Nevin Manimala

Clin Exp Med. 2023 Aug 27. doi: 10.1007/s10238-023-01144-8. Online ahead of print.

ABSTRACT

AIMS: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months.

METHODS: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years.

RESULTS: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of – 3.2%, – 4.6%, – 6.4% and – 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and, of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes.

CONCLUSIONS: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged.

PMID:37634231 | DOI:10.1007/s10238-023-01144-8

J Cancer Res Clin Oncol. 2023 Aug 27. doi: 10.1007/s00432-023-05305-w. Online ahead of print.

ABSTRACT

PURPOSE: The MGMT (O⁶-methylguanine-DNA methyltransferase) gene plays a crucial role in repairing DNA damage caused by alkylating agents, including those used in chemotherapy. Genetic and epigenetic alterations can influence the regulation of MGMT gene, which in turn may impact the response to concomitant chemoradiotherapy (CRT) in cervical cancer. The present study was undertaken to evaluate the correlation of such variations in MGMT gene with the treatment outcome of concomitant chemoradiotherapy (CRT) in cervical cancer.

METHODS: A total of 460 study subjects (240 controls and 220 patients) were subjected to genotypic analysis of MGMT gene variants rs12917(T/C) and rs2308327(A/G) by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Out of them, 48 each of controls and patients were analyzed for promoter methylation and expression by methylation-specific PCR and real-time PCR, respectively. Patients (n = 48) were followed up and evaluated for treatment (CRT) outcome. Statistical analyses were done using GraphPad (9.0) and SPSS version 18.0.

RESULTS: Individuals with GG genotype, G allele of rs2308327, and haplotype ‘TA’ of both variants showed a significant increase in the development of cervical cancer (P ≤ 0.05). In epigenetic regulation, there was a significant hypermethylation of MGMT gene and down-regulation of their expression in patients compared to control individuals. In treatment outcome of CRT, GG genotype of rs2308327(A/G) gene variant showed better response and GG + AG was significantly associated with vital status (alive). Unmethylated MGMT gene showed better median overall survival up to 25 months significant in comparison to methylated MGMT promoter.

CONCLUSION: Gene variant rs2308327(A/G) and promoter hypermethylation regulated MGMT gene can be a good prognostic for treatment response in cervical cancer patients.

PMID:37634205 | DOI:10.1007/s00432-023-05305-w

Circulation. 2023 Aug 27. doi: 10.1161/CIRCULATIONAHA.123.066498. Online ahead of print.

ABSTRACT

Background: Computed tomography (CT) is recommended for guiding transcatheter aortic valve replacement (TAVR). However, as a sizable proportion of TAVR candidates have chronic kidney disease (CKD), the use of iodinated contrast media is a limitation. Cardiac magnetic resonance (CMR) is a promising alternative, yet randomized data comparing the effectiveness of CMR- versus CT-guided TAVR are lacking. Methods: An investigator-initiated, prospective, randomized, open-label, non-inferiority trial was conducted at two Austrian heart centers. Patients evaluated for TAVR according to the inclusion (severe symptomatic aortic stenosis) and exclusion criteria (contraindication to CMR, CT, or TAVR, a life expectancy < 1 year, CKD 4 or 5) were randomized (1:1) to undergo CMR- or CT-guiding. The primary outcome was defined according to the Valve Academic Research Consortium-2 definition of implantation success at discharge, including absence of procedural mortality, correct positioning of a single prosthetic valve, and proper prosthetic valve performance. Non-inferiority was assessed using a hybrid modified intention-to-treat (mITT)/per-protocol (PP) approach based on an absolute risk difference margin of 9%. Results: Between September 11, 2017, and December 16, 2022, 380 candidates for TAVR were randomized to CMR-guided (191 patients) or CT-guided (189 patients) TAVR planning. Of these, 138 patients (72.3%) in the CMR-guided group and 129 patients (68.3%) in the CT-guided group eventually underwent TAVR (mITT cohort). Of these 267, 19 patients had protocol deviations, resulting in a PP cohort of 248 patients (n=121 CMR-guided, n=127 CT-guided). In the mITT cohort, implantation success was achieved in 129 patients (93.5%) in the CMR group and in 117 patients (90.7%) in the CT group (between-group difference, 2.8%; 90% confidence interval [CI]: -2.7 to 8.2%; p<0.01 for non-inferiority). In the PP cohort (n=248), the between-group difference was 2.0% (90% CI: -3.8 to 7.8%; p<0.01 for non-inferiority). Conclusions: CMR-guided TAVR was non-inferior to CT-guided TAVR in terms of device implantation success. CMR can therefore be considered as an alternative for TAVR planning.

PMID:37634187 | DOI:10.1161/CIRCULATIONAHA.123.066498

Dig Dis Sci. 2023 Aug 27. doi: 10.1007/s10620-023-08078-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Peptic ulcers with adherent clots are associated with a high-risk of rebleeding and mortality. However, the optimal management of bleeding ulcers with adherent clots remains unclear. We conducted this systematic review and meta-analysis to compare endoscopic therapy and conservative therapy to manage bleeding ulcers with adherent clots.

METHODS: We systematically searched PubMed, Embase, and Web of Science databases through October 2022 to include all studies comparing the endoscopic and conservative therapeutic approaches for bleeding ulcers with adherent clots. Our primary outcome was rebleeding (overall and 30-day). The secondary outcomes were mortality (overall and 30-day), need for surgery, and length of hospital stay (LOS). The random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding confidence intervals (CI) for proportional and continuous variables, respectively.

RESULTS: Eleven studies (9 RCTs) with 833 patients (431 received endoscopic therapy vs. 402 received conservative therapy) were included. Overall, endoscopic therapy was associated with lower overall rebleeding (OR 0.41, 95% CI 0.22-0.79, P = 0.007), 30-day rebleeding (OR 0.43, 95% CI 0.21-0.89, P = 0.002), overall mortality (OR 0.47, 95% CI 0.23-0.95, P = 0.04), 30-day mortality (OR 0.43, 95% CI 0.21-0.89, P = 0.002), need for surgery (OR 0.44, 95% CI 0.21-0.95, P = 0.04), and LOS (MD – 3.17 days, 95% CI – 4.14, – 2.19, P < 0.00001). However, subgroup analysis of randomized controlled trials (RCTs) showed no significant difference in overall mortality (OR 0.78, 95% CI 0.24-2.52, P = 0.68) between the two strategies, with numerically lower but statistically non-significant rates of overall rebleeding (7.2% vs. 18.5%, respectively; OR 0.42, 95% CI 0.17-1.05, P = 0.06), statistically lower rate of need for surgery (OR 0.28, 95% CI 0.08-0.96, P = 0.04) with endoscopic therapy compared to conservative therapy.

CONCLUSIONS: Our meta-analysis demonstrates that endoscopic therapy was overall associated with lower rates of rebleeding (overall and 30-day), mortality (overall and 30-day), need for surgery, and LOS, compared to conservative therapy for the management of bleeding ulcers with adherent clots. However, subgroup analysis of RCTs showed that endoscopic therapy was associated with numerically lower but statistically non-significant rates of overall rebleeding and a statistically lower rate of need for surgery compared to conservative therapy with similar overall mortality rates. Combined treatment with thermal therapy and injection therapy was the most effective treatment modality in reducing rebleeding risk. Further large-scale RCTs are needed to validate our findings.

PMID:37634184 | DOI:10.1007/s10620-023-08078-x

Eur Heart J Cardiovasc Pharmacother. 2023 Aug 26:pvad063. doi: 10.1093/ehjcvp/pvad063. Online ahead of print.

ABSTRACT

AIMS: To summarise the totality of evidence validating the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, ascertaining its aggregate discrimination and validation power in multiple population subsets.

METHODS AND RESULTS: We searched electronic databases from 2017 (PRECISE-DAPT proposal) up to March 2023 for studies that reported the occurrence of out-of-hospital bleedings according to the PRECISE-DAPT score in patients receiving DAPT following percutaneous coronary intervention (PCI). Pooled odds ratio (OR) with 95% confidence interval (CI) were used as summary statistics and were calculated using a random-effects model. Primary and secondary endpoints were the occurrence of any and major bleeding, respectively. A total of twenty-one studies and 67 283 patients were included; 24.7% of patients (N = 16 603) were at high-bleeding risk (PRECISE-DAPT ≥ 25) and when compared to those at low-bleeding risk, they experienced a significantly higher rate of any out-of-hospital bleeding (OR: 2.71; 95% CI: 2.24-3.29; p-value < 0.001) and major bleedings (OR: 3.51; 95% CI: 2.71-4.55; p-value < 0.001). Pooling data on c-stat whenever available, the PRECISE-DAPT score showed a moderate discriminative power in predicting major bleeding events at 1-year (pooled c-stat: 0.71; 95% CI: 0.64-0.77).

CONCLUSION: This systematic review and meta-analysis confirms the external validity of the PRECISE-DAPT score in predicting out-of-hospital bleeding outcomes in patients on DAPT following PCI. The moderate discriminative ability highlights the need for future improved risk prediction tools in the field.

PMID:37634083 | DOI:10.1093/ehjcvp/pvad063

Sci Rep. 2023 Aug 26;13(1):13993. doi: 10.1038/s41598-023-41260-9.

ABSTRACT

Transient ischemic attack (TIA) was clinically divided into anterior circulation (AC) or posterior circulation (PC). Previous study reported that ABCD2 score could predict the stroke risk after AC-TIA but might have limitation for PC-TIA. We aimed to classify TIA depending on neuroimaging and assess the value of ABCD2 score for predicting stroke risk in different territories. Research data was from TIA database of the First Affiliated Hospital of Zhengzhou University. TIA patients with acute infarction on diffuse weighted imaging [that is, transient symptoms with infarction (TSI)] were divided into anterior and posterior circulation groups according to the location of infarction. The outcome was recurrent stroke within 7 and 90 days. The predictive power of ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. Overall, 382 AC-TSI and 112 PC-TSI patients were included. There were 38 (9.9%) AC-TSI patients and 11(9.8%) PC-TSI patients who had recurrent stroke at 7 days, and 66 (17.3%) AC-TSI patients and 19 (17.0%) PC-TSI patients who had recurrent stroke within 90 days. At 7 days, the AUC for ABCD2 score was 0.637 (95% confidence interval CI 0.554-0.720) in anterior circulation and 0.683 (95% CI 0.522-0.845) in posterior circulation. The C statistics for ABCD2 score in the two groups were not statistically significant (Z = – 0.499; P = 0.62). Similar result was found when the outcome time-point was set at 90 days. ABCD2 score could predict the short-term risk of recurrent stroke after AC-TSI and PC-TSI, and had similar predictive abilities for AC-TSI and PC-TSI.

PMID:37634045 | DOI:10.1038/s41598-023-41260-9

Bone Marrow Transplant. 2023 Aug 26. doi: 10.1038/s41409-023-02087-0. Online ahead of print.

ABSTRACT

Psychosocial health predicts and contributes to medical outcomes for patients undergoing hematopoietic stem cell transplantation (HSCT). Yet, there are no standards for psychosocial assessments or support for both patients and caregivers across the care continuum. To examine the current state of psychosocial care, clinicians were sent a survey of their psychosocial assessment practices for patients and caregivers undergoing HSCT via the Listservs of professional organizations. Descriptive statistics and bivariate analyses were performed to summarize the findings. While 96% of participants reported routine pre-HSCT psychosocial assessment of patients, only 10.6% routinely used a validated transplant risk-assessment measure. Just 27% routinely performed follow-up psychosocial assessments. In contrast, only 47% of participants routinely assessed the psychosocial needs of family caregivers pre-HSCT, and 13% routinely performed follow-up assessments for caregivers. Most (90%) reported social workers were the primary providers of assessments. While patient-report measures were used for evaluation, the majority of assessments were clinical interviews. No significant differences were found between programs that treated adult and pediatric patients versus those only treating adult patients. Our findings highlight the lack of standard psychosocial practices for patients and family caregivers undergoing HSCT and we offer recommendations to fill this gap.

PMID:37634015 | DOI:10.1038/s41409-023-02087-0

Sci Rep. 2023 Aug 26;13(1):14001. doi: 10.1038/s41598-023-41289-w.

ABSTRACT

This research is focused on the constant pavement failure in parts of the Enugu-Onitsha expressway. The failed portions are constructed on the natural subgrade known to be the Shale of Enugu and Mamu formations southeastern Nigeria. Five samples each were obtained from the formations and were subjected to geotechnical test, mineralogical analysis, scanning electron microscopy (SEM) and, statistical analysis. The outcome of the geotechnical test revealed that the liquid limits (LL) are of high plasticity with values ranging from 57.69 to 62.61% and 53.57 to 56.24%, plasticity index (PI) values ranging from 20.32 to 24.37% and 13.37 to 15.32%, Slake durability index (SDI) values ranging from 0.55 to 31.8% and 63.4 to 71.6%, for Enugu and Mamu Shales respectively. From the Unconfined compressive strength (UCS) test, the cohesion (C) values ranged from 37.36 to 43.89 kPa and 24.22 to 27.07 kPa, soaked California bearing ratio (CBR) values ranged from 1.03 to 1.22% and 0.90 to 1.60% for Enugu and Mamu Shales, respectively. The test results are not in the range of specification of the Nigerian Federal Ministry of Works and Housing (FMWH) Nigeria standard for pavement construction. X-ray diffraction (XRD) analysis revealed major minerals to be quartz and kaolinite. Moreover, kaolinite disperses and migrates when moist hence geotechnical failure. Images from Scanning electron microscopy revealed the presence of micropores and fractures which can be used as an inference to the geotechnical test results. Statistical analysis of key geotechnical parameters such as SDI, PI, C, and CBR revealed a strong correlation either positively or negatively with each other. The evaluated results pointed out that the underlined natural subgrade is poor for pavement construction, and thus requires improvement.

PMID:37634005 | DOI:10.1038/s41598-023-41289-w

Crit Care. 2023 Aug 26;27(1):329. doi: 10.1186/s13054-023-04621-4.

ABSTRACT

BACKGROUND: Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium.

METHODS: This is an updated systematic review with meta-analysis and trial sequential analysis of randomised clinical trials investigating haloperidol versus placebo or any comparator in critically ill patients with delirium. We adhered to the Cochrane handbook, the PRISMA guidelines and the grading of recommendations assessment, development and evaluation statements. The primary outcomes were all-cause mortality and proportion of patients with one or more serious adverse events or reactions (SAEs/SARs). Secondary outcomes were days alive without delirium or coma, delirium severity, cognitive function and health-related quality of life.

RESULTS: We included 11 RCTs with 15 comparisons (n = 2200); five were placebo-controlled. The relative risk for mortality with haloperidol versus placebo was 0.89; 96.7% CI 0.77 to 1.03; I² = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I² = 18% (low-certainty evidence). We found no difference in days alive without delirium or coma (moderate-certainty evidence). We found sparse data for other secondary outcomes and other comparators than placebo.

CONCLUSIONS: Haloperidol may reduce mortality and likely result in little to no change in the occurrence of SAEs/SARs compared with placebo in critically ill patients with delirium. However, the results were not statistically significant and more trial data are needed to provide higher certainty for the effects of haloperidol in these patients.

TRIAL REGISTRATION: CRD42017081133, date of registration 28 November 2017.

PMID:37633991 | DOI:10.1186/s13054-023-04621-4

Res Involv Engagem. 2023 Aug 26;9(1):70. doi: 10.1186/s40900-023-00483-w.

ABSTRACT

BACKGROUND: The evaluation of patient engagement in research is understudied and under-reported, making it difficult to know what engagement strategies work best and when. We provide the results of an evaluation of patient engagement in a large Canadian research program focused on the de-implementation of low-value care. We aimed to evaluate the experience and impact of patient engagement in the study.

METHODS: An online cross-sectional survey was administered using Microsoft Forms to (1) researchers and study staff and (2) patient partners. The survey was developed following iterative reviews by the project’s patient partnership council and evaluation committee. Survey content areas included opinions on patient engagement to date, including challenges to engagement and suggestions for improvement. Patient partners also evaluated the partnership council. Descriptive statistics including counts and percentages described Likert scale survey items, while open comments were analyzed using descriptive content analysis.

RESULTS: The survey response rate was 46% (17/37). There were positive attitudes about the value of patient engagement in this project. There was also a high degree of willingness to be involved with patient engagement in future projects, whether as a patient partner or as a researcher including patients on the research team. Most patient partners felt their contributions to the project were valued by researchers and study research staff. Open comments revealed that a co-design approach and full inclusion on the research team were integral to demonstrating the value of patient partner input. Areas for improvement included more frequent and ongoing communication among all team members, as well as earlier training about patient engagement, particularly addressing role expectations and role clarity.

CONCLUSIONS: Our data revealed that despite some challenges, team members recognized the value of patient engagement in research and agreed project decisions had been impacted by patient partner input. Ongoing communication was highlighted as an area for improvement, as well as earlier training and ongoing support for all team members, but particularly researchers and study staff. In response to evaluation data, the team has reinstated a quarterly newsletter and plans to use specific patient engagement planning templates across study sites for all project activities. These tools should help make expectations clear for all team members and contribute to a positive patient engagement experience. Findings can inform patient engagement planning and evaluation for other health research projects.

PMID:37633983 | DOI:10.1186/s40900-023-00483-w