The association of sleep quality and burnout among Chinese medical residents under standardized residency training in a tertiary hospital.

PURPOSE: To investigate the impact of sleep quality and chronotype on job burnout among medical residents under standardized residency training (SRT) in a tertiary hospital in Beijing, China. METHODS: Medical residents in the Department of Internal Medicine of Peking Union Medical College Hospital were assessed by Morning and Evening Questionaire-5 (MEQ-5), Pittsburgh sleep quality index (PSQI), and Maslach Burnout Inventory-General Survey (MBI-GS). Factors associated with burnout were analyzed. RESULTS: A total of 142 respondents returned completed questionnaires. Burnout was present in 85 (60%) residents. Prevalence of high emotional exhaustion, high depersonalization, and low personal accomplishment were 51%, 28%, and 18%, respectively. The global PSQI score of residents was 5.9 ± 2.4, and the self-reported sleep duration was 6.2 ± 0.8 h/day. The MEQ-5 distribution skewed towards morningness, with a median score of 14.5 [13.0, 16.3]. Poor daytime function significantly predicted emotional exhaustion and depersonalization. Chronotypes were not associated with any of the burnout components. CONCLUSION: Sleep-related daytime dysfunction was strongly related to burnout. Strategies protecting the sleep of residents should be incorporated into the SRT programs for both efficiency and sustainability considerations.

Disseminated Tuberculosis Associated Hemophagocytic Lymphohistiocytosis in a Pregnant Woman With Evans syndrome: A Case Report and Literature Review.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review. Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis (M. tuberculosis) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT. Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome.

BAG3-Related Myofibrillar Myopathy Presenting as Hypercapnia: A Case Report and Literature Review.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide. The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia. Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation. Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation. The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3. Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date, including this patient and literature review. The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life. Most patients presented toe/clumsy walking or running as the onset symptom, followed by muscle weakness or atrophy. Creatine kinase levels were elevated in fourteen patients and were normal in three. Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment. Except for one not reported, heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation. Z-disk streaming and aggregation could be observed in most of the patients' muscle histology. In the long-term follow-up, five patients died of cardiac or respiratory failure. Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy. It should be considered as a rare differential diagnosis of hypercapnia.

[Effectiveness of Laparoscopic Sleeve Gastrectomy in Treating Obesity and Its Co-morbidities].

Objective To analyze the effectiveness and safety of laparoscopic sleeve gastrectomy (LSG) in treating obesity and its co-morbidities.Methods The clinical data of obese patients undergoing LSG in Peking Union Medical College Hospital from August 2012 to August 2017 were retrospectively analyzed. Medium-term outcome measures included excess weight loss (%EWL),co-morbidity improvement,and complications.Results Seventy-five obese patients comprising 28 men[ body mass index(BMI):(47.3±7.5)kg/m 2) ] and 47 women [BMI (41.1±7.0) kg/m 2] were enrolled in this analysis. The common co-morbidities were liver dysfunction (53.3%),dyslipidemia (52.0%),obstructive sleep apnea (45.3%),type 2 diabetes mellitus (38.7%),and arterial hypertension (37.3%),which were improved by 75.0%,58.3%,83.3%,75.0% and 58.3% three years after surgery. The mean %EWL at 1,2,and 3 years after surgery was 81.6±34.7,80.9±30.2 and 79.7±30.8,respectively. The proportions of patients achieving successful weight loss were 81.7% (n=49),81.0% (n=34),and 79.3% (n=23) at 1,2,and 3 years (%EWL>50%). Early severe complications (Clavien-Dindo classification>2) occurred in 2.6% of patients,and the most common late complications was gastroesophageal reflux disease,which could be relieved by acid suppressants.Conclusion LSG is effective and safe in treating obesity and its co-morbidities.

[Perioperative Evaluation of Obstructive Sleep Apnea in Bariatric Surgery Population].

Objective To evaluate the prevalence and clinical characteristics of obstructive sleep apnea (OSA) in bariatric surgery population.Methods Consecutive patients undergoing preoperative evaluation for bariatric surgery and referred for sleep monitoring in Peking Union Medical College Hospital from January 2009 to December 2015 were retrospectively analyzed. Age,gender,symptoms of snoring,fatigue,apnea and somnolence,apnea hyponea index (AHI),arterial blood gas,pulmonary function,sleep respiratory monitoring,positive airway therapy of OSA,and postoperative complications were recorded. The clinical characteristics of OSA groups at different severity were compared using AHI≥5 events/hour and AHI≥15 events/hour as cut-off values. Correlation analysis was applied to identify the clinical factors associated with AHI.Results Of 42 patients with complete sleeping monitoring data before bariatric surgery,30(71.4%) were diagnosed as OSA,14 (33.3%) were moderate or severe and 11 (26.2%) were severe. Also,OSA was not detected before the bariatric surgery in 25 cases (83.3%). Compared with patients with AHI<5 events/hour,patients with AHI≥5 events/hour had significantly older age (t=2.869,P=0.007),higher proportion of observed apnea (P=0.035),higher AHI (z=-4.592,P=0.000),higher proportion of night pulse oxygen saturation(SpO2) below 90% (z=-2.746,P=0.006),lower mean SpO2 (t=-2.071,P=0.046) and lower lowest SpO2 (t=-3.914,P=0.000). Compared with AHI<15 events/hour group,the AHI≥15 events/hour group had significantly higher BMI (t=2.281,P=0.043),male ratio (P=0.005),incidence of hypertension (P=0.011),proportion of observed apnea (P=0.001),percentage of smoking history (P=0.017),partial pressure of carbon dioxide(PaCO2)(t=3.478,P=0.002),AHI (z=-4.592,P=0.000),and proportion of night SpO2 below 90% (z=-4.530,P=0.000); in addition,the forced expiratory volume in one second(FEV1)% predicted (t=-3.377,P=0.002),forced vital capacity(FVC)% predicted (t=-2.342,P=0.026),night time mean SpO2 (t=-3.392,P=0.007),lowest SpO2 (t=-5.535,P=0.000) were significantly decreased. Correlation analysis showed that,in populations with normal PaCO2 (n=36),AHI was positively correlated with age (r=0.450,P=0.006) and BMI (r=0.384,P=0.021) and negatively correlated with FEV1% predicted (r=-0.457,P=0.008) and FVC% predicted (r=-0.432,P=0.013). Partial correlation analysis showed that,after age and BMI were adjusted,AHI was not correlated with FEV1% predicted(r=-0.287,P=0.125)and FVC%predicted(r=-0.241,P=0.200).Conclusion The incidence and underdiagnosis rate of OSA are high in bariatric surgery population. OSA should be routinely screened in bariatric population to reduce the postoperative complication.

[Pulmonary Bulla and Bilateral Diffusely-distributed Nodules: Report of One Case and Literature Review].

Lung cancer is mostly characterized by a pulmonary solid mass on CT. In rare cases,patients do not have these typical manifestation but present with diffusely-distributed small nodules and pulmonary bullae,which can easily be misdiagnosed. A special case of lung adenocarcinoma was managed in our hospital from September 24th to December 19th in 2016. Under high-resolution CT,multiple nodules were seen in both lungs,mostly in the upper lungs,involving the pleura and interlobular fissures. Some nodules had cystic changes. A large bulla was seen in the left upper lung. Its wall was thickened with multiple nodules. Lung adenocarcinoma was pathologically confirmed.

Pulmonary alveolar microlithiasis: A case report and review of the literature.

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease characterized by the formation of calcium phosphate microliths in the alveoli. Mutations in the gene encoding the solute carrier family 34 member 2 gene are considered to be involved in the pathogenesis of PAM. Although PAM can develop in children, the majority of patients with PAM are diagnosed in adulthood due to the slow progressive nature of the disease within the lungs. In childhood, the majority of patients with PAM are asymptomatic and changes in the lung parenchyma are usually identified incidentally. Symptoms of PAM typically appear in the third or fourth decade of life and there is often a notable dissociation between the advanced radiological findings and the mild clinical presentation. A positive diagnosis of PAM is reached by the combination of a positive chest radiograph and histological examination. Genetic testing may help to identify other latent patients in the family of the patient with PAM. In the present study, the cases of 3 patients diagnosed with PAM have been reported, including their clinical presentation, radio imaging, pathological symptoms, genetic test results and treatment plans, as well as the associated literature.

Secreted Frizzled-Related Protein 5 (SFRP5) in Patients with Obstructive Sleep Apnea.

Objective Obstructive sleep apnea (OSA) is closely related to obesity, insulin resistance and inflammation. Secreted frizzled-related protein 5 (SFRP5) is a recently discovered adipokine. It is involved in insulin resistance and inflammation in obesity. This study aimed at evaluating the association between SFRP5 and sleeping characteristics as well as biochemical parameters of OSA patients. Methods This was a prospective case control study. Nondiabetic OSA patients and controls were consecutively recruited and divided into three groups: OSA group, apnea-hypopnea Index (AHI)≥5/h; healthy controls with normal body mass index (BMI); obese controls without OSA, and BMI > 24.0 kg/m2. All participants underwent polysomnography (PSG). Plasma SFRP5 was examined using enzyme-linked immunosorbent assay (ELISA). Blood biochemical examinations, including fasting blood glucose (FBG), lipid profile, hypersensitive C-reactive protein (hsCRP), were performed early in the morning after PSG. Patients with severe OSA were treated with nasal continuous positive airway pressure (nCPAP), and plasma SFRP5 was repeatedly measured for comparison. Results Sixty-eight subjects were enrolled in the study, including 38 patients of OSA, whose medium AHI was 58.70 /h (36.63, 71.15), 20 obese controls, and 10 healthy controls. The plasma SFRP5 level of OSA patients was not significantly different from that of healthy controls or obese controls. In OSA patients, SFRP5 level correlated positively with triglyceride level (r=0.447, P=0.005) and negatively with LDL-cholesterol level and HDL- cholesterol level (r=-0.472 and P=0.003; r=-0.478 and P=0.002; respectively). SFRP5 level was not found correlating with FBG, AHI, or any of nocturnal hypoxia parameters. After overnight nCPAP treatment, plasma SFRP5 levels of OSA patients did not change significantly (t=1.557, P = 0.148) compared to that of pretreatment. Conclusions In nondiabetic OSA patients, plasma SFRP5 is associated with the lipid profile. However, no correlation was observed between SFRP5 and FBG or sleep parameters. The SFRP5 level of OSA patients did not differ from that of non-OSA individuals in our study.

Restless Legs Syndrome in Adults in Peking Union Medical College Hospital.

Objective To investigate the clinical characteristics of restless legs syndrome (RLS) in adults in Peking Union Medical College Hospital and explore the sleep quality,fatigue degree,daytime sleepiness,disease severity,depression and anxiety of RLS patients.Methods Totally 4739 consecutive patients who visited the outpatient departments with any sleep complaint or leg discomforts were recruited in the study. Patients under 18 years were excluded. All participants answered RLS questionnaire. The subjects fulfilled all four criteria would be followed up and given advanced examinations to rule out secondary RLS and RLS mimics. Primary RLS patients were evaluated with International Restless Legs Scale (IRLS),Pittsburgh Sleep Quality Index (PSQI),Fatigue Severity Scale (FSS),Epworth Sleepiness Scale (ESS),and Hospital Anxiety and Depression Scale for depression and anxiety (HADD and HADA). Another two groups of age-and gender-matched healthy subjects and non-RLS insomnia patients were served as normal and non-RLS insomnia controls.Results There were 162 (3.42%,162/4739) subjects fulfilling all four criteria for RLS; 42 (0.89%,42/4739) subjects were diagnosed as primary RLS and 33 (0.70%,33/4739) as RLS mimics. In primary RLS patients,41(97.6%) were found to be with poor sleep,13 (31.0%) with anxiety,and 4(9.5%) with depression. The scores of PSQI(q=11.69,P=0.000),HADA(q=8.02,P=0.000),and HADD(q=6.60,P=0.000)in primary RLS patients were significantly higher than those in normal controls. The scores of FSS(q=3.74,P=0.001),ESS(q=2.97,P=0.012),and HADD(q=4.15,P=0.000) in primary RLS patients were significantly lower than those in non-RLS insomnia controls. The scores of HADA and HADD were significantly correlated with those of PSQI(r=0.340,P=0.028;r=0.383,P=0.012),FSS(r=0.445,P=0.003;r=0.511,P=0.001),and IRLS(r=0.477,P=0.001;r=0.578,P=0.000). Conclusions RLS should be considered in the patients with any sleep-related complaint or leg discomforts. Primary RLS patients suffer from bad sleep and are more susceptible to anxiety and depression. Secondary RLS and RLS mimics should be excluded before the diagnosis of primary RLS.

Regulatory effects of miR-155 and miR-146a on repolarization and inflammatory cytokine secretion in human alveolar macrophages in vitro.

Macrophages play an important role in inflammatory responses; however, miRNA-mediated repolarization of macrophages is essential for fulfilling this function. To clarify a series of changes at the RNA level in alveolar macrophages under normal and inflammatory conditions, bronchial alveolar lavage liquid (BALF) was collected from healthy volunteers or patients with pneumonia. This approach, which differs from that used in previously, provides more accurate information about the states of macrophages in different lung microenvironments. In this study, the density plots of macrophage subtypes (M1 and M2) in the BALF of healthy volunteers differed from that of the patients with pneumonia. The M2 subtype dominated in healthy volunteers and was rapidly repolarized to M1 in response to miRNA-mediated gene regulation. Differential miRNA expression in the two macrophage subtypes revealed lower expression of miR-155 and MIR-146a in patients with pneumonia compared with healthy volunteers; this may be related to inflammation and the use of anti-inflammatory drugs. We also found increased TNF-α and IL-6 expression at the RNA level, while macrophage galactose-type C-type lectin 1 (MGL-1) expression decreased with downregulation of miR-155 and miR-146a expression. These results indicate that the gene regulation mediated by miR-155 and miR-146a contributes to human alveolar macrophage phenotype repolarization, thus leading to an early switch from pro-inflammatory to anti-inflammatory cytokine production.

Clinical spectrum of intrathoracic Castleman disease: a retrospective analysis of 48 cases in a single Chinese hospital.

BACKGROUND: Thorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD. METHODS: We conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital. RESULTS: The study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P < 0.05). MCD were more symptomatic (50% vs 96.9%, P < 0.001) and sicker than UCD, including more fever, hepatomegaly and/or splenomegaly and hypoalbuminemia. All of UCD showed solitary mass in various sites and two of them were complicated by small pleural effusion. In the MCD group, their chest CT showed obvious lymphadenopathy in the hilum and/or mediastinum (100%), diffuse parenchymal lung shadows (43.75%), pleural effusion (40.6%), mass in the mediastinum (6.25%) or hilum (3.12%) and bronchiolitis obliterans (BO) (3.12%). Besides LIP-like images, multiple nodules of different size and sites, patchy, ground-glass opacities and consolidation were showed in their chest CT. Surgery were arranged for all UCD for diagnosis and treatment and all were alive. In MCD group, superficial lymph nodes biopsies (21 cases), surgery biopsy (9 cases) and CT-guided percutaneous lung biopsy (2 cases) were performed. Hyaline vascular (HV) variant were more common in the UCD group (75% vs 37.5%, P < 0.05). In MCD group, 28 cases were prescribed with chemotherapy, one refused to receive therapy and the rest three were arranged for regular follow-up. Among MCD, 18 cases was improved, 7 cases was stable, 4 cases lost follow-up and 3 cases died. CONCLUSIONS: Intrathoracic MCD was more common than UCD in our hospital. MCD was older, more symptomic and sicker than UCD. HV variant were more common in UCD. All of UCD showed mass in various intrathoracic locations and surgery resection was performed for all and all were alive. Mass, pleural effusion, BO and diffuse pulmonary shadows, including LIP-like images, multiple nodules of different size and sites, patchy, GGO and consolidations were showed in our MCD. Most of MCD cases were arranged with chemotherapy and their prognosis were worse than UCD's.

Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages.

Staphylococcus aureus (S. aureus) is the most common bacterium in sepsis and pneumonia involving gram-positive bacteria. Lipoteichoic acid (LTA) is a cell wall component of gram-positive bacteria. It is a potent inducer of inflammatory mediators in human dendritic cells, human pulmonary epithelial cells, and murine macrophages. However, the effect of LTA on human alveolar macrophages (AMs) which are the major effector cells in host defense against respiratory tract infections has hardly been studied. Statins have anti-inflammatory, immunomodulatory, antioxidative, anticoagulant, and antibacterial activities. These effects may be contributed to reduce the markers of systemic inflammation. Emerging retrospective studies have demonstrated that statin use decreased the mortality of pneumonia. However, the precise mechanisms responsible for these effects are unclear. The purpose of this study is to define the role of S. aureus LTA in human AMs and the effects of simvastatin (SV) on LTA-stimulated human AMs. The results showed that LTA induced tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), IL-8 mRNA expression, and suppressed IL-10 mRNA expression in human AMs. Simultaneously, LTA induced human AMs apoptosis. These effects were parallel with the up-regulation of the expression of NF-κB-P65 protein in the LTA-stimulated human AMs. The above effects of LTA on human AMs were inhibited significantly by SV. These data indicate that S. aureus LTA induces potent pro-inflammatory and pro-apoptotic effects on human AMs and statins exert anti-inflammatory effects by mediating inhibition of NF-κB activation and cytokine mRNA expression in human AMs. These results may explain, in part, the mechanisms responsible for favorable effects of statins on pneumonia.

[Obesity and sleep-related breathing disorders].

Obesity, with an increasing prevalence,has become one of the most common metabolic diseases. Obesity is associated with many respiratory diseases, especially sleep-related breathing disorders including obstructive sleep apnea-hypopnea syndrome, obesity hypoventilation syndrome, and overlap syndrome. This article reviews the association between obesity and these sleep-related breathing disorders.

[Clinical analysis of invasive pulmonary fungal infections].

OBJECTIVE: To investigate the clinical characteristics of invasive pulmonary fungal infections (IPFI). METHODS: The clinical data of 48 patients with confirmed IPFI at Peking Union Medical College Hospital from January 2004 to December 2008 were retrospectively analyzed. Patients were divided into primary IPFI group and secondary IPFI groups based on their disease courses. RESULTS: The most commonly seen fungi were aspergillus species (37.5%) and cryptococcus species (37.5%), and community acquired infections accounted for 87.5%. The secondary IPFI accounted for 66.7% among all cases, in which the major pathogens were aspergillus species; in the primary IPFI group, the major pathogens were cryptococcus species. The symptoms of IPFI were non-specific and mostly presented as cough, fever, hemoptysis, and dyspnea. The common imaging features included multiple nodules, infiltrates and consolidations, or diffused lesions in bilateral lungs, and cavities were found in 11 patients (22.9%). The clinical symptoms and imaging findings were not significantly different between these two groups. A total of 46 patients (95.8%) received antifungal therapies or surgeries. Ten patients (20.8%; all from the secondary IPFI group) died, making the fatality rate significantly different between the primary IPFI group and secondary IPFI group (P=0.033). CONCLUSIONS: The major pathogens of IPFI are aspergillus species and cryptococcus species, and most of them are community acquired. The secondary IPFI with aspergillus species tend to be highly fatal. The clinical symptoms and imaging features are non-specific. Early diagnosis with prompt antifungal therapies, or even with surgical intervention, may be beneficial for these patients.