MASLD, hepatic steatosis and fibrosis are associated with the prevalence of chronic kidney disease and retinopathy in adults with type 1 diabetes mellitus.

AIM: We examined whether metabolic dysfunction-associated steatotic liver disease (MASLD) with or without significant fibrosis (assessed by validated non-invasive biomarkers) was associated with an increased risk of prevalent chronic kidney disease (CKD) or diabetic retinopathy in people with type 1 diabetes mellitus (T1DM). METHODS: We performed a retrospective multicenter cross-sectional study involving 1,409 adult outpatients with T1DM, in whom hepatic steatosis index (HSI) and fibrosis (FIB)-4 index were calculated for non-invasively detecting hepatic steatosis (defined by HSI > 36), with or without coexisting significant fibrosis (FIB-4 index ≥ 1.3 or < 1.3). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin/creatinine ratio ≥ 3.0 mg/mmol. The presence of diabetic retinopathy was also recorded in all participants. RESULTS: Patients with MASLD and significant fibrosis (n = 93) had a remarkably higher prevalence of CKD and diabetic retinopathy than their counterparts with MASLD without fibrosis (n = 578) and those without steatosis (n = 738). After adjustment for sex, diabetes duration, hemoglobin A1c, hypertension, and use of antihypertensive or lipid-lowering medications, patients with SLD and significant fibrosis had a higher risk of prevalent CKD (adjusted-odds ratio 1.76, 95 % confidence interval 1.05-2.96) than those without steatosis. Patients with MASLD without fibrosis had a higher risk of prevalent retinopathy (adjusted-odds ratio 1.49, 95 % CI 1.13-1.46) than those without steatosis. CONCLUSION: This is the largest cross-sectional study showing that MASLD with and without coexisting significant fibrosis was associated, independently of potential confounders, with an increased risk of prevalent CKD and retinopathy in adults with T1DM.

Efficacy of a training programme for the management of diabetes mellitus in the hospital: A randomized study (stage 2 of GOVEPAZ healthcare).

AIMS: To assess the efficacy of a structured educational intervention for health professionals on the appropriateness of inpatient diabetes care and on some clinical outcomes in hospitalised subjects. METHODS: A multicentre (6 regional hospitals) cluster-randomized (2:1) two parallel-group pragmatic intervention trials, as a part of the GOVEPAZ study, was conducted in three clinical settings, that is, Internal Medicine, Surgery and Intensive Care. Intervention consisted of a 2-month structured education of clinical staff to inpatient diabetes care. Twelve wards - 2 for each hospital - and 6 wards - 1 for each hospital - were randomized to usual care and to the intervention arm, respectively. Consecutively hospitalised diabetic subjects (n = 524, age 74 ± 14 years, 57% males, median HbA1C 57 mmol/mol) were included. The clinical appropriateness of inpatient diabetes management was assessed by a previously validated multi-domain performance score (PS). Clinical outcomes included hypoglycemia, glucose control biomarkers, clinical conditions at discharge and inpatient mortality rate. RESULTS: A numerically, but not statistically significant, higher PS (+0.94; 95% C.I.: -0.53 - +2.4) was achieved in the intervention than in the usual care wards. Hypoglycemias (p = 0.32), glucose control (p = 0.89) and survival rates (p = 0.71) were similar in the two experimental arms. Plasma glucose on admission (OR = 1.52 per 1 SD; C.I. 1.07-2.17; p = 0.021) and the number of hypoglycemic events per patient (OR = 1.55 per 1 SD; C.I.:1.11-2.16; p = 0.011) were independently associated with the inpatient mortality rate. CONCLUSIONS: Structured education of the clinical staff failed to improve the inpatient appropriateness of diabetes care or clinical outcomes. In-hospital hypoglycemia was confirmed to be an independent indicator of death risk.

The Effect of Different Opioids on Acid-Base Balance and Blood Gas Analysis in Hospitalized Dogs.

Pain management is central to veterinary practice, contributing to successful case outcomes and enhancement of the veterinarian-client-patient relationship. Analgesic drugs represent one of the pillars of the multimodal approach to acute and chronic pain management. In dogs, the most used opioids are methadone, buprenorphine and tramadol. Several episodes of hypoglycemia in people treated with tramadol and methadone have recently been described. The aim of this work is to evaluate the changes in the glycemic and acid-base balance induced by tramadol, methadone and buprenorphine in hospitalized dogs. A retrospective review of the medical records of dogs hospitalized for both medical and surgical reasons was performed. During 2018-2020, a total of 876 canine patients were treated with opioids, including 228 with tramadol, 273 with methadone and 375 with buprenorphine. Of all these dogs, only a small percentage met the inclusion criteria presented in the initial design. All the hospitalized animals were monitored daily through clinical examination and blood sampling. Blood samples were obtained before opioid administration (T0), and 24 h (T1) and 48 h (T2) after °pioid administration. The following parameters were evaluated: blood gas value (pH, pCO2), acid-base state (cHCO3), oxymetric values (ctHb, haematocrit), electrolyte values (K+, Na+, iCa, Cl-) and metabolic values (glucose, lactate, anion GAP K+c). The glycemic value in enrolled dogs showed a decrease over time, regardless of the type of opioid used, but remained within the physiological range. The highest average glycemic drop was recorded for methadone, between T0 and T1, followed by tramadol between T1 and T2, while buprenorphine recorded the highest overall glycemic drop between T0-T2 when compared to the other two opioids. Female dogs showed the greatest drop in glycemic value. Lactate concentration always presented values beyond the physiological range at an early stage, which then normalized quickly. Measurement of electrolyte concentrations showed a consistent increase in the values of iCa, Na and Cl. In hospitalized dogs treated with opioids monitoring of gas analytic parameters is important and more attention should be paid to patients hospitalized with certain metabolic and endocrine diseases.

Clinical Features and Prevalence of Spondyloarthritis in a Cohort of Italian Patients Presenting with Acute Nongranulomatous Anterior Uveitis.

PURPOSE: To describe the clinical features of acute nongranulomatous anterior uveitis (NGAU) patients and to estimate the prevalence of concomitant spondyloarthritis (SpA). METHODS: Retrospective study of consecutive patients affected by NGAU referred to the Ocular Immunology Unit of the AUSL-IRCCS di Reggio Emilia, Italy, between January 2016 and January 2019. All patients underwent ophthalmic evaluation and blood test with HLA-B27 typing and were referred to a rheumatologist to identify any undiagnosed SpA. SpA was classified according to the Assessment of SpondyloArthritis international Society (ASAS) criteria in axial or peripheral SpA. Patients were divided into two groups: NGAU with associated SpA (SpA+) and NGAU without SpA (SpA-). Clinical and demographic features of the two groups, including sex, HLA-B27, family history of rheumatic disease, uveitis laterality, course, and severity of ocular inflammation, complications, and treatment, were compared. RESULTS: Ninety-nine patients with NGAU were enrolled, of whom 36 (36%) with a diagnosis of SpA: 14 with peripheral SpA and 22 with axial SpA. The prevalence of SpA was higher in HLA-B27-positive patients than in HLA-B27-negative patients (50% vs. 15%, p < 0.0001). The multivariate logistic regression (R 2 = 0.28) for SpA diagnosis identified as significant predictive factors: age at diagnosis (odds ratio [OR] = 0.95, 95% confidence interval [CI]: 0.91-0.99) and HLA-B27+ (OR = 5.32, 95% CI: 1.80-15.70). CONCLUSIONS: Our results confirmed the high prevalence of undiagnosed SpA in patients with NGAU, suggesting that, regardless of HLA-B27 status, in the presence of IBP and/or peripheral arthritis, patients with NGAU must be referred to the rheumatologist to allow earlier diagnosis.

Clinical Relevance of Subcentimetric Lymph Node Biopsy in the Diagnosis of Ocular Sarcoidosis.

PURPOSE: To evaluate the clinical relevance of subcentimetric lymph node biopsy via mediastinoscopy in patients with presumed ocular sarcoidosis (OS). METHODS: Retrospective study of consecutive patients who underwent biopsy via mediastinoscopy for suspected OS. The biopsy outcomes and clinical features of patients with subcentimetric nodes and of those with lymph nodes >1 cm were compared. RESULTS: A total of 67 patients with presumed OS were included. Forty-two patients (63%) had lymph nodes ≥1 cm in diameter, while 25(37%) showed subcentimetric lymph nodes. Biopsy was consistent with sarcoidosis in 83% of patients with lymph nodes ≥1 cm and in 76% of patients with subcentimetric lymph nodes (p = .60). Patients with OS who had subcentimetric lymph nodes had less lymphopenia (p = .01), lower lysozyme values (p = .03) and a longer diagnostic delay compared to those with larger lymph nodes. CONCLUSIONS: The biopsy of subcentimetric lymph nodes via mediastinoscopy may provide a histological diagnosis and reduce diagnostic delay.

Survival and Recurrence in Vitreoretinal Lymphoma Simulating Uveitis at Presentation: The Possible Role of Combined Chemotherapy.

PURPOSE: To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL). METHODS: Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group. RESULTS: Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P = .03) and death (r = 0.56, P = .009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04- 0.85]) in the entire cohort. CONCLUSION: Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL.

Cataract Surgery with Intraocular Lens Implantation in Juvenile Idiopathic Arthritis-Associated Uveitis: Outcomes in the Era of Biological Therapy.

This study compared the outcomes of cataract surgery with intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis treated with antimetabolite drugs and systemic corticosteroids (Non-Biological Group) versus patients treated with antimetabolites and biological drugs (Biological Group). A cohort of patients with cataract in JIA-associated uveitis undergoing phacoemulsification with IOL implantation was retrospectively evaluated. The main outcome was a change in corrected distance visual acuity (CDVA) in the two groups. Ocular and systemic complications were also recorded. The data were collected preoperatively and at 1, 12, and 48 months after surgery. Thirty-two eyes of 24 children were included: 10 eyes in the Non-Biological Group and 22 eyes in the Biological Group. The mean CDVA improved from 1.19 ± 0.72 logMAR preoperatively to 0.98 ± 0.97 logMAR at 48 months (p = 0.45) in the Non-Biological Group and from 1.55 ± 0.91 logMAR preoperatively to 0.57 ± 0.83 logMAR at 48 months (p = 0.001) in the Biological Group. The postoperative complications, including synechiae, cyclitic membrane, IOL explantation, glaucoma, and macular edema, were not statistically different between the two groups. An immunosuppressive treatment with biological drugs can improve the visual outcome after cataract surgery in patients with JIA-associated uveitis, but it does not significantly reduce postoperative ocular complications.

Association Between Specimen Length and Number of Sections and Diagnostic Yield of Temporal Artery Biopsy for Giant Cell Arteritis.

OBJECTIVE: To investigate the association between specimen length and number of sections evaluated and the diagnostic yield of temporal artery biopsy (TAB) for giant cell arteritis (GCA). METHODS: A pathologist reviewed all TABs performed for suspected GCA between January 1991 and December 2012. The blocks of all the inadequate and negative biopsy specimens were recut, and further slides at deeper levels were stained with hematoxylin and eosin in order to avoid missing inflammatory changes. RESULTS: In total, findings from 662 TABs were included in the study (71% female; mean age 73.2 years). A total of 427 TAB specimens (65%) were classified as negative, and 235 (35%) were classified as positive for GCA. Compared to those with negative TAB results, patients with positive TAB results were older and more frequently female. There was no difference in postfixation TAB specimen length between TAB specimens negative and positive for GCA (mean 6.5 mm versus 6.9 mm; P = 0.068). Cuts of additional biopsy sections revealed inflammation at deeper levels in 26 of 408 TAB specimens (6.4%) originally reported as uninflamed. The inflamed section was the second in 14 TAB specimens, the third in 9 specimens, and the fourth in 3 specimens. Piecewise logistic regression identified 5 mm as the TAB specimen length change point for diagnostic sensitivity. Compared to a TAB specimen length of <5 mm, the age- and sex-adjusted odds ratio for positive TAB results in samples ≥5 mm long was 1.5 (95% confidence interval 1.0-2.0), P = 0.032. CONCLUSION: A postfixation TAB specimen length of at least 5 mm should be sufficient to make a histologic diagnosis of GCA. In order not to miss inflammatory changes, at least 3 further sections at deeper levels should be evaluated in all negative TAB specimens.

A performance score of the quality of inpatient diabetes care is a marker of clinical outcomes and suggests a cause-effect relationship between hypoglycaemia and the risk of in-hospital mortality.

AIMS: To build a tool to assess the management of inpatients with diabetes mellitus and to investigate its relationship, if any, with clinical outcomes. MATERIALS AND METHODS: A total of 678 patients from different settings, Internal Medicine (IMU, n = 255), General Surgery (GSU, n = 230) and Intensive Care (ICU, n = 193) Units, were enrolled. A work-flow of clinical care of diabetes was created according to guidelines. The workflow was divided into five different domains: (a) initial assessment; (b) glucose monitoring; (c) medical therapy; (d) consultancies; (e) discharge. Each domain was assessed by a performance score (PS), computed as the sum of the scores achieved in a set of indicators of clinical appropriateness, management and patient empowerment. Appropriate glucose goals were included as intermediate phenotypes. Clinical outcomes included: hypoglycaemia, survival rate and clinical conditions at discharge. RESULTS: The total PS and those of initial assessment and glucose monitoring were significantly lower in GSU with respect to IMU and ICU (P < .0001). The glucose monitoring PS was associated with lower risk of hypoglycaemia (OR = 0.55; P < .0001), whereas both the PSs of glucose monitoring and medical therapy resulted associated with higher in-hospital survival only in the IMU ward (OR = 6.67 P = .001 and OR = 2.38 P = .03, respectively). Instrumental variable analysis with the aid of PS of glucose monitoring showed that hypoglycaemia may play a causal role in in-hospital mortality (P = .04). CONCLUSIONS: The quality of in-hospital care of diabetes may affect patient outcomes, including glucose control and the risk of hypoglycaemia, and through the latter it may influence the risk of in-hospital mortality.

Relapses and long-term remission in large vessel giant cell arteritis in northern Italy: Characteristics and predictors in a long-term follow-up study.

OBJECTIVE: To evaluate characteristics and predictors of relapses and long-term remission in an Italian cohort of patients with large-vessel (LV) giant cell arteritis (GCA). METHODS: We evaluated 87 consecutive patients with LV-GCA followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for at least 2 years. Patients with relapses and long-term remission were compared to those without. A group of 34 patients with biopsy proven GCA without LV vasculitis (LVV) at diagnosis was considered for comparison. PATIENTS: 37 patients (42.5%) experienced one or more relapses. Nineteen (37.2%) of the 51 relapses were experienced during the first year after diagnosis. The majority of relapses occurred with doses of prednisone (PDN) ≤ 10 mg/day (74.5%). Polymyalgia rheumatica (PMR) (41.2%) and worsening at imaging of LVV (39.2%) were the most frequently observed relapsing manifestations. The total cumulative prednisone dose was significantly higher (p < 0.0001) and the total duration of PDN treatment longer (p < 0.0001) in relapsing patients compared to those without relapses. Relapsing patients had at diagnosis more frequently fever ≥ 38°C (p = 0.03) and visual manifestations (p = 0.03), and less frequently long-term remission (p = 0.002). In the multivariate model fever ≥ 38°C (HR 2.30, 95%CI:1.11-4.78) and total cumulative PDN dose (HR 1.18, 95%CI: 1.08-1.30) were significantly associated with an increased risk of relapses, while aortic arch involvement at imaging at diagnosis (HR 0.26, 95%CI: 0.11-0.59) and long-term remission (HR 0.27, 95%CI: 0.11-0.65) with a reduced risk. 35/84 patients (41.6%) experienced long-term remission. PMR and disease relapses were less frequently observed (p = 0.04 and p = 0.002, respectively), and the total cumulative prednisone dose was lower (p < 0.001) in patients with long-term remission compared to those without. In the multivariate model the presence of relapses (HR 0.21, 95%CI: 0.07-0.62) and the total cumulative PDN dose (HR 0.85, 95%CI: 0.77-0.95) were significantly negatively associated with long-term remission. CONCLUSION: In our cohort of patients with LV GCA we identified predictors of a relapsing course and long-term remission, which were observed in around half of the patients.

Incidental versus clinically diagnosed differentiated thyroid cancer in both adult and elderly subjects: histological characteristics and follow-up in a retrospective analysis from a single institution.

PURPOSE: Most thyroid cancer are incidentally diagnosed. However, little is known on the different modalities of incidental diagnosis in adult versus older patients. METHODS: We retrospectively analyzed data from 440 patients consecutively diagnosed with differentiated thyroid cancer (DTC) in a single institution. Modalities of diagnosis were categorized as follows: (A) clinically diagnosed, nonincidental cases; (B) incidental during carotid power-duplex (CPD); (C) incidental during neck imaging other than carotid power-duplex; (D) incidental during imaging workup of thyroid dysfunction or at histological examination after thyroidectomy for benign lesions. Demographics, histology and follow-up were compared between adult (<65 years) and older (≥65 years) patients according to the different modalities of diagnosis. RESULTS: A total of 363 and 67 cases were recorded in adult and older patients, respectively with incidental proportions of 79% and 85%, respectively. A P < 0.001 significant difference in the modality of diagnosis was found between adult and older subjects, the latter presenting with a higher prevalence of Group B. In the nonincidental group, papillary histotype, larger size, and extrathyroidal invasion were more frequently observed in older subjects. Disease-free survival was comparable between adult and older subjects in the incidental cases, whereas it was reduced, though not significantly, in older subjects. CONCLUSION: Incidental cases of DTC are more frequently diagnosed in the old subjects and are mainly due to CPD. Disease-free survival is comparable between adult and older subjects in both incidental and nonincidental cases, although it may be slightly reduced in nonincidentally diagnosed older patients.

Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.

OBJECTIVE: The purpose of the ULISSE study was to evaluate the prevalence of clinical and ultrasonographic (US) entheseal involvement in patients with psoriatic arthritis (PsA), psoriasis, and fibromyalgia syndrome (FMS). METHODS: In this cross-sectional multicenter study, patients with PsA and psoriasis (not taking systemic therapy) and FMS underwent a clinical evaluation of the entheses, and a B-mode and power Doppler examination of 6 pairs of entheses. RESULTS: The study analyzed 140 patients with PsA, 51 with psoriasis, and 51 with FMS. Clinical and US examinations were performed in 1960 and 1680 entheses in the PsA group, and 714 and 612 entheses both in the psoriasis group and in the FMS group. In both per-patient and per-enthesis evaluation, the frequency of entheseal tenderness was higher in patients with FMS (92% of the patients and 46% of the entheses, compared with 66%/23% in the PsA group and 59%/18% in the psoriasis group). With US examination, signs of entheseal involvement were more frequent in both the per-patient and per-enthesis evaluation in PsA and psoriasis (about 90% of patients in both the PsA and psoriasis groups and 75% of patients in the FMS group had at least 1 site affected, and 54%, 41%, and 27% of the pairs of entheses in, respectively, PsA, psoriasis, and FMS patients showed at least 1 enthesis involved). CONCLUSION: The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.

Aortic dilatation in patients with large vessel vasculitis: A longitudinal case control study using PET/CT.

OBJECTIVE: To evaluate aortic diameter and predictors of aortic dilatation using 18FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls. METHODS: All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls. RESULTS: 93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p = 0.029], descending thoracic [28.42 (4.82) vs 25.72 (3.55) mm, p = 0.007] and suprarenal abdominal aorta, mean [25.34 (7.01) vs 22.16 (3.26) mm, p = 0.005] and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001] and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter. CONCLUSIONS: Patients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.

Long-term remission in biopsy proven giant cell arteritis: A retrospective cohort study.

OBJECTIVE: To evaluate the frequency of long-term remission after glucocorticoids (GCs) suspension in an Italian cohort of patients with biopsy-proven GCA and to identify factors that may predict long-term remission. METHODS: We evaluated 131 patients with biopsy-proven transmural GCA diagnosed and followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 18 months of follow-up. Long-term remission was defined as complete clinical remission without elevation of inflammatory markers for at least one year after the GC withdrawal. RESULTS: 73 patients (56%) experienced long-term remission. Disease flares were less frequently observed in patients with long-term remission compared to those without (p = 0.002). The cumulative doses of prednisone at 1 year and for the entire followup duration were significantly lower (p < 0.0001 for both parameters) in patients with long-term remission; similarly, the duration of prednisone treatment was also significantly lower (p < 0.0001). The presence of PMR at diagnosis (HR 0.46) was significantly negatively associated with long-term remission (p = 0.008), while hemoglobin levels (HR 1.48) were significantly positively associated (p < 0.0001). Patients with long-term remission were able to reach 10 mg/day and 5 mg/day of prednisone sooner than the patients without (p = 0.02 and p < 0.0001, respectively). CONCLUSION: In our cohort of GCA patients around half of the patients were able to attain long-term remission. Recognition of findings which predict disease course may aid decisions regarding therapy.

Causes of referral to the first endocrine visit of patients with thyroid carcinoma in a mildly iodine-deficient area.

To evaluate the causes of the first referral to an endocrine visit of patients with thyroid cancer in a mildly iodine-deficient area and to correlate them with prognostic features. We studied 298 consecutive patients (64 M and 234 F) with thyroid cancer. Of these, 281 had differentiated thyroid cancer. The causes of referral were categorized as follows: (Group A) clinical evidence of a neck lump; (Group B) incidental imaging in subjects without known thyroid diseases; (Group C) incidental imaging during a workup of thyroid disorders. Also, in differentiated thyroid cancer cases, clinical, histomorphologic, and prognostic parameters were compared among the three different groups of referral causes. In both total thyroid cancer and differentiated thyroid cancer cohorts, Group A, B, and C accounted for about 25, 35, and 40 % of causes, respectively. Considering the differentiated thyroid cancer, in Group B, ultrasound accounted for 94 % of cases, with 73 % resulting from screening or serendipitous study. Within a median follow-up of 5.6 [IQR: 2.7-9.5] years, disease-free survival was significantly lower in patients of Group A (Log-Rank test p = 0.030 vs. the other groups of causes). However, at the Cox multivariate analysis only male sex (p = 0.002) and stage (p = 0.005), but not referral cause, resulted independent predictors of events. In patients without known thyroid disease, unjustified thyroid ultrasound represents the main cause of referral of thyroid cancer patients to the first endocrine visit. The fact that this is not related to the disease-free survival strengthens the concept of the uselessness of thyroid cancer screening.

Flares in Biopsy-Proven Giant Cell Arteritis in Northern Italy: Characteristics and Predictors in a Long-Term Follow-Up Study.

This study evaluated the frequency, timing, and characteristics of flares in a large cohort of Italian patients with biopsy-proven giant cell arteritis (GCA) and to identify factors at diagnosis able to predict the occurrence of flares. We evaluated 157 patients with biopsy-proven transmural GCA diagnosed and followed at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 4 years of follow-up. Fifty-seven patients (36.5%) experienced ≥1 flares. Fifty-one (46.4%) of the 110 total flares (88 relapses and 22 recurrences) were experienced during the first 2 years after diagnosis. The majority of relapses occurred with doses of prednisone ≤ 10 mg/day (82.9%), whereas only 3.4% of relapses occurred for doses ≥ 25 mg/day. Polymyalgia rheumatica (46.5%) and cranial symptoms (41.9%) were the most frequent manifestations at the time of the first relapse. Cumulative prednisone dose during the first year and total cumulative prednisone dose were significantly higher in flaring patients compared with those without flares (7.8 ±â€Š2.4 vs 6.7 ±â€Š2.4 g, P = 0.02; 15.5 ±â€Š8.9 vs 10.0 ±â€Š9.2 g, P = 0.0001, respectively). The total duration of prednisone treatment was longer in flaring patients (58 ±â€Š44 vs 30 ±â€Š30 months, P = 0.0001).Patients with disease flares had at diagnosis more frequently systemic manifestations (P = 0.02) and fever ≥ 38°C (P = 0.02), significantly lower hemoglobin levels (P = 0.05), more frequent presence at temporal artery biopsy (TAB) specimens of giant cells (P = 0.04) and intraluminal acute thrombosis (P = 0.007), and more moderate/severe arterial inflammation (P = 0.009) compared with those without flares. In the multivariate model fever ≥ 38 °C (hazard ratio 2.14; 95% confidence interval, 1.06-4.32, P = 0.03) and the severity of inflammatory infiltrate (moderate/severe versus mild) (hazard ratio 5.41; 95% confidence interval, 1.64-17.87, P = 0.006) were significantly associated with an increased risk of flares. In conclusion, a flaring course is common in GCA and it is associated with prolonged GC requirements. Fever at diagnosis and severity of inflammation at TAB appear to predict the development of disease flares.

Correlations between histopathological findings and clinical manifestations in biopsy-proven giant cell arteritis.

OBJECTIVE: To correlate histopathological features of positive temporal artery biopsy (TAB) and clinical manifestations of the disease in a large single-center population-based cohort of patients with biopsy-proven giant cell arteritis (GCA). METHODS: A pathologist with expertise in vasculitis and blinded to clinical data and final diagnosis reviewed all TABs performed for suspected GCA at our hospital between January 1986 and December 2013. Histopathologic features evaluated were: the severity of inflammation and intimal hyperplasia, both graded on a semiquantitative scale (mild = 1, moderate = 2, severe = 3), the presence of intraluminal acute thrombosis, calcifications, giant cells, fibrinoid necrosis and laminar necrosis. RESULTS: 274 patients had a final diagnosis of biopsy-proven GCA and were included in the study. Cranial ischemic events (CIEs) were observed in 161 (58.8%), visual manifestations in 79 (28.8%) and permanent (partial or complete) visual loss in 51 (18.6%) patients. Predictors for the development of CIEs were older age (OR = 1.057, 95% CI 1.019-1.097, p = 0.003), lower ESR values (OR = 0.990, 95% CI 0.981-0.999, p = 0.026) as well as the presence of giant cells (OR = 1.848, 95% CI 1.045-3.269, p = 0.035) and laminar necrosis at TAB (OR = 2.334, 95% CI 1.187-4.587, p = 0.014). Predictors for the development of permanent visual loss were lower CRP values (OR = 0.906, 95% CI 0.827-0.992, p = 0.033) and the presence of calcifications at TAB (OR = 3.672, 95% CI 1.479-9.121, p = 0.005). Fibrinoid necrosis was not observed in any of the TABs evaluated. CONCLUSION: Pathological features of TAB may predict some manifestations of GCA. These findings may have implications for patients' management.

Transcriptomic analysis of human polarized macrophages: more than one role of alternative activation?

BACKGROUND: Macrophages are a heterogeneous cell population which in response to the cytokine milieu polarize in either classically activated macrophages (M1) or alternatively activated macrophages (M2). This plasticity makes macrophages essential in regulating inflammation, immune response and tissue remodeling and a novel therapeutic target in inflammatory diseases such as atherosclerosis. The aim of the study was to describe the transcriptomic profiles of differently polarized human macrophages to generate new hypotheses on the biological function of the different macrophage subtypes. METHODS AND RESULTS: Polarization of circulating monocytes/macrophages of blood donors was induced in vitro by IFN-γ and LPS (M1), by IL-4 (M2a), and by IL-10 (M2c). Unstimulated cells (RM) served as time controls. Gene expression profile of M1, M2a, M2c and RM was assessed at 6, 12 and 24h after polarization with Whole Human Genome Agilent Microarray technique. When compared to RM, M1 significantly upregulated pathways involved in immunity and inflammation, whereas M2a did the opposite. Conversely, decreased and increased expression of mitochondrial metabolism, consistent with insulin resistant and insulin sensitive patterns, was seen in M1 and M2a, respectively. The time sequence in the expression of some pathways appeared to have some specific bearing on M1 function. Finally, canonical and non-canonical Wnt genes and gene groups, promoting inflammation and tissue remodeling, were upregulated in M2a compared to RM. CONCLUSION: Our data in in vitro polarized human macrophages: 1. confirm and extend known inflammatory and anti-inflammatory gene expression patterns; 2. demonstrate changes in mitochondrial metabolism associated to insulin resistance and insulin sensitivity in M1 and M2a, respectively; 3. highlight the potential relevance of gene expression timing in M1 function; 4. unveil enhanced expression of Wnt pathways in M2a suggesting a potential dual (pro-inflammatory and anti-inflammatory) role of M2a in inflammatory diseases.

CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients.

Considering the role of carcinoembryonic antigen (CEA) serum levels as potential useful predictive marker during chemotherapy treatment, we studied its applicability in advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). Our retrospective cohort consists of 79 patients (33 EGFR mutated and 46 EGFR wild type or unknown) affected by advanced NSCLC, for whom CEA serum values at the beginning of TKI therapy and after the first month of treatment were available, regardless of treatment line. Baseline CEA value, percentage of CEA reduction after 1 month, and percentage of patients with ≥20 % CEA decrease after 1 month (CEA response) were correlated with disease control rate (DCR), progression-free (PFS), and overall (OS) survival, according to EGFR mutational status. Median baseline CEA levels were significantly higher in EGFR mutated (40.9 ng/ml; interquartile range (IQR) 8.9-197.6) than in wild-type cases (6.2 ng/ml; IQR 2.8-12.8; p = 0.003). Both percentage reduction in CEA levels (-10.7 vs. +13.4 %) and percentage of cases with CEA response (42 vs. 20 %) were significantly higher in mutated vs. wild-type/unknown patients (p = 0.007 and p = 0.027, respectively). In wild-type/unknown patients, CEA response was significantly correlated with DCR (p = 0.001) and resulted as a significant predictor of PFS both in univariate (p = 0.002) and in multivariate analyses (hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.11-0.66; p = 0.004); only a trend was found for OS prediction (p = 0.082). In EGFR-mutated group, CEA reduction did not show any correlation either with PFS or OS. CEA response after 1 month of EGFR-TKI therapy could be a useful marker, worthy to further studies, as early predictor of treatment outcome in EGFR wild-type/unknown unselected NSCLC cases for which no molecular predictor is yet available.

Searching for viral antibodies and genome in intraocular fluids of patients with Fuchs uveitis and non-infectious uveitis.

BACKGROUND: To characterise the polyspecific intraocular antibody synthesis in aqueous humor of patients with Fuchs uveitis and other types of non-infectious uveitis. METHODS: Aqueous and serum samples collected from 24 patients with Fuchs uveitis, 21 patients with non-infectious uveitis, and 27 healthy subjects undergoing elective cataract surgery (control group) were analysed. In addition, vitreous samples, collected from seven uveitis patients (five Fuchs and two panuveitis) during retinal surgery, were examined. Specific immunoglobulin G antibodies against cytomegalovirus (CMV), rubella virus, herpes simplex virus (HSV), and varicella zoster virus (VZV) were investigated, and Goldmann-Witmer coefficients (GWCs) were calculated. Real-time PCR was performed to detect viral genome for HSV, VZV, and CMV, while nested PCR was conducted to detect rubella RNA. RESULTS: None of the control samples tested positive for any of the viral antibodies investigated. Intraocular antibody production was found in eight samples of patients affected by Fuchs uveitis (6/8 positive for rubella virus and 2/8 positive for herpes virus). Among patients with non-infectious uveitis, three tested positive for intraocular antibody production (one RV, one HSV and one for VZV). PCR was positive for RV in two patients with Fuchs uveitis, in three patients with non-infectious uveitis (one for RV and two for HSV), and in three control subjects (one for CMV and one for HSV). CONCLUSIONS: Our series confirmed the presence of specific viral antibodies, especially against rubella virus, in the subgroup of patients affected by Fuchs uveitis, suggesting that this virus may be responsible for this chronic inflammatory condition. Rubella virus is probably the main causative agent of Fuchs uveitis, but other viruses may also be involved in the pathogenesis of this disease.