Treatment of generalized infantile myofibromatosis with sorafenib and imatinib: A case report

Infantile myofibromatosis (IM) is characterized by solitary musculoskeletal nodules presenting during infancy but can manifest as multiple lesions with visceral involvement. Multicentric IM with visceral involvement carries a high risk of mortality and there is no consensus on treatment. We present a case of a patient with multicentric IM and pulmonary involvement who progressed on several chemotherapeutic regimens and subsequently had a complete response to sorafenib and later imatinib. This report describes the novel use of sorafenib and imatinib to treat generalized IM and the role of continued tyrosine kinase inhibitor therapy to maintain remission.     

Epidemiology of tick‐borne pathogens in the semi‐arid and the arid agro‐ecological zones of Punjab province,Pakistan

Tick‐borne diseases (TBDs) have a large impact on animal health and the livelihood of livestock owners, particularly in developing countries. Although climatic and ecological conditions in Pakistan may favour the transmission of tick‐borne pathogens (TBPs), only a few systematic studies have been carried out on TBPs and the diseases that they cause in this country. To improve our understanding of the distribution of TBPs, 3,807 ticks were collected from ruminants (n = 369) on 108 livestock farms (semi‐arid zone = 36, arid zone = 72) in Punjab Province. After morphological identification ticks were pooled into 405 pools (Hyalomma anatolicum = 300, Rhipicephalus microplus = 89, Hyalomma dromedarii = 9, Rhipicephalus turanicus = 7) based on their species, locality of collection, and the host. DNA from each pool was screened by a Reverse Line Blot (RLB) hybridization assay for the presence of Anaplasma, Ehrlichia, Rickettsia, Babesia, and Theileria species. DNA from at least one TBP was found in 142 (35.1%) pools. Among the positive pools, 91 (64.1%) had a mixed infection with two or more TBPs, whereas 51 (35.9%) pools were infected with a single TBP. The detected pathogens not only included species that were known to be endemic in Pakistan, such as Theileria annulata (6.7%), Theileria orientalis (3.5%), Anaplasma marginale (5.7%), Anaplasma centrale (2.7%), Anaplasma ovis (1.5%), Babesia bigemina (0.7%), and Babesia bovis (0.2%), but also several TBPs that had not been reported to occur in Pakistan before. This included Ehrlichia minasensis (3.2%), an Anaplasma platys‐like organism (1.2%), Babesia occultans (0.2%), and Rickettsia massiliae (0.2%), as well as two previously uncharacterized species: Ehrlichia sp. Multan (18.0%) and Anaplasma sp. (BL099‐6) (2.22%). The pathogenicity of these novel species remains to be examined. This study shows that a much broader spectrum of TBPs is present in Pakistan than previously thought, including several zoonotic pathogens.     

Impaired virus-specific T cell responses in patients with myeloproliferative neoplasms treated with ruxolitinib

Ruxolitinib is effective in myeloproliferative neoplasms (MPN) but can cause reactivation of silent infections. We aimed at evaluating viral load and T-cell responses to human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in a cohort of 25 MPN patients treated with ruxolitinib. EBV-DNA and HCMV-DNA were quantified monthly using real-time polimerase chain reaction (PCR) on peripheral blood samples, and T-cell subsets were analyzed by flowcytometry. HCMV and EBV-directed T-cell responses were evaluated using the IFN-γ ELISPOT assay. Most patients had CD4+ and/or CD8+ T-cells below the normal range; these reductions were related to the duration of ruxolitinib treatment. In fact, reduced T-lymphocytes' subsets were found in 93% of patients treated for ≥5 years and in 45% of those treated for <5 years (P = .021). The former also had lower median numbers of CD4+ and CD8+ cells. Subclinical reactivation of EBV and HCMV occurred in 76% and 8% of patients. We observed a trend to an inverse relationship between EBV and CMV-specific CD4+ and CD8+ T-cell responses and viral load, and a trend to an inverse correlation with ruxolitinib dose. Therefore, our data suggest that the ruxolitinib treatment may interfere with immunosurveillance against EBV and HCMV.     

Neonatal blue light phototherapy increases café-au-lait macules in preschool children

Neonatal blue light phototherapy (NBLP) is an effective treatment for hyperbilirubinaemia. Concerning the influence on melanocytic nevi, conflicting studies have been published. To assess the role of NBLP according to the incidence of melanocytic nevi in preschool children, a cohort of 104 5- to 6-year-old children were included. The case group consisted of 52 NBLP-exposed children, while the control group (n?=?52) never had NBLP and was matched regarding age, gender, gestational age and skin phototype. Six dizygotic twins were included with one twin having received NBLP, respectively. The following parameters were recorded: nevi count, presence of freckles, café-au-lait macules, skin phototype and previous history of sun exposure. There was no significant association between nevi count and exposure to NBLP (median nevi count 17.0 compared to 18.5 in controls). No significant difference was also found in the dizygotic twin pairs with a median nevi count of 10.0 (with NBLP) compared to 14.5 (without NBLP). However, a significantly higher prevalence of café-au-lait macules was found in children with NBLP (mean count 0.5) than in children without NBLP (mean count 0.2; p?=?0.001). Significant predictors for the number of melanocytic nevi included skin phototype, sun exposure and vacations in the South. Conclusion: In this study, NBLP had no significant influence on the development of melanocytic nevi, but on café-au-lait macules which was a new finding. Differences with comparable studies regarding age, differentiation between nevi and other pigmented lesions as well as dose and type of NBLP need to be taken into account for further investigations.     

Alternative treatments for resin-based composite and amalgam restorations with marginal defects: a 12-month clinical trial

This clinical trial sought to evaluate the effectiveness of alternative treatment for replacing amalgam and resin-based composite restorations with marginal defects. The study recruited 66 patients with 271 restorations. Each restoration was assigned randomly to one of five groups: Sealant, Refurbishing, Repair, Replacement, and Untreated. Two clinicians evaluated the restorations according to USPHS/Ryge criteria at baseline (Kappa 0.74) and one year after the treatment (Kappa 0.81). The scoring of the margins improved (from bravo to alfa) after the experimental treatments. None of the treatments showed significant degradation of the margins during the 12-month observation period.     

Wear performance of substructure ceramics and veneering porcelains

Aim

The aim of this in vitro study was to compare the two-body wear resistance of substructure zirconia and veneering porcelain versus steatite and human enamel antagonists, respectively.

Materials and methods

Two-body wear tests were performed in a chewing simulator with steatite and enamel antagonists (enamel cusps). A pin-on-block design with a vertical load of 50 N for 1.2 × 10⁵ cycles; (f = 1.6 Hz; lateral movement: 1 mm, mouth opening: 2 mm) was used for the wear test. For quantification of the wear resistance, wear tests were performed with standardized steatite spheres. Human enamel was used as a reference. Five zirconia ceramics and four veneering porcelains were investigated. One zirconia ceramic was tested with superficial glaze, which was applied after polishing or sandblasting, respectively. Surface roughness R_a (SP6, Perthen-Feinprüf, G) and wear depth were determined using a 3D-Profilometer (Laserscan 3D, Willytec, G). SEM (Quanta FEG 400, FEI, USA) pictures were used for evaluating wear performance of both, ceramics and antagonists.

Results

No wear was found for zirconia substructures. Veneering porcelain provided wear traces between 186.1 ± 33.2 μm and 232.9 ± 66.9 μm (steatite antagonist) and 90.6 ± 3.5 μm and 123.9 ± 50.7 μm (enamel). Wear of the steatite antagonists varied between 0.812 ± 0.256 mm² and 1.360 ± 0.321 mm² for zirconia and 1.708 ± 0.275 mm² and 2.568 ± 0.827 mm² for porcelain. Enamel generally showed wear, cracks or even fractures at the ridge, regardless whether opposed by zirconia or porcelain/glaze. Enamel was polished, when opposed to zirconia, or plowed, provoked and grinded, when opposed to porcelain/glaze.

Conclusion

The results of the wear test with steatite or enamel antagonists indicated no measurable wear on zirconia surfaces. Porcelain showed higher wear than zirconia, but comparable or lower wear than an enamel reference. Antagonistic wear against zirconia was found to be lower than wear against porcelain.