A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea.

AIMS: To evaluate the efficacy and safety of saxagliptin as add-on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea. METHODS: In this 24-week, multicentre, randomized, parallel-group, double-blind study, outpatients aged ≥18 years with type 2 diabetes, body mass index ≤40 kg/m(2) and inadequate glycaemic control, received saxagliptin 5 mg or placebo once-daily added to background medication consisting of a stable maximum tolerated dose of metformin plus a sulphonylurea. The primary end point was change in glycated haemoglobin (HbA1c) from baseline to week 24. Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight. RESULTS: A total of 257 patients were randomized, treated and included in the safety analysis (saxagliptin, n = 129; placebo, n = 128); 255 were included in the efficacy analysis (saxagliptin, n = 127; placebo, n = 128). HbA1c reduction was greater with saxagliptin versus placebo [between-group difference in adjusted mean change from baseline, -0.66%; 95% confidence interval (CI), -0.86 to -0.47 (7 mmol/mol, -9.4 to -5.1); p < 0.0001]. The proportion of patients with ≥1 AE was 62.8% with saxagliptin and 71.7% with placebo. In the saxagliptin and placebo groups, rates of reported hypoglycaemia were 10.1 and 6.3%, respectively, and rates of confirmed hypoglycaemia (symptoms + glucose < 2.8 mmol/l) were 1.6 and 0%. Mean change in body weight was 0.2 kg for saxagliptin and -0.6 kg for placebo (p = 0.0272). CONCLUSION: Addition of saxagliptin 5 mg/day in patients inadequately controlled on metformin and sulphonylurea effectively improved glycaemic control and was well tolerated.

Long-term outcomes of Madrid approach after TAR for complex abdominal wall hernias: a single-center cohort study.

PURPOSE: Undeniably, in the last 2 decades, surgical approaches in the field of abdominal wall repair have notably improved. However, the best approach to provide a durable repair with low morbidity rate has yet to be determined. The purpose of this study is to outline our long-term results following the Transverse Abdominis Release (TAR) approach in patients with complex ventral hernias, focusing on the incidence of recurrence and overall patient satisfaction following surgery. METHODS: This is a retrospective study on 167 consecutive patients who underwent TAR between January 2015 and December 2021 for primary or recurrent complex abdominal hernias. Of these, 117 patients who underwent the open Madrid approach with the use of a double mesh (absorbable and permanent synthetic mesh) were selected and analyzed. A quality of life questionnaire (EuraHS QoL) comparing the preoperative and the postoperative status was administered. RESULTS: Between January 2015 and December 2021, we successfully treated 117 patients presenting with complex ventral defects using the double mesh technique (absorbable and permanent synthetic mesh). Of these, 26 (22.2%) were recurrent cases. At a median follow-up period of 37.7 months, there had been 1 (0.8%) case of recurrence and 8 cases (6.8%) of bulging. The QoL score was significantly improved when compared to the preoperative status in terms of cosmesis, body perception, and physical discomfort. CONCLUSIONS: The Madrid approach for posterior component separation is associated with both a low perioperative morbidity and recurrence rate. In accordance with other studies, we demonstrated that the TAR with reconstruction according to the Madrid approach provides excellent results in the treatment of complex abdominal wall hernias, even at long-term follow-up.

Involvement of transcribed lncRNA uc.291 and SWI/SNF complex in cutaneous squamous cell carcinoma.

While non-melanoma skin cancers (NMSCs) are the most common tumours in humans, only the sub-type cutaneous squamous cell carcinoma (cSCC), might become metastatic with high lethality. We have recently identified a regulatory pathway involving the lncRNA transcript uc.291 in controlling the expression of epidermal differentiation complex genes via the interaction with ACTL6A, a component of the chromatin remodelling complex SWI/SNF. Since transcribed ultra-conserved regions (T-UCRs) are expressed in normal tissues and are deregulated in tumorigenesis, here we hypothesize a potential role for dysregulation of this axis in cSCC, accounting for the de-differentiation process observed in aggressive poorly differentiated cutaneous carcinomas. We therefore analysed their expression patterns in human tumour biopsies at mRNA and protein levels. The results suggest that by altering chromatin accessibility of the epidermal differentiation complex genes, down-regulation of uc.291 and BRG1 expression contribute to the de-differentiation process seen in keratinocyte malignancy. This provides future direction for the identification of clinical biomarkers in cutaneous SCC. Analysis of publicly available data sets indicates that the above may also be a general feature for SCCs of different origins.

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial.

In this trial, acute myeloid leukemia patients (pts) aged 61-80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P=0.15, hazard ratio (HR) =1.18, 95% confidence interval (CI) 0.94-1.49) - primary end point - and survival (median 15.7 vs 17.8 months, P=0.19, HR=1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting (10 vs 2%; P=0.001) and diarrhea (10 vs 4%; P=0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery >20 x 10(9)/l (median: 19 vs 23 days; P=0.02) and duration of hospitalization (mean: 15 vs 27 days; P<0.0001) was shorter. The 'non-infusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.

Effect of troglitazone on the desaturases in a rat model of insulin-resistance induced by a sucrose-rich diet.

A sucrose-rich diet generates time-dependent metabolic disorders similar to those found in diabetes type 2. After 8 month (mo) this diet evoked in the rat an increase of blood glucose, free fatty acids (FFA) and triacylycerides (TG) without insulin modification, an interruption of liver stearoyl-CoA desaturase-1 (SCD-1) mRNA and activity increase found at 6 mo, and an enhacement of Delta6 and Delta5 desaturase mRNA and Delta6 activity. We found that the administration of troglitazone (TRO), a peroxisome-proliferator-activated receptors gamma (PPAR-gamma) agonist, for 2 mo normalized plasma FFA, TG, and glucose without altering the insulinemia. It depressed liver SCD-1 mRNA in both control and sucrose-fed rats, decreasing the 18:1n-9/18:0 ratio in serum and liver lipids, and eliminated the increasing effect on mRNA and activity of Delta6 and Delta5 desaturases. These findings evidence again that desaturases are not affected through an insulin resistant effect evoked by the sucrose-rich diet and TRO recovers the altered metabolic plasma parameters as it corresponds to a PPAR-gamma agonist, but its effect on hepatic desaturases can not be attributed to a direct action on liver by PPAR-gamma, insulin, and even by an insulin sensitizing mechanism, suggesting it would be evoked indirectly through hepatic PPAR-alpha deactivation induced by the FFA decrease.

Comparison of the cost-effectiveness of three approaches to screening for and treating sight-threatening diabetic retinopathy.

The purpose of this study was to analyse and compare the costs involved in screening for and treating sight-threatening diabetic retinopathy in three different clinical settings. In the first setting, diabetologists screened using ophthalmoscopy and color photography, according to the St. Vincent Declaration guidelines, and selected patients for further assessment by a visiting ophthalmologist and for treatment in another hospital. In the second setting, all patients were regularly referred to ophthalmologists, either in the same hospital or elsewhere, for all aspects of eye care. In the third setting, screening was done again with ophthalmoscopy alone by diabetologists who followed the St. Vincent Declaration guidelines; however, further assessment and treatment were carried out in the eye department of the same hospital. Costs to the Italian National Health Service and to patients were calculated per screening performed and per patient subjected to laser treatment as a result of screening. A sensitivity analysis was then performed to simulate the costs of standardised patient populations going through the three different settings. It is concluded that absolute costs would be lower, both for the Italian National Health Service and for patients, if screening, assessment and treatment were all carried out in the same hospital. Equipping a diabetic clinic specially for screening would not be more expensive than delegating eye care to external parties, even for a hospital without an eye department. Moreover, delegating eye care more than doubles costs for patients. Screening for, assessing and treating sight-threatening diabetic retinopathy may be a cost-effective procedure for society as a whole in Italy.

What's new in mammography.

Early diagnosis of breast cancer plays the leading role in reducing mortality rates and improving the patients' prognosis: mammography is the most sensitive technique currently available for the detection of nonpalpable lesions and therefore the method of choice. However, mammography has some limitations and the technique must be improved with technological devices without affecting image quality. This could be the target to increase diagnostic accuracy. Mammography sensitivity and specificity are now improved with the digital computer assisted technique, teleradiology, digital tomosynthesis or digital angiography--used to study microvascularization--3D imaging or synchrotron light, and laser mammography. Such other technological devices as Mammospot reduce breast thickness and provide better breast compression. Digital mammography can be carried out with film or direct digitization. The advantages of the digital technique are a shorter examination time, less storage space, electronic image recording, with image 'adjustments' made by the radiologist, and especially computerized analysis. The computer aided diagnosis can be defined as the diagnosis made by the radiologist who considers the results of computerized analysis as a 'second opinion'. In this way incidental mistakes made by radiologists, can be corrected by the computer analysis. Computers are a basic element also in teleradiology, which needs immediate and simultaneous admittance to the patient's history and permits radiology optimization in rural areas too. As for tomosynthesis, it permits to study a single slice of the breast without glandular tissue overlapping, which is useful in dense breasts where the diagnosis can be made with a lower X-ray dose. Moreover, this method fits the current mammographic systems easily. 3D imaging is still a work in progress. Synchrotron mammography is used only on surgery specimens, where it exhibits high resolution and contrast, depicting structures and details missed by conventional mammography. Breast DSA allows the study of vessels < 0.20 mm in diameter and of fine microvascular details; it can also demonstrate neoangiogenesis. Laser mammography permits bilateral examinations of the breast in 10-15 mins and is currently used also for breast cancer therapy, although only in animal trials. To conclude, after reviewing new techniques and evaluating the real cost/benefit ratio for each of them, conventional mammography remains the most sensitive tool for breast cancer diagnosis.

[The observations in a case of eosinophilic fasciitis]. / Osservazioni su un caso di fascite eosinofila.

We present a typical case of eosinophilic fasciitis, with transient peripheral eosinophilia, indurative swelling of the legs, perivascular infiltrates of mononuclear cells and eosinophils of the subcutis and deep fascia, increased ESR, fever, anemia, complete response to steroids. We consider the literature on this topic, particularly concerning the following question: is eosinophilic fasciitis a distinct disease entity or a variant of scleroderma?

Evolution of bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma and Waldenstrom's macroglobulinemia: a retrospective multicentric study.

Bisphosphonates (BPs) are used intravenously to treat cancer-related conditions for the prevention of pathological fractures. Osteonecrosis of the jaw (BRONJ) is a rare complication reported in 4-15% of patients. We studied, retrospectively, 55 patients with multiple myeloma or Waldenstrom's macroglobulinemia followed up from different haematological departments who developed BRONJ. All patients were treated with BPs for bone lesions and/or fractures. The most common trigger for BRONJ was dental alveolar surgery. After a median observation of 26 months, no death caused by BRONJ complication was reported. In all, 51 patients were treated with antibiotic therapy, and in 6 patients, this was performed in association with surgical debridement of necrotic bone, in 16 with hyperbaric O(2) therapy/ozonotherapy and curettage and in 12 with sequestrectomy and O(2)/hyperbaric therapy. Complete response was observed in 20 cases, partial response in 21, unchanged in 9 and worsening in 3. The association of surgical treatment with antibiotic therapy seems to be more effective in eradicating the necrotic bone than antibiotic treatment alone. O(2) hyperbaric/ozonotherapy is a very effective treatment. The cumulative dosage of BPs is important for the evolution of BRONJ. Because the most common trigger for BRONJ was dental extractions, all patients, before BP treatment, must achieve an optimal periodontal health.

Perception of, and anxiety levels induced by, laser treatment in patients with sight-threatening diabetic retinopathy. A multicentre study.

AIMS: To investigate how laser treatment is perceived, in terms of anxiety and awareness, by diabetic patients attending four centres in Northern Italy with specific interest and expertise in diabetic retinopathy, where work settings and flow are organized differently. METHODS: The Hospital Anxiety and Depression Scale (HADS), Family Apgar-List of Threatening Experiences (FA-LTE), State-Trait Anxiety Inventories 1 and 2 (STAI-1 and STAI-2) questionnaires were completed by 259 patients, 131 waiting for laser treatment and 128 control subejcts awaiting non-intervention visits. Open questions were also asked on whether patients had ever heard the word 'laser' and whether they could describe laser treatment. RESULTS: High scores were detected by HADS, STAI-1 and STAI-2 among patients waiting for photocoagulation. Anxiety was greater in women and people with poor schooling. After controlling for centres, gender, previous laser treatment and schooling, HADS and STAI-1 remained significantly lower among persons waiting for non-intervention visits. Having received photocoagulation previously did not modify anxiety. Anxiety was lower in those centres where facilities and resources were more patient-oriented. Most patients could neither describe photocoagulation nor explain why they were about to receive it, but had a negative perception and some described it with words evoking cruelty and pain. CONCLUSIONS: These data suggest that laser treatment is experienced as an event that causes anxiety. Preoperative education and counselling may help to reduce fear and patients' avoidance of treatment.

NK/T-cell lymphomas 'nasal type': an Italian multicentric retrospective survey.

OBJECTIVE: To evaluate the clinical characteristics and outcome of NK/T-cell lymphoma 'nasal type' developed in Italian patients. PATIENTS: Between 1997 and 2004, 26 new cases of NK/T-cell lymphoma 'nasal type' were diagnosed in 10 Italian Hematology institutions. RESULTS: All patients were Caucasian, male/female ratio was 19/7, with a median age of 50 years (range 20-80). In 23 cases presentation at the onset was in the nasal cavity or adjacent structures, in two cases the lymphoma onset with skin lesions was followed successively by rhynopharyngeal dissemination, while the remaining case had bone marrow and lymph node involvement followed by oro-pharyngeal involvement. Regarding the stage of disease: 12 patients were in stage I; six in stage II; eight in stage IV. Diagnosis was based on the finding of a NK/T-cell phenotype at the histological and immunophenotypic examination of oropharyngeal or cutaneous lesions. All patients but one were treated with chemotherapy, alone in nine cases or associated to radiotherapy in 14 cases; two patients had chemotherapy, radiotherapy and surgery, while one patient underwent only surgery. Chemotherapy was anthracycline-based in 17 out of 25 cases. In those patients in whom radiotherapy was performed, radiation dosages ranged between 36 Gy and 47.5 Gy, with a median dosage of 40 Gy. Nine patients (34%) were responsive to the treatments: six patients obtained a complete remission and other three a partial remission. The remaining 17 patients resulted refractory or presented a limited response to therapy. The median disease-free survival was 14 months and the median overall survival time was 9 months. CONCLUSION: The results of this retrospective survey confirmed that NK/T-cell lymphoma 'nasal type' is a very rare lymphoma in the Italian population, and it is characterized by a very bad prognosis. Due to the rarity of this disease, a standardized therapeutic approach is lacking. More data are needed to know the epidemiology of this kind of lymphoma in Europe.

Non-Hodgkin's lymphoma and subsequent acute lymphoblastic leukaemia in a patient with polymyalgia rheumatica.

A patient presenting with polymyalgia rheumatica-like symptoms was found to have non-Hodgkin's lymphoma which later transformed into acute lymphoblastic leukaemia. The association of polymyalgia rheumatica-like symptoms and lymphoreticular/haematological malignancies is discussed.

The antidoping control in horseraces in Italy.

The results and the improvement of the analytical procedures adopted for the control of doping in horses will be reported. This control has been systematically carried out in Italy for about 10 years in the laboratories of Italian Federation of Sport and Medicine in which the biological samples for the control of doping in various sport activities (football, cycling, athletics etc.) are also examined. In this way it is possible to use the same instruments for all these similar problems and compare the results. The analytical procedure is based on the following steps: 1) Extraction of the samples (mainly urine but sometimes blood or saliva). 2) Screening tests by thin-layer chromatography. 3) Confirmatory tests by gas chromatography on different columns and also by gas chromatography coupled with mass spectrometry. These single steps will be separately discussed, and practical problems encountered will be presented.

Quality of life in young Italian patients with epilepsy.

The objective was to evaluate the quality of life of young Italian patients with epilepsy and to investigate the influence of epilepsy medical variables on patients' quality of life. The settings were the Department of Paediatrics, University of Padua; Children's Hospital Giovanni XXIII, Bari; and three schools of South Italy. A sample of 285 subjects was selected: 140 subjects affected by idiopathic and cryptogenic epilepsy (classified according to the International League Against Epilepsy criteria) and 145 control subjects. Data derived from the comparison between the two groups throughout "Epilepsy and children questionnaire" confirmed the negative epilepsy impact on the young patients' quality of life: in fact they scored significantly lower on psychological and social domains (p

Early-onset encephalopathy and cortical myoclonus in a boy with MECP2 gene mutation.

The authors report the unusual clinical and neurophysiologic features of a sporadic case of a boy carrying an 806delG mutation on the MECP2 gene. A 28-month-old boy was examined for severe developmental delay, seizures, microcephaly, breathing dysfunction, and spontaneous and evoked myoclonic jerks of upper limbs. Neurophysiologic study proved the cortical origin of myoclonus; however, it was not associated with signs of cortical hyperexcitability. 3-Methoxy-4-hydroxy-phenylethylene glycol and valine concentrations were low in CSF.

[Treatment of intrahepatic arteriovenous fistula after biopsy. Results in 5 chemoembolization candidates with hepatocarcinoma]. / Trattamento delle fistole artero venose intraepatiche post bioptiche. Risultati in 5 pazienti con epatocarcinoma candidati a chemioembolizzazione.

We report our experience in the treatment of post-bioptic intrahepatic arterioportal fistulas (HAPF) in 5 patients with hepatocellular carcinoma (HCC) treated February, 1993, to May, 1995. In this retrospective study, we reviewed the imaging findings and clinical records of 3 men and 2 women (age range: 49-71 years) with HCC previously diagnosed with US, CT and biopsy. HAPF was detected by angiography (DSA) performed before chemoembolization (TACE). All HAPFs were referrable to biopsy (14-gauge Thru-Cut needle) and were treated with platinum coils positioned through coaxial catheters. TACE was performed immediately after or within a week of HAPF embolization. Therapeutic response after TACE was assessed on the basis of clinical and CT findings, while HAPF embolization success was assessed on the basis of DSA and color Doppler US findings. Reembolization was required in two patients--7 maneuvers in all in 5 patients. Complete HAPF occlusion was demonstrated in 4 patients during color Doppler follow-up and immediately after and at 13 and 24 months (in 2 patients) at DSA. Two of 5 patients died, one because of liver failure after 15 months' follow-up and the other because of complications related to liver transplantation at 11 months' follow-up. Of the extant 3 patients, one underwent liver transplantation and was followed-up for 25 months, while the other two are alive after 24 and 13 months, respectively. Our experience demonstrates that HAPF embolization in HCC patients is really useful for hemodynamic redistribution before TACE and to avoid further HAPF progression.

Cephotaxime-associated allergic interstitial nephritis and MPO-ANCA positive vasculitis.

We report a case of reversible acute renal failure after cefotaxime treatment in a patient affected by non-Hodgkin lymphoma. Renal biopsy showed necrotizing vasculitis associated with eosinophil-rich interstitial inflammatory infiltrates and patchy infiltrates of CD20+ lymphoid cells. High serum p-ANCA titers were also detected. Drug withdrawal was closely related with recovery of renal function and disappearance of ANCA. Acute renal failure therefore represented a consequence of ANCA-mediated renal vasculitis and acute interstitial nephritis related to cefotaxime treatment.

[Use of SHU 508 A Levovist contrast media in the characterization of solid lesions of the breast]. / Impiego del mezzo di contrasto Levovist SHU 508 A nella caratterizzazione delle lesioni solide della mammella.

INTRODUCTION: We investigated the effectiveness of Levovist (SHU508A, Schering AG, Berlin, Germany) in the characterization of breast lesions. MATERIAL AND METHODS: June, 1996, to May, 1997, we studied 29 solid lesions in 29 patients (aged 17 to 83 years); our patients were 28 women and 1 man. The 29 solid lesions were 20 carcinomas (15 infiltrating ductal carcinomas, 4 ductal carcinomas in situ, 1 lobular carcinoma in situ), 6 fibroadenomas, 1 suspected postoperative recurrence and 2 apparently benign lesions. We used parameters suitable for the study of slow flows. A single bolus of contrast agent (300 mg/mL) was administered at 1-2 mL/s. Before Levovist injection, we studied the lesion signal intensity and the number of vascular poles. After contrast administration we re-evaluated both these parameters and studied the changes or presence of vessels undetected on the previous images. We also investigated the beginning and duration of enhancement and the presence of vessels inside and outside the lesions. RESULTS: We observed no signal enhancement in 17% of cases, mild enhancement in 7% and strong enhancement in 76% of cases. We found 3 more vascular poles (17%) in 5 lesions and 4 more poles in 3 lesions (10%). Increased vascularization was seen inside the lesion in 17% of cases, inside and outside it in 41% and only outside in 35% of cases. Carcinomas showed a rapid and long-lasting enhancement, while fibroadenomas showed a later and weaker enhancement. CONCLUSIONS: Levovist can be useful in the differential diagnosis of benign from malignant lesions, of recurrences from postoperative fibrosis, as well as in the staging and follow-up of the patients treated with neoadjuvant chemotherapy.

[The clinical efficacy of magnetic resonance with diffusion-weighted sequences in the assessment of acute cerebral ischemia]. / Efficacia clinica della Risonanza Magnetica con sequenze pesate in diffusione nella valutazione dell'ischemia cerebrale acuta.

PURPOSE: To evaluate the efficacy of diffusion weighted Magnetic Resonance Imaging in the diagnosis of acute ischemic infarction and correlate the signal changes observed in the acute phase with final brain damage. MATERIAL AND METHODS: Fifteen patients (six women and nine men: mean age 68 years) with acute ischemic stroke (within 12 hours) underwent diffusion MRI. All the patients were selected on the basis of sudden focal neurologic symptoms and CT findings excluding other conditions than ischemia. MRI was performed with a 1.5 T magnet with echo-planar gradients. All the patients underwent follow-up CT and/or MRI. RESULTS: Diffusion MRI, performed in the acute phase, showed signal changes in all the patients whose infarction was later confirmed by CT or MRI. In 10 of 12 patients with positive diffusion imaging, CT was normal. FLAIR sequences showed the lesions in 4 of 12 cases. In the 2 patients with transient ischemic attack diffusion MRI was normal as well as follow-up examinations. Apparent Diffusion Coefficients values in the infarcted area were almost half those of the contralateral normal brain. Final damage (as assessed by CT or MRI) was larger than observed in acute diffusion images in all cases but one. CONCLUSION: Because of its high sensitivity and specificity, diffusion MRI is going to play a more important role in the management of acute ischemic stroke patients.