ESMO Global Consortium Study on the availability, out-of-pocket costs, and accessibility of cancer medicines: 2023 update.

Background: The availability and affordability of safe, effective cancer therapies are core requirements for effective cancer control. Global disparities exist in access, however, yielding unequal cancer outcomes. The goal of this study was to provide updated data regarding the formulary availability, out-of-pocket costs, and accessibility of cancer medicines in countries across the full spectrum of economic development areas.

Voice Quality as Digital Biomarker in Bipolar Disorder: A Systematic Review.

Background: Voice analysis has emerged as a potential biomarker for mood state detection and monitoring in bipolar disorder (BD). The systematic review aimed to summarize the evidence for voice analysis applications in BD, examining (1) the predictive validity of voice quality outcomes for mood state detection, and (2) the correlation between voice parameters and clinical symptom scales.

Methods: A PubMed, Scopus, and Cochrane Library search was carried out by two investigators for publications investigating voice quality in BD according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.

Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer.

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies.

Off-axis electron holography of unstained bacteriophages: Toward electrostatic potential measurement of biological samples.

Transmission electron microscopy, especially at cryogenic temperature, is largely used for studying biological macromolecular complexes. A main difficulty of TEM imaging of biological samples is the weak amplitude contrasts due to electron diffusion on light elements that compose biological organisms. Achieving high-resolution reconstructions implies therefore the acquisition of a huge number of TEM micrographs followed by a time-consuming image analysis.

Chapter 15: RECURRENT OR PERSISTENT PRIMARY HYPERPARATHYROIDISM, PARATHYROMATOSIS.

Persistent primary hyperparathyroidism is defined as the persistence or recurrence of hypercalcemia within 6 months of parathyroid surgery. Recurrent primary hyperparathyroidism is defined as the recurrence of primary hyperparathyroidism more than 6 months after an initially curative parathyroidectomy. In these situations, it is essential to rule out differential diagnoses, and in particular secondary hyperparathyroidism and familial hypocalciuric hypercalcemia.

Chapter 5: THE ROLE OF GENETICS IN PRIMARY HYPERPARATHYROIDISM.

Around 10% of cases of primary hyperparathyroidism are thought to be genetic in origin, some of which are part of a syndromic form such as multiple endocrine neoplasia types 1, 2A or 4 or hyperparathyroidism-jaw tumor syndrome, while the remainder are cases of isolated familial primary hyperparathyroidism. Recognition of these genetic forms is important to ensure appropriate management according to the gene and type of variant involved, but screening for a genetic cause is not justified in all patients presenting primary hyperparathyroidism. The indications for genetic analysis have made it possible to propose a decision tree that takes into account whether the presentation is familial or sporadic, syndromic or isolated, patient age, and histopathological type of parathyroid lesion.

Chapter 8: MANAGEMENT OF AGGRESSIVE FORMS OF PRIMARY HPT: PARATHYROID CARCINOMA AND ATYPICAL PARATHYROID TUMOR.

Parathyroid carcinoma is extremely rare, affecting 1% of cases of primary hyperparathyroidism. For this reason, management is poorly codified and requires expertise in specialized center. PC is genetically determined in a quarter to a third of cases, notably involving the CDC73 gene coding for parafibromin.

Chapter 6: SYNDROMIC PRIMARY HYPERPARATHYROIDISM.

Syndromic primary hyperparathyroidism has several features in common: younger age at diagnosis when compared with sporadic primary hyperparathyroidism, often synchronous or metachronous multi-glandular involvement, higher possibility of recurrence, association with other endocrine or extra-endocrine disorders, and suggestive family background with autosomal dominant inheritance. Hyperparathyroidism in multiple endocrine neoplasia type 1 is the most common syndromic hyperparathyroidism. It is often asymptomatic in adolescents and young adults, but may be responsible for recurrent lithiasis and/or bone loss.

Chapter 11: TREATMENT MODALITIES.

Treatment modalities for primary hyperparathyroidism must take account of the expected benefits and risks of each treatment envisaged, before choosing the definitive option to be proposed to the patient. In this section, a Foreword puts in perspective the difficulties involved in choosing the criteria for a particular treatment method. Treatments are then considered one after the other: surgery, local destruction and medical management.

Chapter 0: Introduction to the Consensus on Primary Hyperparathyroidism from the French Society of Endocrinology, French Association of Endocrine Surgery and French Society of Nuclear Medicine.

This consensus on primary hyperparathyroidism, drawn up under the aegises of the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN), provides an update on positive, etiological and differential diagnosis and treatment in primary hyperparathyroidism. These recommendations take account of recent increase in the prevalence of primary hyperparathyroidism, due to 1. more systematic routine measurement of blood calcium and improved quality of parathyroid hormone assays, 2.

Chapter 13: 2022 WHO CLASSIFICATION OF PARATHYROID TUMORS.

The latest 2022 WHO classification of the parathyroid tumors incorporates recent data on parathyroid pathophysiology, in particular from genetic sequencing. It highlights histological features potentially indicative of underlying genetic abnormalities, because of their implications for patient management. Immunohistochemical markers can help characterize parathyroid lesions and molecular screening.

Chapter 10: WHAT PARATHYROID IMAGING IS REQUIRED FOR HYPERPARATHYROIDISM?

In over 80% of cases, primary hyperparathyroidism results from hypersecretion of PTH by a single parathyroid adenoma. Multi-glandular involvement, combining adenoma and/or hyperplasia in varying proportions, is also possible, although less frequent. When the diagnosis of hyperparathyroidism is certain and surgery is envisaged, imaging is useful for locating the hyperfunctioning gland or glands.

Chapter 7: CLINICAL FORMS AT DIFFERENT AGES OF LIFE: CHILDHOOD, PREGNANCY, LACTATION, OLD AGE.

Primary hyperparathyroidism is rare in children. A germline mutation is identified in half of all children with primary hyperparathyroidism (70% of newborns and infants, and 40% of children and adolescents). The clinical manifestations of primary hyperparathyroidism in children are highly variable (often absent in newborns, rather severe and symptomatic in children and adolescents) and depend on the genetic cause, as well as the severity, rapidity of onset and duration of hypercalcemia.

Chapter 4: DIFFERENTIAL DIAGNOSIS of PRIMARY HYPERPARATHYROIDISM.

The differential diagnosis of primary hyperparathyroidism can be considered clinically, biologically and radiologically. Clinically, primary hyperparathyroidism should be suspected in case of diffuse pain, renal lithiasis, osteoporosis, repeated fracture, cognitive or psychiatric disorder, or disturbance of consciousness. Nevertheless, the differential diagnosis of primary hyperparathyroidism is mainly biological, particularly in atypical forms, which must be differentiated from hypercalcemia with hypocalciuria or non- elevated PTH on the one hand, and from normo-calcemia with elevated PTH, hypophosphatemia or hypercalciuria on the other.

Determinants of cerebrospinal fluid leakage in a large cohort of macroprolactinomas.

Background: Non-functional adrenal incidentaloma (NFAI) is associated with increased risk of adverse cardiometabolic outcome. Identifying predictors of atherosclerotic cardiovascular disease (ASCVD) may enable more appropriate management strategies in patients with NFAI. We aimed to investigate body composition parameters and ASCVD risk in patients with NFAI.

Chapter 1: EPIDEMIOLOGY OF PRIMARY HYPERPARATHYROIDISM.

Primary hyperparathyroidism (PHPT) is a frequent disease. Prevalence continues to rise in Europe, long after the advent of automated calcemia meters, while incidence has stabilized. The disease is much more common in women, at around 75% of cases, and is more prevalent with advancing age, and particularly post-menopause.

Gonadotropic axis following endoscopic surgery for pituitary neuroendocrine tumor in patients of reproductive age.

Purpose: Pituitary neuroendocrine tumor (PitNET), excluding prolactinoma, often requires endoscopic endonasal surgery (EES). Identifying predictive factors for complications, and particularly rare ones such as hypogonadotropic hypogonadism (HH) that may affect fertility, is challenging. This study investigated de-novo postoperative HH and its potential impact on fertility.

Chapter 3: IMPACT OF PRIMARY HYPERPARATHYROIDISM.

At present, primary hyperparathyroidism is most often discovered in an asymptomatic patient, but can sometimes be revealed by a renal or bone complications. In all cases, a full work-up is recommended, with assessment of renal function (glomerular filtration rate), 24-hour calciuria, screening for risk factors for lithiasis, and renal and urinary tract imaging (ultrasound or CT scan) to look for stones or nephrocalcinosis. Bone densitometry, with measurements of the spine, femur and radius, is the recommended reference test for demineralization.

Chapter 2: PRIMARY HYPERPARATHYROIDISM: DIAGNOSIS.

Primary hyperparathyroidism is now predominantly an asymptomatic pathology, as blood calcium assay has become systematic. Diagnosis therefore requires screening for target organ damage when this is not already indicative of primary hyperparathyroidism.Classical clinical manifestations include bone, kidney and muscle signs, and are characterized by reversibility after parathyroid surgery.

Chapter 12: PREPARATION FOR PARATHYROID SURGERY.

Preoperative treatment of PHPT aims to 1) manage severe and/or symptomatic hypercalcemia and 2) prevent postoperative hypocalcemia. Severe hypercalcemia, defined as a blood calcium level ≥ 3.5 mmol/L, requires admission to hospital in a conventional or critical care unit, depending on clinical symptoms and comorbidities.

Chapter 9: INDICATIONS FOR TREATMENT.

The choice of therapeutic method for the management of primary hyperparathyroidism depends on the severity of the disease and its complications at the time of diagnosis, the specific situation of each patient and his/her natural history, and assessment of the risk/benefit ratio for each method (surgery, local destruction or drugs). This chapter summarizes the indications for the treatment of primary hyperparathyroidism, based on the international literature available as of December 31, 2023.

Baricitinib in early polymyalgia rheumatica (BACHELOR): a randomised, double-blind, placebo-controlled, parallel-group trial.

Background: Moderate doses of glucocorticoids result in improvements in nearly all patients with polymyalgia rheumatica, but related adverse events are common in older individuals. We aimed to evaluate whether treatment with baricitinib (a Janus kinase 1/2 inhibitor) results in disease control without the use of oral glucocorticoids in people with recent-onset polymyalgia rheumatica.

Methods: We conducted a randomised, double-blind, placebo-controlled, parallel-group trial at six expert centres in France.

Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Background: Data on the effect of mineralocorticoid receptor antagonist therapy on HbA levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial.

Methods: In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally.

Dissection of type 2 diabetes: a genetic perspective.

Diabetes is a leading cause of global mortality and disability, and its economic burden is substantial. This Review focuses on type 2 diabetes, which makes up 90-95% of all diabetes cases. Type 2 diabetes involves a progressive loss of insulin secretion often alongside insulin resistance and metabolic syndrome.