Nevin Manimala

Breast Cancer Res Treat. 2023 Sep 20. doi: 10.1007/s10549-023-07115-7. Online ahead of print.

ABSTRACT

PURPOSE: Breast cancer often metastasizes to the central nervous system. Although the prognosis of brain metastases from breast cancer has been considered poor, and systemic therapy has not contributed to an improved prognosis, newer agents are expected to be more effective. BRCAness is defined as the status of homologous recombination deficiency (HRD) in tumor tissue, regardless of the presence of pathogenic germline BRCA1/2 variants. A study employing next-generation sequencing analysis showed that HRD was found relatively frequently in brain metastases of breast cancer patients. However, there have been no studies evaluating BRCAness in brain metastases of breast cancer with more efficient, rapid, and cost-effective methods.

METHODS: We retrospectively investigated 17 brain metastases of breast cancer that were surgically resected at our hospital from January 2007 to December 2022. Of these, samples from 15 patients were evaluable for BRCAness by employing multiplex ligation-dependent probe amplification (MLPA) assay.

RESULTS: Of the 15 patients, five patients (33%) had tumors with BRCAness. Clinicopathological factors of patients with brain metastases with BRCAness were not statistically different from those of patients who possessed tumors without BRCAness. Patients with brain metastases with BRCAness had shorter overall survival compared to those without BRCAness (BRCAness, median 15 months (95% CI 2-30) vs. non-BRCAness, median 28.5 months (95% CI 10-60); P = 0.013).

CONCLUSION: In this study, we evaluated BRCAness in brain metastases of breast cancer with the MLPA method, and found that about one-third of patients had BRCAness-positive tumors. The analysis of BRCAness using MLPA has the potential for practical clinical use.

PMID:37728693 | DOI:10.1007/s10549-023-07115-7

J Comp Physiol B. 2023 Sep 20. doi: 10.1007/s00360-023-01508-2. Online ahead of print.

ABSTRACT

The annual cycle of migratory birds requires significant phenotypic remodeling. We sought to induce the migratory phenotype in Gray Catbirds by exposing them to a short-day light cycle. While adipose storage was stimulated, exceeding that typically seen in wild birds, other aspects of the migratory phenotype were unchanged. Of particular interest, the rate of lipid export from excised adipose tissue was nearly halved. This is in contrast to wild migratory birds in which lipid export rates are increased. These data suggest that exposure to an altered light cycle only activated the lipid storage program while inhibiting the lipid transport program. The factors governing lipid mobilization and transport remain to be elucidated.

PMID:37728689 | DOI:10.1007/s00360-023-01508-2

J Psycholinguist Res. 2023 Sep 20. doi: 10.1007/s10936-023-10019-8. Online ahead of print.

ABSTRACT

Numerous studies suggest that children with Autism Spectrum Disorder (ASD) encounter language problems related to syntax. In particular, these children face difficulties in comprehending and answering complex language structures in Arabic.This paper examines whether a prototype Arabic assistive application can have an impact on the ability of children with ASD to comprehend and answer content questions and on their communicative skills. Via two questionnaires targeting 57 caregivers and ASD specialists in Jordan and a focus-group discussion with three teachers working in three autism centers in Jordan, a prototype assistive application named Aseel was created. To test the effect of using this app on enhancing ASD children’s ability to comprehend and answer Arabic questions, a sample consisting of two groups of children: 20 verbal and 5 nonverbal children with ASD enrolled in three autism centers in Amman, Jordan was recruited. A pre-test containing 55 content questions was designed and tested on the two groups. Then, a treatment for three weeks took place in which the teachers trained the children on answering these questions using the app. A post-test was conducted after a three-day break to test whether the app affected the ability of verbal and nonverbal children with ASD to comprehend and answer the questions accurately. The data analysis revealed that the differences between the answers of the two groups in the pre- and post-tests were statistically significant. This suggests that this technology has the potential to aid both verbal and nonverbal children with ASD in effectively learning complex Arabic content questions. This assistive application enhances collaboration between teacher and children with ASD, visual-spatial thinking and communication with others. Another advantage of this app is increasing ASD children’s vocabulary repertoire. Preliminary results involving nonverbal children showed that the icons which visually and auditorily represent the most basic needs for a person are proving effective in helping this group communicate with their caregivers and teachers.

PMID:37728685 | DOI:10.1007/s10936-023-10019-8

Eur J Nucl Med Mol Imaging. 2023 Sep 20. doi: 10.1007/s00259-023-06396-w. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this work is to provide the currently missing evidence that may allow an update of the Paediatric Dosage Card provided by the European Association of Nuclear Medicine (EANM) for conventional PET/CT systems.

METHODS: In a total of 2082 consecutive [¹⁸F]FDG-PET scans performed within the EuroNet-PHL-C2 trial, the administered [¹⁸F]FDG activity was compared to the activity recommended by the EANM Paediatric Dosage Card. None of these scans had been rejected beforehand by the reference nuclear medicine panel of the trial because of poor image quality. For detailed quality assessment, a subset of 91 [¹⁸F]FDG-PET scans, all performed in different patients at staging, was selected according to pre-defined criteria, which (a) included only patients who had received substantially lower activities than those recommended by the EANM Paediatric Dosage Card, and (b) included as wide a range of different PET systems and imaging parameters as possible to ensure that the conclusions drawn in this work are as generally valid as possible. The image quality of the subset was evaluated visually by two independent readers using a quality scoring system as well as analytically based on a volume-of-interest analysis in 244 lesions and the healthy liver. Finally, recommendations for an update of the EANM Paediatric Dosage Card were derived based on the available data.

RESULTS: The activity recommended by the EANM Paediatric Dosage Card was undercut by a median of 99.4 MBq in 1960 [¹⁸F]FDG-PET scans and exceeded by a median of 15.1 MBq in 119 scans. In the subset analysis (n = 91), all image data were visually classified as clinically useful. In addition, only a very weak correlation (r = 0.06) between activity reduction and tumour-to-background ratio was found. Due to the intended heterogeneity of the dataset, the noise could not be analysed statistically sound as the high range of different imaging variables resulted in very small subsets. Finally, a suggestion for an update of the EANM Paediatric Dosage Card was developed, based on the analysis presented, resulting in a mean activity reduction by 39%.

CONCLUSION: The results of this work allow for a conservative update of the EANM Paediatric Dosage Card for [¹⁸F]FDG-PET/CT scans performed with conventional PET/CT systems.

PMID:37728668 | DOI:10.1007/s00259-023-06396-w

Clin Oral Investig. 2023 Sep 20. doi: 10.1007/s00784-023-05249-y. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the multilayer panoramic radiography (MPAN) and conventional panoramic radiography (CPAN) in the evaluation of mandibular third molars using cone-beam computed tomography (CBCT) as a reference.

METHODS: CPAN, MPAN, and CBCT scans from 33 dry human mandibles were acquired using the OP300 Maxio unit, totalizing 56 mandibular third molars to be evaluated. Three examiners evaluated each third molar according to their position, depth of impaction in the mandibular ramus, proximity between the dental root apexes and the mandibular canal, and the presence of radiographic signs of proximity to the mandibular canal. In addition, when there was a distance between the root apexes and the mandibular canal, it was measured. As a reference, these same parameters were assessed in the CBCT scans by a fourth examiner. For the statistical analysis, the weighted Kappa, Bland Altman, and Wilcoxon tests were performed (α = 0.05).

RESULTS: The agreement between the assessments performed in the panoramic modalities with the CBCT ranged from 66.1% to 100.0% for the categorical variables. Overall, the agreement values of CPAN and MPAN with CBCT were similar. The distances between the dental root apex and the mandibular canal for both CPAN and MPAN were significantly underestimated compared to CBCT (p < 0.05). The intra- and interexaminer agreements of the examiners ranged from poor to almost perfect; in general, the agreements were higher in the evaluation performed in the MPAN than in the CPAN.

CONCLUSIONS: The MPAN performs similarly to CPAN for evaluating mandibular third molars and their proximity relationship to the mandibular canal.

CLINICAL RELEVANCE: Preoperative evaluation of lower mandibular third molars is usually performed using CPAN. Recently, a new tool, MPAN, was developed, which has not yet been tested for the evaluation of mandibular third molars and showed similar performance to CPAN in the present study. Future studies using MPAN are encouraged to evaluate other diagnostic tasks.

PMID:37728617 | DOI:10.1007/s00784-023-05249-y

Sex Reprod Health Matters. 2023 Dec;31(4):2250621. doi: 10.1080/26410397.2023.2250621. Epub 2023 Sep 20.

ABSTRACT

Abortion in Ghana is legally permissible under certain conditions. Updated in June 2021, the National Comprehensive Abortion Care Services Standards and Protocols included telemedicine as a recognised option for early medical abortion (EMA). Subsequently, Marie Stopes Ghana launched this pilot project to understand the feasibility and acceptability of providing EMA services through telemedicine. The pilot evaluation drew on two research protocols – a process evaluation and a qualitative study. The process evaluation focused on existing routine data sources and additional pilot-specific monitoring, while the qualitative protocol included in-depth interviews with a range of key stakeholders, including telemedicine and in-person patients, healthcare managers, and service providers. Telemedicine for EMA is feasible, acceptable, and has likely expanded access to safe abortion in Ghana. The MSIG telemedicine service package enabled 97% of patients to have a successful EMA at home. Thirty-six per cent of the total 878 patients during the pilot reported that they had no other option for accessing an abortion. Patients described telemedicine EMA services as a highly acceptable and appealing service option. Eighty-four per cent reported they would opt for the telemedicine service again and 83% reported they were very likely to recommend the service. There is potential for telemedicine to expand and improve access to critical SRH services. EMA via telemedicine can be delivered effectively in a low-resource setting. This pilot also showed how telemedicine provides access to patients who feel they do not have other safe service options, meeting specific patient needs in terms of discretion, convenience, and timing.

PMID:37728548 | DOI:10.1080/26410397.2023.2250621

Cancer Res Commun. 2023 Sep 20. doi: 10.1158/2767-9764.CRC-23-0084. Online ahead of print.

ABSTRACT

PURPOSE: RTOG 0617 was a Phase III randomized trial for patients with unresectable stage IIIA/IIIB non-small-cell lung cancer comparing standard-dose (60Gy) versus high-dose (74Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617.

EXPERIMENTAL DESIGN: From RTOG 0617 328/496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran-Mantel-Haenzel tests and multivariable logistic regression models were used. All statistical tests were two-sided, and a p-value <0.05 was considered significant.

RESULTS: A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients – while the hazard of death was higher in cetuximab treated patients within year one (HR=3.37, 95% CI: 1.13-10.10, p=0.030), death was lower from year one to four (HR=0.33, 95% CI: 0.11-0.97, p=0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR=1.59, 95% CI: 1.11-2.28, p=0.012).

CONCLUSIONS/DISCUSSION: Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy.

PMID:37728512 | DOI:10.1158/2767-9764.CRC-23-0084

Minerva Urol Nephrol. 2023 Oct;75(5):616-624. doi: 10.23736/S2724-6051.23.05394-6.

ABSTRACT

BACKGROUND: Both mini-percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) are two major strategies for the endourological management of kidney stones. In the current study, we aimed to compare the efficacy and safety of mPNL and RIRS for the treatment of 10-20 mm kidney stones in patients with ileal conduit.

METHODS: Patients with a history of bladder cancer and ileal conduit who had undergone mPNL or RIRS for unilateral kidney stones 10-20 mm in size between January 2015 and June 2022 were retrospectively included. Baseline characteristics and perioperative outcomes were analyzed and compared between mPNL and RIRS.

RESULTS: The failure rate of the initial surgery was 2.5% and 18.9% for mPNL and RIRS, respectively (P=0.025). In total, 39 and 30 patients were finally included in the mPNL and RIRS groups. One-session stone-free rate (SFR) was higher in the mPNL group than the RIRS group (97.4% vs. 66.7%, P=0.002). However, there was no statistically significant difference between the two groups with regard to operation time, postoperative hospitalization, complications according to Clavien-Dindo classification, as well as the change in hemoglobin, creatinine, procalcitonin, and pain Visual Analogue Scale Score before and after the surgery. Moreover, Results were consistent across subgroup analyses in patients stratified by years (2015-2018 and 2019-2022).

CONCLUSIONS: Both mPNL and RIRS were feasible and safe for the treatment of 10-20 mm kidney stones in patients with ileal conduit. However, mPNL achieved superior SFR outcomes with a similar incidence of complications, and it might be a sensible alternative for selected patients.

PMID:37728497 | DOI:10.23736/S2724-6051.23.05394-6

Arthritis Care Res (Hoboken). 2023 Sep 20. doi: 10.1002/acr.25237. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the relationship between bone shape and radiographic severity in individuals with first metatarsophalangeal joint osteoarthritis (first MTP joint OA).

METHODS: Weightbearing lateral and dorso-plantar radiographs were obtained for the symptomatic foot of 185 participants (105 females, aged 22 to 85 years) with clinically diagnosed first MTP joint OA. Participants were classified into either none/mild, moderate, or severe categories using a standardised atlas. An 80-point model for lateral radiographs and 77-point model for dorso-plantar radiographs was used to define independent modes of variation using statistical shape modelling software. Odds ratios adjusted for confounders were calculated using ordinal regression to determine the association between radiographic severity and mode scores.

RESULTS: After assessment and grading of radiographs, 35 (18.9%) participants were included in the none/mild first MTP joint OA severity category, 69 (37.2%) in the moderate severity, and 81 (43.7%) in the severe category. For lateral view radiographs, 16 modes of variation were included, which collectively represented 83.2% of total shape variance. Of these, four modes were associated with radiographic severity. For dorso-plantar view radiographs, 15 modes of variation were included, representing 82.6% of total shape variance. Of these, six modes were associated with radiographic severity.

CONCLUSIONS: Variations in the shape and alignment of the medial cuneiform, first metatarsal, proximal and distal phalanx of the hallux are significantly associated with radiographic severity of first MTP joint OA. Prospective studies are required to determine whether bone shape characteristics are associated with the development and/or progression of this condition.

PMID:37728065 | DOI:10.1002/acr.25237

Ren Fail. 2023;45(2):2258987. doi: 10.1080/0886022X.2023.2258987. Epub 2023 Sep 20.

ABSTRACT

BACKGROUND: This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score and renal venous Doppler waveform (RVDW) pattern in predicting acute kidney injury (AKI) in critically ill patients and establish prediction models.

METHODS: This prospective observational study included 234 critically ill patients. Renal ultrasound was measured within 24 h after intensive care unit admission. The main outcome was the highest AKI stage within 5 days after admission according to the Kidney Disease Improving Global Outcomes criteria.

RESULTS: Patients in the AKI stage 3 group had significantly higher RRI, RVDW pattern and lower PDU score (p < 0.05). Only lactate, urine volume, serum creatinine (SCr) on admission, PDU score and RVDW pattern were statistically significant predictors (p < 0.05). Model 1 based on these five variables (area under the curve [AUC] = 0.938, 95% confidence interval [CI] 0.899-0.965, p < 0.05) showed the best performance in predicting AKI stage 3, and difference in AUC between it and the clinical model including lactate, urine volume and SCr (AUC = 0.901, 95% CI 0.855-0.936, p < 0.05) was statistically significant (z statistic = 2.224, p = 0.0261). The optimal cut-off point for a nomogram based on Model 1 was ≤127.67 (sensitivity: 95.8%, specificity: 82.3%, Youden’s index: 0.781).

CONCLUSIONS: The nomogram model including SCr, urine volume, lactate, PDU score and RVDW pattern upon admission exhibited a significantly stronger capability for AKI stage 3 than each single indicator and clinical model including SCr, urine volume and lactate.

PMID:37728063 | DOI:10.1080/0886022X.2023.2258987