How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Diabetes and severity of COVID-19: What is the link?

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.

Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

DWI findings in a iatrogenic lumbar epidermoid cyst. A case report.

Epidermoid cysts comprise less than 1% of intraspinal tumors. They can be congenital, frequently associated with other spinal malformations, or iatrogenic, resulting from the implantation of epidermal cells within the spinal canal during the execution of a variety of procedures such as spinal puncture. At MR imaging epidermoid tumors can mimic cystic lesions with fluid content such as arachnoid cysts. DWI can help obtain a correct diagnosis. We describe a case of iatrogenic lumbar epidermoid cyst with DWI findings in a young woman who had undergone epidural anesthesia for Cesarean section three years before the onset of symptoms.

Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study.

AIMS: Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients. METHODS: Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed. RESULTS: Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2) < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups. CONCLUSIONS: Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.

Large capillary telangiectasia and developmental venous anomaly of the Basal Ganglia: an unusual finding.

Brain capillary telangiectasias are small, benign, asymptomatic, angiographically occult lesions that are incidentally discovered either at autopsy or on MR imaging in most cases. They are commonly located in the pons and can be associated with other vascular malformations. We describe a case of an unusually large capillary telangiectasia associated with a developmental venous anomaly involving the basal ganglia in a young woman, in which MR serial imaging suggested the diagnosis and avoided an unnecessary stereotaxic biopsy.

Combined atherogenic effects of celiac disease and type 1 diabetes mellitus.

OBJECTIVE: Previous studies have shown a high cardiovascular risk in patients with autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Conversely, few data are available about patients with celiac disease (CD). The aim of our study was to assess carotid intima-media thickness (c-IMT), in patients with T1DM, CD or both (T1DM+CD) as compared with age- and sex-matched healthy individuals (H). METHODS: We enrolled 120 patients, 30 with T1DM, 30 with CD, 30 with T1DM+CD and 30 H. Clinical, metabolic and anthropometric data were collected. All T1DM patients were on insulin while all CD patients were on a gluten-free diet. c-IMT was evaluated by high frequency linear digital ultrasound. RESULTS: c-IMT was significantly greater in patients with T1DM+CD than in patients with T1DM or CD (P<0.001 for both), while no difference was found between T1DM and CD. Moreover, c-IMT was greater in CD than in H (P<0.001). Glycemic control and disease duration were similar between T1DM+CD and T1DM. Lipid and anthropometric parameters were similar among groups. Furthermore, in a pooled multivariate analysis, only age and disease type were significantly correlated with c-IMT (P<0.001 for both). CONCLUSION: Our study demonstrates that celiac patients have greater c-IMT as compared with healthy individuals. Thus, non-invasive monitoring of c-IMT in CD might be useful in preventing cardiovascular disease. Moreover, patients with T1DM+CD show more severe subclinical atherosclerosis as compared with those presenting T1DM or CD only, suggesting that the association of these autoimmune diseases might accelerate the atherosclerotic process.

A case of chronic hepatitis C developing insulin-dependent diabetes, thyroid autoimmunity and stiff-person syndrome as complications of interferon therapy.

We describe the case of a 66-year-old man with chronic hepatitis C who developed type 1 diabetes mellitus (T1DM) and thyroid autoimmunity during Interferon alpha (INFalpha) therapy and then stiff-person syndrome (SPS). This is the first reported case in which SPS has appeared as complication of IFNalpha therapy.

Effect of carbohydrate counting and medical nutritional therapy on glycaemic control in Type 1 diabetic subjects: a pilot study.

AIMS: The effect of a balanced, carbohydrate-counting diet on glycaemic control in Type 1 diabetic subjects is unclear. Our aim was to determine its effect in a small, pilot trial. METHODS: We randomized 256 Type 1 diabetic subjects to a Nutritional Education Programme (group A) or not (group B). Weight, body mass index, glycated haemoglobin (HbA1c), lipid profile, urate, creatinine, microalbuminuria and daily insulin requirements were measured at baseline and at the end of the study (9 months). During the study, the number of hypoglycaemic events (blood glucose<3.9 mmol/l) was also measured. RESULTS: Compared with group B, group A showed: (i) a reduction in HbA1c (group A: 7.8+/-1.3-7.4+/-0.9%; group B: 7.5+/-0.8-7.5+/-1.1%; P<0.01); (ii) less hypoglycaemic events (4% vs. 7%; P<0.05); (iii) a reduction in dose of rapid insulin analogues (23.5+/-10.9 vs. 27.7+/-17.1 IU/24 h; P=0.03). No other between-group changes were observed. CONCLUSIONS: This study shows the importance of medical nutritional therapy on glycaemic control in Type 1 diabetic subjects.

MRI in a woman with late onset ornithine transcarbamylase deficiency.

We describe the brain MR imaging findings of a woman who developed neurologic symptoms due to an acute hyperammonemic encephalopathy resulting from late onset ornithine transcarbamylase deficiency (OCTD). MR images revealed injury (hyperintense foci on long TR images) to the subcortical white matter of the left precentral and supramarginal gyrus and in the left frontal lobe. These findings presumably reflect the distribution of brain injury from hypoperfusion secondary to severe hyperammonemia. If MR findings suggesting hypoperfusion are detected in a patient with hyperammonemia, the diagnosis of OCTD should be considered. Knowledge of the physiopathological mechanisms of OTCD and of MR imaging of hyperammonemic injury may help expedite diagnosis and treatment and prevent the exitus of patients with this genetic disorder.

DWI Reversibility after Intra-Arterial Thrombolysis. A Case Report and Literature Review.

We report our case and review the literature on reversal DWI lesions, ADC thresholds and correlation between DWI lesion and outcome measured with clinical scales. A 30-years old woman was admitted to our hospital 18 hours after stroke onset. Considering the absence of alterations on CT and the worsening of symptomatology, the patient underwent MRI, which showed a slightly hyperintense signal in FLAIR images in the left portion of the pons and midbrain and a more evident bilateral DWI hyperintensity of the pons. The patient was treated with mechanical and pharmacological intra-arterial thrombolysis. The patient showed a rapid improvement of symptoms. Two weeks after the treatment her clinical conditions were characterized by a residual right hemiparesis and complete recovery of right motility, respiratory and swallowing difficulties. MR examination demonstrated a slight signal alteration of the pons left hemiportion and a disappearance of the mesencephalic signal alteration and of the right portion of the pons. DWI lesions represent irreversibly damaged tissue but new evidence suggests that DWI lesions may be reversible, especially with reperfusion, by now well demonstrated in animal models. Therefore acute DWI lesions probably contain not only irreversibly injured tissue but also parts of the penumbra. The debate on the capability of ADC maps to discriminate irreversibly from reversibly damaged tissue is a matter of controversy. ADC values in human stoke are not an independent indicator of tissue viability. The use of thresholds may improve reproducibility but not validity.

Slight association between type 1 diabetes and "ff" VDR FokI genotype in patients from the Italian Lazio Region. Lack of association with diabetes complications.

BACKGROUND: Vitamin D receptor (VDR) mediates the effects of vitamin D. Our paper evaluates the FokI and BsmI VDR genotypes in 246 Caucasian (Italian from Lazio Region) T1DM patients compared with 246 Caucasian healthy controls, sharing age and gender and regional provenience with the patients. In addition, T1DM patients without complications were compared with those carrying three complications. METHODS: Genotyping has been obtained by RFLP-PCR technique. RESULTS: A slight significant association of T1DM with FokI homozygous "f" genotype was observed. No association was observed with the presence of multiple complications by a multivariate analysis. CONCLUSION: T1DM patients showed slightly increased prevalence of "ff" VDR genotype.

Blunted erythropoietin response to anemia in patients with Type 1 diabetes.

BACKGROUND: It is known that patients with renal failure have normochromic normocytic anemia due to impaired endogenous erythropoietin (EPO) synthesis. The aim of this work was to determine whether low serum erythropoietin (s-EPO) levels play a role in the pathogenesis of anemia in patients with Type 1 diabetes without overt nephropathy. METHODS: We included in the study 13 patients with Type 1 diabetes whose Hb levels were <11 g/dl. Blood cell count, s-EPO, urinary albumin excretion rate (AER), HbA(1c), glomerular filtration rate, serum iron, serum ferritin, the presence of neuropathy, retinopathy and nephropathy were determined. RESULTS: Ten out of 13 patients with anemia (77%) had a blunted EPO response to anemia. All ten patients with low EPO levels had autonomic neuropathy; five had clinical nephropathy but with serum creatinine<1.6 mg/dl. Three patients were treated with rHuEPO and showed an improvement in their anemia after treatment. CONCLUSION: The majority of patients with Type 1 diabetes who had anemia also had low EPO levels. The pathogenesis of this phenomenon is probably multifactorial. Autonomic neuropathy appears to play a role, but it is not sufficient, per se, to be the only cause. Dysautonomia might enhance the effect of renal damage.

Pharmacosurveillance in hospitalized patients in Italy. Study design of the 'Gruppo Italiano di Farmacovigilanza nell'Anziano' (GIFA).

The Italian Group of Pharmacoepidemiology in the Elderly (Gruppo Italiano di Farmacovigilanza nell'Anziano, GIFA) is a collaborative pharmacosurveillance study in hospitalized patients, sponsored by the Italian National Research Council (CNR) and the Italian Society of Gerontology and Geriatrics. It was founded in 1987 with the aim to constitute a multicentre research group to study quality of care and problems related to pharmacological therapy in the elderly. Until now the GIFA study has completed seven periodical surveys and enrolled a total of 28,411 hospitalized patients in 83 clinical centres. The database of the study contains approximately 174,000 in-hospital drug prescriptions, approximately 88,000 discharge diagnoses and a great deal of data on topical geriatric items such as cognitive performance, disability, comorbidity, adverse drug reactions and incontinence. This paper describes the general organization and the methods of the GIFA study and shows in detail the type of data collected.

Early renal involvement in diabetes mellitus: comparison of renal Doppler US and radioisotope evaluation of glomerular hyperfiltration.

PURPOSE: To evaluate the usefulness of Doppler ultrasonography (US) in the diagnosis of hyperfiltration in patients with insulin-dependent diabetes mellitus (IDDM). MATERIALS AND METHODS: Eighty-one consecutive patients with IDDM were studied. All patients were normotensive and had normal creatinine and blood urea nitrogen levels. The glomerular filtration rate (GFR) was evaluated by means of plasma clearance of chromium-51 ethylenediaminetetraacetic acid, urinary albumin excretion, US evaluation of renal volume, and Doppler evaluation of resistance index (RI) in the renal interlobar arteries. The patients were divided according to GFR into the following groups: those with hyperfiltering kidneys (group 1, n = 40) and those with normofiltering kidneys (group 2, n = 41). RESULTS: The median renal volume was 351 mL (95% CI = 337 mL, 379 mL) in group 1 and 318 mL (95% CI = 300 mL, 335 mL) in group 2 (P = .005). The number of patients with microalbuminuria was significantly lower in group 1 than in group 2 (P = .02). The median RI was significantly lower in group 1 (0.55; 95% CI = 0.53, 0.57) than in group 2 (0.57; 95% CI = 0.56, 0.59) (P = .04). An RI of less than 0.5, a renal volume greater than 410 mL/m2, and the absence of microalbuminuria were independent predictors of hyperfiltration. An RI of less than 0.5 and a renal volume greater than 410 mL/m2 showed high specificity (98% and 95%, respectively) and poor sensitivity (25% and 23%, respectively) in the diagnosis of hyperfiltration in IDDM patients. CONCLUSION: Both RI and renal volume showed correlation with GFR, but neither parameter is sufficiently sensitive in screening for hyperfiltration in IDDM patients.

Hyperfiltration in patients with type I diabetes mellitus: a prevalence study.

AIM: An increase in glomerular filtration rate (GFR) and renal plasma flow (EFPR) may be considered as prognostic factors for the progression of diabetic nephropathy; however the real predicting value of hyperfiltration in the development of incipient and overt nephropathy is as yet unknown. We have examined the prevalence of hyperfiltration in a population of normotensive adult IDDM patients and the possible effect of long-term metabolic control on glomerular hemodynamics. MATERIALS AND METHODS: We measured GFR and ERPF values in 177 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 30 healthy subjects by single bolus intravenous injection of 1 miroCu/kg [51Cr]-EDTA and 0.2 microCu/kg [125I]-Hippuran intravenously. We have correlated the GFR values with parameters of metabolic control over the last 3 years and with age, sex, and duration of diabetes. RESULTS: Patients with a GFR greater than the 95 degrees percentile value of controls (135 ml/min/1,73 m2) were defined as hyperfiltering. They represented the 55.9% (99/177) of our population. We found a strong correlation between GFR and ERPF (p <0.001), and between GFR and average HbA1c levels (p = 0.016) in multiple regression analysis, with age, sex, ERPF, and average HbA1c levels entered as variables (r2 = 0.45). There appeared to be no correlation with the duration of the disease. CONCLUSIONS: Long-term hyperglycemia provides a significant contribution in GFR and a poor metabolic control is predictive of overt nephropathy. In this study hyperfiltration does not appear to be the major factor of diabetic nephropathy. A follow-up of these patients is necessary to clarify the role of hyperfiltration in the development of overt nephropathy in diabetes.

Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.