Observational study of effects of pharyngeal stimulation by carbonated solution on repetitive voluntary swallowing in humans.

In this study, we conducted observational study to examine the effects of pharyngeal stimulation by a bolus of carbonated solution on repetitive voluntary swallowing in humans. Twelve healthy participants had a fine silicone tube inserted into their pharyngeal region, through which various solutions were slowly infused (0.2 mL/minute) to stimulate the pharyngeal mucosa without activating mechanoreceptors. The solutions included 0.3M NaCl (NaCl), carbonated 0.3M NaCl (NaCl + CA), 0.3M NaCl with acetic acid, distilled water, and carbonated distilled water. We used NaCl to inhibit water-sensitive neurons in the pharyngeal mucosa and enable the evaluation of the effects of carbonic acid stimulation on swallowing. Participants were instructed to repeat swallows as rapidly as possible during the infusion, and the swallowing interval (SI) was measured via submental surface electromyographic activity. SI was significantly shorter during the infusion of NaCl + CA, distilled water, and carbonated distilled water than during the infusion of NaCl. There was a significant positive correlation between SI with NaCl stimulation and the facilitative effects of the other solutions. Longer SIs with NaCl stimulation indicated potent facilitative effects. Thus, stimulation with NaCl + CA facilitated swallowing by reducing SI. Furthermore, the facilitative effects of SI were more pronounced in participants who had difficulty with repetitive voluntary swallowing. The sensation induced by carbonated solution may enhance the ability for repetitive voluntary swallowing, making it a potentially useful approach for rehabilitating patients with dysphagia.

Ninjin'yoeito Ameliorates Skeletal Muscle Complications in COPD Model Mice by Upregulating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Expression.

Purpose: Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin'yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice. Materials and Methods: Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks. Results: Cigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution. Conclusion: NYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.

The Comparison of the Efficacy of Baloxavir and Neuraminidase Inhibitors for Patients with Influenza A in Clinical Practice.

Objective Baloxavir marboxil is a novel anti-influenza drug reported to have an early antiviral effect, although it also causes the appearance of variant viruses with a reduced susceptibility to baloxavir. In Japan, four neuraminidase inhibitors (NAIs) have been commonly used to treat patients with influenza. In clinical practice, the differences in the effects of baloxavir and NAIs have not been sufficiently examined. Our objective was to clarify the clinical differences in efficacy between baloxavir and NAIs. Methods A multicenter, observational study was conducted using postcard questionnaires during the 2018-19 influenza season. Patients who were prescribed anti-influenza drugs were provided postcard questionnaires asking about their background characteristics and their body temperatures. The factors associated with the early alleviation of the fever were analyzed, and the duration of the fever was compared between the baloxavir group and the NAI group. Results A total of 295 patients with influenza A, ranging in age from 0-91 years old, were enrolled in this study. A multivariate analysis showed that treatment with baloxavir and a duration from the onset to the start of treatment ≥2.5 days were factors contributing to the early alleviation of the fever from the start of treatment. The duration of the fever was significantly shorter in the baloxavir group than in the NAI group (p=0.002). Conclusion The present survey showed that baloxavir was significantly more effective than NAIs for treating patients with influenza A in clinical practice.

Nuclear Protein in Testis Carcinoma of the Thorax.

Nuclear protein in testis (NUT) carcinoma (NUT-C) is an exceedingly rare and aggressive neoplasm. We herein report a case of a 57-year-old man with a rapidly progressing tumor of the thorax and left pleural effusion. The pathological features and immunohistochemical staining of specimens obtained by a transbronchial lung biopsy initially indicated poorly differentiated squamous cell carcinoma. However, given the clinical presentation along with the additional histopathologic features, NUT-C was considered. Immunohistochemical staining for NUT was positive in the pleural fluid cell block, confirming the diagnosis of NUT-C. This report indicates the utility of immunohistochemical staining for diagnosing NUT in the pleural fluid cell block.

Difficult intubation due to unknown congenital tracheal stenosis in the adult: a case report and literature review.

Congenital tracheal stenosis (CTS) is a rare disorder almost always diagnosed in infancy due to respiratory failure and other cardiopulmonary abnormalities. We experienced a 42-year-old female undiagnosed with CTS until difficult intubation upon surgery. Chest X-ray and computed tomography (CT) images revealed bronchial narrowing, which could already be seen prior to intubation, but was left unnoticed. Difficult airway management is a potentially lethal airway emergency. This life-threatening situation is preventable with the appropriate awareness. We report this clinically valuable case for the safety of future patient care. In English and Japanese literature, there are only 12 reported cases of CTS diagnosed in the adult. Ours and six previous cases were discovered with difficult intubation, a preventable life-threatening airway emergency. Pre-intubation images should be examined carefully for the possibility of CTS, as its frequency may be underestimated. Moreover, in treatment resistant recurrent asthmatic episodes, CTS should be kept in mind.

Three Simultaneous Cases of Spontaneous Pneumomediastinum With Epidural Pneumatosis During Vocal Training.

OBJECTIVE: The aim of this study was to describe a case series of three simultaneous cases of spontaneous pneumomediastinum (SPM) with epidural pneumatosis during vocal training. METHODS: A report of three cases with chart review was performed. Literature review was carried out using PubMed. RESULTS: This was an extremely rare case series where at least three of the 20 participants of a vocal training in a self-development seminar developed SPM, epidural pneumatosis, pneumothorax, and subcutaneous emphysema. All cases improved with bed rest. Simultaneous cases of SPM have been reported in the past. However, the cause of simultaneous occurrence has not been explained clearly. In our cases, continuous excessive vocal training may have caused intrathoracic pressure to rise, causing SPM at a high prevalence. Epidural pneumatosis is a rare finding. Studies on epidural pneumatosis complicating SPM are limited. Air is said to easily pass through the cervical region owing to the close proximity between the mediastinum and the upper spine, resulting in epidural pneumatosis. Elevated intrathoracic pressure while the glottis is closed may worsen the risk for epidural pneumatosis. In this seminar, continuous effortful vocal training at full pitch with few pauses for breath may have contributed to this simultaneous occurrence. CONCLUSIONS: We report three simultaneous cases of SPM and epidural pneumatosis due to demanding vocal training. Further research on this subject is desired to identify risk factors.

Construction of multi-gene classifier for prediction of response to and prognosis after neoadjuvant chemotherapy for estrogen receptor positive breast cancers.

The aims of this study were to develop a multi-gene expression-based prediction model for pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) and to evaluate its prognosis prediction for estrogen receptor (ER) positive breast cancers. The training set included the NAC-treated patients (n = 104) with ER+ breast tumors in our hospital and the validation set included the NAC-treated patients (n = 259) with ER+/HER2- breast tumors in the public database (GSE25066). Gene expression in the tumor biopsy specimens obtained before NAC was analyzed with DNA microarray, and the prediction model (MPCP155) for pCR was constructed for the training set by using the genes (155 probes) involved in the metabolic pathways which the pathway analysis identified as being significantly associated with pathological response. With MPCP155, the tumors in the validation set could be classified into low chemo-sensitive (low-CS) (pCR rate = 2.6%) and high-CS (pCR rate = 15.3%; P = 0.0006) groups. Furthermore, the low-CS group showed a significantly better prognosis than the high-CS group (P = 2.0E-6). Moreover, prognosis prediction by MPCP155 was independent of the residual cancer burden score. MPCP155 may be helpful for decision making regarding the indication for neoadjuvant chemotherapy. In addition, MPCP155 was found to be useful for prognosis prediction for NAC-treated patients with ER+/HER2- tumors.

Prediction of pathological complete response to neoadjuvant chemotherapy by magnetic resonance imaging in breast cancer patients.

The purpose of this study was to evaluate whether the baseline breast MRI findings would be useful for the prediction for pathological complete response (pCR) by breast cancer patients to neoadjuvant chemotherapy. Primary breast cancer patients (stage II-III) preoperatively treated with sequential paclitaxel (12 cycles) and fluorouracil, epirubicin, and cyclophosphamide (4 cycles), followed by surgery were retrospectively enrolled, and 229 patients were eligible. Before chemotherapy, breast MRI studies were performed. Breast tumors were dichotomized into round + oval and irregular types based on MRI morphology. The round + oval tumors showed a significantly higher pCR rate than the irregular tumors (42.0% vs 17.3%; P < 0.001). In addition, PAM50 analysis revealed that basal and HER2-enriched tumors were significantly more prevalent among round + oval than irregular type tumors (P = 0.015). Baseline MRI morphology appears to be a significant predictor for pCR. The higher rate of the basal and HER2-enriched tumors among the round + oval tumors may explain their better chemo-sensitivity.

PIK3CA mutations in serum DNA are predictive of recurrence in primary breast cancer patients.

We attempted to develop a highly sensitive and specific method for the detection of circulating tumor DNA (ctDNA) using a digital PCR (dPCR) assay for PIK3CA mutations (i.e., H1047R, E545K, and E542K) in primary breast cancer patients. The sensitivity of the dPCR assay for the mutant alleles was examined using cell lines with PIK3CA mutations and proved to be 0.01 %. Serum samples were collected pre-operatively from 313 stage I-III breast cancer patients, of whom 110 were found to have PIK3CA mutant tumors. The serum samples from these patients with PIK3CA mutant tumors were subjected to the dPCR assay, and 25 (22.7 %) were found to be positive. No PIK3CA mutant ctDNA was detected in the serum samples of 50 healthy women and 30 breast cancer patients with PIK3CA non-mutant tumors. The patients with PIK3CA mutant ctDNA were dichotomized into mutant ctDNA-high (ctDNA(high)) and ctDNA-low (ctDNA(low)) groups based on the median. The ctDNA(high) patients exhibited significantly shorter recurrence-free survival (RFS; P = 0.0002) and overall survival rates (OS; P = 0.0048) compared to those exhibited by the combined ctDNA(low) patient and ctDNA-free patient group. Multivariate analysis revealed that ctDNA(high) status significantly predicted poor RFS and OS and did so independently of conventional histological parameters. These results suggest that dPCR is a highly sensitive and specific method for the detection of PIK3CA mutant ctDNA and that ctDNA(high) but not ctDNA(low) status is a significant and independent prognostic factor for primary breast cancer patients.

BRCA1 promoter methylation of normal breast epithelial cells as a possible precursor for BRCA1-methylated breast cancer.

The breast cancer susceptibility gene 1 (BRCA1) and glutathione S-transferase P1 (GSTP1) promoters are reportedly often methylated in breast cancer tissues. Their methylation status in surrounding normal breast tissues has not been examined thoroughly although this may well be important for a better understanding of breast carcinogenesis. In this study, BRCA1 and GSTP1 promoter methylation was examined by methylation-specific PCR assay. Patients with BRCA1-methylated (n = 15) or BRCA1-unmethylated (n = 15) tumors and those with GSTP1-methylated (n = 9) or GSTP1-unmethylated (n = 11) tumors were included in the present study. Methylation status of manually micro-dissected normal epithelial cells from the formalin-fixed paraffin-embedded sections of normal breast tissues adjacent to and distant from the tumors was examined at multiple sites (n = 1-5). Of the 15 patients with BRCA1-methylated tumors, 9 harbored BRCA1 promoter methylation in at least one site of the normal breast tissues. However, no BRCA1 promoter methylation was observed at any site of the normal tissues of the 15 patients with BRCA1-unmethylated tumors. No GSTP1 promoter methylation was observed in the normal tissues regardless of the methylation status of the tumors. The presence of BRCA1 promoter methylation in the normal tissues was confirmed in the epithelial cells enriched with the magnetic-activated cell sorting method. Our findings suggest that a small proportion of normal breast epithelial cells with BRCA1 promoter methylation can be precursor cells from which BRCA1-methylated breast tumors may originate. This does not apply to GSTP1 promoter methylation.