Assessment of post-COVID-19 fatigue among female survivors 2 years after hospital discharge: a nested case-control study.

BACKGROUND: Fatigue is a common symptom of long COVID syndrome. Compared to male survivors, females have a higher incidence of post-COVID fatigue. Therefore, long-term follow-up is necessary to understand which groups of females are more vulnerable to post-COVID fatigue. METHODS: This is a nested case-control study of female COVID-19 survivors who were discharged from two designated hospitals in Wuhan, China in 2020, and received 2-year follow-up from March 1 to April 6, 2022. All patients completed the Checklist Individual Strength-subscale subjective fatigue (CIS-fatigue), a chronic obstructive pulmonary disease (COPD) assessment test (CAT), and the Hospital Anxiety and Depression Scale (HADS; including the HADS-Anxiety [HADS-A] and the HADS-Depression [HADS-D]). Individuals with CIS-fatigue scores of 27 or higher were classified as cases. The risk factors for fatigue was analysed with multivariable logistic regression analysis. RESULTS: A total of 899 female COVID-19 survivors were enrolled for analysis, including 47 cases and 852 controls. Compared with controls, cases had higher CAT, HADS-A and HADS-D scores, and showed a higher prevalence of symptoms, including anxiety (cases vs. controls, 44.7% vs. 4.0%, p < 0.001), chest tightness (21.2% vs. 2.3%, p < 0.001), dyspnoea (19.1% vs. 0.8%, p < 0.001) and so on. In multivariable logistic regression analysis, age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.02) and cerebrovascular disease (OR, 11.32; 95% CI, 2.87-43.00; p < 0.001) were risk factors for fatigue. Fatigue had a statistically significant moderate correlation with depression (r = 0.44, p < 0.001), but not with CAT ≥ 10. CONCLUSION: Female COVID-19 patients who had cerebrovascular disease and older age have higher risk of fatigue. Patients with fatigue have higher CAT scores, and are more likely to have concurrent depression.

Multifocal pleural capillary hemangioma: a rare cause of hemorrhagic pleural effusion-case report.

BACKGROUND: Capillary hemangioma can be found in many organs, but rarely in pleura. Previously, only localized pleural capillary hemangioma cases have been reported. Corticosteroids are the most commonly recommended drugs in capillary hemangioma. CASE PRESENTATION: Here, we present a case of a young woman with recurrent hemorrhagic pleural effusion. Despite repeatedly thoracentesis, the routine examinations, including chest computed tomography (CT) scan, pleural effusion biochemical test, and cytology all failed to make a definite diagnosis. Thus, single port video-assisted thoracoscopy (VATS) was then performed. Numerous nodules arising from the parietal pleura were found, and biopsies showed multifocal pleural capillary. However, recurrent pleural effusion was successfully managed by oral azathioprine, after failure of dexamethasone treatment. CONCLUSIONS: To our knowledge, this is the first case of a patient with recurrent hemorrhagic pleural effusion masquerading as malignant pleurisy, but in fact caused by multifocal pleural capillary hemangioma.

Hyperglycemia and Correlated High Levels of Inflammation Have a Positive Relationship with the Severity of Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. METHODS: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). RESULTS: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes (n = 366), patients with diabetes (n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. CONCLUSION: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.

Identification of invasion-metastasis-associated microRNAs in hepatocellular carcinoma based on bioinformatic analysis and experimental validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancer, mainly attributing to its high tendency to metastasis. Vascular invasion provides a direct path for solid tumor metastasis. Mounting evidence has demonstrated that microRNAs (miRNAs) are related to human cancer onset and progression including invasion and metastasis. METHODS: In search of invasion-metastasis-associated miRNAs in HCC, microarray dataset GSE67140 was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were obtained by R software package and the potential target genes were predicted by miRTarBase. The database for annotation, visualization and integrated discovery (DAVID) was introduced to perform functional annotation and pathway enrichment analysis for these potential targets of DE-miRNAs. Protein-protein interaction (PPI) network was established by STRING database and visualized by Cytoscape software. The effects of the miR-494-3p and miR-126-3p on migration and invasion of HCC cell lines were evaluated by conducting wound healing assay and transwell assay. RESULTS: A total of 138 DE-miRNAs were screened out, including 57 upregulated miRNAs and 81 downregulated miRNAs in human HCC tumors with vascular invasion compared with human HCC tumors without vascular invasion. 762 target genes of the top three upregulated and downregulated miRNAs were predicted, and they were involved in HCC-related pathways, such as pathway in cancer, focal adhesion and MAPK signaling pathway. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and MYC. Through constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-494-3p and miR-126-3p. Of note, miR-494-3p and miR-126-3p was markedly upregulated and downregulated in HCC cell lines and tissues, respectively. In addition, overexpression of miR-494-3p could significantly promote HCC migration and invasion whereas overexpression of miR-126-3p exerted an opposite effect. CONCLUSIONS: Targeting miR-494-3p and miR-126-3p may provide effective and promising approaches to suppress invasion and metastasis of HCC.

A Novel Corynebacterium glutamicum l-Glutamate Exporter.

Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering.IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to product excretion as well as product reuptake, making transporter engineering a useful strategy for strain improvement. The significance of our research is in identifying and characterizing a novel l-glutamate exporter from the industrial workhorse Corynebacterium glutamicum, which will enrich the understanding of l-glutamate excretion and provide a new target for studying bacterial amino acid transport and engineering transport reactions.

Polymorphisms of FGFR1 in HBV-related hepatocellular carcinoma.

Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in China. It is important to understand the genetic mechanisms underlying the development and progression of HBV-related HCC and to identify new biomarkers for clinical treatment. The important role of fibroblast growth factor receptors (FGFRs) has been widely recognized in many types of cancers, but the association between FGFR polymorphisms and HCC carcinogenesis has been rarely reported. In this study, 199 patients with HBV-associated cirrhosis, 203 with HBV-associated HCC, and 184 healthy controls with no liver diseases were enrolled as participants. Using SNaPshot assays, five SNPs (rs13317, rs7825208, rs1047057, rs1047111, and rs1966265) of growth factor receptor genes were genotyped. Our results showed that the G/A and G/G genotypes at rs7825208 of FGFR1 were negatively correlated with HBV-related HCC (odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.22-0.93, P = 0.027). However, after Bonferroni correction, these significant differences no longer existed (P > 0.05). Our results indicated that these five polymorphisms of fibroblast growth factor receptor genes do not play any independent roles in the tumorigenesis and progression of HBV-related HCC in Han Chinese patients.

Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis.

BACKGROUND: The overexpression of key enzymes in a metabolic pathway is a frequently used genetic engineering strategy for strain improvement. Metabolic control analysis has been proposed to quantitatively determine key enzymes. However, the lack of quality data often makes it difficult to correctly identify key enzymes through control analysis. Here, we proposed a method combining in vitro metabolic pathway analysis and proteomics measurement to find the key enzymes in threonine synthesis pathway. RESULTS: All enzymes in the threonine synthesis pathway were purified for the reconstruction and perturbation of the in vitro pathway. Label-free proteomics technology combined with APEX (absolute protein expression measurements) data analysis method were employed to determine the absolute enzyme concentrations in the crude enzyme extract obtained from a threonine production strain during the fastest threonine production period. The flux control coefficient of each enzyme in the pathway was then calculated by measuring the flux changes after titration of the corresponding enzyme. The isoenzyme LysC catalyzing the first step in the pathway has the largest flux control coefficient, and thus its concentration change has the biggest impact on pathway flux. To verify that the key enzyme identified through in vitro pathway analysis is also the key enzyme in vivo, we overexpressed LysC in the original threonine production strain. Fermentation results showed that the threonine concentration was increased 30% and the yield was increased 20%. CONCLUSIONS: In vitro metabolic pathways simulating in vivo cells can be built based on precise measurement of enzyme concentrations through proteomics technology and used for the determination of key enzymes through metabolic control analysis. This provides a new way to find gene overexpression targets for industrial strain improvement.

Developing a high-throughput screening method for threonine overproduction based on an artificial promoter.

BACKGROUND: L-Threonine is an important amino acid for animal feed. Though the industrial fermentation technology of threonine achieved a very high level, there is still significant room to further improve the industrial strains. The biosensor-based high-throughput screening (HTS) technology has demonstrated its powerful applications. Unfortunately, for most of valuable fine chemicals such as threonine, a HTS system has not been established mainly due to the absence of a suitable biosensor. In this study, we developed a HTS method to gain high-yielding threonine-producing strains. RESULTS: Novel threonine sensing promoters including cysJp and cysHp were discovered by proteomic analyses of Escherichia coli in response to extracellular threonine challenges. The HTS method was constructed using a device composed of the fused cysJp and cysHp as a promoter and a linked enhanced green fluorescent protein gene as a reporter. More than 400 strains were selected with fluorescence activated cell sorting technology from a library of 20 million mutants and tested within 1 week. Thirty-four mutants have higher productivities than the starting industrial producer. One mutant produced 17.95 % more threonine in a 5-L jar fermenter. CONCLUSIONS: This method should play a functional role for continuous improvement of threonine industry. Additionally, the threonine sensor construction using promoters obtained by proteomics analyses is so convenient that it would be easily extended to develop HTS models for other biochemicals.

Single-center experience in the diagnosis and treatment of lymphoepithelioma-like hepatic carcinoma.

PURPOSE: Lymphoepithelioma-like hepatic carcinoma (LELC) is a rare malignant liver tumor and its preoperative diagnosis is challenging. The aim of this study was to optimize the diagnosis and treatment of LELC in a single large center. METHODS: We conducted this retrospective analysis of 16 patients diagnosed with LELC in the First Affiliated Hospital of Zhejiang University between 2010 and 2022. Thirty-two cases of cholangiocarcinoma (ICC) and 48 cases of hepatocellular carcinoma (HCC) served as controls. RESULTS: Most of the 16 patients with LELC included in this study had no specific symptoms. Histologically, 9 patients had lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC), 5 had lymphoepithelioma-like cholangiocarcinoma (LEL-ICC) and 2 had LEL-HCC-ICC. LEL-HCC was usually accompanied by hepatitis B virus infection, while LEL-ICC was often accompanied by Epstein Barr virus (EBV) infection. During the follow-up period, no complication and deaths were observed and only one patient experienced recurrence. These results were obviously better than those in patients with HCC and ICC. CONCLUSION: LELC is a rare malignant hepatic tumor. There are no specific symptoms or imaging modalities for accurate preoperative diagnosis of LELC. The diagnosis can be confirmed by pathology; however, the prognosis of LELC after resection is promising.

Symptom Burden among Older COVID-19 Survivors Two Years after Hospital Discharge.

To study the long-term symptom burden among older COVID-19 survivors 2 years after hospital discharge and identify associated risk factors. The current cohort study included COVID-19 survivors aged 60 years and above, who were discharged between February 12 and April 10, 2020, from two designated hospitals in Wuhan, China. All patients were contacted via telephone and completed a standardized questionnaire assessing self-reported symptoms, the Checklist Individual Strength (CIS)-fatigue subscale, and two subscales of the Hospital Anxiety and Depression Scale (HADS). Of the 1,212 patients surveyed, the median (IQR) age was 68.0 (64.0-72.0), and 586 (48.3%) were male. At the two-year follow-up, 259 patients (21.4%) still reported at least one symptom. The most frequently self-reported symptoms were fatigue, anxiety, and dyspnea. Fatigue or myalgia, which was the most common symptom cluster (11.8%; 143/1212), often co-occurred with anxiety and chest symptoms. A total of 89 patients (7.7%) had CIS-fatigue scores ≥ 27, with older age (odds ratio [OR], 1.08; 95% CI: 1.05-1.11, P < 0.001) and oxygen therapy (OR, 2.19; 95% CI: 1.06-4.50, P= 0.03) being risk factors. A total of 43 patients (3.8%) had HADS-Anxiety scores ≥ 8, and 130 patients (11.5%) had HADS-Depression scores ≥ 8. For the 59 patients (5.2%) who had HADS total scores ≥ 16, older age, serious illness during hospitalization and coexisting cerebrovascular diseases were risk factors. Cooccurring fatigue, anxiety, and chest symptoms, as well as depression, were mainly responsible for long-term symptom burden among older COVID-19 survivors 2 years after discharge.

Identification of Bacillus subtilis SipW as a bifunctional signal peptidase that controls surface-adhered biofilm formation.

Biofilms of microbial cells encased in an exopolymeric matrix can form on solid surfaces, but how bacteria sense a solid surface and upregulate biofilm genes is largely unknown. We investigated the role of the Bacillus subtilis signal peptidase, SipW, which has a unique role in forming biofilms on a solid surface and is not required at an air-liquid interface. Surprisingly, we found that the signal peptidase activity of SipW was not required for solid-surface biofilms. Furthermore, a SipW mutant protein was constructed that lacks the ability to form a solid-surface biofilm but still retains signal peptidase activity. Through genetic and gene expression tests, the non-signal peptidase role of SipW was found to activate biofilm matrix genes specifically when cells were on a solid surface. These data provide the first evidence that a signal peptidase is bifunctional and that SipW has a regulatory role in addition to its role as a signal peptidase.

Use of nonprescription medicines by patients with COPD: a survey in Chongqing Municipality, China.

To study the impact of self-administration of nonprescription medicines (NPMs) on patients with chronic obstructive pulmonary disease (COPD), in Chongqing Municipality, China. A total of 85 patients who had used NPM were assigned to the NPM group. Another 83 patients who had only used prescription medicines (PMs) were assigned to the PM group. Their income, educational levels, health status, public health insurance coverage, the expense of drugs during exacerbation, and the numbers of acute exacerbations during the past year were surveyed, and the approved drugs for COPD were evaluated. The contents of corticosterone in various types of NPMs were determined by high-performance liquid chromatography. The proportion of use of NPM in hospitalized patients with COPD was 12.96%. The percentage of illiteracy and low income was significantly higher in COPD patients in the NPM group than those in the PM group. The cost of drugs per day and the quality of life in the NPM group were lower than those in the PM group. Further analysis revealed that 15 of 21 NPMs contained corticosteroids. More importantly, medical advice from doctors and nurses appeared to be effective. Some Chinese patients with COPD living in the Chongqing area of China used NPMs that contained corticosteroids. Health education and advisement can effectively limit the use of NPMs.

Facilitated Photocatalytic Degradation of Rhodamine B over One-Step Synthesized Honeycomb-Like BiFeO3/g-C3N4 Catalyst.

In the present work, a facile one-step methodology was used to synthesize honeycomb-like BiFeO3/g-C3N4 composites, where the well-dispersed BiFeO3 strongly interacted with the hg-C3N4. The 10BiFeO3/hg-C3N4 could completely degrade RhB under visible light illumination within 60 min. The degradation rate constant was remarkably improved and approximately three times and seven times that of pristine hg-C3N4 and BiFeO3, respectively. This is ascribed to the following factors: (1) the unique honeycomb-like morphology facilitates the diffusion of the reactants and effectively improves the utilization of light energy by multiple reflections of light; (2) the charged dye molecules can be tightly bound to the spontaneous polarized BiFeO3 surface to form the Stern layer; (3) the Z-scheme heterojunction and the ferroelectric synergistically promoted the efficient separation and migration of the photogenerated charges. This method can synchronously tune the micro-nano structure, surface property, and internal field construction for g-C3N4-based photocatalysts, exhibiting outstanding potential in environmental purification.

Post-sequelae one year after hospital discharge among older COVID-19 patients: A multi-center prospective cohort study.

BACKGROUND: To systematically evaluate the prevalence of post-sequelae and chronic obstructive pulmonary disease assessment test (CAT) scoring one year after hospital discharge among older COVID-19 patients, as well as potential risk factors. METHODS: A multi-center prospective cohort study involving 1,233 eligible older COVID-19 patients was conducted. All patients were followed-up between Mar 1, 2021 and Mar 20, 2021. CAT scoring was adopted to measure symptom burden in COVID-19 patients. RESULTS: Of the 1233 eligible cases, 630 (51.1%) reported at least one sequelae. The top six post-sequelae included fatigue (32.4%), sweating (20.0%), chest tightness (15.8%), anxiety (11.4%), myalgia (9.0%), and cough (5.8%). Severe patients had significantly higher percentage of fatigue, sweating, chest tightness, myalgia, and cough (P<0.05), while anxiety was universal in all subjects. Sweating, anxiety, palpitation, edema of lower limbs, smell reduction, and taste change were emerging sequelae. Disease severity during hospitalization (OR: 1.46, 95% CI: 1.15-1.84, P = 0.002), and follow-up time (OR: 0.71, 95% CI: 0.50-0.99, P = 0.043) were independently associated with risk of post-sequelae, while disease severity during hospitalization was significantly associated with increased risk of emerging sequelae (OR: 1.33, 95% CI: 1.03-1.71, P = 0.029). The median of CAT score was 2 (0-5) in all patients, and a total of 120 patients (9.7%) had CAT scores ≥10. Disease severity during hospitalization (OR: 1.81, 95% CI: 1.23-2.67, P = 0.003) and age (OR: 1.07, 95% CI: 1.04-1.09, P<0.001) were significantly associated with increased risk of CAT scores ≥10. CONCLUSIONS: While the dramatic decline in the prevalence rate of persistent symptoms is reassuring, new sequelae among older COVID-19 patients cannot be ignored. Disease severity during hospitalization, age, and follow-up time contributed to the risk of post-sequelae and CAT scoring one year after hospital discharge among older COVID-19 patients. Our study provides valuable clues for long-term post-sequelae of the older COVID-19 patients, as well as their risk factors.

Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China.

Importance: Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness. Objective: To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms. Design, Setting, and Participants: This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19-designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19. Exposures: COVID-19. Main Outcomes and Measures: The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits. Results: Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years; 926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69; 95% CI, 1.02-7.06; P = .04) and CAT scores of 10 or higher (odds ratio, 2.83; 95% CI, 1.21-6.66; P = .02). Conclusions and Relevance: In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.

A modified electro-transformation method for Bacillus subtilis and its application in the production of antimicrobial lipopeptides.

A modified electroporation method using trehalose is presented for the transformation of Bacillus subtilis. The new method improved the transformation efficiency of B. subtilis nearly 2,000-fold compared with the usual method, giving 4×10(5) transformants/µg DNA. Using this method, B. subtilis was engineered to improve production of antimicrobial lipopeptides and produced 1.8-fold more surfactin and 2.9-fold more fengycin.

Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China.

Importance: The long-term health outcomes and symptom burden of COVID-19 remain largely unclear. Objective: To evaluate health outcomes of COVID-19 survivors 1 year after hospital discharge and to identify associated risk factors. Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted at 2 designated hospitals, Huoshenshan Hospital and Taikang Tongji Hospital, both in Wuhan, China. All adult patients with COVID-19 discharged between February 12 and April 10, 2020, were screened for eligibility. Of a consecutive sample of 3988 discharged patients, 1555 were excluded (796 declined to participate and 759 were unable to be contacted) and the remaining 2433 patients were enrolled. All patients were interviewed via telephone from March 1 to March 20, 2021. Statistical analysis was performed from March 28 to April 18, 2021. Exposures: COVID-19. Main Outcomes and Measures: All patients participated in telephone interviews using a series of questionnaires for evaluation of symptoms, along with a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Logistic regression models were used to evaluate risk factors for fatigue, dyspnea, symptom burden, or higher CAT scores. Results: Of 2433 patients at 1-year follow-up, 1205 (49.5%) were men and 680 (27.9%) were categorized into the severe disease group as defined by the World Health Organization guideline; the median (IQR) age was 60.0 (49.0-68.0) years. In total, 1095 patients (45.0%) reported at least 1 symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age (odds ratio [OR], 1.02; 95% CI, 1.01-1.02; P < .001), female sex (OR, 1.27; 95% CI, 1.06-1.52; P = .008), and severe disease during hospital stay (OR, 1.43; 95% CI, 1.18-1.74; P < .001) were associated with higher risks of fatigue. Older age (OR, 1.02; 95% CI, 1.01-1.03; P < .001) and severe disease (OR, 1.51; 95% CI, 1.14-1.99; P = .004) were associated with higher risks of having at least 3 symptoms. The median (IQR) CAT score was 2 (0-4), and a total of 161 patients (6.6%) had a CAT score of at least 10. Severe disease (OR, 1.84; 95% CI, 1.31-2.58; P < .001) and coexisting cerebrovascular diseases (OR, 1.95; 95% CI, 1.07-3.54; P = .03) were independent risk factors for CAT scores of at least 10. Conclusions and Relevance: This study found that patients with COVID-19 with severe disease during hospitalization had more postinfection symptoms and higher CAT scores.

Personalized Variable vs Fixed-Dose Systemic Corticosteroid Therapy in Hospitalized Patients With Acute Exacerbations of COPD: A Prospective, Multicenter, Randomized, Open-Label Clinical Trial.

BACKGROUND: Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear. RESEARCH QUESTION: Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations? STUDY DESIGN AND METHODS: This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost. RESULTS: A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027). INTERPRETATION: Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02147015; URL: www.clinicaltrials.gov.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of COVID-19: a multicenter retrospective cohort study of 4086 cases in China.

To establish an effective nomogram for predicting in-hospital mortality of COVID-19, a retrospective cohort study was conducted in two hospitals in Wuhan, China, with a total of 4,086 hospitalized COVID-19 cases. All patients have reached therapeutic endpoint (death or discharge). First, a total of 3,022 COVID-19 cases in Wuhan Huoshenshan hospital were divided chronologically into two sets, one (1,780 cases, including 47 died) for nomogram modeling and the other (1,242 cases, including 22 died) for internal validation. We then enrolled 1,064 COVID-19 cases (29 died) in Wuhan Taikang-Tongji hospital for external validation. Independent factors included age (HR for per year increment: 1.05), severity at admission (HR for per rank increment: 2.91), dyspnea (HR: 2.18), cardiovascular disease (HR: 3.25), and levels of lactate dehydrogenase (HR: 4.53), total bilirubin (HR: 2.56), blood glucose (HR: 2.56), and urea (HR: 2.14), which were finally selected into the nomogram. The C-index for the internal resampling (0.97, 95% CI: 0.95-0.98), the internal validation (0.96, 95% CI: 0.94-0.98), and the external validation (0.92, 95% CI: 0.86-0.98) demonstrated the fair discrimination ability. The calibration plots showed optimal agreement between nomogram prediction and actual observation. We established and validated a novel prognostic nomogram that could predict in-hospital mortality of COVID-19 patients.

Behçet's disease with invasive pulmonary aspergillosis and Aspergillus auriculatus infection: A case report.

RATIONALE: Behçet's disease (BD) is an inflammatory disease that leads to multisystemic immune dysfunction and that involves pulmonary system alterations. PATIENT CONCERNS: A 26-year-old woman presented with dull right chest pain for 30 days and intermittent cough with expectoration for 5 days. She had a history of recurrent oral ulcer and constitutional rash 2 months prior. DIAGNOSES: The patient was diagnosed with BD complicated by IPA and Aspergillus auriculatus infection. INTERVENTIONS: The patient was administered itraconazole oral solution (200 mg b.i.d) to treat the fungal infection. After a diagnosis of BD was made, she received 40 mg of methylprednisolone sodium succinate daily for 1 week.Then, she also received 24 mg of methylprednisolone sodium succinate daily, which was decreased by 2 mg per half month, until the rash had resolved. The patient continued to receive 200 mg Q. D itraconazole orally for 3 months. Thereafter, itraconazole was stopped, while daily oral administration of 10 mg of methylprednisolone sodium succinate was continued. OUTCOMES: The rash was observed to resolve, and CT revealed that the lesions in both the right and left lung were reduced. During a telephone follow-up performed after 6 months, the patient stated that no symptoms had recurred during the follow-up period. LESSONS: This case illustrates that for patients with BD, ignoring extrapulmonary symptoms often leads to a delayed diagnosis. Physicians should perform a thorough medical history and physical examination of these patients, as the information obtained in this manner may provide important clues for disease diagnosis and treatment.