Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial.

BACKGROUND: In atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor. OBJECTIVES: To demonstrate the superiority of topical difamilast to vehicle in Japanese paediatric patients with AD. METHODS: This was a phase III randomized, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received difamilast 0·3% (n = 83), difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks. RESULTS: The primary endpoint was the percentage of patients with an IGA score of 0 or 1 with improvement by at least two grades at week 4. The success rates in IGA score at week 4 were 44·6%, 47·1% and 18·1% in the difamilast 0·3%, difamilast 1% and vehicle groups, respectively. Both difamilast groups demonstrated significantly higher success rates in IGA score compared with vehicle at week 4 [difamilast 0·3% (P < 0·001); difamilast 1% (P < 0·001)]. Regarding secondary endpoints, improvements in Eczema Area and Severity Index (EASI; improvement of ≥ 50%, ≥ 75% and ≥ 90% in overall score) at week 4 were significantly higher in patients in the difamilast 0·3% and 1% groups than those in the vehicle group. EASI score in the difamilast 0·3% and 1% groups was significantly reduced compared with that of patients in the vehicle group at week 1. The significant difference between both the difamilast groups and the vehicle groups was maintained from week 1 through to week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported. CONCLUSIONS: Difamilast 0·3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.

Influence of lingual plate fracture pattern on remodelling site during the healing process of sagittal split ramus osteotomy.

The purpose of this study was to investigate whether differences in the pattern of the lingual plate split in sagittal split ramus osteotomy (SSRO) affect the remodelling of the split site. Sixty-one patients with mandibular prognathism (122 sides) underwent SSRO. Computed tomography (CT) was performed at 1 week and 1 year after SSRO. Bone splits were classified according to the lingual split scale (LSS) and the lateral bone cut end (LBCE) by evaluating CT images at 1 week. The remodelling at the split sites was evaluated by superimposing the CT images obtained at 1 week and 1 year. Regarding the LSS pattern, significant differences were observed in the distance between anteroposterior ramus points (P = 0.033) and the ramus area in the axial image (P = 0.011). The LBCE pattern also showed a significant difference in the distance between anteroposterior ramus points (P = 0.043). In conclusion, the differences in the lingual plate split and ramus cut end of the SSRO influence the postoperative remodelling in the anteroposterior region of the split site.

Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study).

BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. PATIENTS AND METHODS: We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. RESULTS: Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). CONCLUSIONS: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

Shift-and-add image processing incorporated with the unsharp masking method.

Shift-and-add (SAA) is a simple image processing procedure. SAA was devised to reconstruct a diffraction-limited image from atmospherically degraded stellar images. Recently SAA has been applied to biological imaging. There are several variants of SAA. Here proposed is an SAA procedure incorporated with unsharp masking (USM). The SAA procedure proposed here encompasses an extended version of USM. The proposed SAA method retains the simplicity and easiness, and the basic features of SAA. The effectiveness of the proposed method is examined by restoring atmospherically degraded solar images. It is shown that the USM SAA reconstructed image exhibits high contrast and reveals fine structures blurred by atmospheric turbulence. It is also shown that the USM SAA performs better with a data frame selection scheme.

A study of 87 mycetoma patients seen at three health facilities in Nouakchott, Mauritania.

BACKGROUND: Mycetoma is a chronic, progressive and destructive inflammatory disease that affects the skin, subcutaneous and other tissues. The objective of this study was to identify all cases of mycetoma diagnosed in three health facilities in Nouakchott, Mauritania during 2016-2018. METHODS: This retrospective hospital-based study was conducted at the Dermatology, Orthopedics, Mycology and Pathology departments of the National Hospital Center of Nouakchott, the Military Hospital of Nouakchott and the National Institute for Research in Public Health of Nouakchott. RESULTS: Eighty-seven patients were included in this study. They comprised 65 male patients (74.71%) and 22 females (25.28%) with a gender ratio of 4:1. The mean age was 41.87 y and ages ranged from 14 to 70 y. The most common age group was 40-45 y (11%). The foot was the most frequently affected site seen in 60 patients (69%), followed by ankle and hand with 6 patients each (7%). In the study, 56 patients (64%) had regional lymphadenopathy. Forty-nine patients (56%) had bone involvement. Thirty-two patients (37%) had medical treatment. Twenty-seven patients (87%) received fluconazole and four patients (13%) had co-trimoxazole treatment. CONCLUSION: The mycetoma patients seen in these three centres were mainly male farmers from rural areas. The lesions were seen mainly in the lower limbs and the majority had bone involvement radiologically.

[Survival in HIV-1 patients receiving antiretroviral therapy in Morocco]. / Survie des patients vivant avec le VIH-1 sous thérapie antirétrovirale au Maroc.

BACKGROUND: The purpose was to study factors associated with the survival of HIV-1 patients receiving antiretroviral therapy in Morocco. MATERIAL AND METHOD: This was a retrospective study of a cohort of 182 HIV-1 patients receiving antiretroviral therapy in the department of dermatology venereology at the Military Instruction Hospital Mohamed V in Rabat during the period from 1 January 2006 to 1 January 2017. Death of any cause during the study period was considered to be the result of HIV infection. The log-rank test was used to compare the survival curves based on determinants. The Cox regression model analyzed the determinants of survival since induction of antiretroviral therapy. RESULTS: The median follow-up time was 4.7 years (IQR: 1.97-8.18). The mortality rate was 75 deaths per 1000 person-years. Advanced clinical stage CDC C (RR: 2.72; CI 95%: 1.33-5.56) and treatment with indinavir (RR: 1.41; CI 95%: 0.77-2.59) were significantly associated with death. CONCLUSION: Initiation of antiretroviral therapy in the early stage of the disease and use of less toxic molecules are recommended to reduce mortality.

Basophils are recruited to inflamed lungs and exacerbate memory Th2 responses in mice and humans.

BACKGROUND: Although the contribution of basophils as inducers or amplifiers of Th2 responses is still debated, prolonged basophil/CD4 T cell interactions were observed in lungs but not lymph nodes (LNs) of parasite-infected mice. However, the impact of basophils on the function of tissue CD4 effector T cells remains unknown. METHODS: Basophils were purified from the lungs of ovalbumin (OVA)-sensitized and OVA-challenged (OVA-immunized) mice or human peripheral blood for in vivo and in vitro functional studies. Pulmonary basophils were adoptively transferred to OVA-sensitized hosts to assess airway inflammation in bronchoalveolar lavage fluid (BALF) and Th2 responses in lung explants and draining LNs. Basophils were co-cultured with effector T cells or Ag-specific naïve T cells alone or in combination with dendritic cells (DCs); IL-4 production was determined by flow cytometry and ELISA. RESULTS: Basophils accumulated in lungs of OVA-immunized mice. Adoptive transfer of basophils to OVA-sensitized hosts enhanced lung IL-4 and IL-13 release while co-administration of OVA further aggravated airway inflammation and Th2 responses in LNs. Mechanistic in vitro studies revealed that pulmonary basophils interacted with lung CD4 effectors, in the absence of DCs, to increase T cell survival and Th2 cytokine expression at the single cell level but amplified OVA-loaded DC-driven Th2 differentiation. Finally, human basophils augmented in vitro IL-4 expression in effector memory CD4 T cells that include CRTH2(+) cells through IL-4 and TCR-independent pathways. CONCLUSIONS: Basophils may worsen Th2 inflammatory disorders through direct interactions with pathogenic CD4 T cells as well as by enhancing DC-induced Th2 cell development.

Caries risk management: effect on caries incidence in a sample of Lebanese preschool children.

OBJECTIVES: This clinical prospective study describes how caries preventive measures applied according to caries risk affect new caries incidence in a group of preschoolers, as compared to a group where standardized caries prevention is applied, regardless of risk. METHOD AND MATERIALS: Healthy children, aged four years or less, recruited at the Faculté de Médecine Dentaire, Université Saint-Joseph, Beirut, Lebanon were assigned, after parental consent, to an experimental or a control group. Caries risk was determined based on a parental questionnaire, salivary levels of Steptococcus mutans (Sm) and Lactobacillus (Lb), salivary buffer capacity, plaque levels and carious lesions prevalence, then subjects were classified into four caries risk categories. In the experimental group, preventive measures designed for each risk category were applied periodically, whereas control subjects received only standardized preventive measures at regular intervals. All subjects were reevaluated for Sm, Lb, salivary buffer capacity, plaque and new carious lesions after 24 months. RESULTS: Statistically significant reductions in salivary Sm (p=0.001) and Lb (p=0.003) levels, plaque scores (p=0) and caries incidence (p=0.003) were observed in the experimental group. In the control group, no significant differences were observed between initial and final Sm (p=0.18) and Lb (p=0.109) levels or plaque scores (p=0.255), and caries incidence was not significantly reduced (p=0.584). CONCLUSION: The present study's results suggest that caries preventive measures applied according to caries risk may reduce caries risk factors and new caries incidence in preschool-aged children. These findings deserve further investigation to benefit early childhood caries prevention on a larger scale.

Caries prevalence and caries risk in a sample of Lebanese preschool children.

OBJECTIVES: This study describes early childhood caries prevalence and caries risk in a group of Lebanese preschoolers. METHOD AND MATERIALS: 99 healthy children, aged four years or less, were recruited at the Dental medicine faculty, Saint-Joseph university, Beirut, Lebanon. After parental consent, questionnaires investigated children's dietary and oral hygiene habits and parents' education and health behaviors. Oral examinations, with bite-wing radiographs when necessary, determined decayed-filled surfaces and plaque scores. Salivary testing assessed buffer capacity and streptococcus mutans (Sm) and lactobacillus (Lb) presence. The three tests (questionnaire, oral examination, salivary testing) established a caries risk assessment tool, determining subjects' caries risk scores, classified as low (C0), moderate (C1), high (C2) or very high (C3). RESULTS: 25.3% of subjects were caries-free, 24.2% had 4 carious lesions or less, 28.3%, 5 to 9 lesions and 22.2% over 10 lesions. 11.1% of plaque scores were low to mild, 18.2% moderate, 46.4% high, and 24.3% very high. Salivary buffer capacity was: 29.3% high, 57.6% medium and 13.1% low. High levels of Sm, (66.7%) correlated with plaque presence and proximal caries. High levels of Lb (52.5%) correlated with plaque presence and smooth-surface caries, and correlated significantly with occlusal caries. Regular tooth brushing yielded lower plaque, but not significantly lower caries levels. Systemic fluorides were associated with lower plaque and caries scores. Children of educated parents with regular dental visits and oral hygiene had lower plaque and caries scores. Caries risk distribution was: CO: 16.2%, C1: 29.3%, C2: 15.1% and C3: 39.4%. CONCLUSION: Most subjects had at least one carious lesion (74.7%), and 70.7% showed high to very high plaque scores. Over half the sample presented high or very high caries risk. These findings deserve further investigation of the Lebanese preschoolers' population.

[Erysipelas of the face revealing a mucormycosis]. / Érysipèle de la face révélant une mucormycose.

BACKGROUND: Mucormycosis is an opportunistic fungal infection, typically affecting immunocompromised patients. Rhino-orbital location is the most frequent form with cerebral blood vessels invasion and a fatal outcome. CASE REPORT: An immunocompetent 38-year-old woman, with previous history of primary cutaneous mucormycosis, was admitted for a febrile erythemato-oedematous lesion of the face with well-demarcated edge evoking erysipelas. No cutaneous portal of entry was identified. Oral cavity examination found an ulceronecrotic lesion of the hard palate. Diagnosis of mucormycosis was retained after nasal endoscopy and histological findings. The patient was first treated for erysipelas, then by ascending dose of intravenous amphotericin B. A good outcome was observed despite the occurrence of nephrotoxicity which normalized by alkaline hyperhydratation. Healing was obtained after 1month of effective dose leaving cleft palate sequelae. DISCUSSION: Mucormycosis occurs rarely in immunocompetent, even more if it is a second episode. Affecting the face, it may simulate or be revealed by superficial skin infection. Within that, a meticulous otorhinolaryngeal examination is required when the portal of entry is not obvious.

Study of Pd-Ag dental alloys: examination of effect of casting porosity on fatigue behavior and microstructural analysis.

The goals of this study were to investigate the fatigue limits of two Pd-Ag alloys (Ivoclar Vivadent) with differing mechanical properties and varying proportions of secondary alloying elements, examine the effect of casting porosity on fatigue behavior, and determine the effect of casting size on microstructures and Vickers hardness. The alloys selected were: IPS d.SIGN 59 (59.2Pd-27.9Ag-8.2Sn-2.7In-1.3Zn); and IS 64 (59.9Pd-26.0Ag-7.0Sn-2.8Au-1.8 Ga-1.5In-1.0Pt). Tension test bars, heat-treated to simulate dental porcelain application, were subjected to cyclic loading at 10 Hz, with R-ratio of -1 for amplitudes of compressive and tensile stress. Two replicate specimens were tested at each stress amplitude. Fracture surfaces were examined with a scanning electron microscope (SEM). Sectioned fatigue specimens and additional cast specimens simulating copings for a maxillary central incisor restoration were also examined with the SEM, and Vickers hardness was measured using 1 kg load. Casting porosity was evaluated in sectioned fatigue fracture specimens, using an image analysis program. The fatigue limit (2 × 10(6) loading cycles) of IS 64 was approximately 0.20 of its 0.2% yield strength, while the fatigue limit of d.SIGN 59 was approximately 0.25 of its 0.2% yield strength. These relatively low ratios of fatigue limit to 0.2% yield strength are similar to those found previously for high-palladium dental alloys, and are attributed to their complex microstructures and casting porosity. Complex fatigue fracture surfaces with striations were observed for both alloys. Substantial further decrease in the number of cycles for fatigue failure only occurred when the pore size and volume percentage became excessive. While the heat-treated alloys had equiaxed grains with precipitates, the microstructural homogenization resulting from simulated porcelain firing differed considerably for the coping and fatigue test specimens; the latter specimens had significantly higher values of Vickers hardness.

The immature platelet fraction is a useful marker for predicting the timing of platelet recovery in patients with cancer after chemotherapy and hematopoietic stem cell transplantation.

Prediction of the timing of platelet recovery after chemotherapy and hematopoietic stem cell transplantation (HSCT) allows for optimal platelet transfusion. We assessed the clinical utility of the percentage value of the immature platelet fraction (IPF%) monitored using an XE-2100 automated hematology analyzer to predict the timing of platelet recovery after chemotherapy and HSCT. The IPF% was serially monitored in 31 patients with cancer who received 66 courses of chemotherapy and HSCT. In patients with cancer undergoing chemotherapy and HSCT, a transient increase in IPF% was observed 1-11 days prior to platelet recovery (>30 × 109 /l). In patients undergoing chemotherapy with a peak IPF% >10%, platelet recovery occurred significantly earlier than in those with IPF% peak values ≤10% (median periods were 2 and 5 days; P < 0.05). Platelet recovery appears to occur earlier in patients undergoing HSCT with a peak IPF% >10% than in those with IPF% peak values ≤10% (median periods were 2 and 6 days). Thus, the IPF% peak value is a useful parameter for predicting the timing of platelet recovery after chemotherapy and HSCT and has the potential to facilitate optimal platelet transfusion.

Immature platelet fraction measurement in patients with chronic liver disease: a convenient marker for evaluating cirrhotic change.

Platelet number is often used as an indicator of the severity of liver disease. Although inadequate thrombopoietin production and decreased platelet production have been proposed as major causes of cirrhotic thrombocytopenia, the underlying mechanism has not yet been fully clarified. We examined whether the measurement of the immature platelet fraction (IPF) in thrombocytopenic patients with liver dysfunction is useful as a rapid and noninvasive method for the differential diagnosis of chronic liver diseases. We examined 20 liver cirrhosis patients, 56 patients with chronic hepatitis, 9 patients with fatty liver, and 86 patients without liver disease. The percentage value of IPF (IPF%) was measured using an XE-2100 multiparameter automatic hematology analyzer. Using a receiver operating characteristic curve, we found diagnostic significance of the absolute platelet count and the absolute number of the IPF between cirrhotic patients and noncirrhotic patients, and developed a powerful multivariate discriminant analysis (MDA) function based on the platelet count and the IPF%. The diagnostic accuracy obtained by the MDA function was superior to that obtained by the absolute number of platelets and the IPF. We therefore propose our IPF% measurement for the diagnosis of liver cirrhosis.

Furuncular myiasis: unusual case of African Dermatobia hominis.

Human cutaneous myiasis is a common disease in endemic tropical zones. Increased international travel has produced increases in imported cases. We present an unusual patient with myiasis infestation of the leg caused by Dermatobia hominis, which manifested after returning from the Democratic Republic of Congo. This particular infestation has not been reported in Morocco prior to this case. Furuncular cutaneous miyasis must be considered when travellers exhibit draining nodules. Medical treatment consists of occlusion of the furuncular punctum with vaseline to stimulate extrusion of the larva or surgical debridement under local anesthesia.

Method to reconstruct exoplanetary spectrum.

We present a method for spectroscopic observations of exoplanets. Coronagraphic image of a star-planet system and its objective spectra are observed simultaneously. Stellar image and objective spectrum without coronagraphic suppression are also obtained as reference. By convolution of the coronagraphic image with the reference stellar spectrum, pseudo-objective spectra are synthesized. The difference between the observed and the synthesized pseudospectra reveals the distinctive features of planetary spectrum. We carry out laboratory demonstration of the proposed technique and show that the planetary spectrum is reconstructed.

A case of Evans syndrome combined with systemic lupus erythematosus successfully treated with rituximab.

Evans syndrome is a rare autoimmune disorder with unknown aetiology. Although corticosteroids and/or intravenous immunoglobulin (IVIG) are commonly used in its treatment, no standard strategy has been established. We report here a 44-year-old male with refractory Evans syndrome combined with systemic lupus erythematosus (SLE) who responded well to rituximab. He was admitted to our hospital with severe bleeding caused by worsening of Evans syndrome. Despite treatment with a high-dose corticosteroid and IVIG, his thrombocytopaenia and haemolytic anaemia did not improve. We started rituximab at a dose of 375 mg/m(2) once a week for a total of two doses. There was significant improvement in his thrombocytopaenia and anaemia 1 month after administration of rituximab. Although the total immunoglobulin G (IgG) level did not change, the titres of platelet-associated IgG (PA-IgG) and of an indirect antiglobulin test (IAT) decreased under the treatment with rituximab. It is suggested that rituximab would be a powerful candidate in the treatment of refractory Evans syndrome by depleting abnormal clone-producing autoantibody.

[Pseudo-Kaposi's sarcoma secondary to superficial arteriovenous malformation: Stewart-Bluefarb syndrome]. / Pseudomaladie de Kaposi secondaire à une malformation artérioveineuse superficielle: syndrome de Stewart-Bluefarb.

BACKGROUND: Pseudo-Kaposi's sarcoma or Stewart-Bluefarb subtype acroangiodermatitis is uncommon and is caused by arteriovenous fistula and malformation. We report a new case. CASE REPORT: A 33-year-old man presented with painful red-violet plaque on the dorsum of the toes with angiomatous nodules on the sole. Histological and immunohistochemical studies for CD34 were consistent with Kaposi's sarcoma. Doppler ultrasonography and femoral angiography showed multiple distal arteriovenous shunts. Free-flow embolisation with fragments of Ethibloc gelatin sponge was performed and arteriography, performed immediately afterwards, showed delayed venous drainage. The outcome was good with complete drainage of the angiomatous lesions. DISCUSSION: Pseudo-Kaposi's sarcoma Stewart-Bluefarb subtype begins early in life in male subjects, with unilateral skin lesions. It bears clinical and histological resemblance to Kaposi's sarcoma. Doppler ultrasonography and angiography show arteriovenous fistulas that classically develop at shunts, explaining the role of traumatism and high vascular pressure in the genesis of this disease.

[Cutaneous blastomycosis revealing intravascular B-cell lymphoma: a case in Morocco]. / Blastomycose cutanée révélant un lymphome B intravasculaire: une observation marocaine.

Blastomycosis is a systemic fungal infection caused by a thermally dimorphic fungus, Blastomyces dermatitidis. The incidence in immunocompromised patients has increased in the last two decades. A 55-year-old man consulted for inflammatory nodules on the forearm. Biopsy of one nodules showed a pseudoepitheliomatous hyperplastic epidermis overlaying a dense agranulomatous inflammatory infiltrate containing free-formed ovoid bodies enclosing giant macrophageous cells. These findings were consistent with blastomycosis. After a month of treatment cutaneous lesions regressed partially but the patient's general status continued to deteriorate with the appearance of an edematous-ascitic syndrome and icterus. Laboratory blood testing demonstrated cholestasia and abdominal ultrasound showed hepatosplenomegaly. Needle liver biopsy revealed giant B-cell lymphomatous infiltration of the hepatic ducts. The patient's condition worsened rapidly and he died five months after diagnosis despite four rounds of chemotherapy. Blastomycosis is rare in Morocco. Primary infection is usually a pneumonic process. Isolated cutaneous infection is possible but uncommon. To our knowledge the association of blastomycosis and intravascular lymphoma has not been previously reported. In immunocompromised patients, clinical findings can be alarming and the outcome can be rapidly fatal.

Polarization degree analysis of objective spectrum in polarization differential stellar coronagraph.

It is shown that the degree of polarization analysis is useful to find objective spectra of exoplanets immersed in noisy stellar spectra. We report the laboratory experiment of polarization differential objective spectroscopy with a four-quadrant polarization mask coronagraph, where partially polarized planetary signal is expected to be discerned from unpolarized stellar noise. The detection of the planet signal is impeded by the stellar noise remained after subtracting mutually orthogonally polarized components of light. We distinguish clearly the planetary spectrum by use of the degree of polarization. We also show the refinement of the spectrum of the planet model.