Sitosterolemia Exhibiting Severe Hypercholesterolemia with Tendon Xanthomas Due to Compound Heterozygous ABCG5 Gene Mutations Treated with Ezetimibe and Alirocumab

We herein report a rare case presenting with severe hypercholesterolemia, massive Achilles tendon xanthomas, and multi-vessel coronary artery disease. Initially, the patient was misdiagnosed with familial hypercholesterolemia. However, a genetic analysis using our custom sequencing panel covering genes associated with Mendelian lipid disorders revealed him to have a genetic basis of sitosterolemia with compound heterozygous mutations in the adenosine triphosphate binding cassette subfamily G5 (ABCG5) gene. A comprehensive genetic analysis can be particularly useful for diagnosing cases with severe phenotypes, leading to appropriate and medical therapies. Our patient was refractory to statins, whereas ezetimibe and PCSK9 inhibitor with a low-plant-sterol diet successfully reduced his serum levels of low-density lipoprotein cholesterol.     

Infliximab Was Found to Be Effective for Treating Immunosuppressive Drug-resistant Hepatitis due to Durvalumab

A 69-year-old man with stage III lung squamous cell carcinoma developed immune-related hepatitis following treatment with durvalumab, and was given high-dose corticosteroids and immunosuppressive drugs (mycophenolate mofetil, azathioprine, tacrolimus) but without demonstrating any improvement. Two cycles of infliximab (5 mg/kg) were then administered and thereafter the hepatitis improved. At the time of writing (9 months after the initiation of first course of durvalumab), the patient is alive without either any hepatitis symptoms nor any lung cancer progression. Infliximab may be effective for treating non-small cell lung cancer (NSCLC) patients who develop immunosuppressive drug-resistant immune-related hepatitis caused by durvalumab.     

Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25

BACKGROUND AND PURPOSE: Moyamoya disease is a cerebrovascular disease of unknown cause that mainly affects Japanese children. The incidence of familial occurrence accounts for 9% of cases. The characteristic lesions of moyamoya disease are occasionally seen in neurofibromatosis type 1, of which the causative gene (NF1) has been assigned to chromosome 17q11.2. METHODS: To determine whether a gene related to moyamoya disease is located on chromosome 17, we conducted microsatellite linkage analyses on 24 families containing 56 patients with moyamoya disease. Leukocyte DNA extracted from the family members was subjected to polymerase chain reaction for a total of 22 microsatellite markers on chromosome 17. The amplified polymerase chain reaction fragments were analyzed with GeneScan on an automated sequencer. RESULTS: Two-point linkage analysis gave a maximum log(10) odds (LOD) score of 3.11 at the recombination fraction of 0.00 for the marker at locus D17S939. The affected pedigree member method also showed a significantly low P value (<1. 0x10(-5)) for the 5 adjacent markers at 17q25. Multipoint linkage analysis also indicated that the disease gene is contained within the 9-cM region of D17S785 to D17S836, with a maximum LOD score of 4. 58. CONCLUSIONS: A gene for familial moyamoya disease is located on chromosome 17q25.     

Tissue Doppler imaging and strain Doppler imaging as modalities for predicting clinical improvement in patients receiving biventricular pacing.

BACKGROUND: The purpose of this study was to determine the utility and efficacy of tissue Doppler imaging (TDI) and strain Doppler imaging (SDI) for evaluating ventricular synchrony and function, and for predicting the long-term clinical improvement in patients undergoing biventricular pacing (BVP). METHODS AND RESULTS: TDI and SDI were performed before and <1 month after initiating BVP in 17 patients with advanced heart failure. An intraventricular conduction delay between the left ventricular (LV) septal and lateral walls was measured by TDI. The average LV strain (LV-strain) was calculated from data obtained at the center of 6 regions of the LV (base and mid-point between the basal and apical portions, and the mid-point between these 2 points on the septal and lateral walls). During a 23+/-7 month follow-up period, 12 patients improved clinically and did not require re-hospitalization for heart failure (responder group), but the remaining 5 did not improve (nonresponder group). Before BVP, the intraventricular conduction delay was greater in the responder group than in the nonresponder group (p<0.01), but after BVP, it did not differ between the 2 groups. LV-strain improved after BVP in the responder group but not in the nonresponder group (p<0.05). CONCLUSION: A high intraventricular conduction delay before BVP and decreased strain shortly after BVP may predict long-term clinical improvement in patients undergoing this treatment.     

Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study

We conducted a multicenter phase I/II study using mesenchymal stem cells (MSCs) manufactured from the bone marrow of healthy unrelated volunteers to treat steroid-refractory acute graft-versus-host disease (aGVHD). Fourteen patients with hematological malignancies who suffered from grade II (9 patients) or III aGVHD (5) were treated. Affected organs were gut (10 patients), skin (9 patients), and liver (3 patients). Seven patients had two involved organs. The median age was 52. No other second-line agents were given. MSCs were given at a dose of 2 × 10⁶ cells/kg for each infusion twice a week for 4 weeks. If needed, patients were continuously given MSCs weekly for an additional 4 weeks. By week 4, 13 of 14 patients (92.9 %) had responded to MSC therapy with a complete response (CR; n = 8) or partial response (PR; n = 5). At 24 weeks, 11 patients (10 with CR and 1 with PR) were alive. At 96 weeks, 8 patients were alive in CR. A total of 6 patients died, attributable to the following: underlying disease relapse (2 patients), breast cancer relapse (1), veno-occlusive disease (1), ischemic cholangiopathy (1), and pneumonia (1). No clear adverse effects associated with MSC infusion were observed. Third party-derived bone marrow MSCs may be safe and effective for patients with steroid-refractory aGVHD.