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Objective: To evaluate 1) the new ulceration, the new major amputation, and the survival rates of 115 diabetic subjects hospitalized for foot ulceration from 1990 to 1993, with an average follow-up of 6.5 years, and 2) the demographic and clinical characteristics associated with these events.Research Design and Methods: A total of 115 subjects, 31 women and 84 men, were monitored until 31 December 1998. All subjects were provided with therapeutic shoes and received intense education. Data concerning new ulceration, new major amputation, and reamputation events and the date and cause of death were recorded for each patient. The prognostic factors for these events were then evaluated.Results: The average follow-up was 78.3 +/- 15.3 months (range 60-106). During this time, 13 homolateral and 12 contralateral episodes of new ulceration occurred. At univariate analysis, none of the variables considered were significantly associated with the new ulceration. There were three major amputations: two of the limb previously healed and one of the contralateral limb. Of the 115 subjects, 51 (44.3%) died: 24 of the 31 women (77.4%) and 27 of the 84 men (32.1%). Ischemic cardiopathy was the most frequent cause of death (60.8%). Mortality concerned 20 of the 27 subjects (74.1%) undergoing major amputation from 1990 to 1993 and 31 of the 88 healed subjects (35.2%), with a significant difference (P < 0.0001). Multivariate analysis showed the independent role of the ankle-brachial index < or =0.5 (P = 0.005), age (P = 0.003), and female sex (P = 0.027).Conclusions: We believe that the use of therapeutic shoes and intense educational training, including the education of the family, have contributed to the low incidence of new ulceration and major amputation in our study population. The high frequency of ischemic cardiopathy as a cause of death should, perhaps, lead to a more aggressive diagnostic and therapeutic attitude toward this pathology in diabetic subjects admitted to hospitals for foot ulceration. [ABSTRACT FROM AUTHOR]

Introduction: Lenvatinib (LEN) is a multi-kinase anti-angiogenic drug recently approved in several cancers. LEN is not easily manageable due to its complex safety profile. Proteinuria and renal failure (RF) were reported among the most frequent LEN-induced adverse events (AEs), often leading to discontinuations or dose modifications. Understanding the pathogenesis of these AEs could ameliorate the management of LEN-induced renal toxicity. Areas covered: We present two cases of LEN-induced renal failure (LIRF) with different pathogenesis. 1) LIRF with severe proteinuria in a man treated for a metastatic papillary thyroid carcinoma. Kidney biopsy showed a glomerular damage secondary to LEN, having excluded other causes of RF. 2) LIRF without proteinuria in a woman with metastatic adenoid cystic carcinoma of minor salivary gland. A tubulointerstitial nephropathy was supposed by clinical evaluation and laboratory tests. Effective management was obtained by oral steroids without interrupting LEN. Expert opinion: The case 1 presented for the first time the histological picture of LIRF with a classical glomerular damage leading to secondary proteinuria and tubular failure. Case 2 showed an alternative LIRF pattern of likely tubulointerstitial injury without proteinuria. These reports reflect two sides of the same coin, both to be considered in case of LIRF.

Purpose: The purpose of this study was to investigate efficacy, safety and tolerability of Xonrid®, a new medical device, in preventing radiation dermatitis associated with head and neck cancer (HNC) radiotherapy (RT)., Methods: In this monocentric, prospective pilot study, adult consecutive HNC patients who were planned to receive curative RT with or without chemotherapy were enrolled. Patients were instructed to apply Xonrid® on the irradiated area during treatment continuing until 2 weeks after the completion of RT or the development of severe skin toxicity. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 scale. The patient reported outcome measures included the Skindex-16 questionnaire and patient satisfaction. Skin reflectance spectra were analyzed to objectively evaluate dermatitis., Results: In total, 41 subjects were enrolled (30 males, median age 60 years). No skin adverse events were recorded either in the skin area where the product was applied or in the nearby skin over the entire period of administration. At the end of RT, nine patients (22%) presented G1, 31 (76%) G2, and one patient (2%) G3 skin toxicity (after 5 weeks). Seven and 20 patients reached skin maximum toxicity at the fourth week and after the seventh week, respectively. An increasing trend of median spectrophotometry scores along with skin toxicity grades was observed. A correlation between Skindex-16 scores and skin toxicity grade during treatment was found., Conclusions: Our study results suggest that Xonrid® is well tolerated, safe, and effective in minimizing and delaying high-grade radiation dermatitis in HNC patients.

Objectives: There are no commonly accepted standards for monitoring patients treated for head and neck cancer. The aim of this study was to assess patients' preferences for different aspects of follow-up., Methods: A best-worst survey was conducted in a sample of head and neck cancer patients in clinical follow-up at the National Cancer Institute (Milan, Italy). Conditional logit regression with choice as the dependent variable was run to analyse the data. A covariate-adjusted analysis was performed in order to identify socio-demographic and clinical factors related to the selection of best-worst items. The participants were asked to report any difficulties encountered during the survey., Results: A total of 143 patients, predominantly male (74%) and with a mean age of 58 years were enrolled in the survey. The strongest positive preference was expressed for a hospital-based program of physical examinations with frequency decreasing over time. Conversely, the lowest valued item was not performing any positron emission tomography (PET) scan during follow-up. Patients with high educational levels were more likely to value attending a primary care-based program and undergoing intensive radiological investigations. Other patient-specific variables significantly associated with the choice of items were employment and living status, time already spent in follow-up and number of treatments received., Conclusions: Overall, patients were more likely to choose an intensive follow-up scheme broadly consistent with the program currently administered by the hospital. There is little evidence of preference heterogeneity that might justify customized programs based on demographics. The best-worst scaling task appeared feasible for most participants., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC) and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS) in patients treated with cetuximab-based approaches. Through sparse partial least square-discriminant analysis (sPLS-DA) and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients. Gene set enrichment analysis identified a significant correlation between the miRNA first-component and EGFR signaling, keratinocyte differentiation, and p53. Another significant correlation was identified between the second component and RAS, NOTCH, immune/inflammatory response, epithelial-mesenchymal transition (EMT), and angiogenesis pathways. Regularized canonical correlation analysis of sPLS-DA miRNA and gene data combined with the MAGIA2 web-tool highlighted 16 miRNAs and 84 genes that were interconnected in a total of 245 interactions. After feature selection by a smoothed t-statistic support vector machine, we identified three miRNAs and five genes in the miRNA-gene network whose expression result was the most relevant in predicting PFS (Area Under the Curve, AUC = 0.992). Overall, using a well-defined clinical setting and up-to-date bioinformatics tools, we are able to give the proof of principle that an integrative miRNA-mRNA expression could greatly contribute to the refinement of the biology behind a predictive model., Competing Interests: The authors declare no conflicts of interest.

Purpose: To identify the tumor portrait of the minority of head and neck squamous cell carcinoma (HNSCC) patients with recurrent-metastatic (RM) disease who upon treatment with platinum-based chemotherapy plus cetuximab present a long-lasting response., Experimental Design: The gene expression of pretreatment samples from 40 HNSCC-RM patients, divided in two groups [14 long-progression-free survival (PFS) and 26 short-PFS (median = 19 and 3 months, respectively)], was associated with PFS and was challenged against a dataset from metastatic colon cancer patients treated with cetuximab. For biologic analysis, we performed functional and subtype association using gene set enrichment analysis, associated biology across all currently available HNSCC signatures, and inferred drug sensitivity using data from the Cancer Genomic Project., Results: The identified genomic profile exhibited a significant predictive value that was essentially confirmed in the single publicly available dataset of cetuximab-treated patients. The main divergence between long- and short-PFS groups was based on developmental/differentiation status. The long-PFS patients are characterized by basal subtype traits such as strong EGFR signaling phenotype and hypoxic differentiation, further validated by the significantly higher association with the hypoxia metagene. The short-PFS patients presented a strong activation of RAS signaling confirmed in an in vitro model of two isogenic HNSCC cell lines sensitive or resistant to cetuximab. The predicted drug sensitivity for all four EGFR inhibitors was higher in long- versus short-PFS patients (P range: <0.0022-1e-07)., Conclusions: Our data uncover the biology behind response to platinum-based chemotherapy plus cetuximab in RM-HNSCC cancer and may have translational implications improving treatment selection. Clin Cancer Res; 22(15); 3961-70. ©2016 AACRSee related commentary by Chau and Hammerman, p. 3710., (©2016 American Association for Cancer Research.)

Objective: The aim of this study was to evaluate the feasibility and effectiveness of this vascular procedure in diabetic inpatients with foot ulcers., Research Design and Methods: In 80 consecutive inpatient diabetic subjects with a foot ulcer, an angiographic study of the lower limbs was carried out to evaluate the necessity and possibility of performing vascular procedures. In 22 subjects, vascular procedure was not necessary; in 26 subjects, peripheral transluminal angioplasty was carried out; in 10 subjects, angioplasty was considered impossible and a peripheral bypass graft was performed; and in 22 subjects, no vascular procedure was considered possible., Results: Of the 26 angioplasties, 8 were performed in iliac or femoral arteries and 18 were performed in the popliteal artery and its branches. The angioplasty was considered unsuccessful in 4 subjects and successful in 22. After angioplasty, on discharge, parameters of limb perfusion improved significantly: transcutaneous oxygen tension was 27.0 +/- 14 mm/Hg on admission and 44.6 +/- 14 mm/Hg on discharge (P < 0.001); ankle-brachial index was 0.61 +/- 0.23 on admission and 0.77 +/- 0.20 on discharge (P = 0.018). Of 22 subjects who underwent successful angioplasty, 21 ended the follow-up of 12 months: during this period, they showed no relapses in the salvaged limb, and their parameters of limb perfusion did not significantly vary., Conclusions: Angioplasty is feasible in a large percentage of diabetic subjects with peripheral occlusive arterial disease and foot ulcer and is often also practicable in the popliteal artery and its branches. In these subjects, angioplasty significantly improves the parameters of limb perfusion. Angioplasty is therefore an important therapeutic tool in ulcerated diabetic foot care.

Diabetic and non-diabetic subjects with angina who underwent angiography and were subsequently treated surgically or medically and followed up for 5 years were analysed in order to assess coronary angiographic findings, efficacy of coronary artery bypass grafting and prognostic criteria in Type 2 diabetic patients with angina as compared to non-diabetic subjects. A total of 1853 of non-diabetic and 145 diabetic subjects underwent angiography, including respectively 857 and 68 who had surgery. Perioperative mortality, survival, reinfarction and asymptomaticity rates were measured. Multivariate analysis of risk factors and clinical features was performed. Diabetic patients had a higher frequency of multi-vessel stenoses (p < 0.001), a greater diffusion of stenoses (p < 0.005) and worse left ventricular motion (p < 0.005). No differences were found in perioperative infarction and mortality. Operated diabetic patients had a higher survival rate (p < 0.001) and a longer symptom-free period (p < 0.05) than unoperated diabetic patients. Operated diabetic patients had similar survival and more frequent recurrence of angina (p < 0.05) than operated non-diabetic patients. Survival rate was lower for unoperated diabetic patients than unoperated non-diabetic patients (p < 0.05). Recurrence of angina was similar. Multivariate analysis did not indicate diabetes as a factor affecting survival. It is concluded that surgery for Type 2 diabetic patients with coronary artery disease is a suitable therapeutic option conferring a reduction in mortality regardless of the presence of diabetes.

Objective: To evaluate the efficacy of manufactured shoes specially designed for diabetic patients (Podiabetes by Buratto Italy) to prevent relapses of foot ulcerations., Research Design and Methods: A prospective multicenter randomized follow-up study of patients with previous foot ulcerations was conducted. Patients were alternatively assigned to wear either their own shoes (control group, C; n = 36) or therapeutic shoes (Podiabetes group, P; n = 33). The number of ulcer relapses was recorded during 1-year follow-up., Results: Both C and P groups had similar risk factors for foot ulceration (i.e., previous foot ulceration, mean vibratory perception threshold > 25 mV). After 1 year, the foot ulcer relapses were significantly lower in P than in C (27.7 vs. 58.3%; P = 0.009; odds ratio 0.26 [0.2-1.54]). In a multiple regression analysis, the use of therapeutic shoes was negatively associated with foot ulcer relapses (coefficient of variation = -0.315; 95% confidence interval = -0.54 to -0.08; P = 0.009)., Conclusions: The use of specially designed shoes is effective in preventing relapses in diabetic patients with previous ulceration.

A total of 89 diabetic patients with foot lesions were treated using amputation during the past 5 years at Niguarda-Ca' Grande Hospital. All patients suffered from gangrene which in 76% of cases was classified as Wagner's stage IV. The lesion was infected in 67 patients. Emergency surgical cleansing was performed in order to drain abscesses and remove necrotic tissue, taking care not to damage healthy tissue. An accurate multidisciplinary study was performed in all cases which included neurological, oculistic and vascular assessment. 83% of patients presented retinopathy and 62.5% were nephropathic. Angiographic tests revealed the presence of distal vascular lesions in 90% of cases. A femoro-distal by-pass was used in 17 cases and the limb was salvaged in 13 patients; ileal-femoral PTA was performed in 10 cases and the limb was salvaged in 7 patients. Amputations were limited wherever possible to distal segments: toes (55 cases), transmetatarsal (12 case), leg (12 cases), thigh (5 cases), atypical resections or ample cleansing of the foot (5 cases). This approach allowed us to record: 1) a low operative mortality (1 case); 2) higher quality of life; 3) the possibility of reoperating on more proximal portions of the limb in the event of immediate or long-term failure. This was necessary in 19 cases which can be classified as follows: reamputation of toe (11 cases), transmetatarsal (4 cases), amputation of leg (4 cases).

When choosing an intensified conventional insulin therapy, no specific differentiation is made between the three-injection regimen (regular insulin at breakfast and lunch, and regular+intermediate-acting insulin at dinner) and the four-injection regimen (regular insulin at breakfast, lunch and dinner, and intermediate-acting insulin at bedtime). No published studies have evaluated to our knowledge the differences between these two regimens. In 1991, we proposed to 30 stable type 1 diabetic patients without residual insulin secretion a change from three to four daily injections: 7 refused, 4 were later excluded for intercurrent events; 19 followed the four daily injection regimen for 2 years. In these non randomized 19 patients, the Student's test for paired data was used to compare with a self-controlled study the 1989-90 three-daily injection period with the 1991-92 four-daily-injection period in order to evaluate any differences in daytime blood glucose values (bi-monthly out-patient measurements taken at 8 am, 10 am, 3 pm and 5 pm), nocturnal blood glucose levels at 3 am (bi-monthly patient self-monitoring by means of a blood glucose meter, for a total of 188 vs 188 measurements), HbA1c (a total of 203 vs 207 bi-monthly out-patient measurements), the number of nocturnal hypoglycaemic attacks, body weight and mean insulin requirement.(ABSTRACT TRUNCATED AT 250 WORDS)