Efficacy of ustekinumab in the treatment of patients with Crohn's disease with failure to previous conventional or biologic therapy: a prospective observational real-life study.

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

Very Early Development and Recognition of Coronary Involvement in a Febrile Infant with Typical Signs of Kawasaki Disease.

Kawasaki disease (KD) is an acute, self-limited, inflammatory disease affecting medium-sized arteries and particularly the coronary arteries in about 25% of untreated cases. KD is a clinical diagnosis based on the presence of ≥5 days of fever and the presence of ≥4 of the 5 principal clinical criteria. We described, for the first time to our knowledge, a case of a very early development (on day 1) of typical KD with transient coronary involvement, diagnosed on day 2 of disease and treated with aspirin and steroids on day 3, with complete resolution of clinical signs and coronary involvement.

[Ketamine i. v. for the treatment of cluster headaches : An observational study]. / Ketamin i. v. zur Behandlung von Clusterkopfschmerz : Eine Beobachtungsstudie.

Cluster headaches have an incidence of 1-3 per 10,000 with a 2.5:1 male-to-female gender ratio. Although not life threatening, the impact of the attacks on the individual patient can result in tremendous pain and disability. The pathophysiology of the disease is unclear, but it is known that the hypothalamus, the brainstem, and genetic factors, such as the G1246A polymorphism, play a role. A distinction is made between episodic and chronic cluster headaches. In a controlled setting, we treated 29 patients with cluster headaches (13 with chronic cluster and 16 with the episodic form), who had been refractory to conventional treatments, with a low dose of ketamine (an NMDA receptor antagonist) i.v. over 40 min to one hour every 2 weeks or sooner for up to four times. It was observed that the attacks were completely aborted in 100 % of patients with episodic headaches and in 54 % of patients with chronic cluster headaches for a period of 3-18 months. We postulated neuroplastic brain repair and remodulation as possible mechanisms.

High hydrostatic pressure processing of murine norovirus 1-contaminated oysters inhibits oral infection in STAT-1(-/-)-deficient female mice.

We have previously demonstrated that high pressure processing (HPP) is effective in preventing in vitro replication of murine norovirus strain 1 (MNV-1), a human norovirus surrogate, in a monocyte cell line following extraction from MNV-1-contaminated oysters. In the present study, the efficacy of HPP to prevent in vivo replication within mice fed HPP-treated MNV-1-seeded oyster extracts was evaluated. Oyster homogenate extracts seeded with MNV-1 were given 5-min, 400-MPa (58,016-psi) treatments and orally gavaged into immunodeficient (STAT-1(-/-)) female mice. Mice orally gavaged with HPP-treated MNV-1 showed significant (P ≤ 0.05) weight loss leading to enhanced morbidity, whereas those given 100 and 200 PFU of HPP-treated MNV-1 were comparable to uninfected controls. MNV-1 was detected, via real-time PCR, within the liver, spleen, and brain of all mice fed non-HPP-treated homogenate but was not detected in the tissues of mice fed HPP-treated homogenates or in uninfected control mice. Hepatocellular necrosis and lymphoid depletion in the spleen were observed in non-HPP-treated MNV-1 mice only. These results clearly show that HPP prevents MNV-1 infection in vivo and validates that viral inactivation by HPP in vitro is essentially equivalent to that in vivo. Further, the data suggest that HPP may be an effective food processing intervention for norovirus-contaminated shellfish and thus may decrease risk to both immunocompromised and immunocompetent individuals who consume shellfish.

[Evaluation of the efficacy of a program to control nosocomial spread of methicillin-resistant Staphylococcus aureus]. / Valutazione dell'efficacia di un sistema di controllo della diffusione intraospedaliera di Staphylococcus aureus meticillino-resistente.

OBJECTIVE: To evaluate the efficacy of a program to control nosocomial spread of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Analysis of the incidence of infection and contamination due to MRSA in patients admitted to the hospital of Cremona 6 months before and 3 years after the introduction of the guidelines (July 1997). RESULTS: During the 42 months of the study period, on 80705 admissions, 511 cases of MRSA contamination/infection were identified, the incidence being 0.57 cases per 100 admissions. The infection rate dropped from 0.34 (IC95%: 0.25-0.45) in the first 6 months of the study, before the introduction of guidelines, to 0.17 (IC95%: 0.14-0.20) in the following 3 years (p=0.01). Severe infection decreased from 0.18 to 0.1 per 100 admissions, with a 44% decrease (p=0.058), while mild infections diminished from 0.16 to 0.07 per 100 admissions (p=0.045). Methicillin resistance among nosocomial isolates of Staphylococcus aureus was reduced from 53 % to 35 % (p<0.0001). CONCLUSIONS: The introduction of a program to control the nosocomial spread of MRSA proved effective in reducing both the incidence of infection and the methicillin-resistance of Staphylococcus aureus isolates. The cost effectiveness of the program seems very favourable.

[Diabetic foot. A clinical case]. / Piede diabetico. Un caso clinico.

Diabetic neuropathy may cause an alteration of the function of the muscles of the sole of the foot. This is at the origin of the chronic dislocation of the articular heads, mainly of the little metatarsal bones (neuro diabetes arthropathy), with formation of areas of pathological pressure. The tissues below being chronically under pressure are affected by trophic lesions called "plantar perforating disease". Recovery may be obtained by not exposing the injured area of the foot to pressure and through careful local therapy. This doesn't prevent disease from appearing again, even though some specially conceived soles are being used, aiming at a correct weight redistribution on the sole of the foot. The clinical case we are describing applies to a man affected by insulin dependent diabetes mellitus, with relapsing diabetic foot ulcers, in spite of him using a specifically designed sole. Such lesion is aggravated by a serious infection which, by gradually penetrating in depth, leads to osteomyelitis, affecting the 5th Metatarsal head. The bone area, dislocated by neuroarthropathy, was presumably responsible for the persisting plantar lesion. The amputation of this infected necrotic structure, has led to the overcoming of the serious septic problem. By eliminating the bone link responsible for the transmission of the pathological pressure, the plantar lesion the patient had been suffering from for a long time, has consequently disappeared.

[Evaluation in experimental animals of a mathematical model of foreseeing variations in values of stable glycosylated hemoglobin]. / Valutazione sull'animale da esperimento di un modello matematico per la previsione delle variazioni dei valori di emoglobina glicosilata stabile.

Assay of glycosylated hemoglobin provides reliable information on metabolic control in diabetes mellitus over a period of about 90 days. This is why it is currently used as a parameter of blood glucose control in diabetic patients. However, at present little is known about the kinetics of stable glycosylated hemoglobin variations as a result of circadian changes in blood glucose level. The authors describe a mathematical model which allows to foresee glycosylated hemoglobin variability as a result of alterations of blood glucose equilibrium.

[Evaluation of the changes in glycosylated hemoglobin in a sample of hospitalized diabetic patients. Significance and limitations of this diagnostic method]. / Valutazione delle variazioni dell'emoglobina glicosilata in un campione di soggetti diabetici ospedalizzati. Significato e limiti di questa diagnostica.

Stable glycosylated hemoglobin measurement provides an index for plasma glucose control over an average three month period. It is not clear whether stable HbA1C can undergo rapid changes induced by short-term variations in glucose concentration. The present study was aimed at investigating whether variation of total HbA1C in response to changes in blood glucose, over a short period can be detected by routine methods of determination. Our result show that due to the sensitivity of the methods, stable HbA1C has to be considered only as an index of glucose control over long period of time.

[Therapeutic use of glutathione]. / Utilizzo terapeutico del glutatione.

Liver pathology is very frequent in western countries. The numerous therapeutic approaches suggested so far for the prevention or limitation of liver damage in the course of hepatic diseases have often had disappointing results. Considering that at least part of the liver injury is caused by free radicals, the authors have tried an antioxidant, glutathione, as a hepatoprotective agent. Although particularly brilliant results were not achieved, clinical conditions and laboratory findings were improved in hall patients treated with glutathione.

[Therapy of trophic ulcers in diabetes mellitus]. / Terapia delle ulcere trofiche in corso di diabete mellito.

Trophic lesions of the lower limbs are very frequent in diabetic patients, especially after long periods of poor glycemic control. These lesions are caused by some diabetic sequelae, namely neuropathy and angiopathy. The human and social cost of trophic lesions is very high; for this reason education of diabetics who are likely to develop such lesions is extremely important. When trophic lesions have developed, conservative management is based on local and general therapy. Amputation is taken into account only when conservative management has failed.

[Removable electromagnetic transducer for the study of cardiac minute volume in the conscious dog]. / Trasduttore elettromagnetico rimovibile per lo studio del volume minuto cardiaco ne cane sveglio.

The study aimed at evaluating the reliability of a new type of aortic flow probes to be used in conscious dogs and easy to be removed without a second surgical intervention, 48-72 hours after they have been implanted. The probes, which have been made in the Department of Human Physiology of the University of Turin, are light and thin enough to be cronically implanted around the aorta without removing the fat which surrounds the artery, and to be taken away without injuring the tissues. The records obtained 24 and 48 hours after they have been positioned, demonstrate the reliability of the probes. Histological examination of the aorta has not evidenced any tissue reaction.