Effectiveness of cyclosporine A in patients with moderate to severe plaque psoriasis in a real-life clinical setting in Italy: the TRANSITION study.

BACKGROUND: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. RESULTS: A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). CONCLUSION: Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA.

Secukinumab treatment leads to normalization of quality of life and disease symptoms in psoriasis patients with or without prior systemic psoriasis therapy: the PROSE study results.

INTRODUCTION: Psoriatic disease is associated with considerable impairment of quality of life (QoL). The PROSE study (NCT02752776) investigated the impact of secukinumab treatment on patient-reported outcomes (PRO) in patients with moderate to severe psoriasis stratified by their treatment history. METHODS: PROSE was a prospective, non-randomised, multicentre study. Patients were categorized at baseline according to treatment history as naïve [naïve to any systemic therapy (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic (CS) therapy (N = 673)] and biologics [previously exposed to ≥1 biologic therapy (N = 324)]. QoL PROs, efficacy and safety of secukinumab 300 mg were assessed for a period of 52 weeks. RESULTS: The primary objective was met with 70.8% patients achieving a Dermatology Life Quality Index (DLQI) 0/1 response at Week 16 (naϊve, 74.7%; CS, 71.3%; biologic, 61.7%), with effects sustained up to Week 52. Mean Family DLQI (FDLQI) score decreased from 11.5 at baseline (naϊve, 11.3; CS, 11.4; biologic, 12.1) to 2.5 at Week 16 (naϊve, 2.5; CS, 2.3; biologic: 3.5). Substantial improvements in EuroQoL 5-Dimension Health Questionnaire, Numeric Rating Scale for pain, itching and scaling, Health Assessment Questionnaire-Disability Index, Treatment Satisfaction Questionnaire for Medication, and Patient Benefit Index were also observed at Week 16. The QoL gains were associated with substantial improvements in Psoriasis Area and Severity Index and Investigator Global Assessment mod 2011 0/1 response. No meaningful difference was observed in the efficacy or QoL improvements across patient subpopulations. All QoL and efficacy parameter improvements were sustained up to Week 52. Secukinumab treatment was well-tolerated, and no new safety signals were observed. CONCLUSION: Secukinumab treatment resulted in complete normalization of QoL in a substantial proportion of psoriasis patients, and their families, regardless of their prior treatment history.

An unusual presence of primary retention of permanent teeth in subject with hyperthyroidism.

To date neither the eruption mechanism nor the factors controlling eruption have been completely understood. Primary retention of permanent teeth is an isolated condition associated with a localized failure of eruption with no other identifiable local or systemic involvement. Multiple primary retention may be related to lack of eruptive force, rotation of tooth buds, syndromes and metabolic disorders. This article reports an unusual case of primary retention of permanent teeth inclusion in a 21-year-old woman with hyperthyroidism, diagnosed at 14 years of age.

Osteopathic manual therapy versus conventional conservative therapy in the treatment of temporomandibular disorders: a randomized controlled trial.

OBJECTIVE: Temporomandibular disorders (TMD) is a term reflecting chronic, painful, craniofacial conditions usually of unclear etiology with impaired jaw function. The effect of osteopathic manual therapy (OMT) in patients with TMD is largely unknown, and its use in such patients is controversial. Nevertheless, empiric evidence suggests that OMT might be effective in alleviating symptoms. A randomized controlled clinical trial of efficacy was performed to test this hypothesis. METHODS: We performed a randomized, controlled trial that involved adult patients who had TMD. Patients were randomly divided into two groups: an OMT group (25 patients, 12 males and 13 females, age 40.6+/-11.03) and a conventional conservative therapy (CCT) group (25 patients, 10 males and 15 females, age 38.4+/-15.33). At the first visit (T0), at the end of treatment (after six months, T1) and two months after the end of treatment (T2), all patients were subjected to clinical evaluation. Assessments were performed by subjective pain intensity (visual analogue pain scale, VAS), clinical evaluation (Temporomandibular index) and measurements of the range of maximal mouth opening and lateral movement of the head around its axis. RESULTS: Patients in both groups improved during the six months. The OMT group required significantly less medication (non-steroidal medication and muscle relaxants) (P<0.001). CONCLUSIONS: The two therapeutic modalities had similar clinical results in patients with TMD, even if the use of medication was greater in CCT group. Our findings suggest that OMT is a valid option for the treatment of TMD.

Modeling antibiotic resistance to project future rates: quinolone resistance in Escherichia coli.

While the development of resistance to a new antibiotic is expected, the time course and degree of resistance that will develop are uncertain. Some best projections of the future extent of resistance can be highly impactful for activities, such as antimicrobial development, that require significant lead time. We focus on the surge among hospital isolates in fluoroquinolone-resistant Escherichia coli and use data on resistance and consumption to explore and quantify trends in increasing resistance and their relationship to antibiotic use from 2001 to 2007. A mixed-effects logistic regression model produced a good fit to the observed resistance rates during this period in the United States and Europe. The model contained significant effects of time, consumption, and country on developing fluoroquinolone resistance in E. coli. There was a larger projected increase in resistance for high fluoroquinolone-consuming countries projected to 2013: 45% (95% confidence interval [CI]: 38%, 53%) for high consumers vs. 33% (95% CI: 25%, 41%) for low consumers. The model was also used to obtain regional projections of resistance that can be used by local prescribers. In order to better understand and predict trends in antimicrobial resistance, it is vital to implement and expand current surveillance systems.

The natural head position. Different techniques of head positioning in the study of craniocervical posture.

The aim of this paper was to describe the most important definitions of head posture and the most important methodology to get an natural head posture. After a careful analysis of the literature with no limitations of language or time period, 31 papers were selected. Relevant information was also derived from reference lists of the publications retrieved. The key words used in the search were head posture, cranio-cervical posture, cephalometric analysis, natural head position, lateral cephalometric radiographs, cephalostat, self balance position, mirror position. The definitions of natural head position are various. An accurate head posture registration is time consuming and not particularly feasible on a clinical field. Nevertheless it is possible to apply a craniostat to the patient before the execution of the radiograph without modifying the NHP. The execution of radiographs of the craniocervical zone is connected to the correct position of the head. The NHP is a reproducible positions, and can be useful for making comparisons at any time in the case of the same patient or in comparing different patients cephalometrically.

Correlation of the temporomandibular dysfunction classification index with cephalometric indicators of facial structure: a study on adult female subjects.

AIM: The aim of this study was to determine whether associations exist between temporomandibular dysfunction index (TMI) and craniofacial morphology. METHODS: The sample consisted of 30 symptomatic (mean age 28.3+/-6.7; range 24-39 years, TMI 0.48+/-0.21) and 30 asymptomatic women (mean age 27.4+/-9.2; range 22-42 years, TMI 0.1+/-0.05) seeking orthodontic treatment at Department of Dental Sciences ''G. Messina'', University of Palermo, who had routine lateral cephalograms. Symptoms and signs of temporomandibular joint dysfunction (TMD) were assessed by a standardized clinical examination and the TMI (a clinical measure of dysfunction used to evaluate the severity of TMD). Linear and angular cephalometric measurements were taken to evaluate skeletal and dental characteristics of the two groups. Unpaired t test was used to compare the symptomatic subjects with the control subjects. RESULTS: The sella-nasion-supramentale (SNB) angle (P<0.038, indicating mandibular retrognathism relative to cranial base), the lower facial height and the palatal plane-mandibular plane angle (P<0.025 and P<0.037 respectively, indicating hypodivergent facial profile) were significantly smaller in the symptomatic than in the asymptomatic women. The occlusal plane was steeper (P<0.033) and the cranial flexion was higher (P<0.035) in the symptomatic group than in the asymptomatic group. In addition the overjet (P<0.008) and the overbite (P<0.005) were significantly greater in symptomatic group than in the asymptomatic group. CONCLUSION: This study showed a significant correlation between dentofacial characteristics and TMD.

Mandibular advancement devices: indications and predictors of treatment outcome. A review.

Obstructive sleep apnea syndrome (OSAS) is a chronic sleep and respiratory disorder, which causes a partial or total obstruction of the air passage at the upper airway level. Mandibular advancement devices (MADs) have been used in the treatment of snoring, but may be a valid alternative to the continuous nasal positive airway pressure (CPAP) for certain OSAS cases. Therapy by means of MADs arises the interest of the scientific community and now there are many sleep-centres where dentists work as experts in sleep disorders. MADs are instruments of value because they are simple to use, reversible, portable and they generally have a low complication rate. They mechanically increase the oropharyngeal space by advancing the mandible and/or the tongue and reduce pharyngeal collapsibility. More than 60 different MADs are in use, with considerable variations in design. Several studies show that their systematic use produces an evident improvement in the global quality of life as well as in the symptoms of patients with OSAS, especially sleepiness. Even though significant progress has been made in proving the efficacy of MADs for OSAS, the ability to predict the treatment outcome and hence pre-select suitable candidates for this treatment still remains in its early stage. The first aim of this review is to supply to the clinician informations on the cephalometric and polysomnographic parameters that can be used to predict the efficacy of the outcome of MAD therapy in OSAS. Moreover, we examine the cases for which the use of a MAD is indicated.

Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defects.

We evaluated a 11-year-old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work-up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments.

Extracorporeal photopheresis affects interleukin (IL)-10 and IL-12 production by monocytes in patients with chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photopheresis (ECP) has recently been introduced as an alternative treatment for cases of cGVHD refractory to conventional immunosuppressive treatment, but its mechanism of action is not yet clear. OBJECTIVES: To investigate in seven patients with cGVHD the effects of ECP on resistance of monocytes to apoptosis and on monocyte cytokine production. METHODS: We designed an in vitro model that could mimic the potential in vivo effect of reinfusion of peripheral blood mononuclear cells treated by ECP. The model was based on coculture of ECP-treated lymphocytes with untreated monocytes from the same patient. RESULTS: ECP did not accelerate spontaneous apoptosis of monocytes. However, ECP-treated monocytes produced increased amounts of interleukin (IL)-12. In contrast, IL-12 production by monocytes did not increase in cocultures, but IL-10 production was upregulated. CONCLUSIONS: These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through upregulation of IL-10, which is an immunosuppressive cytokine.

Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease.

Recent studies suggest that extracorporeal photochemotherapy (ECP) may be beneficial in patients with steroid-refractory chronic graft-versus-host disease (cGvHD). However, it is not yet clear whether certain conditions, such as age, mode of onset of cGvHD etc., influence clinical response and whether certain affected organs are more sensitive to ECP than others. We analysed the main clinical and laboratory parameters related to evolution of the disease in 32 steroid-refractory cGvHD patients, to identify any useful response predictors to ECP. ECP affected the course of the disease positively in 78% (25/32) of our cases.

ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family.

Chronic graft-versus-host disease (cGVHD) is a severe and frequent complication of allogenic bone marrow transplantation which is often treated with extracorporeal photochemotherapy (ECP) with a positive clinical outcome in patients resistant to conventional protocols. The mechanism of action of ECP has not been fully elucidated, although several authors have reported that it is able to induce apoptosis. Using samples obtained from ten cGVHD patients, we sought to determine whether lymphocytes treated with ECP underwent apoptosis and, above all, the mechanisms involved. Lymphocytes at four stages were isolated: immediately before ECP, from the last buffy coat collected, after UV irradiation prior to reinfusion, and the day after ECP. When cultured for 48 h, lymphocytes treated with ECP underwent accelerated apoptosis (tested as annexin V binding cells and as intracellular histone-associated DNA fragments) in comparison with lymphocytes from the other samples. This enhanced programmed cell death could not be prevented by IL-2. Immediately after isolation, there was no difference in Bcl-2 or bax expression among the four different samples, or in Fas and FasL mRNA. However, when cultured, lymphocytes treated with ECP showed a rapid downregulation of Bcl-2, an upregulation of bax with an increased bax/Bcl-2 ratio, a decrease in bcl-2 mRNA and an increase in Fas. No changes were detectable in lymphocytes from the other samples. IL-2 and TNF-alpha production was not significantly different among lymphocytes from the four samples. In conclusion, in patients affected by cGVHD, ECP induced apoptosis of lymphocytes with the involvement of both the Fas/FasL system and the Bcl-2 protein family.

An unusual case of tinea capitis due to Trichophyton soudanense.

A case of tinea capitis due to Trichophyton soudanense observed in a 4-year-old African girl is described. The infection manifested with diffuse pustular lesions of the scalp. Diagnosis was based on culture. Genome study by single primer PCR fingerprinting was also performed. A younger sister, aged 10 months, was the healthy carrier of the mycete.

Digital dermoscopy analysis of atypical pigmented skin lesions: a stepwise logistic discriminant analysis approach.

BACKGROUND: Digital microscopy is a non-invasive diagnostic technique enabling determination of characteristics that cannot be appreciated by direct observation. If correctly applied, this technique can be useful for the diagnosis of pigmented skin lesions. PURPOSE: To evaluate the utility of digital microscopy for analysing atypical benign and malignant pigmented skin lesions exploiting digital numerical filtering and automatic measurements. METHODS: Forty-eight parameters were identified as possible discriminating variables, and were grouped in four categories: geometries, colours, textures, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. RESULTS: The high quality of the digital image made it possible to observe diagnostic signs in pigmented skin lesion images, acquired by the present technique, in great detail. Specially designed filtering enhanced certain diagnostic patterns. Stepwise discriminant analysis selected only 10 variables (the means of these variables were higher in melanomas than in nevi). CONCLUSIONS: The combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing atypical nevi and early melanoma.

Aerosolized antibiotics in mechanically ventilated patients: delivery and response.

OBJECTIVES: To determine whether aerosolized antibiotics can be delivered efficiently to the lower respiratory tract in mechanically ventilated patients and to define possible clinical responses to these agents. DESIGN: Prospective serial study with cases as their own control. SETTING: A 10-bed respiratory care unit for patients with chronic respiratory failure in a tertiary university hospital. PATIENTS: Ventilator dependent patients who are otherwise medically stable. All subjects had a tracheostomy in place, were colonized with gram-negative organisms, and produced purulent secretions which could be sampled daily. INTERVENTIONS: Six patients received nine courses of nebulized therapy, which consisted of treatments every 8 hrs of gentamicin (80 mg) or amikacin (400 mg) for 14 to 21 days. MEASUREMENTS AND MAIN RESULTS: Doses to the lung were measured using radiolabeled aerosols and antibiotic concentrations in sputum. The response was assessed by a) changes in the volume of respiratory secretions; b) effect on bacterial cultures; and c) changes in the inflammatory cells and mediators of inflammation of the respiratory secretions (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha], soluble intercellular adhesion molecule-1 [sICAM-1], and human leukocyte elastase). On average, patients inhaled 35.4 +/- 5.08% (SD) of the initial drug placed in the nebulizer (neb-charge). Of this neb-charge, 9.50 +/- 2.78% was found on the respirator tubing and tracheostomy tube and 21.9 +/- 7.15% was actually deposited in the lungs. The remainder of the neb-charge was sequestered in the nebulizer or exhaled. Trough sputum concentrations averaged 4.3 +/- 3.2 microg/mL/mg neb-charge (range 234 to 520 microg/mL) and increased to 16.6 +/- 8.1 microg/mL/mg neb-charge (range 1005 to 5839 microg/mL) immediately after therapy (p = .011). Serum concentrations were undetectable in most determinations except for a single patient who was in renal failure (8.7 microg/mL amikacin). Treatment caused a significant reduction in the volume of secretions (p = .002). Weekly cultures revealed eradication of Pseudomonas species, Serratia marcescens, and Enterobacter aerogenes in most of the trials. Before antibiotic treatment, concentrations of IL-1beta were higher than those reported in acute respiratory distress syndrome. Throughout the duration of the study, IL-1beta correlated significantly with the absolute number of macrophages, neutrophils, and lymphocytes, respectively (r2 = .55, p = .002; r2 = .50, p < .0004, r2 = .36, p = .005). TNF-alpha concentrations correlated with lymphocytes and neutrophils, respectively (r2 =.27, p = .013, r2 = .21, p = .033). sICAM-1 concentrations increased two-fold (p < .001) during treatment and then returned to baseline. The volume of secretions was related to neutrophil and IL-1beta concentrations, respectively (r2 = .25, p = .008, r2= .35, p = .006). CONCLUSIONS: Nebulizer delivery of aerosolized aminoglycosides is efficient and predictable. In our clinical model, aerosolized antibiotics can make a significant impact on respiratory secretions. Their efficacy in treatment of critically ill patients remains to be determined.

Utility of technetium-99m-DTPA in determining regional ventilation.

UNLABELLED: The goal of this study was to determine the usefulness of radiolabeled aerosols in the assessment of regional ventilation in tracheotomized patients maintained on mechanical ventilation. METHODS: Three commercially available radioaerosol nebulizer kits were studied on the bench to determine nebulizer efficiency and particle distribution of 99mTc-DTPA aerosols. We studied ventilated tracheotomized human subjects with a gamma camera and simultaneously measured regional ventilation with 81mKr gas and 99mTc-DTPA aerosol. Images were compared by analysis of radioactivity distributions in computer-generated regions of interest. RESULTS: The UltraVent nebulizing system produced the smallest particles with a mass median aerodynamic diameter of 0.9 micron compared to the AeroTech I and Venti-Scan II systems, which both produced aerosols of 1.3 microns. Despite relatively small particle sizes, 99mTc-DTPA deposition images with the UltraVent nebulizer did not accurately represent regional ventilation as measured by 81mKr equilibrium. Visual inspection of images revealed significant amounts of particle deposition in the region of the trachea which was diminished but not eliminated following replacement of the tracheotomy tube inner cannula. Based on regional analysis, correlation between radioactivity distributions of both isotopes was poor (r = 0.262, p = 0.162) with segmental analysis suggesting that the upper and middle lung regions were significantly affected by residual tracheal activity. CONCLUSION: The lungs of patients maintained on mechanical ventilation can be imaged after the inhalation of 99mTc-DTPA from commercially available delivery kits, but the correlation between aerosol deposition and regional ventilation is poor. Better definition of ventilated lung segments is obtained when using a gas such as 81mKr because tracheal activity with the radiolabeled gas is minimized.