A randomized, double-blind, placebo-controlled phase II study of olanzapine-based prophylactic antiemetic therapy for delayed and persistent nausea and vomiting in patients with HER2-positive or HER2-low breast cancer treated with trastuzumab deruxtecan: ERICA study (WJOG14320B).

BACKGROUND: Nausea and vomiting are common adverse events associated with trastuzumab deruxtecan (T-DXd). We evaluated the efficacy of an olanzapine-based triplet regimen for preventing nausea and vomiting in patients receiving their first cycle T-DXd. PATIENTS AND METHODS: This multi-institutional, randomized, double-blind, placebo-controlled (ERICA) phase II study enrolled patients with human epidermal growth factor receptor 2-positive/human epidermal growth factor receptor 2-low metastatic breast cancer receiving their first cycle of T-DXd. Patients were randomized to olanzapine 5 mg or placebo once daily (1 : 1 ratio) from day 1 to day 6, plus a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone 6.6 mg intravenously or 8 mg orally on day 1. The total observation period was 504 h (21 days) from the first T-DXd administration. The primary endpoint was complete response (CR), defined as no emetic events and no rescue medications, in the delayed phase (24-120 h after T-DXd), with the type I error rate of 0.2 (one-sided) for the comparison. Secondary endpoints included no nausea rate in the delayed and persistent phases (120-504 h), adverse event by Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported outcomes version of the CTCAE (PRO-CTCAE). RESULTS: In total, 168 patients were enrolled at 43 sites in Japan (November 2021-September 2023) with 162 patients (olanzapine, n = 80; placebo, n = 82) included in the per protocol set. The primary endpoint was met as the delayed phase CR rate was significantly greater with olanzapine than placebo (70.0% versus 56.1%, P = 0.047). Efficacy was maintained in the persistent phase (63.9% versus 44.4%). No nausea rate was also greater with olanzapine (delayed phase: 57.5% versus 37.8%; persistent phase: 51.4% versus 31.9%). CR rates in the delayed phase favored olanzapine across subgroups. Appetite loss was also decreased with olanzapine. Hyperglycemia and somnolence were mostly of low-grade severity. CONCLUSION: Olanzapine 5 mg for 6 days with 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone appears effective for T-DXd-treated patients to prevent delayed and persistent nausea and vomiting.

Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Coherent Beam Splitting of Flying Electrons Driven by a Surface Acoustic Wave.

We develop a coherent beam splitter for single electrons driven through two tunnel-coupled quantum wires by surface acoustic waves (SAWs). The output current through each wire oscillates with gate voltages to tune the tunnel coupling and potential difference between the wires. This oscillation is assigned to coherent electron tunneling motion that can be used to encode a flying qubit and is well reproduced by numerical calculations of time evolution of the SAW-driven single electrons. The oscillation visibility is currently limited to about 3%, but robust against decoherence, indicating that the SAW electron can serve as a novel platform for a solid-state flying qubit.

Reduction of Pneumocystis jirovecii pneumonia and bloodstream infections by trimethoprim-sulfamethoxazole prophylaxis in patients with rheumatic diseases.

Objective: Trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is routinely administered to patients with rheumatic diseases in Japan. The present study aimed to evaluate the effect of TMP/SMX prophylaxis on PJP and non-central line-associated bloodstream infections (BSIs) in patients receiving high-dose glucocorticoids for the treatment of rheumatic diseases.Method: This study enrolled patients who were admitted between 1 October 2003 and 31 March 2018 and began high-dose glucocorticoid therapy for rheumatic diseases during hospitalization. The observation period was 4 months from the commencement of high-dose glucocorticoid therapy. The effect of TMP/SMX prophylaxis on PJP and non-central line-associated BSI was analysed.Results: Of the 437 patients included in the study, 376 received TMP/SMX prophylaxis and 61 patients did not. During the observation period, TMP/SMX prophylaxis was discontinued in 76 patients (20.2%). Three PJP cases (0.7%) occurred. Among the 399 patients included in our analysis of non-central line-associated BSI, eight experienced non-central line-associated BSI (2.0%). Among the covariates, TMP/SMX prophylaxis was associated with reduced PJP and non-central line-associated BSI incidence [odds ratio (OR) 0, 95% confidence interval (CI) 0.00-0.38, and OR 0.08, 95% CI 0.01-0.42, respectively].Conclusion: Routine TMP/SMX prophylaxis reduced the incidence of both PJP and BSI in patients with rheumatic diseases undergoing high-dose glucocorticoid therapy.

Percutaneous fetoscopic spina bifida repair: effect on ambulation and need for postnatal cerebrospinal fluid diversion and bladder catheterization.

OBJECTIVE: A trial comparing prenatal with postnatal open spina bifida (OSB) repair established that prenatal surgery was associated with better postnatal outcome. However, in the trial, fetal surgery was carried out through hysterotomy. Minimally invasive approaches are being developed to mitigate the risks of open maternal-fetal surgery. The objective of this study was to investigate the impact of a novel neurosurgical technique for percutaneous fetoscopic repair of fetal OSB, the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique, on long-term postnatal outcome. METHODS: This study examined descriptive data for all patients undergoing fetoscopic OSB repair who had available 12- and 30-month follow-up data for assessment of need for cerebrospinal fluid (CSF) diversion and need for bladder catheterization and ambulation, respectively, from eight centers that perform prenatal OSB repair via percutaneous fetoscopy using a biocellulose patch between the neural placode and skin/myofascial flap, without suture of the dura mater (SAFER technique). Univariate and multivariate logistic regression analyses were used to examine the effect of different factors on need for CSF diversion at 12 months and ambulation and need for bladder catheterization at 30 months. Potential cofactors included gestational age at fetal surgery and delivery, preoperative ultrasound findings of anatomical level of the lesion, cerebral lateral ventricular diameter, lesion type and presence of bilateral talipes, as well as postnatal findings of CSF leakage at birth, motor level, presence of bilateral talipes and reversal of hindbrain herniation. RESULTS: A total of 170 consecutive patients with fetal OSB were treated prenatally using the SAFER technique. Among these, 103 babies had follow-up at 12 months of age and 59 had follow-up at 30 months of age. At 12 months of age, 53.4% (55/103) of babies did not require ventriculoperitoneal shunt or third ventriculostomy. At 30 months of age, 54.2% (32/59) of children were ambulating independently and 61.0% (36/59) did not require chronic intermittent catheterization of the bladder. Multivariate logistic regression analysis demonstrated that significant prediction of need for CSF diversion was provided by lateral ventricular size and type of lesion (myeloschisis). Significant predictors of ambulatory status were prenatal bilateral talipes and anatomical and functional motor levels of the lesion. There were no significant predictors of need for bladder catheterization. CONCLUSION: Children who underwent prenatal OSB repair via the percutaneous fetoscopic SAFER technique achieved long-term neurological outcomes similar to those reported in the literature after hysterotomy-assisted OSB repair. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Safety and feasibility of minimally invasive esophagectomy for elderly esophageal cancer patients.

The number of elderly patients with esophageal cancer has increased in recent years. The use of thoracoscopic esophagectomy has also increased, and its minimal invasiveness is believed to contribute to postoperative outcomes. However, the short- and long-term outcomes in elderly patients remain unclear. This study aimed to elucidate the safety and feasibility of minimally invasive esophagectomy in elderly patients. This retrospective study included 207 patients who underwent radical thoracoscopic esophagectomy for thoracic esophageal squamous cell carcinoma at Kobe University Hospital between 2005 and 2014. Patients were divided into non-elderly (<75 years) and elderly (≥75 years) groups. A propensity score matching analysis was performed for sex and clinical T and N stage, with a total of 29 matched pairs. General preoperative data, surgical procedures, intraoperative data, postoperative complications, in-hospital death, cancer-specific survival, and overall survival were compared between groups. The elderly group was characterized by lower preoperative serum albumin levels and higher American Society of Anesthesiologists grade. Intraoperative data and postoperative complications did not differ between the groups. The in-hospital death rate was 4% in the elderly group, which did not significantly differ from the non-elderly group. Cancer-specific survival was similar between the two groups. Although overall survival tended to be poor in the elderly group, it was not significantly worse than that of the non-elderly group. In conclusion, the short- and long-term outcomes of minimally invasive esophagectomy in elderly versus non-elderly patients were acceptable. Minimally invasive esophagectomy is a safe and feasible modality for elderly patients with appropriate indications.

Topological Kagome Magnet Co3Sn2S2 Thin Flakes with High Electron Mobility and Large Anomalous Hall Effect.

Magnetic Weyl semimetals attract considerable interest not only for their topological quantum phenomena but also as an emerging materials class for realizing quantum anomalous Hall effect in the two-dimensional limit. A shandite compound Co3Sn2S2 with layered kagome-lattices is one such material, where vigorous efforts have been devoted to synthesize the two-dimensional crystal. Here, we report a synthesis of Co3Sn2S2 thin flakes with a thickness of 250 nm by chemical vapor transport method. We find that this facile bottom-up approach allows the formation of large-sized Co3Sn2S2 thin flakes of high-quality, where we identify the largest electron mobility (∼2600 cm2 V-1 s-1) among magnetic topological semimetals, as well as the large anomalous Hall conductivity (∼1400 Ω-1 cm-1) and anomalous Hall angle (∼32%) arising from the Berry curvature. Our study provides a viable platform for studying high-quality thin flakes of magnetic Weyl semimetal and stimulate further research on unexplored topological phenomena in the two-dimensional limit.

Risk model for severe postoperative complications after total pancreatectomy based on a nationwide clinical database.

BACKGROUND: Total pancreatectomy is required to completely clear tumours that are locally advanced or located in the centre of the pancreas. However, reports describing clinical outcomes after total pancreatectomy are rare. The aim of this retrospective observational study was to assess clinical outcomes following total pancreatectomy using a nationwide registry and to create a risk model for severe postoperative complications. METHODS: Patients who underwent total pancreatectomy from 2013 to 2017, and who were recorded in the Japan Society of Gastroenterological Surgery and Japanese Society of Hepato-Biliary-Pancreatic Surgery database, were included. Severe complications at 30 days were defined as those with a Clavien-Dindo grade III needing reoperation, or grade IV-V. Occurrence of severe complications was modelled using data from patients treated from 2013 to 2016, and the accuracy of the model tested among patients from 2017 using c-statistics and a calibration plot. RESULTS: A total of 2167 patients undergoing total pancreatectomy were included. Postoperative 30-day and in-hospital mortality rates were 1·0 per cent (22 of 2167 patients) and 2·7 per cent (58 of 167) respectively, and severe complications developed in 6·0 per cent (131 of 2167). Factors showing a strong positive association with outcome in this risk model were the ASA performance status grade and combined arterial resection. In the test cohort, the c-statistic of the model was 0·70 (95 per cent c.i. 0·59 to 0·81). CONCLUSION: The risk model may be used to predict severe complications after total pancreatectomy.

ANTECEDENTES: La pancreatectomía total está indicada cuando se requiere la resección completa de tumores localmente avanzados o ubicados en el centro del páncreas. Sin embargo, existen pocos artículos que describan los resultados clínicos después de una pancreatectomía total. El objetivo de este estudio observacional retrospectivo fue evaluar los resultados clínicos después de una pancreatectomía total utilizando un registro nacional y crear un modelo de riesgo de complicaciones postoperatorias graves. MÉTODOS: Se incluyeron aquellos pacientes que se sometieron a una pancreatectomía total entre 2013 y 2017 y que fueron registrados en la base de datos de la Sociedad Japonesa de Cirugía Gastrointestinal y de la Sociedad Japonesa de Cirugía Hepato-Bilio-Pancreática. Las complicaciones graves a los 30 días se definieron como Clavien-Dindo grado III con reintervención o grado IV/V. Se analizó la aparición de complicaciones graves de los pacientes desde 2013 a 2016 y se evaluó la precisión del modelo entre los pacientes operados desde 2017 usando estadísticos c y un gráfico de calibración. RESULTADOS: Se incluyeron 2.167 pacientes sometidos a una pancreatectomía total. La mortalidad postoperatoria a los 30 días y la mortalidad hospitalaria fueron del 1,0% (22/2167) y del 2,7% (58/2167), respectivamente, y las complicaciones graves ocurrieron en el 6,0% (131/2167) de los pacientes. Los factores que mostraron una fuerte asociación positiva con los resultados en este modelo de riesgo fueron el estado funcional según la Sociedad Americana de Anestesiología y la resección arterial combinada. En la cohorte de prueba, el estadístico c del modelo fue de 0,70 (i.c. del 95% 0,59-0,81). CONCLUSIÓN: El modelo de riesgo puede usarse para predecir las complicaciones graves después de una pancreatectomía total.

Daytime Dynamo Electrodynamics With Spiral Currents Driven by Strong Winds Revealed by Vapor Trails and Sounding Rocket Probes.

We investigate the forces and atmosphere-ionosphere coupling that create atmospheric dynamo currents using two rockets launched nearly simultaneously on 4 July 2013 from Wallops Island (USA), during daytime Sq conditions with ΔH of -30 nT. One rocket released a vapor trail observed from an airplane which showed peak velocities of >160 m/s near 108 km and turbulence coincident with strong unstable shear. Electric and magnetic fields and plasma density were measured on a second rocket. The current density peaked near 110 km exhibiting a spiral pattern with altitude that mirrored that of the winds, suggesting the dynamo is driven by tidal forcing. Such stratified currents are obscured in integrated ground measurements. Large electric fields produced a current opposite to that driven by the wind, believed created to minimize the current divergence. Using the observations, we solve the dynamo equation versus altitude, providing a new perspective on the complex nature of the atmospheric dynamo.

A case with good response to belimumab for lupus nephritis complicated by IgG4-related disease.

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an unusual complication of systemic lupus erythematosus (SLE). We report a case in which belimumab proved efficacious for not only SLE, but also IgG4-RD. A 58-year-old Japanese woman had suffered from photodermatosis and erythema on the limbs for 20 years. She presented in slight fever and fatigue since 2016. Laboratory data showed hypergammaglobulinemia, proteinuria and positive results for anti-nuclear antibody and anti-double-stranded DNA antibody. Furthermore, elevated levels of serum IgG4 were detected. Contrast-enhanced computed tomography disclosed multiple areas of poor enhancement in the kidneys. The patient was diagnosed with lupus nephritis and IgG4-RD from renal biopsy. Treatment was started with prednisolone at 40 mg/day and mycophenolate mofetil. Proteinuria and serological findings improved initially, but tapering the dose of glucocorticoid proved difficult. After treatment was started with belimumab, clinical symptoms and proteinuria resolved completely. The dose of glucocorticoid was successfully tapered and serum concentration of IgG4 fell further. This appears to represent the first report of a case in which both SLE and IgG4-RD were effectively treated using belimumab.

Prognostic significance of sarcopenia in patients undergoing esophagectomy for superficial esophageal squamous cell carcinoma.

Nononcological prognostic factors in superficial esophageal squamous cell carcinoma (SESCC) patients remain unclear. The aim of this study is to evaluate the relationship between sarcopenia and surgical outcome in patients with SESCC who had undergone definitive surgery. A total of 194 SESCC patients who had undergone thoracic esophagectomy with three-field lymphadenectomy without neoadjuvant therapy at Tokai University Hospital between January 2006 and December 2015 were analyzed retrospectively. Manual tracing using CT imaging was used to measure the cross-sectional areas of the skeletal muscle mass. The cutoff values for the skeletal muscle index used to define sarcopenia were based on the results of a previous study. Twenty-eight patients (14.4%) had sarcopenia, while the remaining 166 patients (85.6%) did not. A multivariate analysis suggested that sarcopenia was an independent risk factor for postoperative pulmonary complications (OR = 3.232, P = 0.026). The overall survival rate and the disease-free survival rate were both significantly worse in the sarcopenia group than in the nonsarcopenia group (P < 0.001). In a multivariate analysis, sarcopenia was an independent prognostic factor affecting overall survival (HR = 7.121, P < 0.001) and disease-free survival (HR = 6.000, P < 0.001). Patients with sarcopenia and lymph node metastasis (n = 18) had a worse outcome than the other patients (P < 0.001). This study suggests that the alleviation of sarcopenia through nutritional support and rehabilitation in SESCC patients scheduled to undergo surgery might help to prevent postoperative pulmonary complications and to improve the long-term outcome.

Prognostic impact of lymphovascular invasion in lymph node-negative superficial esophageal squamous cell carcinoma.

The relationship between lymphovascular invasion (LVI) and prognosis in patients with superficial esophageal squamous cell carcinoma (SESCC) is unclear. The aim of this study is to evaluate prognostic factors in patients with lymph node-negative SESCC. A total of 195 patients with pathologically confirmed T1a-MM, T1b, and lymph node-negative SESCC were retrospectively reviewed in this study. Overall, the disease-free survival (DFS) rate was poorer in the lymphatic invasion-positive group than in the lymphatic invasion-negative group (p = 0.002) and a multivariate analysis suggested that lymphatic invasion was the only independent prognostic factor of DFS in patients with lymph node-negative SESCC (HR = 4.075, p = 0.005). Distant organ recurrence occurred in one patient (1/52, 1.9%) in the T1b-SM2 group and in six patients (6/61, 9.7%) in the T1b-SM3 group; all of these patients had LVI. LVI-positive patients had a poorer DFS than invasion-negative patients in the T1b-SM2 and SM3 groups (p = 0.026), and a multivariate analysis suggested that LVI was the only independent prognostic factor of DFS in patients with lymph node-negative SM2 and SM3 SESCC (HR = 5.165, p = 0.031). Lymph node-positive patients had a significantly poorer DFS rate than lymph node negative and LVI positive patients among the SM2 and SM3 SESCC patients (p = 0.018). The present results suggested that LVI was an independent prognostic factor in patients with SM2 and SM3 lymph node-negative SESCC; however their prognosis was not worse than that of patients with lymph node-positive SM2 and SM3 SESCC, for whom adjuvant therapy is indicated as a standard treatment.

Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer.

BACKGROUND: Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. METHODS: This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location. Gemcitabine was given intravenously at a dose of 1000 mg/m2 , administered on days 1, 8 and 15 every 4 weeks for six cycles. The primary endpoint was overall survival, and secondary endpoints were relapse-free survival, subgroup analysis and toxicity. RESULTS: Some 225 patients were included (117 gemcitabine, 108 observation). Baseline characteristics were well balanced between the gemcitabine and observation groups. There were no significant differences in overall survival (median 62·3 versus 63·8 months respectively; hazard ratio 1·01, 95 per cent c.i. 0·70 to 1·45; P = 0·964) and relapse-free survival (median 36·0 versus 39·9 months; hazard ratio 0·93, 0·66 to 1·32; P = 0·693). There were no survival differences between the two groups in subsets stratified by lymph node status and margin status. Although haematological toxicity occurred frequently in the gemcitabine group, most toxicities were transient, and grade 3/4 non-haematological toxicity was rare. CONCLUSION: The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).

High-resolution copy number variation analysis of schizophrenia in Japan.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Enterococcal bacteraemia: predictive and prognostic risk factors for ampicillin resistance.

To identify the predictive and prognostic factors associated with ampicillin-resistant enterococcal bacteraemia, we retrospectively reviewed demographic, microbiological and clinical data of patients attending the Kyoto University Hospital, Japan, between 2009 and 2015. Logistic regression and Cox regression analyses were performed to determine the predictive and prognostic factors, respectively. In total, 235 episodes of enterococcal bacteraemia were identified. As ampicillin susceptibility was uniform for Enterococcus faecalis isolates and almost all ampicillin-resistant isolates were E. faecium, bacteraemia due to these species was investigated separately. E. faecalis and E. faecium accounted for 41.7% (98/235) and 48.1% (113/235) of the isolates, respectively and 91.2% of all E. faecium were ampicillin resistant. Nosocomial E. faecium bacteraemia acquisition (odds ratio (OR), 13.6; 95% confidence intervals, 3.16-58.3) was associated with ampicillin-resistant isolates. Bacteraemia from an unknown source (hazard ratio (HR), 2.91; 95% CI 1.36-6.21) and an increased Pitt bacteraemia score (PBS) (HR, 1.36; 95% CI 1.21-1.52) were associated with 30-day mortality in E. faecium infections. Likewise, bacteraemia from an unknown source (HR, 4.17; 95% CI 1.25-13.9) and increased PBS (HR, 1.27; 95% CI 1.09-1.48) were associated with 30-day mortality in patients with E. faecalis bacteraemia. The empirical therapeutic administration of glycopeptides is recommended for patients with bacteraemia from an unknown source in whom severe E. faecium bacteraemia is suspected.

Foetal development of the human gluteus maximus muscle with special reference to its fascial insertion.

The human gluteus maximus muscle (GMX) is characterised by its insertion to the iliotibial tract (a lateral thick fascia of the thigh beneath the fascia lata), which plays a critical role in lateral stabilisation of the hip joint during walking. In contrast, in non-human primates, the GMX and biceps femoris muscle provide a flexor complex. According to our observations of 15 human embryos and 11 foetuses at 7-10 weeks of gestation (21-55 mm), the GMX anlage was divided into 1) a superior part that developed earlier and 2) a small inferior part that developed later. The latter was adjacent to, or even continuous with, the biceps femoris. At 8 weeks, both parts inserted into the femur, possibly the future gluteal tuberosity. However, depending on traction by the developing inferior part as well as pressure from the developing major trochanter of the femur, most of the original femoral insertion of the GMX appeared to be detached from the femur. Therefore, at 9-10 weeks, the GMX had a digastric muscle-like appearance with an intermediate band connecting the major superior part to the small inferior mass. This band, most likely corresponding to the initial iliotibial tract, extended laterally and distally far from the muscle fibres. The fascia lata was still thin and the tensor fasciae latae seemed to develop much later. It seems likely that the evolutionary transition from quadripedality to bipedality and a permanently upright posture would require the development of a new GMX complex with the iliotibial tract that differs from that in non-human primates. (Folia Morphol 2018; 77, 1: 144-150).

Changes in apolipoprotein B and oxidized low-density lipoprotein levels in gingival crevicular fluids as a result of periodontal tissue conditions.

BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic inflammatory disease caused by bacterial infection that can lead to tooth loss. Gingival crevicular fluid can be collected easily and noninvasively. We previously discovered the presence of apolipoprotein B (apoB), the main constituent of low-density lipoprotein, and oxidized low-density lipoprotein (oxLDL) in the gingival crevicular fluid of healthy subjects. In this study, we investigated whether periodontal conditions affect the levels of apoB and oxLDL in gingival crevicular fluid. MATERIAL AND METHODS: The study population comprised 11 patients with chronic periodontitis. A pair of gingival crevicular fluid samples was collected from each patient at a healthy site and at a site with periodontitis (baseline samples). Thereafter, gingival crevicular fluid samples were collected from the same patients again at 4 and 8 wk after scaling and root planing (SRP). The levels of apoB, oxLDL, protein and cytokines in gingival crevicular fluid, in addition to gingival crevicular fluid volume, were measured. RESULTS: At baseline, the levels of apoB and oxLDL in gingival crevicular fluid were higher at the sites with periodontitis than at the healthy sites. The levels of apoB and oxLDL at periodontal sites decreased after SRP. The level of oxLDL in gingival crevicular fluid correlated well with the probing pocket depth. The oxLDL : apoB ratio in gingival crevicular fluid was significantly higher than that in plasma. CONCLUSIONS: The levels of apoB and oxLDL in gingival crevicular fluid change according to the periodontal tissue conditions.

Combined effects of starvation and butyrate on autophagy-dependent gingival epithelial cell death.

BACKGROUND AND OBJECTIVE: Bacteria in the dental biofilm surrounding marginal gingival grooves cause periodontal diseases. Numerous bacteria within the biofilm consume nutrients from the gingival crevicular fluid. Furthermore, some gram-negative bacteria in mature dental biofilms produce butyrate. Thus, gingival epithelial cells in close proximity to mature dental biofilms are at risk of both starvation and exposure to butyrate. In the present study, we determined the combined effects of starvation and butyrate exposure on gingival epithelial cell death and the underlying mechanisms. MATERIAL AND METHODS: The Ca9-22 cell line was used as an in vitro counterpart of gingival epithelial cells. Cell death was measured as the amount of total DNA in the dead cells using SYTOX Green dye, which penetrates through membranes of dead cells and emits fluorescence when it intercalates into double-stranded DNA. AMP-activated protein kinase (AMPK) activity, the amount of autophagy, and acetylation of histone H3 were determined using western blot. Gene expression levels of microtubule-associated protein 1 light chain 3b (lc3b) were determined using quantitative reverse transcription-polymerase chain reaction. RESULTS: Butyrate-induced cell death occurred in a dose-dependent manner whether cells were starved or fed. However, the induction of cell death was two to four times higher when cells were placed under starvation conditions compared to when they were fed. Moreover, both starvation and butyrate exposure induced AMPK activity and autophagy. While AMPK inactivation resulted in decreased autophagy and butyrate-induced cell death under conditions of starvation, AMPK activation resulted in butyrate-induced cell death when cells were fed. Combined with the results of our previous report, which demonstrated butyrate-induced autophagy-dependent cell death, the results of this study suggest that the combination of starvation and butyrate exposure activates AMPK inducing autophagy and subsequent cell death. Notably, this combination markedly induced LC3B production and the induction was attenuated by AMPK inhibition. LC3B knockdown, in turn, significantly decreased butyrate-induced cell death. Therefore, AMPK-dependent LC3B induction apparently plays an important role in butyrate-induced cell death. There was a lack of correspondence between the levels of AMPK activation and LC3B induction; this may reflect the histone deacetylase-inhibitory capacity of butyrate on histone proteins. CONCLUSION: Taken together, starvation and butyrate exposure promote autophagy via AMPK signaling, while the histone deacetylase-inhibitory effects of butyrate alter chromatin to transcriptionally active state, resulting in strong LC3B induction and subsequent cell death. These findings may help improve the understanding of the cellular processes underlying periodontal disease initiation.

Surgical strategy of esophageal resection and reconstruction for aortoesophageal fistula.

Aortoesophageal fistula is a critical and life-threatening disease. The cardiovascular strategy for graft replacement has been widely discussed. However, the surgical strategy of esophageal resection and reconstruction for aortoesophageal fistula has rarely been discussed. The objective of this study is to establish a surgical strategy and procedure of esophageal resection and reconstruction for aortoesophageal fistula. Eleven patients with aortoesophageal fistula who underwent aortic graft replacement and esophagectomy between 2008 and 2015 at Kobe University Hospital were enrolled in this study. Patient characteristics, operative methods, and clinical outcomes were obtained by retrospective chart review. All 11 patients underwent graft replacement, esophagectomy, and omental wrapping. Ten esophagectomies were simultaneously accomplished in the same operative field as aortic graft replacement. Seven patients underwent subtotal esophagectomy from a left thoracotomy, and three patients underwent upper hemiesophagectomy from a median sternotomy. The other patient underwent staged esophagectomy from a right thoracotomy. Seven of 11 patients (63.6%) successfully underwent staged esophageal reconstruction. Pedicled jejunal transfer with supercharge and superdrainage were performed in six patients, and ileocecal reconstruction was performed in one patient. Median survival time in the patients with esophageal reconstruction was 21 months while that in the patients without esophageal reconstruction was 10 months. Six of 7 patients (85.7%) who underwent esophageal reconstructions were alive. Our surgical strategy for aortoesophageal fistula, which includes simultaneous graft replacement and esophagectomy in the same operative field and staged reconstruction by pedicled jejunal transfer to ensure omental wrapping, is feasible and promising.

C-reactive protein to albumin ratio is a prognostic factor for patients with cStage II/III esophageal squamous cell cancer.

C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, was first developed as a prognostic score for septic patients. Recent reports show that CRP/Alb ratio is also a prognostic score for cancer patients, including esophageal cancer. However, the role of CRP/Alb ratio for those with neoadjuvant chemotherapy (NAC) and the changes of CRP/Alb ratio around NAC have never been discussed. The aim of this study is to evaluate the significance of CRP/Alb ratio around NAC for patients with cStage II/III esophageal squamous cell cancer (ESCC). A total of 149 patients who were diagnosed as cStage II/III ESCC were enrolled between February 2007 and December 2014. We retrospectively investigated the relation between pre-NAC and post-NAC CRP/Alb ratio and short and long outcomes. The optimal cutoff level for pre-NAC and post-NAC CRP/Alb ratio was 0.030 and 0.048, respectively. There was no relation between CRP/Alb ratio level and postoperative outcomes. Post-NAC CRP/Alb ratio < 0.048 had a significantly higher overall survival rate than CRP/Alb ratio ≥0.048 (P< 0.001). Univariate analysis showed that cT, cN, pre-NAC CRP/Alb ratio < 0.030 and post-NAC CRP/Alb ratio < 0.048 was prognostic factors (P= 0.003, P= 0.022, P= 0.033, and P< 0.001, respectively). Multivariate analysis showed that cT and post-NAC CRP/Alb ratio < 0.048 was independent prognostic factors (P= 0.030 and P< 0.001, respectively). Post-NAC CRP/Alb ratio is an independent prognostic factor in patients with cStage II/III ESCC.