, p < 0.05) and 0.82 for high-risk PLGC (95% CI 0.82-0.83, p < 0.05), which were significantly and robustly better than those of the independent use of either tongue images or inquiry information alone. In addition, AITonguequiry has superior performance compared to existing PLGC screening methodologies, with the AUC value enhancing 45% in terms of PLGC screening (0.74 vs. 0.51, p < 0.05) and 52% in terms of high-risk PLGC screening (0.82 vs. 0.54, p < 0.05). In the independent external verification, the AUC values were 0.69 for PLGC and 0.76 for high-risk PLGC.
CONCLUSION
Our AITonguequiry artificial intelligence model, for the first time, incorporates inquiry information and tongue images, leading to a higher precision and finer-grained pre-endoscopic screening of PLGC. This enhances patient screening efficiency and alleviates patient burden.
PubMed: 38951913
DOI: 10.1186/s13020-024-00963-5 -
Breast Cancer Research : BCR Jun 2024HER3, a member of the EGFR receptor family, plays a central role in driving oncogenic cell proliferation in breast cancer. Novel HER3 therapeutics are showing promising...
PURPOSE
HER3, a member of the EGFR receptor family, plays a central role in driving oncogenic cell proliferation in breast cancer. Novel HER3 therapeutics are showing promising results while recently developed HER3 PET imaging modalities aid in predicting and assessing early treatment response. However, baseline HER3 expression, as well as changes in expression while on neoadjuvant therapy, have not been well-characterized. We conducted a prospective clinical study, pre- and post-neoadjuvant/systemic therapy, in patients with newly diagnosed breast cancer to determine HER3 expression, and to identify possible resistance mechanisms maintained through the HER3 receptor.
EXPERIMENTAL DESIGN
The study was conducted between May 25, 2018 and October 12, 2019. Thirty-four patients with newly diagnosed breast cancer of any subtype (ER ± , PR ± , HER2 ±) were enrolled in the study. Two core biopsy specimens were obtained from each patient at the time of diagnosis. Four patients underwent a second research biopsy following initiation of neoadjuvant/systemic therapy or systemic therapy which we define as neoadjuvant therapy. Molecular characterization of HER3 and downstream signaling nodes of the PI3K/AKT and MAPK pathways pre- and post-initiation of therapy was performed. Transcriptional validation of finings was performed in an external dataset (GSE122630).
RESULTS
Variable baseline HER3 expression was found in newly diagnosed breast cancer and correlated positively with pAKT across subtypes (r = 0.45). In patients receiving neoadjuvant/systemic therapy, changes in HER3 expression were variable. In a hormone receptor-positive (ER +/PR +/HER2-) patient, there was a statistically significant increase in HER3 expression post neoadjuvant therapy, while there was no significant change in HER3 expression in a ER +/PR +/HER2+ patient. However, both of these patients showed increased downstream signaling in the PI3K/AKT pathway. One subject with ER +/PR -/HER2- breast cancer and another subject with ER +/PR +/HER2 + breast cancer showed decreased HER3 expression. Transcriptomic findings, revealed an immune suppressive environment in patients with decreased HER3 expression post therapy.
CONCLUSION
This study demonstrates variable HER3 expression across breast cancer subtypes. HER3 expression can be assessed early, post-neoadjuvant therapy, providing valuable insight into cancer biology and potentially serving as a prognostic biomarker. Clinical translation of neoadjuvant therapy assessment can be achieved using HER3 PET imaging, offering real-time information on tumor biology and guiding personalized treatment for breast cancer patients.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Middle Aged; Receptor, ErbB-3; Prospective Studies; Adult; Aged; Biomarkers, Tumor; Receptor, ErbB-2; Receptors, Estrogen; Gene Expression Regulation, Neoplastic; Signal Transduction; Positron-Emission Tomography
PubMed: 38951909
DOI: 10.1186/s13058-024-01859-w -
BMC Public Health Jun 2024Obesity leads to increased disease burden, decreased life expectancy, and disrupted sexual life. One of the most effective ways of obesity treatment is bariatric... (Comparative Study)
Comparative Study
BACKGROUND
Obesity leads to increased disease burden, decreased life expectancy, and disrupted sexual life. One of the most effective ways of obesity treatment is bariatric surgery. This study was conducted aiming to determine and compare sexual self-concept in women with obesity pre- and post-bariatric surgery.
METHOD
A longitudinal study comparing sexual self-concept pre and post- surgery was conducted on women with obesity referring to obesity clinics in the city of Tehran in 2020-2021. Data collection was performed using Snell's Multidimensional Sexual Self-Concept Questionnaire (MSSCQ), which was completed online. Data were analyzed using SPSS version 16 statistical software and Fisher's exact test, chi-square, Mann-Whitney, independent t, and logistic and linear regression tests. A p-value of less than 0.05 was considered significant.
RESULTS
According to the findings, the mean (standard deviation) score of sexual self-concept was 240.26 (26.82) in the post-surgery group and 200.26 (32.24) in the pre-surgery group (P = 0.001), and the highest mean (standard deviation) score of sexual self-concept both in the pre-surgery group (13.06 [4.00]) and in the post-surgery group (15.46 [2.16]) was related to the area of sexual depression (P = 0.05). Also, with increasing educational level, the odds of bariatric surgery increased by 33%, and those who had no private bedroom had lower odds of bariatric surgery by 65%. In those who did not have other individuals living in their house and their spouse was not a smoker, the self-concept score was 52.35 and 23.11 units higher.
CONCLUSION
In general, bariatric surgery can improve sexual self-care. Considering the issue of sexual self-concept in bariatric surgery, it is recommended to design appropriate counseling and planning before surgery according to the culture of each country.
Topics: Humans; Female; Bariatric Surgery; Self Concept; Adult; Obesity; Longitudinal Studies; Iran; Middle Aged; Surveys and Questionnaires; Sexual Behavior; Young Adult
PubMed: 38951823
DOI: 10.1186/s12889-024-19279-y -
BMC Cancer Jun 2024The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been...
BACKGROUND AND AIMS
The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort.
METHODS
The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted.
RESULTS
Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 10/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 10/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 10/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98).
CONCLUSION
Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.
Topics: Humans; Fluorouracil; Colorectal Neoplasms; Male; Female; Middle Aged; Cardiotoxicity; Retrospective Studies; Aged; Inflammation; Antimetabolites, Antineoplastic; Monocytes; Adult
PubMed: 38951749
DOI: 10.1186/s12885-024-12568-0 -
Annals of Rehabilitation Medicine Jun 2024We conducted a systematic review and meta-analysis to examine the protective effects of botulinum toxin-A (Botox-A) on spasticity and nociceptive pain in individuals...
We conducted a systematic review and meta-analysis to examine the protective effects of botulinum toxin-A (Botox-A) on spasticity and nociceptive pain in individuals with spinal cord injuries (SCIs). PubMed, Embase, and Cochrane Library databases were searched from inception to July 2023. The primary outcome of interest was spasticity and nociceptive pain. We pooled the available data using the generic inverse variance method, and we used a fixed-effect/random-effects model. We then calculated standardized mean difference (SMD) and 95% confidence intervals (95% CIs) to estimate the effect size. A total of fourteen studies meeting the inclusion criteria comprised two randomized controlled trials, five pre-post studies, and seven case reports. Across the various study designs, the majority of trials were assessed to have fair to high quality. The meta-analysis shows that Botox-A significantly decreased spasticity (SMD, -1.73; 95% CI, -2.51 to -0.95; p<0.0001, I2=48%) and nociceptive pain (SMD, -1.79; 95% CI, -2.67 to -0.91; p<0.0001, I2=0%) in SCI patients. Furthermore, Botox-A intervention improved motor function, activities of daily living (ADL), and quality of life. Our study suggests that Botox-A may alleviate spasticity and nociceptive pain in SCI patients. Moreover, the observed improvements in motor function, ADL, and overall quality of life following Botox-A intervention underscore its pivotal role in enhancing patient outcomes.
PubMed: 38950971
DOI: 10.5535/arm.240034 -
ACR Open Rheumatology Jul 2024Rheumatoid arthritis (RA) has a "pre-RA" period in which multiple autoantibodies, including antibodies to citrullinated (cit) proteins (ACPA), rheumatoid factor (RF),...
OBJECTIVE
Rheumatoid arthritis (RA) has a "pre-RA" period in which multiple autoantibodies, including antibodies to citrullinated (cit) proteins (ACPA), rheumatoid factor (RF), anti-peptidyl arginine deiminase (anti-PAD), among others, have been described; however, few studies have tested all autoantibodies in a single pre-RA cohort. This study aims to evaluate the prevalence of multiple autoantibodies in pre-RA and potentially identify an autoantibody profile in pre-RA that indicates imminent onset of clinical RA.
METHODS
We evaluated 148 individuals with two pre- and one post-RA diagnosis samples available from the Department of Defense Serum Repository and matched controls. Samples were tested for immuglobulin (Ig) G anti-cyclic cit peptide-3 (anti-CCP3), five ACPA fine specificities, five anti-PAD isoforms, as well as RF IgA and RF IgM using commercial platforms; cutoffs were determined using levels present in <1% of controls.
RESULTS
Positivity of anti-CCP3, RF IgA and RF IgM, anti-PAD1, anti-cit-vimentin 2, anti-cit-fibrinogen, and anti-cit-histone 1 increased over time in pre-RA, although anti-PAD and ACPA fine specificities were predominately present within anti-CCP3-positive individuals. Within anti-CCP3-positive samples from the pre-RA period, positivity for RFs as well as anti-PAD and ACPA fine specificities classified samples as being closer to the time of RA diagnosis.
CONCLUSION
Multiple autoantibodies are present in pre-RA and increase in positivity as the time of RA diagnosis approaches. These results confirm previous findings predicting imminent RA and provide a pathway using commercial-grade assays to assess the risk for and timing of development of clinical RA.
PubMed: 38950890
DOI: 10.1002/acr2.11704