Certolizumab for the treatment of psoriasis and psoriatic arthritis: a real-world multicentre Italian study.

BACKGROUND: Certolizumab, a pegylated tumour necrosis factor-α inhibitor, reduced disease activity in randomized trials of patients with psoriasis and psoriatic arthritis. Real-life data are missing. OBJECTIVE: To confirm the effectiveness and safety of certolizumab in patients with psoriasis and psoriatic arthritis in routine clinical practice. METHODS: In this retrospective study involving 11 Italian sites, patients with psoriasis and psoriatic arthritis received subcutaneous certolizumab (400 mg loading dose at 0, 2 and 4 weeks, followed by 200 mg every 2 weeks) for up to 52 weeks. Primary outcomes included mean change from baseline in Psoriasis Area and Severity Index (PASI) and modified Nail Psoriasis Severity Index (mNAPSI) scores, and the proportion of patients achieving a 75%, 90% or 100% reduction in PASI score. Other endpoints included Disease Activity Score computed on 44 joints correlated with the erythrocyte sedimentation rate during the first hour (DAS44-ESR), Tender Joint Count (TJC), Swollen Joint Count (SJC), pain [visual analogue scale (VAS) score], inflammatory markers and quality of life (QOL). RESULTS: In the study were enrolled 153 patients (mean age: 55 years). Certolizumab reduced the mean PASI score from baseline by 4.45, 6.30 and 7.58 at weeks 12, 24 and 52, respectively (P < 0.001 for all). At weeks 24 and 52, 69.6% and 83.3% of patients had a PASI score ≤3. DAS44-ESR, TJC, SJC and mNAPSI scores, and pain VAS were also all significantly improved from baseline at each time point. C-reactive protein levels decreased during treatment, being significant at week 24. On multivariate analysis, psoriasis duration, baseline PASI, mNAPSI and pain VAS scores were found to be predictive of the improvement in PASI score at week 12. CONCLUSION: Certolizumab displayed also in the real-life encouraging results in both psoriasis and psoriatic arthritis patients.

Dermoscopic Analysis of 72 "Atypical" Seborrheic Keratoses. / Análisis dermatoscópico de 72 queratosis seborreicas «atípicas¼.

BACKGROUND: Seborrheic keratoses (SK) are easily recognizable by clinical and dermoscopic approach, nevertheless, some lesions act as a simulator of different skin conditions lacking typical clinical and dermoscopic criteria. OBJECTIVE: The aim of our study was to find specific dermoscopic features or a global pattern to improve diagnostic skills for challenging SK. MATERIALS AND METHODS: We examined 72 atypical SK excised from September 2014 up to September 2017 by using the 2-step algorithm modified by Malvehy (2002) and Argenziano (2003). RESULTS: In our study population, an average of 4.04 out of 15 dermoscopic specific criteria for SK was found (for example, multiple milia-like cysts). Additional criteria not included in 2-step algorithm were blue-whitish veil (found in 3 SK; 4.2%), polymorphous vessels (18 SK; 25%), blotch/globules (6 SK; 8.3%), shiny white streaks (3 lesions; 4.2%). The most represented global patterns were reticular (27 SK; 37.5%) and not specific (15 SK; 20.8%). All lesions exhibited peculiar findings of SK, furthermore elements suggestive for melanocytic lesion were found in 79.2% of all lesions. Comparing the literature and our results, we found 3 significant differences: a) the less prevalence of SK specific criteria in our study population; b) the description of findings usually not related to SK, among which blue-whitish veil, polymorphous vessels, blotch/globules and shiny white streaks, and c) 2 patterns not previously defined represented by "not specific pattern" (20.9% of all lesions examined) and "vascular pattern" (12.5% of all lesions examined) were also described. No specific feature or global pattern, statistically significant for dermoscopic diagnosis of difficult-to-diagnose SK have been found. CONCLUSION: Nevertheless the useful findings, no specific feature or global pattern statistically significant for dermoscopic diagnosis of challenging SK have been found. According to the 2-step algorithm and the dermatoscopic scoring system for melanocytic and not melanocytic lesion, SK with one or more dermatoscopic findings typical of melanocytic lesion should be removed surgically to exclude classic melanoma or melanoma mimicking SK.

Laparoscopic sleeve gastrectomy for morbid obesity: role of intraluminal and intraperitoneal postoperative drainage.

BACKGROUND AND AIMS: Bleeding and staple line leak are the most common postoperative complications of LSG. To prevent and/or to promptly identify such complications, conventional peri-operative protocols imply post-operative gastric decompression (NGT) and staple line drain (IAD). Our aim was to evaluate the role of naso-gastric tube (NGT) and intra-abdominal drain (IAD) in preventing and/or facilitating identification and treatment of post-operative complications after sleeve gastrectomy. PATIENTS AND METHODS: A retrospective observational study on two consecutive series has been undertaken to evaluate the real utility of routine placement of NGT and IAD at the end of a LSG to prevent (primary end-point), promptly identify (secondary end-point) and manage (tertiary end-point) bleeding and staple line leakage. Collected outcome data of all consecutive cases, which underwent primary LSG at our Department, were analyzed. The first 100 consecutive patients (group A) received the standard perioperative protocol and the other consecutive 100 (group B) received a fast track protocol (no NGT neither IAD). RESULTS: The two groups were not different in their outcome. Two bleeding occurred in Group A and were conservatively treated. One abscess developed in group B soon after surgery. It was diagnosed by an abdominal CT performed because patients presented fever, leucocitosis and tachycardia. It was successfully treated by percutaneous ultrasound-guided drainage. One fistula occurred in group B after discharge on 30th post-operative day. Fistula was suspected based on fever and tachycardia in absence of any abdominal discomfort and was confirmed by an abdominal CT. The patient was successfully treated in 40 days by endoscopic positioning of a gastric tube-prosthesis and percutaneous ultrasound-guided drainage of abdominal collection. A third patient in group B experienced bleeding suspected due to hemoglobin drop and confirmed by abdominal CT. He also was conservatively treated. CONCLUSIONS: In conclusion, placement of drains does not facilitate detection of leak, abscess, or bleeding after primary LSG.

Prevalence of Polysubstance Abuse and Dual Diagnosis in Patients Admitted to Alcohol Rehabilitation Units for Alcohol-Related Problems in Italy: Changes in 15 Years.

AIMS: Alcohol abuse has long been known as a disease with social and economic burden to society. Given the complex nature of alcohol treatment, it is worthwhile to examine the change over time of patients admitted to residential alcohol abuse rehabilitation units. METHODS: The data were collected from two Italian projects on alcoholics performed in the mid-1990s (ASSALT) and in 2009 (CORRAL), respectively. Categorical variables were considered in terms of absolute and relative frequencies. Comparisons of relative frequencies between groups were assessed by means of Fisher's exact test. Mixed logistic regression models were fitted to CORRAL data to identify the predictors of the probability of being a polysubstance abuser or having a dual diagnosis. The association estimates were reported as adjusted odds ratios and relative 95% confidence intervals. RESULTS: Compared to the mid-1990s, in 2009 patients were older (P= 0.0003), with a higher level of education (P= 0.0204), with fewer comorbidities (liver disease except cirrhosis, P < 0.0001; polyneuropathy, P= 0.0001), more frequently polysubstance abusers (P < 0.0001), affected by dual diagnosis (P < 0.0001). In 2009, the probability of being a polysubstance abuser was higher in younger and in patients with dual psychiatric diagnosis. Female gender and polysubstance abuse were positively associated to the probability of being affected by dual psychiatric diagnosis. CONCLUSIONS: The increment of patients admitted to residential programs for alcohol dependence with polysubstance abuse and/or dual psychiatric diagnoses suggests the need to pay more attention to both psychological/psychiatric interventions and internal medicine/physical rehabilitation. SHORT SUMMARY: The results of this study suggest that further research is needed to identify the best treatment strategy that is safe and effective for the new population of alcoholics.

Safety evaluation of apremilast for the treatment of psoriasis.

INTRODUCTION: Psoriasis (PSo) is a chronic inflammatory skin disease associated with co-morbidities such as hypertension, diabetes, dyslipidemia and metabolic syndrome. It is a typothypical Th1/Th17 disease that affects from 2 to 3% of the world population. Numerous are the drugs that can be used in our clinical practice; the choice of these drugs depends on the characteristics of the patient. Areas covered: Apremilast is the first oral small molecules to receive FDA approval for the treatment of adults with active psoriasis and psoriatic arthritis. It is a small-molecule that specifically inhibits the activity of cyclic AMP phosphodiesterase-4 (PDE4). Several analyses have been performed on data from phase III studies to assess apremilast safety and efficacy on psoriasis and psoriatic arthritis (PsA). Apremilast could also represent a treatment opportunity for those patients unresponsive to both systemic and biological agents or whose treatment was contraindicated. Expert opinion: For its safety profile and easy route of administration, apremilast may offer an oral treatment option for those patients that discontinue treatments because of ineffectiveness, intolerability or ineligibility to the currently available drugs.

The Aquamantys® system as alternative for parenchymal division and hemostasis in liver resection for hepatocellular carcinoma: a preliminary study.

OBJECTIVE: To evaluate the clinical feasibility and safety of a new technique for liver resection using a new saline-coupled bipolar sealing device (Aquamantys®) that has shown high performance in the animal setting. PATIENTS AND METHODS: Twelve Child-Pugh A cirrhotic patients with hepatocellular carcinoma underwent partial hepatectomies using Aquamantys®. Our primary end-point was to observe occurrence of early specific surgical complications as bleeding, biliary leakage and abscess development. Our secondary end-point was to evaluate local recurrence along resection margin after a minimum follow-up of 1 year. RESULTS: One bisegmentectomy, five monosegmentectomies and six atypical resections were performed. Mean resection time was 45 minutes (range, 30-100 min). Mean blood loss was 20 mL (range 5-80 mL). Mean post-operative stay was 6 days (range 5-16 days). All specimens presented negative margins (R0) at pathological examination. No blood transfusion were required both intra-operatively and post-operatively. No mortality was observed within 30-days post-operatively. One fluid collection occurred after  6-7 bisegmentectomy and was successfully treated by ultrasound-guided percutaneous drainage. At 1 year follow-up two patients died: one because of new lesions into the liver and one because of distant metastases and multifocal new liver disease. Ten patient are alive disease free at 1 year follow-up. CONCLUSIONS: Liver resection using Aquamantys® is feasible and safe and allows to achieve almost bloodless parenchymal division with minimal necrosis and negative margins even in atipycal resection. Comparative trials are needed to confirm our preliminary results.

[Alcohol-addiction inpatient: characteristics of patients and rehabilitation program]. / La residenzialità alcologica ospedaliera: caratteristiche dei pazienti e dei percorsi terapeutici/riabilitativi.

AIM: The treatment of alcohol addiction in Italy has had a progressive evolution of therapeutic structures for in-and outpatients. During the last 20 years there had been a crescent presence of short residential treatment facilities (1-6 months) characterized by a high level of medical and psychotherapeutic intervention. About two years ago 12 of them jointed together in an association called CORRAL (COordinamento of Residenzialità Riabilitive Alcologiche). The aim of this study was to describe the socio-demographic medical and other characteristics of the patients coming for this type of treatment and to describe the characteristics of the residential treatment itself including referring and aftercare. METHODS: Two thousand sixty-one hospitalized patients of the 12 rehabilitative alcohol units were examined by using a questionnaire and collecting various sociodemographic variables and clinical diagnosis of the patients. Even it was asked who had referred the patients, the characteristics of the residential treatment and of the planned aftercare. RESULTS: The present residential facilities are mainly distributed in the North of Italy. The typical patient is male, with a high school instruction and with a comorbidity regarding psychiatric and liver disorders. The majority of the patients were referred by the public ambulatory services for addictions (SerT/SerD). The characteristics of the residential treatment were medical, pharmacological and psychotherapeutic interventions with a high intensity and the presence of a general-purpose staff. CONCLUSIONS: This study outlined a model of residential rehabilitation of alcohol disorders characterized by short duration and a complex, intense therapeutic intervention mainly addressed to patients with a severe clinical condition and a low level of social problems. Further research should be useful to understand better which sort of patient characteristics obtain a better clinical result and for that even economically a major effectiveness from this type of residential treatment.

Role of Th17 in the pathogenesis of cutaneous inflammatory diseases.

Th17 cells are a new T-cell subtype characterized by the capability of producing IL-17. They are reported to be involved in a wide range of cutaneous immune-mediated conditions and, particularly in this review, we sought to elucidate the Th17 role in the pathogenesis of some common inflammatory diseases including psoriasis, allergic contact dermatitis and atopic dermatitis.

New insights into the pathogenesis of cutaneous autoimmune disorders.

T helper 17 (Th17) cells are characterized by the secretion of IL-17, a proinflammatory cytokine. They represent a newly described T helper subpopulation that is distinct from Th1 and Th2 lineages. Because of their pleiotropic activity on fibroblasts, keratinocytes, endothelial cells, neutrophils and memory T cells, Th17 cells are thought to be crucial in mediating tissue inflammation and autoimmunity. Autoimmune diseases were classically considered as Th1-mediated disorders such as rheumatoid arthritis or mixed Th1/Th2 diseases such as inflammatory bowel diseases, systemic lupus erythematosus, bullous diseases, but new evidence suggests the deep involvement of Th17 cells in their pathogenesis that, potentially, may address a selective therapeutic approach targeting the IL23/Th17 pathway. This review summarizes the current knowledge of the pathogenic contribution of Th17 cells in select cutaneous autoimmune disorders, including lupus erythematosus, scleroderma, dermatomyositis, bullous pemphigoid and pemphigus vulgaris.

Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience.

Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were undergoing peripheral haematopoietic progenitor cell collection with apheresis (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most frequent short-term adverse event (71.2%). Other commonly observed short-term symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%) and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular disorders or cardiac disease occurred. Long-term follow-up included monitoring of adverse events, neoplastic disease or other pathologies. Transit ischaemic attack occurred in one donor (39 months post-donation). One autoimmune event was reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing spondylitis); one donor with a history of chronic obstructive pulmonary disease developed secondary polyglobulia (50 months post-rhG-CSF). One donor was diagnosed with lung cancer at 19 months post-donation. No haematological disease was observed. In conclusion, the short-term safety appears to be verified, whereas, although the study identified no increased risks of malignancy among HDs who received rhG-CSF, long-term safety requires more complete data sets, especially a longer follow-up and a larger number of HDs.

Harvesting peripheral blood progenitor cells from healthy donors with a short course of recombinant human granulocyte-colony-stimulating factor.

A short-course administration of non-glycosylated granulocyte-colony-stimulating factor (G-CSF) was investigated in 68 healthy donors (HDs) in order to collect > or = 4 x 10(6) CD34+ cells per kilogram of recipient's body weight. G-CSF was given at 10 microg/kg per day administered in two divided doses for 3 days. Leukapheresis was scheduled on day 4, 12 h after the last dose of G-CSF. A median of 35.6 circulating CD34+ cells microL(-1) (range, 3.1-185) was found on the day of leukapheresis. This allowed a median collection of CD34+ cells of 4.2 x 10(6) per kilogram of recipient's weight (range, 1.0-17.4). One single procedure was sufficient to reach the target level of CD34+ cells in 36 (53%) of 68 donors; significant correlations were found between the number of CD34+ cells collected on day 4 and the patient's sex, body-weight and volume of blood processed. A retrospective analysis was made with a historical group of HDs collected on day 5. The day 5 schedule allowed a more consistent achievement of the target cell dose with one leukapheresis (P = 0.005) and resulted in the initial collection of a significantly larger number of CD34+ cells (P = 0.006).

Inguino-crural hernias: preoperative diagnosis and post-operative follow-up by high-resolution ultrasonography. A personal experience.

BACKGROUND: Hernia is an important pathology with an incidence of 5% in world population. The more affect region is the inguino-femoral. Normally the diagnosis was based on the clinical exam. A short time ago the high resolution ultrasonographic study was introduced. The purpose of our study was to value the sensitivity of US-HR in the preoperative diagnosis, in the postoperative follow-up and to compare the results to clinical exam. METHODS: 140 patients affect by inguino-femoral hernia underwent this study, 112 inguinal hernias, 28 femoral, 8 pediatric patients. 106 patients underwent repair through the prosthesis, in 34 Halstad-Postempsky's technique was carried out. Ultrasonography studied: a) inguino-femoral region, cord and scrotum (the study was effected in basal condition and through Valsalva's manoeuver, decubitus changes); b) hernia content (omenutm, bowel); c) hernial orifice and of hernial content's transit (direct or indirect); d) the relation with the inguinal ligament; e) the vascularization (power-doppler) and the pathological situation (presence or absence of liquid in the sac, parietal thickness, presence/absence of peristalsis), in case of hernia complication; f) the presence/absence of simultaneous pathologies (hydrocele, varicocele, cord's cyst). The postoperative study was effected after 7 days, 1-6-12 months we have observed: a) haematomas and seromes (under the skin, under the aponeurosis, scrotal); b) prosthesis displacement; c) prosthesis infection; d) prosthesis reject; e) recurrence (importance, site); f) we have carried out the treatment of the complications (echoguided drainage of serous and hematic collection). RESULTS: The sensitivity of US-HR in the diagnosis of hernia was 87.5%. The clinical exam arrived at an average of 72%, the comparison was favourable to US-HR (15.5%). The sensitivity in the diagnosis of complication arrived at an average of 85.5% for US-HR, and of 36% for clinical exam; the gap between the two techniques was elevated (49.5%). CONCLUSIONS: The US-HR showed an important accuracy and sensitivity thus to cover today an important role, after the clinical exam, in the preoperative diagnosis and in the postoperative follow-up of the inguino-femoral hernias.

[Palliative treatment of neoplasms of the bilio-pancreatic area. Surgical diversion treatment versus endoscopic-percutaneous approach]. / Trattamento palliativo delle neoplasie del distretto bilio-pancreatico. Terapia derivativa chirurgica versus approccio endoscopico-percutaneo.

Bilio-pancreatic (BPD) tumours are pathologies with an overall resectability rate of 20-25%, with a high percentage of patients directed towards palliative treatment (70-90%). One hundred and twenty-eight patients underwent palliative treatment for BPD tumours. The M:F ratio was 1:1.5 and the mean age 61 years. The tumours were topographically divided into: 84 (63%) localised in the pancreatic head region; 34 (25%) biliary duct tumours and 6 arising in the ampulla of Vater. 42 patients (30%) underwent palliative surgical treatment (group 1) and 86 (70%) received non-surgical treatment (endoscopic percutaneous) (group 2). We also performed 6 gastrointestinal by-passes (GEA). The early morbidity rate was 36% in the first group and 12.8% in the second. The incidence of late morbidity in the first group was nil, with a mean survival of 10 months. Mortality was nil in both groups. Surgical by-pass is advisable in the presence of patients with a longer life expectancy and in good clinical condition but presents a high rate of early morbidity and a low percentage of late complications. The authors conclude that validity of the methods is similar. They believe that, in selected cases, surgical treatment remains the therapy of choice for BPD tumours.

[Sensitivity and specificity of transrectal ultrasonography in the preoperative staging and postoperative follow-up in rectal neoplasms. Experience with 100 clinical cases]. / Sensibilità e specificità dell'ultrasonografia trans-rettale nello staging preoperatorio e nel follow-up post-chirurgico delle neoplasie del retto. Esperienza su 100 casi clinici.

UNLABELLED: Preoperative staging plays an important role in the surgical treatment of rectal cancer. The most sensitive imaging techniques currently available are CT, MRI and transanal ultrasound (TAUS). The aim of the study was to evaluate the sensitivity and specificity of TAUS in the preoperative staging and postoperative follow-up of rectal cancer. METHODS: From January 1992 to May 1999, TAUS was used to study 100 patients with rectal cancer. RESULTS: Patients were staged according to the Astler-Coller classification: 1) A: 8 patients; 2) B1: 16 patients; 3) B2: 22 patients; C1: 30 patients; C2: 24 patients. The sensitivity and specificity of TAUS in the preoperative staging of these tumors were 96% for the T parameter, and 100% for the N parameter. The N but not the T parameter results are in line with the values reported in the international literature. CONCLUSION: Transanal ultrasound, in our personal experience, has proved to be a very accurate imaging technique in the preoperative staging and postoperative follow-up of rectal cancer.