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Karyotype analysis is not commonly performed in existing genetic screening protocols for patients with VHL. Based on this case, protocols should be updated to include karyotype analysis in patients who are clinically diagnosed with VHL but demonstrate no detectable mutation by existing genetic testing.
Although 60% of patients with de novo neurofibromatosis type 2 (NF2) are presumed to have mosaic NF2, the actual diagnostic rate of this condition remains low at around 20% because of the existing difficulties in detecting
variants with low variant allele frequency (VAF). Here, we examined the correlation between the genotype and phenotype of mosaic NF2 after improving the diagnostic rate of mosaic NF2.

We performed targeted deep sequencing of 36 genes including
using DNA samples from multiple tissues (blood, buccal mucosa, hair follicle and tumour) of 53 patients with de novo NF2 and elucidated their genotype-phenotype correlation.

Twenty-four patients (45.2%) had the
germline variant, and 20 patients with NF2 (37.7%) had mosaic NF2. The mosaic NF2 phenotype was significantly different from that in patients with
germline variant in terms of distribution of NF2-related disease, tumour growth rate and hearing outcome. The behaviour of schwannoma correlated to the extent of VAF with
variant in normal tissues unlike meningioma.

We have improved the diagnostic rate of mosaic NF2 compared with that of previous studies by targeted deep sequencing of DNA from multiple tissues. Many atypical patients with NF2 diagnosed with 'unilateral vestibular schwannoma' or 'multiple meningiomas' presumably have mosaic NF2. Finally, we suggest that the highly diverse phenotype of NF2 could result not only from the type and location of
variant but also the extent of VAF in the
variant within normal tissue DNA.
We have improved the diagnostic rate of mosaic NF2 compared with that of previous studies by targeted deep sequencing of DNA from multiple tissues. Many atypical patients with NF2 diagnosed with 'unilateral vestibular schwannoma' or 'multiple meningiomas' presumably have mosaic NF2. Finally, we suggest that the highly diverse phenotype of NF2 could result not only from the type and location of NF2 variant but also the extent of VAF in the NF2 variant within normal tissue DNA.
Hospitalization provides an opportunity to address sexual health needs of adolescents who may not otherwise receive regular medical care. We investigated documentation of a sexual health discussion with adolescents hospitalized at our medical center to determine if previous primary care physician (PCP) visits in the same health system were associated with sexual health documentation during the hospital admission.

We retrospectively identified adolescents aged 13 to 17 years discharged from the pediatric general ward. Documented discussion of sexual health was reviewed in the electronic medical record. Previous PCP visits were identified from the affiliated primary care clinics within 12 months before hospitalization. We also queried follow-up PCP visits within 90 days of discharge to determine if a sexual health discussion during hospitalization was followed-up in the outpatient setting.

We analyzed 394 patients (49% girls; median age 15 years), of whom 122 (31%) had documentation of a sexual health disxual health intervention among adolescents who may not regularly see a PCP.
In several states, payers penalize hospitals when an inpatient readmission follows an inpatient stay. Observation stays are typically excluded from readmission calculations. Previous studies suggest inconsistent use of observation designations across hospitals. We sought to describe variation in observation stays and examine the impact of inclusion of observation stays on readmission metrics.

We conducted a retrospective cohort study of hospitalizations at 50 hospitals contributing to the Pediatric Health Information System database from January 1, 2018, to December 31, 2018. We examined prevalence of observation use across hospitals and described changes to inpatient readmission rates with higher observation use. We described 30-day inpatient-only readmission rates and ranked hospitals against peer institutions. Finally, we included observation encounters into the calculation of readmission rates and evaluated hospitals' change in readmission ranking.

Most hospitals (
= 44; 88%) used observation statdmission metric, and inclusion of observation stays in the calculation of readmission rates significantly affected hospital performance compared with peer institutions. selleck chemicals Consideration should be given to include all admission types for readmission rate calculation.Cross-linking MS (XL-MS) has been recognized as an effective source of information about protein structures and interactions. In contrast to regular peptide identification, XL-MS has to deal with a quadratic search space, where peptides from every protein could potentially be cross-linked to any other protein. To cope with this search space, most tools apply different heuristics for search space reduction. We introduce a new open-source XL-MS database search algorithm, OpenPepXL, which offers increased sensitivity compared with other tools. OpenPepXL searches the full search space of an XL-MS experiment without using heuristics to reduce it. Because of efficient data structures and built-in parallelization OpenPepXL achieves excellent runtimes and can also be deployed on large compute clusters and cloud services while maintaining a slim memory footprint. We compared OpenPepXL to several other commonly used tools for identification of noncleavable labeled and label-free cross-linkers on a diverse set of XL-MS experiments. In our first comparison, we used a data set from a fraction of a cell lysate with a protein database of 128 targets and 128 decoys. At 5% FDR, OpenPepXL finds from 7% to over 50% more unique residue pairs (URPs) than other tools. On data sets with available high-resolution structures for cross-link validation OpenPepXL reports from 7% to over 40% more structurally validated URPs than other tools. Additionally, we used a synthetic peptide data set that allows objective validation of cross-links without relying on structural information and found that OpenPepXL reports at least 12% more validated URPs than other tools. It has been built as part of the OpenMS suite of tools and supports Windows, macOS, and Linux operating systems. OpenPepXL also supports the MzIdentML 1.2 format for XL-MS identification results. It is freely available under a three-clause BSD license at https//openms.org/openpepxl.Radionuclide therapy targeting prostate-specific membrane antigen (PSMA) is a promising treatment for prostate cancer. We reported a ligand featuring two lysine-ureido-glutamate groups, 64Cu-CuSarbisPSMA previously. Here, we report the therapeutic potential of 67Cu-CuSarbisPSMA. Methods Growth of PSMA-positive xenografts was evaluated following treatment with 67Cu-CuSarbisPSMA or 177Lu-LuPSMA I&T. Results At 13 days post-injection, tumor growth was similarly inhibited by the two tracers in a dose-dependent manner. Survival was comparable after single (30 MBq) or fractionated administrations (2 x 15MBq, two weeks apart). Conclusion67Cu-CuSarbisPSMA is efficacious in a PSMA-expressing model of prostate cancer.Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratification and optimal choice of therapy. Currently, grading is based on histologically assessed degree of tumor proliferation. The aim of the present study was to assess the long-term prognostic value of 18F-FDG-PET imaging for risk stratification of NENs and compare it with tumor grading (World Health Organization (WHO) 2010 classification). Methods We conducted a prospective cohort study evaluating the prognostic value of 18F-FDG-PET imaging and compared it to histological grading. Enrolled were 166 patients of all grades and with histologically confirmed NENs of gastro-entero-pancreatic origin. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint. In addition, OS in relation to Peptide Receptor Radionuclide Therapy (PRRT) was analyzed as an exploratory endpoint. The median follow-up time was 9.8 years. Results Analysis of the whole cohort revealed that a positive stological grading. 18F-FDG-PET could differentiate G1 and G2 tumors into low and high-risk groups. In the selection of therapy and for risk stratification of NEN patients, 18F-FDG-PET status should be considered.Quantitative analysis has been applied extensively to image processing and interpretation in nuclear cardiology to improve disease diagnosis and risk stratification. This is Part 2 of a two-part continuing medical education article, which will review the potential clinical role for emerging quantitative analysis tools. The article will describe advanced methods for quantifying dyssynchrony, ventricular function and perfusion, and hybrid imaging analysis. This article discusses evolving methods to measure myocardial blood flow with positron emission tomography and single-photon emission computed tomography. Novel quantitative assessments of myocardial viability, microcalcification and in patients with cardiac sarcoidosis and cardiac amyloidosis will also be described. Lastly, we will review the potential role for artificial intelligence to improve image analysis, disease diagnosis, and risk prediction. The potential clinical role for all these novel techniques will be highlighted as well as methods to optimize their implementation. (J Nucl Cardiol 2020).This first-in-human study investigated the safety, biodistribution and radiation dosimetry of the novel 18F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) positron emission tomography (PET) imaging agent, 18F-rhPSMA-7.3. Methods Six healthy volunteer subjects (3 males, 3 females) underwent multiple whole-body PET acquisitions at scheduled time points up to 248 minutes after the administration of 18F-rhPSMA-7.3 (mean activity 220; range, 210-228 MBq). PET scans were conducted in three separate sessions and subjects were encouraged to void between sessions. Blood and urine samples were collected for up to 4 hours post-injection to assess metabolite-corrected radioactivity in whole blood, plasma and urine. Quantitative measurements of 18F radioactivity in volumes of interest (VOIs) over target organs were determined directly from the PET images at 8 time points and normalized time-activity concentration curves were generated. These normalized cumulated activities were then inputted into the OLIN-7.3 are considered favorable for PET imaging.131I-meta-iodobenzylguanidine (131I-MIBG) radiotherapy has shown some survival benefits in metastatic neuroendocrine tumors (NETs). European Association of Nuclear Medicine (EANM) clinical guidelines for 131I-MIBG radiotherapy suggest a repeated treatment protocol, although none currently exists. The existing single-high-dose 131I-MIBG radiotherapy (444 MBq/kg) has been shown to have some benefits for patients with metastatic NETs. However, this protocol increases adverse effects and it requires alternative therapeutic approaches. Therefore, the aim of this study was to evaluate the effects of repeated 131I-MIBG therapy on tumor size and tumor metabolic response in patients with metastatic NETs. Methods Eleven patients with metastatic NETs (age 49.2±16.3) prospectively had repeated 5550 MBq of 131I-MIBG therapy within 6-month intervals. A total of 31 treatments were performed. Mean treatments were 2.8 ± 0.4 times and cumulative 131I-MIBG dose was 15640.9 ±2245.1 MBq (286.01 MBq/kg). The tumor responses were observed by computed tomography (CT), 18F-FDG PET or PET/CT before and 3 to 6 months after the final 131I-MIBG treatment.
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