Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Recruitment manoeuvres dislodge mucus towards the distal airways in an experimental model of severe pneumonia.

BACKGROUND: Recruitment manoeuvres generate a transient increase in trans-pulmonary pressure that could open collapsed alveoli. Recruitment manoeuvres might generate very high inspiratory airflows. We evaluated whether recruitment manoeuvres could displace respiratory secretions towards the distal airways and impair gas exchange in a porcine model of bacterial pneumonia. METHODS: We conducted a prospective randomised study in 10 mechanically ventilated pigs. Pneumonia was produced by direct intra-bronchial introduction of Pseudomonas aeruginosa. Four recruitment manoeuvres were applied randomly: extended sigh (ES), maximal recruitment strategy (MRS), sudden increase in driving pressure and PEEP (SI-PEEP), and sustained inflation (SI). Mucus transport was assessed by fluoroscopic tracking of radiopaque disks before and during each recruitment manoeuvre. The effects of each RM on gas exchange were assessed 15 min after the intervention. RESULTS: Before recruitment manoeuvres, mucus always cleared towards the glottis. Conversely, mucus was displaced towards the distal airways in 28.6% ES applications and 50% of all other recruitment manoeuvres (P=0.053). Median mucus velocity was 1.26 mm min-1 [0.48-3.89] before each recruitment manoeuvre, but was reversed (P=0.007) during ES [0.10 mm min-1 [-0.04-1.00]], MRS [0.10 mm min-1 [-0.4-0.48]], SI-PEEP [0.02 mm min-1 [-0.14-0.34]], and SI [0.10 mm min-1 [-0.63-0.75]]. When PaO2 failed to improve after recruitment manoeuvre, mucus was displaced towards the distal airways in 68.7% of the cases, compared with 31.2% recruitment manoeuvres associated with improved PaO2 (odds ratio: 4.76 (95% confidence interval: 1.13-19.97). CONCLUSIONS: Recruitment manoeuvres dislodge mucus distally, irrespective of airflow generated by different recruitment manoeuvres. Further investigation in humans is warranted to corroborate these pre clinical findings, as there may be limited benefits associated with lung recruitment in pneumonia.

Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults.

BACKGROUND: Near-infrared spectroscopy, a non-invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods. We investigated UT-NIRS in healthy volunteers and in brain-dead patients. METHODS: We studied 20 healthy volunteers and 20 brain-dead patients with two UT-NIRS devices, CerOx™ and c-FLOW™ (Ornim Medical, Kfar Saba, Israel), which measure cerebral flow index (CFI), a parameter related to changes in cerebral blood flow (CBF). Monitoring started after the patients had been declared brain dead for a median of 34 (range: 11-300) min. In 11 cases, we obtained further demonstration of absent CBF. RESULTS: In healthy volunteers, CFI was markedly different in the two hemispheres in the same subject, with wide variability amongst subjects. In brain-dead patients (median age: 64 yr old, 45% female; 20% traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial haemorrhage), the median (inter-quartile range) CFI was 41 (36-47), significantly higher than in volunteers (33; 27-36). CONCLUSIONS: In brain-dead patients, where CBF is absent, the UT-NIRS findings can indicate an apparently perfused brain. This might reflect an insufficient separation of signals from extra-cranial structures from a genuine appraisal of cerebral perfusion. For non-invasive assessment of CBF-related parameters, the near-infrared spectroscopy still needs substantial improvement.

Cyclosporin-A efficacy in chronic idiopathic urticaria.

Common drugs in the therapy of chronic idiopathic urticaria (CIU) include antihistamines alone or combined with corticosteroids, but severe unresponsive patients require alternative treatments. This retrospective study aims to evaluate clinical response and safety of low-dose and long-term oral Cyclosporin-A (CyA) in unresponsive patients. One hundred and ten CIU patients, unresponsive to a previous treatment (antihistamines plus prednisone 0.2 mg/kg/day), received additional oral CyA 1–3 mg/kg/day for 6 months. The patients were subdivided into three groups (A, B, C) according to the different CyA doses. Parameters of clinical efficacy including pruritus, and size and number of wheals were evaluated at baseline, after three and six months. All adverse events were recorded. The mean total symptom severity score decreased by 63% in Group A, 76% in Group B, and 85% in Group C after 6 months. Total disappearance of the symptoms was recorded in 43 patients (39.1%): 7 (28%) of Group A; 12 (37.5%) of Group B and 24 (45%) of Group C. After a mean of 2 months from CyA suspension, 14 patients (11%) had recurrence of symptoms. Minor side effects were noted in 8 patients (7%). Our study indicates that low-dose, long-term CyA therapy is efficacious and safe in severe unresponsive CIU.

Oral supplementation with a nutraceutical containing Echinacea, methionine and antioxidant/immunostimulating compounds in patients with cutaneous viral warts.

AIM: The aim of thos paper was to determine the effect of oral supplementation (OS) with a nutraceutical, containing methionine, Echinacea, zinc, probiotics and other antioxidant and immunostimulating compounds, on the response of cutaneous warts to conventional standard therapy (CST). METHODS: This was an open-label study in adults and adolescents aged 14 years or more and with a body weight ≥40 kg, who had at least one cutaneous viral wart. Eligible patients were consecutively allocated to CST (topical therapy with a preparation containing salicylic acid and lactic acid or liquid nitrogen cryotherapy) alone or CST combined with nutraceutical OS for 4 months. RESULTS: A total of 172 patients were enrolled: 83 received CST alone and 89 CST+OS. During the 6-month observation period, a statistically significant reduction of the mean number of warts was obtained in each treatment group and subgroup. The addition of nutraceutical OS was associated with a significantly lower number of warts at 6 months as compared to CST alone. Complete remission was obtained in 54.5% and 86% of patients in the CST group and CST+OS arm, respectively (P<0.001). The influence of the nutraceutical on the response rate appeared to be more prominent in the subgroup of patients treated with topical therapy. The development of new warts during the study period occurred significantly less frequently with CST+OS compared to CST (9% versus 25%; P=0.004). No adverse events possibly related to the nutraceutical administration were observed. CONCLUSION: Our pilot experience seems to suggest that nutraceutical OS is safe and beneficial in patients with cutaneous warts, and capable of enhancing the response to CST.

Body Composition Change, Unhealthy Lifestyles and Steroid Treatment as Predictor of Metabolic Risk in Non-Hodgkin's Lymphoma Survivors.

Unhealthy lifestyle, as sedentary, unbalanced diet, smoking, and body composition change are often observed in non-Hodgkin's lymphoma (NHL) survivors, and could be determinant for the onset of cancer treatment-induced metabolic syndrome (CTIMetS), including abdominal obesity, sarcopenia, and insulin resistance. The aim of this study was to assess whether changes in body composition, unhealthy lifestyles and types of anti-cancer treatment could increase the risk of metabolic syndrome (MetSyn) and sarcopenia in long-term NHL survivors. We enrolled 60 consecutive NHL patients in continuous remission for at least 3 years. Nutritional status was assessed by anthropometry-plicometry, and a questionnaire concerning lifestyles and eating habits was administered. More than 60% of survivors exhibited weight gain and a change in body composition, with an increased risk of MetSyn. Univariate analysis showed a significantly higher risk of metabolic disorder in patients treated with steroids, and in patients with unhealthy lifestyles. These data suggest that a nutritional intervention, associated with adequate physical activity and a healthier lifestyle, should be indicated early during the follow-up of lymphoma patients, in order to decrease the risk of MetSyn's onset and correlated diseases in the long term.

COVID-19-Associated PRES-like Encephalopathy with Perivascular Gadolinium Enhancement.

We describe the case of a 63-year-old woman who developed a coronavirus disease 2019-associated acute encephalopathy with perivascular gadolinium enhancement.

Sensitization, asthma and allergic disease in young soccer players.

BACKGROUND: The aim of this study was to identify the prevalence of allergic disease in young soccer players compared to age-matched students and to evaluate if this prevalence changes as the intensity of training increases. METHODS: A modified ECRHS questionnaire was administered to 194 soccer players divided by age as Beginners (8-11 years), Juniors (12-16 years) and Under 21 (17-20 years) to evaluate the prevalence of allergic diseases and symptoms as well as drug consumption. Subjects with a positive personal history of allergic diseases underwent skin prick and/or patch tests. Age-matched students (n = 136) were used as a control group. RESULTS: The prevalence of allergic diseases was 34.5% in soccer players and 31.6% in control subjects (n.s.). Skin sensitization to inhalant allergens was detected in 14.4% of symptomatic soccer players and in 19.2% of control students (n.s.). Patch tests were positive in 35.7% of soccer players and 23.0% of controls with allergic dermatitis (n.s.). The prevalence of allergic diseases did not significantly change in relation to the intensity of training. Although the relative prevalence of sensitization to perennial allergens and asthma was less frequent in soccer players than in controls, and the occurrence of exercise-induced bronchoconstriction was similar in the two groups, soccer players used twice as many anti-allergic and anti-asthmatic drugs as control students. CONCLUSIONS: An increasingly intensive training programme is not associated with greater risk of allergic disease in soccer players. Therapy regimens of allergic athletes and exercisers should be monitored more closely to guarantee adequate treatment yet avoid inappropriate drug use and doping practices.

Nasal irrigation with lavonase as ancillary treatment of acute rhinosinusitis: a pilot study.

A wide variety of nasal irrigation systems are currently available for improving nasal symptoms, but few studies have compared their effectiveness with respect to patient age and type of nasal disease. This pilot study aims to compare the efficacy of two irrigation systems in 20 patients (12 males and 8 females; age range, 19-54 years; mean age, 36) with acute rhinosinusitis and treated only with antibiotic (levofloxacin 500 mg/day for 10 days) and topical nasal decongestant (naphazoline 2 puffs in each nostril twice daily for 7 days). Patients were randomly assigned to the treatments, using either a nasal syringe (10 mL saline solution, 3 times daily for 14 days) (Group 1) or the recently available Lavonase system (250 mL saline solution sac, twice daily for 14 days) (Group 2). Work-up included history, evaluation of signs and symptoms (nasal obstruction, rhinorrhea), nasal endoscopy, and anterior rhinomanometry. Nasal irrigation with the Lavonase system was found to be more effective in reducing symptoms, as all significantly diminished (p<0.05). In addition, the Lavonase system significantly decreased nasal resistances (p<0.05). This preliminary study shows that the ancillary treatment of acute rhinosinusitis with Lavonase may be useful.

Local and systemic reactions occurring during immunotherapy: an epidemiological evaluation and a prospective safety-monitoring study.

The efficacy of specific immunotherapy in allergic patients with IgE-mediated rhino-conjunctivitis, asthma and allergic reaction for stinging insects suggests the opportunity of improving technical procedures to minimize risk and optimise the safety of immunotherapy. This study investigated both local and systemic reactions, occurring in a population of 218 patients undergoing immunotherapy, in an attempt to correlate them with some parameters as well as age, sex and allergenic extracts. The epidemiological evaluation was based on the administration of a questionnaire to 218 patients in order to assess possible reactions to immunotherapy. The following data were evaluated: personal data, diagnosis, specific allergens, adverse reactions undergone during treatment, number of reactions and symptoms. The patients were followed-up by the medical staff of the Section of Allergological and Immunological Disease (SAID), University of Bari (Bari-Italy) for compilation of questionnaires. We found a correlation between female sex and adverse reactions. Among 107 patients referring reactions to the immunotherapy, 71 patients (66.3%) presented only local reactions; 11 patients (10.3%) systemic reactions and 25 patients (23.4%) systemic reactions associated with local reactions. Parietaria was mostly involved in patients with local reactions, instead, in patients with systemic reactions the prevalent allergens seem to be Dermatophagoides and grass-pollen. Rhinitis was the most frequent diagnosis for patients who have presented both local and systemic reactions. In our study, we had frequently mild systemic reactions and some cases of respiratory difficulties, while it is evident that in our group of patients no cases of anaphylaxis occurred. In addition, we considered some events before the administration of immunotherapy, such as assumption of drugs, meals, exposure to sun, stress or physical activity and the percentage of adverse reactions. On the light of a small number of fatality, immunotherapy represents a safer therapy for allergic diseases; nevertheless, our data suggest that safety is strictly correlated with prescriptions by specialists, administration by trained physicians and accurate follow-up of patients. In particular it is recommended to avoid some events before the administration of immunotherapy, above all the assumption of drugs and physical exercise.

Poor reliability of facial indices for comparative metric facial identification without parametrical superimposition.

The relationship between the craniometric indices that can be evinced from the comparison of two faces for identification purposes is considered a reliable method for the personal identification of faces. Our study aims to assess whether facial indices are susceptible to substantial variations even if the two faces being compared are a different size, looking in a different direction, or differently angled. Our results showed high variability as regards both the facial indices thus obtained and the relative relations. This underlines the fact that regardless of the validity of the metric analysis method used, no numerical comparison can be reliable unless prior parametrical somato-physical superimposition of the images of the subjects has been performed to assess the complete comparability of the faces of the suspects. In conclusion, no reliable identification can be made with the simplified techniques that bypass this difficult, demanding and time-consuming phase of parametric superimposition, as we have shown that they can lead to gross errors.

A multicenter study on the prevalence of clinical patterns and clinical phenotypes in adult atopic dermatitis

No disponible

Cytosolic calcium and hemorheological patterns during arterial hypertension.

Hypertension can be considered as a progressive ischaemic syndrome interesting micro- and macrovasculature. In hypertensives it is possible to observe a link between an increase in peripheral resistance and blood viscosity, and a decrease in red blood cell (RBC) deformability. It is important to underline the link between the increase of blood viscosity, the decrease of RBC deformability and the cytosolic calcium level, which is related to the ischaemic syndrome in hypertension. The aim of this study was to evaluate the level of Ca++ and its possible correlation with hemorheological patterns during arterial hypertension. Two groups were studied: Group 1 consisted of 18 mild hypertensives (11 males and 7 pre-menopausal females, aged 39 +/- 3 years). This group was of medium risk according to WHO and ISH (1999) with no other pathologies apart from peripheral occlusive arterial disease II stage type A. Group 2 was made up of 14 healthy subjects (9 males and 5 females, aged 34 +/- 4 years). The intraerythrocytic cytosolic calcium was evaluated using a fluorescent marker FURA 2/AM (Calbiochem). The following hemorheological parameters were also assessed using the new Laser assisted Optical Rotational Red Cell Analyzer (LORCA) according to the Hardeman method (1994): RBC deformability-Elongation Index (EI), RBC aggregability- aggregation half time (t 1/2). The data obtained showed that compared to the control group the hypertensives had a significantly higher level of intraerythrocytic cytosolic calcium (p < 0.01), plus a significant decrease in EI and t 1/2 evaluated using LORCA. We also observed a significant correlation (p < 0.01) between an increase in Ca++ and a decrease in EI in the hypertensive patients. Moreover our study revealed a significant correlation between the increase in intraerythrocytic Ca++ and the t 1/2 decrease. The evaluation of the hemorheological patterns and cytosolic calcium could explain the impairment in peripheral perfusion and oxygenation in hypertensive patients and could provide a good model for a better evaluation and treatment of microvasculature perfusion in subjects with essential and complicated hypertension.

Tissular oxygenation and erythrocyte deformability in haemodialyzed patients using different dialytic membranes.

We studied the effect of some dialytic membrane on tissular oxygenation (TO) and erythrocyte deformability (ED). Sixteen patients (10 M and 6 F, aged 59 +/- 12 years) have been submitted to bicarbonate dialysis (BD) and subdivided into four groups (GR) of 4 patients each: GR 1 (hemophan membrane, 35 BD), GR 2 (polyacrylonitrile, PAN AN 69, 42 BD), GR 3 (polysulphone, 38 BD) and GR 4 (polycarbonate, 37 BD). The TO has been detected with the transcutaneous oxygen pressure (Tc pO2) using a transcutaneous oxymeter and the ED has been evaluated with the EMI (Erythrocyte Morphometric Index), which results from the ratio between deformable erythrocytes (bowl shape) and rigid erythrocytes (discocyte shape), for every 100 red cells fixed in vitro with 0.3% glutaraldehyde. The ED was also evaluated using a laser instrument: Laser Optical Rotational Cell Analyser. During BD was observed a significant decrease of Tc pO2 in the 1st hour only in the 1st and 2nd GR and, in contrast with results obtained in the 3rd and 4th GR, in the same GRs the EMI showed a significant reduction of ED at the end of BD. Finally the LORCA results, showing a significant decrease of ED only in the 1st and 2nd GR, confirmed the data obtained with EMI. In conclusion, our study has suggested that hemophan and PAN AN 69 are less biocompatible than polysulphone and polycarbonate membranes according to effects on ED and TO.

[Indoor radon pollution in houses in the Apulian Region of Italy and evaluation of the probability of lung cancer in the population]. / Contaminazione da radon indoor nelle abitazioni pugliesi e valutazione della probabilità di insorgenza di tumore polmonare nella popolazione residente.

BACKGROUND: Radon-222 is a gaseous radioactive chemical which can be transformed into other radioactive chemicals, defined as "products of decay" or "radon's daughter". The modality of radon penetration into the buildings depends on the convection motion created in the ground, which suck it back, so causing the penetration. The principal effect on human health is the increase risk of lung cancer, in proportion to the concentration and the time people spend indoors with exposure to radon. OBJECTIVES: The study proposed to estimate the expected cases of radon-induced lung cancer in the population of Apulia due to contamination by indoor radon. METHODS: The study used the data obtained in a national survey made by ANPA (National Environmental Protection Agency) and ISS (High Health Institute), with the collaboration of the Regional Reference Centres for the Control of Environmental Radioactivity (CRR). In the Apulia Region 310 families (5000 nationwide) were involved, which were selected so as to constitute a representative sample both of the region and the country. Appropriate instruments for the measurement of mean concentrations of indoor radon (passive nuclear trace monitors were installed in the homes of the sample families in two different periods of year). We evaluated the variations of indoor radon concentration in the houses during spring-summer and autumn-winter periods, observing a predictable increase in the latter period. We assessed concentrations in relation to: 1. architectural features and location, 2. construction year, 3. building material, 4. presence of windows. RESULTS: We found higher contamination in the oldest non-cement buildings and on the lower floors. In Lecce and Castrì di Lecce we found a mean radon concentration higher than the national and the regional mean, which is equivalent to annual exposure of 0.54 and 0.46 WLM respectively. For these levels we estimated that the expected cases of radon-induced lung cancer will be 1.5 in Lecce and 1.3 in Castrì per 10,000 inhabitants. CONCLUSION: The results of our investigations confirm that indoor radon pollution is a significant problem as it is one of the main causes of lung cancer. Hence, precautionary measures to reduce as much as possible exposure to indoor radon are highly recommended.