Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Background: The purpose of the present study was to assess the daily protein uptake and its relationship with sarcopenia, as defined by the Asian Working Group for Sarcopenia (AWGS), among elderly patients with hip fractures. Methods: Forty-seven elderly patients with hip fractures were enrolled in this retrospective observational study. The main outcome measures included protein uptake, muscle mass, and grip strength for sarcopenia in elderly patients. Sarcopenia was diagnosed according to AWGS. Wholebody densitometry was used to measure skeletal muscle mass, and muscle strength was evaluated using handgrip testing. Results: Of 47 patients with hip fractures (12 men and 35 women), 37 (79%) patients exhibited insufficient protein intake (range, 0.01-0.588 g/kg/day), and 10 (21%) patients exhibited excessive protein intake (range, 1.215-2.121 g/kg/day). The mean daily protein intake was 56.5 g (range, 7.2–136.0 g). Prevalence of low muscle strength (handgrip strength <18 kg in women and <26 kg in men) was detected in 13 (37%) women and 8 (67%) men (P=0.076). Sarcopenia (lower muscle mass and lower muscle strength) was detected in 9 (26%) women and 6 (50%) men (P=0.119). Although lower protein intake was marginally associated with sarcopenia (P=0.189), it was significantly associated with lower grip strength (P=0.042). Conclusions The present study demonstrated that insufficient protein intake in elderly patients with hip fractures was common, and lower protein intake was significantly associated with lower muscle strength.

OBJECTIVE: The aims of the present study were to evaluate the changes in the maximum lip-closing force (MLF) after orthodontic treatment with or without premolar extractions and verify the correlation of these changes with dentoskeletal changes. METHODS: In total, 17 women who underwent nonextraction orthodontic treatment and 15 women who underwent orthodontic treatment with extraction of all four first premolars were included in this retrospective study. For all patients, lateral cephalograms and dental models were measured before (T0) and after (T1) treatment. In addition, MLF was measured at both time points using the Lip De Cum LDC-110R® device. Statistical analyses were performed to evaluate changes in clinical variables and MLF and their correlations. RESULTS: Both groups showed similar skeletal patterns, although the extraction group showed greater proclination of the maxillary and mandibular incisors and lip protrusion compared to the nonextraction group at T0. MLF at T0 was comparable between the two groups. The reduction in the arch width and depth and incisor retroclination from T0 to T1 were more pronounced in the extraction group than in the nonextraction group. MLF in the extraction group significantly increased during the treatment period, and this increase was significantly greater than that in the nonextraction group. The increase in MLF was found to be correlated with the increase in the interincisal angle and decrease in the intermolar width, arch depth, and incisor–mandibular plane angle. CONCLUSIONS This study suggests that MLF increases to a greater extent during extraction orthodontic treatment than during nonextraction orthodontic treatment.

Objectives: . This study aimed to elucidate the patterns of upper airway collapse in obstructive sleep apnea (OSA) patients with a low body mass index (BMI). Methods: . We designed and conducted a retrospective cohort study. Consecutive patients diagnosed with OSA who underwent drug-induced sleep endoscopy (DISE) were included. Patients were classified into four groups according to their BMI. Age, sex, and polysomnography data were investigated. The patterns of upper airway collapse were characterized by the structures involved (soft palate, tongue base, lateral pharyngeal wall, and epiglottis). We compared the patterns of upper airway collapse in the supine and lateral decubitus position among the four BMI groups using the chi-square test and multivariate binary logistic regression analysis. Results: . A total of 627 patients (male, 517; mean age, 47.6±12.8 years) were included, consisting of 45, 79, 151, and 352 patients who were underweight or lower normal-weight (defined as the low BMI group), upper normal-weight, overweight, and obese, respectively. Severity indicators of OSA, such as the overall apnea-hypopnea index and duration of SaO2 below 90%, were significantly lower in patients with a low BMI than in obese patients, while their average oxygen saturation was significantly higher. The most common obstruction site in the supine position was the tongue base in patients with a low BMI (100%), whereas this obstruction site was significantly less common in obese patients (54.8%). Tongue base obstruction was mostly relieved in the lateral position, with no discernible obstruction in 86.7% of the low BMI patients. Conclusion . Airway obstruction in OSA patients with a low BMI is mostly due to tongue base obstruction, which improves in the lateral position. These characteristics should be kept in mind when considering treatment options for this subgroup of OSA patients.

BACKGROUND: The structure and function of bone tissue is maintained through a constant remodeling process, which is maintained by the balance between osteoblasts and osteoclasts. The failure of bone remodeling can lead to pathological conditions of bone structure and function. Remifentanil is currently used as a narcotic analgesic agent in general anesthesia and sedation. However, the effect of remifentanil on osteoclasts has not been studied. Therefore, we investigated the effect of remifentanil on pre-osteoclast (pre-OCs) differentiation and the mechanism of osteoclast differentiation in the absence of specific stimulus. METHODS: Pre-OCs were obtained by culturing bone marrow-derived macrophages (BMMs) in osteoclastogenic medium for 2 days and then treated with various concentration of remifentanil. The mRNA expression of NFATc1 and c-fos was examined by using real-time PCR. We also examined the effect of remifentanil on the osteoclast-specific genes TRAP, cathepsin K, calcitonin receptor, and DC-STAMP. Finally, we examined the influence of remifentanil on the migration of pre-OCs by using the Boyden chamber assay. RESULTS: Remifentanil increased pre-OC differentiation and osteoclast size, but did not affect the mRNA expression of NFATc1 and c-fos or significantly affect the expression of TRAP, cathepsin K, calcitonin receptor, and DC-STAMP. However, remifentanil increased the migration of pre-OCs. CONCLUSIONS: This study suggested that remifentanil promotes the differentiation of pre-OCs and induces maturation, such as increasing osteoclast size. In addition, the increase in osteoclast size was mediated by the enhancement of pre-OC migration and cell fusion.
Anesthesia, General ; Bone and Bones ; Bone Remodeling ; Cathepsin K ; Cell Differentiation ; Cell Fusion ; Cell Movement ; In Vitro Techniques ; Macrophages ; Osteoblasts ; Osteoclasts ; Real-Time Polymerase Chain Reaction ; Receptors, Calcitonin ; RNA, Messenger

BACKGROUND: The skin consists of tightly connected keratinocytes, and prevents extensive water loss while simultaneously protecting against the entry of microbial pathogens. Excessive cellular levels of reactive oxygen species can induce cell apoptosis and also damage skin integrity. Propofol (2,6-diisopropylphenol) has antioxidant properties. In this study, we investigated how propofol influences intracellular autophagy and apoptotic cell death induced by oxidative stress in human keratinocytes. METHOD: The following groups were used for experimentation: control, cells were incubated under normoxia (5% CO₂, 21% O₂, and 74% N₂) without propofol; hydrogen peroxide (H₂O₂), cells were exposed to H₂O₂ (300 µM) for 2 h; propofol preconditioning (PPC)/H₂O₂, cells pretreated with propofol (100 µM) for 2 h were exposed to H₂O₂; and 3-methyladenine (3-MA)/PPC/H₂O₂, cells pretreated with 3-MA (1 mM) for 1 h and propofol were exposed to H₂O₂. Cell viability, apoptosis, and migration capability were evaluated. Relation to autophagy was detected by western blot analysis. RESULTS: Cell viability decreased significantly in the H₂O₂ group compared to that in the control group and was improved by propofol preconditioning. Propofol preconditioning effectively decreased H₂O₂-induced cell apoptosis and increased cell migration. However, pretreatment with 3-MA inhibited the protective effect of propofol on cell apoptosis. Autophagy was activated in the PPC/H₂O₂ group compared to that in the H₂O₂ group as demonstrated by western blot analysis and autophagosome staining. CONCLUSION: The results suggest that propofol preconditioning induces an endogenous cellular protective effect in human keratinocytes against oxidative stress through the activation of signaling pathways related to autophagy.
Apoptosis ; Autophagy* ; Blotting, Western ; Cell Death ; Cell Movement ; Cell Survival ; Humans* ; Hydrogen Peroxide ; Keratinocytes* ; Methods ; Oxidative Stress* ; Propofol* ; Reactive Oxygen Species ; Skin ; Water

BACKGROUND: The shortage of human hearts for allotransplantation makes xenotransplantation a possible option for controllable organ providers. To detect acute xenograft rejection, invasive biopsy seems inevitable; however, this occasionally results in poor incision wound healing or infection. To date, no method of noninvasive imaging for early detection of xenograft rejection has been established. We hypothesized that ultrasound speckle tracking would better detect xenograft failure than routine left ventricular ejection fractions (EF). METHODS: From August 2013 to July 2015, a total of six cardiac heterotopic xenotransplants (α 1, 3-galactosyltransferase gene-knockout porcine heart) into cynomolgus monkeys were monitored with echocardiography every 3 to 7 days. M-mode and two-dimensional (2D)-EF measurements and myocardial strain analyses were performed. Cardiac xenograft pathology was reviewed from the immediate postoperative biopsy, as well as the necropsy. RESULTS: Myocardial speckle tracking analysis was feasible in all six cases. The longest survival was 43 days. Only one pathology-proven immunologic rejection occurred. Cardiac xenograft failure appeared as two types: a dilated pattern with decreased EF or a myocardial-thickening pattern with preserved EF. Both antibody-mediated rejection (n=1) and sepsis-induced myocardial dysfunction (n=2) revealed decreased radial or circumferential strains, but normal-range EF. Xenograft functional decline was significant with respect to radial or circumferential strain (P=0.028), but not to conventional M-mode or 2D-EFs (P=0.600, P=0.340, respectively). CONCLUSIONS: Radial and circumferential strains were significantly decreased in both types of xenograft failure, regardless of EF. Further studies are warranted to correlate the strain analysis and immunopathological details.
Biopsy ; Echocardiography ; Heart ; Heart Transplantation ; Heterografts ; Humans ; Macaca fascicularis ; Methods ; Pathology ; Stroke Volume ; Transplantation, Heterologous* ; Transplants* ; Ultrasonography ; Wound Healing

BACKGROUND: Empyema is the collection of purulent exudate within the pleural space. Overall, 36%–65% of patients with empyema cannot be treated by medical therapy alone and require surgery. Multiloculated empyema is particularly difficult to treat with percutaneous drainage. Therefore, we describe our experiences with early aggressive surgical treatment for rapid progressive multiloculated empyema. METHODS: From January 2001 to October 2015, we retrospectively reviewed 149 patients diagnosed with empyema who received surgery. The patients were divided into 2 groups according to whether they underwent emergency surgery or not. We then compared surgical outcomes between these groups. RESULTS: The patients in group A (emergency surgery, n=102) showed a more severe infectious state, but a lower complication rate and shorter length of hospital stay. The incidence of lung abscess was higher in group A, and abscesses were associated with diabetes and severe alcoholism. CONCLUSION: Early aggressive surgical treatment resulted in good surgical outcomes for patients with rapid progressive multiloculated empyema. Furthermore, we suspect that the most likely causes of multiloculated empyema are lung abscesses found in patients with diabetes mellitus as well as severe alcoholism.
Abscess ; Alcoholism ; Diabetes Mellitus ; Drainage ; Emergencies ; Empyema* ; Exudates and Transudates ; Humans ; Incidence ; Length of Stay ; Lung Abscess ; Pleural Diseases ; Retrospective Studies

Mask ventilation, the first step in airway management, is a rescue technique when endotracheal intubation fails. Therefore, ordinary airway management for the induction of general anesthesia cannot be conducted in the situation of difficult mask ventilation (DMV). Here, we report a case of awake intubation in a patient with a huge orocutaneous fistula. A 58-year-old woman was scheduled to undergo a wide excision, reconstruction with a reconstruction plate, and supraomohyoid neck dissection on the left side and an anterolateral thigh flap due to a huge orocutaneous fistula that occurred after a previous mandibulectomy and flap surgery. During induction, DMV was predicted, and we planned an awake intubation. The patient was sedated with dexmedetomidine and remifentanil. She was intubated with a nasotracheal tube using a video laryngoscope, and spontaneous ventilation was maintained. This case demonstrates that awake intubation using a video laryngoscope can be as good as a fiberoptic scope.
Airway Management ; Anesthesia, General ; Dexmedetomidine ; Female ; Fistula* ; Humans ; Intubation* ; Intubation, Intratracheal ; Laryngoscopes ; Mandibular Reconstruction ; Masks ; Middle Aged ; Neck Dissection ; Thigh ; Ventilation