The Role of Alarmins in Osteoarthritis Pathogenesis: HMGB1, S100B and IL-33.

Osteoarthritis (OA) is a multifactorial disease in which genetics, aging, obesity, and trauma are well-known risk factors. It is the most prevalent joint disease and the largest disability problem worldwide. Recent findings have described the role of damage-associated molecular patterns (DAMPs) in the course of the disease. In particular, alarmins such as HMGB1, IL-33, and S100B, appear implicated in enhancing articular inflammation and favouring a catabolic switch in OA chondrocytes. The aims of this review are to clarify the molecular signalling of these three molecules in OA pathogenesis, to identify their possible use as staging biomarkers, and, most importantly, to find out whether they could be possible therapeutic targets. Osteoarthritic cartilage expresses increased levels of all three alarmins. HMGB1, in particular, is the most studied alarmin with increased levels in cartilage, synovium, and synovial fluid of OA patients. High levels of HMGB1 in synovial fluid of OA joints are positively correlated with radiological and clinical severity. Counteracting HMGB1 strategies have revealed improving results in articular cells from OA patients and in OA animal models. Therefore, drugs against this alarmin, such as anti-HMGB1 antibodies, could be new treatment possibilities that can modify the disease course since available medications only alleviate symptoms.

Effect of biological DMARDs and JAK inhibitors in pain of chronic inflammatory arthritis.

INTRODUCTION: The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs) and, more recently, of Janus kinase inhibitors (JAKi) has had a major impact on the long-term outcomes of chronic inflammatory arthritis (IA). However, the persistence of pain, even in patients with a complete pharmacological control of peripheral inflammation, represents an important clinical challenge in the treatment of IA. AREAS COVERED: In this review, we provide an overview of possible mechanisms underlying pain in IA and its assessment, as well as the effects of bDMARDs and JAKi on pain management. EXPERT OPINION: The overall data showed a good effect of bDMARDs and JAKi on pain, which is more pronounced for JAKi. However, it is challenging to distinguish the effect on the different types of pain (nociceptive, neuropathic, and nociplastic).

[Thyroid microcarcinoma in benign thyroid diseases]. / Il microcarcinoma tiroideo nelle tireopatie benigne.

INTRODUCTION: Thyroid microcarcinoma is a malignant thyroid tumor with potential multifocality and a maximum of 1 cm of diameter. This carcinoma has been discovered more frequently like incidentaloma. AIM OF THE STUDY: To appraise the incidence of MCT in the benign thyroid diseases and the advantages offered from the total thyroidectomy, performed for benign diffused thyroid diseases, which surgical treatment "therapeutic" performed for these malignant tumors. MATERIALS AND METHODS: The study was conducted on 600 patients operated with total thyroidectomy for benign thyroid disease, admitted from 1999 to 2003. RESULTS: All patients were alive and free of disease at last control. DISCUSSION: The MCT is a carcinoma that presents frequently a behavior little malignant and a good prognosis. His principal characteristic is the absence of clinical demonstrations. Therefore his discovery, almost always accidental on a thyroid removed for other pathology, it has signaled by histologic study CONCLUSIONS: Thyroid microcarcinoma is a slow growing tumor, with a good prognosis and with a good disease-free survival. It can present a better aggressiveness for his multifocal localization and invasion. Therefore total thyroidectomy can be considered best treatment and also be surgical treatment oncologically correct for this tumor.

[Zuckerkandl's tuberculum: could it be useful in thyroid surgery?]. / Il tubercolo di Zuckerkandl: è un ausilio nella chirurgia della tiroide?

A thorough knowledge of thyroid anatomy could reduce the incidence of lesions to the inferior laryngeal nerve. In view of its relationship with the recurrent laryngeal nerve and the parathyroid gland, Zuckerkandl's tuberculum should be considered an anatomical landmark for the recurrent laryngeal nerve in thyroid surgery. The aim of the study was to verify whether the identification of Zuckerkandl's tuberculum could be useful to reduce the incidence of recurrent laryngeal nerve lesions. Four hundred and thirty-two patients underwent thyroid surgery over the period from January 2001 to December 2003 for benign (377 patients) or malignant disease (55 patients). Three-hundred and forty-eight (81%) underwent total thyroidectomy. Zuckerkandl's tuberculum was found in 74.5% of patients, with a high prevalence in the right lobe: in 5% of patients it was grade I, in 50% grade II and in 45% grade III. Its presence was associated with the recurrent laryngeal nerve in almost all cases. Eight of the patients undergoing total thyroidectomy suffered recurrent nerve paralysis, only 4 of which proved definitive. Identification of Zuckerkandl's tuberculum allows safer isolation of the recurrent laryngeal nerve and superior parathyroid gland dissection.