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GFR

was highly variable, increased after cisplatin, and exceeded 150ml/min/1.73m

. GFR

was less variable and decreased at the end of therapy. AKI biomarkers were elevated indicating acute tubular dysfunction, however, did not differ between 4 and 12h infusions. Radiographic and histological response were similar for patients receiving 4h or 12h infusions; the median percent tumor necrosis was > 95%.

Reducing peak serum and urine MTX concentration by prolonging the infusion duration did not alter risk of acute kidney injury. GFR

was decreased at the end of therapy. Proteinuria and elevations in AKI biomarkers indicate that direct tubular damage contributes to HDMTX nephrotoxicity.

NCT01848457.

NCT01848457.

To evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial.

Pharmacokinetic parameters (C

, T

, AUC

, λz, t

, and AUC

) were evaluated in six participants (male or female, ≥ 18years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma samples were collected prior to instillation and 30min, 1, 2, 3, 4, 5, and 6h post-instillation. Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring.

The mean age of the six participants was 69years; most were male (5/6) and Caucasian (5/6). Mean (SD) C

was 6.24 (4.11) ng/mL and mean T

was 1.79 (1.89) hours after instillation. Mean apparent t

following instillation was 1.27 (0.63) hours. Mean total systemic exposure to mitomycin up to 6h post-instillation was 20.30 (19.69) ngh/mL. At 6h post-instillation, mitomycin plasma concentrations of 5/6 participants were < 2ng/mL. There were no clinically important adverse events or changes in laboratory values in any participant after a single instillation of UGN-101.

The reverse thermal gel formulation of UGN-101 is associated with higher concentration and extended dwell time of mitomycin in contact with the urothelium of the upper urinary tract while limiting systemic absorption of mitomycin.

NCT02793128; registered June 8, 2016.

NCT02793128; registered June 8, 2016.

There are contentious data about the role calcium pyrophosphate (CPP) crystals and chondrocalcinosis (CC) play in the progression of osteoarthritis (OA), as well as in the outcomes after knee arthroplasty. Hence, the purpose of this systematic review was to analyse the clinical and functional outcome, progression of OA and prosthesis survivorship after unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) in patients with CC compared to patients without CC.

A systematic review of the literature in PubMed, Medline, Embase and Web of Science was performed using the "Preferred Reporting Items for Systematic Reviews and Meta-Analysis" (PRISMA) guidelines. Articles which reported the outcome and survival rates of prosthesis after TKA or UKA in patients with CC were included.

A total of 3718 patient knees were included in eight selected publications, with a median sample sizes of 234 knees (range 78-1000) and 954 knees (range 408-1500) for publications including UKA and TKA, respectively. At time of surgery, the mean age was 69years and the prevalence for CC ranged from 12.6 to 36%. Chondrocalcinosis did not significantly influence the functional and clinical outcome, the implant survival as well as the radiologic progression of OA disease after UKA and TKA.

The presence of CPP crystals in tissue samples, synovial fluid or evidence of calcifications on preoperative radiographs did not significantly influence the postoperative functional and activity scores. It also had no significant influence on prosthesis survival rate, whether it was a UKA or a TKA. This study shows that the impact of a subclinical form of chondrocalcinosis may not be of clinical relevance in the context of arthroplasty.

IV.

IV.

Accurate differentiation between simple and complex appendicitis is important since differences in treatment exist. This study aimed to assess the accuracy of ultrasonography in differentiating between simple and complex appendicitis.

Data from children aged < 18years who underwent appendectomy between the 1st of January 2013 and the 1st of January 2018 were analyzed retrospectively. Ultrasonography reports of eligible children were divided into simple (test negative) and complex appendicitis (test positive) based on predefined criteria and compared to a gold standard (a combination of predefined perioperative and histopathological criteria). Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated to measure ultrasonographic accuracy in differentiating between simple and complex appendicitis.

176 children were eligible for inclusion. The mean age at the time of operation was 10.1 ± SD 4.6years. 84 (47.7%) children had simple appendicitis and 92 (52.3%) had complex appendicitis. The use of ultrasonography yielded a sensitivity 46%, specificity 90%, PPV 84%, and NPV 60%.

Ultrasonography as standalone modality is not suitable for differentiating between simple and complex appendicitis in children. To improve preoperative differentiation, other variables such as clinical signs and laboratory data are necessary in conjunction with ultrasonography findings.

Ultrasonography as standalone modality is not suitable for differentiating between simple and complex appendicitis in children. To improve preoperative differentiation, other variables such as clinical signs and laboratory data are necessary in conjunction with ultrasonography findings.The CIAO project (Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway framework) aims at a holistic assembly of knowledge to deliver a truly transdisciplinary description of the entire COVID-19 physiopathology starting with the initial contact with the SARS-CoV-2 virus and ending with one or several adverse outcomes, e.g., respiratory failure. On 27-28 January 2021, a group of 50+ scientists from numerous organizations around the world met in the 2nd CIAO AOP Design Workshop to discuss the depiction of the COVID-19 disease process as a series of key events (KEs) in a network of AOPs. During the workshop, 74 such KEs forming 13 AOPs were identified, covering COVID-19 manifestations that affect the respiratory, neurological, liver, cardiovascular, kidney and gastrointestinal systems. Modulating factors influencing the course and severity of the disease were also addressed, as was a possible extension of the investigations beyond purely biological phenomena. The workshop ended with the creation of seven working groups, which will further elaborate on the AOPs to be presented and discussed in the 3rd CIAO workshop on 28-29 April 2021.Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%-100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3-2.8 (95% confidence limits from 1.2-3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI 2.5-3.4) and 3.6 (95% CI 2.2-3.1) ng/ml, respectively, compared to less then 1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. HKI-272 This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.

Surgery of insular glial tumors remains a challenge because of high incidence of postoperative neurological deterioration and the complex anatomy of the insular region.

To explore the prognostic role of our and Berger-Sanai classifications on the extent of resection (EOR) and clinical outcome.

From 2012 to 2017, a transsylvian removal of insular glial tumors was performed in 79 patients. The EOR was assessed depending on magnetic resonance imaging scans performed in the first 48 h after surgery.

The EOR ≥90% was achieved in 30 (38%) cases and <90% in 49 (62.0%) cases. In the early postoperative period, the new neurological deficit was observed in 31 (39.2%) patients, and in 5 patients (6.3%), it persisted up to 3 mo.We proposed a classification of insular gliomas based on its volumetric and anatomical characteristics. A statistically significant differences were found between proposed classes in tumor volume before and after surgery (P<.001), EOR (P=.02), rate of epileptic seizures before the surgical treatment (P=.04), and the incidence of persistent postoperative complications (P=.03).In the logistic regression model, tumor location in zone II (Berger-Sanai classification) was the predictor significantly related to less likely EOR of ≥90% and the maximum rate of residual tumor detection (P=.02).

The proposed classification of the insular gliomas was an independent predictor of the EOR and persistent postoperative neurological deficit. According to Berger-Sanai classification, zone II was a predictor of less EOR through the transsylvian approach.

The proposed classification of the insular gliomas was an independent predictor of the EOR and persistent postoperative neurological deficit. According to Berger-Sanai classification, zone II was a predictor of less EOR through the transsylvian approach.

Vitamin D deficiency (VDD) is rampant in neonates. Recommendations for supplementation are variable.

An observational study was done on less than 32 weeks of very low birth weight neonates to find prevalence of VDD (<20 ng/ml) at baseline; at 38 ± 2 weeks post-menstrual age (PMA) after daily intake of 800 IU vitamin D (vit D). Secondary objectives were to find determinants of VDD, to compare growth in deficient; vit D sufficient (VDS) neonates; to find vit D toxicity.

Of 83 neonates, 81 (97.6%) were VDD at baseline and 5 (6%) at 38 ± 2 weeks PMA. Determinants for VDD at baseline were inadequate maternal sun exposure (p < 0.001) and vit D supplementation (p = 0.007). Factors for VDD at 38 ± 2 weeks PMA were male gender (p = 0.049), morbidities (p = 0.006), ventilation >24 h (<0.001), sepsis (p = 0.032), caffeine (p ≤ 0.001) and missed supplements (p < 0.001). Weight and length gain of VDD to VDS neonates were (6.70 ± 2.40 to 8.96 ± 2.21 g/day); (0.82 ± 0.34 to 1.08 ± 0.37 cm/week), respectively (p < 0.