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Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure < 130/80 mmHg, glycated haemoglobin < 7%, LDL, HDL and total cholesterol < 100 mg/dL, > 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925

It goes without saying that all people with diabetes should be taught the best injection technique before starting insulin treatment. Nevertheless the extremely high rate of local injection-related skin reactions-i.e., lipodysthrophic lesions-described in literature, proves otherwise. We are hereby presenting a Consensus Document on Injecting Techniques which highlights 18 key points based on a thorough analysis of the available literature and ranked by "Level of evidence" and "Strength of recommendation" according to our National Guideline System. It is meant at providing all professionals involved in diabetes care with a practical guide on how to help patients on insulin perform well.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are reliably detected by referral laboratories, even if most lung cancer cytology specimens sent to such laboratories contain very few cells. However, EGFR mutations may be distributed heterogeneously within tumors, thereby raising concerns that mutations detected on cytology are not representative of the entire tumor and, thus, are less reliable in predicting response to tyrosine kinase inhibitor (TKI) treatment than mutations detected on histology. To address this issue, the authors reviewed their clinical practice archives and compared the outcome of TKI treatment among patients who were selected by cytology versus patients who were selected by histology. METHODS: From July 2010 to July 2012, 364 cytology samples and 318 histology samples were received. Exon 19 deletions and the L858R point mutation in exon 21, detected by fragment assay and TaqMan assay, respectively, were confirmed by direct sequencing; discrepancies were resolved by cloning polymerase chain reaction products. The response rate (RR) and progression-free survival (PFS) at 12 months (range, 3-34 months) were evaluable in 13 EGFRmutated patients who were selected for treatment by cytology and 13 patients who were selected by histology. RESULTS: The mutation rate was similar in histology samples (8.5%) and cytology samples (8.8%). The RR (54%) and PFS (9.2 months) were similar in histologically selected patients and cytologically selected patients (RR, 62%; PFS, 8.6 months; P5.88). The disease control rate (responsive plus stable disease) was 92% in histologically selected patients and 100% in cytologically selected patients. CONCLUSIONS: EGFR mutations detected on cytology specimens by a centralized laboratory can predict TKI treatment response equally well as mutations identified on histology samples.

Adiponectin (Acrp30) is an insulin-sensitizing hormone with beneficial effects on a number of biological and metabolic processes by two widely expressed receptors, AdipoR1 and AdipoR2. To date, the role of Acrp30 in lung is not completely assessed but altered levels of Acrp30 and modulated expression of both AdipoRs have been described in Chronic Obstructive Pulmonary disease (COPD) (1). Lung inflammation, a crucial component of COPD progression, is mainly sustained by two potent pro-inflammatory cytokines: Tumor Necrosis Factor α (TNFα) and Interleukin 1β (IL-1β). These mediators in turn propagate and perpetuate the inflammation also through NF-κB, a transcriptional factor for many genes involved in inflammation, injury and stress in lung. In this study we analyzed the effects of Acrp30 on human alveolar epithelial cell line (A549) selected as an in vitro model of lung epithelia. We treated A549 cells with TNFα or IL-1β and visualized the NF-κB nuclear transactivation by confocal microscopy. Successively, we evaluated the role of Acrp30 in this process: we treated the cells with Acrp30 and subsequently with TNFα or IL-1β and analyzed NF-κB nuclear transactivation. Finally, we investigated by western blotting the phosphorylation status of ERK1/2 kinase, one of the main molecules involved in Acrp30 signal pathway. A better elucidation of the Acrp30 role in the control of local lung inflammatory state may contribute to develop new therapeutic approaches in inflammatory diseases as COPD, a major cause of morbidity and death worldwide

In the absence of distail metastases, accurate evaluation of TNM classification parameter N is the predictfve parameter whlch most often influences therapy and prognosis in NSCLC patients. Inaccuratc evaluation could easìly reclassìfy a patient from eligibility for resection to an exclu-sively pharmacologic treatment pian. Parameter N evaluation ìs commorily based on computer tomography (CT) and positron emission tomog-raphy (PET) fmdings; although both imaging techniques offer satisfactory results when com-bincd, thè specificity rates are suboptimal. Transbroiichial needle aspiratlon (TBNA) per-mits cytohistologìc sampling and can provide additional information to be intcgrated with imaging study data

Epithelioid hemangioendothelioma (EHE) is an uncommon vascular tumor characterized by epithelioid or histiocytoid cells exhibiting primitive vascular differentiation. This lesion may involve lung, soft tissue, bone, liver, breast, brain andlymphnodes. The pulmonary EHE is of “borderline malignancy”, the prognosis is unpredictable (mean survival 4.6 years) and death usually occurs for a progressive respiratory failure. About 50 cases have been reported in literature. In February 2000 a 20-year-old woman with a one year history of dry cough had a HRCT scan showing multiple bilateral nodules in the lungs. The patient underwent thoracoscopic lung biopsy and an interstitial lung disease was suspected. After a nine months course of corticosteroid therapy a remission of symptoms was obtained and the HRCT scan periodically perfomed for three years did not show a progression of the disease. In September 2004 she was admitted to our Department for a suspected pneumonia and a bronchoscopy was performed. The histological examen of bronchial biopsies revealed a poorly differentiated neoplasm immunohistochemically positive for vimentin and endothelial markers (factor VIII-related antigen and CD34). A diagnosis of angiosarcoma (malignant hemangioendothelioma) was made. Chemotherapy with paclitaxel (80 mg/mq 1, 8, 15 every 28 days for three cycles) was admnistered but after six months from the diagnosis the patient died. The revision of the former CT scan and histological examen suggested a diagnosis of pulmonary EHE (intravascular bronchiolo-alveolar tumor- IVBAT). At our knowledge, this is the first reported case of EHE, a low grade neoplasm, transformed into a very high grade angiosarcoma.

Parosteal lipoma is a rare benign tumor composed of adipose tissue contiguous to the periosteum of the underlying bone. These tumors are slow-growing, nontender masses that affect, almost exclusively, the diaphysis of the long bones of the upper and lower limbs. We hereby describe the CT characteristics with the correlative pathological findings in a rare case of parosteal lipoma of the rib.

Diabetes is an independent risk factor for the development of coronary heart disease and has a tremendous impact on mortality. In patients with noninsulin-dependent diabetes mellitus, coronary heart disease is the leading cause of death. Both hyperinsulinemia and hyperglycemia have been suggested as risk factors for accelerated atherogenesis in diabetes. Whichever mechanism is implicated, a beneficial effect of therapy in preventing cardiovascular disease is a major requirement. Until now, it is not clear whether stringent control of blood glucose levels reduces the risk of development of coronary heart disease in patients with noninsulin-dependent diabetes mellitus. This review emphasizes the relative roles of insulin and glucose on coronary heart disease development in noninsulin-dependent diabetes mellitus. The different therapeutic options of pharmacological treatment in hyperglycemia in noninsulin-dependent diabetes mellitus are discussed, as well as their impact on coronary heart disease risk.

We report a case of pilomatrix carcinoma in a 42 year old woman. The patient presented a rapidly growing 4-cm subcutaneous mass in the right preauricular area. She was free of recurrence 24 months after surgery. Immunoreactivity was studied for cytokeratins, epithelial membrane antigen, S-100 protein, blood group antigens, Leu-M1, β-2-microglobulin, vimentin, neuron-specific-enolase and cellular binding for peanut agglutinin. Squamous cells were reactive for cytokeratin AE1/3, epithelial membrane antigen, blood group antigens B and H, and peanut agglutinin. Basaloid cells were focally reactive for cytokeratin AE1/3 and epithelial membrane antigen. Flow cytometry revealed a euploid DNA content and a high proliferative rate of the pilomatrix carcinoma and in benign pilomatrixoma studied for comparison. The pathological diagnosis must be based on histomorphological criteria.

The metabolic and cardiovascular effects of nitrendipine and cilazapril in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM) were compared. After at least 6 weeks of a washout period, 20 NIDDM patients who had diastolic blood pressure in the range of 90-105 mm Hg received a single-blind placebo for 4 weeks and then were randomized to receive 20 mg nitrendipine once daily and 5 mg cilazapril once daily each for 12 weeks according to a crossover, double-blind procedure. Nitrendipine and cilazapril reduced diastolic blood pressure levels 12% and 13%, left ventricular mass index (LVMI) levels 13% and 12%, and raised whole glucose disposal levels 18% and 19.5%, respectively. Only nitrendipine reduced glucose-stimulated insulin levels. Nitrendipine is as effective as cilazapril in lowering diastolic blood pressure and LVMI levels and in increasing glucose disposal levels in these patients.