Current status of a helicopter transportation system on remote islands for patients undergoing mechanical thrombectomy

Background: Mechanical thrombectomy (MT) is standard treatment for acute ischemic stroke (AIS) with large-vessel occlusion within 6 h of symptom onset to treatment initiation (OTP). Recent trials have extended the therapeutic time window for MT to within 24 h. However, MT treatment remains low in remote areas. Nagasaki Prefecture, Japan has many inhabited islands with no neurointerventionalists. Our hospital on the mainland is a regional hub for eight island hospitals. We evaluated clinical outcomes of MT for patients with AIS on these islands versus on the mainland. Methods: During 2014–2019, we reviewed consecutive patients with AIS who received MT at our hospital. Patients comprised the Islands group and Mainland group. Patient characteristics and clinical outcomes were compared between groups. Results: We included 91 patients (Islands group: 15 patients, Mainland group: 76 patients). Seven patients (46.7%) in the Islands group versus 43 (56.6%) in the Mainland group achieved favorable outcomes. Successful recanalization was obtained in 11 patients (73.3%) on the islands and 67 (88.2%) on the mainland. The median OTP time in the Islands was 365 min. In both the Islands and Mainland groups, the OTP time and successful recanalization were associated with functional outcome. The modified Rankin Scale (mRS) score at 90 days ≤2 was obtained in two patients and mRS = 3 in four patients among eight patients with OTP time >6 h. Conclusions: Few patients with AIS on remote islands have received MT. Although patients who underwent MT on the islands had longer OTP, the clinical outcomes were acceptable. OTP time on remote islands must be shortened, as this is related to functional outcome. In some cases with successful recanalization, a favorable outcome can still be obtained even after 6 h. Even if OTP exceeds 6 h, it is desirable to appropriately select patients and actively perform MT

Conditional deletion of Npt2b in phosphate transport

Background Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na+-dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. Methods In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption. Results Although the Na+-dependent Pi transport in brush-border membrane vesicle uptake levels were significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals. Conclusion These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency

Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair

UV-sensitive syndrome (UVSS) is a genodermatosis characterized by cutaneous photosensitivity without skin carcinoma1, 2, 3, 4. Despite mild clinical features, cells from individuals with UVSS, like Cockayne syndrome cells, are very UV sensitive and are deficient in transcription-coupled nucleotide-excision repair (TC-NER)2, 4, 5, which removes DNA damage in actively transcribed genes6. Three of the seven known UVSS cases carry mutations in the Cockayne syndrome genes ERCC8 or ERCC6 (also known as CSA and CSB, respectively)7, 8. The remaining four individuals with UVSS, one of whom is described for the first time here, formed a separate UVSS-A complementation group1, 9, 10; however, the responsible gene was unknown. Using exome sequencing11, we determine that mutations in the UVSSA gene (formerly known as KIAA1530) cause UVSS-A. The UVSSA protein interacts with TC-NER machinery and stabilizes the ERCC6 complex; it also facilitates ubiquitination of RNA polymerase IIo stalled at DNA damage sites. Our findings provide mechanistic insights into the processing of stalled RNA polymerase and explain the different clinical features across these TC-NER–deficient disorders

A nonsense mutation in mouse Adamtsl2 causes uterine hypoplasia and an irregular estrous cycle

The spontaneous mutation stubby (stb) in mice causes chondrodysplasia and male infertility due to impotence through autosomal recessive inheritance. In this study, we conducted linkage analysis to localize the stb locus within a 1.6 Mb region on mouse chromosome 2 and identified a nonsense mutation in Adamtsl2 of stb/stb mice. Histological analysis revealed disturbed endochondral ossification with a reduced hypertrophic chondrocyte layer and stiff skin with a thickened dermal layer. These phenotypes are similar to those observed in humans and mice with ADAMTSL2/Adamtsl2 mutations. Moreover, stb/stb female mice exhibited severe uterine hypoplasia at 5 weeks of age and irregular estrous cycles at 10 weeks of age. In normal mice, Adamtsl2 was more highly expressed in the ovary and pituitary gland than in the uterus, and this expression was decreased in stb/stb mice. These findings suggest that Adamtsl2 may function in these organs rather than in the uterus. Thus, we analyzed Gh expression in the pituitary gland and plasma estradiol and IGF1 levels, which are required for the development of the female reproductive tract. There was no significant difference in Gh expression and estradiol levels, whereas IGF1 levels in stb/stb mice were significantly reduced to 54–59% of those in +/+ mice. We conclude that Adamtsl2 is required for the development of the uterus and regulation of the estrous cycle in female mice, and decreased IGF1 may be related to these abnormalities

UBE3C Facilitates the ER-Associated and Peripheral Degradation of Misfolded CFTR

The ubiquitin E3 ligase UBE3C promotes the proteasomal degradation of cytosolic proteins and endoplasmic reticulum (ER) membrane proteins. UBE3C is proposed to function downstream of the RNF185/MBRL ER-associated degradation (ERAD) branch, contributing to the ERAD of select membrane proteins. Here, we report that UBE3C facilitates the ERAD of misfolded CFTR, even in the absence of both RNF185 and its functional ortholog RNF5 (RNF5/185). Unlike RNF5/185, UBE3C had a limited impact on the ubiquitination of misfolded CFTR. UBE3C knockdown (KD) resulted in an additional increase in the functional ∆F508-CFTR channels on the plasma membrane when combined with the RNF5/185 ablation, particularly in the presence of clinically used CFTR modulators. Interestingly, although UBE3C KD failed to attenuate the ERAD of insig-1, it reduced the ERAD of misfolded ∆Y490-ABCB1 and increased cell surface expression. UBE3C KD also stabilized the mature form of ∆F508-CFTR and increased the cell surface level of T70-CFTR, a class VI CFTR mutant. These results suggest that UBE3C plays a vital role in the ERAD of misfolded CFTR and ABCB1, even within the RNF5/185-independent ERAD pathway, and it may also be involved in maintaining the peripheral quality control of CFTR

Clinical Usefulness of Ultrasound-Guided Fine Needle Aspiration and Core Needle Biopsy for Patients with Axillary Lymphadenopathy

Background and Objectives: It is necessary to properly diagnose and manage axillary lymphadenopathy caused by a variety of diseases. This study aimed to evaluate the utility of ultrasound (US)-guided sampling in patients with axillary lymphadenopathy. Materials and Methods: Patients with axillary lymphadenopathy (excluding patients with newly diagnosed breast cancer) who underwent US-guided fine needle aspiration (FNA) or core needle biopsy (CNB) at a single center between February 2016 and September 2020 were retrospectively examined. The association between US imaging findings and malignancy was investigated and the diagnostic performance of US-guided sampling was assessed. Results: Fifty-five patients (including eight males) were included in the study; of these, 34 patients (61.8%) were finally diagnosed with a malignant lymph node lesion. Twenty-two patients (40.0%) had undergone FNA and 33 (60.0%) had undergone CNB. Larger short and long axis diameters, thicker lymph node cortex, and the absence of fatty hilum on the US were significantly associated with malignancy (p < 0.05). The diagnostic performance of FNA, CNB, and FNA + CNB was excellent (sensitivity, specificity, and accuracy of 0.909, 0.900, and 0.917 for FNA, 0.958, 1.000, and 0.970 for CNB, and 0.941, 0.952, and 0.945 for FNA + CNB, respectively). Conclusions: US-guided FNA and CNB play an important role in the diagnosis and management of patients with axillary lymphadenopathy

Active Herpes Zoster Mimicking Worsening of Axillary Lymph Node Metastases of Breast Cancer after Chemotherapy on 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography

A woman in her 60s presented to our hospital with a left breast mass that was diagnosed as breast cancer. 18F-Fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) revealed intense, hot uptake in the cancerous mass and left axillary lymph node metastasis. After chemotherapy, another PET/CT scan was performed. Although the mass and left axillary lymph nodes shrank and FDG uptake decreased, enlarged lymph nodes with high FDG uptake appeared in the right axilla. The patient had a painful vesicular eruption on the front to the back of the right upper hemithorax, which was diagnosed as active herpes zoster. Active herpes zoster mimics a worsening axillary lymph node metastasis on the PET/CT scan

A Rare Case of Primary Breast Osteosarcoma Evaluated with Multiple Modalities

Primary breast osteosarcoma (PBO) is very rare. This report presents a case of POB that was evaluated by multiple modalities. A woman in her 70s presented with a mass of increasing size in her right breast. A mammogram and an ultrasound visualized a lobulated mass containing coarse calcification in the right breast. Magnetic resonance imaging showed a strong enhancement effect and high signal on diffusion-weighted imaging. Further imaging on 18F-fluorodeoxyglucose positron-emission tomography and computed tomography exhibited a high uptake. A right total mastectomy was performed. Histologic examination revealed abundant periosteal formation, areas of calcification and moderately pleomorphic oval to spindle-shaped stromal cells, leading to the diagnosis of PBO. The presence of calcified breast tumors exhibiting aggressive growth indicates that PBO should be added to the differential diagnosis