Simplifying clinical use of TCGA molecular subtypes through machine learning models.

In this issue of Cancer Cell, Ellrott et al. present machine learning models to classify samples into The Cancer Genome Atlas molecular subtypes using compact sets of genomic features. These validated, ready-to-use models are publicly available, although some clinical hurdles need to be cleared before they are fully implemented.

Radical cystectomy in patients aged < 80 years versus ≥ 80 years: analysis of preoperative geriatric assessment scores in predicting postoperative morbidity and mortality.

Purpose: Pre-operative assessment of surgical risk is essential for patient counselling in the elderly patient population. Our purpose was to compare validated geriatric assessment scores (GAS) in predicting postoperative morbidity and mortality in patients ≥ 80 years.

Methods: Overall, eight preoperative GAS were assessed for each patient who received RC from 2016 to 2021.

Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C.

Aims/hypothesis: Genome-wide association studies (GWAS) have identified hundreds of type 2 diabetes loci, with the vast majority of signals located in non-coding regions; as a consequence, it remains largely unclear which 'effector' genes these variants influence. Determining these effector genes has been hampered by the relatively challenging cellular settings in which they are hypothesised to confer their effects.

Methods: To implicate such effector genes, we elected to generate and integrate high-resolution promoter-focused Capture-C, assay for transposase-accessible chromatin with sequencing (ATAC-seq) and RNA-seq datasets to characterise chromatin and expression profiles in multiple cell lines relevant to type 2 diabetes for subsequent functional follow-up analyses: EndoC-BH1 (pancreatic beta cell), HepG2 (hepatocyte) and Simpson-Golabi-Behmel syndrome (SGBS; adipocyte).

Do Not Get Your Uterus Twisted: A Case Report of a 180-Degree Torsion of Term Gravid Uterus and a Review of the Literature.

Gravid uterine torsion less than 45 degrees is a common phenomenon of the third trimester. Torsion greater than 45 degrees represents a rare, pathologic, and obstetric emergency. The rotation of the uterus on a longitudinal plane can result in vascular compromise, and it has potential for catastrophic maternal-fetal complications.

Treatment trends for undescended testis and impact of guideline changes a medical health care analysis of orchidopexy and cryptorchidism in Germany between 2006 und 2020.

Background: The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery.

Methods: We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.

Accelerative Solid-State Oxidation Behaviour of Amorphous and Partially Crystalline Venetoclax.

There is a growing focus on solid-state degradation, especially for its relevance in understanding interactions with excipients. Performing a solid-state degradation of Venetoclax (VEN), we delve into VEN's stability in different solid-state oxidative stress conditions, utilizing Peroxydone™ complex and urea peroxide (UHP). The investigation extends beyond traditional forced degradation scenarios, providing insights into VEN's behavior over 32 h, considering temperature and crystallinity conditions.

Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study.

Purpose: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men.

Methods: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe.

Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2.

The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as a putative causal variant by leveraging our in-house 3D genomic data and public domain datasets.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

Purpose: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center.

Materials And Methods: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution.

Variant to gene mapping for carpal tunnel syndrome risk loci implicates skeletal muscle regulatory elements.

Background: Carpal tunnel syndrome (CTS) is a common disorder caused by compression of the median nerve in the wrist, resulting in pain and numbness throughout the hand and forearm. While multiple behavioural and physiological factors influence CTS risk, a growing body of evidence supports a strong genetic contribution. Recent genome-wide association study (GWAS) efforts have reported 53 independent signals associated with CTS.

PI-RADS upgrading as the strongest predictor for the presence of clinically significant prostate cancer in patients with initial PI-RADS-3 lesions.

Purpose: Unclear lesions on multiparametric magnetic resonance tomography (mpMRI) are challenging for the indication of biopsy in patients with clinical suspicion of prostate cancer (PCa). The aim of this study is the validation of the detection rate of clinically significant PCa (csPCa) in patients with PI-RADS 3 findings and to determine the appropriate follow-up strategy.

Methods: In this retrospective single-center study, patients with maximum PI-RADS 3 lesions underwent targeted MRI/ultrasound-fusion biopsy (tPbx) combined with systematic 12-core biopsy (sPbx) and follow-up mpMRI with further control biopsy.

The Role of Multiparametric MRI (mpMRI) in the Prediction of Adverse Prostate Cancer Pathology in Radical Prostatectomy Specimen.

Introduction: Prostate cancer (PCa) risk stratification is essential in guiding therapeutic decision. Multiparametric magnetic resonance tomography (mpMRI) holds promise in the prediction of adverse pathologies (AP) after prostatectomy (RP). This study aims to identify clinical and imaging markers in the prediction of adverse pathology.

Follow-up of vascular-targeted photodynamic therapy in a real-world setting.

Purpose: Vascular-targeted photodynamic therapy (VTP) is an approved treatment option for unilateral low-risk prostate cancer (PCa).

Methods: Patients with unilateral low- or intermediate-risk PCa undergoing hemiablation by VTP were evaluated in a real-world setting. Oncological outcome after VTP was measured by MRI-based re-biopsy at 12 and 24 months.

PD-L1 mRNA Detection in Immunohistochemically Negative Patients: A Complementary Method for a Better Treatment Selection?

Background/aim: PD-L1 inhibitors have been approved for cisplatin-ineligible urothelial cancer patients relapsing after radical cystectomy. A prerequisite for therapy is a positive PD-L1 expression in the tumor tissue, whereas no options are available for patients with negative PD-L1 status. However, studies revealed that many PD-L1-negative patients also responded to PD-L1 therapy.

Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of .

The ch12q13 obesity locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within ; thus, the underlying causal variant(s) presumably influence disease susceptibility via an influence on -regulation within the genomic region. We implicated rs7132908 as a putative causal variant at this locus leveraging a combination of our inhouse 3D genomic data, public domain datasets, and several computational approaches.

Single-center, prospective phase 2 trial of high-intensity focused ultrasound (HIFU) in patients with unilateral localized prostate cancer: good functional results but oncologically not as safe as expected.

Purpose: Focal therapy (FT) for localized prostate cancer (PCa) is only recommended within the context of clinical trials by international guidelines. We aimed to investigate oncological follow-up and safety data of focal high-intensity focused ultrasound (HIFU) treatment.

Methods: We conducted a single-center prospective study of 29 patients with PCa treated with (focal) HIFU between 2016 and 2021.

Hospital rating websites play a minor role for uro-oncologic patients when choosing a hospital for major surgery: results of the German multicenter NAVIGATOR-study.

Purpose: Hospital rating websites (HRW) offer decision support in hospital choice for patients. To investigate the impact of HRWs of uro-oncological patients undergoing elective surgery in Germany.

Methods: From 01/2020 to 04/2021, patients admitted for radical prostatectomy, radical cystectomy, or renal tumor surgery received a questionnaire on decision-making in hospital choice and the use of HRWs at 10 German urologic clinics.

Ovarian cancer mutational processes drive site-specific immune evasion.

High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability patterned by distinct mutational processes, tumour heterogeneity and intraperitoneal spread. Immunotherapies have had limited efficacy in HGSOC, highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC.

Contralateral testicular hypertrophy is associated with a higher incidence of absent testis in children with non-palpable testis.

Background And Objective: The objective of our study is to examine the impact of monorchism on contralateral testicular size in children with non-palpable testis (NPT). Enhanced contralateral testicular volume or longitudinal diameter (length) serves as a predictor of monorchism. In the present study, we assessed the ability of ultrasound measured enlarged contralateral testicular length for predicting monorchism (and hence a testicular nubbin) in children with NPT.

Negative multiparametric magnetic resonance imaging for prostate cancer: further outcome and consequences.

Purpose: EAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI.

Collagenase for the Treatment of Cellulite in the Buttocks and Thigh: Early Insights From Clinical Practice.

Background: Collagenase (CCH-aaes; QWO [Endo Aesthetics, Malvern, PA]) is an injectable, enzyme-based treatment indicated for the treatment of moderate to severe cellulite on the buttocks of adult women. The minimally invasive nature of the treatment makes it an attractive option for targeted disruption of the fibrous septae which give rise to the dimples characteristic of cellulite in buttocks and thighs.

Objectives: The article provides an overview of cellulite treatment with CCH-aaes, including patient identification and education, treatment planning, CCH-aaes dilution, injection technique, safety, and early experience with mitigation of adverse events, including bruising.

3D chromatin maps of the human pancreas reveal lineage-specific regulatory architecture of T2D risk.

Three-dimensional (3D) chromatin organization maps help dissect cell-type-specific gene regulatory programs. Furthermore, 3D chromatin maps contribute to elucidating the pathogenesis of complex genetic diseases by connecting distal regulatory regions and genetic risk variants to their respective target genes. To understand the cell-type-specific regulatory architecture of diabetes risk, we generated transcriptomic and 3D epigenomic profiles of human pancreatic acinar, alpha, and beta cells using single-cell RNA-seq, single-cell ATAC-seq, and high-resolution Hi-C of sorted cells.