Muscle weakness is more strongly associated with functional outcomes in patients with stroke than sarcopenia or muscle wasting: an observational study.

BACKGROUND: Stroke-related sarcopenia is an important prognosis factor and an intervention target for improving outcomes in patients with stroke. AIM: This study aimed to identify the association between sarcopenia, possible sarcopenia, muscle weakness, muscle mass and calf circumference, and the functional outcomes 3 months after stroke. METHODS: In this single-centre prospective observational study, muscle strength, muscle mass, and calf circumference were measured in patients with acute stroke at hospital discharge. Diagnosis of sarcopenia, possible sarcopenia, muscle weakness, low muscle mass, and low calf circumference were defined according to the 2019 Asian Working Group for Sarcopenia criteria. The primary outcome measure was the modified Rankin Scale (mRS) score at 3 months, with an mRS score of 3 or higher indicating a poor outcome. Logistic regression analysis was conducted to examine independent associations between each assessment and functional outcomes. RESULTS: A total of 247 patients (median age: 73 years) were included in this study. The prevalence of sarcopenia was 28% (n = 70), and in the adjusted model, sarcopenia (aOR = 2.60, 95% CI 1.07-6.31, p = 0.034), muscle weakness (aOR = 3.40, 95% CI 1.36-8.52, p = 0.009), and low muscle mass (aOR = 2.61, 95% CI 1.04-6.52) were significantly associated with poor functional outcome. Nevertheless, other evaluations did not demonstrate an independent association with the outcome. CONCLUSION: Sarcopenia, muscle weakness, and low muscle mass were found to be independently associated with functional outcomes 3 months after stroke, and muscle weakness exhibited the strongest association with outcomes among them.

Modification of the lesser curvature incision line enhanced gastric conduit perfusion as determined by indocyanine green fluorescence imaging and decreased the incidence of anastomotic leakage following esophagectomy.

AIM: This study aimed to investigate the effectiveness of a modified incision line on the lesser curvature for gastric conduit formation during esophagectomy in enhancing the perfusion of gastric conduit as determined by indocyanine green fluorescence imaging and reducing the incidence of anastomotic leakage. METHODS: A total of 272 patients who underwent esophagectomy at our institute between 2014 and 2022 were enrolled in this study. These patients were divided based on two different types of cutlines on the lesser curvature: conventional group (n = 141) following the traditional cutline and modified group (n = 131) adopting a modified cutline. Gastric conduit perfusion was assessed by ICG fluorescence imaging, and clinical outcomes after esophagectomy were evaluated. RESULTS: The distance from the pylorus to the cutline was significantly longer in the modified group compared with the conventional group (median: 9.0 cm vs. 5.0 cm, p < 0.001). The blood flow speed in the gastric conduit wall was significantly higher in the modified group than that in the conventional group (median: 2.81 cm/s vs. 2.54 cm/s, p = 0.001). Furthermore, anastomotic leakage was significantly lower (p = 0.024) and hospital stay was significantly shorter (p < 0.001) in the modified group compared with the conventional group. Multivariate analysis identified blood flow speed in the gastric conduit wall as the only variable significantly associated with anastomotic leakage. CONCLUSIONS: ICG fluorescence imaging is a feasible, reliable method for the assessment of gastric conduit perfusion. Modified lesser curvature cutline could enhance gastric conduit perfusion, promote blood circulation around the anastomotic site, and reduce the risk of anastomotic leakage after esophagectomy.

Effectiveness of computed tomography scoring for the early diagnosis of anastomotic leakage after esophagectomy.

PURPOSE: Anastomotic leakage after esophagectomy is associated with increased mortality; therefore, early diagnosis is highly important. This study aimed to identify the characteristic computed tomography (CT) findings of cervical anastomotic leakage after esophagectomy for esophageal cancer and evaluate the effectiveness of CT scoring in screening the anastomotic leakage. METHODS: Overall, 91 patients who underwent thoracoscopic esophagectomy with cervical esophago-gastric anastomosis were included. We investigated the correlation between anastomotic leakage and the presence of the microbubble sign, evident air retention, and fluid collection in the cervical and mediastinal regions. CT findings were scored, and the cutoff value was set to 2 points on the receiver operating characteristic curve. The patients were divided into two groups based on the CT score (≥ 2 points and ≤ 1 point). RESULTS: CT findings of the microbubble sign (p = 0.01; odds ratio [OR], 8.545; 95% confidence interval [CI], 1.596-45.73), cervical air retention (p < 0.01; OR, 12.43; 95% CI, 2.084-74.17), and cervical fluid collection (p < 0.01; OR, 9.359; 95% CI, 1.753-49.96) significantly correlated with anastomotic leakage. The ≥ 2-point CT score group showed a significantly higher incidence of anastomotic leakage than the ≤ 1-point group (p < 0.01; OR, 16.28; 95% CI [4.704-56.38]). A ≥ 2-point CT score had higher sensitivity (84.2%) than upper gastrointestinal series (36.8%). CONCLUSION: The presence of microbubble sign, air retention, and fluid collection in the cervical area correlated with anastomotic leakage after cervical anastomosis in thoracoscopic esophagectomy. CT scores are useful early anastomotic leakage detectors.

Usefulness of skeletal muscle measurement by computed tomography in patients with esophageal cancer: changes in skeletal muscle mass due to neoadjuvant therapy and the effect on the prognosis.

PURPOSE: This analysis was performed to clarify the usefulness of skeletal muscle measurements using computed tomography (CT) in patients with esophageal cancer and the effect of treatment-induced changes in the skeletal muscle mass on the prognosis. METHODS: Ninety-seven male patients who underwent thoracoscopic esophagectomy for esophageal squamous cell carcinoma were included in the study. The preoperative CT images were analyzed retrospectively. RESULTS: In a survival analysis performed according to the preoperative data of skeletal muscle, the low-skeletal muscle index (l-SMI) group had a poorer outcome than the normal skeletal muscle index (n-SMI) group in terms of both the overall survival (OS) and the relapse-free survival (RFS) (OS: P < 0.01, RFS: P = 0.01). In the multivariate analysis for the OS, preoperative l-SMI was an independent predictor (hazard ratio: 3.68, 95% confidence interval 1.32-10.2, P = 0.01). In patients who underwent neoadjuvant therapy (NAT), the SMI was significantly reduced after NAT (P < 0.01). The preoperative skeletal muscle area on CT was strongly correlated with the results of a bioelectrical impedance analysis (BIA) (ρ = 0.77, P < 0.01). CONCLUSIONS: A decreased preoperative skeletal muscle mass was associated with a poor outcome. In patients who underwent NAT, the SMI was significantly reduced after NAT. An analysis of the skeletal muscle mass using CT images was found to be useful for providing data that corresponded with BIA data.

Predictive impact of the thoracic inlet space on ICG fluorescence blood flow speed in the gastric conduit wall and anastomotic leakage after esophagectomy.

PURPOSE: The thoracic inlet space might influence the blood vessel perfusion in the gastric conduit. The purpose of this study was to clarify the impacts of the thoracic inlet space on blood vessel perfusion in the gastric conduit and anastomotic leakage after esophagectomy. METHODS: One hundred and forty-two esophageal cancer patients underwent esophagectomy followed by gastric conduit reconstruction via the retrosternal route. The blood flow speed in the gastric conduit was measured using indocyanine green fluorescence before and after reconstruction. Parameters at the thoracic inlet space were measured using CT. We then investigated the correlation between these two parameters and whether they could predict anastomotic leakage after esophagectomy. RESULTS: Blood flow speed in the gastric conduit was slower after reconstruction than before reconstruction (P < 0.001). The incidence of anastomotic leakage (n = 23) was higher among patients with a delayed blood flow speed before reconstruction (n = 27) than among those with a non-delayed blood flow speed before reconstruction (n = 115) (P < 0.001). Among the patients with a non-delayed blood flow speed before reconstruction, the thoracic inlet area (TIA, sternum-tracheal distance × clavicle head distance) was positively correlated with the blood flow speed after reconstruction (P = 0.023) and was identified as an independent predictor of anastomotic leakage (P < 0.001). CONCLUSION: A narrow TIA was associated with a delayed blood flow speed in the gastric conduit after reconstruction and was capable of predicting anastomotic leakage in the patients with a non-delayed blood flow speed before reconstruction.

Clinicopathological Role of Vasohibin in Gastroenterological Cancers: A Meta-Analysis.

Vasohibin-1 (VASH1) is an angiogenesis inhibitor, while vasohibin-2 (VASH2) is a proangiogenic factor. The roles of VASH1 and VASH2 expression in gastroenterological cancers remain unclear. We searched for relevant literature, specifically studies on gastroenterological cancer, and evaluated the relationship between VASH expression and clinical outcomes. Nine studies on VASH1 involving 1,574 patients were included. VASH1 expression was associated with the TNM stage [OR (odds ratio) 2.05, 95% CI (confidence interval) 1.24-3.40], lymph node metastasis (OR 1.79, 95% CI 1.24-2.58), lymphatic invasion (OR 1.95, 95% CI 1.41-2.68), and venous invasion (OR 2.49, 95% CI 1.60-3.88); poor clinical outcomes were associated with high VASH1 expression. High VASH1 expression was associated with a significantly shorter overall survival (OS) [HR (hazard ratio) 1.69, 95% CI 1.25-2.29] and disease-free survival (DFS) (HR 2.01, 95% CI 1.28-3.15). Three studies on VASH2 involving 469 patients were analyzed. VASH2 expression was associated with the TNM stage (OR 4.21, 95% CI 1.89-9.51) and venous invasion (OR 2.10, 95% CI 1.15-3.84); poor clinical outcomes were associated with high VASH2 expression. High VASH2 expression was associated with a significantly lower OS (HR 1.61, 95% CI 1.09-2.37). In conclusion, high VASH1 and VASH2 expression levels were associated with poor clinical outcomes and prognosis in patients with gastroenterological cancers.

Indocyanine green fluorescence imaging for evaluating blood flow in the reconstructed conduit after esophageal cancer surgery.

We investigated the effectiveness of indocyanine green (ICG) fluorescence blood flow imaging of the gastric conduit to evaluate anastomotic leakage after esophagectomy. We identified 19 articles using the PRISMA standard for systematic reviews. The more recent studies reported attempts at objective quantification of ICG fluorescence imaging, rather than qualitative assessment. Anastomotic leakage after esophagectomy occurred in 0-33% of the patients who underwent ICG fluorescence imaging. According to the six studies that compared the incidence of anastomotic leakage in the ICG group and the control group, it ranged from 0 to 18.3% in the ICG group and from 0 to 25.2% in the control group, respectively. Overall, the incidence of anastomotic leakage in the ICG group (8.4%) was lower than that in the control group (18.5%). Although the incidence of anastomotic leakage was as high as 43.1% in patients who did not undergo any intraoperative intervention for poor blood flow, it was only 24% in patients who underwent intraoperative intervention. This systematic review revealed that ICG fluorescence imaging may be a crucial adjunctive tool for reducing anastomotic leakage after esophagectomy, suggesting that it should be performed during esophageal reconstruction.

Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion.

BACKGROUND: Subcortical ischemic vascular dementia, one of the major subtypes of vascular dementia, is characterized by lacunar infarcts and white matter lesions caused by chronic cerebral hypoperfusion. In this study, we used a mouse model of bilateral common carotid artery stenosis (BCAS) to investigate the role of B-cell translocation gene 2 (BTG2), an antiproliferation gene, in the white matter glial response to chronic cerebral hypoperfusion. METHODS: Btg2-/- mice and littermate wild-type control mice underwent BCAS or sham operation. Behavior phenotypes were assessed by open-field test and Morris water maze test. Brain tissues were analyzed for the degree of white matter lesions and glial changes. To further confirm the effects of Btg2 deletion on proliferation of glial cells in vitro, BrdU incorporation was investigated in mixed glial cells derived from wild-type and Btg2-/- mice. RESULTS: Relative to wild-type mice with or without BCAS, BCAS-treated Btg2-/- mice exhibited elevated spontaneous locomotor activity and poorer spatial learning ability. Although the severities of white matter lesions did not significantly differ between wild-type and Btg2-/- mice after BCAS, the immunoreactivities of GFAP, a marker of astrocytes, and Mac2, a marker of activated microglia and macrophages, in the white matter of the optic tract were higher in BCAS-treated Btg2-/- mice than in BCAS-treated wild-type mice. The expression level of Gfap was also significantly elevated in BCAS-treated Btg2-/- mice. In vitro analysis showed that BrdU incorporation in mixed glial cells in response to inflammatory stimulation associated with cerebral hypoperfusion was higher in Btg2-/- mice than in wild-type mice. CONCLUSION: BTG2 negatively regulates glial cell proliferation in response to cerebral hypoperfusion, resulting in behavioral changes.

Combined Small-Angle Neutron Scattering/Small-Angle X-ray Scattering Analysis for the Characterization of Silver Nanoparticles Prepared via Photoreduction in Water-in-Oil Microemulsions.

In this study, we used small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) to investigate the formation process of silver (Ag) nanoparticles (NPs) in water-in-oil (w/o) reverse microemulsions comprising sodium bis(2-ethylhexyl) sulfosuccinate (AOT), water, and organic solvents (such as benzene, octane, and decane) by the photoreduction of silver perchlorate (AgClO4). Combining SANS and SAXS, the structural changes in the w/o microemulsions before and after the formation of Ag NPs via photoreduction were quantitatively evaluated. From the SANS experiments performed using the contrast-variation method, the size of water cores containing Ag NPs and the thickness of the AOT shells were calculated using the core-shell hard-sphere model. The size of the Ag NPs and their aggregates was calculated via SAXS analysis based on the polydisperse sphere model with a Schulz-Zimm distribution. We found that aggregates of three or four primary Ag NPs are formed by, first, the aggregation of water droplets through the entanglement of the tails of the AOT shell, followed by the self-assembly of Ag NPs into their aggregates because of particle-particle attractive interactions.

Prevalence of Malnutrition Diagnosed with GLIM Criteria and Association with Activities of Daily Living in Patients with Acute Stroke.

BACKGROUND: Malnutrition is associated with a poor functional outcome in patients with stroke. However, the prevalence of malnutrition diagnosed with the Global Leadership Initiative on Malnutrition (GLIM) criteria or its association with activity of daily living (ADL) in patients with acute stroke have not been reported. OBJECTIVE: To investigate the prevalence of the malnutrition diagnosed with the GLIM criteria and its association with ADL or discharge destination in patients with acute stroke. MATERIALS AND METHODS: In this cross-sectional study, we diagnosed malnutrition with the GLIM criteria and the European Society for Clinical Nutrition and Metabolism (ESPEN) criteria and assessed ADL by functional independence measure motor domain (FIM-M) score in patients with acute stroke. Multivariate regression analysis was used to investigate the relationship between FIM-M score or home discharge and malnutrition defined with GLIM or ESPEN criteria. RESULTS: A total of 115 acute stroke patients (39 females; median age: 72 years) were enrolled in this study. The prevalence of malnutrition according to GLIM-criteria and ESPEN-criteria was 28.7% and 16.5%, respectively. Multivariate analyses for FIM-M score after adjusting for potential confounders showed that GLIM criteria and ESPEN criteria were independently associated with FIM-M score (ß = -0.238, p < 0.001; ß = -0118, p = 0.040, respectively). A multivariate analysis for discharge destination found that only malnutrition from the GLIM criteria was significantly associated with home discharge (OR = 0.08, 95% confidential interval = 0.01-0.69, p = 0.02). CONCLUSIONS: Malnutrition with the GLIM criteria is negatively associated with ADL and is also associated with discharge destination in patients with acute stroke.

Association between indocyanine green fluorescence blood flow speed in the gastric conduit wall and superior mesenteric artery calcification: predictive significance for anastomotic leakage after esophagectomy.

BACKGROUND: Near-infrared fluorescence using indocyanine green (ICG) has been applied as a real-time navigation tool to observe blood flow in gastric conduit wall after esophagectomy. Atherosclerosis might impair the blood flow of the systemic organs. The aim of the study was to investigate the significances of ICG blood flow speed in the gastric conduit wall and atherosclerotic calcification for the prediction of anastomotic leakage after esophagectomy. METHODS: The 109 esophageal cancer patients were prospectively enrolled. ICG fluorescence blood flow speed in the gastric conduit wall and abdominal aortic calcification index (ACI), celiac artery (CA) calcification, and superior mesenteric artery (SMA) calcification were determined. Then, the correlation between ICG fluorescence blood flow speed and anastomotic leakage as well as ACI, CA, and SMA calcification were evaluated. RESULTS: Anastomotic leakage occurred in 15 patients. ACI ranged from 0 to 65. CA calcification and SMA calcification were present in 25 and 12 patients. Multivariate analysis demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall of 2.07 cm/s or less (P < 0.001) and SMA calcification (P = 0.026) were the significant independent predictors of anastomotic leakage. Only SMA calcification was significantly associated with ICG fluorescence blood flow speed in the gastric conduit wall (P = 0.026). CONCLUSIONS: This study demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall can predict anastomotic leakage after esophagectomy and microvascular perfusion of capillary vessels of the gastric conduit might be impaired by systemic atherosclerosis.

Clinical impacts of magnetic resonance thoracic ductography on preventing postoperative chylothorax after thoracoscopic esophagectomy for esophageal cancer.

PURPOSE: The study aimed to determine whether magnetic resonance thoracic ductography (MRTD) is useful for preventing injury to the thoracic duct (TD) during thoracoscopic esophagectomy and for reducing the incidence of postoperative chylothorax. MATERIALS AND METHOD: A total of 389 patients underwent thoracoscopic esophagectomy between September 2009 and February 2019 in Tokai University Hospital. Of them, we evaluated 228 patients who underwent preoperative MRTD (MRTD group) using Adachi's classification and our novel classification (Tokai classification). Then, the clinicopathological factors of the MRTD group (n = 228) were compared with those of the non-MRTD group (n = 161), and comparative analyses were conducted after propensity score matching (PSM). RESULTS: The TD could be visualized by MRTD in 228 patients. The MRTD findings were divided into 9 classifications including normal findings and abnormal TD findings (Adachi classification vs Tokai classification; 5.3% vs 16.2%). After PSM, both groups consisted of 128 patients. The rate of postoperative chylothorax after thoracoscopic esophagectomy was significantly lower in the MRTD group (0.8%) than in the non-MRTD group (6.3%) (p = 0.036). In the multivariate analysis for risk factors for chylothorax, the independent prognostic factors were preoperative therapy and the presence of MRTD. CONCLUSIONS: This study revealed that MRTD was useful for preventing of chylothorax after thoracoscopic esophagectomy for esophageal cancer.

Usefulness of prone-position computed tomography as preoperative simulation prior to thoracoscopic esophagectomy for thoracic esophageal cancer.

PURPOSE: The study aimed to evaluate the usefulness of prone-position computed tomography (CT) for predicting relevant thoracic procedure outcomes in minimally invasive esophagectomy (MIE) for thoracic esophageal cancer. MATERIALS AND METHODS: A total of 59 patients underwent esophagectomy between May 2019 and December 2020 in Tokai University Hospital. Preoperative CT imaging was conducted with the patient in both the supine and prone positions, and the magnitude of change in the intramediastinal space was calculated. In the 56 patients (94.9%) who had undergone MIE, the effects of such a difference on the surgical outcomes were analyzed. RESULTS: A significant correlation of the magnitude of change in VE (distance between ventral aspect of the vertebral body and the midpoint of the esophagus) with the surgical outcome was revealed in the 17 patients (30.4%) in whom the magnitude of change in VE was over the 75th percentile. That is, in this subgroup, the magnitude of change in VE showed a negative correlation with the thoracic operation time (rs = - 0.57, p = 0.01) and blood loss during the thoracic procedure (rs = - 0.46, p = 0.01). Multivariate analysis identified a magnitude of change in VE ≥ 9 mm (OR = 0.14, p = 0.03) as an independent risk factor for postoperative pneumonia. CONCLUSIONS: This study indicates that preoperative prone-position CT imaging is useful for predicting the level of ease or difficulty of securing an adequate operative field, surgical outcomes, and the risk of postoperative pneumonia in MIE.

Prognostic significance of vasohibin-1 and vasohibin-2 immunohistochemical expression in gastric cancer.

PURPOSE: It was recently identified that the vasohibin family may regulate angiogenesis through suppression by the vasohibin-1 gene and promotion by the vasohibin-2 gene. We assessed vasohibin expression in gastric cancer patients and its effect on their prognosis. METHODS: We evaluated vasohibin immunohistochemical expression in 210 patients with gastric cancer, who underwent radical surgery. The patients were divided first into a vasohibin-1-positive group and a vasohibin-1-negative group, and then into groups with high or low vasohibin-2 expression, to allow us to investigate the clinicopathological factors of prognosis retrospectively. RESULTS: There were 139 patients in the vasohibin-1-positive group and 71 patients in the vasohibin-1-negative group, among which there were and 108 with high vasohibin-2 expression and 102 with low vasohibin-2 expression. Vasohibin-1 was associated with Ly (P = 0.003) and pT (P = 0.037), whereas vasohibin-2 was associated with Ly (P < 0.001), V (P < 0.001) and pStage (P < 0.001). Overall, cancer-specific and relapse-free survival rates were lower in the vasohibin-1-positive (P = 0.034, P < 0.001, P = 0.002, respectively) and high vasohibin-2 expression (P = 0.004, P = 0.003, P < 0.001, respectively) groups. Multivariate analysis revealed that vasohibin-1 expression was associated with cancer-specific (P = 0.014, hazard ratio [HR] 4.454) and relapse-free (P = 0.035, HR 2.557) survival and vasohibin-2 expression tended to influence relapse-free survival (P = 0.051, HR 2.061). Grouping patients by vasohibin expression status combinations showed correlation among their expressions (P = 0.005). Overall, cancer-specific and relapse-free survival rates were lowest in the vasohibin-1-positive and high vasohibin-2 expression group. CONCLUSION: Our findings demonstrate that vasohibin-1 and vasohibin-2 could be novel biomarkers for predicting gastric cancer prognosis.

Plasma vasohibin-1 and vasohibin-2 are useful biomarkers in patients with esophageal squamous cell carcinoma.

BACKGROUND: Vasohibins (VASH), which are angiogenesis regulators, consist of Vasohibin-1 (VASH1) and Vasohibin-2 (VASH2). VASH1 is an angiogenesis inhibitor, while VASH2 is a proangiogenic factor. Patients with esophageal squamous cell carcinoma (ESCC) with high tumor expression levels of VASH1 and VASH2 have been reported to show a poor prognosis. The clinical significance of VASH concentrations in the blood of patients with ESCC has not yet been investigated. METHODS: Plasma samples from 89 patients with ESCC were analyzed, and the relationships between the plasma VASH concentrations and the clinicopathological factors of the patients were evaluated. Immunohistochemical examination (IHC) of the resected tumor specimens for VASH was performed in 56 patients, and the correlation between the plasma VASH concentrations and tumor expression levels of VASH was analyzed. RESULTS: The patient group with high plasma concentrations of VASH1 showed a higher frequency of lymph node metastasis (P = 0.01) and an invasive growth pattern (P = 0.05). Furthermore, poorly differentiated cancer occurred at a higher frequency in the patient group with high plasma concentrations of VASH2 (P < 0.01). High tumor expression levels of VASH1 were encountered more frequently in the patient group with high plasma concentrations of VASH1 (P = 0.03), and high tumor expression levels of VASH2 were encountered more frequently in the patient group with high plasma concentrations of VASH2 (P = 0.04). CONCLUSIONS: In patients with ESCC, high plasma concentrations were associated with poor clinical outcomes for both VASH1 and VASH2. We propose that results indicate that plasma VASH1 and VASH2 are useful biomarkers in patients with ESCC.

Evaluation of the effectiveness of caspofungin against febrile neutropenia and the factors related to the alteration in its plasma concentration.

Caspofungin (CPFG) is an echinocandin antifungal agent that inhibits the synthesis of ß-1, 3-D-glucan, a critical component of the cell wall of target fungi. Several clinical studies have confirmed the efficacy and safety of CPFG in patients with febrile neutropenia (FN); however, there are no reports available in Japanese patients with FN. Therefore, we investigated the therapeutic efficacy and pharmacokinetics of CPFG as an empirical therapy in a Japanese hospital. Twenty-four Japanese patients, who were diagnosed with FN at Gifu University Hospital from February 2014 to August 2017, were enrolled. Blood samples were collected at the end of CPFG dosing (0.5 h after the infusion) on day 1 and immediately prior to the next infusion on days 2, 3, and 4. The concentration of CPFG in plasma was measured by high-performance liquid chromatography. The efficacy was assessed by five of the component endpoints, and safety was monitored according to the Common Terminology Criteria for Adverse Events. CPFG showed an excellent effect against FN (75%, 18/24), without any serious hepatic or renal toxicity. Regarding the pharmacokinetics, the plasma concentration of CPFG was significantly correlated with body weight; although, no correlation was observed between the plasma concentration of CPFG and the other factors investigated, such as gender or laboratory results. These results suggest the high efficacy, safety, and tolerability of CPFG as an empirical antifungal therapy for Japanese patients with FN.

Prestroke Sarcopenia and Stroke Severity in Elderly Patients with Acute Stroke.

OBJECTIVE: The association between prestroke sarcopenia and stroke severity has not been evaluated previously. The purpose of this study was to determine whether prestroke sarcopenia is associated with stroke severity in elderly patients with acute stroke. METHODS: We assessed prestroke sarcopenia of elderly patients with acute stroke by using a questionnaire for sarcopenia (SARC-F). Patients were divided into groups according to their SARC-F score: SARC-F score less than 4 (nonsarcopenia) and SARC-F score ≥4 (prestroke sarcopenia). Stroke severity was assessed according to the National Institute of Health Stroke Scale. Logistic regression was used to derive crude and adjusted odds ratio for the presence of prestroke sarcopenia and stroke severity. RESULTS: Among the 183 patients enrolled (age, median [interquartile range]: 75 [11] years; 103 men), the prevalence of prestroke sarcopenia was 15% (n = 27). Crude odds ratio for the presence of prestroke sarcopenia and moderate-to-severe stroke (National Institute of Health Stroke Scale score > 5) was 4.00 (95% confidence interval, 1.68-9.53; P = .002). After adjusting for confounding variables (age, sex, and stroke risk factors), the presence of prestroke sarcopenia remained an independent predictor of severe stroke, with an odds ratio of 3.54 (95% confidence interval, 1.32-9.49; P= .01). CONCLUSIONS: Prestroke sarcopenia can predict moderate to severe stroke in elderly patients with acute stroke.

Prognostic significance of pathological tumor response and residual nodal metastasis in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery.

BACKGROUND: The present study investigated prognostic factors in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC) among various clinicopathological features related to neoadjuvant chemotherapy (NAC) and surgery, and the indications for additional treatment after surgery were considered. METHODS: A total of 113 patients with clinical stage II or III ESCC, who had undergone NAC followed by a thoracic esophagectomy with a three-field lymphadenectomy were retrospectively reviewed. NAC consisted of either two courses of cisplatin and 5-fluorouracil or three courses of docetaxel, cisplatin and 5-fluorouracil, with a new course beginning every 3 weeks. RESULTS: The overall survival (OS) rate was poorer in the pN-positive group than in the pN-negative group (P < 0.001). In terms of the histological therapeutic effect, the OS rate was poorer in the worse pathological responder group than in the better pathological responder group (P = 0.001). A multivariate analysis examining overall survival suggested that only pN (HR 3.204, P = 0.007) and worse pathological responder (HR 2.347, P = 0.041) were independent prognostic factors. The OS rate was compared among four groups classified according to the different combinations of pN and pathological response. A group of patients with pN-positive and worse pathological response had a significantly poorer outcome than the other groups. CONCLUSIONS: The present study suggested that patients with resectable advanced ESCC undergoing NAC followed by surgery, who have both pN and worse pathological response, have a poor prognosis.

Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis.

The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy against gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, the plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, the AZM MIC values for the Neisseria gonorrhoeae isolates were determined, and the microbiological outcomes were assessed. AZM-SR monotherapy eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve (AUC), estimated by population PK analysis using a two-compartment model, was 20.8 mg · h/liter. Logistic regression analysis showed that the PK/PD target value required to predict an N. gonorrhoeae eradication rate of ≥95% was a calculated AUC/MIC of ≥59.5. The AUC/MIC value was significantly higher in patients who achieved microbiological cure than in patients who achieved microbiological failure. Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution for strains isolated in this study was mostly consistent with that for strains currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, use of a single 2-g dose of AZM-SR either with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or are diagnosed to be infected with an AZM-sensitive strain.

Heart Rate Variability During Early Mobilization in Patients with Acute Ischemic Stroke.

Autonomic dysfunction is one of the predictors of poor outcome in patients with acute ischemic stroke. We compared the heart rate variability (HRV) during early mobilization in patients with or without neurological deterioration (ND). We enrolled 7 acute ischemic patients with ND and 14 without ND and measured their HRV in the rest and mobilization by electrocardiography. There was a significant difference in sympathetic nervous activity during mobilization between the 2 groups. However, no significant differences in blood pressure, heart rate, and parasympathetic nerve activity were observed. In patients with acute ischemic stroke, it is likely that the increase in sympathetic nervous activity during mobilization is associated with ND.