Association of multidimensional comorbidities with survival,toxicity, and unplanned hospitalizations in older adults with metastatic colorectal cancer treated with chemotherapy

BackgroundStudies of older patients with colorectal cancer(CRC) have found inconsistent results about the correlation of various comorbidities with overall survival(OS) and treatment tolerance. To refine our understanding, we evaluated this correlation using the Cumulative Illness Rating Scale-Geriatric(CIRS-G) and heat maps to identify subgroups with the highest impact.MethodsWe retrospectively reviewed 153 patients aged 65 years and older with stage IV CRC undergoing chemotherapy. We calculated CIRS-G scores, and a Total Risk Score(TRS) derived from a previous heat map study. The association between CIRS-G scores/TRS and OS, unplanned hospitalizations, and chemotoxicity was examined by the Cox proportional hazards model.ResultsMedian age was 71 years. Median MAX2 score of chemotherapies was 0.134(0.025–0.231). The most common comorbidities were vascular(79.8%), eye/ear/nose/throat(68%), and respiratory disease(52.4%). Median OS was 25.1 months(95% confidence interval: 21.2–27.6). In univariate analysis, ECOG PS ≥ 2(HR 1.86(1.1–3.17), p = 0.019), poorly differentiated histology(HR 2.03(1.27–3.25), p = 0.003), primary site(rectum vs colon)(HR 0.58 (0.34–0.98), p = 0.04), age at diagnosis(HR per 5y 1.20 (1.04–1.39), p = 0.012), and number of CIRS-G grade 4 comorbidities(HR 1.86 (1.1–3.17), p = 0.019) were associated with OS. In multivariate analysis, the number of CIRS-G grade 4 comorbidities lost significance, although it retained it in the subgroup of patients with colon cancer. Conversely, the TRS was associated with OS in patients with rectal cancer. No association of comorbidity with unplanned hospitalization or chemotoxicity was observed.ConclusionsIn older adults with metastatic CRC, the number of CIRS-G grade 4 comorbidities was associated with worse OS but no specific CIRS-G category was independently associated with OS, unplanned hospitalization, or toxicities.     

National level data analysis of facial lacerations in Korea using the National Health Insurance Service (NHIS) database

No national epidemiological investigations have been conducted recently regarding facial lacerations. The study was performed using the data of 3,634,229 people during the 5-year period from 2014 to 2018 archived by the National Health Information Database (NHID) of the Health Insurance Review and Assessment Service. Preschool and children under 10 years old accounted for about one-third of patients. Facial lacerations were concentrated in the “T-shaped” area, which comprised forehead, nose, lips, and the perioral area. The male to female ratio for all study subjects was 2.16:1. Age and gender are significantly related with each other (P < .001). Mean hospital stays decreased, and numbers of outpatient department visits per patient were highest for hospitals and lowest for health agencies. Over the study period, hospital costs per patient in tertiary and general hospitals increased gradually. Preschool and school-aged children are vulnerable to trauma. Male patients outnumbered female patients by a factor of more than 2. The “T-shaped’” area around forehead is vulnerable to injury. Total cost of medical care benefits per patient in tertiary hospitals was about 7 times on average than in health agencies. Regarding functional, behavioral, and aesthetic outcomes, more attention should be paid to epidemiologic data and hospital costs for facial lacerations.     

LncRNA GAS5 upregulates Smad4 to suppress the apoptosis of chondrocytes induced by lipopolysaccharide

Background: Osteoarthritis (OA) is closely correlated with inflammation. It has been reported that lncRNA GAS5 plays an important role in inflammation, indicating the potential involvement of GAS5 in OA. This study was carried out to investigate the function of GAS5 in OA.Methods: Expression levels of GAS5 in synovial fluid from 45 OA patients and 45 healthy controls were measured by RT-qPCR. Cell transfections were performed to explore the potential interactions among GAS5, miR-146a, and Smad4 in chondrocytes. Lipopolysaccharide (LPS)-induced cell apoptosis after overexpression of GAS5, miR-146a, and Smad4 was analyzed by cell apoptosis assay.Results: GAS5 was downregulated in OA. Moreover, LPS treatment downregulated GAS5 in chondrocytes. Interaction between GAS5 could with miR-146a was predicted by bioinformatics analysis and further confirmed by RNA-RNA pulldown assay. However, overexpression of GAS5 and miR-146a did not affect the expression of each other. GAS5 overexpression increased Smad4 expression in chondrocytes. In contrast, miR-146a overexpression downregulated Smad4 in chondrocytes. Moreover, GAS5 and Smad4 overexpression inhibited LPS- induced chondrocytes apoptosis, while miR-146a overexpression played an opposite role and attenuated the effects of GAS5 and Smad4 overexpression on cell apoptosis.Conclusion: GAS5 might sponge miR-146a to upregulate Smad4, thereby suppressing LPS- induced chondrocytes apoptosis.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

Ultrasonographic Analyses of the Forehead Region for Injectable Treatments

Botulinum toxin type A (BoNT-A) injections in the forehead region should only target the frontalis. This study applied ultrasonography with the aim of providing guidelines for predicting the layered structure and soft-tissue thickness of the forehead. We performed ultrasound scanning at 7 facial landmarks in 40 Korean adults. Allowing for the error range, the minimum depth from the skin to exclude the muscle layer was 2.3 mm, and the maximum depth from the skin to include the muscle layer was 2.8 mm. Of the total 7 points from the skin to muscle surface, significant differences between the males and females were found in 6 points (p < 0.05). Clinicians can use ultrasonography to identify the structural layers of the scalp. Even if ultrasound-guided injections are not performed, it is possible to target only muscle layers in BoNT-A injections by maintaining a needle depth of around 2.5 mm.     

Registries,Databases and Repositories for Developing Artificial Intelligence in Cancer Care

Modern artificial intelligence techniques have solved some previously intractable problems and produced impressive results in selected medical domains. One of their drawbacks is that they often need very large amounts of data. Pre-existing datasets in the form of national cancer registries, image/genetic depositories and clinical datasets already exist and have been used for research. In theory, the combination of healthcare Big Data with modern, data-hungry artificial intelligence techniques should offer significant opportunities for artificial intelligence development, but this has not yet happened. Here we discuss some of the structural reasons for this, barriers preventing artificial intelligence from making full use of existing datasets, and make suggestions as to enable progress. To do this, we use the framework of the 6Vs of Big Data and the FAIR criteria for data sharing and availability (Findability, Accessibility, Interoperability, and Reuse). We share our experience in navigating these barriers through The Brain Tumour Data Accelerator, a Brain Tumour Charity-supported initiative to integrate fragmented patient data into an enriched dataset. We conclude with some comments as to the limits of such approaches.     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.