Orthodontic Approach to Hemifacial Microsomia

Aim and objective: To present a growing patient with unilateral mandibular hypoplasia and microtia involved in the first and second branchial arch syndrome (FSBAS) treated with functional appliance. Background: The FSBAS comprises several developmental facial hypoplasia in ear and maxillofacial bones, resulting in hemifacial microsomia. Treatment for hemifacial microsomia varies greatly depending on the grade of mandibular deformities. Functional appliance treatment during growth period is available for mild to moderate mandibular deformities. However, there are few reports of hemifacial microsomia treated with functional appliance. Case description: The patient, an 8-year-and-5-month-old girl, had a chief complaint of mandibular deviation. She had been diagnosed with the FSBAS at birth. Her facial profile was straight and panoramic radiograph indicated that the mandibular ramal height of the affected side was about 60.4% compared to the unaffected side. The occlusal cant was 6°, and the right maxilla and mandible showed severe growth deficiency. At the age of 10 years, functional appliance with expander was used; for 2 years 6 months, the maxillomandibular growth was controlled and from panoramic radiograph, the ramus height of the affected side was increased to 65.0% compared to the unaffected left mandibular ramus. At the age of 12 years and 8 months, multibracket treatment was initiated. After 32 months of active treatment, proper occlusion with functional Class I canine and molar relationships was obtained, although facial asymmetry associated with the difference of ramus heights still existed. The resulting occlusion was stable during 1.5-year retention period. Conclusion: Our results indicated the importance of orthopedic treatment during growth period in the patient with hemifacial macrosomia involving the FSBAS. Clinical significance: This report proposes an efficacy of conventional orthodontic treatment for growing patients with hemifacial macrosomia involved in the FSBAS

A treatment case of Sotos syndrome

Sotos syndrome is a genetic disorder characterized by overgrowth in childhood, specific facial manifestations, advanced bone age, and mental retardation. Although only one case report of Sotos syndrome treated with surgical orthodontics has thus far been published, there have also been a few detailed reports of long-term observation of Sotos syndrome through total orthodontic treatment. This article aimed to present the case of a growing patient with skeletal mandibular protrusion and unilateral posterior crossbite as present in Sotos syndrome treated with a non-surgical orthodontic technique. A 10-year-old boy was diagnosed with skeletal mandibular protrusion and posterior crossbite associated with Sotos syndrome. After maxillary lateral expansion, the skeletal Class III relationship with an anterior crossbite improved owing to mandibular clockwise rotation, while the facemask had a marginal effect. At the completion of growth at 16 years, he had a skeletal Class I relationship, and thus, conventional orthodontic treatment with preadjusted edgewise appliances was initiated. After 41 months of multibracket treatment, acceptable occlusion with a functional Class I relationship was obtained. At 12 months postretention, no or few changes in occlusion and facial features were observed. Our results demonstrate that considering the maxillofacial vertical growth during peripubertal period associated with Sotos syndrome, much attention should be paid to the early orthopedic treatment with the facemask and/or chin cap

Cord Blood Transplantation from Unrelated Donors for Children with Acute Lymphoblastic Leukemia in Japan: The Impact of Methotrexate on Clinical Outcomes

Cord blood transplantation (CBT) from an unrelated donor is recognized as one of the major treatment modalities in allogeneic stem cell transplantation (SCT) for children with hematologic malignancies. We analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified the risk factors for the transplant outcomes. From 1997 to 2006, 332 children with ALL underwent CBT from unrelated donors, 270 of which had no prior transplant. Their disease statuses at transplant were first complete remission (CR) (n = 120), second CR (n = 71), and more advanced stages (n = 75). As preconditioning for SCT, total body irradiation (TBI) was given to 194 patients and, for the prophylaxis of graft-versus-host disease (GVHD), methotrexate (MTX) was given to 159 patients. The cumulative incidents of neutrophil and platelet recovery (>20 K) were 88.5% and 78.4%, respectively. The incidents of grade II-IV, III-IV acute GVHD (aGVHD), and chronic GVHD (cGVHD) were 45.6%, 20.4%, and 19.2%, respectively, and treatment-related mortality was 22.6%. The 5-year event-free survival (EFS) and overall survival (OS) at CR1, CR2, and advanced status were 47.4%, 45.5%, 15.0%, and 63.7%, 59.7%, and 20.7%, respectively. Multivariate analysis revealed that MTX with calcineurin inhibitor (CNI) was associated with decreased incidence of grade II-IV GVHD (CNI alone: hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.06-2.83, P = .027; CNI + prednisolone (PSL), HR = 1.61, 95% CI = 1.03-2.50, P = .036), III-IV aGVHD (CNI alone: HR = 3.02, 95% CI = 1.55-5.91, P = 0.001; CNI + PSL, HR = 1.89, 95% CI = 0.93-3.83, P = .078), or cGVHD (CNI alone: HR = 1.78, 95% CI = 0.83-3.82, P = .143; CNI + PSL, HR = 2.44, 95% CI = 1.24-4.82, P = .01), compared with CNI alone or CNI + PSL. At an advanced stage of disease, GVHD prophylaxis with MTX + CNI is associated with improved OS compared with CNI alone (CNI alone: HR = 3.20, 95% CI = 1.43-7.15, P = .005; CNI + PSL, HR = 1.47, CI = 0.67-3.20, P = .332). Our retrospective study showed that CBT for children with ALL is feasible and GVHD prophylaxis with MTX + CNI is associated with significant favorable outcomes in prevention of aGVHD and cGVHD as well as survival advantage in advanced cases

Refractory Cryptococcus neoformans Meningoencephalitis in an Immunocompetent Patient: Paradoxical Antifungal Therapy-Induced Clinical Deterioration Related to an Immune Response to Cryptococcal Organisms

We present a case of refractory Cryptococcus neoformans meningoencephalitis in an immunocompetent woman. Her clinical symptoms did not improve with 6 months of antifungal therapy, and MRI abnormalities, indicating severe meningeal and cerebral inflammation, persisted despite a decreasing cryptococcal antigen titer. The patient continued to deteriorate despite antifungal therapy, and her condition clearly improved following treatment with adjunctive corticosteroid. We postulate that the paradoxical antifungal therapy-related clinical deterioration was due to an immune response to cryptococcal organisms, which responded to corticosteroids. These observations provide rationale for a further evaluation of corticosteroids in the management of select cases of C. neoformans central nervous system infection

Ceramide profiling of stratum corneum in Sjögren–Larsson syndrome

Background: Sjogren-Larsson syndrome (SLS) is a neurocutaneous disorder whose causative gene is the fatty aldehyde dehydrogenase ALDH3A2 and of which ichthyosis is the major skin symptom. The stratum corneum contains a variety of ceramides, among which omega-O-acylceramides (acylceramides) and protein -bound ceramides are essential for skin permeability barrier formation.Objectives: To determine the ceramide classes/species responsible for SLS pathogenesis and the enzymes that are impaired in SLS. Methods: Genomic DNA was collected from peripheral blood samples from an SLS patient and her parents, and whole-genome sequencing and Sanger sequencing were performed. Lipids were extracted from stratum corneum samples from the SLS patient and healthy volunteers and subjected to ceramide profiling via liquid chromatography coupled with tandem mass spectrometry.Results: A duplication (c.55_130dup) and a missense mutation (p.Lys447Glu) were found in the patient's ALDH3A2 gene. The patient had reduced levels of all acylceramide classes, with total acylceramide levels at 25 % of healthy controls. Reductions were also observed for several nonacylated ceramides: ceramides with phytosphingosine or 6-hydroxysphingosine in the long-chain base moiety were reduced to 24 % and 41 % of control levels, respectively, and ceramides with an alpha-hydroxy fatty acid as the fatty acid moiety were re-duced to 29 %. The fatty acid moiety was shortened in many nonacylated ceramide classes.Conclusion: These results suggest that reduced acylceramide levels are a primary cause of the ichthyosis symptoms of SLS, but reductions in other ceramide classes may also be involved

Responses of perivascular macrophages to circulating lipopolysaccharides in the subfornical organ with special reference to endotoxin tolerance

Abstract Background Circulating endotoxins including lipopolysaccharides (LPS) cause brain responses such as fever and decrease of food and water intake, while pre-injection of endotoxins attenuates these responses. This phenomenon is called endotoxin tolerance, but the mechanisms underlying it remain unclear. The subfornical organ (SFO) rapidly produces proinflammatory cytokines including interleukin-1β (IL-1β) in response to peripherally injected LPS, and repeated LPS injection attenuates IL-1β production in the SFO, indicating that the SFO is involved in endotoxin tolerance. The purpose of this study is to investigate features of the IL-1β source cells in the SFO of LPS-non-tolerant and LPS-tolerant mice. Methods We first established the endotoxin-tolerant mouse model by injecting LPS into adult male mice (C57BL/6J). Immunohistochemistry was performed to characterize IL-1β-expressing cells, which were perivascular macrophages in the SFO. We depleted perivascular macrophages using clodronate liposomes to confirm the contribution of IL-1β production. To assess the effect of LPS pre-injection on perivascular macrophages, we transferred bone marrow-derived cells obtained from male mice (C57BL/6-Tg (CAG-EGFP)) to male recipient mice (C57BL/6N). Finally, we examined the effect of a second LPS injection on IL-1β expression in the SFO perivascular macrophages. Results We report that perivascular macrophages but not parenchymal microglia rapidly produced the proinflammatory cytokine IL-1β in response to LPS. We found that peripherally injected LPS localized in the SFO perivascular space. Depletion of macrophages by injection of clodronate liposomes attenuated LPS-induced IL-1β expression in the SFO. When tolerance developed to LPS-induced sickness behavior in mice, the SFO perivascular macrophages ceased producing IL-1β, although bone marrow-derived perivascular macrophages increased in number in the SFO and peripherally injected LPS reached the SFO perivascular space. Conclusions The current data indicate that perivascular macrophages enable the SFO to produce IL-1β in response to circulating LPS and that its hyporesponsiveness may be the cause of endotoxin tolerance

Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis

(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma