The COVIDTW2 study: Role of COVID-19 vaccination in intubated patients with COVID-19-related acute respiratory distress syndrome in Taiwan.

BACKGROUND: COVID-19 vaccines have reduced the risk of disease progression to respiratory failure or death. However, in patients with breakthrough infections requiring invasive mechanical ventilation, the effect of prior COVID-19 vaccination on mortality remains inconclusive. METHOD: We retrospectively analyzed data on patients intubated due to COVID-19 pneumonia between May 1, 2022 and October 31, 2022. Receipt of two or more doses of vaccine were considered as fully vaccinated. The primary outcome was the time from intubation to all-cause intensive care unit (ICU) mortality. RESULT: A total of 84 patients were included (40 fully vaccinated versus 44 controls). The baseline characteristics, including age, comorbidities, and Sequential Organ Failure Assessment (SOFA) score on the day of intubation were similar between the two groups. The difference in ICU mortality rate between the fully vaccinated and control groups was not significant (35 % vs. 25 %, P = 0.317; hazard ratio with 95 % confidence interval = 1.246 (0.575-2.666), P = 0.571). The SOFA score (hazard ratio: 1.319, P = 0.001) and body mass index (BMI) (hazard ratio: 0.883, P = 0.022) were significantly associated with ICU mortality. CONCLUSION: Being fully vaccinated was not associated with a mortality benefit in intubated patients with COVID-19. A higher SOFA score on the day of intubation and lower BMI were poor prognostic factors.

The validation of Chinese version of workplace PERMA-profiler and the association between workplace well-being and fatigue.

BACKGROUND: Well-being is an important issue in workplace. One of these assessment tools of well-being, Workplace PERMA Profiler, is based on Seligman's five dimensions well-being. Prolonged fatigue may last for a long time, leading a great impact on both employees and enterprises. However, rare studies about the association between well-being and fatigue had been investigated. Our aim is to establish the Chinese version Profiler, and to discovery the association between workplace well-being and fatigue. METHODS: The Chinese version was established according to International Society of Pharmacoeconomics and Outcomes Research (ISPOR) task force guidelines. In the study, researchers employed simple random sampling by approaching individuals undergoing health checkups or receiving workplace health services, inviting them to participate in a questionnaire-based interview. Prolonged Fatigue was evaluated by Checklist Individual Strength (CIS). The reliability was evaluated by Cronbach's alphas, Intra-class Correlation Coefficients (ICCs), and measurement errors. Moreover, confirmatory factor analysis and correlational analyses were assessed for the validity. RESULTS: The analyses included 312 Chinese workers. Cronbach's alphas of the Chinese version ranged from 0.69 to 0.93, while the ICC ranged from 0.70 to 0.92. The 5-factor model of confirmatory factor analysis revealed a nearly appropriate fit (χ2 (82) = 346.560, Comparative Fit Index [CFI] = 0.887, Tucker-Lewis Index [TLI] = 0.855, Root Mean Square Error of Approximation [RMSEA] = 0.114, Standardized Root Mean Square Residual [SRMR] = 0.060). Moreover, the CIS and its four dimensions were significantly and negatively associated with the Positive Emotion, while they are positively associated with Engagement dimension except CIS-Motivation dimension. CONCLUSION: The Chinese version Workplace PERMA-Profiler indicate nice reliability and validity. Furthermore, all CIS dimensions were negatively influenced by Positive Emotion, while commonly positively associated with Engagement.

The COVIDTW study: Clinical predictors of COVID-19 mortality and a novel AI prognostic model using chest X-ray.

BACKGROUND: There is a lack of published research on the impact of the first wave of the COVID-19 pandemic in Taiwan. We investigated the mortality risk factors among critically ill patients with COVID-19 in Taiwan during the initial wave. Furthermore, we aim to develop a novel AI mortality prediction model using chest X-ray (CXR) alone. METHOD: We retrospectively reviewed the medical records of patients with COVID-19 at Taipei Tzu Chi Hospital from May 15 to July 15 2021. We enrolled adult patients who received invasive mechanical ventilation. The CXR images of each enrolled patient were divided into 4 categories (1st, pre-ETT, ETT, and WORST). To establish a prediction model, we used the MobilenetV3-Small model with "Imagenet" pretrained weights, followed by high Dropout regularization layers. We trained the model with these data with Five-Fold Cross-Validation to evaluate model performance. RESULT: A total of 64 patients were enrolled. The overall mortality rate was 45%. The median time from symptom onset to intubation was 8 days. Vasopressor use and a higher BRIXIA score on the WORST CXR were associated with an increased risk of mortality. The areas under the curve of the 1st, pre-ETT, ETT, and WORST CXRs by the AI model were 0.87, 0.92, 0.96, and 0.93 respectively. CONCLUSION: The mortality rate of COVID-19 patients who receive invasive mechanical ventilation was high. Septic shock and high BRIXIA score were clinical predictors of mortality. The novel AI mortality prediction model using CXR alone exhibited a high performance.

Milrinone effects on cardiac mitochondria, hemodynamics, and death in catecholamine-infused rats.

BACKGROUND: Catecholamine-storm is considered the major cause of enterovirus 71-associated cardiopulmonary death. To elucidate the effect of milrinone on cardiac mitochondria and death, a rat model of catecholamine-induced heart failure was investigated. METHODS: Young male Spray-Dawley rats received a continuous intravenous infusion of norepinephrine then followed by co-treatment with and without milrinone or esmolol. Vital signs were monitored and echocardiography was performed at indicated time points. At the end of experiments, hearts were extracted to study mitochondrial function, biogenesis, and DNA copy numbers. RESULTS: Hypernorepinephrinemia induced persistent tachycardia, hypertension, and high mortality and significantly impaired the activities of the electron transport chain and suppressed mitochondrial DNA copy number, mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-α. Norepinephrine-induced hypertension could be significantly suppressed by milrinone and esmolol. Milrinone improved but esmolol deteriorated the survival rate. The left ventricle was significantly enlarged shortly after norepinephrine infusion but later gradually reduced in size by milrinone. The impairment and suppression of mitochondrial function could be significantly reversed by milrinone but not by esmolol. CONCLUSIONS: Milrinone may protect the heart via maintaining mitochondrial function from hypernorepinephrinemia. This study warrants the importance of milrinone and the preservation of mitochondrial function in the treatment of catecholamine-induced death. IMPACT: Milrinone may protect the heart from hypernorepinephrinemia-induced death via maintaining myocardial mitochondrial activity, function, and copy number. Maintenance of cardiac mitochondrial function may be a potential therapeutic strategy in such catecholamine-induced heart failure.

Deep Learning-based Artificial Intelligence Improves Accuracy of Error-prone Lung Nodules.

Introduction: Early detection of lung cancer is one way to improve outcomes. Improving the detection of nodules on chest CT scans is important. Previous artificial intelligence (AI) modules show rapid advantages, which improves the performance of detecting lung nodules in some datasets. However, they have a high false-positive (FP) rate. Its effectiveness in clinical practice has not yet been fully proven. We aimed to use AI assistance in CT scans to decrease FP. Materials and methods: CT images of 60 patients were obtained. Five senior doctors who were blinded to these cases participated in this study for the detection of lung nodules. Two doctors performed manual detection and labeling of lung nodules without AI assistance. Another three doctors used AI assistance to detect and label lung nodules before manual interpretation. The AI program is based on a deep learning framework. Results: In total, 266 nodules were identified. For doctors without AI assistance, the FP was 0.617-0.650/scan and the sensitivity was 59.2-67.0%. For doctors with AI assistance, the FP was 0.067 to 0.2/scan and the sensitivity was 59.2-77.3% This AI-assisted program significantly reduced FP. The error-prone characteristics of lung nodules were central locations, ground-glass appearances, and small sizes. The AI-assisted program improved the detection of error-prone nodules. Conclusions: Detection of lung nodules is important for lung cancer treatment. When facing a large number of CT scans, error-prone nodules are a great challenge for doctors. The AI-assisted program improved the performance of detecting lung nodules, especially for error-prone nodules.

Association between secondhand smoke and peripheral arterial disease: a meta-analysis of cross-sectional studies.

PURPOSE: The association between secondhand smoke (SHS) and peripheral arterial disease (PAD) was inconsistent and the studies were relatively scarce, hence, we conducted a meta-analysis of the association between SHS and PAD. MATERIALS AND METHODS: We systematically searched three electronic databases (PubMed, EMBASE, and Web of Science), and calculated the pooled prevalence risk ratio (RR) and estimated standard error by random effect model from the meta-analysis. Furthermore, we performed a subgroup meta-analysis according to the location of SHS exposure. RESULTS: We initially identified 502 articles from the electronic database, and 6 articles, cross-sectional data from 4 cross-sectional studies and 2 prospective cohort studies, were included in the meta-analysis. Among these six articles, two studies showed a significant correlation between SHS exposure and PAD, whereas no study showed a negative correlation between SHS exposure and PAD. In the meta-analysis, pooled prevalence showed a significant association between SHS exposure and PAD (RR = 1.23; 95% confidence interval [CI] 1.08-1.41; z = 3.02, p = 0.003). In the subgroup analysis based on location of SHS exposure, the prevalence RR of PAD at home was 1.30 (95% CI 1.14-1.49, Z-3.99, p < 0.0001). The prevalence RR in the subgroup of SHS exposure at work was not significant (RR = 0.89; 95% CI 0.55-1.44; z = 0.48, p = 0.63). CONCLUSION: Exposure to SHS was significantly and positively associated with PAD. Moreover, we found a significant association between exposure to SHS and PAD at home, but the association was not significant at work.

Fructose milieu undermines the therapeutic effect of Tribulus terrestris extract on neuroblastoma cell line via maintaining mitochondrial function.

Fructose overconsumption promotes tumor progression. Neuroblastoma is a common extracranial tumor with about 50% 5-year survival rate in high-risk children. The anti-tumor effect of Tribulus terrestris might bring new hope to neuroblastoma therapy. However, whether fructose disturbs the therapeutic effect of T. terrestris is currently unknown. In this study, the mouse neuroblastoma cell line, Neuro 2a (N2a) cells, was used to investigate the therapeutic effects of T. terrestris extract at various dosages (0.01, 1, 100 ng/ml) in regular EMEM medium or extra added fructose (20 mM) for 24 h. 100 ng/ml T. terrestris treatment significantly reduced the cell viability, whereas the cell viabilities were enhanced at the dosages of 0.01 or 1 ng/ml T. terrestris in the fructose milieu instead. The inhibition effect of T. terrestris on N2a migration was blunted in the fructose milieu. Moreover, T. terrestris effectively suppressed mitochondrial functions, including oxygen consumption rates, the activities of electron transport enzymes, the expressions of mitochondrial respiratory enzymes, and mitochondrial membrane potential. These suppressions were reversed in the fructose group. In addition, the T. terrestris-suppressed mitofusin and the T. terrestris-enhance mitochondrial fission 1 protein were maintained at basal levels in the fructose milieu. Together, these results demonstrated that T. terrestris extract effectively suppressed the survival and migration of neuroblastoma via inhibiting mitochondrial oxidative phosphorylation and disturbing mitochondrial dynamics. Whereas, the fructose milieu blunted the therapeutic effect of T. terrestris, particularly, when the dosage is reduced.

Maternal high-fructose diet induced early-onset retinopathy via the suppression of synaptic plasticity mediated by mitochondrial dysfunction.

Retinopathy is a leading cause of blindness, and there is currently no cure. Earlier identification of the progression of retinopathy could provide a better chance for intervention. Diet has profound effects on retinal function. A maternal high-fructose diet (HFD) triggers diseases in multiple organs. However, whether maternal HFD impairs retinal function in adult offspring is currently unknown. By using the rodent model of maternal HFD during pregnancy and lactation, our data indicated a reduced b-wave of electroretinography (ERG) in HFD female offspring at 3 mo of age compared with age-matched offspring of dams fed regular chow (ND). Immunofluorescence and Western blot analyses indicated that the distributions and expressions of synaptophysin, postsynaptic density protein 95 (PSD95), and phospho(p)-Ca2+/calmodulin-stimulated protein kinase IIα (CaMKIIα) were significantly suppressed in the HFD group. Furthermore, the ATP content and the mitochondrial respiratory protein, Mt CPX 4-2, were decreased. Moreover, the expressions of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the retina of the HFD group were downregulated. Treatment with coenzyme Q10 (Q10), a key mediator of the electron transport chain, effectively reversed these abovementioned dysfunctions. Together, these results suggested that maternal HFD impaired retinal function in adult female offspring. The mechanism underlying early-onset retinopathy may involve the reduction in the capacity of mitochondrial energy production and the suppression of synaptic plasticity. Most importantly, mitochondria could be a feasible target to reprogram maternal HFD-damaged retinal function.NEW & NOTEWORTHY In this study, we provide novel evidence that maternal high-fructose diet during gestation and lactation could induce early-onset retinopathy in adult female offspring. Of note, the insufficient energy content, downregulated mitochondrial respiratory complex 4-2, and impaired mitochondrial biogenesis might contribute to the decrease of synaptic plasticity resulting in retinal function suppression. Oral application with coenzyme Q10 for 4 wk could at least partially reverse the aforementioned molecular events and retinal function.

The BUILT study: a single-center 5-year experience of Lung Cancer screening in Taiwan.

Background: There are no uniform guidelines on low-dose computed tomography (LDCT) follow-up in lung cancer screening. Few studies have analyzed the incidental abnormalities and role of tumor markers in lung cancer screening. The purpose of this study was to investigate the diagnostic performance of LDCT, optimal follow-up duration, incidental findings, and role of tumor markers in diagnosing lung cancer. Methods: We retrospectively analyzed subjects who underwent their first LDCT in Taipei Tzu Chi Hospital between September 1, 2015, and August 31, 2016. All chest CT scans until August 31, 2020, were recorded. A non-calcified nodule with a diameter ≥2 mm on LDCT was defined as a positive result. We extracted the data, including possible risk factors of lung cancer and follow-up outcomes. Results: A total of 1502 subjects were recruited. Of the 38 subjects who underwent biopsy, 31 had confirmed lung cancer. Lung cancer in all patients was diagnosed within 4 years. Univariate logistic regression analysis revealed that a family history of lung cancer in first-degree relatives and abnormal serum carcinoembryonic antigen (CEA) levels were the significant risk factors for lung cancer. A cumulative lung cancer incidence of 54.7 patients per 1000 person-years was determined solely via radiological follow-up. In total, 271 (18%) subjects exhibited incidental findings on baseline LDCT. Conclusion: The overall lung cancer detection rate in this study was 2.1% in the 5-year study period. A family history of lung cancer and abnormal serum CEA levels are important risk factors for lung cancer. A minimum of 4-year follow-up is required to track suspicious nodules. A purely radiological follow-up detects a high incidence of lung cancer.

The COPD-readmission (CORE) score: A novel prediction model for one-year chronic obstructive pulmonary disease readmissions.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) results in deterioration of lung function and mortality. Previous prediction models have been designed for severe exacerbation of COPD, leading to readmission. However, these models lacked newly established predictors such as the eosinophil count. The present study developed a novel CO PD-re admission (CORE) score. METHODS: We retrospectively reviewed medical records of patients visiting Taipei Tzu Chi Hospital between January 1, 2014, and May 31, 2017. We analyzed all covariates by univariate and then multivariate logistic regressions. Numeric or ordinal variables showing statistical significance were transformed into dichotomous variables by cut-off values determined by the Youden Index. The CORE score was designed to predict one-year readmission rates. RESULTS: A total of 625 patients were recruited. After analysis, the CORE score included five predictors (eosinophil count, lung function, triple inhaler therapy, previous hospitalization, and neuromuscular disease). We observed a highly linear relationship between the CORE score and COPD readmission (R = 0.981; R 2 = 0.963; P < 0.001). The CORE score had a higher predictive accuracy than that for hospitalization in the previous year (area under the curve = 0.703 vs. 0.619; P < 0.001). Patients with higher CORE scores had a shorter time to first COPD readmission (P < 0.001). Using the zero point as a reference, the hazard ratios for each score from 1 to 4 were 1.209, 2.211, 3.359, and 4.510, respectively. CONCLUSION: The CORE score includes two novel predictors (eosinophil count and triple inhaler therapy). The model has a high predictive power for one-year COPD readmission.

Pioglitazone reversed the fructose-programmed astrocytic glycolysis and oxidative phosphorylation of female rat offspring.

Excessive maternal high-fructose diet (HFD) during pregnancy and lactation has been reported to cause metabolic disorders in the offspring. Whether the infant's brain metabolism is disturbed by maternal HFD is largely unknown. Brain energy metabolism is elevated dramatically during fetal and postnatal development, whereby maternal nutrition is a key factor that determines cellular metabolism. Astrocytes, a nonneuronal cell type in the brain, are considered to support the high-energy demands of neurons by supplying lactate. In this study, the effects of maternal HFD on astrocytic glucose metabolism were investigated using hippocampal primary cultures of female infants. We found that glycolytic capacity and mitochondrial respiration and electron transport chain were suppressed by maternal HFD. Mitochondrial DNA copy number and mitochondrial transcription factor A expression were suppressed by maternal HFD. Western blots and immunofluorescent images further indicated that the glucose transporter 1 was downregulated whereas the insulin receptor-α, phospho-insulin receptor substrate-1 (Y612) and the p85 subunit of phosphatidylinositide 3-kinase were upregulated in the HFD group. Pioglitazone, which is known to increase astrocytic glucose metabolism, effectively reversed the suppressed glycolysis, and lactate release was restored. Moreover, pioglitazone also normalized oxidative phosphorylation with an increase of cytosolic ATP. Together, these results suggest that maternal HFD impairs astrocytic energy metabolic pathways that were reversed by pioglitazone.

Anti-neuroinflammation ameliorates systemic inflammation-induced mitochondrial DNA impairment in the nucleus of the solitary tract and cardiovascular reflex dysfunction.

BACKGROUND: Decreased heart rate variability (HRV) leads to cardiovascular diseases and increased mortality in clinical studies. However, the underlying mechanisms are still inconclusive. Systemic inflammation-induced neuroinflammation is known to impair the autonomic center of cardiovascular regulation. The dynamic stability of blood pressure and heart rate (HR) is regulated by modulation of the reciprocal responses of sympathetic and parasympathetic tone by the baroreflex, which is controlled by the nucleus of the solitary tract (NTS). METHODS: Systemic inflammation was induced by E. coli lipopolysaccharide (LPS, 1.2 mg/kg/day, 7 days) peritoneal infusion via an osmotic minipump in normotensive Sprague-Dawley rats. Systolic blood pressure (SBP) and HR were measured by femoral artery cannulation and recorded on a polygraph under anesthesia. The low-frequency (LF; 0.25-0.8 Hz) and high-frequency (HF; 0.8-2.4 Hz) components of SBP were adopted as the indices for sympathetic vasomotor tone and parasympathetic vasomotor tone, while the baroreflex effectiveness index (BEI) was adopted from the analysis of SBP and pulse interval (PI). The plasma levels of proinflammatory cytokines and mitochondrial DNA (mtDNA) oxidative damage were analyzed by ELISA. Protein expression was evaluated by Western blot. The distribution of oxidative mtDNA was probed by immunofluorescence. Pharmacological agents were delivered via infusion into the cisterna magna with an osmotic minipump. RESULTS: The suppression of baroreflex sensitivity was concurrent with increased SBP and decreased HR. Neuroinflammatory factors, including TNF-α, CD11b, and Iba-1, were detected in the NTS of the LPS group. Moreover, indices of mtDNA damage, including 8-OHdG and γ-H2AX, were significantly increased in neuronal mitochondria. Pentoxifylline or minocycline intracisternal (IC) infusion effectively prevented mtDNA damage, suggesting that cytokine and microglial activation contributed to mtDNA damage. Synchronically, baroreflex sensitivity was effectively protected, and the elevated blood pressure was significantly relieved. In addition, the mtDNA repair mechanism was significantly enhanced by pentoxifylline or minocycline. CONCLUSION: These results suggest that neuronal mtDNA damage in the NTS induced by neuroinflammation could be the core factor in deteriorating baroreflex desensitization and subsequent cardiovascular dysfunction. Therefore, the enhancement of base excision repair (BER) signaling in mitochondria could be a potential therapeutic strategy for cardiovascular reflex dysregulation.

Impact of nucleic acid amplification test on pulmonary tuberculosis notifications and treatments in Taiwan: a 7-year single-center cohort study.

BACKGROUND: Nucleic acid amplification tests (NAAT) have been used as a diagnostic tool for pulmonary tuberculosis (PTB) in Taiwan for many years. In accordance with Taiwanese legislation, health care personnel are required to notify the Centers for Disease Control and Prevention (CDC) in case of suspected PTB. This study aimed to investigate the impact of NAAT(Gen-Probe) on the notification system for PTB and anti-tuberculosis treatments in Taiwan. METHODS: A retrospective study on the impact of NAAT (Enhanced Amplified Mycobacterium tuberculosis Direct Test [E-MTD], Gen-Probe, San Diego, CA, USA) [NAAT(Gen-Probe)] was carried out at Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation from March 2011 to December 2017. During the study period, microscopic acid-fast-bacilli smears and mycobacterial cultures were available for PTB diagnosis. NAAT(Gen-Probe) was first introduced at the hospital in January 2014 for use as a diagnostic method for PTB. Positive sputum culture was considered as the gold standard for PTB diagnosis. We excluded clinically-diagnosed PTB cases. RESULTS: When NAAT(Gen-Probe) was applied, the rate of error notification to CDC decreased from 64.3 to 7.0% (P < 0.001), and unnecessary anti-TB treatments administered to suspected cases decreased from 14.9 to 6.5% (P = 0.005). In the non-PTB group, the mean duration of unnecessary anti-TB treatments changed from 38.9 ± 38.3 days to 37.0 ± 37.9 days (P = 0.874). In the PTB group, the mean time from notifying CDC to initiating treatment decreased from 3.05 ± 6.95 days to 1.48 ± 1.99 days (P = 0.004). The sensitivity, specificity, positive predictive value, and negative predictive value of NAAT(Gen-Probe) were 99.0, 92.3, 99.0, and 92.3%, respectively. CONCLUSIONS: Use of NAAT(Gen-Probe) led to decrease in the rate of error notification of suspected PTB cases to the CDC, avoidance of unnecessary use of anti-TB treatments, and accelerated initiation of appropriate treatments.

Nipple-sparing Mastectomy and Immediate Breast Reconstruction After Recurrence From Previous Breast Conservation Therapy.

PURPOSE: Breast conservation therapy (BCT) is widely accepted for breast cancer treatment. Nipple-sparing mastectomy has been newly developed to preserve the nipple-areolar complex and enhance aesthetic results. The purpose of this study was to evaluate the oncological safety and results of nipple-sparing mastectomy (NSM) after previous BCT. METHODS: Eighteen patients who received NSM and immediate breast reconstruction for local recurrence after BCT were identified. An additional 127 affected breasts with NSM and immediate breast reconstruction for primary breast cancer were selected as the control group. The patient disease status, reconstructive method, postoperative complications, and oncological outcome were investigated. RESULTS: No apparent significant differences between the 2 groups were found regarding patient demographic data, tumor stage, reconstructive method, surgical complication, or tumor recurrence rate (all P values >0.05), except preoperative radiotherapy was higher in secondary NSM group (0% vs 77.8%, P < 0.001). The further nipple and secondary deep inferior epigastric artery perforator flap reconstruction rate was higher in the secondary NSM group (11.1% vs 0.8%, P = 0.041 and 16.7% vs 2.4%, P = 0.026, respectively). CONCLUSIONS: Prior BCT did not contribute to higher surgical complications in patients who received NSM and immediate reconstruction as a salvage procedure after tumor local recurrence. The oncological safety, general surgical result, and postoperative patient-reported satisfaction remain safe and reliable despite prior ipsilateral surgery and radiation. Care should be taken for possible higher nipple necrosis in the secondary NSM patients.

Oral pioglitazone ameliorates fructose-induced peripheral insulin resistance and hippocampal gliosis but not restores inhibited hippocampal adult neurogenesis.

Diet-associated insulin resistance (IR) is intimately correlated with the progression of metabolic syndrome and hippocampal dysfunction. Pioglitazone (PIO), a selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has been applied to enhance insulin sensitivity. With limited permeability to blood-brain-barrier, it is unclear that whether oral PIO available to cure both the peripheral IR and the impairment in the hippocampus. We evaluated the levels of peripheral and hippocampal IR via the homeostatic model assessment of insulin resistance and hippocampal IRS-1/Akt phosphorylation, respectively, of Wistar Kyoto rats fed with a regular chew or high fructose diet (HFD) for 12weeks. Gavage with PIO (30mg/kg/day, 2weeks) significantly reduced the peripheral IR and reversed the level of hippocampal PPARγ. Moreover, HFD-activated microglia and astrocyte were effectively relieved by PIO. The suppressed brain-derived neurotrophic factor, CaMKIIα, and postsynaptic density protein 95 in the hippocampus were effectively reversed by PIO. However, the hippocampal IR and inhibition of adult neurogenesis in dentate gyrus were not restored by PIO. Together, PIO oral application may reverse the HFD-induced peripheral IR and maintain the existed neuronal circuit by ameliorating glial activation and enhancing synaptic density through BDNF but failed to restore adult neurogenesis in the hippocampus.

Nose resurfacing with free fasciocutaneous flaps in burns patients.

BACKGROUND: Nasal reconstruction after burn injury can be challenging due to limited availability of local flaps. We present our experience of free flap reconstruction for full-thickness nasal defect after severe facial burn injury. METHODS: Between August 1998 and September 2015, six patients underwent nasal reconstruction with seven free flaps after burn injury. Among them, flame burn occurred in two patients, chemical burn in two, explosive burn in one, and contact thermal burn in one patient. The percentage of total body surface area ranged from 4% to 48%, and the face and forehead were involved in all patients. Their clinical and photographic records were retrospectively reviewed to evaluate the aesthetic results. RESULTS: Four ulnar forearm flaps, one radial forearm flap, one anterolateral thigh flap, and one medial sural artery perforator flap were used for nasal reconstruction. The nasal framework was constructed simultaneously using costal cartilage or conchal cartilage. The facial artery and vein were typically used as recipient vessels. One case each of partial necrosis and infection were noted during the average follow-up of 59 months (range, 16-126 months). Patients had satisfactory aesthetic and functional outcomes after 4.5 times (range, 2-7 times) refinement operation. CONCLUSIONS: Free flap is an applicable alternative to restore nasal skin envelope, with rebuilding the nasal framework performed in the same stage after severe facial burn injury. Through thoughtful planning and sufficient refinement, satisfactory aesthetic, and functional results are achievable.

Hyperbaric Oxygen Therapy Alleviates Carbon Monoxide Poisoning-Induced Delayed Memory Impairment by Preserving Brain-Derived Neurotrophic Factor-Dependent Hippocampal Neurogenesis.

OBJECTIVE: To test the hypothesis that hyperbaric oxygen therapy ameliorates delayed cognitive impairment after acute carbon monoxide poisoning by promoting neurogenesis through upregulating the brain-derived neurotrophic factor in the hippocampus. DESIGN: Laboratory animal experiments. SETTING: University/Medical center research laboratory. SUBJECTS: Adult, male Sprague-Dawley rats. INTERVENTIONS: Rats were divided into five groups: (1) non-carbon monoxide-treated control, (2) acute carbon monoxide poisoning, (3) acute carbon monoxide poisoning followed by 7-day hyperbaric oxygen treatment, (4) carbon monoxide + hyperbaric oxygen with additional intracerebroventricular infusion of Fc fragment of tyrosine kinase receptor B protein (TrkB-Fc) chimera, and (5) acute carbon monoxide poisoning followed by intracerebroventricular infusion of brain-derived neurotrophic factor. Acute carbon monoxide poisoning was achieved by exposing the rats to carbon monoxide at 2,500 ppm for 40 minutes, followed by 3,000 ppm for 20 minutes. Hyperbaric oxygen therapy (at 2.5 atmospheres absolute with 100% oxygen for 60 min) was conducted during the first 7 days after carbon monoxide poisoning. Recombinant human TrkB-Fc chimera or brain-derived neurotrophic factor was infused into the lateral ventricle via the implanted osmotic minipump. For labeling of mitotic cells in the hippocampus, bromodeoxyuridine was injected into the peritoneal cavity. Distribution of bromodeoxyuridine and two additional adult neurogenesis markers, Ki-67 and doublecortin, in the hippocampus was evaluated by immunohistochemistry or immunofluorescence staining. Tissue level of brain-derived neurotrophic factor was assessed by enzyme-linked immunosorbent assay. Cognitive behavior was evaluated by the use of eight-arm radial maze. MEASUREMENTS AND MAIN RESULTS: Acute carbon monoxide poisoning significantly suppressed adult hippocampal neurogenesis evident by the reduction in number of bromodeoxyuridine-positive, Ki-67⁺, and doublecortin⁺ cells in the subgranular zone of the dentate gyrus. This suppression of adult neurogenesis by the carbon monoxide poisoning was appreciably alleviated by early treatment of hyperbaric oxygen. The hyperbaric oxygen treatment also promoted a sustained increase in hippocampal brain-derived neurotrophic factor level. Blockade of hippocampal brain-derived neurotrophic factor signaling with intracerebroventricular infusion of recombinant human TrkB-Fc chimera significantly blunted the protection by the hyperbaric oxygen on hippocampal neurogenesis; whereas intracerebroventricular infusion of brain-derived neurotrophic factor mimicked the action of hyperbaric oxygen and preserved hippocampal neurogenesis after acute carbon monoxide poisoning. Furthermore, acute carbon monoxide poisoning resulted in a delayed impairment of cognitive function. The hyperbaric oxygen treatment notably restored the cognitive impairment in a brain-derived neurotrophic factor-dependent manner. CONCLUSIONS: The early hyperbaric oxygen treatment may alleviate delayed memory impairment after acute carbon monoxide poisoning by preserving adult neurogenesis via an increase in hippocampal brain-derived neurotrophic factor content.

Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4.

Impairment of learning and memory has been documented in the later life of offspring to maternal consumption with high energy diet. Environmental stimulation enhances the ability of learning and memory. However, potential effects of environmental stimulation on the programming-associated deficit of learning and memory have not been addressed. Here, we examined the effects of enriched-housing on hippocampal learning and memory in adult female offspring rats from mother fed with 60% high fructose diet (HFD) during pregnancy and lactation. Impairment of spatial learning and memory performance in HFD group was observed in offspring at 3-month-old. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased in the offspring. Moreover, the HFD group showed an up-regulation of histone deacetylase 4 (HDAC4) in the nuclear fractions of hippocampal neurons. Stimulation to the offspring for 4weeks after winning with an enriched-housing environment effectively rescued the decrease in cognitive function and hippocampal BDNF level; alongside a reversal of the increased distribution of nuclear HDAC4. Together these results suggest that later life environmental stimulation effectively rescues the impairment of hippocampal learning and memory in female offspring to maternal HFD intake through redistributing nuclear HDAC4 to increase BDNF expression.

Minimizing osteoradionecrosis after mandibular reconstruction and radiation in advanced head and neck cancer patients.

BACKGROUND: Osteoradionecrosis may develop on the residual mandible or reconstructed fibula because of inadequate soft tissue coverage and compromised tissue perfusion post mandibular reconstruction, and radiation. This study was to investigate the incidence of osteoradionecrosis following class III mandibular defect reconstructions with an OPAC flap versus a fibula OSC flap. METHODS: A retrospective review of a consecutive series of mandibular reconstructions between 1999 and 2010 was performed. Mandibular defects and corresponding flap types were analyzed with emphasis on outcome, complications, and rates of osteoradionecrosis among the two subgroups. RESULTS: A total of 121 fibula flaps were performed, consisting of 53 OPAC and 68 fibula OSC flaps. Complications trended higher for OPAC flaps in partial and total flap loss rates as well as venous congestion when compared with the OSC flap cohort. The OPAC group had statistically significant lower rates of osteoradionecrosis and plate exposure than the OSC group (P = 0.04). CONCLUSION: The OPAC flap may be preferable to fibula OSC flap in mandibular reconstruction given its lower rates of osteoradionecrosis and plate exposure. This flap type may be the flap of choice for class III defects where additional vascularized tissue may be critical for addressing significant soft tissue deficiency. J. Surg. Oncol. 2016;114:399-404. © 2016 Wiley Periodicals, Inc.

Routine sampling of internal mammary lymph nodes during microsurgical breast reconstruction-Experience based on 524 microsurgical breast reconstructions.

PURPOSE: Exploration of the internal mammary vessels during microsurgical reconstruction presents an ideal opportunity for identifying and sampling the internal mammary lymph node (IMLN) basin. METHODS: A retrospective review of patients undergoing microsurgical breast reconstruction using the internal mammary vessels as recipient vessels was conducted from March 2000 to December 2014. Patient demographics, tumor characteristics, preoperative lymph node mapping, reconstructive timing, and outcomes were studied. RESULTS: A total of 524 microsurgical breast reconstructions in 516 patients were performed using the internal mammary vessels. IMLNs were sampled in 53 immediate and 42 delayed breast reconstructions. Eight (seven in the immediate and one in the delayed group) of the sampled nodes were positive for cancer metastasis, for an incidence of 8.4% in identified lymph nodes. All patients with metastatic IMLNs subsequently received local-regional radiation and chemotherapy. All patients were alive, and six were disease-free at the conclusion of the study period, which had an average follow up of 67.3 months. CONCLUSION: Incidentally encountered IMLNs during microsurgical breast reconstruction are frequently positive. With negligible downside and the possibility to provide additional information for treatment, the procedure should be encouraged. J. Surg. Oncol. 2016;114:133-139. © 2016 Wiley Periodicals, Inc.