Reggio Emilia (Northern Italy) Interdisciplinary Uveitis Clinic: What We Have Learned in the Last 20 Years.

PURPOSE: To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center. METHODS: Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center. RESULTS: Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients (p < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs. CONCLUSIONS: The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay.

The Italian Society of Rheumatology clinical practice guidelines for the management of large vessel vasculitis.

OBJECTIVE: Since of the last publication of last recommendations on primary large-vessel vasculitis (LVV) endorsed by the Italian Society of Rheumatology (SIR) in 2012, new evidence emerged regarding the diagnosis and the treatment with conventional and biologic immunosuppressive drugs. The associated potential change of clinical care supported the need to update the original recommendations. METHODS: Using the grading of recommendations assessment, development and evaluation (GRADE)-ADOLOPMENT framework, a systematic literature review was performed to update the evidence supporting the European Alliance of Associations for Rheumatology (EULAR) guidelines on LVV as reference. A multidisciplinary panel of 12 expert clinicians, a trained nurse, and a patients' representative discussed the recommendation in cooperation with an Evidence Review Team. Sixty-one stakeholders were consulted to externally review and rate the recommendations. RESULTS: Twelve recommendations were formulated. A suspected diagnosis of LVV should be confirmed by imaging or histology. In active GCA or TAK, the prompt commencement of high dose of oral glucocorticoids (40-60 mg prednisone-equivalent per day) is strongly recommended to induce clinical remission. In selected patients with GCA (e.g., refractory or relapsing disease or patients at risk of glucocorticoid related adverse effects) the use of an adjunctive therapy (tocilizumab or methotrexate) is recommended. In all patients diagnosed with TAK, adjunctive therapies, such as conventional synthetic or biological immunosuppressants, should be given in combination with glucocorticoids. CONCLUSIONS: The new set of SIR recommendations was formulated in order to provide a guidance on both diagnosis and treatment of patients suspected of or with a definite diagnosis of LVV.

Vogt-Koyanagi-Harada patients show higher frequencies of circulating NKG2Dpos NK and NK T cells.

Vogt-Koyanagi-Harada (VKH) is an autoimmune disease characterized by inflammation in tissues that contain melanocytes. We aimed to increase the knowledge regarding immunological pathways deregulated in VKH disease. We compared the percentages of circulating natural killer (NK), NK T and T cells expressing the activatory markers: CD16, CD69, NK group 2D (NKG2D), natural cytotoxicity triggering receptor 3 (Nkp30), natural cytotoxicity triggering receptor 1 (Nkp46) and the inhibitory marker: NK group 2 member A (NKG2A) in 10 active VKH patients, 20 control subjects (CTR) and seven patients with Behçet disease (BD) by flow cytometry. Cytotoxic potential of NK cells was determined through the degranulation marker CD107a expression after contact with K562 cells by flow cytometry. Moreover, plasmatic levels of 27 cytokines were determined with a multiplex bead-based assay. VKH patients showed higher percentages of NKG2Dpos NK and NK T cells versus CTR. The cytotoxic potential of NK cells induced by K562 cells was comparable between VKH patients and CTR. Finally, higher concentrations of interleukin (IL)-4, IL-5, IL-7, IL-17 and platelet-derived growth factor-subunits B (PDGF-bb) were detected in plasma of VKH patients versus CTR. The immune profile of VKH patients was similar to that of BD patients.

Contribution of the new 2012 EULAR/ACR classification criteria for the diagnosis of polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory disorders in people aged over 50. It is characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdles and neck. To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based on its characteristic clinical manifestations, laboratory evidence of systemic inflammation, rapid response to low doses of glucocorticoids and exclusion of other disorders that may present with proximal pain and stiffness. For classification purposes, several criteria have been proposed over time based on retrospective clinical series, but none have been validated and received universal acceptance. Recently, an international collaborative initiative between the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica classification criteria. In this review, the provisional 2012 EULAR/ACR classification criteria will be presented and their contribution for the diagnosis of polymyalgia rheumatica will be discussed.

Biotherapies in large vessel vasculitis.

The mainstay of therapy of large vessel vasculitides (LVV) remains glucocorticoids (GC). Although most patients initially achieve disease remission, relapses and GC dependence are seen in more than two-thirds of cases. Conventional synthetic disease-modifying antirheumatic drugs (DMARDs) showed little or no steroid sparing effects, while biological agents represent a valid therapeutic option in patients with severe and/or relapsing LVV.

Decreased bone cortical density at the forearm in subjects with subclinical peripheral arterial disease.

UNLABELLED: The association between peripheral arterial disease (PAD) and low bone mass is controversial. In our study, peripheral quantitative computed tomography shows a reduction of cortical but not trabecular, bone mineral density (BMD) at the forearm, in patients with subclinical PAD. INTRODUCTION: Some controversy exists regarding the association between peripheral arterial disease (PAD) and low bone mass. Previous studies have evaluated bone mineral density (BMD) in patients with subclinical PAD, with mixed results. Inconsistency of data may depend on the fact that most studies measured areal bone mineral density (aBMD) by Dual-energy-x ray absorptiometry (DXA). Because DXA cannot distinguish between cortical and trabecular compartments, we reasoned that a study aimed to establish whether these compartments were differentially affected by PAD status could give more information on the nature of this association. METHODS: In this cross-sectional study, we used peripheral quantitative computed tomography (pQCT) to examine volumetric cortical and trabecular mineral density at the radius (vBMD) in a cohort of subjects with subclinical PAD as defined by ABI ≤0.90 and compared them with healthy subjects with no evidence of PAD. RESULTS: Patients with subclinical PAD had significantly reduced cortical density (1101.0 ± 45.4 vs 1156.2 ± 51.3 mg/cm(3), p < 0.001) and cortical area (75.0 ± 20.9 vs 99.9 ± 18.2 mm(2), p < 0.001) than healthy subjects. Trabecular density (178.1 ± 47.9 vs 165.8 ± 29.6 mg/cm(3)) was not significantly different in the two groups. CONCLUSION: Subclinical PAD induces a selective bone loss at the radius compartment, not identified by standard DXA, which seems to occur primarily at the cortical level.

L-arginine supplementation normalizes bone turnover and preserves bone mass in streptozotocin-induced diabetic rats.

Osteopenia, an important complication of diabetes mellitus, is responsible of an increase in bone fracture and of a delay in fracture healing. The pathogenesis of this complication is unclear, however decreased availability and synthesis of nitric oxide (NO) may be regarded as a possible cause of disregulation of bone turnover. The aim of our study was to evaluate the effect of streptozotocin (STZ)-induced diabetes in the rat on bone mineral density (BMD) and bone turnover. We also examined whether supplementation of L-arginine (which acts as a NO substrate) could be beneficial for bone. After 6 weeks of STZ treatment, diabetic rats showed a significant decrease of BMD in the whole body, at the spine, at the pelvis, and at the femur. Bone turnover evaluation revealed a significant decrease in the serum levels of osteocalcin (a marker of bone formation), and an increase of the serum levels of the C-terminal telopeptide of type I collagen (RatLaps; a marker of bone resorption). L-arginine supplementation prevented the diabetes-induced reduction of BMD and osteocalcin, and the increase of RatLaps. These pharmacological actions of L-arginine produce a new suggestion that increase of NO synthesis and availability is potentially useful for effective prevention and treatment of osteopenia associated with diabetes.

Cerec 3 for orthodontics: a tool for treating deep bite.

Bite-opening procedures are used in the early stages of orthodontic fixed treatment in order to: ease antero-posterior tooth movements; bracket the mandibular arch and level the Curve of Spee; prevent mandibular brackets from debonding; use regular straight archwires to proceed with treatment. For these purposes, removable or bonded biteplanes are universally recognized as very effective when the bite-opening is needed. Conventional orthodontic procedures include clinical solutions which effectively open the bite, but they all lack sufficient hygiene, comfort, and esthetics. The authors propose the use of the CAD-CAM technology with the Cerec 3 system (Sirona, Bensheim, Germany) to create an overcrown able to open the bite through clinical crown lengthening of the mandibular second premolars. The laboratory steps are described and the clinical efficacy is demonstrated with an orthodontic case report.

How to improve digital dental radiograph reproducibility: an individualized technique.

Today, the advantages of the use of digital dental radiography as a valid alternative to conventional techniques are well known. In clinical dental practice, it can be useful to realize intraoral dental x-rays that can be compared, even after some years. The use of a conventional XCP instrument with the "long cone" technique helps to limit image distortion, but the comparison is poor. Moreover, in digital radiography, obtaining almost identical images is essential to superimpose them with dedicated software. The aim of the present work was to obtain fully superimposable and reproducible intraoral digital images through the use of an individual resin positioner. The laboratory phases are all described to create a system that enables exact placement of the digital sensor SIDEXIS (Sirona, Germany) in the mouth of the patient. The authors present a case report where the described technique is applied in the orthodontic field to evaluate molar distalization with a fixed appliance.

A pharmacodynamic study of two omeprazole regimens suitable for long-term treatment of duodenal ulcer.

BACKGROUND: The experience with long-term treatment of peptic ulcer with omeprazole is still scant, but the possibility cannot be excluded that its better pharmacodynamic effect on gastric acidity also has a positive result in the relapse rate. Moreover, this drug acts via a mechanism other than receptorial binding, and therefore its efficacy should not dissipate with time. This study was carried out to assess the pharmacodynamic properties and the possible changes with time of two dose regimens of omeprazole that could be suitable for long-term treatment in duodenal ulcer. METHODS: Twenty patients with endoscopically proven duodenal ulcer were studied by means of 24-h gastric pH-metry both in basal conditions and on the 5th day of acute treatment with 40 mg omeprazole in the morning. All the ulcers healed after 4 weeks, and thereafter 10 patients were randomized to receive orally 20 mg omeprazole daily at 0800 h in single-blind fashion (group A) and 10 to receive 20 mg omeprazole every other day (group B) for up to 6 months. At the end of the 1st, 3rd, and 6th month of these maintenance treatments 24-h gastric pH-metry was repeated to assess the antisecretory effect of each regimen over time. In group-B patients the test was performed on 2 consecutive days (without and with medication) at each time interval. The fasting gastrin values were also determined. The patients underwent esophagogastroduodenoscopy every 2 months. RESULTS: Three patients in group B were lost to follow-up for various reasons, and only seven remained eligible for final analysis. The two long-term regimens of omeprazole were able to increase significantly pH values (p < 0.02-0.001) and the times spent at and above pH 3.0 (p < 0.001) over 24 h compared with basal conditions. In group A the 24-h pH value obtained in the 6th month was higher (p < 0.02) than that in the 3rd month of maintenance treatment. In group B the pharmacologic effect tended to decrease on the day without medication compared with the day with medication, but the difference between them was significantly (p < 0.05) only at the 6-month interval. There was no significant difference between the gastrin levels of the two groups in the long-term treatment. No ulcer relapse was detected at any long-term endoscopic control in the two groups of patients. CONCLUSIONS: The two omeprazole regimens we tested are effective in reducing gastric acidity, and their pharmacodynamic action does not decrease with time. They are therefore suitable for maintenance treatment in acid-related disorders.

[Bullous pneumopathy and spontaneous pneumothorax. Atypical radiologic patterns of Pneumocystis carinii pneumonia]. / Pneumopatia bollosa e pneumotorace spontaneo. Quadri radiologici atipici della polmonite da Pneumocystis carinii.

Pneumocystis carinii pneumonia (PCP) is certainly the most frequent opportunistic pulmonary infection in AIDS patients. Besides the conventional radiographic features demonstrating bilateral infiltrates and airspace consolidation, atypical radiologic patterns are reported in the literature, which are characterized by spontaneous pneumothorax and by the presence of bullae, cysts and areas of pulmonary cavitation. Forty consecutive PCP patients were investigated, ten of them presenting with atypical radiographic findings: 1 case of spontaneous pneumothorax with no evidence of bullae and 9 cases of bullous lung disease--5 of them complicated by spontaneous pneumothorax. Several pathogenetic hypotheses were considered; lesions evolution and the differential radiologic diagnosis were discussed. As for diagnosis, the value of chest CT scans is emphasized, together with that of HRCT which is extremely valuable to localize, characterize and evaluate bullous lesions and associated parenchymal signs.

[Destructive cervical amyloidotic spondyloarthropathy in patients undergoing periodic dialysis. Personal experience]. / La spondiloartropatia cervicale destruente amiloidotica nei pazienti in dialisi periodica. Esperienza personale.

The accumulation of amyloid (beta 2-microglobulin) in several organs and tissues of patients in chronic dialysis is a recent pathologic condition. A wide range of cases, supported by specific tests for amyloid on bioptic and autoptic samples, showed a radiographic semiology of osteostructural alterations in various areas which allows amyloidotic condition of bone to be diagnosed with high reliability. In 11 of 62 patients (17.74%) we observed destructive cervical amyloidotic spondyloarthropathy (DCAS). The radiological patterns common to all patients were subchondral sclerosis, erosions of vertebral body plates, widening/narrowing of intervertebral spaces, no/poor osteophytosis. Over-hanging was present in 54.5% of cases, and deformation of vertebral bodies in 45.4%. CT was useful in improving the definition of the various alterations, and in locating others, such as cavitations in vertebral bodies and involvement of apophyseal joints. Constant factors were the association with extravertebral osseous amyloidosis, dyalitic age over 60 months, and the use of Cuprophan membranes for dialysis. The frequent (72.72%) association with alterations involving the lumbar rachis (subchondral sclerosis, erosions and geodes) was suggestive of amyloidotic condition.

[Role of endoscopy in lymphomatous pathology of the digestive tract]. / Il ruolo dell'endoscopia nella patologia linfomatosa del tubo digerente.

Increasingly frequent reports of lymphoma with a gastro-intestinal primary location have stimulated much interest. Symptomatology has been shown not to be very specific, and scarcely different to that of other gastro-intestinal pathologics, both benign and malignant. The identification of some endoscopic pictures which suggest a lymphomatosic pathology and the possibility of collecting targeted biopsy samples, have placed endoscopy among the most important tests in the diagnostic and staging phase of gastro-intestinal lymphoma. This technique plays an equally important role in the follow-up period, since it allows the therapeutic efficacy of treatment to be assessed and the early identification of possible relapses.

[Therapy of resistant duodenal ulcer]. / Terapia dell'ulcera duodenale resistente.

Significant progress has been made in the treatment of duodenal ulcers since cimetidine went on the market. Furthermore widespread use of the H2 blockers has enable us to identify a group of patients who take 8-12 weeks to heal, despite effective treatment and who are now known as "slow" or non-responders. In tackling the problem of ulcers resistant to medical treatment, the paper details the possibilities offered by current solutions on the basis of personal experience as well as reports in the literature. The results obtainable by surgery are also assessed with emphasis on the identification of suitable patients for and the appropriate timing of his surgical option. Finally a therapeutic flow-chart providing guidelines for the rational selection of therapeutic strategies that still had to be based on uncodified personal preferences is proposed.