Oxidative DNA Damage by N4-hydroxycytidine, a Metabolite of the SARS-CoV-2 Antiviral Molnupiravir.

Molnupiravir is an antiviral agent recently used for treating coronavirus disease 2019 (COVID-19). Here, we demonstrate that N4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)-mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC. The site specificity of DNA damage also suggested involvement of hydroxylamine in the damage. Furthermore, Cu(I) and H2O2 play an important role in the DNA damage. We propose oxidative DNA damage via CDA-mediated metabolism as a possible mutagenic mechanism of NHC, highlighting the need for careful risk assessment of molnupiravir use in therapies for viral diseases, including COVID-19.

Free-Standing Electrode and Fixed Surface Tiny Electrode Implemented Triboelectric Nanogenerator with High Instantaneous Current.

Conventional triboelectric nanogenerators (TENGs) face challenges pertaining to low output current density at low working frequencies and high internal impedance. While strategies, such as surface modification to enhance surface charge density, permittivity regulation of materials, and circuit management, have partially mitigated these issues. However, they have also resulted in increased complexity in the fabrication process. Therefore, there is an urgent demand for a universal and simplified approach to address these challenges. To fulfill this need, this work presents a free-standing electrode and fixed surface tiny electrode implemented triboelectric nanogenerator (FFI-TENG). It is fabricated by a straightforward yet effective method: introducing a tiny electrode onto the surface of the tribo-negative material. This approach yields substantial enhancements in performance, notably a more than tenfold increase in output current density, a reduction in effective working frequencies, and a decrease in matching resistance as compared to vertical contact-separation TENGs (CS-TENGs) or single-electrode TENGs (SE-TENGs). Simultaneously, a comprehensive examination and proposition regarding the operational mechanism of FFI-TENG, highlighting its extensive applicability are also offered. Significantly, FFI-TENG excels in mechanical energy harvesting even under ultra-low working frequencies (0.1 Hz), outperforming similar contact-separation models. This innovation positions it as a practical and efficient solution for the development of low-entropy energy harvesters.

Effect of cerebrospinal fluid drainage pressure in descending and thoracoabdominal aortic repair: a prospective multicenter observational study.

PURPOSE: Cerebrospinal fluid drainage (CSFD) is recommended during open or endovascular thoracic aortic repair. However, the incidence of CSFD complications is still high. Recently, CSF pressure has been kept high to avoid complications, but the efficacy of CSFD at higher pressures has not been confirmed. We hypothesize that CSFD at higher pressures is effective for preventing motor deficits. METHODS: This prospective observational study included 14 hospitals that are members of the Japanese Society of Cardiovascular Anesthesiologists. Patients who underwent thoracic and thoracoabdominal aortic repair were divided into four groups: Group 1, CSF pressure around 10 mmHg; Group 2, CSF pressure around 15 mmHg; Group 3, CSFD initiated when motor evoked potential amplitudes decreased; and Group 4, no CSFD. We assessed the association between the CSFD group and motor deficits using mixed-effects logistic regression with a random intercept for the institution. RESULTS: Of 1072 patients in the study, 84 patients (open surgery, 51; thoracic endovascular aortic repair, 33) had motor deficits at discharge. Groups 1 and 2 were not associated with motor deficits (Group 1, odds ratio (OR): 1.53, 95% confidence interval (95% CI): 0.71-3.29, p = 0.276; Group 2, OR: 1.73, 95% CI: 0.62-4.82) when compared with Group 4. Group 3 was significantly more prone to motor deficits than Group 4 (OR: 2.56, 95% CI: 1.27-5.17, p = 0.009). CONCLUSION: CSFD is not associated with motor deficits in thoracic and thoracoabdominal aortic repair with CSF pressure around 10 or 15 mmHg.

Photon transport enhancement through a coupled-cavity QED system with dynamic modulation.

We investigate photonic transport through fiber optical cavities under tunable fast modulation, which is induced by modulating atom-cavity coupling in a cavity quantum electrodynamics (CQED) system. The modulation bandwidth exceeds the timescales of all other system processes, such as cavity decay and atom-cavity coupling, and allows control of the dynamics of photonic transport through the cavity array. The transmission as a function of the modulation frequency clearly shows enhancement peaks in single cavity and two coupled-cavity cases. In particular, in the coupled-cavity case, the position of the enhancement peak is shifted due to the delocalized cavity field in the coupled system.

Single-frequency fiber Fabry-Perot Brillouin laser.

We demonstrate single-frequency stimulated Brillouin lasing in short fiber Fabry-Perot resonators. A sub-milliwatt threshold for lasing is observed in resonators with high quality factors of ∼1.5 × 108 and effective resonator lengths as short as ∼5 mm. The strong dispersion of fiber Bragg gratings results in unequal frequency separations for neighboring pairs of longitudinal modes with separation differences larger than the Brillouin gain bandwidth, thereby avoiding cascaded lasing. Our achievement will enable compact, robust, efficient narrow-linewidth light sources.

Comparison of Body Fluid Volumes Determined by Kinetic Modeling and by Bioimpedance Spectroscopy.

INTRODUCTION: The bioimpedance spectroscopy (BIS) method is used in individual patients requiring body fluid volume measurement. In a hemodialysis facility, however, regular screening of body fluid volumes is also necessary. Such screening, by kinetic modeling, may become possible by calculating distribution volumes of urea and uric acid from regular blood test results. OBJECTIVE: The aim is to compare uric acid distribution volumes with BIS-extracellular volume, urea distribution volume with BIS-total body water, and difference between urea and uric acid distribution volumes with BIS-intracellular volume. METHODS: We reanalyzed stored blood test data of 53 hemodialysis patients obtained together with BIS data of the same patients in our previous study. RESULTS: Significant correlations were found between urea distribution volume and total body water predicted by the BIS method, between uric acid distribution volume and extracellular volume predicted by the BIS method, and between the difference of uric acid distribution volume from urea distribution volume and intracellular volume predicted by the BIS method. In Bland-Altman analysis, comparison of each pair showed no systematic error. The mean difference between each pair was minimal. CONCLUSION: Fluid volumes in different body compartments can be estimated by kinetic modeling as well as by the BIS method.

Thioxothiazolidin derivative, 4-OST, inhibits melanogenesis by enhancing the specific recruitment of tyrosinase-containing vesicles to lysosome.

Tyrosinase catalyzes the rate-limiting step in melanin synthesis. Melanin is synthesized from l-tyrosin in the melanosomes, where tyrosinase and other melanogenic factors are recruited via the vesicle transport system. Genetic and biochemical approaches have revealed a correlation between impairments in the vesicle transport system and albinism. However, the specificity of the individual transport systems for the corresponding melanogenic factors has not been well elucidated yet. Here, we report that the thioxothiazolidin derivative, 4-OST (4-[(5E)-5-[(4-fluorophenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-4-azatricyclo [5.2.1.02 ,6]dec-8-ene-3,5-dione: CAS RN. 477766-87-3) strongly inhibited melanogenesis in mouse melanoma B16F10 cells. 4-OST reduces tyrosinase protein levels without affecting its messenger RNA levels or enzymatic activity. Although a reduction in tyrosinase protein level was observed in the presence of a protein synthesis inhibitor, the reduction may be coupled with protein synthesis. Similarly, GIF-2202 (a derivative of 4-OST) lowers tyrosinase protein levels without affecting the levels of another melanogenic enzyme, tyrosinase-related protein 1 (TYRP1) level. The reduction in tyrosinase protein level is associated with an increase in the levels of the lysosomal proteinase cathepsin S. Chloroquine, a lysosome inhibitor, restored the tyrosinase protein level downregulated by GIF-2202, although no effects of other inhibitors (against proteasome, autophagy, or exocytosis) were observed. In addition, GIF-2202 segregated the immunofluorescence signals of tyrosinase from those of TYRP1. Chloroquine treatment resulted in co-localization of tyrosinase and cathepsin S signals near the perinuclear region, suggesting that 4-OST and GIF-2202 may alter the destination of the tyrosinase vesicle from the melanosome to the lysosome. 4-OST and GIF-2202 can be new tools for studying the tyrosinase-specific vesicle transport system.

Heat-retention effects of hydrogen-rich water bath assessed by thermography for humans.

Hydrogen-rich water bath devices are commercially available, but have been scarcely clarified for heat-retention effects. In this study, heat-retention effects of hydrogen-rich water bath were assessed by thermographic clinical trials, which employed twenty-four healthy subjects. The thermograms indicated that, under the same conditions (41 °C, 10-min bathing), hydrogen-rich water bath (hydrogen concentrations: 185-548 µg/L; oxidation-reduction potentials: -167 to -91 mV, versus 0.8 µg/L and +479 mV for normal bath, respectively) brought about the heat-retention being more marked than those of normal water bath for several body-parts in the order as follows: abdomen > upper legs > arms > hands > feet, for 30- and 60-min post-bathing, being in contrast to scarce heat-retention for head, armpits and lower legs. Then, as reflection to promotive effects on blood stream, we also examined the thickness of fingertip-capillary in hands. The thickness was expanded in the hydrogen-rich water bath more markedly than that in the normal water bath, suggesting that the hydrogen-rich water bath may have the hydrogen-based promotive effect, exceeding over mere heat retention-based effects, on blood circulation of the whole body. Meanwhile, the heat-retention in hydrogen-rich water bath weakly or moderately correlated with contents of the subcutaneous fat, whole body fat and body mass index, and inversely correlated with skeletal muscle rates, although their correlation degrees did not obviously exceed over normal water bath, with a poor relation with the basal metabolism rate. Thus, the hydrogen-rich water bath was suggested to exert heat-retention effects exceeding over normal water bath, in diverse body-parts such as abdomen, upper legs, arms and hands, via promotion to blood flow which was reflected by expanding the thickness of capillary. The heat-retention after bathing can be noted as effects of the hydrogen-rich water bath, which is applicable for most of people widespread regardless of their body composition index.

Cerebrospinal fluid drainage to prevent postoperative spinal cord injury in thoracic aortic repair.

BACKGROUND: Cerebrospinal fluid drainage (CSFD) is recommended as a spinal cord protective strategy in open and endovascular thoracic aortic repair. Although small studies support the use of CSFD, systematic reviews have not suggested definite conclusion and a large-scale study is needed. Therefore, we reviewed medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open and endovascular repair) at multiple institutions to assess the association between CSFD and postoperative motor deficits. METHODS: Patients included in this study underwent descending or thoracoabdominal aortic repair between 2000 and 2013 at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery. We conducted a retrospective study to investigate whether motor-evoked potential monitoring is effective in reducing motor deficits in thoracic aortic aneurysm repair. We use the same dataset to examine whether CSFD reduces motor deficits after propensity score matching. RESULTS: We reviewed data from 1214 patients [open surgery, 601 (49.5%); endovascular repair, 613 (50.5%)]. CSFD was performed in 417 patients and not performed in the remaining 797 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. After propensity score matching (n = 700), mixed-effects logistic regression performed revealed that CSFD is associated with postoperative motor deficits at discharge [adjusted odds ratio (OR), 3.87; 95% confidence interval (CI), 2.30-6.51]. CONCLUSION: CSFD may not be effective for postoperative motor deficits at discharge.

Comparison of Right Ventricular Function Between Patients With and Without Pulmonary Hypertension Owing to Left-Sided Heart Disease: Assessment Based on Right Ventricular Pressure-Volume Curves.

OBJECTIVES: Right ventricular (RV) failure with pulmonary hypertension (PH) is frequently encountered in patients with advanced left-sided heart disease (LHD). However, RV energetics in patients with postcapillary PH because of LHD has not been well studied. The authors investigated intraoperative RV energetics in patients with PH due to LHD based on pressure-volume curves with three-dimensional transesophageal echocardiography and pulmonary artery catheterization. DESIGN: Exploratory study. SETTING: National center. PARTICIPANTS: Thirty-three patients who underwent cardiac surgery for LHD were enrolled. Ten patients had PH (mean pulmonary artery pressure ≥ 25 mmHg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: RV stroke work index (RVSWI) was calculated by integrating the area bounded by the pressure-volume curve. RV minute work index (RVMWI) was calculated as RVSWI × heart rate. Right ventriculo-arterial coupling was estimated as stroke volume divided by end-systolic volume (SV/ESV). The authors compared RV energetics between patients with and without PH because of LHD. RVSWI and RVMWI were significantly higher in patients with PH (690.7 mmHg·mL/m2 [601.6-737.1] v 440.9 mmHg·mL/m2 [330.8-585.3], p = 0.015, and 60,068 mmHg·mL/m2/min [35,547-68,741] v 26,351 mmHg·mL/m2/min [17,316-32,517], p = 0.011, respectively), although cardiac index was nearly identical. SV/ESV was significantly lower in patients with PH (0.520 [0.305-0.810] v 0.820 (0.650-1.090), p = 0.007). CONCLUSIONS: Although cardiac index was similar, RVSWI and RVMWI were significantly higher and SV/ESV was significantly lower in patients with PH because of LHD, suggesting that patients with postcapillary PH have inefficient RV performance.

Azepine derivative T4FAT, a new copper chelator, inhibits tyrosinase.

Melanin plays an important role in the protection of the skin from ultraviolet irradiation. However, excessive melanin deposition leads to hyperpigmentation and freckles, which are recognized as skin problems, and signs of aging. Tyrosinase, a copper-containing protein, is the rate-limiting enzyme in melanin biosynthesis and first catalyzes the hydroxylation of l-tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and the further oxidization to dopaquinone. To assist the proper regulation of melanin production, we screened compounds and found that 5,6,7,8-tetrahydro-4H-furo[3,2-c]azepine-4-thione (T4FAT), a thioamide derivative, inhibited melanogenesis in B16F10 mouse melanoma cells. T4FAT was not toxic to cells and was stable in water; in addition, it inhibited the activity of tyrosinase derived from mushroom and B16F10 cells in a non-competitive manner. T4FAT downregulated tyrosinase protein expression in B16F10 cells without affecting mRNA expression. As copper binding to the tyrosinase protein is required for both enzymatic activity, correct folding, and maturation, we examined the metal-chelating activities of T4FAT. Equimolar amount of T4FAT resulted in almost complete chelation of copper ions. The thioamide group of T4FAT is essential for copper chelation and tyrosinase inhibition, which subsequently resulted in melanogenesis inhibition in B16F10 cells. Although T4FAT has similar in vitro properties to kojic acid, which is also a copper chelator and approved as a component of cosmetic formulations, T4FAT inhibited melanogenesis in B16F10 cells 30 times more efficiently than kojic acid. These results suggested that T4FAT, a novel copper chelator, may be helpful for the development of new cosmetics for skin whitening.

Cavity Dark Mode of Distant Coupled Atom-Cavity Systems.

We report on a combined experimental and theoretical investigation into the normal modes of an all-fiber coupled cavity-quantum-electrodynamics system. The interaction between atomic ensembles and photons in the same cavities, and that between the photons in these cavities and the photons in the fiber connecting these cavities, generates five nondegenerate normal modes. We demonstrate our ability to excite each normal mode individually. We study particularly the "cavity dark mode," in which the two cavities coupled directly to the atoms do not exhibit photonic excitation. Through the observation of this mode, we demonstrate remote excitation and nonlocal saturation of atoms.

Association Between Motor-Evoked Potentials and Spinal Cord Damage Diagnosed With Magnetic Resonance Imaging After Thoracoabdominal and Descending Aortic Aneurysm Repair.

OBJECTIVES: The authors investigated the association between intraoperative motor-evoked potential (MEP) changes and the severity of spinal cord infarction diagnosed with magnetic resonance imaging (MRI) to clarify the discrepancy between them, which was observed in patients with postoperative motor deficits after thoracic and thoracoabdominal aortic surgery. DESIGN: A multicenter retrospective study. SETTING: Motor-evoked potential <25% of control values was deemed positive for spinal cord ischemia. The severity of spinal cord infarction was categorized into grades A to D based on previous studies using the most severe axial MRI slices. The associations between MRI grade, MEP changes, and motor deficits were examined using logistic regression. PARTICIPANTS: Twenty-three of 1,245 patients (from 1999 to 2013, at 12 hospitals in Japan) were extracted from medical records of patients who underwent thoracic and thoracoabdominal aortic repair, with intraoperative MEP examinations and postoperative spinal MRI. INTERVENTIONS: No intervention (observational study). MEASUREMENTS AND MAIN RESULTS: Motor-evoked potential <25% of control value was associated significantly with motor deficits at discharge (adjusted odds ratio [OR], 130.0; p = 0.041), but not with severity of spinal cord infarction (adjusted OR, 0.917; p = 0.931). Motor deficit at discharge was associated with severe spinal cord infarction (adjusted OR, 4.83; p = 0.043), MEP <25% (adjusted OR, 13.95; p = 0.031), and combined deficits (motor and sensory, motor and bowel or bladder, or sensory and bowel or bladder deficits; adjusted OR, 31.03; p = 0.072) in stepwise logistic regression analysis. CONCLUSION: Motor-evoked potential <25% was associated significantly with motor deficits at discharge, but not with the severity of spinal cord infarction.

[A Case of Two Curative Resections for the Peritoneal Dissemination of Transverse Colon Cancer].

No large clinical trials have been conducted to prove the efficacy of peritoneal dissemination resection for colorectal cancer, and no evidence has shown the usefulness of resection for metachronous peritoneal dissemination. An elderly woman in her 70s underwent a laparoscopic transverse colectomy for transverse colon cancer in 2014, which was performed by another physician. The pathological diagnosis was tub2-por>muc, pT3, ly2, v0, pN2, and pStage Ⅲb. The patient was followed up with capecitabine plus oxaliplatin(CapeOX)therapy as an adjuvant chemotherapy for 6 months. Three years postoperatively, the CEA level increased to 10 ng/mL, and CT showed a nodular shadow in front of the left prerenal fascia. After the diagnosis of peritoneal dissemination recurrence and 8 courses of capecitabine plus bevacizumab therapy, other metastases were not observed. She was referred to our hospital for surgery and underwent laparoscopic peritoneal dissection at 3 years and 6 months after the first operation. Only one apparent disseminated recurrent lesion, which was resectable, was observed. However, at 4 years and 9 months after the initial operation, CT showed a recurrence of Douglas pouch peritoneal dissemination without any other obvious metastasis. Laparoscopic low anterior resection of the rectum and hysterectomy were performed. Here, we encountered a case that could be radically resected for peritoneal dissemination twice after the colon cancer surgery.

Clinical Utility of Intraoperative Motor-Evoked Potential Monitoring to Prevent Postoperative Spinal Cord Injury in Thoracic and Thoracoabdominal Aneurysm Repair: An Audit of the Japanese Association of Spinal Cord Protection in Aortic Surgery Database.

BACKGROUND: Spinal cord ischemic injury is the most devastating sequela of descending and thoracoabdominal aortic surgery. Motor-evoked potentials (MEPs) have been used to intraoperatively assess motor tract function, but it remains unclear whether MEP monitoring can decrease the incidence of postoperative motor deficits. Therefore, we reviewed multicenter medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open surgery and endovascular repair) to assess the association of MEP monitoring with postoperative motor deficits. METHODS: Patients included in the study underwent descending or thoracoabdominal aortic repair at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery between 2000 and 2013. Using multivariable mixed-effects logistic regression analysis, we investigated whether intraoperative MEP monitoring was associated with postoperative motor deficits at discharge after open and endovascular aortic repair. RESULTS: We reviewed data from 1214 patients (open surgery, 601 [49.5%]; endovascular repair, 613 [50.5%]). MEP monitoring was performed in 631 patients and not performed in the remaining 583 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. Multivariable logistic regression analysis revealed that postoperative motor deficits at discharge did not have a significant association with MEP monitoring (adjusted odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69-1.88; P = .624), but with other factors: history of neural deficits (adjusted OR, 6.08; 95% CI, 3.10-11.91; P < .001), spinal drainage (adjusted OR, 2.14; 95% CI, 1.32-3.47; P = .002), and endovascular procedure (adjusted OR, 0.45; 95% CI, 0.27-0.76; P = .003). The sensitivity and specificity of MEP <25% of control value for motor deficits at discharge were 37.8% (95% CI, 26.5%-49.5%) and 95.5% (95% CI, 94.7%-96.4%), respectively. CONCLUSIONS: MEP monitoring was not significantly associated with motor deficits at discharge.

Radiosensitization by Liposome-Encapsulated Fullerenes to Mitochondria/DNA-Damages on Human Melanoma Cells.

The polyhydroxy small-gap fullerenes [C120O30(OH)30 · 30H2O · 25Na+: SGFs] were encapsulated in multilamellar liposomes (Lpsm) composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS), which are designated as LpsmSGFs (DOPC/DOPS/SGFs = 35 mM:15 mM:246-445 µM, diameter = 141.2 nm, ζ-potential = -35.65 mV). Radiosensitization by LpsmSGFs under X-ray irradiation was evaluated on human melanoma HMV-II cells. On 7th day after X-ray irradiation, cell proliferation degree assessed by WST-8 decreased more markedly on cells pretreated with LpsmSGFs than Lpsm or free-SGFs. Fluorescent imaging of cells with Rhodamine123, dihydroethidium or anti-8-hydroxydeoxyguanosine antibody was monitored as an indicator for mitochondrial membrane potentials, intracellular superoxide anion radicals (O˙-2) or oxidative DNA-damages, respectively. After X-ray irradiation, LpsmSGFs obviously exhibited more augmented mitochondrial membrane potentials on perinuclear region of cells than Lpsm or free-SGFs. Without X-ray irradiation, superoxide anion radicals were found principally in the cytoplasm, but, when exposed to X-ray, they were found in cell nuclei associated with oxidative DNA-damages on cells pretreated with LpsmSGFs. Meanwhile, the oxidation-reduction potentials of SGFs aqueous solution increased by X-ray irradiation. These results suggest that LpsmSGFs-mediated generation of reactive oxygen species results in damages to cellular components such as mitochondria and DNA on cells, and thereby cell proliferation decreased. The LpsmSGFs has a potential as a pro-oxidative type radiosensitizer.

Reappearance of Motor-Evoked Potentials During the Rewarming Phase After Deep Hypothermic Circulatory Arrest.

OBJECTIVE: Although motor-evoked potentials (MEPs) disappear in deep hypothermic circulatory arrest (DHCA), MEPs have been used to confirm whether motor function is intact after DHCA. It is crucial to know the timing, body temperature, and MEP amplitude at MEP reappearance to detect spinal cord ischemia after DHCA. However, data on these parameters are sparse. The authors investigated the characteristics of MEPs at reappearance after DHCA. DESIGN: A retrospective observational study. SETTING: Single national center. PARTICIPANTS: Sixty-one patients who underwent descending aortic replacement and thoracoabdominal aortic replacement with DHCA between January 2013 and December 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors extracted the following data: time to MEP reappearance after the end of lower extremity circulatory arrest, bladder temperature (BT) and nasopharyngeal temperature (NPT) when MEPs recovered, and %amplitude of MEPs relative to control values at MEP reappearance. The median time to MEP reappearance was approximately 70 minutes. BT at MEP reappearance ranged from 34.3°C to 34.6°C and NPT ranged from 36.2°C to 36.4°C. At MEP reappearance, %amplitude less than 50% of the control value was observed in more than 50% of patients. Time to MEP reappearance had a significant positive association with rewarming time (p < 0.01) and BT (p = 0.03). CONCLUSIONS: There was a wide variation in MEP amplitude at reappearance during the rewarming phase. BT was approximately 34°C when MEPs in the leg recovered. The time to MEP reappearance is influenced significantly by rewarming time and BT.

[A Case of Peritoneal Dissemination of Metastatic Gastric Cancer with Successful Docetaxel and S-1 Combination Therapy].

Here, we report a long-term survival case treated with docetaxel and S-1 combination therapy(DS therapy)for peritoneal dissemination of gastric cancer. A 58-year-old man was diagnosed with gastric cancer in 2006. Distal gastrectomy, D2 dissec- tion, and RY reconstruction were performed. The pathological diagnosis was gastric cancer, por2, pT3(SS), pN3a(8/27), pStage ⅢB. S -1 monotherapy was administered as an adjuvant chemotherapy for 1 year from 3 months after surgery. Five years after surgery, peritoneal dissemination and bladder recurrence caused rectal stenosis and hydronephrosis. We performed ileostomy and left nephrostomy. DS therapy was started 5 years and 2 months after the initial surgery. A complete clinical remission was observed 2 years and 10 months after starting DS therapy(23 courses). Multiple lymph node metastasis and bone metastasis were confirmed at 5 years and 5 months(57 courses). Even though irinotecan monotherapy was performed for five courses, the bone and lymph node metastasis increased at 5 years and 9 months after starting DS therapy, and the patient died at 69 years of age. DS therapy may be a useful option for peritoneal metastasis of gastric cancer.

Effect of posture and extracranial contamination on results of cerebral oximetry by near-infrared spectroscopy.

BACKGROUND: Near-infrared spectroscopy (NIRS)-based cerebral oximetry is a noninvasive technology used to estimate regional cerebral oxygen saturation (rSO2). Extracranial blood flow is known to substantially affect rSO2 values measured by most clinically available devices. Several studies have also reported that the Trendelenburg position and upright position have a larger effect on rSO2 measurements than the supine position. Therefore, we investigated the effect of these two positions (the Trendelenburg position versus the upright position) and extracranial contamination on rSO2 measurements obtained using two commercially available devices and one prototype device. METHODS: Twelve healthy volunteers were enrolled in the study. They each had three cerebral oximetry devices applied to their forehead (FORE-SIGHT ELITE™, CAS Medical Systems Inc., Branford, CT, USA; INVOS 5100c™, Medtronic, Minneapolis, MN, USA; and NIRO-TRS, Hamamatsu Photonics, Hamamatsu, Japan). A circumferential pneumatic head cuff was positioned proximal to the NIRS cerebral oximetry sensors. We measured rSO2, heart rate (HR), and blood pressure (BP) in six conditions (supine, Trendelenburg and upright positions, with and without scalp ischemia induced by head cuff inflation) every 5 min with each oximetry device. Total hemoglobin (tHb), which is associated with cerebral blood volume (CBV) as measured by positron emission tomography, was measured using the NIRO-TRS device to determine extracranial blood volume in each position. RESULTS: Measurements of rSO2 with all the devices were affected by extracranial contamination. The percentage of extracranial contamination was highest with INVOS 5100c™ in the upright position (INVOS, 21.3%; FORE-SIGHT, 14.3%; NIRO-TRS, 3.6%). Measurements of rSO2 obtained in the upright position were significantly lower than those obtained in the supine position, using INVOS-5100c™ and FORE-SIGHT ELITE™ (71 vs. 74% and 67 vs. 72%, respectively), but not using NIRO-TRS (62 vs. 64%). A significant decrease in tHb was observed after head cuff inflation in the supine and Trendelenburg positions (supine, 0.132-0.123 µmol/l; Trendelenburg, 0.133-0.125 µmol/l). CONCLUSIONS: Except when using NIRO-TRS, measurements of rSO2 in the forehead are significantly lower when measured in the upright position than in the supine position. All devices in this study were affected by extracranial contamination.

Cardiac Resynchronization Therapy-Induced Cardiac Index Increase Measured by Three-Dimensional Echocardiography Can Predict Decreases in Brain Natriuretic Peptide.

OBJECTIVES: First, to examine the perioperative association between increased cardiac index (CI) measured using three-dimensional echocardiography (CI3D), two-dimensional echocardiography (CI2D), and FloTrac/Vigileo (CIFT) (Edwards Lifesciences, Irvine, CA) after cardiac resynchronization therapy (CRT) and decreased brain natriuretic peptide (BNP) 6 months after CRT. Second, to evaluate the accuracy and tracking ability of CI2D and CIFT. DESIGN: A prospective clinical study. SETTING: A cardiac surgery operating room in a single cardiovascular center. PARTICIPANTS: Forty-five patients undergoing elective CRT lead implantation. INTERVENTIONS: CIFT and CI2D were determined simultaneously before and after CRT using CI3D as the reference method. MEASUREMENTS AND MAIN RESULTS: BNP was measured before CRT and 6 months after CRT. Areas under the receiver operator characteristic curves (AUCs) were calculated for each method of measurement to predict BNP decrease. AUC was largest for CI3D (AUC = 0.735, p = 0.017). Bland-Altman analysis revealed that the percentage error was 58% for CIFT and 28% for CI2D. A polar plot analysis showed that the mean angular bias was -7.26° and 0.64°, the radial limits of agreement were 70° and 29.4°, and the concordance rate was 67.7% and 93.8% for CIFT and CI2D, respectively. CONCLUSIONS: CI significantly increased after CRT in patients whose BNP level decreased 6 months after CRT. However, only CI3D could predict decreases in BNP 6 months after CRT. Although CI2D was acceptable compared with CI3D, the tracking ability of CI changes was just below acceptable. CIFT has a wide limit of agreement with CI3D, with a poor tracking ability.