Readmissions after continuous flow left ventricular assist device implantation

Continuous flow left ventricular assist device (CF-LVAD) therapy has improved the survival of patients with advanced heart failure. However, the readmission rate of CF-LVAD patients is still relatively high. A total of 90 patients who received CF-LVADs between April 2011 and March 2016 at our institute and were discharged home were analyzed retrospectively. They were followed up through March 2017. Clinical data, including frequency, length and etiology of readmission, were obtained from medical records. The mean observation period after initial discharge was 713 ± 322 days. In total, 73 patients (81%) had 236 readmissions, 214 unplanned and 22 planned. The overall and unplanned readmission rates were 1.34 and 1.22 per patient-year, respectively. The rate of freedom from unplanned first readmission at 1 year after initial discharge was 39%. The median interval between the previous hospital discharge and first and second readmissions was 311 and 213 days, respectively (log-rank test, p = 0.117). The rate of readmission after more than three readmissions was significantly higher than that of first or second readmission (log-rank test, p < 0.001). The most common etiology of readmission was driveline infection (DLI) (36%), followed by stroke (9%). The median length of hospital stay due to DLI was 23 days. The patients with repeated unplanned readmissions had significantly lower EuroQol 5 dimensions questionnaire utility score than those with no or just one readmission. Readmission was common in CF-LVAD patients, and the most common etiology of readmissions was DLI. The interval to the next readmission seemed shorter for patients with repeated readmissions.     

Therapeutic Action of Honokiol on Postoperative Ileus <Emphasis Type="Italic">via</Emphasis> Downregulation of iNOS Gene Expression

Postoperative ileus is a common complication after intra-abdominal surgery. Nitric oxide produced by macrophages in the inflamed gastrointestinal tract plays a crucial role in the pathogeny of postoperative ileus. Honokiol, extracted from the bark of Magnolia spp., is a natural compound with a biphenolic structure. In the present study, we examined the effect of honokiol on postoperative ileus and discussed its site of action. Postoperative ileus model mice were generated by surgical intestinal manipulation. Mice were administered honokiol (10 mg kg^?1, per os) 1 h before and after intestinal manipulation. Gastrointestinal transit, leukocyte infiltration, and messenger RNA (mRNA) expression of inflammatory mediators were measured in postoperative ileus model mice with or without honokiol. We also investigated the inflammatory effect of honokiol in lipopolysaccharide-stimulated peritoneal macrophages. Gastrointestinal transit was delayed in postoperative ileus model mice and honokiol recovered the impaired transit. Honokiol significantly inhibited leukocyte infiltration and upregulation of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and inducible nitric oxide synthase in the ileal muscle layer of postoperative ileus model mice. In peritoneal macrophages activated by lipopolysaccharide, honokiol significantly inhibited the upregulated mRNA expression of proinflammatory cytokines and inducible nitric oxide synthase. Honokiol significantly recovered gastrointestinal dysmotility and inhibited intestinal inflammation in postoperative ileus. Moreover, honokiol was suggested to have effects on macrophages, namely, inhibiting mRNA expression of proinflammatory cytokines and inducible nitric oxide synthase. Taken together, honokiol represents a potential novel therapeutic agent for postoperative ileus.     

Effective high-dose chemotherapy combined with CD34+-selected peripheral blood stem cell transplantation in a patient with cutaneous involvement of nasal NK/T-cell lymphoma

The prognosis of nasal natural killer (NK)/T-cell lymphoma with cutaneous involvement especially is morbid despite intensive chemotherapy and radiotherapy. We treated a 52-yr-old Japanese woman with cutaneous dissemination of nasal NK/T-cell lymphoma. Six cycles of chemotherapy, irradiation to skin lesion were administered and complete remission (CR) was attained. High-dose chemotherapy (HDC; etoposide 750 mg/m(2) x 2 d, cyclophosphamide 60 mg/kg x 2 d, total body irradiation 12 Gy two daily fractions x 3 d) followed by CD34(+)-selected autologous peripheral blood stem cell transplantation (CD34(+)-APBSCT) was then prescribed. Complete remission (CR) was obtained and she has been free of disease for 34 months since CD34(+)-APBSCT. We suggest that marrow-ablative chemotherapy facilitated by autologous stem cell transplantation should be considered part of the primary therapy for subjects with a poor prognosis for nasal NK/T-cell lymphoma with cutaneous involvement.     

High-capacity electrode materials for rechargeable lithium batteries: Li3NbO4-based system with cation-disordered rocksalt structure

Rechargeable lithium batteries have rapidly risen to prominence as fundamental devices for green and sustainable energy development. Lithium batteries are now used as power sources for electric vehicles. However, materials innovations are still needed to satisfy the growing demand for increasing energy density of lithium batteries. In the past decade, lithium-excess compounds, Li₂MeO₃ (Me = Mn⁴⁺, Ru⁴⁺, etc.), have been extensively studied as high-capacity positive electrode materials. Although the origin as the high reversible capacity has been a debatable subject for a long time, recently it has been confirmed that charge compensation is partly achieved by solid-state redox of nonmetal anions (i.e., oxide ions), coupled with solid-state redox of transition metals, which is the basic theory used for classic lithium insertion materials, such as LiMeO₂ (Me = Co³⁺, Ni³⁺, etc.). Herein, as a compound with further excess lithium contents, a cation-ordered rocksalt phase with lithium and pentavalent niobium ions, Li₃NbO₄, is first examined as the host structure of a new series of high-capacity positive electrode materials for rechargeable lithium batteries. Approximately 300 mAh⋅g⁻¹ of high-reversible capacity at 50 °C is experimentally observed, which partly originates from charge compensation by solid-state redox of oxide ions. It is proposed that such a charge compensation process by oxide ions is effectively stabilized by the presence of electrochemically inactive niobium ions. These results will contribute to the development of a new class of high-capacity electrode materials, potentially with further lithium enrichment (and fewer transition metals) in the close-packed framework structure with oxide ions.To realize sustainable energy development in the future, it is widely admitted that the substitution of energy sources for fossil fuels must be considered. An efficient energy storage system using an electrochemical method, such as rechargeable lithium batteries (Li-ion batteries, LIBs), potentially provides the solution to meet these tough challenges. Now, electric vehicles equipped with an electric motor and LIB have been launched in the market, and LIBs are starting to substitute for fossil fuels as power sources in the transportation system using the technology of internal combustion engines. Since their first appearance as power sources for portable electronic devices in 1991, the technology of LIBs has now become sufficiently sophisticated. Nevertheless, the demands for a further increase in energy density are still growing to extend the driving distance for electric vehicles.In 1980, LiCoO₂ with a cation-ordered rocksalt structure (layered type) was first proposed as a positive electrode material for LIBs (1) and is still widely used for high-energy mobile applications. After this finding, lithium insertion materials with cation-ordered rocksalt-type structures, LiMeO₂ (Me = Co³⁺, Ni³⁺, etc.) have been extensively studied as electrode materials. In the past decade, Li-enriched materials, Li₂MeO₃-type layered materials (Me = Mn⁴⁺, Ru⁴⁺, etc.), which are also classified as having cation-ordered rocksalt-type structures (2), have been extensively studied as potential high-capacity electrode materials, especially for the Mn⁴⁺ system (Li₂MnO₃) (3–7). Li₂MnO₃ had been originally thought to be electrochemically inactive because oxidation of Mn ions beyond the tetravalent state is difficult. However, the fact is that Li₂MnO₃ is electrochemically active, presumably because of the contribution of oxide ions for redox reaction. Although the oxidation of oxide ions in Li₂MnO₃ results in partial oxygen loss with irreversible structural changes (5, 6), solid-state redox reaction of oxide ions is effectively stabilized in the Li₂Ru_1-xSn_xO₃ system (8). Nearly 1.6 mol of Li⁺ are reversibly extracted from Li₂Ru_0.75Sn_0.25O₃ with excellent capacity retention, indicating that unfavorable phase transition is effectively suppressed in this system.Historically, such charge compensation by nonmetal anions has already been evidenced in sulfides before 1990 (9). Because sulfide ions are relatively soft and polarizable anion compared with oxide ions, oxidation of sulfide ions to persulfide ions is easier than that of oxide ions. The voltage as positive electrode materials is also much more attractive for the oxide ions [∼2 V vs. Li for S²⁻/S₂²⁻ (9) and more than 3 V vs. Li for O²⁻/O₂²⁻ (8)]. The possibility of charge compensation by oxide ions on lithium extraction was also discussed for late-transition metal oxides before 2000 (10, 11). Similarly, such rearrangement of charge was known when metal 3d orbital was heavily hybridized with oxygen 2p orbital, for instance Fe⁴⁺ in SrFeO₃ (12). Nevertheless, a clear and unambiguous contribution of the oxide ions for charge compensation on “electrochemical lithium extraction” was first evidenced in 2013 on the basis of an arsenal of characterization techniques with a concept of a reductive coupling mechanism (8).The use of oxide ion redox is an important strategy to further increase the reversible capacity of positive electrode materials for LIBs because the lithium content is potentially further enriched with a lower amount of transition metals in the framework structure. Reversible capacity as electrode materials is not limited by the absence of oxidizable transition metals as a redox center. Negatively charged oxide ions can potentially donate electrons instead of transition metals. However, oxidation without transition metals inevitably results in the release of oxygen molecules (e.g., electrochemical decomposition of Li₂O₂) (13).Based on these considerations, we have decided to investigate the rocksalt phase with pentavalent niobium ions (i.e., Li₃NbO₄). Approximately 300 mAh⋅g⁻¹ of reversible capacity at 50 °C is experimentally observed for a manganese-substituted Li₃NbO₄-based sample. Large reversible capacity is seen to partly originate from charge compensation by reversible solid-state redox of oxide ions, coupled with conventional redox reactions of transition metals. From these results, we will discuss the possibility of a new class of high-capacity electrode materials, potentially with further lithium enrichment in the close-packed framework structure with oxide ions.     

Transnodal lymphangiography and post-CT for protein-losing enteropathy in Noonan syndrome

Noonan syndrome, which is a multiple congenital disorder, may be associated with lymphatic abnormalities. Protein-losing enteropathy (PLE) developing in Noonan syndrome is rare. We performed transnodal lymphangiography by directly accessing bilateral inguinal nodes under ultrasound guidance in a 17-year-old female with PLE developing in Noonan syndrome to assess detailed anatomical findings regarding lymphatic vessels. There have been no reports on transnodal lymphangiography for Noonan syndrome. Post-lymphangiographic CT images revealed multiple lymphatic abnormalities and lipiodol extravasation into the duodenum and the proximal jejunum. Transnodal lymphangiography was easy and safe for PLE developing in Noonan syndrome, and post-lymphangiographic CT provided invaluable information.     

Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort

Objective

Concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer. We studied prognostic factors for patients treated with CCRT.

Methods

We retrospectively reviewed records of 85 consecutive patients with cervical cancer who were treated with CCRT between 2002 and 2011, with external beam radiation therapy, intracavitary brachytherapy, and platinum-based chemotherapy. Survival data were analyzed with Kaplan-Meier methods and Cox proportional hazard models.

Results

Of the 85 patients, 69 patients (81%) had International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease; 25 patients (29%) had pelvic lymph node enlargement (based on magnetic resonance imaging), and 64 patients (75%) achieved clinical remission following treatment. Median maximum tumor diameter was 5.5 cm. The 3- and 5-year overall survival rates were 60.3% and 55.5%, respectively. Cox regression analysis showed tumor diameter >6 cm (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2 to 4.6), pelvic lymph node enlargement (HR, 2.2; 95% CI, 1.1 to 4.5), and distant metastasis (HR, 10.0; 95% CI, 3.7 to 27.0) were significantly and independently related to poor outcomes.

Conclusion

New treatment strategies should be considered for locally advanced cervical cancers with tumors >6 cm and radiologically enlarged pelvic lymph nodes.     

Adjuvant treatment with tumor-targeting Salmonella typhimurium A1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model

Colon cancer liver metastasis is often the lethal aspect of this disease. Well-isolated metastases are candidates for surgical resection, but recurrence is common. Better adjuvant treatment is therefore needed to reduce or prevent recurrence. In the present study, HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used to establish liver metastases in nude mice. Mice with a single liver metastasis were randomized into bright-light surgery (BLS) or the combination of BLS and adjuvant treatment with tumor-targeting S. typhimurium A1-R. Residual tumor fluorescence after BLS was clearly visualized at high magnification by fluorescence imaging. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase survival and disease-free survival after BLS of liver metastasis. The results suggest the future clinical potential of adjuvant S. typhimurium A1-R treatment after liver metastasis resection.     

Radiation sensitivity assay with a panel of patient‐derived spheroids of small cell carcinoma of the cervix

Small cell carcinoma of the uterine cervix (SCCC) is a rare cancer with a poor prognosis for which no standard treatment exists. Here, we successfully established panels of patient‐derived spheroid cultures from six SCCC patient samples by cancer tissue–originated spheroids (CTOS) method. To assess the intrinsic radiosensitivity and mechanism of radioresistance in individual SCCC patients, we further developed an in vitro sensitivity assay for radiation. Radiation sensitivity in the CTOS assay varied among individual cases and was consistent with in vivo radiation sensitivity using CTOS‐derived xenograft tumors in the examined cases. Furthermore, by comparing gene expression in CTOSs with different radiosensitivity, we found that expression of hypoxia‐inducible factor‐1α (HIF‐1α) target genes was upregulated in resistant CTOSs. HIF‐1α protein levels increased several hours after irradiation. In a radioresistant CTOS, an inhibitor of heat shock protein 90 (HSP90) suppressed radiation‐induced HIF‐1α expression. Suppression of HIF‐1α by small hairpin RNA significantly enhanced the effect of radiation, at least in part by promoting radiation‐induced apoptosis. HSP90 inhibitor also increased radiation sensitivity. Our results indicate that radiation‐induced HIF‐1α upregulation was one mechanism of radioresistance in a radioresistant SCCC CTOS. Accumulating CTOS lines may provide a good platform to study characters of rare cancers like SCCC.