A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately

Implementasi manajemen sarana dan prasarana dalam meningkatkan mutu pendidikan pada madrasah tsanawiyah negeri (MTSN) Rantauprapat Kabupaten Labuhanbatu

Penelitian ini bertujuan untuk mengetahui perencanaan, pengorganisasian, pelaksanaan, pengawasan manajemen sarana dan prasarana dalam meningkatkan mutu pendidikan pada Madrasah Tsanawiyah Negeri (MTsN) Rantauprapat Kabupaten Labuhanbatu. Penelitian ini dilakukan dengan menggunakan pendekatan kualitatif, Teknik pengumpulan data dalam penelitian ini menggunakan observasi, wawancara dan dokumen. Data yang didapat kemudian dianalisis dengan menggunakan analisis data kualitatif yang terdiri dari: (a).reduksi data, (b).penyajian data, dan (c) penarikan kesimpulan. Temuan penelitian: (1) perencanaan manajemen sarana dan prasarana di Madrasah Tsanawiyah Negeri (MTsN) Rantauprapat Kabupaten Labuhanbatu terlebih dahulu dilakukan analisis kebutuhan riil baik yang menyangkut kebutuhan administrasi maupun pendukung kegiatan proses pembelajaran, seperti ruang kelas, moubilair, dan lain sebagainya. Yang melibatkan: Kepala Madrasah, KTU, bendahara, PKM, dan bahkan utusan dari komite sekolah. (2).Pengorganisasian manajemen sarana dan prasarana pada Madrasah Tsanawiyah Negeri (MTsN) Rantauprapat Kabupaten Labuhanbatu dilakukan berdasarkan rumpun (kelompok) dari setiap jenis sarana itu sendiri, misalnya: bangunan fisik, moubilair, ATK, lingkungan, dan lain sebagainya yang kesemuanya itu di arsiparis berdasarkan ketentuan yang berlaku. (3) Pelaksanaan manajemen sarana dan prasarana di Madrasah Tsanawiyah Negeri (MTsN) Rantauprapat Kabupaten Labuhanbatu berjalan baik dan lancar. Pelaksanaannya masing-masing pihak bekerja sesuai job/pekerjaan masing-masing dan sesuai kepentingannya, sehingga sistem kerja tidak ada tumpang tindih antara satu sama lain. Dan pertanggung jawabannya langsung kepada Kepala madrasah MTsN Rantauprapat walaupun tetap di bawah koordinasi PKM sarana dan prasarana. (4).Pengawasan manajemen sarana dan prasarana pada Madrasah Tsanawiyah Negeri (MTsN) Rantauprapat Kabupaten Labuhanbatu dilakukan dengan cara: a) Pengawasan rutin setiap harinya yang dilakukan oleh PKM sarana jika menyangkut persoalan sarana pendukung pembelajaran, sedangkan yang menyangkut administrasi dilakukan oleh KTU. b) Secara berkala yakni setiap 6 (enam) bulan sekali diadakan rapat evaluasi tentang keadaan sarana dan prasarana. (5) Terkait dengan evaluasi diketahui bahwa sarana dan prasarana di Madrasah Tsanawiyah Negeri (MTsN) Rantauprapat Kabupaten Labuhanbatu sudah terpenuhi dan sesuai dengan standar pendidikan nasional.

Applicability of radiocolloids, blue dyes and fluorescent indocyanine green to sentinel node biopsy in melanoma

Patients with primary cutaneous melanoma underwent sentinel node (SN) mapping and biopsy at 25 facilities in Japan by the combination of radiocolloid with gamma probe and dye. Technetium-99m (99mTc)-tin colloid, 99mTc-phytate, 2% patent blue violet (PBV) and 0.4% indigo carmine were used as tracers. In some hospitals, 0.5% fluorescent indocyanine green, which allows visualization of the SN with an infrared camera, was concomitantly used and examined. A total of 673 patients were enrolled, and 562 cases were eligible. The detection rates of SN were 95.5% (147/154) with the combination of tin colloid and PBV, 98.9% (368/372) with the combination of phytate and PBV, and 97.2% (35/36) with the combination of tin colloid or phytate and indigo carmine. SN was not detected in 12 cases by the combination method, and the primary tumor was in the head and neck in six of those 12 cases. In eight of 526 cases (1.5%), SN was detected by PBV but not by radiocolloid. There were 13 cases (2.5%) in which SN was detected by radiocolloid but not by PBV. In 18 of 36 cases (50%), SN was detected by radiocolloid but not by indigo carmine. Concomitantly used fluorescent indocyanine green detected SN in all of 67 cases. Interference with transcutaneous oximetry by PVB was observed in some cases, although it caused no clinical trouble. Allergic reactions were not reported with any of the tracers. 99mTc-tin colloid, 99mTc-phytate, PBV and indocyanine green are useful tracers for SN mapping.ArticleJOURNAL OF DERMATOLOGY. 39(4):336-338 (2012)journal articl

Clinical and molecular features of 66 patients with musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14)

Background Musculocontractural Ehlers-Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated. Methods We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations. Results Sixty-six patients in 48 families (33 males/females; 0-59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype-phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE. Conclusion This first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.Genetics of disease, diagnosis and treatmen

Graphene oxide/carbon nanoparticle thin film based IR detector: Surface properties and device characterization

This work deals with the synthesis, characterization, and application of carbon nanoparticles (CNP) adorned graphene oxide (GO) nanocomposite materials. Here we mainly focus on an emerging topic in modern research field presenting GO-CNP nanocomposite as a infrared (IR) radiation detector device. GO-CNP thin film devices were fabricated from liquid phase at ambient condition where no modifying treatments were necessary. It works with no cooling treatment and also for stationary objects. A sharp response of human body IR radiation was detected with time constants of 3 and 36 sec and radiation responsivity was 3 mAW−1. The current also rises for quite a long time before saturation. This work discusses state-of-the-art material developing technique based on near-infrared photon absorption and their use in field deployable instrument for real-world applications. GO-CNP-based thin solid composite films also offer its potentiality to be utilized as p-type absorber material in thin film solar cell, as well

Tibia Rotational Technique to Drill Femoral Bone Tunnel in Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction

In anatomic anterior cruciate ligament (ACL) reconstruction, several pitfalls in creating the femoral bone tunnels at the correct position are of great concern. Our new method, the tibia rotational (TR) technique, may contribute to resolving these. The purpose of this study is to describe further details about the TR technique in anatomic double-bundle ACL reconstruction. Both anteromedial and posterolateral femoral bone tunnels were drilled through a posterolateral tibial bone tunnel using tibial rotation without deep knee flexion. When it is difficult to reach the mark with the rigid guide pin, the narrow curved TR technique guide and the flexible drill system allow drilling femoral bone tunnels in the correct position. The TR technique offers the technical ease required for widespread acceptance while prioritizing the fundamental goals of an anatomic double-bundle ACL reconstruction

Preferential and Comprehensive Reconstitution of Severely Damaged Sciatic Nerve Using Murine Skeletal Muscle-Derived Multipotent Stem Cells

<div><p>Loss of vital functions in the somatic motor and sensory nervous systems can be induced by severe peripheral nerve transection with a long gap following trauma. In such cases, autologous nerve grafts have been used as the gold standard, with the expectation of activation and proliferation of graft-concomitant Schwann cells associated with their paracrine effects. However, there are a limited number of suitable sites available for harvesting of nerve autografts due to the unavoidable sacrifice of other healthy functions. To overcome this problem, the potential of skeletal muscle-derived multipotent stem cells (Sk-MSCs) was examined as a novel alternative cell source for peripheral nerve regeneration. Cultured/expanded Sk-MSCs were injected into severely crushed sciatic nerve corresponding to serious neurotmesis. After 4 weeks, engrafted Sk-MSCs preferentially differentiated into not only Schwann cells, but also perineurial/endoneurial cells, and formed myelin sheath and perineurium/endoneurium, encircling the regenerated axons. Increased vascular formation was also observed, leading to a favorable blood supply and waste product excretion. In addition, engrafted cells expressed key neurotrophic and nerve/vascular growth factor mRNAs; thus, endocrine/paracrine effects for the donor/recipient cells were also expected. Interestingly, skeletal myogenic capacity of expanded Sk-MSCs was clearly diminished in peripheral nerve niche. The same differentiation and tissue reconstitution capacity of Sk-MSCs was sufficiently exerted in the long nerve gap bridging the acellular conduit, which facilitated nerve regeneration/reconnection. These effects represent favorable functional recovery in Sk-MSC-treated mice, as demonstrated by good corduroy walking. We also demonstrated that these differentiation characteristics of the Sk-MSCs were comparable to native peripheral nerve-derived cells, whereas the therapeutic capacities were largely superior in Sk-MSCs. Therefore, Sk-MSCs can be a novel/suitable alternative cell source for healthy nerve autografts.</p></div

Cellular engraftment and comparison of regenerated axons, myelin and blood vessels in damaged portion of Sk-MSC-7d-, BMSC-7d- and SNDC-D-transplanted nerves at 4 weeks after injection.

<p>Comparisons were performed among 7-day cultured Sk-MSCs (Sk-MSC-7d) and BMSCs (BMSC-7d), freshly isolated SNDCs from damaged sciatic nerve (SNDC-D), and medium control (MC) groups based on the results shown in Fig. 1. (F–H). (A–C) Typical engraftment on whole cross-sections of each transplantation group (except for MC group). (D–F) Typical staining of regenerated axons as N200⁺, and myelin as MBP⁺ (G–I) and blood vessel formation as CD31⁺ regions (J–L). (M–P) Comparison of the above factors (Sk = Sk-MSC-7d, BM = BMSC-7d, SN = SNDC-D and MC = medium control). (M) Percentage of mean GFP⁺ area/total area on whole cross-sections, as compared to relative engraftment ratio. (N) Mean number of axons. (O) Mean number of myelin signals. (P) Mean number of blood vessels. Dotted lines in (N, O and P) indicate the mean number of axons, myelin signals and blood vessels in the corresponding portion of normal sciatic nerve (4625±470, 3179±760 and 27±4, respectively). Significantly greater cellular engraftment ratio and blood vessel formation was evident in the Sk-MSC group. N-200; Neurofilament 200, MBP; Myelin basic protein. *P≤0.05; all scale bars represent 200 µm.</p