Meta-analysis of risk of developing malignancy in congenital choledochal malformation

BackgroundCholedochal malformations comprise various congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. Choledochal malformation is generally considered a premalignant condition, but reliable data on the risk of malignancy and optimal surgical treatment are lacking. The objective of this systematic review was to assess the prevalence of malignancy in patients with choledochal malformation and to differentiate between subtypes. In addition, the risk of malignancy following cystic drainage versus complete cyst excision was assessed. MethodsA systematic review of PubMed and Embase databases was performed in accordance with the PRISMA statement. A meta-analysis of the risk of malignancy following cystic drainage versus complete cyst excision was undertaken in line with MOOSE guidelines. Prevalence of malignancy was defined as the rate of biliary cancer before resection, and malignant transformation as new-onset biliary cancer after surgery. ResultsEighteen observational studies were included, reporting a total of 2904 patients with a median age of 36 years. Of these, 312 in total developed a malignancy (107 per cent); the prevalence of malignancy was 73 per cent and the rate of malignant transformation was 34 per cent. Patients with types I and IV choledochal malformation had an increased risk of malignancy (P = 0016). Patients who underwent cystic drainage had an increased risk of developing biliary malignancy compared with those who had complete cyst excision, with an odds ratio of 397 (95 per cent c.i. 240 to 655). ConclusionThe risk of developing malignancy among patients with choledochal malformation was almost 11 per cent. The malignancy risk following cystic drainage surgery was four times higher than that after complete cyst excision. Complete surgical resection is recommended in patients with choledochal malformation. Choledochal cysts should be resecte

Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells.

In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDP-sensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 43 degrees C during cDDP exposure was found to increase drug accumulation significantly in the cDDP-resistant cell lines but had little effect on drug accumulation in the cDDP-sensitive cell lines. DNA adduct formation, however, was significantly increased in all cell lines studied. Furthermore, ongoing formation of platinum (Pt)-DNA adducts after the end of cDDP treatment was enhanced and/or adduct removal was decreased in heated cells, resulting in relatively more DNA damage remaining at 24 h after the end of cDDP exposure. Correlation plots with survival revealed weak correlations with cellular Pt accumulation (r2 = 0.59) and initial Pt-DNA adduct formation (r2 = 0.64). Strong correlations, however, were found with Pt-DNA adducts at 6 h (r2 = 0.97) and 24 h (r2 = 0.89) after the incubation with the drug. In conclusion, the mechanism by which heat sensitizes cells for cDDP action seems to be the sum of multiple factors, which comprise heat effects on accumulation, adduct formation and adduct processing. This mechanism did not seem to differ between cDDP-sensitive and -resistant cells, emphasizing the potential of hyperthermia to reduce cDDP resistance

Real-world keystroke dynamics are a potentially valid biomarker for clinical disability in multiple sclerosis

Background: Clinical measures in multiple sclerosis (MS) face limitations that may be overcome by utilising smartphone keyboard interactions acquired continuously and remotely during regular typing. Objective: The aim of this study was to determine the reliability and validity of keystroke dynamics to assess clinical aspects of MS. Methods: In total, 102 MS patients and 24 controls were included in this observational study. Keyboard interactions were obtained with the Neurokeys keyboard app. Eight timing-related keystroke features were assessed for reliability with intraclass correlation coefficients (ICCs); construct validity by analysing group differences (in fatigue, gadolinium-enhancing lesions on magnetic resonance imaging (MRI), and patients vs controls); and concurrent validity by correlating with disability measures. Results: Reliability was moderate in two (ICC = 0.601 and 0.742) and good to excellent in the remaining six features (ICC = 0.760–0.965). Patients had significantly higher keystroke latencies than controls. Latency between key presses correlated the highest with Expanded Disability Status Scale (r = 0.407) and latency between key releases with Nine-Hole Peg Test and Symbol Digit Modalities Test (ρ = 0.503 and r = −0.553, respectively), ps < 0.001. Conclusion: Keystroke dynamics were reliable, distinguished patients and controls, and were associated with clinical disability measures. Consequently, keystroke dynamics are a promising valid surrogate marker for clinical disability in MS

Estimating VO_2peak in 18–90 Year-Old Adults:Development and Validation of the FitMáx©-Questionnaire

Purpose: Cardiorespiratory fitness (CRF) plays an essential role in health outcomes and quality of life. However, it is often not assessed nor estimated. Objective CRF assessment is costly, labour intensive and not widely available. Patient-reported outcome measures estimate CRF more cost-efficiently, but current questionnaires lack accuracy. The aim of this study is to develop a new self-reported questionnaire to estimate CRF.</p

Extending the viability of human precision-cut intestinal slice model for drug metabolism studies

Human Precision-cut intestinal slices (hPCIS) are used to study intestinal physiology, pathophysiology, drug efficacy, toxicology, kinetics, and metabolism. However, the use of this ex vivo model is restricted to approximately a 24 h timeframe because of declining viability of the hPCIS during traditional culture. We hypothesized that we could extend the hPCIS viability by using organoid medium. Therefore, we cultured hPCIS for up to 72 h in organoid media [expansion medium (Emed) and differentiation medium (Dmed)]. After incubation, we assessed culture-induced changes on viability markers, specific cell type markers and we assessed the metabolic activity of enterocytes by measuring midazolam metabolite formation. We show that the adenosine triphosphate (ATP)/protein ratio of Emed-cultured hPCIS and morphology of both Emed- and Dmed-cultured hPCIS was improved compared to WME-cultured hPCIS. Emed-cultured hPCIS showed an increased expression of proliferation and stem cell markers, whereas Dmed-cultured hPCIS showed an increased expression of proliferation and enterocyte markers, along with increased midazolam metabolism. Using the Emed, the viability of hPCIS could be extended for up to 72 h, and proliferating stem cells remained preserved. Using Dmed, hPCS also remained viable for up to 72 h, and specifically rescued the metabolizing enterocytes during culture. In conclusion, by using two different organoid culture media, we could extend the hPCIS viability for up to 72 h of incubation and specifically steer stem cells or enterocytes towards their original function, metabolism, and proliferation, potentially allowing pharmacokinetic and toxicology studies beyond the 24 h timeframe

Development of a set of patient reported outcome measures for patients with benign liver tumours and cysts:patient focus groups and systematic review

BACKGROUND: Patient reported outcome measures (PROMs) may be useful for patients with benign liver tumours and cysts (BLTC) to evaluate the impact of treatment and/or guide shared decision making. Yet, a set of PROMs relevant to patients with BLTC is currently unavailable. In this study, we selected a PROMs set for patients with BLTC. METHODS: Potentially relevant patient reported outcomes (PROs) were selected by psychologist-researchers based on keywords used or suggested by participants of two virtual focus groups meetings consisting of thirteen female BLTC patients with a median age of 50 years. Subsequently, patients were asked to report their most relevant PROs. PROMs identified by systematic literature review and computerized adaptive tests (CATs) in the Patient-Reported Outcomes Measurement Information System (PROMIS) were considered in selecting the final PROMs set to assess relevant outcomes. RESULTS: The most important PROs were: insecurity/anxiety (11/12 patients), pain (9/12 patients), fatigue (8/12 patients), and limitations in daily life (5/12 patients). The literature review included 23 studies, which used various generic and disease-specific PROMs, often not measuring (all) relevant PROs. The final selected PROMs set included numerical rating scales for pain, two questions on overall health and quality of life and four PROMIS CATs. CONCLUSIONS: A PROMs set generically and efficiently measuring outcomes relevant for patients with BLTC was developed and may be used in future research and clinical practice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41687-022-00531-1

Effect of centralization and regionalization of pancreatic surgery on resection rates and survival

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