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Lysosomal cathepsins D (CD), B (CB), and L (CL) serum levels were determined by immunoassays in patients with chronic (CHP) or acute (AP) pancreatitis and in patients with ductal pancreatic carcinoma (DPC) and correlated with some biological and clinical parameters of this tumor. CB serum concentrations significantly higher than those measured in healthy subjects (NS) were observed in CHP, AP, and DPC patients (p < 0.01). However, no significant difference was noted among these groups. Increased CL serum levels were evident only in cancer patients compared to NS, AP, or CHP groups (p < 0.05), while no difference was observed among these groups. Elevated CD serum values were observed in CHP and AP patients compared to healthy subjects or cancer patients (p < 0.01). In cancer patients no correlation between CD, CB, and CL and clinical stage or tumor size was found. However, significant correlations were observed only between serum CD and CA50 (p < 0.02) and between CD and CL (p < 0.05). No further relationship among the biochemical parameters examined was observed. The present data suggest that the different serum patterns of CD, CB, and CL in patients with pancreatitis and pancreatic cancer may be of clinical interest as additional biochemical parameters for the differential diagnosis of these diseases. However, further prospective clinical studies are needed to assess better their potential value as prognostic parameters to identify patients with pancreatitis at increased risk to develop pancreatic cancer.

The possibility of assaying antiendomysial antibodies (EmA) on the human umbilical cord instead of monkey esophagus has recently been suggested. We therefore evaluated in patients with celiac disease (CD) the sensitivity and specificity of EmA and of antigliadin antibodies (AGA) for both umbilical cord and monkey esophagus.We studied 36 patients with CD and atrophy of the intestinal mucosa (median age, 1.4 years), 14 patients with CD on gluten-free diet for 8-12 months (median age, 3.0 years), 36 controls without gastrointestinal disease (median age, 4.0 years), and 72 patients with cow's milk protein enteropathy (CMPE) (median age, 1.2 years). AGA and EmA on monkey esophagus were assayed with commercially available kits; the slides with umbilical cord were prepared in our laboratory.There was a perfect concordance between EmA results evaluated on umbilical cord and those on monkey esophagus; there was a doubtful result in only one case on human umbilical cord, which was positive with low titer on monkey esophagus. EmA specificity was 100%; the specificity of AGA IgG varied between 72% and 94% and of AGA IgA between 90% and 100% depending on whether controls without gastrointestinal disorders or patients with CMPE were considered. EmA sensitivity was 97%, AGA IgG was 89%, and AGA IgA 72% sensitive. The only false negative for EmA was positive for AGA IgG and AGA IgA.Using human umbilical cord as a substrate for EmA may provide the same sensitivity and specificity as offered by the test using monkey esophagus substrate, thus reducing costs and avoiding the use of endangered species.

We report the case of a 54-year-old male patient hospitalized for diarrhea and weight loss (8 kg over the previous three months). At admission, we observed pale oral and conjunctival mucosa and peripheral edema of the lower limbs. Stool frequency was 8-10 per day. Laboratory data were as follows: hemoglobin, 11 g/dL; total proteins, 4.3 g/dL; albumin, 2 g/dL; pseudocholinesterase, 1248 U/L; triglycerides, 54 mg/dL; serum cholesterol, 102 mg/dL; calcium, 7.9 mg/dL. Fecal fat was 8.2 g/24 hr. Fecal chymotrypsin (FCT) was 2.3 U/g. A duodenal probe was performed after administration of intravenous secretin and cerulein stimulation, and a contemporaneous mucosal biopsy was taken at the ligament of Treitz. Microscopic examination showed numerous Giardia lamblia in the fluid collected. Pancreatic enzyme activity in the duodenal fluid showed a severe reduction in lipase: 120 U/ml/min (normal value = 600 U/ml/min). Small bowel bacterial overgrowth was excluded by microbiologic examination of intestinal fluid. The patient was treated with metronidazole, leading to a complete remission of symptoms. Immediately after stopping treatment, the FCT was 15.2 U/g. Four months after hospitalization, the patient's weight had increased by 11 kg and he was asymptomatic; total proteins were 6.7 g/dL; albumin, 3.8 g/dL; triglycerides, 104 mg/dL; cholesterol, 152 mg/dL; pseudocholinesterase, 3,567 mg/dL; calcium, 10 mg/dL; steatorrhea was 3.6 g/24 hr and fecal chymotrypsin was 88 U/g. This case describes a severe, reversible impairment in pancreatic function leading to clinical malabsorption in the presence of Giardia infection.

Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, are nephroprotective in case of diabetes, but whether a similar beneficial effect may be detectable also in case of chronic non-diabetic kidney diseases remains still unknown. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, on the progression of cyclosporine nephropathy, in the absence of diabetes. Methods Sprague Dawley rats (n = 27) have been fed with low-salt diet starting 10 days before the beginning and finished at the end of the experimental period. Cyclosporine-A (CsA, 15 mg/kg/day, intraperitoneal injection, n = 8) and CsA plus empagliflozin (Empa, 10 mg/kg/day, per os, n = 7) were administered for 4 weeks. The control groups were treated with placebo (Control, n = 7) or empagliflozin (Control + Empa, n = 5). Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental period. At the end of the experimental protocol, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages), type I and type IV collagen expression, and tyrosine hydroxylase expression, used as marker of sympathetic nerve activity. Results CsA-treated rats showed a significant increase (p p p p p p p p p p p Conclusion Empagliflozin administration caused a reduction in blood pressure in CsA-treated rats and showed a protective effect on CsA nephropathy by decreasing renal fibrosis, type I and type IV collagen expression, macrophage infiltration and tyrosine hydroxylase expression. These data suggest that empagliflozin promotes nephroprotection also in non-diabetic kidney disease.

Background: Clinical trials have shown that empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, promotes nephroprotective effects in diabetic patients. The mechanisms underlying nephroprotection are not completely known and it is not known whether the renal beneficial action is present even in non-diabetic kidney disease. The aim of this study was to evaluate the effect of Empa administration on the development of renal fibrosis in an experimental model of angiotensin II (Ang II)-dependent hypertension. Methods: Sprague Dawley rats (n = 31) were divided into 4 experimental groups. Ang II (200 ng/kg/min, osmotic minipumps, s.c., n = 9) or Ang II + Empa (10 mg/kg/day, per os, n = 10) were administered for 2 weeks. Control rats were treated with placebo (physiological saline, n = 6), and another group was treated with placebo plus Empa (n = 6) for the same period. Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental protocol. After 2 weeks, the rats were euthanized and the kidneys were excised for histomorphometric evaluation of glomerular and tubulo-interstitial fibrosis and for the immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages) and types I and IV collagen expression. Results: The administration of Ang II resulted in an increase in blood pressure (p < 0.01), glomerular (p < 0.05) and tubulo-interstitial (p < 0.01) fibrosis, renal inflammatory infiltrates (p < 0.01) and type I (p < 0.01) and type IV collagen expression (p < 0.05) compared to the control group. Treatment with Empa did not significantly modify the increase in blood pressure due to Ang II, but prevented the development of renal glomerular and tubulo-interstitial fibrosis, and the increase in inflammatory infiltrates and types I and IV collagen expression in Ang II-treated rats (p < 0.01). Conclusions: These data demonstrate that the treatment with Empa prevents the development of renal fibrosis in Ang II-dependent hypertension. In Ang II-dependent hypertension, the anti-fibrotic effect due to SGLT2 inhibition is caused by the reduction of inflammatory infiltrates and it is independent on the modulation of blood pressure increase.

Objective To study pathogenic features of the somatic testicular microenvironment associated with idiopathic germ cell aplasia. Design Cross-sectional study. Setting Tertiary referral center for reproductive medicine. Patient(s) Testicular specimens from men with idiopathic nonobstructive azoospermia (iNOA) prospectively submitted to microdissection testicular sperm extraction. Of 20 specimens used for histology, 10 were also available for proteomic analysis. Primary Sertoli cells with normal karyotype and phenotype were also used. Intervention(s) Patients with iNOA were dichotomized according to a positive versus negative sperm retrieval at microdissection testicular sperm extraction, and on the isolated extracellular matrix (ECM) the proteomic analysis was performed. Main Outcome Measure(s) Proteomic analysis of the ECM from testicular specimens with positive versus negative sperm retrieval. Gene ontology enrichment was used to identify upstream regulators based on the 11 deregulated ECM proteins, which were validated by immunohistochemistry and quantitative polymerase chain reaction. Continuous variables were expressed as medians and interquartile range. Result(s) Germ cell aplasia was characterized by an increased signaling of the retinoic acid in Sertoli cells and associated with decreased expression of the basal membrane markers nidogen-2 and heparan sulfate proteoglycan-2. Decreased levels of the interstitial matrisome-associated factor IX and its regulator VKORC1 were, instead, coupled with decreased signaling of vitamin K in Leydig cells. An altered expression of a further eight ECM proteins was also found, including laminin-4 and laminin-5. Peripheral levels of the two vitamins were within the reference range in the two cohorts of iNOA men. Conclusion(s) We identified the pathogenetic signature of the somatic human testicular microenvironment, providing two vitamin-related mechanistic insights related to the molecular determinants of the idiopathic germ cell aplasia.

Background: Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as Systemic Sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score (mRSS). Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to L-T4 malabsorption in patients with HT and SSc. Case report: Here we report a case of a 56-year-old female affected by both SSc and Hashimoto's thyroiditis (HT) who developed severe hypothyroidism due to the loss of therapeutic efficacy of L-thyroxine (L-T4). Therapeutic failure resulted from the altered L-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid L-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. Conclusion: A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

Recently, the cohort of men from the European Male Ageing Study has been stratified into different categories distinguishing primary, secondary and compensated hypogonadism. A similar classification has not yet been applied to the infertile population. We performed a cross-sectional study enrolling 786 consecutive Caucasian-European infertile men segregated into eugonadal [normal serum total testosterone (≥3.03 ng/mL) and normal luteinizing hormone (≤9.4 mU/mL)], secondary (low total testosterone, low/normal luteinizing hormone), primary (low total testosterone, elevated luteinizing hormone) and compensated hypogonadism (normal total testosterone; elevated luteinizing hormone). In this cross-sectional study, logistic regression models tested the association between semen parameters, clinical characteristics and the defined gonadal status. Eugonadism, secondary, primary and compensated hypogonadism were found in 80, 15, 2, and 3% of men respectively. Secondary hypogonadal men were at highest risk for obesity [OR (95% CI): 3.48 (1.98-6.01)]. Primary hypogonadal men were those at highest risk for azoospermia [24.54 (6.39-161.39)] and testicular volume

The aim was to retrospectively analyse the clinical–histopathological characteristics of patients with newly diagnosis of differentiated thyroid cancer (DTC) referred to two Italian centres, one in Northern and the other in Southern Italy, between 2000 and 2013. 1081 patients were included and subdivided into two groups: group A (474 patients from Novara) and group B (607 patients from Naples). The group A came from the industrial area of Novara, while the Group B came from the areas around Vesuvius and Campi Flegrei. The two groups were comparable for iodine levels, body mass index, diagnostic timing and clinical procedures. For all patients, demographic and clinical data were collected. No difference was found in gender, whereas the age at diagnosis was later in the group A (group A 53.1 ± 15.16 years, group B 41.9 ± 14.25 years, p < 0.001). In both groups, the most frequent histotype was papillary thyroid cancer (PTC) with prevalence of follicular variant in group A (p < 0.0001) and classical variant in group B (p < 0.0001). Aggressive histological features were mainly seen in group A (bilaterality p < 0.0001, multifocality p < 0.0001 and thyroid capsular invasion p < 0.0001). Microcarcinomas were more frequent in group A (p < 0.0001) but mostly characterized by bilaterality (p < 0.001) and multifocality (p < 0.04). In both groups, tumour-associated thyroiditis showed a significant increase over the years (group A p < 0.05, group B p < 0.04). Environmental factors could justify the differences found in our study. These preliminary data should stimulate the need for an Italian Cancer Registry of DTC in order to allow an epidemiological characterization, allowing the identification of specific etiological factors and an improvement in the management of the disease

To retrospectively validate the American Society for Reproductive Medicine (ASRM) guidelines/recommendations concerning endocrine evaluation in a cohort of white European men presenting for couple's infertility.Retrospective study.Academic reproductive medicine outpatient clinic.Cohort of 1,056 consecutive infertile men (noninterracial infertile couples).Testicular volume was assessed with a Prader orchidometer. Serum hormones were measured (8-10 a.m.) in all cases. Hypogonadism was defined as total T3 ng/mL, according to the Endocrine Society definition. Semen analysis values were assessed based on the 2010 World Health Organisation reference criteria.ASRM indications for endocrine assessment in infertile men (sperm concentration10 million/mL, impaired sexual function, and other clinical findings suggesting a specific endocrinopathy) were used to predict hypogonadism in our cohort. Moreover, a clinically user-friendly three-item nomogram was developed to predict hypogonadism and was compared to the ASRM guidelines assessment.Biochemical hypogonadism was diagnosed in 156 (14.8%) men. Overall, 669 (63.4%) patients would have necessitated total T assessment according to the ASRM criteria; of these, only 119 (17.8%) were actually hypogonadal according to the Endocrine Society classification criteria. Conversely, 37 (23.7%) out of 156 patients with biochemical hypogonadism would have been overlooked. The overall predictive accuracy, sensitivity, and specificity of the ASRM guidelines was 58%, 76%, and 39%, respectively. Our nomogram was not reliable enough to predict hypogonadism, despite demonstrating a significantly higher predictive accuracy (68%) than the ASRM guidelines.The current findings show that the ASRM guidelines/recommendations for male infertility workup may not be suitable for application in white European infertile men.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland. An algorithm for the diagnosis and treatment of SETTLE has yet to be established. The aim of this study was to identify all case reports of SETTLE and to compare the clinical-pathological features and therapy of the cases identified. We performed a PubMed search for case reports of SETTLE in English published up to November 2014 in which "SETTLE" and "Spindle epithelial tumor with thymus-like differentiation" were keywords. We identified 35 articles for a total of 42 cases. We found that SETTLE usually occurs in children and adolescents as an asymptomatic neck mass. Thyroid function tests and tumor markers are invariably within normal range in all patients, and fine needle aspiration biopsy is rarely diagnostic for SETTLE. All 42 patients had undergone thyroidectomy. After surgical resection, chemotherapy (adjuvant or first/second-line treatment) and/or radiotherapy were administered to control tumor growth in cases with metastatic involvement. Although SETTLE presents a low-grade malignancy, it can metastasize to lymph nodes, the mediastinum, lung, vertebrae, and kidney even many years after the initial diagnosis. SETTLE may have a good prognosis if appropriately treated at initial presentation and if patients undergo long-term monitoring with regular clinical and morphological evaluations.

Known genetic alterations play a major role in perturbing male reproductive health. We sought to retrospectively validate the European Association of Urology (EAU) guidelines for karyotype analysis (KA) in a homogenous cohort of 1168 White European men presenting for primary couple's infertility (noninterracial infertile couples only) and to develop a novel nomogram capable of predicting karyotype alterations. Overall, 742 (63.5%) patients would have deserved KA according to the EAU guidelines. Of those, 48 (6.9% of the assessable patients according to EAU guidelines) displayed any kind of alteration at KA. Conversely, hypothetically relying on the EAU criteria, 12 (20%) out of 60 patients with karyotype abnormalities would not have been candidates for the same genetic assessment. Overall, 694 (62.6%) patients would have been candidates for genetic workup despite having a normal karyotype. As a whole, the EAU guideline sensitivity, specificity, and discrimination were 80%, 37%, and 59%, respectively. We developed a novel nomogram, with a 2% probability cut-off, which allows for a more careful detection of KA alterations. Patient summary The application of the European Association of Urology guidelines for karyotype analysis does not ensure an adequate diagnostic process. In this regard, we propose a novel diagnostic tool to improve detection of alterations at karyotype analysis.

We report the history of a pitfall in thyroid histopathology of a 47-yr-old man with a euthyroid nodular goiter involving the right lobe. The ultrasound-guided fineneedle aspiration of the dominant (3 cm) nodule, showing benign-appearing follicular cells, colloid, and scattered Hurthle cells, was consistent with a benign hyperplastic nodule (1). Because the left lobe had not shown evidence of nodular disease, the patient was submitted to a right lobectomy. The pathologist described a heavy lymphoplasmacyticbackgroundwithoccasionalgerminalcenter formation, as observed in Hashimoto thyroiditis, and a microscopic ( 1cm) follicularproliferationofepithelial thyroidcellswhose nucleidisplayedmembrane irregularityandchromatinclearing with occasional grooves. Thus, a histological report of a follicular variant of papillary microcarcinoma was issued. The patient underwent a completion thyroidectomy at the Federico II UniversityofNaples.At thatoccasion, thecompletesetofslides from both surgeries was reviewed by expert pathologists in the field of thyroid disease.

Our study was prompted by the observation that a large number of patients with DTC attending our hospital were from the area around the volcano Mt. Vesuvius (Campania, Italy). In an attempt to shed light on a possible association between volcanoes and DTC, we retrospectively examined 500 new cases admitted to the University of Federico II of Naples in Campania from 2000 to 2009. Age, sex, tumor size, lymph-node invasion, distant metastases, and cancer histotype were analyzed. We recorded the place of birth and of residence of each patient.In conclusion, we found a higher risk of papillary thyroid cancer and an earlier onset of this disease in the Vesuvius area than in other areas of Campania, although the risk was not as high as around Mt. Etna