Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

PURPOSE: The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). METHODS: We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007-2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). RESULTS: Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6-240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight (p < 0.03), dehydroepiandrosterone sulfate (DHEAS) (p < 0.05) and direct renin concentration (DRC) (p < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia (p < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. CONCLUSIONS: Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Long-term trajectories of bone metabolism parameters and bone mineral density (BMD) in obese patients treated with metabolic surgery: a real-world, retrospective study.

PURPOSE: Potential negative effects of metabolic surgery on skeletal integrity remain a concern, since long-term data of different surgical approaches are poor. This study aimed to describe changes in bone metabolism in subjects with obesity undergoing both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: A single center, retrospective, observational clinical study on real-world data was performed enrolling subjects undergoing metabolic surgery. RESULTS: 123 subjects were enrolled (males 31: females 92; ages 48.2 ± 7.9 years). All patients were evaluated until 16.9 ± 8.1 months after surgery, while a small group was evaluated up to 4.5 years. All patients were treated after surgery with calcium and vitamin D integration. Both calcium and phosphate serum levels significantly increased after metabolic surgery and remained stable during follow-up. These trends did not differ between RYGB and SG (p = 0.245). Ca/P ratio decreased after surgery compared to baseline (p < 0.001) and this decrease remained among follow-up visits. While 24-h urinary calcium remained stable across all visits, 24-h urinary phosphate showed lower levels after surgery (p = 0.014), also according to surgery technique. Parathyroid hormone decreased (p < 0.001) and both vitamin D (p < 0.001) and C-terminal telopeptide of type I collagen (p = 0.001) increased after surgery. CONCLUSION: We demonstrated that calcium and phosphorous metabolism shows slight modification even after several years since metabolic surgery, irrespective of calcium and vitamin D supplementation. This different set point is characterized by a phosphate serum levels increase, together with a persistent bone loss, suggesting that supplementation alone may not ensure the maintenance of bone health in these patients.

Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception.

Purpose: The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemiaMaterials and methods: A concise communication was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented.Results: Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method.Conclusion: At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.

MTHFR, TS and XRCC1 genetic variants may affect survival in patients with myelodysplastic syndromes treated with supportive care or azacitidine.

We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0.001; P=0.026; P=0.058; P=0.024). MTHFR 677T/T, TS 3'-UTR -6 bp/-6 bp and XRCC1 399G/G genotypes were associated with short survival in patients receiving azacitidine by multivariate analysis (P<0.001; P=0.004; P=0.002). We then performed an exploratory analysis to evaluate the effect of the simultaneous presence of multiple adverse variant genotypes. Interestingly, patients with ⩾1 adverse genetic variants had a short survival, independently from their International Prognostic Scoring System (IPSS) and therapy received. To our knowledge, this is the first study showing that polymorphisms in folate-metabolizing pathway, DNA synthesis and DNA repair genes could influence survival of MDS patients.

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

BACKGROUND: In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. MATERIALS AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. RESULTS: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.

Glioblastoma stem cells: a new target for metformin and arsenic trioxide.

The high malignancy of glioblastoma has been recently attributed to the presence, within the tumor, of glioblastoma stem cells (GSC) poorly responsive to chemo- and radiotherapy. Here, the potential employment of metformin and arsenic trioxide (ATO) in glioblastoma therapy is discussed focusing on their effects on GSC. Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells. Metformin and ATO induce autophagy and apoptosis in glioma cells by inhibiting and stimulating the PI3K/Akt and the mitogen-activated protein kinase pathways, respectively. Both drugs promote differentiation of GSC into non-tumorigenic cells. In this regard, metformin acts via activation of the AMPK-FOXO3 axis, whereas ATO blocks the interleukin 6-induced promotion of STAT3 phosphorylation. Blood-brain barrier, easily crossed by metformin but not by ATO, undergoes important glioblastoma-induced alterations that increase its permeability, thus allowing ATO to distribute more into the glioblastoma bulk than in the normal brain parenchyma. A prompt clinical assessment of metformin and ATO in glioblastoma patients would represent a valid attempt to improve their survival.

The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age.

STUDY QUESTION: What is the effect of FSHB-211G>T together with the FSHR 2039 A>G on serum FSH in women? SUMMARY ANSWER: Serum FSH levels are affected by the combination of genetic polymorphisms in FSHR and FSHB. WHAT IS KNOWN ALREADY: The relationship between SNPs of the FSHR gene and serum FSH has not been completely clarified. Genetic variants of the FSHB gene have been associated with variation in gene transcription and serum FSH levels in men. No data have been published on the effect of the FSHB-211G>T in women, alone or in combination with the FSHR 2039 A>G. STUDY DESIGN, SIZE, DURATION: This study was a prospective study including 193 healthy women of reproductive age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile and otherwise healthy eumenorrheic women (n = 193) with normal BMI and serum FSH levels were recruited for the study. In all women early follicular phase FSH and AMH were measured by commercial assays, and antral follicle count was measured by transvaginal ultrasound. Genomic DNA was purified from total peripheral blood and genotyping for the two SNPs was performed. MAIN RESULTS AND THE ROLE OF CHANCE: No significant gradients of increasing or decreasing Day 3 FSH across the FSHR 2039 (AA/AG/GG) and FSHB-211 (GG/GT/TT) genotypes, respectively, were observed. When women were stratified according to the FSHR 2039, and FSHB-211 genotypes a statistically significant reduction of d3 FSH was shown in the group of women with the FSHB-211 GT + TT/FSHR2039 AA genotype compared with the FSHB-211 GG/FSHR2039 GG genotype, hence confirming a possible additive effect of the different SNPs in FSHR and FSHB on regulating serum FSH. LIMITATIONS, REASONS FOR CAUTION: This finding requires an independent confirmation. However, it confirms the relationship between serum FSH and FSHB together with FSHR gene polymorphisms already reported in males. WIDER IMPLICATIONS OF THE FINDINGS: The knowledge of the FSHB/FSHR genotype combination is fundamental for the proper interpretation of serum FSH levels in women of reproductive age. STUDY FUNDING/COMPETING INTERESTS: Merck Serono supported the study in the form of a research grant for the laboratory session. None of the authors have any competing interest to declare.

Effects of physical exercise on the female reproductive system.

The excess in physical activity could be closely linked to considerable negative consequences on the whole body. These dysfunctions called as "female athlete triad"' by the American College of Sports Medicine (ACSM) include amenorrhea, osteoporosis and disorder eating. The female athlete triad poses serious health risks, both on the short and on the long term, to the overall well-being of affected individuals. Sustained low energy availability can impair health, causing many medical complications within skeletal, endocrine, cardiovascular, reproductive and central nervous system. On the contrary, several studies have shown, that physical activity improves cardiovascular risk factors, hormonal profile and reproductive function. These improvements include a decrease in abdominal fat, blood glucose, blood lipids and insulin resistance, as well as improvements in menstrual cyclicity, ovulation and fertility, decreases in testosterone levels and Free Androgen Index (FAI) and increases in sex hormone binding globulin (SHBG). Other studies reported that physical activity improved self-esteem, depression and anxiety. Thus, the aim of this review is to elucidate the effect of physical exercise on female reproductive system and viceversa the impact of hormonal status on physical activity and metabolism. In addition this review supports the idea that physical exercise is a helpful tool for the management of obesity, prevention of cardiovascular, metabolic diseases and female reproductive organs related diseases (e.g. breast cancer). When the excess in physical activity leads up to the female athlete triad, it is imperative to treat each component of the triad by employing both pharmacological and non pharmacological treatments.

Prevalence of Dio2(T92A) polymorphism and its association with thyroid autoimmunity.

The 3,5,3'-L-triiodothyronine (T3) partly derives by the deiodination of the prohormone 3,5,3',5'-L-tetraiodothyronine (T4) by the type 2 iodothyronine deiodinase (D2). The single-nucleotide polymorphism in the D2 gene at position 92 (Dio(2T92A)), generates an enzyme with a reduced T4 to T3 conversion velocity. Because thyroid hormones can modulate the immune response, we hypothesized a pathophysiological role for Dio(2T92A) polymorphism in autoimmunity. The objective of this study was to investigate the Dio(2T92A) polymorphism in relation to thyroid autoimmunity (TA). We compared the prevalence of Dio(2T92A) polymorphism and serum thyroid hormone levels in healthy subjects and subjects with TA. A total of 110 subjects with TA and 106 controls were genotypized for Dio(2T92A) polymorphism. Free T3 (FT3), free T4 (FT4) and TSH were measured and compared with the Dio(2T92A) polymorphism. Dio(292T/A), Dio(292A/A), and Dio(292T/T) healthy subjects were 40.9%, 46.4%, and 12.7%, respectively. These prevalences were similar to those of some European countries whilst significantly different from that of Brazil. In the two groups of healthy subjects and TA subjects, Dio(2T92A) polymorphism had a similar distribution with non-significant differences. Similarly, no significant differences were observed in the serum concentration of FT3, FT4, and TSH between subjects with different Dio(2T92A) polymorphism. The FT4/FT3, and TSH/FT3 ratios were higher in Dio(292T/T) than in Dio(292T/A) and Dio(292A/A) subjects in both TA and healthy groups, but these differences were not significant. In conclusion, the distribution of Dio(2T92A) polymorphism may reflect geographical and ethnic differences, and it is not associated with TA.

Management of localized and locally advanced renal tumors. A contemporary review of current treatment options.

About 70% of patients with renal cell carcinoma present with localized or locally advanced disease at primary diagnosis. Whereas these patients are potentially curable by surgical treatment alone, a further 20% to 30% of patients are diagnosed with primary metastatic disease. Although over the past years medical treatment for metastatic patients has nearly completely changed from immunotherapy to effective treatment with targeted agents, metastatic disease still represents a disease status which is not curable. Also in patients with metastatic disease, surgical treatment of the primary tumor plays an important role, since local tumor related complications can be avoided or minimized by surgery. Furthermore, also improvement of overall survival has been proven for surgery in metastatic patients when combined with cytokine treatment. Hence, surgical combined with systemic treatment as a multi-modal, adjuvant, and neo-adjuvant treatment is also required in patients with advanced or metastatic disease. A growing number of elderly and comorbid patients are currently diagnosed with small renal masses, which has led to increased attention paid to alternative ablative treatment modalities as well as active surveillance strategies, which are applied in order to avoid unnecessary overtreatment in these patients. Since surgical treatment also might enhance the risk of chronic kidney disease with consecutive cardiac disorders as well as reduced overall survival, ablative techniques and active surveillance are increasingly applied. In this review article we focus on current surgical and none-surgical treatment options for the management of patients with localized, locally advanced, and metastatic renal cell carcinoma.

Transdermal scopolamine and perioperative anisocoria in craniofacial surgery: a report of 3 patients.

Postoperative nausea and vomiting (PONV) is a common complaint after plastic and reconstructive surgery. Transdermal scopolamine is a commonly used agent for prevention of PONV. Anisocoria from transdermal scopolamine use is an adverse effect that has not been reported in the plastic surgery literature. We present a series of 3 craniofacial patients in which ipsilateral mydriasis occurred and spontaneously resolved after removal of the scopolamine patch. Given the various causes and potentially grave implications of unilateral mydriasis, we discourage the use of transdermal scopolamine in craniofacial surgery, and especially in orbital surgery. However, if transdermal scopolamine is decided to be used for PONV prophylaxis, we recommend educating the patient, the operating room staff, and the surgical team regarding this potential adverse effect and to avoid finger-to-eye contamination after patch manipulation.

Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle-stimulating hormone starting dose in in vitro fertilisation cycles.

OBJECTIVE: To elaborate a nomogram based on markers of ovarian reserve for the calculation of the appropriate starting dose of follicle-stimulating hormone (FSH). DESIGN: Cohort study of infertile women. SETTING: In vitro fertilisation (IVF) unit, University Hospital of Modena, Italy. POPULATION: Women aged 18-40 years (n = 346) and undergoing their first IVF cycle. METHODS: Serum FSH and anti-Müllerian hormone (AMH) measurement. MAIN OUTCOME MEASURES: Development of a model for the prediction of ovarian response to FSH. RESULTS: A model based on age, AMH and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting FSH dose <225 IU in 55.1 and 25.9% of women younger and older than 35 years, respectively. CONCLUSIONS: In the present study we clearly demonstrated that the daily FSH dose may be calculated on the basis of a woman's age and two markers of ovarian reserve, namely AMH and FSH, with the first two vari;s (age and AMH) being the most significant predictors. The nomogram we developed seems easily applicable for clinicians during their daily clinical practice.

Menopausal symptoms and risk factors for cardiovascular disease in postmenopause.

OBJECTIVES: Conflicting evidence indicates an increased risk for cardiovascular disease in postmenopausal women suffering from hot flushes. In this study, we tested whether, beyond hot flushes, menopausal symptoms are associated with biochemical and biophysical risk factors for cardiovascular disease. METHODS: Retrospective cross-sectional analysis on 951 women in surgical or physiological postmenopause, recruited at the menopause outpatient service of our university hospital between April 2002 and December 2009. The Greene Climacteric Scale and its subscales for anxiety, depression, somatic symptoms, vasomotor symptoms and sexuality were used to evaluate menopausal complaints. Blood pressure, fasting glucose and lipids levels were evaluated as risk factors for cardiovascular disease. Anthropometric parameters and those derived by remote and reproductive medical history were used as possible confounders. All data were anonymously retrieved from an electronic database. RESULTS: By multiple regression analysis, high density lipoprotein (HDL) cholesterol was inversely related to body mass index, the Greene Climacteric Scale score and years since menopause (R = 0.390; p = 0.0001). The total cholesterol/HDL cholesterol ratio was positively related to waist circumference and the Greene Climacteric Scale score (R = 0.356; p = 0.0001). Triglycerides (R = 0.353; p = 0.0001) and triglyceride/HDL cholesterol (R = 0.425; p = 0.0001) were positively related to waist circumference, the Greene Climacteric Scale score and the Greene vasomotor subscore. Glucose was positively related to waist circumference, years since menopause and the Greene Climacteric Scale score (R = 0.390; p = 0.0001). Blood pressure was not related to menopausal symptoms. The 10-year risk for cardiovascular disease calculated by the Framingham formula was related independently and directly to body mass index and the Greene Climacteric Scale score (R = 0.183; p = 0.0001). CONCLUSIONS: Menopausal symptoms evaluated by a validated climacteric scale are associated with a worsening of biochemical risk factors for atherosclerosis and cardiovascular disease.

The ovarian follicular pool and reproductive outcome in women.

Both quantitative and qualitative aspects of the ovarian reserve are inversely related to age, hence the relationship existing between low quantity and low quality may be only indirect and depending on their strong relationship with the third variable, namely women's age. However the possibility exists that they may also be directly related. The objective of this study was to investigate the relationship between ovarian reserve and female reproductive outcome. Eight published studies reporting histological data on the human ovaries have been carefully reviewed. Only studies where the reproductive history of women was reported have been included for the analysis. The non-growing follicle count was plotted versus age and the best fit line through the data was calculated. All patients were assigned as to be above or below the calculated median hence differentiating women with high or low ovarian reserve for their age. A similar number of pregnancies ended in miscarriage in women with low and high ovarian reserve. The number of deliveries per woman in both the groups was not statistically different. The results of the study do not support the hypothesis that quality and quantity of the follicular pool are directly related.

Thermochemotherapy for non-muscle-invasive bladder cancer: is there a chance to avoid early cystectomy?.

OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. RESULTS: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

Paclitaxel-hyaluronic acid for intravesical therapy of bacillus Calmette-Guérin refractory carcinoma in situ of the bladder: results of a phase I study.

PURPOSE: Carcinoma in situ represents high grade anaplasia of the bladder mucosa. Intravesical immunotherapy with bacillus Calmette-Guérin is the gold standard treatment for patients with carcinoma in situ. Patients with carcinoma in situ refractory to bacillus Calmette-Guérin are candidates for major surgery such as radical cystectomy. We identified the maximum tolerated dose and the recommended dose, and evaluated the safety profile of paclitaxel-hyaluronic acid bioconjugate given by intravesical instillation to patients with carcinoma in situ refractory to bacillus Calmette-Guérin. MATERIALS AND METHODS: A total of 16 patients with carcinoma in situ refractory to bacillus Calmette-Guérin were enrolled in a phase I, open label, single institution study. A minimum of 3 eligible patients were included per dose level. Paclitaxel-hyaluronic acid solution (ONCOFID-P-B™) was administered for 6 consecutive weeks. The primary objective was to identify the maximum tolerated dose and the recommended dose. As secondary objectives the safety profile of ONCOFID-P-B, the pharmacokinetic profile after each instillation and the tumor response were also evaluated. RESULTS: No dose limiting toxicity occurred at any drug level evaluated. The plasma levels of the study drug were always below the lower limit of quantification at all tested doses after each instillation. A total of 11 adverse events were reported by 7 patients and 9 (60%) showed complete treatment response. CONCLUSIONS: Intravesical instillation of ONCOFID-P-B for carcinoma in situ refractory to bacillus Calmette-Guérin showed minimal toxicity and no systemic absorption in the first human intravesical clinical trial to our knowledge. Finally, satisfactory response rates were observed.

Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction.

Prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. This study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a model to enhance the prediction of a live birth in women undergoing their first IVF cycle, by analysing a database containing clinical and laboratory information on IVF cycles carried out between 2005 and 2008 at the Mother-Infant Department of University Hospital, Modena. Logistic regression was used to examine the association of live birth with baseline patient characteristics. Only AMH and age were demonstrated in regression analysis to predict live birth, so a model solely based on these two criteria was generated. The model permitted the identification of live birth with a sensitivity of 79.2% and a specificity of only 44.2%. In the prediction of a live birth following IVF, a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve.

Ultrasonography in early assessment of elderly patients with polymyalgic symptoms: a role in predicting diagnostic outcome?

OBJECTIVE: To study the usefulness of ultrasonography (US) in predicting the diagnostic outcome in patients with polymyalgic symptoms. METHODS: Sixty-one elderly patients with polymyalgic syndrome were recruited in a secondary care setting and followed up in a prospective way. Clinical, laboratory, and US data obtained at onset were re-evaluated after 1 year when diagnostic outcome was defined. RESULTS: A diagnostic shift was observed in 32 polymyalgic patients (52%). Calcium pyrophosphate deposition disease (CPDD) was diagnosed in nine patients, elderly-onset rheumatoid arthritis (EORA) in 18, and elderly-onset spondyloarthritis (EOSpA) in five. In polymyalgia rheumatica (PMR) patients US demonstrated synovitis in 90% of cases, in both proximal (90%) and peripheral joints (41%). The best predictive US model for the definitive diagnosis of PMR comprised: the presence of subacromial-subdeltoid bursitis [odds ratio (OR) 5.603, p = 0.003], low frequency of wrist (OR 0.074, p < 0.001), metacarpophalangeal (OR 0.052, p < 0.001), and metatarsophalangeal effusion/synovitis (OR 0.107, p < 0.027), low frequency of knee menisci chondrocalcinosis (OR 0.091, p = 0.013), tendinous calcaneal calcifications (OR 0.078, p = 0.006), and Achilles enthesitis (OR 0.107, p = 0.027), and low power Doppler US (PDUS) scores at wrist (OR 0.052, p < 0.001). CONCLUSIONS: US and PDUS can be useful in distinguishing, at onset of disease, pure PMR from other diseases mimicking this condition.

Surfactant protein D and KL-6 serum levels in systemic sclerosis: correlation with lung and systemic involvement.

OBJECTIVE: The aim of this study was to investigate the relationship between SP-D and KL-6 serum concentrations and the extent of interstitial lung involvement, as measured by a quantitative HRCT score and the functional impairment, in patients with systemic sclerosis (SSc). Moreover we analysed the association between these lung-specific biomarkers and skin involvement, anti-Scl-70 antibody titres and an index of disease activity. METHODS: Serum SP-D, KL-6 and anti-Scl-70 concentrations were determined by ELISA in 25 SSc patients. Disease activity and lung function parameters were assessed, and the extent of ILD was measured by a HRCT score. RESULTS: SP-D and KL-6 concentrations were higher in patients with SSc and lung fibrosis than in healthy controls. KL-6 correlated positively with the HRCT-fibrosis score (r=0.68, p<0.001), SP-D showed a weaker correlation (r=0.44, p=0.025). Increased KL-6 concentrations were associated with decreased DLCO and decreased FVC in SSc patients, SP-D showed no association. Furthermore KL-6, but not SP-D, showed a strong association with skin involvement as expressed by the modified Rodnan skin score (r=0.71, p<0.0001) and a disease activity index (r=0.73, p<0.0001). CONCLUSION: KL-6 is more strongly associated than SP-D with the HRCT-fibrosis score, and, different from SP-D, it correlates with skin involvement and disease activity. We suggest that KL-6 may be a useful biomarker in the assessment of scleroderma patients.