Clinical,cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.     

Effect of Switching Therapy to Pegaptanib in Eyes With the Persistent Cases of Exudative Age-Related Macular Degeneration

Purpose of this study was to evaluate the efficacy of switching to pegaptanib monotherapy for persistent cases of exudative age-related macular degeneration (AMD).Out of 296 eyes of 296 patients treated with ranibizumab or ranibizumab combined with photodynamic therapy (PDT), 50 eyes of 50 AMD patients were found to be resistant to these treatments. Over a 12-month period, intravitreal pegaptanib (IVP) 0.3 mg was administered at intervals of 6 weeks until the exudation disappeared prospectively. All patients were examined with the following tests: best-corrected visual acuity (BCVA) and central retinal thickness (CRT), determined at the initial visit, before the first IVP (baseline), and at 12 months. The factors responsible for achieving dry macula with IVP were examined statistically.The rate of persistent cases with intravitreal ranibizumab (IVR) and/or PDT was 17.0%. The mean number of IVPs administered was 5.4 (range, 2–9). Logarithm of the minimal angle of resolution BCVA at 12 months was stable or improved by ≥0.3 in 49 eyes (98.0%), with a significant improvement noted between the baseline and final BCVA (P = 0.01, paired t test). The CRT (mean ± standard deviation) was 446.9 ± 150.6 µm at the initial visit, 414.5 ± 146.5 µm at baseline, and 318.7 ± 99.0 µm at 12 months. There was a significant decrease in the mean CRT between the measurements at baseline and at 12 months after the first IVP (P = 0.002, Bonferroni correction). At 12 months, the exudative change was completely resolved in 27 eyes (54.0%) and reduced in 21 eyes (42.0%). The number of previous IVR treatments was significantly correlated with dry macula at 12 months.After switching therapy to pegaptanib in persistent cases of AMD, most patients maintained or improved their BCVA and exhibited a positive treatment response at 12 months.     

pH-Tolerant giant vesicles composed of cationic lipids with imine linkages and oleic acids

Giant vesicles (GVs) have attracted attention as functional materials because they can encapsulate both hydrophilic and hydrophobic compounds. For next generation functional GVs, both tolerance and stimuli-sensitivity are needed. So far, vesicles tolerant to acidic or basic conditions were generated using a mixture of cationic lipids and fatty acids. Here, to create functional GVs that are tolerant to a wide pH range but sensitively respond at below a specific pH, the behaviour of GVs composed of a cationic lipid with an imine bond and oleic acid was investigated. Even though the GVs prepared by the film swelling method were tolerant to strongly acidic conditions, GVs without oleic acid gradually shrank, accompanied by the generation of oil droplets at the same pH. ¹H NMR analysis revealed that during hydration of the film, the imine bond hydrolysed to provide a cationic surfactant and an oil component in the presence of oleic acid due to its own Lewis basicity, suggesting the dissociation of oleic acid. The results of fluorescence spectroscopy using an environment-responsive probe and IR spectroscopy indicated that the GV tolerance originated from the intermolecular interactions of cationic lipids and anionic oleate.

Giant vesicles composed of cationic lipids having an imine linkage and oleic acid were stable at strong acidic conditions.     

Clinical utility of treatment method conversion during single-session endoscopic ultrasound-guided biliary drainage

BACKGROUND Although several techniques for endoscopic ultrasound-guided biliary drainage(EUS-BD)are available at present,an optimal treatment algorithm of EUS-BD has not yet been established.AIM To evaluate the clinical utility of treatment method conversion during single endoscopic sessions for difficult cases in initially planned EUS-BD.METHODS This was a single-center retrospective analysis using a prospectively accumulated database.Patients with biliary obstruction undergoing EUS-BD between May 2008 and April 2016 were included.The primary outcome was to evaluate the improvement in EUS-BD success rates by converting the treatment methods during a single endoscopic session.Secondary outcomes were clarification of the factors leading to the conversion from the initial EUS-BD and the assessment of efficacy and safety of the conversion as judged by technical success,clinical success,and adverse events(AEs).RESULTS A total of 208 patients underwent EUS-BD during the study period.For 18.8%(39/208)of the patients,the treatment methods were converted to another EUSBD technique from the initial plan.Biliary obstruction was caused by pancreatobiliary malignancies,other malignant lesions,biliary stones,and other benign lesions in 22,11,4,and 2 patients,respectively.The reasons for the difficulty with the initial EUS-BD were classified into the following 3 procedures:Target puncture(n=13),guidewire manipulation(n=18),and puncture tract dilation(n=8).Technical success was achieved in 97.4%(38/39)of the cases and clinical success was achieved in 89.5%of patients(34/38).AEs occurred in 10.3%of patients,including bile leakage(n=2),bleeding(n=1),and cholecystitis(n=1).The puncture target and drainage technique were altered in subsequent EUSBD procedures in 25 and 14 patients,respectively.The final technical success rate with 95%CI for all 208 cases was 97.1%(95%CI:93.8%-98.9%),while that of the initially planned EUS-BD was 78.8%(95%CI:72.6%-84.2%).CONCLUSION Among multi-step procedures in EUS-BD,guidewire manipulation appeared to be the most technically challenging.When initially planned EUS-BD is technically difficult,treatment method conversion in a single endoscopic session may result in successful EUS-BD without leading to severe AEs.     

Nodding syndrome in Mundri county,South Sudan: environmental,nutritional and infectious factors

Background

Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.

Objective

To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.

Methods

Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.

Results

Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.

Conclusion

Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.     

Ultra‐short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

We conducted an adaptive design single‐center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra‐short‐term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)‐nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R?). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12‐week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first‐line DAA therapy; and two after retreatment with second‐line DAA). At a median follow‐up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4‐day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%‐20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R ? transplants.     

Involvement of the synaptotagmin/stonin2 system in vesicular transport regulated by semaphorins in Caenorhabditis elegans epidermal cells

Vesicular transport serves as an important mechanism for cell shape regulation during development. Although the semaphorin signaling molecule, a well‐known regulator of axon guidance, induces endocytosis in the growth cone and the axonal transport of vertebrate neurons, the underlying molecular mechanisms remain largely unclear. Here, we show that the Caenorhabditis elegans SNT‐1/synaptotagmin‐UNC‐41/stonin2 system, whose role in synaptic vesicle recycling in neurons has been studied extensively, is involved in semaphorin‐regulated vesicular transport in larval epidermal cells. Mutations in the snt‐1/unc‐41 genes strongly suppressed the cell shape defects of semaphorin mutants. The null mutation in the semaphorin receptor gene, plx‐1, altered the expression and localization pattern of endocytic and exocytic markers in the epidermal cells while repressing the transport of SNT‐1‐containing vesicles toward late endosome/lysosome pathways. Our findings suggest that the nematode semaphorins regulate the vesicular transport in epidermal cells in a manner distinct from that of vertebrate semaphorins in neurons.     

Protection of cultured Cyprinus carpio against a lethal viral disease by an attenuated virus vaccine

Massive mortality of koi and common carp--Cyprinus carpio species--has been observed since 1998 in many countries worldwide, resulting in severe economic losses. The cause of the disease is an as yet unclassified large DNA virus, designated carp nephritis gill necrosis virus (CNGV) or koi herpes virus (KHV). Previously, we demonstrated that the wild type CNGV lost its pathogenecity following serial transfer in cell culture, and that clones isolated from the attenuated population can be used as a prophylactic vaccine. Here, we describe the basic conditions required for proper fish immunization so that a protection protocol may be devised. We demonstrated that carps are very sensitive to the pathogenic and the attenuated viruses, and short immersion of fish in water containing the viruses is sufficient for infection. The infection of fish with the pathogenic and the attenuated viruses is temperature-restricted; fish held at the non-permissive temperature, immediately following infection, were not affected by the pathogenic virus, and were not rendered resistant to the disease. Thus, propagation of the virus in the fingerlings is a pre-requisite for immunization. In order to increase the number of random mutations in the genome of the attenuated virus, and thus, reduce the possibility of the attenuated virus reverting to pathogenic, we irradiated it and selected additional clones appropriate for vaccination. The results of our study suggest that a safe and efficient prophylactic vaccine can be developed by selecting an appropriate attenuated virus.