New and Consolidated Therapeutic Options for Pubertal Induction in Hypogonadism: In-depth Review of the Literature.

Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention.

Risk of Malignant Transformation in 3173 Subjects with Histopathologically Confirmed Oral Lichen Planus: A 33-Year Cohort Study in Northern Italy.

Background: Oral lichen planus (OLP) is considered an oral potentially malignant disorder. The aim of our study was to estimate the risk for oral cancer in patients diagnosed with OLP.

Methods: A population-based cohort study between January 1988 and December 2020 at one hospital in Northern Italy was performed.

Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism.

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines.

Therapeutic effects of androgens for cachexia.

Cachexia is a complex wasting syndrome, accompanying a variety of end-stage chronic diseases, such as cancer, heart failure and human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS). It significantly affects patients' quality of life and survival. Multiple therapeutic approaches have been studied over time.

Journal submissions, review and editorial decision patterns during initial COVID-19 restrictions.

We use the full administrative records from four leading agricultural economics journals to study the impacts of the COVID-19 pandemic on manuscript submission, editorial desk rejection and reviewer acceptance rates, and time to editorial decision. We also test for gender differences in these impacts. Manuscript submissions increased sharply and equi-proportionately by gender.

Confocal Endomicroscopy of Neuromuscular Junctions Stained with Physiologically Inert Protein Fragments of Tetanus Toxin.

Live imaging of neuromuscular junctions (NMJs) in situ has been constrained by the suitability of ligands for inert vital staining of motor nerve terminals. Here, we constructed several truncated derivatives of the tetanus toxin C-fragment (TetC) fused with Emerald Fluorescent Protein (emGFP). Four constructs, namely full length emGFP-TetC (emGFP-865:TetC) or truncations comprising amino acids 1066-1315 (emGFP-1066:TetC), 1093-1315 (emGFP-1093:TetC) and 1109-1315 (emGFP-1109:TetC), produced selective, high-contrast staining of motor nerve terminals in rodent or human muscle explants.

Insulin and the insulin receptor collaborate to promote human gastric cancer.

Background: Gastric adenocarcinoma is common and consequent mortality high. Presentation and mortality are increased in obese individuals, many of whom have elevated circulating insulin concentrations. High plasma insulin concentrations may promote, and increase mortality from, gastric adenocarcinoma.

Inconsistencies in fertility preservation for young people with cancer in the UK.

Objective: To assess the utilisation of and funding structure for fertility preservation for children diagnosed with cancer in the UK.

Design: Survey of paediatric oncologists/haematologists. Questionnaires were sent electronically with reminder notifications to non-responders.

Mass production methods for mass vaccination: improving flow and operational performance in a COVID-19 mass vaccination centre using Lean.

The COVID-19 pandemic has infected tens of millions of people worldwide causing many deaths. Healthcare systems have been stretched caring for the most seriously ill and lockdown measures to interrupt COVID-19 transmission have had adverse economic and societal impacts. Large-scale population vaccination is seen as the solution.

IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial.

IKZF1 deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+ and BCR-ABL1- B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420).

Contribution of Heparan Sulphate Binding in CCL21-Mediated Migration of Breast Cancer Cells.

Chemokine receptor CCR7 is implicated in the metastasis of breast cancer to the lymph nodes. Chemokine function is dependent upon their binding to both cell-surface heparan sulphate (HS) and to their specific receptors; thus, the role of HS in CCR7-mediated lymph node metastasis was investigated by creating a non-HS binding chemokine CCL21 (mut-CCL21). Mut-CCL21 (Δ103-134) induced leukocyte chemotaxis in diffusion gradients but did not stimulate trans-endothelial migration of PBMCs ( < 0.

The rise and rise of NMAHPs in UK clinical research.

Over the past decade, the role of nurses, midwives and allied health professionals (NMAHPs) have been transformed within the UK research community. Assisted by new funding opportunities and a recognition of their role in interdisciplinary working, NMAHPs are driving innovative patient care. Challenges still remain to maximise the potential of NHAMPs in clinical research; signposting opportunities to become involved in research, promoting clear career pathways and developing innovative roles with the NHS to attract and retain this community are critical.

Regional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson's disease.

Previous studies have reported substantial involvement of the noradrenergic system in Parkinson's disease. Neuromelanin-sensitive MRI sequences and PET tracers have become available to visualize the cell bodies in the locus coeruleus and the density of noradrenergic terminal transporters. Combining these methods, we investigated the relationship of neurodegeneration in these distinct compartments in Parkinson's disease.

An observational clinical study of the influence of phacoemulsification on choroidal neovascular membrane activity in age related macular degeneration.

Background: Thousands of phacoemulsification surgeries are performed on eyes with age-related macular degeneration (AMD) complicated by choroidal neovascular membrane (CNV) in the United Kingdom each year. As populations age this number is expected to rise. Controversy over phacoemulsification's influence on CNV activity limits the information which clinicians and these patients use to decide on surgery.

New Classification for the Reporting of Complications in Retinal Detachment Surgical Trials.

Importance: Quantifying severity of complications in rhegmatogenous retinal detachment (RRD) surgical trials is needed. A consensus classification system will help surgeons to more effectively compare harms of different surgical techniques.

Objective: To develop a new consensus-based classification to quantify severity of complications of RRD surgery.

Reporting of Complications in Retinal Detachment Surgical Trials: A Systematic Review Using the CONSORT Extension for Harms.

Importance: Knowledge on the frequency and severity of complications in surgical trials for rhegmatogenous retinal detachment (RRD) is essential to determine whether surgical procedures are developed and compared adequately, taking into account not only efficacy but also harms.

Objective: To review standards of reporting of complications in recent randomized clinical trials of RRD surgery.

Evidence Review: This systematic review included randomized clinical trials on RRD surgery published between January 2008 and January 2021 in Embase, MEDLINE, and Web of Science Core Collection databases.

Recent advances in understanding and managing Kallmann syndrome.

Many of the recent advances in our understanding of human reproductive biology and its genetic basis have arisen directly via the genetic investigation of patients with Kallmann syndrome and their families. The disease is characterised by the association of an isolated defect in the secretion (or, less commonly, action) of gonadotropin-releasing hormone (GnRH) and consequent infertility, with anosmia and potentially other associated non-reproductive features. GnRH-producing neurons are located in the hypothalamic brain region after a peculiar migration during embryonic life.

Vitamin D Supplementation for Patients with Chronic Kidney Disease: A Systematic Review and Meta-analyses of Trials Investigating the Response to Supplementation and an Overview of Guidelines.

A large proportion of patients with chronic kidney disease (CKD) are vitamin D deficient (plasma 25-hydroxyvitamin D (25(OH)D) < 25 or 30 nmol/L per UK and US population guidelines) and this contributes to the development of CKD-mineral bone disease (CKD-MBD). Gaps in the evidence-base for the management of vitamin D status in relation to CKD-MBD are hindering the formulation of comprehensive guidelines. We conducted a systemic review of 22 RCTs with different forms of vitamin D or analogues with CKD-MBD related outcomes and meta-analyses for parathyroid hormone (PTH).

Prostatic urethral lift (UroLift): a real-world analysis of outcomes using hospital episodes statistics.

Background: To determine real-world outcomes of prostatic urethral lift (UroLift) procedures conducted in hospitals across England.

Methods: A retrospective observational cohort was identified from Hospital Episode Statistics data including men undergoing UroLift in hospitals in England between 2017 and 2020. Procedure uptake, patient demographics, inpatient complications, 30-day accident and emergency re-attendance rate, requirement for further treatment and catheterization were captured.

Comparison of identifiable and non-identifiable data linkage: health technology assessment of MitraClip using registry, administrative and mortality datasets.

Objectives: The UK MitraClip registry was commissioned by National Health Service (NHS) England to assess real-world outcomes from percutaneous mitral valve repair for mitral regurgitation using a new technology, MitraClip. This study aimed to determine longitudinal patient outcomes by linking to routine datasets: Hospital Episode Statistics (HES) Admitted Patient Care (APC) and Office of National Statistics.

Methods: Two methods of linkage were compared, using identifiable (NHS number, date of birth, postcode, gender) and non-identifiable data (hospital trust, age in years, admission, discharge and operation dates, operation and diagnosis codes).

Electronic clinical decision support tool for assessing stomach symptoms in primary care (ECASS): a feasibility study.

Objective: To determine the feasibility of a definitive trial in primary care of electronic clinical decision support (eCDS) for possible oesophago-gastric (O-G) cancer.

Design And Setting: Feasibility study in 42 general practices in two regions of England, cluster randomised controlled trial design without blinding, nested qualitative and health economic evaluation.

Participants: Patients aged 55 years or older, presenting to their general practitioner (GP) with symptoms associated with O-G cancer.