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Is there a relationship between CSF Interleukin 34 Level and clinicoradiological activity and IgG index in patients with MS?

Mult Scler Relat Disord. 2024 Nov 8;92:106150. doi: 10.1016/j.msard.2024.106150. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple sclerosis is an autoimmune, inflammatory, and disabling disease that is subject to research, with the aspects of its pathogenesis awaiting clarification. It is essential to predict the prognosis of the disease and find the responsible mechanisms and molecules to become a treatment option. In this regard, researching the impact of Interleukin 34, with its immunomodulatory properties, on the clinicoradiological activity effect of MS and determining its role, if any, may be guiding.

METHODS: The study included 52 MS patients who underwent lumbar puncture at the diagnosis stage, and dimethyl fumarate treatment was initiated in these patients. During a one-year prospective follow-up, CSF IL-34 levels of 26 patients with clinical and/or radiological activity and 26 patients without activity were evaluated for prediction of disease activity. Additionally, CSF IL-34 levels of 26 control patients who underwent lumbar puncture due to pseudotumor cerebri but were not diagnosed with this disorder and whose CSF examinations were normal and were compared with MS patients. Our study also included the Immunoglobulin G index and investigated its relationship with IL-34.

RESULTS: The IL-34 level was higher in the MS patient group compared to the control group. No significant difference was identified between MS patient groups with and without clinical and/or radiological activity. A weak correlation without statistical significance was found between IL-34 and the IgG index.

CONCLUSION: The IL-34 level did not correlate with clinical and radiological activity in MS patients. However, the high IL-34 level observed in the patient group in comparison with the control group may be significant for MS pathogenesis. Furthermore, IL-34 may be a useful biomarker candidate for MS diagnosis, similar to the IgG index.

PMID:39571220 | DOI:10.1016/j.msard.2024.106150

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Patterns of cognitive decline across different multiple sclerosis clinical courses

Mult Scler Relat Disord. 2024 Nov 12;92:106172. doi: 10.1016/j.msard.2024.106172. Online ahead of print.

ABSTRACT

BACKGROUND: It is still unclear whether patients with progressive MS (PMS) present a distinct pattern of cognitive impairment (CI) and different trajectories of cognitive and clinical decline compared to patients with relapsing-remitting MS (RRMS) with similar age. In addition, the role of reserve (cognitive and cerebral) in cognitive decline in the different forms of MS is not fully understood, and some studies suggest that its effects reduce in the progressive forms.

OBJECTIVE: To assess the trajectories of cognitive decline in RRMS and PMS patients with similar age, also evaluating the predictive power of baseline clinical and MRI features on cognitive outcomes at follow-up.

METHODS: Fifty-four patients were enrolled (30 PMS, 24 RRMS) and underwent brain MRI (3T – FreeSurfer and Spinal Cord Toolbox), clinical examination (Expanded Disability Status Scale – EDSS; Timed 25-Foot Walk Test – T25FW; and the Nine Hole Peg Test – 9HPT) and neuropsychological evaluation (Brief Repeatable Battery of Neuropsychological Tests – BRBN, Tower of London (TOL) test and Boston Naming Test at baseline (time 1) and after 4 years (time 2). We also evaluated cognitive and brain reserve. We defined CI as the presence of impairment in >1 domain.

RESULTS: At baseline (time 1), 37.2 % of the individuals presented CI and 52.4 % at time 2, which was more frequent in the PMS group. There was also a higher frequency of impairment in the visual memory and Information Processing Speed (IPS) cognitive domains in the PMS group in both study times. However, there were no major statistical differences between RMS/PMS groups in the evolution of clinical, cognitive and neuroimaging variables after 4 years of follow-up, except for a worse verbal memory decline (p = 0.040) and corpus callosum atrophy (p = 0.014) in PMS group. For EDSS worsening, the best predictive factor was the spinal cord area (β = -0.428), and for T25FW, the striatum volume (β = -0.467). For cognitive deterioration, striatum volume and cortical thickness were the best predictors. We found a protective effect of cognitive reserve on the decline of the domains of planning (β = 0.601) and IPS (β = 0.482) for the overall sample and the PMS group (β = 0.498 and β = 0.468, respectively).

CONCLUSIONS: We found cognitive deterioration after four years of follow-up in RRMS and PMS groups. Nevertheless, there were no major differences between these groups (with similar age, education and disease duration) in the trajectories of clinical, cognitive and neuroimaging variables during this 4-year period. We observed a protective effect of cognitive reserve in the overall sample and the PMS group.

PMID:39571219 | DOI:10.1016/j.msard.2024.106172

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Stereotactic Ablative Radiotherapy for Bone-Only Oligometastatic Breast Cancer: On a Quest to Find the Optimum Cohort

Clin Oncol (R Coll Radiol). 2024 Oct 29;37:103670. doi: 10.1016/j.clon.2024.103670. Online ahead of print.

ABSTRACT

AIMS: We aimed to evaluate the treatment outcomes and associated prognostic factors in breast cancer (BC) patients who had bone-only oligometastatic disease (OMD) and we tried to determine the subgroup that would benefit most from stereotactic ablative radiotherapy (SABR).

MATERIALS AND METHODS: We enrolled 47 patients with a total of 63 lesions with bone-only oligometastatic BC who underwent SABR for all bone lesions between July 2013 and March 2022. Cases with bone-only metastatic disease with up to 5 metastatic lesions that can be safely treated with SABR were included in this study. All statistical analyses were performed using SPSS 23.0 software (SPSS, Chicago, IL).

RESULTS: The median follow-up time was 34 months. The 2- and 5-year overall survival (OS) rates were 90% and 66%, and the progression-free survival (PFS) rates were 49% and 29%, respectively. The local control rate in the SABR-treated foci was 85%. In multivariate analysis, OMD state (genuine vs. induced), de-novo OMD state (synchronous vs. metachronous), and histology (luminal vs. HER-2 enriched) were prognostic for OS. Molecular subtype switch was observed in 21 (42%) patients, and 0% PFS was observed in 5 years in patients with phenotypic discordance. SABR was well tolerated and there were no ≥grade 4 acute or late toxicities.

CONCLUSION: Our study showed that in patients with bone-only OMD, in HER2-enriched subtypes with genuine & de-novo & synchronous OMD, SABR should be strongly considered for all metastatic foci, especially if there is phenotypic discordance in the primary tumor and metastasis.

PMID:39571205 | DOI:10.1016/j.clon.2024.103670

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Normal Bone Matrix Mineralization but Altered Growth Plate Morphology in the LmnaG609G/G609G Mouse Model of Progeria

Aging Dis. 2024 Nov 14. doi: 10.14336/AD.2024.1094. Online ahead of print.

ABSTRACT

Hutchison-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by a mutation in LMNA, the gene encoding A-type lamins, leading to premature aging with severely reduced life span. HGPS is characterized by growth deficiency, subcutaneous fat and muscle issue, wrinkled skin, alopecia, and atherosclerosis. Patients also develop a bone phenotype with reduced bone mineral density, osteolysis and striking demineralization of long bones. To further clarify the tissue modifications in HGPS, we characterized bone mineralization in the LmnaG609G/G609G progeria mouse model. Femurs from 8-week-old mice and humeri from 15-week-old mice were analyzed using quantitative backscattered electron imaging to assess bone mineralization density distribution, osteocyte lacunae sections and structural bone histomorphometry. Tissue sections were stained with Giemsa and Goldner trichrome for histologic evaluation. Bone tissue from Lmna+/+ and LmnaG609G/G609G mice had similar mineral content at 3 different bone sites with specific tissue ages. The osteocyte lacunae features were not statistically different, but more empty lacunae were found in LmnaG609G/G609G at both animal ages. Bone histomorphometry and histology demonstrated decreased bone volume per tissue volume in primary (8W: -23%, p=0.001; 15W: -38%, p=0.002) and secondary spongiosa (8W: -36%, p=0.001; 15W: -49 %, ns), as well as growth plate dysplasia with thinner unmineralized resting and proliferative zones in the LmnaG609G/G609G mice versus controls (8W: -18%, p=0.006; 15W: -25%, p=0.001). Overall, the LmnaG609G/G609G mouse develops chondrodysplasia with reduced trabecular bone volume. Mineral content findings at several tissue sites and ages suggest that bone dysplasia results from impaired bone formation with normal bone turnover.

PMID:39571160 | DOI:10.14336/AD.2024.1094

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German Version of the Telehealth Usability Questionnaire and Derived Short Questionnaires for Usability and Perceived Usefulness in Health Care Assessment in Telehealth and Digital Therapeutics: Instrument Validation Study

JMIR Hum Factors. 2024 Nov 21;11:e57771. doi: 10.2196/57771.

ABSTRACT

BACKGROUND: The exponential growth of telehealth is revolutionizing health care delivery, but its evaluation has not matched the pace of its uptake. Various forms of assessment, from single-item to more extensive questionnaires, have been used to assess telehealth and digital therapeutics and their usability. The most frequently used questionnaire is the “Telehealth Usability Questionnaire” (TUQ). The use of the TUQ is limited by its restricted availability in languages other than English and its feasibility.

OBJECTIVE: The aims of this study were to create a translated German TUQ version and to derive a short questionnaire for patients-“Telehealth Usability and Perceived Usefulness Short Questionnaire for patients” (TUUSQ).

METHODS: As a first step, the original 21-item TUQ was forward and back-translated twice. In the second step, 13 TUQ items were selected for their suitability for the general evaluation of telehealth on the basis of expert opinion. These 13 items were surveyed between July 2022 and September 2023 in 4 studies with patients and family members of palliative care, as well as patients with chronic autoimmune diseases, evaluating 13 health care apps, including digital therapeutics and a telehealth system (n1=128, n2=220, n3=30, and n4=12). Psychometric exploratory factor analysis was conducted.

RESULTS: The analysis revealed that a parsimonious factor structure with 2 factors (“perceived usefulness in health care” and “usability”) is sufficient to describe the patient’s perception. Consequently, the questionnaire could be shortened to 6 items without compromising its informativeness.

CONCLUSIONS: We provide a linguistically precise German version of the TUQ for assessing the usability and perceived usefulness of telehealth. Beyond that, we supply a highly feasible shortened version that is versatile for general use in telehealth, mobile health, and digital therapeutics, which distinguishes between the 2 factors “perceived usefulness in health care” and “usability” in patients.

TRIAL REGISTRATION: German Clinical Trials Register DRKS00030546; https://drks.de/search/de/trial/DRKS00030546.

PMID:39571151 | DOI:10.2196/57771

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Immigrant Health and Early-Onset Colorectal Cancer Disparities: Results From the Spanish Early-Onset Colorectal Cancer Consortium

JCO Glob Oncol. 2024 Nov;10:e2400393. doi: 10.1200/GO-24-00393. Epub 2024 Nov 21.

ABSTRACT

PURPOSE: To better understand immigration disparities among a Spanish Early-Onset Colorectal Cancer (SECOC) subset, according to the country of origin.

PATIENTS AND METHODS: We selected 250 consecutive participants from the SECOC consortium. Data on baseline patient and tumor characteristics, family history of colorectal cancer (CRC), and follow-up were collected. The presence of mismatch repair deficiency was also assessed. Special data regarding country of origin, time of stay in Spain in case of other different country, and a 10-year cutoff that specifies the obtaining of Spanish nationality defined the variables of interest for comparison.

RESULTS: Seventy-five percent of patients with early-onset CRC (EOCRC) (188) were born in Spain, whereas the other 25% were born outside of Spain. The mean time of living in Spain until the EOCRC diagnosis was 16.5 years. Comparatively, most of the analyzed features showed equivalent proportions between cohorts. Only Spanish patients appeared to have more familial cancer component in first degree in general (32.3%; P = .01), compared with non-Spaniards, which showed a predominant sporadic component (56.4%; P < .001). Among immigrants, those patients living in Spain before CRC diagnosis ≤10 years were younger at diagnosis (39.1 v 42.5), more frequently male (77.8 v 47.7), were in more advanced stages (88.8% diagnosed at stage III and IV [P = .01]), and had a worse prognosis regarding recurrence rates (29.4% v 6.3%).

CONCLUSION: Although there were few differences between Spanish and non-Spanish EOCRC, the most remarkable difference was that linked with the situation of those immigrants who have recently arrived in Spain, in relation to their lower health coverage, which could be associated with the delay in the diagnosis and their subsequent worse prognosis.

PMID:39571135 | DOI:10.1200/GO-24-00393

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Evaluation of a Chronic Care Management Model for Improving Efficiency and Fiscal Sustainability

Am J Public Health. 2024 Nov 21:e1-e5. doi: 10.2105/AJPH.2024.307886. Online ahead of print.

ABSTRACT

Chronic care management is effective. Barriers to program durability include dependence on the provider-nurse duo to carry out labor-intensive services and the lack of a fiscally sustainable model. Between January and October 2022, an expanded chronic care management team-consisting of a provider, nurse, community health worker, and pharmacist-conducted a four-month intervention in an ambulatory setting. This intervention, using a convenience sample of 134 Medicare patients with uncontrolled type 2 diabetes or hypertension, demonstrated statistically significant improvements in controlling type 2 diabetes (P < .01) and blood pressure (P < .001). Direct provider workload decreased, and the Medicare reimbursement rate was 85.5%. (Am J Public Health. Published online ahead of print November 21, 2024:e1-e5. https://doi.org/10.2105/AJPH.2024.307886).

PMID:39571131 | DOI:10.2105/AJPH.2024.307886

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Cross-Sectional National Survey of Practice Patterns in Radiotherapy for Rectal Cancer: A Snapshot of India

JCO Glob Oncol. 2024 Nov;10:e2400410. doi: 10.1200/GO-24-00410. Epub 2024 Nov 21.

ABSTRACT

PURPOSE: The information on the practice of radiotherapy, including intensity-modulated radiotherapy (IMRT) use for rectal cancer in India, is lacking. This national survey was planned to understand the current status of knowledge, attitudes, and practice among radiation oncologists, specifically concerning the practice of IMRT for rectal cancers.

MATERIALS AND METHODS: A national survey was sent to radiation oncologists through e-mail or a WhatsApp message, where feasible, with a request letter containing the link to the survey questionnaire. The survey questionnaire was adapted from the UK IMRT survey with permission from the authors. It explored rectal cancer management, IMRT use, reasons for nonadoption, total neoadjuvant therapy (TNT), dose fractionation schedules and radiotherapy processes like radiotherapy simulation, target volume/organ at risk definition, and treatment planning, evaluation, and verification. Descriptive statistics is used to present the results.

RESULTS: Over 300 radiation oncologists were approached, and 182 (60.6%) of the 153 institutes responded. Around 88% (160 of 182) indicated using IMRT or volumetric modulated arc therapy (VMAT) to treat rectal cancer, of whom 32% used exclusively IMRT/VMAT in all their patients. The reasons for not adopting IMRT were affordability/lack of insurance, resource constraints, and lack of guidelines. Long-course chemoradiation (capecitabine-based) followed by surgery was the most common neoadjuvant approach, with short course and TNT in less than a third of patients. Daily verification feasibility was reported by 60%. Seventy-three percent emphasized the need for a national IMRT guidance document.

CONCLUSION: This national survey from India indicates a scope of routine implementation of IMRT in rectal cancer, highlighting the urgent need for a national IMRT guidance document, which could significantly enhance the quality of care for patients with rectal cancer in India.

PMID:39571114 | DOI:10.1200/GO-24-00410

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Indonesian Society of Gynecologic Oncology Cancer Registration Information System: 10 Years of Implementation, Challenge, and Future

JCO Glob Oncol. 2024 Nov;10:e2400176. doi: 10.1200/GO.24.00176. Epub 2024 Nov 21.

ABSTRACT

PURPOSE: Indonesia still faces high disease burden from cancer and needs valid gynecologic cancer epidemiology data. The Indonesian Society of Gynecologic Oncology (INASGO) established a web-based gynecologic cancer registry. This research aims to observe and report the situation of INASGO cancer registration information system from 2011 to 2021 and provide the most recent data.

METHODS: This is a quality assurance research using nonexperimental design and did not perform data manipulation. This study will evaluate comparability, validity, and completeness of cancer registry data. Information was obtained by registration files, direct observation, and interviewing cancer registry supervisors in Cipto Mangunkusumo Hospital, Jakarta.

RESULTS: This cancer registry coded its data according to international standards with many participants and large cases registered. A total of 28,692 cases were reported to the cancer registry. Cervical cancer ranked highest (68.6%) with stage III being the most common found. The most frequent age group at diagnosis is 36-55 years. The most valid basic diagnostic of gynecologic cancer is histology of primary malignancy. The main challenge of the INASGO cancer registry is the lack of data validity and completeness because of poor coordination and financial support.

CONCLUSION: INASGO cancer registration information system has good prospects to provide data information of patients with gynecologic cancer in policy or research matters. Poor coordination and limited financial support have to be anticipated for the sake of this cancer registry existence in the future.

PMID:39571112 | DOI:10.1200/GO.24.00176

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Timeliness of Breast Cancer Patients’ Presentation to Health Care Facilities in Ethiopia: A Systematic Review and Meta-Analysis

JCO Glob Oncol. 2024 Nov;10:e2400263. doi: 10.1200/GO-24-00263. Epub 2024 Nov 21.

ABSTRACT

PURPOSE: Low breast cancer survival rates are often linked to late-stage diagnosis. The patient interval, the time between symptom detection and the first health care visit, is a key indicator of early diagnosis. This study aimed to assess the prevalence of patient delay and its associated factors in Ethiopia.

METHODS: This systematic review used a combined approach of meta-analysis and meta-synthesis of quantitative and qualitative data, respectively. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.

RESULTS: Eleven studies that satisfied the eligibility criteria were included in the review. More than half (58.48%) of the patients with breast cancer delayed seeking medical help at health facilities, with a median delay time of 120 days. Presence of a painful breast ulcer/wounded mass (odds ratio [OR], 0.23 [95% CI, 0.09 to 0.58]), having swelling or a lump in the armpit (OR, 0.27 [95% CI, 0.15 to 0.46]), residing in urban area (OR, 0.27 [95% CI, 0.15 to 0.49]), and having a secondary school education or higher (OR, 0.28 [95% CI, 0.12 to 0.64]) were less likely to delay in seeking formal health care. However, patients who travel more than 5 km (OR, 6.33 [95% CI, 4.10 to 9.75]) were more likely to delay in our meta-analysis. Moreover, the meta-synthesis showed that the nature and progression of symptoms, symptom disclosure, social support, emotional responses, use of alternative therapies, misconceptions about breast cancer, financial limitations, accessibility issues, and other personal-environmental factors were associated with patient delay.

CONCLUSION: Nearly three fifths of patients with breast cancer delayed seeking health care at health facilities. Inaccessibility, low awareness, cultural beliefs, and socioeconomic factors contributed to these delays. Increasing public awareness, especially in rural areas, and improving health care access could encourage earlier presentation.

PMID:39571108 | DOI:10.1200/GO-24-00263