Clinical impact of portal vein pulsatility on the prognosis of hospitalized patients with acute heart failure.

BACKGROUND: Heart failure (HF) causes extracardiac organ congestion, including in the hepatic portal system. Reducing venous congestion is essential for HF treatment, but evaluating venous congestion is sometimes difficult in patients with chronic HF. The portal vein (PV) flow pattern can be influenced by right atrial pressure. Ultrasound images of the PV are quite easy to obtain and are reproducible among sonographers. However, the association between PV pulsatility and the condition of HF remains unclear. We hypothesize that PV pulsatility at discharge reflects the condition of HF. AIM: To evaluate the usefulness of PV pulsatility as a prognostic marker for hospitalized patients with acute HF. METHODS: This observational study was conducted from April 2016 to January 2017 and April 2018 to April 2019 at Shinko Hospital. We enrolled 56 patients with acute HF, and 17 patients without HF served as controls. PV flow velocity was measured by ultrasonography on admission and at discharge. We calculated the PV pulsatility ratio (PVPR) as the ratio of the difference between the peak and minimum velocity to the peak velocity. The primary endpoint was cardiac death and HF re-hospitalization. The observation period was 1 year from the first hospitalization. The Kaplan-Meier method was used to determine the stratified composite event-free rates, and the log-rank test was used for comparisons between groups. RESULTS: On admission, the PVPR was significantly higher in patients with acute HF than controls (HF: 0.29 ± 0.20 vs controls: 0.08 ± 0.07, P < 0.01). However, the PVPR was significantly decreased after the improvement in HF (admission: 0.29 ± 0.20 vs discharge: 0.18 ± 0.15, P < 0.01) due to the increase in minimum velocity (admission: 12.6 ± 4.5 vs discharge: 14.6 ± 4.6 cm/s, P = 0.03). To elucidate the association between the PVPR and cardiovascular outcomes, the patients were divided into three groups according to the PVPR tertile at discharge (PVPR-T1: 0 ≤ PVPR ≤ 0.08, PVPR-T2: 0.08 < PVPR ≤ 0.21, PVPR-T3: PVPR > 0.21). The Kaplan-Meier analysis showed that patients with a higher PVPR at discharge had the worst prognosis among the groups. CONCLUSION: PVPR at discharge reflects the condition of HF. It is also a novel prognostic marker for hospitalized patients with acute HF.

T-cell large granular lymphocytic (LGL) leukemia consists of CD4+/CD8dim and CD4-/CD8+ LGL populations in association with immune thrombocytopenia, autoimmune neutropenia, and monoclonal B-cell lymphocytosis.

CD3+/CD57+ T-cell large granular lymphocyte leukemia (T-LGLL) is an indolent neoplasm, exhibiting mostly CD8+, less frequently CD4+ phenotypes, and T-LGLL consisting of 2 populations with CD8+ and CD4+ phenotypes is markedly rare. An 87-year-old female was admitted under a diagnosis of immune thrombocytopenia (ITP) with a platelet count of 5.0×109/L and increased number of LGL with unknown etiology. Her neutrophil count also decreased to 0.27×109/L and she was positive for antineutrophil antibody. The WBC count was 2.7×109/L with 34.7% LGL and flow cytometry (FCM) analysis revealed 16% CD3+/CD4+/CD8dim/CD57+ and 20.9% CD3+/CD8+/CD57+ populations. These populations also expressed granzyme B and perforin. Circulating mononuclear cells were found to be clonal by PCR analysis of T-cell receptor ß-chain gene. Serum immunofixation and bone marrow FCM analyses demonstrated 2 clonal B-cells producing IgG-λ and IgA-λ. Deep amplicon sequencing of STAT3 and STAT5B genes revealed a STAT3 R302G mutation with an allele burden of 2.6%. The thrombocytopenia and neutropenia were successfully treated by prednisolone and romiplostim with negative conversion of antineutrophil antibody. This is the first reported case of T-LGLL with dual components of CD4+/CD8dim and CD4-/CD8+ populations in terms of multiple comorbidities related to the respective CD8+ and CD4+ T-LGLLs.

Heterologous production of kasugamycin, an aminoglycoside antibiotic from Streptomyces kasugaensis, in Streptomyces lividans and Rhodococcus erythropolis L-88 by constitutive expression of the biosynthetic gene cluster.

Kasugamycin (KSM), an aminoglycoside antibiotic isolated from Streptomyces kasugaensis cultures, has been used against rice blast disease for more than 50 years. We cloned the KSM biosynthetic gene (KBG) cluster from S. kasugaensis MB273-C4 and constructed three KBG cassettes (i.e., cassettes I-III) to enable heterologous production of KSM in many actinomycetes by constitutive expression of KBGs. Cassette I comprised all putative transcriptional units in the cluster, but it was placed under the control of the P neo promoter from Tn5. It was not maintained stably in Streptomyces lividans and did not transform Rhodococcus erythropolis. Cassette II retained the original arrangement of KBGs, except that the promoter of kasT, the specific activator gene for KBG, was replaced with P rpsJ , the constitutive promoter of rpsJ from Streptomyces avermitilis. To enhance the intracellular concentration of myo-inositol, an expression cassette of ino1 encoding the inositol-1-phosphate synthase from S. avermitilis was inserted into cassette II to generate cassette III. These two cassettes showed stable maintenance in S. lividans and R. erythropolis to produce KSM. Particularly, the transformants of S. lividans induced KSM production up to the same levels as those produced by S. kasugaensis. Furthermore, cassette III induced more KSM accumulation than cassette II in R. erythropolis, suggesting an exogenous supply of myo-inositol by the ino1 expression in the host. Cassettes II and III appear to be useful for heterologous KSM production in actinomycetes. Rhodococcus exhibiting a spherical form in liquid cultivation is also a promising heterologous host for antibiotic fermentation.

Assessment of pesticide residues in freshwater areas affected by rice paddy effluents in Southern Japan.

Pesticide residues in five freshwater areas that are directly affected by rice paddy effluents in southern Japan were measured to determine their maximum concentrations and temporal variations. Water samples were collected every week during the 2005 rice planting season in Kagoshima Prefecture and stations were established in Amori River, Sudo River, Nagaida River (that drains into the bigger Kotsuki River), rice paddy drainage canal, and wastewater reservoir (that collects effluents from rice paddy fields). Of the 14 target pesticides examined, a total of 11 were detected in all stations. Mefenacet, fenobucarb, and flutolanil were the three pesticides with the highest maximum concentrations and were also detected frequently. Analysis of temporal variations of pesticides showed that herbicides had relatively higher concentrations in the earlier stages of the rice planting season, while insecticides and fungicides had relatively higher concentrations at the later stages. There was no significant difference among stations with regards to the temporal patterns of the top three pesticides. The calculated toxic units were less than 1 in all stations, implying low or negligible environmental risk of pesticides detected to freshwater organisms.