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Prognosis of breast cancer patients has been improved along with the progress in cancer therapies. However, cancer therapeutics-related cardiac dysfunction (CTRCD) has been an emerging issue. For early detection of CTRCD, we examined whether native T1 mapping and global longitudinal strain (GLS) using cardiac magnetic resonance (CMR) and biomarkers analysis are useful.We prospectively enrolled 83 consecutive chemotherapy-naïve female patients with breast cancer (mean age, 56 ± 13 yrs.) between 2017 and 2020. CTRCD was defined based on echocardiography as left ventricular ejection fraction (LVEF) below 53% at any follow-up period with LVEF10% points decrease from baseline after chemotherapy. To evaluate cardiac function, CMR (at baseline and 6 months), 12‑lead ECG, echocardiography, and biomarkers (at baseline and every 3 months) were evaluated.A total of 164 CMRs were performed in 83 patients. LVEF and GLS were significantly decreased after chemotherapy (LVEF, from 71.2 ± 4.4 to 67.6 ± 5.8%; GLS, from -27.9 ± 3.9 to -24.7 ± 3.5%, respectively, both P 0.01). Native T1 value also significantly elevated after chemotherapy (from 1283 ± 36 to 1308 ± 39 msec, P 0.01). Among the 83 patients, 7 (8.4%) developed CTRCD. Of note, native T1 value before chemotherapy was significantly higher in patients with CTRCD than in those without it (1352 ± 29 vs. 1278 ± 30 msec, P 0.01). The multivariable logistic regression analysis revealed that native T1 value was an independent predictive factor for the development of CTRCD [OR 2.33; 95%CI 1.15-4.75, P = 0.02].These results indicate that CMR is useful to detect chemotherapy-related myocardial damage and predict for the development of CTRCD in breast cancer patients.

There are no evidence-based reports on the proper duration of antimicrobial therapy following video-assisted thoracoscopic surgery debridement (VATS-D) in thoracic empyema (TE) or complicated parapneumonic effusion (PPE). This study aimed to investigate the optimal duration of antimicrobial therapy after VATS-D.Between January 2011 and December 2019, 33 patients corresponding to American College of Chest Physicians (ACCP) category 3 or 4 undergoing VATS-D were included. The times until the body temperature (BT) was confirmed to be less than 37.5 °C and 37.0 °C, white blood cell count (WBC) less than 10,000/μl, segmented neutrophils (seg) less than 80%, and C-reactive protein (CRP) level less than 25% of the preoperative value were retrospectively analyzed.The median time from the onset of TE/PPE to surgery was 13 days. The median durations of preoperative and postoperative antibiotic use were five and seven days, respectively. Major complications occurred in four cases (three and one cases of respiratory failure and cerebral infarction, respectively). The median postoperative hospital stay was 14 days. Recurrence or progression to chronic empyema was seen in four cases. The median numbers of days until the conditions were met were three days for BT 37.5 °C, six days for BT 37.0 °C, four days for WBC10,000, seven days for seg80% and seven days for CRP25%.The proper duration of antimicrobial therapy after VATS-D for TE/PPE is approximately three to seven days. Urgent VATS-D may shorten the total antibiotic usage.

Objective Transglutaminase (TGM)2 and peroxisome proliferator-activated receptor (PPAR)γ are thought to participate in the pathogenesis of nasal polyp formation in cystic fibrosis (CF). We herein investigated expressions of cystic fibrosis transmembrane conductance regulator (CFTR), TGM2, PPARγ and isopeptide bonds, a reaction product of TGM, in non-CF nasal polyps. Methods Nasal polyps and inferior turbinates were collected from chronic rhinosinusitis patients without CF during transnasal endoscopic sinonasal surgery. Expressions of CFTR, TGM2, isopeptide bonds and PPARγ were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Expression of CFTR was also analyzed by Western blot. Results Immunohistochemical fluorescence of the nasal polyp was significantly lower for CFTR and PPARγ, and significantly higher for TGM2 and isopeptide bonds than that of the turbinate mucosa. Lower expression of CFTR in the nasal polyp than in the turbinate mucosa was also observed in Western blot. Expression of PPARG mRNA was significantly lower in the nasal polyp than in the turbinate mucosa, whereas expressions of CFTR mRNA or TGM2 mRNA did not differ between the two tissues. Immunohistochemical fluorescence for CFTR showed significant negative correlation with that for TGM2 and isopeptide bonds, and significant positive correlation with that for PPARγ. The fluorescence for TGM2 was positively correlated with that for isopeptide bonds and negatively correlated with that for PPARγ. The fluorescence for isopeptide bonds tended to be negatively correlated with that for PPARγ. Conclusions These results suggest a possible role of the CFTR-TGM2-PPARγ cascade in the pathogenesis of nasal polyp formation in non-CF patients as in CF patients.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Acute appendicitis is a common disease that often requires emergency surgery. However, recently, not all cases are treated as an urgent operation, but surgery may be delayed to when medical resources are abundant to perform the operation safely. In such cases, preoperative antibiotics are administered during the waiting period. Though the choice is empiric, an appropriate choice is needed to avoid emergency surgery. Guidelines for the choice of antibiotics recognized as international standards cannot be applied in Asia due to the high rate of extended-spectrum β-lactamase (ESBL) producers or fluoroquinolone-resistantBacterial culture results and antibiotic susceptibility were retrospectively examined in 106 cases who underwent surgery for appendicitis.Bacterial cultures were positive in 53 cases (50%). Twenty-six strains ofIn Japan, from the point of view of reducing carbapenem use, CMZ must be considered a first-choice drug during the in-hospital waiting period for appendectomy.

Chemoradiation therapy is standard practice for hypopharyngeal and laryngeal cancer, but its impact on skin health can cause complications if salvage surgery is required.To develop simple objective indices for the early detection of complications following head-and-neck salvage surgery.Preoperatively and on postoperative days 1, 3, 5 and 7, we measured skin hardness (N), interstitial liquid content (П) and intracellular liquid content (W) as biophysical properties in patients who underwent post-CRT salvage therapy and those who underwent total organ resection without CRT as controls. We then analyzed these data in relation to occurrence of complications.In 11 patients undergoing salvage surgery and 23 controls, complications tended to be higher (N, П and W are useful measurements for the early identification of patients likely to develop complications.

To investigate the association between hypoxic-ischaemic insult timing and brain injury type in infants with severe cerebral palsy (CP).Longitudinal study.Database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy.Infants with severe CP born at ≥34 weeks of gestation.The intrapartum fetal heart rate (FHR) strips were categorised as continuous bradycardia; persistently non-reassuring (NR-NR); reassuring-prolonged deceleration (R-PD); Hon's pattern (R-Hon); persistently reassuring (R-R); and unclassified. The brain magnetic resonance imaging (MRI) scans were categorised based on the predominant site involved: basal ganglia-thalamus (BGT); white matter (WM); watershed (WS); stroke; normal; and unclassified.Manifestations of the brain MRI types and the association between FHR evolution pattern and MRI type were analysed.Among 672 eligible infants, 76% had BGT-dominant injury, 5.4% WM, 1.2% WS, 1.6% stroke, 1.9% normal, and 14% unclassified. Placental abruption and small-for-gestational age were associated with an increased (adjusted odds ratio [aOR] 8.02) and decreased (aOR 0.38) risk of BGT injury, respectively. The majority of infants had BGT injury in most FHR groups (bradycardia, 97%; NR-NR, 75%; R-PD, 90%; R-Hon, 76%; and R-R, 45%). The risk profiles in case of BGT in the NR-NR group were similar to those in the R-PD and R-Hon groups.BGT-dominant brain damage accounted for three-fourths of the cases of CP in term or near-term infants, even in prenatal onset cases. Hypoxic-ischaemic insult has a major impact on CP development during the antenatal period.Basal ganglia-thalamus injury constitutes 76% of severe cerebral palsy cases, predominant even in antenatal-onset cases.

A 26-year-old woman developed a sudden headache, ptosis, and diplopia. Magnetic resonance imaging and angiography demonstrated a symmetrical lesion from the midbrain to the brainstem, involving the solitary nucleus and multifocal cerebral artery narrowing. Reversible cerebral vasospasm syndrome (RCVS) was suspected, and the patient improved after vasodilatation. Leigh syndrome was suspected due to the elevated serum lactate levels, so mitochondrial DNA was analyzed, and an m.9176 TC mutation was detected. The final diagnosis was adult-onset Leigh syndrome manifesting as RCVS. An uncontrolled baroreflex due to a solitary nuclear lesion or endothelial dysfunction may have contributed to her unique presentation.

Background Mucociliary transport function in the airway mucosa is essential for maintaining a clean mucosal surface. This function is impaired in upper and lower airway diseases. Nasal polyps are a typical pathological feature of prolonged rhinosinusitis. Like the ordinary nasal mucosa, nasal polyps have a ciliated pseudostratified epithelium with vigorous ciliary beating. We herein measured ex vivo mucociliary transport velocity (MCTV) and ciliary beat frequency (CBF) and explored the expressions of planar cell polarity (PCP) proteins in nasal polyps in comparison with turbinate mucosae. Methods Inferior turbinates and nasal polyps were collected from patients with chronic rhinosinusitis during endoscopic sinonasal surgery. Ex vivo MCTV and CBF were measured using a high-speed digital imaging system. Expressions of PCP proteins were explored by fluorescence immunohistochemistry and quantitative RT-PCR. Results The MCTV of nasal polyps was significantly lower than that of the turbinates (7.43±2.01 vs. 14.56±2.09μm/s; P=0.0361), whereas CBF did not differ between the two tissues. The MCTV vector was pointed to the posteroinferior direction in all turbinates with an average inclination angle of 41.0 degrees. Immunohistochemical expressions of Dishevelled-1, Dishevelled-3, Frizzled3, Frizzled6, Prickle2 and Vangl2 were lower in the nasal polyps than in the turbinates. The expression levels of mRNAs for Dishevelled-1, Dishevelled-3 and Frizzled3 in the nasal polyps were also decreased in comparison with the turbinates. Conclusions These results indicate that ciliary transport in nasal polyps is impaired although vigorous ciliary beating is maintained, and that the impairment may be caused by a decrease in Dishevelled/Frizzled proteins and resultant PCP disarrangement.

The selection of appropriate recipient vessels is important for the success of head and neck reconstruction. Vessels located outside of previously-dissected neck regions tend to be more frequently selected due to relative ease of preparation. However, some advantages are offered regarding dead space filling and formation by using vascular anastomoses within regions previously dissected, or reusing former free flap pedicle due to their proximity to the defect. We analyzed microsurgical anastomoses in patients requiring oral reconstruction who had previously undergone neck dissection. Contralateral vascular anastomoses were preoperatively planned in 10 cases of which 9 could be successfully performed (achievement rate, 90%). Ipsilateral side anastomoses were planned in 28 cases, with 26 anastomosed as planned (achievement rate, 92.9%). There was no statistically significant difference between the two groups. Vascular anastomosis within the scar region can be performed safely, based on preoperative planning and intraoperative judgment.

To verify validity of the criteria used for the Japan Obstetric Compensation System for Cerebral Palsy (JOCS-CP) in preterm infants, the association between the criteria and the development of CP was studied using a neonatal database. Our hypothesis was that the criteria would not be sufficient due to the recent advances made in perinatal care.Preterm infants born between 2003 and 2019 and registered in the Neonatal Research Network of Japan database with a birth weight of 1500 g or less or a gestational age of less than 32 weeks were analyzed. The database included the clinical information of registered infants during their stay in NICUs and outcomes at 3 years of age.The database included 73 615 infants. After excluding those with an unknown outcome at discharge, 73 464 infants were analyzed for short-term outcomes, including mortality and morbidities. The incidence of CP at 3 years of age was analyzed in 36 151 infants. Furthermore, 16 467 infants born between 28 and 31 weeks of gestation were examined in terms of the validity of the current eligibility criteria. The mortality and incidences of severe intraventricular hemorrhage and periventricular leukomalacia significantly decreased during the study period (Cochrane-Armitage test, p 0.01). Furthermore, the eligibility criteria were not sufficiently nor strongly associated with indicators for detecting perinatal hypoxia-ischemia resulting in CP.The existing eligibility criteria of the JOCS-CP used for preterm infants born between 28 and 31 weeks were no longer suitable because of the advances in perinatal care in Japan.

Background: Maintaining cognitive function is integral to a healthy social life in the aged. Although neuropsychological tests and brain imaging methods can assess cognitive dysfunction, these techniques are subjective, psychologically burdensome, and cannot be conducted easily. Objective: We sought to develop an objective, low-burden novel cognitive function scale based on functional near-infrared spectroscopy (fNIRS) of hemodynamic changes in the cerebral cortex during daily task performance. Methods: A total of 63 participants (aged 60–80 years) identified as non-dementia controls (NDC) or with mild cognitive impairment (MCI) were recruited and randomly assigned to training and test data sets. Explanatory variables were hemodynamic responses during low-burden sensory and simple tasks without higher-order brain functioning. Results: A logistic regression analysis of the fNIRS index in NDCs and MCI patients revealed area under the curve, sensitivity, specificity, and holdout results of 0.98, 94%, 88%, and 62% respectively. Correlation between fNIRS index and MCI odds showed positive linearity (R2 = 0.96). Conclusion: Positive correlation between the fNIRS index and MCI odds indicated effectiveness of this fNIRS measurement. Although additional experiments are necessary, the fNIRS index representing degree of cognitive decline can be an onsite monitoring tool to assess cognitive status.

Introduction Takotsubo syndrome (TTS) is triggered mostly by physical and/or emotional stress that is processed in stress-associated brain regions, including the amygdala. However, it remains unclear whether such stress-induced brain activity is associated with TTS onset. Methods and results We acquired brain [18F]-2-fluoro-deoxy- d -glucose (18F-FDG) positron emission tomography in 4 TTS patients (44–82 yrs., 3 women) on days 2–4 (acute phase) and days 29–40 (recovery phase) after diagnosis of TTS was made by coronary angiography and left ventriculogram. The 18F-FDG uptake was measured globally and also in the pre-defined regions of interest of the bilateral amygdala on the common Montreal Neurological Institute space; all 18F-FDG images were normalized using automated image pre-processing. Amygdalar activity was calculated by dividing the 18F-FDG uptake of the amygdala by the global brain uptake. Left ventriculograms showed that apical ballooning was typical at diagnosis and was then relieved in the recovery phase. Amygdalar activity in the acute phase (0.872 ± 0.032) was higher than in the recovery phase (0.805 ± 0.037) (P = 0.013). Conclusions We report here 4 cases of TTS showing higher amygdalar activity in the acute phase as compared with the recovery phase, suggesting that increased stress-induced neurobiological activity is associated with TTS onset.

Background: Nasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa. Methods and Results: Inferior turbinates were collected from patients with chronic hypertrophic rhinitis, and ex vivo ciliary beat frequency (CBF) was immediately measured using a high-speed digital video camera attached to a phase-contrast light microscope. The samples were also subjected to fluorescence immunohistochemistry and real-time RT-PCR for TRPA1/TRPM8. CBF was significantly increased by adding either cinnamaldehyde (TRPA1 agonist) or l-menthol (TRPM8 agonist), and this increase was inhibited by pannexin-1 blockers, carbenoxolone and probenecid. Immunohistochemistry detected TRPA1 and TRPM8 on the epithelial surface and in the submucosal nasal glands. Expressions of mRNAs for these receptors were confirmed by real-time RT-PCR. Conclusions: These results indicate the stimulatory effect of the activation of TRPA1/TRPM8 on ciliary beating in the nasal mucosa, which would be advantageous to maintain airway mucosal defense under normal nasal breathing. This stimulatory effect is likely to be mediated by pannexin-1. Understanding the regulatory mechanism of airway ciliary beating should aid in the development of new, effective treatments for intractable airway diseases. BackgroundNasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa.

A primary pathology of Alzheimer’s disease (AD) is Aβ deposition in brain parenchyma and blood vessels, the latter being called cerebral amyloid angiopathy (CAA). Parenchymal amyloid plaques presumably originate from neuronal Aβ precursor protein (APP), but vascular amyloid deposits’ origins remain unclear. Endothelial APP expression in APP-knock-in mice was recently shown to expand CAA pathology, highlighting endothelial APP’s importance. Furthermore, two types of endothelial APP—with and without O-glycans—have been biochemically identified, but only the former is cleaved for Aβ production, indicating the critical relationship between APP O-glycosylation and processing. Here, we analyzed APP glycosylation and its intracellular trafficking in neurons and endothelial cells. Although protein glycosylation is generally believed to precede cell surface trafficking, which was true for neuronal APP, we unexpectedly observed that APP lacking O-glycans is externalized to the endothelial cell surface and transported back to the Golgi apparatus, where it then acquires O-glycans. Knockdown of genes encoding enzymes initiating APP O-glycosylation significantly reduced Αβ production, suggesting this non-classical glycosylation pathway contributes to CAA pathology and is a novel therapeutic target.

Cerebral palsy is more common among preterm infants than among full-term infants. Although there is still no clear evidence that fetal heart rate monitoring effectively reduces cerebral palsy incidence, it is helpful to estimate the timing of brain injury leading to cerebral palsy and the causal relationship with delivery based on the fetal heart rate evolution patterns. Understanding the relationship between the timing and the type of brain injury can help to identify preventive measures in obstetrical care.This study aimed to examine the relationship between the timing of insults and the type of brain injury in preterm infants with severe cerebral palsy.This longitudinal study was based on a nationwide database for cerebral palsy. The data of infants with severe cerebral palsy (equivalent to levels 3-5 of the Gross Motor Function Classification System-Expanded and Revised), born between 2009 and 2014 at 28 to 33 weeks of gestation, were included. The intrapartum fetal heart rate evolution patterns were evaluated by 3 obstetricians blinded to clinical information other than gestational age at birth, and these were categorized after agreement by at least 2 of the 3 reviewers into (1) continuous bradycardia, (2) persistently nonreassuring (prenatal onset), (3) reassuring-prolonged deceleration, (4) Hon's pattern (intrapartum onset), (5) persistently reassuring (pre- or postnatal onset), and (6) unclassified. Infant brain magnetic resonance imaging findings at term-equivalent age were assessed by a pediatric neurologist blinded to the background details, except for gestational age at birth and corrected age at image acquisition, and these were categorized as (1) basal ganglia-thalamus, (2) white matter, (3) watershed cortex or subcortex, (4) stroke, (5) normal, and (6) unclassified based on the predominant site involved. The risk factors for the basal ganglia-thalamus group were compared with those of the combined white matter and watershed injuries group.Among 1593 infants with severe cerebral palsy, 231 were born at 28 to 33 weeks of gestation, and 140 met the eligibility criteria. Fetal heart rate evolution patterns were categorized as bradycardia (17% [24]); persistently nonreassuring (40% [56]); reassuring-prolonged deceleration (7% [10]); reassuring-Hon (6% [8]); persistently reassuring (7% [10]); and unclassified (23% [32]). Cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in 13% of infants. Magnetic resonance imaging showed that 34% (n=48) of infants developed basal ganglia-thalamus-dominant brain injury. Of the remaining 92 infants, 43% (60) showed white matter injuries, 1% (1) showed watershed injuries, 4% (5) showed stroke, 1% (1) had normal findings, and 18% (25) had unclassified findings. Infants with continuous bradycardia (adjusted odds ratio, 1033.06; 95% confidence interval, 15.49-68,879.92) and persistently nonreassuring fetal heart rate patterns (61.20; 2.09-1793.12) had a significantly increased risk for basal ganglia-thalamus injury.Severe cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in only 13% of infants born at 28 to 33 weeks of gestation. Although the white matter-watershed injury was predominant in the study populations, severe acute hypoxia-ischemia may be an important prenatal etiology of severe cerebral palsy in preterm infants.

Background: The ciliary beat of the airway epithelium, including the sinonasal epithelium, has a significant role in frontline defense and is thought to be controlled by the level of intracellular Ca2+. Involvement of calmodulin and adenylate/guanylate cyclases in the regulation of ciliary beats has been reported, and here we investigated the interrelation between these components of the ciliary beat regulatory pathway. Methods: The inferior turbinates were collected from 29 patients with chronic hypertrophic rhinitis/rhinosinusitis during endoscopic sinonasal surgery. The turbinate mucosa was cut into thin strips, and mucociliary movement was observed under a phase-contrast light microscope equipped with a high-speed digital video camera. Results: The ciliary beat frequency (CBF) was significantly increased by stimulation with 100 μM CALP3 (calmodulin agonist), which was completely suppressed by adding 100 µM SQ22536 (adenylate cyclase inhibitor) and 10 µM ODQ (guanylate cyclase inhibitor) together and by adding 1 µM KT5720 (protein kinase A inhibitor) and 1 µM KT5823 (protein kinase G inhibitor) together. The CBF was significantly increased by stimulation with 10 µM forskolin (adenylate cyclase activator) and 10 µM BAY41-2272 (guanylate cyclase activator) and by stimulation with 100 µM 8-bromo-cAMP (cAMP analog) and 100 µM 8-bromo-cGMP (cGMP analog), which was not changed by adding 1 µM calmidazolium (calmodulin antagonist). Conclusions: These results confirmed that the regulatory pathway of ciliary beats in the human nasal mucosa involves calmodulin, adenylate/guanylate cyclases, and protein kinases A/G and indicate that adenylate/guanylate cyclases and protein kinases A/G act downstream of calmodulin, but not vice versa, and that these cyclases relay calmodulin signaling.

Objectives Delirium is an important prognostic factor in postoperative patients undergoing cardiovascular surgery and intervention, including transcatheter aortic valve implantation (TAVI). However, delirium after transcatheter aortic valve implantation (DAT) is difficult to predict and its pathophysiology is still unclear. We aimed to investigate whether preoperative cerebral blood flow (CBF) is associated with DAT and, if so, whether CBF measurement is useful for predicting DAT. Methods We evaluated CBF in 50 consecutive patients before TAVI (84.7±4.5 yrs., 36 females) using 99mTc ethyl cysteinate dimer single-photon emission computed tomography. Preoperative CBF of the DAT group (N = 12) was compared with that of the non-DAT group (N = 38) using whole brain voxel-wise analysis with SPM12 and region of interest-based analysis with the easy-Z score imaging system. Multivariable logistic regression analysis with the presence of DAT was used to create its prediction model. Results The whole brain analysis showed that preoperative CBF in the insula was lower in the DAT than in the non-DAT group (P Conclusions These results suggest that preoperative CBF in the insula is associated with DAT and may be useful for its prediction.

Background The aim of the present study was to clarify fetal heart rate (FHR) evolution patterns in infants with cerebral palsy (CP) according to different types of umbilical cord complications. Methods This case–control study included children born: with a birth weight ≥2000 g, at gestational age ≥33 weeks, with disability due to CP, and between 2009 and 2014. Obstetric characteristics and FHR patterns were compared among patients with CP associated with (126 cases) and without (594 controls) umbilical cord complications. Results There were 32 umbilical cord prolapse cases and 94 cases with coexistent antenatal umbilical cord complications. Compared with the control group, the persistent non-reassuring pattern was more frequent in cases with coexistent antenatal umbilical cord complications (p = 0.012). A reassuring FHR pattern was observed on admission, but resulted in prolonged deceleration, especially during the first stage of labor, and was significantly identified in 69% of cases with umbilical cord prolapse and 35% of cases with antenatal cord complications, compared to 17% of control cases (p Conclusion Hypercoiled cord and abnormal placental umbilical cord insertion, may be associated with CP due to acute hypoxic-ischemic injury as well as sub-acute or chronic adverse events during pregnancy, while umbilical cord prolapse may be characterized by acute hypoxic-ischemic injury during delivery.

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart-brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.

Although depressive symptoms increased mortality and hospitalization in chronic heart failure (CHF) patients, the underlying mechanism remains unclear. The aim of this study was to investigate whether an alteration in hippocampal perfusion, which is the neural substrate of depressive symptoms, is associated with changes in cardiac structures and/or functions in CHF patients.We used baseline data of 70 CHF patients (66.8 ± 8.9 yrs, 32.5% women), including cerebral blood flow (CBF) in the hippocampus, geriatric depression scale (GDS) scores and echocardiographic parameters, in the Brain Assessment and Investigation in Heart Failure Trial (B-HeFT) (UMIN000008584). Echocardiography was repeated at 3.1 ± 0.5 years after the baseline evaluation. We first tested voxel-wise regression model with hippocampal CBF as dependent variable and each of echocardiographic parameter change as independent variable, adjusted for age and sex. Structural equation modeling was used to test a mediation effect of cognitive test scores on associations between hippocampal perfusion and changes in cardiac structures and/or functions.Baseline anterior hippocampal CBF was negatively correlated with changes in left ventricular posterior wall thickness (PWT) (P 0.05 with family-wise error corrections). An existence of depressive symptoms was positively correlated with the baseline anterior CBF and negatively with the PWT changes (P 0.05, both). There were both direct effects of the baseline anterior hippocampal CBF on PWT thinning and effects mediated through the depressive symptoms (P 0.05, both).This study provides the first evidence that the alteration in hippocampal perfusion may lead to changes in cardiac structures via increase in depressive symptoms in CHF patients.

Background: Hearing recovery would be different in each sound frequency in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).Aims/objectives: To analyze frequency-specific efficac...

Nasal polyp formation is a common sequela of prolonged chronic rhinosinusitis, but the mechanism underlying this disease state is still controversial. We compared the expressions of Cl− channels/transporters in nasal polyps with those in inferior turbinates to explore whether a deficiency in Cl− transport may participate in the pathophysiology of nasal polyp formation as in patients with cystic fibrosis. Nasal polyps and inferior turbinates were collected from 12 chronic rhinosinusitis patients with hypertrophic rhinitis and/or nasal polyps. Expressions of cystic fibrosis transmembrane conductance regulator (CFTR), pendrin, Na+–K+–2Cl− cotransporter 1 (NKCC1), SLC26A3, TMEM16A and anion exchanger 2 (AE2) were examined by fluorescence immunohistochemistry using Alexa Fluor 488. CFTR was weakly expressed on the epithelial surface of the turbinate mucosa whereas the nasal polyps showed almost no fluorescence. Pendrin was mainly expressed on the epithelial surface in both tissues. The fluorescence was moderate in the nasal polyps and strong in the turbinate mucosa. For NKCC1, moderate fluorescence was observed throughout the entire epithelial layer of the nasal polyps, but the turbinate mucosa exhibited almost no fluorescence. On the other hand, no fluorescence for SLC26A3, TMEM16A or AE2 was seen in either tissue. These results suggest that CFTR, pendrin and NKCC1 may participate in the pathogenesis of nasal mucosal edema and play roles in the mechanism of nasal polyp formation.

Although cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed.In 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia.CyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (both p0.05) and were linearly correlated with mean pulmonary arterial pressure (r=0.50, p = 0.0003) and pulmonary vascular resistance (r=0.32, p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p0.01 and p = 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35pg/mL) and normal (35pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (both p0.05). In contrast, BNP decreased only in patients with higher BNP (p0.05). Also, CyPA decreased both in patients with lower (25 kg/mCyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI.

AIMS The aim of this study was to examine the mechanisms of cognitive impairment and reversibility in elderly patients with severe aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI) with special reference to cerebral blood flow (CBF). METHODS AND RESULTS We examined 15 elderly patients with severe AS (mean age 83.2±4.5 years, 12 female) who underwent TAVI. Before and three months after TAVI, we evaluated cognitive function with the Logical Memory II test (LM II), cardiac output (CO) with echocardiography, and CBF with 99mTc single-photon emission computed tomography (SPECT). LM II score and CO were significantly increased after TAVI compared with baseline (p

Since the last quarter of the 18th century, the suppression of the transoceanic slave trade had been under way. A popular movement became active in Britain, while a number of US states abolished the trade in the last quarter of the 18th century. Denmark abolished the trade completely in 1803, Britain in 1807, and the United States in 1808. After the Congress of Vienna, the British took the initiative in creating a network of bilateral and multilateral treaties to legalize naval suppression of the slave trade in the Atlantic, and, accordingly, Britain, the United States, France, and Portugal stationed naval squadrons off the African coast. From the 1840s onwards, another network to suppress slave supply was formed with African rulers, those agreements providing in some cases both justification and the practical basis for European territorial expansion in Atlantic Africa. The Europeans’ antislave-trade activity caused the Atlantic African economy to shift toward so-called legitimate commerce, and, since the 1960s, evaluation of that economic transition has been at the core of debate among historians of West Africa. In the 1810s in the Indian Ocean, similar progress toward suppression of the slave trade took place almost simultaneously with that of its Atlantic counterpart, although progress was much quicker in the Atlantic. In fact, the suppression campaign in the Indian Ocean, which began with various treaties concluded by the British with local polities, gathered full force only from the 1860s. Interestingly, in Indian Ocean Africa the relationship between the suppression of the slave trade and imperial territorial occupation was more distant than on Africa’s Atlantic rim. The suppression of the transoceanic slave trade cannot be understood without a multifaceted perspective, because this subject is connected to and so must be integrated with various fields, including naval, political, economic, legal, and social history. The transoceanic slave trade must therefore be located within a much wider context.

After treatment with an immune checkpoint inhibitor (ICI) is discontinued, retreatment with an ICI is a potential sequential treatment, but the clinical efficacy/safety data for this treatment of recurrent and/or metastatic head and neck cancer (R/M-HNC) are limited.This study aimed to evaluate the efficacy and safety of retreatment with nivolumab in R/M HNC.We divided the 29 eligible R/M-HNC patients who discontinued ICI treatment at our hospital into two cohorts to analyze the clinical characteristics and the efficacy of the salvage therapy: the Niv cohort (nivolumab retreatment) and the no-Niv cohort (no nivolumab retreatment).The Niv cohort's median overall survival (OS) of 17.5 months (95% confidence interval [CI]: 2.7-32.3) was significantly prolonged compared to that of the no-Niv cohort: 5.8 months (95%CI: 2.4-9.2,Nivolumab retreatment is an option for sequential treatment post-immunotherapy.

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cerebral small vessel disease derived from its most common MRI features: white matter hyperintensities and lacunes. Seventeen population-based cohorts of older persons with MRI measurements and genome-wide genotyping (n = 41 326), whole-exome sequencing (n = 15 965), or exome chip (n = 5249) data contributed 13 776 and 7079 extreme small vessel disease samples for the genome-wide association study and whole-exome association study, respectively. The genome-wide association study identified significant association of common variants in 11 loci with extreme small vessel disease, of which the chr12q24.11 locus was not previously reported to be associated with any MRI marker of cerebral small vessel disease. The whole-exome association study identified significant associations of extreme small vessel disease with common variants in the 5′ UTR region of EFEMP1 (chr2p16.1) and one probably damaging common missense variant in TRIM47 (chr17q25.1). Mendelian randomization supports the causal association of extensive small vessel disease severity with increased risk of stroke and Alzheimer’s disease. Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. We observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology. Overall, our comprehensive gene-mapping study and preliminary functional evaluation suggests a putative role of TRIM47 in the pathophysiology of cerebral small vessel disease, making it an important candidate for extensive in vivo explorations and future translational work.

Background It is crucial to interpret fetal heart rate patterns with a focus on the pattern evolution during labor to estimate the relationship between cerebral palsy and delivery. However, nationwide data are not available. Objective The aim of our study was to demonstrate the features of fetal heart rate pattern evolution and estimate the timing of fetal brain injury during labor in cerebral palsy cases. Study Design In this longitudinal study, 1069 consecutive intrapartum fetal heart rate strips from infants with severe cerebral palsy at or beyond 34 weeks of gestation, were analyzed. They were categorized as follows: (1) continuous bradycardia (Bradycardia), (2) persistently nonreassuring, (3) reassuring-prolonged deceleration, (4) Hon’s pattern, and (5) persistently reassuring. The clinical factors underlying cerebral palsy in each group were assessed. Results Hypoxic brain injury during labor (those in the reassuring-prolonged deceleration and Hon’s pattern groups) accounted for 31.5% of severe cerebral palsy cases and at least 30% of those developed during the antenatal period. Of the 1069 cases, 7.86% were classified as continuous bradycardia (n=84), 21.7% as persistently nonreassuring (n=232), 15.6% as reassuring-prolonged deceleration (n=167), 15.9% as Hon’s pattern (n=170), 19.8% as persistently reassuring (n=212), and 19.1% were unclassified (n=204). The overall interobserver agreement was moderate (kappa 0.59). Placental abruption was the most common cause (31.9%) of cerebral palsy, accounting for almost 90% of cases in the continuous bradycardia group (64 of 73). Among the cases in the Hon’s pattern group (n=67), umbilical cord abnormalities were the most common clinical factor for cerebral palsy development (29.9%), followed by placental abruption (20.9%), and inappropriate operative vaginal delivery (13.4%). Conclusion Intrapartum hypoxic brain injury accounted for approximately 30% of severe cerebral palsy cases, whereas a substantial proportion of the cases were suspected to have either a prenatal or postnatal onset. Up to 16% of cerebral palsy cases may be preventable by placing a greater focus on the earlier changes seen in the Hon’s fetal heart rate progression.

BackgroundThere is no evidential report about the optimal duration of antibiotic use following video-assisted thoracoscopic surgery debridement (VATS-D) in thoracic empyema (TE) or complicated parapneumonic effusion (PPE). The purpose of this study was to determine the optimal duration of antibiotic therapy after VATS-D for TE /PPE.MethodsBetween January 2011 and December 2019, total thirty-three patients (28 men, 5 women; median age 63 years) corresponding to ACCP category 3 or 4 receiving VATS-D were included in the study. Time until the body temperature (BT) was to be less than 37.5 ºC and 37.0 ºC, WBC count to be less than 10,000/μl and segmented neutrophil (seg) count to be less than 80% were retrospectively analyzed.ResultsThe median time from the onset of TE/PPE to the operation was 13 days. Pre and postoperative antibiotic had median values of 5 and 7 days, respectively. There were no hospital deaths within 30 days of the operation. Major complications occurred in 4 cases (3 respiratory failures and one celebral infarction). Median postoperative hospital stay was 14 days. Success rate in TE/PPE treatment was 88%. The median number of days until the conditions met were BT>37.5 ºC for 3 days, BT>37.0 ºC for 6 days, WBC

The hearing outcome of idiopathic sudden sensorineural hearing loss (ISSNHL) is hard to predict. We herein constructed a multiple regression model for hearing outcomes in each frequency separately in an attempt to achieve practical prediction in ISSNHL.We enrolled 235 consecutive in-patients with ISSNHL who were treated in our department from 2015 to 2020 (average hearing level at 250-4000 Hz ≥ 40 dB; time from onset to treatment ≤ 14 days; 126 males/109 females; age range 17-87 years (average 61.0 years)). All patients received systemic prednisolone administration combined with intratympanic dexamethasone injection. The pure-tone hearing threshold of 125-8000 Hz was measured at every octave before (HLThe multiple correlation coefficient increased as the frequency increased. Strong correlations were seen in high frequencies, with multiple correlation coefficients of 0.784/0.830 for 4000/8000 Hz. The width of the 70% prediction interval was narrower for 4000/8000 Hz (± 18.2/16.3 dB) than for low to mid-frequencies. Among the five explanatory variables, HLThe present model would be of practical use for predicting hearing outcomes in high frequencies in patients with ISSNHL.

Advances in perinatal care have improved the prognoses of both mothers and neonates; however, cerebral palsy continues to occur. In this study, we examined methods for the intragestational evaluation of the health of infants who later developed cerebral palsy. A retrospective review was conducted on light-for-dates cases among the 2113 cause analysis reports issued by the Japan Obstetric Compensation System between January 2009 and September 2018. In our examination, we determined that non-stress tests and ultrasonic Doppler tests were used to evaluate fetal well-being. Moreover, we observed cases in which additional testing was not performed even when fetal growth restriction (FGR) was identified. Appropriate management of FGR may help reduce the incidence of cerebral palsy.

Takotsubo syndrome (TTS) is triggered mostly by physical and/or emotional stress that is processed in stress-associated brain regions, including the amygdala. However, it remains unclear whether such stress-induced brain activity is associated with TTS onset.We acquired brain [We report here 4 cases of TTS showing higher amygdalar activity in the acute phase as compared with the recovery phase, suggesting that increased stress-induced neurobiological activity is associated with TTS onset.