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World Journal of Surgery Jun 2024In colorectal cancer, the morphological categorization of fibrotic cancer stroma in the invasive frontal zone of the primary tumor is well reflected in the prognosis....
BACKGROUND/PURPOSE
In colorectal cancer, the morphological categorization of fibrotic cancer stroma in the invasive frontal zone of the primary tumor is well reflected in the prognosis. Conversely, the histological characteristics of pancreatic cancer (PC) reveal fibrotic hyperplasia of stroma known as desmoplasia; however, its characterization is unknown. Therefore, this study aimed to evaluate the prognostic factors according to the histological categorization of desmoplastic reactions in PC.
METHODS
We retrospectively enrolled 167 patients who underwent curative resection for PC. The desmoplastic pattern was histologically classified as mature, intermediate, or immature. Clinicopathological features were evaluated, and disease-free and overall survival (OS) were analyzed in the three groups. Prognostic factors were assessed using univariate and multivariate analyses.
RESULTS
In total, 19 mature, 87 intermediate, and 61 immature desmoplastic patterns were evaluated. Jaundice decompression, white blood cell count, and platelet/lymphocyte ratio were significantly different among the groups. The mature group had a better disease-free survival (DFS) prognosis than the other two groups; however, OS did not differ between the groups. Desmoplastic patterns showed significant differences between the three groups for DFS.
CONCLUSIONS
Desmoplastic patterns are a prognostic factor of DFS for PC, with mature desmoplastic reactions associated with good prognosis. Thus, they may aid in individualized therapeutic approaches in patients with PC.
PubMed: 38943046
DOI: 10.1002/wjs.12269 -
Internal and Emergency Medicine Jun 2024It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation...
It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). The aim of the study was to compare safety and effectiveness of DOACs and VKAs in patients with NVAF and stage 4 CKD (creatinine clearance 15-29 mL/min). We searched the hospital databases of two academic centers to retrospectively identify patients with stage 4 CKD who were on treatment with DOACs or VKAs for NVAF. Safety was the primary outcome of the study and was assessed in terms of incidence of major bleeding (MB). Secondary outcomes were clinically relevant non-major bleeding (CRNMB) and death for any cause. A total of 176 patients (102 on DOACs and 74 on VKAs) were found and included in the analysis. The incidence rate of MB was not statistically different between groups (8.6 per 100 patients-year in the DOAC group and 5.6 per 100 patients-year in the VKA group). Rates of IS/SSE and CRNMB were statistically similar in the two treatment groups, as well. There were less deaths for any cause in the DOAC group than in the VKA group (8.6 and 15.8 per 100 patients-year, respectively), but the difference was not statistically significant. This study found no difference in terms of safety and effectiveness between patients with NVAF and stage 4 CKD treated with DOACs and VKAs. Larger prospective or randomized studies are needed to confirm these findings.
PubMed: 38943034
DOI: 10.1007/s11739-024-03658-9 -
Irish Journal of Medical Science Jun 2024In Irish orthopaedic centres without dedicated spinal services, the care of patients is facilitated through tertiary referral centres in Dublin, Cork & Galway. The...
INTRODUCTION
In Irish orthopaedic centres without dedicated spinal services, the care of patients is facilitated through tertiary referral centres in Dublin, Cork & Galway. The outpatient waiting list for elective spinal opinion remains lengthy and challenging. Previous practice in University Hospital Waterford (UHW) necessitated an assessment with a local non-spinal orthopaedic specialist following a GP referral, incurring up to a 2-year wait prior to subspecialist spinal referral. These patients subsequently incurred a further wait for an appointment at the tertiary referral centre. A novel virtual spine clinic in collaboration with the Mater Misericordiae University Hospital (MMUH) was developed to fast-track this process.
AIMS AND METHODS
A retrospective study was performed to audit efficiency by assessing time to initial consultation and time to virtual consultation, treatment outcomes, and patient satisfaction using an adapted patient-satisfaction questionnaire (PSQ-18) and a semi-structured interview. This study reflected the unique nature of patient experience in this pathway.
RESULTS
The median time from referral to being seen in an in-person rapid access physiotherapist combined orthopaedic clinic was 185 days. The median time from initial consultation to virtual consultation was 36 days. The median time interval from virtual consultation to intervention was 110 days. Twenty percent of patients underwent surgery, 14% were further seen in the MMUH outpatients, 7% managed with the trial of physiotherapy, 7% required no follow-up, and 50% planned for radiologically guided spinal injections.
DISCUSSION AND CONCLUSION
This novel pathway is efficient for orthopaedic units without a dedicated spinal service. This can easily be replicated across other orthopaedic centres with minimal cost implications.
PubMed: 38943033
DOI: 10.1007/s11845-024-03742-1 -
Cardiovascular and Interventional... Jun 2024Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.
PURPOSE
Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.
MATERIALS AND METHODS
An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS).
RESULTS
Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0-52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3-8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively.
CONCLUSION
IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.
PubMed: 38943032
DOI: 10.1007/s00270-024-03795-w -
Cellular and Molecular Life Sciences :... Jun 2024Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes...
Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs.
Topics: Humans; MicroRNAs; Cetuximab; Drug Resistance, Neoplasm; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Jumonji Domain-Containing Histone Demethylases; Argonaute Proteins; Animals; Mice; Cell Nucleus; Female; Mice, Nude
PubMed: 38943031
DOI: 10.1007/s00018-024-05324-x -
Gastric Cancer : Official Journal of... Jun 2024In 2019, the Gastrectomy Complications Consensus Group (GCCG) published a standardized set of complications aiming toward uniform reporting of post-gastrectomy...
BACKGROUND
In 2019, the Gastrectomy Complications Consensus Group (GCCG) published a standardized set of complications aiming toward uniform reporting of post-gastrectomy complications. This study aimed to report outcomes after gastrectomy in the Netherlands according to GCCG definitions and compare them to previously reported national results and the European database reported by the GCCG.
METHODS
This nationwide, population-based cohort study included all patients undergoing gastrectomy for gastric cancer registered in the DUCA in 2020-2021. Postoperative morbidity and 30-day/in-hospital mortality were analyzed according to the GCCG definitions. For all patients, baseline characteristics and outcomes were compared with the GCCG cohort consisting of 27 European expert centers (GASTRODATA; 2017-2018).
RESULTS
In 2020-2021, 782 patients underwent gastrectomy in the Netherlands. Variation was seen in baseline characteristics between the Dutch and the GCCG cohort (N = 1349), most notably in minimally invasive surgery (80.6% vs 19.6%, p < 0.001). In the Netherlands, 223 (28.5%) patients developed a total of 407 complications, the most frequent being non-surgical infections (28.5%) and anastomotic leakage (13.4%). The overall complication and 30-day mortality rates were similar between the Dutch and GCCG cohort (28.5% vs 29.8%, p = 0.563; 3.7% vs 3.6%, p = 0.953). Higher surgical and endoscopic/radiologic reintervention rates were observed in the Netherlands compared to the GCCG cohort (10.7% vs 7.8%, p = 0.025; 10.9% vs 2.9%, p < 0.001).
CONCLUSION
Reporting outcomes according to the standardized GCCG definitions allows for international benchmarking. Postoperative outcomes were comparable between Dutch and GCCG cohorts, but both exceed the international benchmark for expert gastrectomy care, highlighting targets for national and international quality improvement.
PubMed: 38943030
DOI: 10.1007/s10120-024-01527-0 -
International Ophthalmology Jun 2024To investigate the clinical significance of the correlation between optical densitometry and both biomechanical and morphological parameters in keratoconus (KC) and to...
PURPOSE
To investigate the clinical significance of the correlation between optical densitometry and both biomechanical and morphological parameters in keratoconus (KC) and to verify the diagnostic value of optical densitometry in KC.
METHOD
This cross-sectional study included 436 eyes of 295 patients with KC. Corneal optical densitometry, morphological parameters and biomechanical parameters were measured. Spearman's correlation analysis was employed to investigate the association between optical densitometry and both biomechanical and morphological parameters.
RESULT
Optical densitometry of the anterior (0-2 mm and 2-6 mm), central (0-2 mm), posterior (2-6 mm) and total (2-6 mm) layers correlated positively with SPA1, while the posterior layer (0-2 mm) correlated negatively. Optical densitometry of the anterior layers 2-6 mm, 6-10 mm, and the central layer 6-10 mm negatively affected AL1, while the posterior layer 0-2 mm positively affected it. Optical densitometry of the anterior, central, and posterior layers 0-2 mm and 2-6 mm positively influenced the morphological parameters K, K, K and the absolute values of K, K, K. Optical densitometry of the center (0-2 mm) and posterior (2-6 mm) layers negatively influenced TCT. Optical densitometry of the anterior (0-2 mm and 2-6 mm), center (0-2 mm), posterior (2-6 mm) and total (2-6 mm) layers correlated positively with ACE and PCE, whereas the posterior layer (0-2 mm) correlated negatively.
CONCLUSION
Optical densitometry was correlated with biomechanical and morphological parameters in keratoconus, suggesting its potential as a diagnostic indicator for assessing keratoconus progression and treatment efficacy.
Topics: Humans; Keratoconus; Cross-Sectional Studies; Female; Densitometry; Male; Cornea; Adult; Corneal Topography; Young Adult; Adolescent; Middle Aged; Biomechanical Phenomena
PubMed: 38943020
DOI: 10.1007/s10792-024-03212-8 -
Neurological Sciences : Official... Jun 2024Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS)...
Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.
PubMed: 38943019
DOI: 10.1007/s10072-024-07674-7 -
Journal of General Internal Medicine Jun 2024South Asian immigrants in the United States face an elevated risk of developing type 2 diabetes (T2DM). This phenomenon has been linked to lifestyle factors and social...
South Asian immigrants in the United States face an elevated risk of developing type 2 diabetes (T2DM). This phenomenon has been linked to lifestyle factors and social determinants of health (SDOH) such as high-carbohydrate diet, limited physical activity, and stress from assimilation and other life challenges. Unfortunately, barriers stemming from language discordance, low health literacy, and certain cultural practices can hinder effective clinical management of T2DM among South Asian immigrants. In this perspective, we address these sociocultural barriers and propose culturally informed recommendations to improve healthcare delivery for South Asian groups and empower South Asian patients to self-manage T2DM. Our recommendations include (1) considerations and support for SDOH in South Asian communities, (2) culturally tailored healthcare delivery for South Asians, (3) mHealth technologies for T2DM education and self-management; and (4) enhanced epidemiological and South Asian-centric research.
PubMed: 38943015
DOI: 10.1007/s11606-024-08902-8 -
Journal of General Internal Medicine Jun 2024Diabetes self-management education and support can be effectively and efficiently delivered in primary care in the form of shared medical appointments (SMAs)....
BACKGROUND
Diabetes self-management education and support can be effectively and efficiently delivered in primary care in the form of shared medical appointments (SMAs). Comparative effectiveness of SMA delivery features such as topic choice, multi-disciplinary care teams, and peer mentor involvement is not known.
OBJECTIVE
To compare effects of standardized and patient-driven models of diabetes SMAs on patient-level diabetes outcomes.
DESIGN
Pragmatic cluster randomized trial.
PARTICIPANTS
A total of 1060 adults with type 2 diabetes in 22 primary care practices.
INTERVENTIONS
Practice personnel delivered the 6-session Targeted Training in Illness Management (TTIM) curriculum using either standardized (set content delivered by a health educator) or patient-driven SMAs (patient-selected topic order delivered by health educators, behavioral health providers [BHPs], and peer mentors).
MAIN MEASURES
Outcomes included self-reported diabetes distress and diabetes self-care behaviors from baseline and follow-up surveys (assessed at 1st and final SMA session), and HbA1c, BMI, and blood pressure from electronic health records. Analyses used descriptive statistics, linear regression, and linear mixed models.
KEY RESULTS
Both standardized and patient-driven SMAs effectively improved diabetes distress, self-care behaviors, BMI (- 0.29 on average), and HbA1c (- 0.45% (mmol/mol) on average, 8.3 to 7.8%). Controlling for covariates, there was a small, significant effect of condition on overall diabetes distress in favor of standardized SMAs (F(1,841) = 4.3, p = .04), attributable to significant effects of condition on emotion and regimen distress subscales. There was a small, significant effect of condition on diastolic blood pressure in favor of standardized SMAs (F(1,5199) = 4.50, p = .03). There were no other differences between conditions.
CONCLUSIONS
Both SMA models using the TTIM curriculum yielded significant improvement in diabetes distress, self-care, and HbA1c. Patient-driven diabetes SMAs involving BHPs and peer mentors and topic selection did not lead to better clinical or patient-reported outcomes than standardized diabetes SMAs facilitated by a health educator following a set topic order.
NIH TRIAL REGISTRY NUMBER
NCT03590041.
PubMed: 38943014
DOI: 10.1007/s11606-024-08868-7