Prognostic Value of Bone Scintigraphy in Cancer Patients With Osteonecrosis of the Jaw

identifying imaging predictors of healing of osteonecrosis of the jaw (ONJ) in cancer patients may assist in better stratification of treatment strategies. MATERIALS AND METHODS: patients with ONJ were followed prospectively and underwent bone scintigraphy, both planar and single-photon emission computed tomography (SPECT) imaging. End points were time to healing and the number of recurrences. Studied parameters included lesion visibility, pattern of uptake, and quantification of uptake relative to the unaffected side. RESULTS: a total of 22 patients were recruited (3 men; 19 women) with a stage 1 ONJ lesion in 8, stage 2 in 9, and stage 3 ONJ in 5 patients. Median duration of follow-up was 12 months (range, 6-37). SPECT acquisitions proved superior over planar images in detecting ONJ lesions (P = 0.03). Quantification of tracer uptake in the ONJ lesion relative to the unaffected side showed increasing uptake with higher stages of ONJ: mean, 1.67 (95% confidence interval [CI], 1.17-2.18) in stage 1, 2.72 (95% CI, 2.24-3.20) in stage 2, and 4.62 (95% CI, 3.98-5.26) in stage 3. In addition, this relative ratio of uptake was found to be an independent predictor of ONJ healing (hazard ratio, 0.24; 95% CI, 0.07-0.82; P = 0.02). Neither ONJ stage nor relative ratio of uptake were predictors of the occurrence of ONJ relapses. CONCLUSIONS: bone scintigraphy in patients with ONJ is feasible and SPECT acquisitions are preferred over planar images. Relative quantification of tracer uptake provides prognostic information independent of clinical stage that may assist in identifying patients with a poor prognosis

Verifying Class Invariants in Concurrent Programs

Class invariants are a highly useful feature for the verification of object-oriented programs, because they can be used to capture all valid object states. In a sequential program setting, the validity of class invariants is typically described in terms of a visible state semantics, i.e., invariants only have to hold whenever a method begins or ends execution, and they may be broken inside a method body. However, in a concurrent setting, this restriction is no longer usable, because due to thread interleavings, any program state is potentially a visible state. In this paper we present a new approach for reasoning about class invariants in multithreaded programs. We allow a thread to explicitly break an invariant at specific program locations, while ensuring that no other thread can observe the broken invariant. We develop our technique in a permission-based separation logic environment. However, we deviate from separation logic's standard rules and allow a class invariant to express properties over shared memory locations (the invariant footprint), independently of the permissions on these locations. In this way, a thread may break or reestablish an invariant without holding permissions to all locations in its footprint. To enable modular verification, we adopt the restrictions of Muller's ownership-based type system

Risk of Necrotizing Enterocolitis Associated With the Single Nucleotide Polymorphisms VEGF C-2578A, IL-18 C-607A, and IL-4 Receptor α-Chain A-1902G : A Validation Study in a Prospective Multicenter Cohort

The etiology of necrotizing enterocolitis (NEC) is multifactorial and an underlying genetic predisposition to NEC is increasingly being recognized. A growing number of studies identified single nucleotide polymorphisms (SNPs) of selected genes with potential biological relevance in the development of NEC. However, few of these genetic studies have been replicated in validation cohorts. We aimed to confirm in a cohort of 358 preterm newborns (gestational age <30 weeks, 26 cases of NEC ≥ Bell stage II) the association with NEC of three candidate SNPs: the vascular endothelium growth factor (VEGF) C-2578A polymorphism (rs699947), the interleukin (IL)-18 C-607A polymorphism (rs1946518), and the IL-4 receptor α-chain (IL-4Rα) A-1902G polymorphism (rs1801275). We observed that allele and genotype frequencies of the three SNPs did not significantly differ between the infants with and without NEC. In contrast, the minor G-allele of the IL-4Rα A-1902G polymorphism was significantly less frequent in the group of 51 infants with the combined outcome NEC or death before 34 weeks postmenstrual age than in the infants without the outcome (0.206 vs. 0.331, P = 0.01). In addition, a significant negative association of the G-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.44, 95% CI 0.21–0.92), recessive (aOR 0.15, 95% CI 0.03–0.74), and additive (aOR 0.46, 95% CI 0.26–0.80) genetic models. In conclusion our study provides further evidence that a genetic variant of the IL-4Rα gene may contribute to NEC

Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3) results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE) at residues 172–176. RESULTS: Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20°C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD) did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. CONCLUSION: HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking

Clinical and Organizational Factors Related to the Reduction of Mechanical Restraint Application in an Acute Ward: An 8-Year Retrospective Analysis

Background: The purpose of this study was to describe the frequency of mechanical restraint use in an acute psychiatric ward and to analyze which variables may have significantly influenced the use of this procedure. Methods: This retrospective study was conducted in the Servizio Psichiatrico di Diagnosi e Cura (SPDC) of Modena Centro. The following variables of our sample, represented by all restrained patients admitted from 1-1-2005 to 31-12-2012, were analyzed: age, gender, nationality, psychiatric diagnoses, organic comorbidity, state and duration of admission, motivation and duration of restraints, nursing shift and hospitalization day of restraint, number of patients admitted at the time of restraint and institutional changes during the observation period. The above variables were statistically compared with those of all other non-restrained patients admitted to our ward in the same period. Results: Mechanical restraints were primarily used as a safety procedure to manage aggressive behavior of male patients, during the first days of hospitalization and night shifts. Neurocognitive disorders, organic comorbidity, compulsory state and long duration of admission were statistically significantly related to the increase of restraint use (p<.001, multivariate logistic regression). Institutional changes, especially more restricted guidelines concerning restraint application, were statistically significantly related to restraint use reduction (p<.001, chi2 test, multivariate logistic regression). Conclusion: The data obtained highlight that mechanical restraint use was influenced not only by clinical factors, but mainly by staff and policy factors, which have permitted a gradual but significant reduction in the use of this procedure through a multidimensional approach

A systematic review and meta-analysis of bioresorbable vascular scaffolds for below-the-knee arterial disease

INTRODUCTION: Different types of bioresorbable vascular scaffolds (BVSs) have been developed and used in below-the-knee (BTK) arterial diseases. This is the first study reviewing and analyzing the literature on BVS treatment for BTK arterial disease. EVIDENCE ACQUISITION: MEDLINE, Embase, and Cochrane were searched for studies published until October 21, 2019. The search, study selection, quality assessment, and data extraction were performed by 2 authors independently. Articles that studied the treatment of BTK arterial disease by using BVSs were eligible. Exclusion criteria were studies with a variant design (e.g. case reports <5 patients), non-BTK indications for BVS use, and nonhuman studies. Primary endpoint was 12-month primary patency. Secondary endpoints were 12-month freedom from clinically driven target lesion revascularization (CD-TLR), limb salvage, survival, and amputation-free survival (AFS). Study quality was assessed by the Methodological Index for Non-randomized Studies score. EVIDENCE SYNTHESIS: Five studies representing 155 patients with 160 treated limbs met the inclusion criteria. Pooled 12-month primary patency per limb was 90% (143/160; 95% confidence interval [CI]: 0.84-0.95), freedom from CD-TLR 96% (124/130; 95% CI: 0.91-0.99), limb salvage rate 97% (156/160; 95% CI: 0.94-1.00), survival rate 90% (112/125; 95% CI: 0.82-0.96), and AFS rate 89% (110/125; 95% CI: 0.81-0.94). Subgroup analyses of included Absorb BVS studies showed similar results. All studies were assessed as moderate quality. CONCLUSIONS: This meta-analysis of case series showed good 12-month patency and clinical results with BVSs for BTK arterial disease, even in patients with multimorbidity and short but complex lesions. These results encourage a revival of this scaffold

Belt restraint reduction in nursing homes: design of a quasi-experimental study

<p>Abstract</p> <p>Background</p> <p>The use of physical restraints still is common practice in the nursing home care. Since physical restraints have been shown to be an ineffective and sometimes even hazardous measure, interventions are needed to reduce their usage. Several attempts have been made to reduce the use of physical restraints. Most studies used educational approaches and introduced a nurse specialist as a consultant. However, the success rate of these interventions has been inconsistent. We developed a new multi-component intervention (EXBELT) comprising an educational intervention for nursing home staff in combination with a policy change (belt use is prohibited by the nursing home management), availability of a nurse specialist and nursing home manager as consultants, and availability of alternative interventions. The first aim of this study is to further develop and test the effectiveness of EXBELT on belt restraint reduction in Dutch psychogeriatric nursing homes. However, the reduction of belts should not result in an increase of other restrictive restraints (such as a chair with locked tray table) or psychoactive drug use. The overall aim is an effective and feasible intervention that can be employed on a large scale in Dutch nursing homes.</p> <p>Methods and design</p> <p>Effects of EXBELT will be studied in a quasi-experimental longitudinal study design. Alongside the effect evaluation, a process evaluation will be carried out in order to further develop EXBELT. Data regarding age, gender, use of physical restraints, the number of falls and fall related injuries, psychoactive drug use, and the use of alternative interventions will be collected at baseline and after four and eight months of follow-up. Data regarding the process evaluation will be gathered in a period of eight months between baseline and the last measurement. Furthermore, changing attitudes will become an important addition to the educational part of EXBELT.</p> <p>Discussion</p> <p>A quasi-experimental study is presented to investigate the effects of EXBELT on the use of belts on wards in psychogeriatric nursing homes. The study will be conducted in 26 wards in 13 psychogeriatric nursing homes. We selected the wards in a manner that contamination between control- and intervention group is prevented.</p> <p>Trial registration</p> <p>(NTR2140)</p

Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study

The p.Thr1406Asn (rs1047891) polymorphism of the carbamoyl-phosphate synthetase 1 (CPS1) gene has been linked to functional consequences affecting the downstream availability of the nitric oxide precursor L-arginine. L-arginine concentrations are decreased in preterm infants with necrotizing enterocolitis (NEC). In this multicenter prospective study, we investigated the association of the p.Thr1406Asn polymorphism with NEC in 477 preterm infants (36 cases of NEC) from 4 European neonatal intensive care units (Maastricht, Las Palmas de Gran Canaria, Mantova, and Milan). Allele and genotype frequencies of the p.Thr1406Asn polymorphism did not significantly differ between the infants with and without NEC. In contrast, the minor A-allele was significantly less frequent in the group of 64 infants with the combined outcome NEC or death before 34 weeks of corrected gestational age than in the infants without the outcome (0.20 vs. 0.31, P = 0.03). In addition, a significant negative association of the A-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.54, 95% CI 0.29-0.99) and the additive (aOR 0.58, 95% CI 0.36-0.93) genetic models. In conclusion, our study provides further evidence that a functional variant of the CPS1 gene may contribute to NEC susceptibility

Biobanking for Viral Hepatitis Research

Introduction: Viral hepatitis is a worldwide, important health issue. The optimal management of viral hepatitis infections faces numerous challenges. In this paper, we describe how biobanking of biological samples derived from viral hepatitis patients collected both in-hospital and during community outreach screenings provides a unique collection of samples. Materials and Methods: All samples and materials were provided with a study code within the SLIMS system Study protocols and an informed consent form were approved by the Antwerp University Hospital/University of Antwerp Ethical Committee. Systematic biobanking was initiated in October 2014. Collected sample types include: (1) serum and plasma of all newly diagnosed HBV, HCV, HDV, and HEV positive patients; (2) left-over serum and plasma samples from all PCR analyses for HBV and HCV performed in the context of routine clinical care; (3) left-over liver tissue not needed for routine histological diagnosis after liver biopsy; and (4) additional virus-specific, appropriate sample types using a scientific rationale-based approach. A community outreach screening program was performed in three major Belgian cities. Serum, EDTA, Tempus Blood RNA and BD Vacutainer CPT were collected. CPT tubes were centrifuged on-site and mononuclear cells collected within 24 h. Results: Concerning community screening: 298 individuals supplied all 4 sample types. Samples were stored at −150◦C and were logged in the biobank SLIMS database. Samples were used for HBV-related immunological and biomarker studies. DNA isolated from plasma samples derived from chronic HBV patients was used to investigate Single Nucleotide Polymorphism rs 1790008. Serum samples collected from chronic hepatitis C patients were used to assess the efficacy of HCV treatment. Peripheral Blood Mononuclear Cells (PBMC) isolated from chronic HBV patients and healthy controls were used for different immunological study purposes. Virus isolated from biobanked stool of a chronic hepatitis E patient was used to establish a mouse model for Hepatitis E infections, allowing further HEV virology studies. Conclusion: The establishment of a biobank with samples collected both in-hospital and during community-outreach screening resulted in a unique, continuously expanding collection of biological samples which provides an excellent platform for prompt answers to clinically and translational relevant research questions

Intra-arterial peptide-receptor radionuclide therapy for neuro-endocrine tumour liver metastases:an in-patient randomised controlled trial (LUTIA)

Purpose: Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1–2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [177Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity. Methods: Twenty-seven patients with grade 1–2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a “second-pass” effect and the contralateral lobe was used as the control lobe. Up to three metastases (&gt; 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [177Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test. Findings: After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/NIA = 17·4 vs. T/Ncontrol = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle. Conclusion: Intra-arterial [177Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.</p