The endocrine function of osteocalcin regulated by bone resorption. a lesson from reduced and increased bone mass diseases

Bone is a peculiar tissue subjected to a continuous process of self-renewal essential to assure the integrity of the skeleton and to explicate the endocrine functions. The study of bone diseases characterized by increased or reduced bone mass due to osteoclast alterations has been essential to understand the great role played by osteocalcin in the endocrine functions of the skeleton. The ability of osteoclasts to regulate the decarboxylation of osteocalcin and to control glucose metabolism, male fertility, and cognitive functions was demonstrated by the use of animal models. In this review we described how diseases characterized by defective and increased bone resorption activity, as osteopetrosis and osteoporosis, were essential to understand the involvement of bone tissue in whole body physiology. To translate this knowledge into humans, recently published reports on patients were described, but further studies should be performed to confirm this complex hormonal regulation in humans

Bone control of muscle function

Bone and muscle represent a single functional system and are tightly connected to each other. Indeed, diseases characterized by alterations of muscle physiology have effects on bone remodeling and structure and vice versa. Muscle influence on bone has been deeply studied, and recent studies identified irisin as new molecule involved in this crosstalk. Muscle regulation by bone needs to be extensively investigated since in the last few years osteocalcin was recognized as a key molecule in the bone–muscle interaction. Osteocalcin can exist in two forms with different degrees of carboxylation. The undercarboxylated form of osteocalcin is a hormone released by the bone matrix during the osteoclast bone resorption and can bind its G-protein coupled receptor GPRC6A expressed in the muscle, thus regulating its function. Recently, this hormone was described as an antiaging molecule for its ability to regulate bone, muscle and cognitive functions. Indeed, the features of this bone-related hormone were used to test a new therapeutic approach for sarcopenia, since injection of osteocalcin in older mice induces the acquirement of physical abilities of younger animals. Even if this approach should be tested in humans, osteocalcin represents the most surprising molecule in endocrine regulation by the skeleton

Cost-effectiveness of routine mediastinoscopy in computed tomography– and positron emission tomography–screened patients with stage I lung cancer

ObjectiveAccurate preoperative staging is essential for the optimal management of patients with lung cancer. An important goal of preoperative staging is to identify mediastinal lymph node metastasis. Computed tomography and positron emission tomography may identify mediastinal lymph node metastasis with sufficient sensitivity to allow omission of mediastinoscopy. This study utilizes our experience with patients with clinical stage I lung cancer to perform a decision analysis addressing whether mediastinoscopy should be performed in clinical stage I lung cancer patients staged by computed tomography and positron emission tomography.MethodsWe retrospectively reviewed our thoracic surgery database for cases between May 1999 and May 2004. Patients deemed clinical stage I by computed tomography and positron emission tomography were chosen for further study. Individual computed tomography, positron emission tomography, and operative and pathology reports were reviewed. The postresection pathologic staging and long-term survival were recorded. A decision model was created using TreeAgePro software and our observed data for the prevalence of mediastinal lymph node metastases and for the rate of benign nodules. Data reported in the literature were also utilized to complete the decision analysis model. A sensitivity analysis of key variables was performed.ResultsA total of 248 patients with clinical stage I lung tumors were identified. One hundred seventy-eight patients (72%) underwent mediastinoscopy before resection, and 5/178 (3%) showed N2 disease. An additional 9 patients were found to have N2 metastasis in the final resected specimen, resulting in a total of 14/248 patients (5.6%) with occult mediastinal lymph node metastases. Benign nodules were found in 19/248 (8%) of patients. Decision analysis determined that mediastinoscopy added 0.008 years of life expectancy at a cost of $250,989 per life-year gained. The outcome was sensitive to the prevalence of N2 disease in the population and the benefit of induction versus adjuvant therapy for N2 lung cancer. If the prevalence of N2 disease exceeds 10$100,000 per life-year gained.ConclusionPatients with clinical stage I lung cancer staged by computed tomography and positron emission tomography benefit little from mediastinoscopy. The survival advantage it confers is very small and is dependent on the prevalence of N2 metastasis and the unproven superiority of induction therapy over adjuvant therapy

Not simply a matter of psoriatic arthritis: epidemiology of rheumatic diseases in psoriatic patients

This study investigated the occurrence of rheumatic conditions (RCs) in a psoriasis (PSO)-dedicated dermatological clinic. PSO subjects with musculo-skeletal discomfort, and/or carrying signs (articular/systemic, even asymptomatic) of RCs; and/or suffering flares of previously established psoriatic arthritis (PsA) were referred to rheumatologist for evaluation. Laboratory tests/imaging were performed as needed. Categorization adhered to RCs classification endorsed by the Italian Society of Rheumatology. Of the 1,200 psoriatic subjects, 277 (23.1 %) were enrolled (146 females). The mean age was 55.7 years (range 21–81), PSO duration was 13.5 years (range 0–62). Thirty-seven patients (13.4 %) were asymptomatic. On an average, 92 (7.6 %) patients/year were evaluated, of whom 79.4 % näive to rheumatological consultations (NRC). Osteoarthritis (OA) and PsA (isolated or combined) showed the highest prevalence, with 156 (56.3 %) and 110 cases (39.7 %), respectively. Among NRC subjects, the mean PsA annual incidence was 29.5 % (standard error of the mean ±5.4 %). Other RCs, isolated or associated with PsA/OA, were diagnosed in 31 cases (11.2 %). Thirty-two subjects (11.5 %) had arthralgias, 20 of whom due to congenital/mechanical disorders, the remaining were unclassifiable. In conclusion, the largest part (88.5 %) of PSO subjects referred to rheumatologist showed some RCs. On annual basis, 29.5 % of näive enrolled patients were diagnosed as PsA

Long-term survival of methotrexate in psoriatic arthritis

Objective. The purpose of this study was to evaluate the long-term survival rate of Methotrexate (MTX) in the peripheral joint involvement of psoriatic arthritis (PsA) in a setting of everyday clinical practice. Methods. This was an observational restrospective study performed using the data from a dermatological-rheumatological PsA clinic. All of the patients evaluated at this clinic from March 1997 to December 2007 who were started on MTX alone, had a three-year follow-up time or had discontinued the therapy were included into the survey. Results. Of the 174 evaluable patients, 104 (59.8%) were still taking MTX after three years of treament. The reasons of therapy discontinuation in the remaining 70 (40.2%) patients were: 34 (19.5%) lost-to-follow-up, 18 (10.3%) adverse events, 14 (8%) inefficacies, and 4 (2.3%) deaths (none related to the therapy). MTX was effective in controlling joint inflammation but not in preventing their deterioration. Overall, adverse events were recorded in 43 patients (36.4% of the 114 patients with a three-year follow-up). No serious side effect occurred in the study population. Conclusions. The results of this study showed that, in a setting of clinical pratice, MTX had a good three-year performance in patients with peripheral PsA. Almost 60% of them were still taking this drug at the end of the study period and the toxicity was more than acceptable. In our opinion, MTX might be considered the non-biological DMARD of choice for the treatment of this condition. However it should be used earlier and at higher doses

Disability quotas: past or future policy?

This article considers the issues associated with the use of quota systems for the employment of workers with a disability. It examines the use and experiences of such quotas in Italy, Russia and the United Kingdom. Italy has a long established quota for the employment of such workers, whilst the modern Russian system it is a more recent innovation. In contrast the UK abandoned its quotas in the 1990s. We draw on the experiences of the three countries to consider generally whether the use of quotas is either an acceptable means of encouraging employers to take on disabled workers, or is necessary to achieve this objective

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p<0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p<0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved