Roberto Citarrella

Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis

The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism.

Predictors of microvascular complications in type 1 diabetic patients at onset: The role of metabolic memory

BACKGROUND Several epidemiological studies showed a close association between metabolic control and microvascular complications in type 1 Diabetes Mellitus (T1DM). The aim of our longitudinal observational study was to evaluate the predictive role of the main clinical and biochemical parameters in determining microvascular complications. METHODS 376 T1DM patients, hospitalized in our division from 1991 to 2005 (mean follow-up=10.93±4.26 years) were studied. Stepwise Cox regression analysis was used to identify the influence of residual ß-cell function, ß-cell autoimmunity, HbA1c levels and other clinical and laboratory parameters in the development of microalbuminuria and retinopathy. RESULTS The probability of developing microalbuminuria was higher in males than in females (HR 1.82; 95% CI 1.01-3.28; p=0.044), in patients with higher mean HbA1c values (HR 2.80; 95% CI 1.63-4.83; p<0.001), longer duration of disease (HR 1.98; 95% CI 1.10-3.57; p=0.022) and younger age of diabetes onset (HR 0.53; 95% CI 0.03-0.92; p=0.026). An increased probability of developing retinopathy was found in patients with higher mean HbA1c levels during follow-up (HR 2.35; 95% CI 1.34-4.12, p=0.003), as well as at onset (HR 1.85; 95% CI 1.06-3.24; p=0.030). CONCLUSIONS Our study suggests that among the clinical, metabolic, immunological and biochemical factors evaluated at onset, only HbA1c is predictive for the microangiopathy development in T1DM.

Neck Lymph Nodes in Chronic Autoimmune Thyroiditis: The Sonographic Pattern

BACKGROUND Neck lymph nodes may be involved in the pathogenesis of chronic autoimmune thyroiditis (CAT). This study was undertaken to identify which of the sonographic features of cervical lymph nodes are readily applicable to patients affected by CAT compared to healthy control subjects. METHODS We recruited 106 patients (92 females and 14 males) with CAT and 70 control subjects (53 females and 17 males) without clinical, biochemical, and ultrasonographic evidence of thyroid and neck diseases. We performed laboratory tests (thyrotropin, antithyroperoxidase antibodies, antithyroglobulin antibodies, and ultrasonography) to evaluate in each group: (i) thyroid function, autoimmunity, and morphology; (ii) number, topographic distribution (levels I-VI), and morphology of neck nodes (long-axis diameter; short-axis diameter; short-axis/long-axis ratio; absence or presence of hilus). RESULTS Total number of neck nodes with long-axis diameter >10 mm was significantly higher in the CAT group than in the control group (mean±standard deviation [SD]: 3.7±2.4 vs. 0.8±1.3; p<0.001) with significantly increased differences in levels II (1.4±0.8 vs. 0.3±0.5; p<0.001), III (2±1.2 vs. 0.3±0.7; p<0.001), and IV (0.7±0.7 vs. 0.07±0.2; p<0.001). More nodes with a hilus were found in the CAT group than in the control group (mean number of nodes±SD: 2.8±1.9 vs. 0.7±1.1; p<0.001). Short-axis diameter of level III (4.4±1 vs. 3.7±1.2 mm; p=0.002) and level IV nodes (3.9±1 vs. 3.1±0.5 mm p=0.030) was increased in CAT patients when compared with healthy controls. CONCLUSIONS The present study is the first one aiming at a systematic description of the sonographic pattern of cervical lymph nodes in CAT. An increased number of benign hyperplastic neck nodes, especially in levels II-IV, appears to be a characteristic sonographic finding associated with CAT.

In vitro generation of pancreatic endocrine cells from human adult fibroblast-like limbal stem cells.

Stem cells might provide unlimited supply of transplantable cells for β-cell replacement therapy in diabetes. The human limbus is a highly specialized region hosting a well-recognized population of epithelial stem cells, which sustain the continuous renewal of the cornea, and the recently identified stromal fibroblast-like stem cells (f-LSCs), with apparent broader plasticity. However, the lack of specific molecular markers for the identification of the multipotent limbal subpopulation has so far limited the investigation of their differentiation potential. In this study we show that the human limbus contains uncommitted cells that could be potentially harnessed for the treatment of diabetes. Fourteen limbal biopsies were obtained from patients undergoing surgery for ocular diseases not involving the conjunctiva or corneal surface. We identified a subpopulation of f-LSCs characterized by robust proliferative capacity, expressing several pluripotent stem cell markers and exhibiting self-renewal ability. We then demonstrated the potential of f-LSCs to differentiate in vitro into functional insulin-secreting cells by developing a four-step differentiation protocol that efficiently directed f-LSCs towards the pancreatic endocrine cell fate. The expression of specific endodermal, pancreatic, islet, and β-cell markers, as well as functional properties of f-LSC-derived insulin-producing cells, were evaluated during differentiation. With our stage-specific approach, up to 77% of f-LSCs eventually differentiated into cells expressing insulin (also assessed as C-peptide) and exhibited phenotypic features of mature β-cells, such as expression of critical transcription factors and presence of secretory granules. Although insulin content was about 160-fold lower than what observed in adult islets, differentiated cells processed ~98% of their proinsulin content, similar to mature β-cells. Moreover, they responded in vitro in a regulated manner to multiple secretory stimuli, including glucose. In conclusion, f-LSCs represent a possible relevant source of autologous, transplantable, insulin-producing cells that could be tested for the reversal of diabetes.

Three-dimensional (3D) versus two-dimensional (2D) laparoscopic adrenalectomy: A case-control study

INTRODUCTION Laparoscopic adrenalectomy is today considered the gold standard of treatment for adrenal tumors. The development of high definition cameras does not eliminate the major limitation of two-dimensional (2D) laparoscopy: lack of depth perception and loss of spatial orientation. Tree-dimensional (3D) HD laparoscopy was developed as an alternative to conventional 2D laparoscopy. METHODS We report our experience with use of 3D vision system for laparoscopic adrenalectomy. Between January 2009 and March 2015 we performed a total of 52 laparoscopic adrenalectomies. In this case-control study we considered 13 laparoscopic adrenalectomies performed with three-dimensional (3D) vision system as case group. The last 26 procedures made with two-dimensional (2D) HD laparoscopic system represented the control group. We considered primary end-points: operative time, intraoperative complications and conversion rate. We evaluated also quality of depth perception and surgical strain. RESULTS Although the operative time for the entire surgical procedure was shorter in 3D group, there were no significant differences. The surgeon experienced better depth perception with 3D system and subjectively reported less strain using 3D vision system. Residents and medical students confirmed these data on surgical outcome. CONCLUSION 3D system vision does not seem to influence the operative time of laparoscopic adrenalectomy performed by experienced surgeon because the surgical technique request simple tasks. We obtain the better visualization in depth perception with effect on surgical precision. Comparative studies are necessary to verify if 3D can reduce perioperative complication with similar operative time.

Diabetic Microagiopathy of Oral Mucosa Depends on Disease Duration and Therapy

Background Diabetes mellitus is a chronic degenerative systemic disease whose prevalence is increasing. This paper aims to evaluate the effects of diabetic microangiopathy, depending on its duration and the type of treatment administered, by using polarized light videocapillaroscopy of the oral mucosa. Material/Methods We enrolled 120 subjects: 60 healthy subjects and 60 patients with diabetes mellitus. In turn, patients were divided into 3 subgroups according to the type of diabetes, the duration of the disease, and the type of treatment administered. A videocapillaroscopic examination of the oral mucosa was carried out on the diabetic and healthy subjects. Results Changes in microcirculation were detected in diabetic patients: at the level of the labial, buccal, and lingual mucosa, the density of the loops is on average reduced; there is an increase in the length and the total diameter of the loops, while the average density of the periodontal capillaries is much higher. The most significant changes were noted in patients who had had type 1 diabetes for more than 10 years and had received insulin therapy. Conclusions This study, performed using polarized light videocapillaroscopy, which for the first time was used to analyze the capillaries of the oral mucosa in patients with diabetes, confirms the presence of changes that are instrumentally “objectifiable” and “quantifiable” through the videocapillaroscopic technique. Videocapillaroscopy can be a reliable method in the study and monitoring of complications in patients with type 1 and 2 diabetes mellitus.

Late-onset Sheehan’s syndrome presenting with rhabdomyolysis and hyponatremia: a case report

IntroductionHyponatremia associated with rhabdomyolysis is a rare event and a correct diagnostic approach is required to rule out this or other diseases as a primary cause and to avoid other complications resulting from a lack of appropriate treatment.Case presentationA 64-year-old Caucasian woman presented to our facility with worsening fatigue, slurred speech, nausea and vomiting, and high serum levels of creatine kinase and myoglobin together with hyponatremia. Normal arterial blood gas analysis results, normal serum potassium levels, increased urine sodium levels, urine specific gravity of >1003N/m3 and low urine volume suggested an endocrine etiology. Her low cortisol and thyroid hormone serum levels suggested a pituitary disorder. A magnetic resonance imaging study showed atrophy of her pituitary gland. A more detailed study of our patient’s obstetric history revealed a post-partum hemorrhage 30 years earlier. She was diagnosed as having late-onset Sheehan’s syndrome and treated with hormone replacement therapy, which normalized her clinical picture.ConclusionsThis case report shows that, in hyponatremia-associated rhabdomyolysis, an endocrinological origin should always be considered. This should include Sheehan’s syndrome as it can occur with late onset.

Median arcuate ligament syndrome, a rare case of chronic abdominal pain

The median arcuate ligament syndrome (MALS) is a rare disease characterized by abdominal pain caused by the external compression of the celiac artery by the median arcuate ligament. Surgical treatment is indicated, but given the non-specific symptoms, these patients are often hospitalized in the Departments of Internal Medicine where the diagnosis may be unknown. We present a case of MALS admitted to our Internal Medicine Division. An abdominal ultrasound in a woman with longstanding abdominal pain showed elevated celiac artery velocities during forced expiration. Computed tomography angiography (CTA) of the abdomen showed stenosis of the origin of the celiac artery and confirmed the diagnosis of MALS. MALS is a syndrome that has to be considered, especially in young women with abdominal pain of unclear etiology; evaluated by color Doppler ultrasound, in the presence of elevated hepatic artery velocities during forced expiration, the confirmatory test is CTA.

Innovation in endocrine surgery: Robotic versus laparoscopic adrenalectomy. Meta-analysis and systematic literature review

Several studies in the last years demonstrated the better surgical outcome of laparoscopic approach to adrenal gland. Laparoscopic surgery is more difficult to learn and requires different psychomotor skills than open surgery, especially with regard to complex maneuvers requiring precision and dexterity. The development of robotic platform with three-dimensional vision and increased degrees of freedom of the surgical instruments has the aim to overcome these problems. We performed a systematic literature review with meta-analysis to evaluate preoperative data and surgical outcomes of robotic adrenalectomy compared with laparoscopic technique. In September 2016 we performed a systematic literature review using the Pubmed, Scopus and ISI web of knowledge database with search term “robotic adrenalectomy”. We identified 13 studies with eligible criteria that compared surgical outcomes. This present systematic review with meta-analysis includes 798 patients: 379 underwent to robotic adrenalectomy (cases group) and 419 to laparoscopic adrenalectomy (controls group). There were no significant differences between the two groups of patients respect to age, gender, laterality and tumor size. BMI instead was significant lower in the robotic group. In this group we found also patients with higher incidence of previous abdominal surgery. The results from operative time demonstrated lower operative time for laparoscopic group but there were no significant differences with robotic group. Robotic adrenalectomy showed a significant lower blood loss. Robotic adrenalectomy is a safe and feasible technique with reduced blood loss and shorter hospital stay than laparoscopic adrenalectomy. Laparoscopic approach seems to be a more rapid technique when comparing to robotic technique, although recent studies demonstrate a significant operative time reduction in robotic group with the learning curve improvement and the development of new surgical technology.

Adrenal cavernous hemangioma: which correct decision making process?

AGRUSA ANTONINO1, ROMANO GIORGIO1, DOMINGUEZ LIGIA JULIANA2, AMATO GIUSEPPE1, CITARRELLA ROBERTO3, VERNUCCIO LAURA2, DI BUONO GIUSEPPE1, SORCE VINCENZO1, GULOTTA LEONARDO1, GALIA MASSIMO4, MANSUETO PASQUALE2, GULOTTA GASPARE1 1Department of General Surgery, Urgency and Organ Transplantation, University of Palermo 2Department of Clinical Medicine and Emerging Disease, Geriatric Unit, University of Palermo 3Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo 4Section of Radiology Di.Bi.Me.F., University of Palermo