Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

Single-cell DNA sequencing reveals pervasive positive selection throughout preleukemic evolution.

The representation of driver mutations in preleukemic hematopoietic stem cells (pHSCs) provides a window into the somatic evolution that precedes acute myeloid leukemia (AML). Here, we isolate pHSCs from the bone marrow of 16 patients diagnosed with AML and perform single-cell DNA sequencing on thousands of cells to reconstruct phylogenetic trees of the major driver clones in each patient. We develop a computational framework that can infer levels of positive selection operating during preleukemic evolution from the statistical properties of these phylogenetic trees.

Supplemental Screening With MRI in Women With Dense Breasts: The European Perspective.

Breast cancer is the most prevalent cancer in women in Europe, and while all European countries have some form of screening for breast cancer, disparities in organization and implementation exist. Breast density is a well-established risk factor for breast cancer; however, most countries in Europe do not have recommendations in place for notification of breast density or additional supplementary imaging for women with dense breasts. Various supplemental screening modalities have been investigated in Europe, and when comparing modalities, MRI has been shown to be superior in cancer detection rate and in detecting small invasive disease that may impact long-term survival, as demonstrated in the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial in the Netherlands.

Expert consensus recommendations for the diagnosis and treatment of chronic non-bacterial osteitis (CNO) in adults.

Background: There is considerable practice variation in labelling, diagnosis and treatment of adults with sterile bone inflammation. We developed a expert consensus recommendations on the disease definition, diagnosis and treatment of this rare condition.

Methods: Systematic literature review and Grading of Recommendations, Assessment, Development and Evaluations-based appraisal of evidence, two Delphi surveys and three digital and in-person consensus meetings with a multidisciplinary expert panel and patient representatives.

Expression of transglutaminase-2 (TGM2) in the prognosis of female invasive breast cancer.

Background: Transglutaminase 2 (TGM2) is a protein expressed in several isoforms in both intra- and extra-cellular tissue compartments. It has multiple functions that are important in cancer biology and several small studies have suggested expression of TGM2 in breast cancers is associated with a poorer prognosis. The aim of this study was to evaluate the role of intra-cellular and extra-cellular TGM2 expression in breast cancer and to determine whether there were any differences by hormone receptor status.

Diagnosis and management of rectal syphilis-case report.

The incidence and prevalence of syphilis are rising worldwide. Rectal syphilis is a rare condition with few reported cases in the literature and therefore often missed from differential diagnosis of atypical anorectal ulceration. We report a case of a 64-year-old male who presented with change in the bowel habit and a palpable rectal mass on examination.

Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study.

Purpose: The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND.

Methods: The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.

New horizons in hospital-associated deconditioning: a global condition of body and mind.

Hospital-associated deconditioning is a broad term, which refers non-specifically to declines in any function of the body secondary to hospitalisation. Older people, particularly those living with frailty, are known to be at greatest risk. It has historically been most commonly used as a term to describe declines in muscle mass and function (i.

Effectiveness, Safety, and Patterns of Real-World Isavuconazole Use in Europe (2015-2019).

Introduction: Real-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe.

Methods: A retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18 years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019).

Review article: Novel therapies in inflammatory bowel disease - An update for clinicians.

Background: Several new treatments including small molecules and biologics have been approved for the treatment of inflammatory bowel diseases in recent years. Clinicians and patients now have a wide variety of therapeutic options to choose from and these novel therapies provide several advantages including oral administration, lower immunogenicity, better selectivity and arguably better safety profiles. An increase in treatment options has increased the complexity of decision-making.

Differences in axillary ultrasound protocols among prospective de-escalating axillary surgical staging trials in clinically node negative early breast cancer patients.

Background: Surgical axillary staging of the axilla is a topic of debate regarding the potential of de-escalation in clinically node negative (cN0) early breast cancer patients treated with breast-conserving therapy. Axillary ultrasound is important to determine clinical nodal status. The aim of the current narrative review is to provide an overview of prospective trials on de-escalating axillary surgical staging in cN0 early breast cancer patients, with an emphasis on axillary ultrasound protocols.

Predicting Adverse Events to Thiopurines in IBD: Are We a Step Closer?

Thiopurines remain an important option in the treatment of IBD. However, the unpredictable and sometimes serious side effects and intolerance remain a major challenge. Pretreatment of extended genetic panel analysis, identification of novel variants, and monitoring of intermediate metabolites will help improve the overall outcome and reduce the toxicity.

Early vocational rehabilitation and psychological support for trauma patients to improve return to work (the ROWTATE trial): study protocol for an individually randomised controlled multicentre pragmatic trial.

Background: Moderately severe or major trauma (injury severity score (ISS) > 8) is common, often resulting in physical and psychological problems and leading to difficulties in returning to work. Vocational rehabilitation (VR) can improve return to work/education in some injuries (e.g.