Seatbelt: A Double-Edged Sword

Intra-abdominal vascular injury due to blunt trauma is unusual in children. Due to its rarity, detailed reports dealing with its management are scarce in paediatric literature. Diagnosis of these injuries is challenging, and a high degree of awareness is necessary for rapid identification and treatment of these injuries. We report the case of a child with seatbelt sign and mesenteric vein injury due to blunt trauma to the abdomen during a motor vehicle accident where the seatbelt was incorrectly placed. She also sustained cervical vertebral injury. The pattern of injuries in children in these situations may differ from that found in adults. While seatbelts have undoubtedly saved many lives, awareness about correct placement of these restraints is extremely necessary

Vitamin d and the risk of non-melanoma skin cancer: A systematic literature review and meta-analysis on behalf of the italian melanoma intergroup

We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation

Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System

Background: Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 or its ligand (PD1/PDL1), elicit different immune-related adverse events (irAEs), but their global safety is incompletely characterized. Objective: The aim of this study was to characterize the spectrum, frequency, and clinical features of ICI-related adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS). Patients and methods: AEs from FAERS (up to June 2018) recording ICIs (ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab) as suspect were extracted. Comprehensive disproportionality analyses were performed through the reporting odds ratio (ROR) with 95% confidence interval (95% CI), using other oncological drugs as comparison. An overview of systematic reviews (OoSRs) was also undertaken to identify irAEs with consistent positive associations. Results: ICIs were recorded in 47,266 reports, submitted mainly by consumers receiving monotherapy with anti-PD1/PDL1 drugs. Three areas of toxicity emerged from both disproportionality analysis and the OoSRs (32 studies): endocrine (N = 2863; ROR = 6.91; 95% CI 6.60–7.23), hepatobiliary (2632; 1.33; 1.28–1.39), and respiratory disorders (7240; 1.04; 1.01–1.06). Different reporting patterns emerged for anti-CTLA4 drugs (e.g., hypophysitis, adrenal insufficiency, hypopituitarism, and prescribed overdose) and anti-PD1/PDL1 agents (e.g., pneumonitis, cholangitis, vanishing bile duct syndrome, tumor pseudoprogression, and inappropriate schedule of drug administration). No increased reporting emerged when comparing combination with monotherapy regimens, but multiple hepatobiliary/endocrine/respiratory irAEs were recorded. Conclusions: This parallel approach through contemporary post-marketing analysis and OoSRs confirmed that ICIs are associated with a multitude of irAEs, with different reporting patterns between anti-CTLA4 and anti-PD1/PDL1 medications. Close clinical monitoring is warranted to early diagnose and timely manage irAEs, especially respiratory, endocrine, and hepatic toxicities, which warrant further characterization; patient- and drug-related risk factors should be assessed through analytical pharmaco-epidemiological studies and prospective multicenter registries

Dietary total antioxidant capacity and colorectal cancer in the Italian EPIC cohort

Background Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed. Methods We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center. Results Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44\u20130.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19\u20133.66; 3rd tertile 2.48 95%CI: 1.32\u20134.66; P trend 0.007). Intakes of vitamin C, vitamin E, and f-carotene were not significantly associated with colorectal cancer risk. Conclusions Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers

Video-assisted parathyroidectomy: a series of 85 cases

Abstract AIM OF THE STUDY: To verify the feasibility of video-assisted parathyroidectomy, set up the indications and report the results in a series of 85 patients. MATERIAL AND METHODS: From 1997 to 1999, 85 patients affected by primary hyperparathyroidism due to single gland disease, with an adenoma smaller than 35 mm as demonstrated by preoperative imaging, were referred for video-assisted parathyroidectomy. There were 62 females and 23 males. Mean age was 53 years, (range 23-82). Video-assisted parathyroidectomy was associated with intra-operative PTH quick-assay. Calcium testing was controlled before leaving the hospital, 1 month and 3 months later, and postoperative laryngoscopy was performed in all patients. RESULTS: There were five conversions to open cervicotomy: three due to a contra-lateral second adenoma, two because of an intrathyroidal adenoma. The mean operative time for video-assisted procedure was 59 minutes (range: 25-180). Circulating PTH levels 10 minutes after the removal of the affected gland(s) always dropped significantly, and pathological report confirmed the parathyroid nature of the specimens (mean diameter 13 mm, range 7-35). Morbidity consisted of five cases of transient hypocalcemia and one permanent laryngeal nerve paralysis. We registered no persistent or recurrent disease (mean follow-up 12.8 months, range 1-28). CONCLUSIONS: Video-assisted parathyroidectomy is feasible, and its results are similar to those of traditional procedure, while it seems superior as regards postoperative course and aesthetic results. It also allows different strategical decisions even during operation (i.e. bilateral exploration or thyroid lobectomy) by the same approach

Estimating Black Hole Masses in Triaxial Galaxies

Most of the super massive black hole mass estimates based on stellar kinematics use the assumption that galaxies are axisymmetric oblate spheroids or spherical. Here we use fully general triaxial orbit-based models to explore the effect of relaxing the axisymmetric assumption on the previously studied galaxies M32 and NGC 3379. We find that M32 can only be modeled accurately using an axisymmetric shape viewed nearly edge-on and our black hole mass estimate is identical to previous studies. When the observed 5 degrees kinematical twist is included in our model of NGC 3379, the best shape is mildly triaxial and we find that our best-fitting black hole mass estimate doubles with respect to the axisymmetric model. This particular black hole mass estimate is still within the errors of that of the axisymmetric model and consistent with the M-sigma relationship. However, this effect may have a pronounced impact on black hole demography, since roughly a third of the most massive galaxies are strongly triaxial.Comment: Accepted for publication in MNRAS. 11 pages, 9 figures. PDFlate

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. © 2013 Zhang et al

Human glioblastoma multiforme: p53 reactivation by a novel MDM2 inhibitor

Cancer development and chemo-resistance are often due to impaired functioning of the p53 tumor suppressor through genetic mutation or sequestration by other proteins. In glioblastoma multiforme (GBM), p53 availability is frequently reduced because it binds to the Murine Double Minute-2 (MDM2) oncoprotein, which accumulates at high concentrations in tumor cells. The use of MDM2 inhibitors that interfere with the binding of p53 and MDM2 has become a valid approach to inhibit cell growth in a number of cancers; however little is known about the efficacy of these inhibitors in GBM. We report that a new small-molecule inhibitor of MDM2 with a spirooxoindolepyrrolidine core structure, named ISA27, effectively reactivated p53 function and inhibited human GBM cell growth in vitro by inducing cell cycle arrest and apoptosis. In immunoincompetent BALB/c nude mice bearing a human GBM xenograft, the administration of ISA27 in vivo activated p53, inhibited cell proliferation and induced apoptosis in tumor tissue. Significantly, ISA27 was non-toxic in an in vitro normal human cell model and an in vivo mouse model. ISA27 administration in combination with temozolomide (TMZ) produced a synergistic inhibitory effect on GBM cell viability in vitro, suggesting the possibility of lowering the dose of TMZ used in the treatment of GBM. In conclusion, our data show that ISA27 releases the powerful antitumor capacities of p53 in GBM cells. The use of this MDM2 inhibitor could become a novel therapy for the treatment of GBM patients

High SPARC expression starting from dysplasia, associated with breast carcinoma, is predictive for bone metastasis without enhancement of plasma levels

In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer