The Impact of Early Antibiotic Use on Clinical Outcomes of Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis.

Purpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown. Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness. Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246-4.060), p = 1.000) and ICU admission (HR=0.436(0.093-2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296-1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221-8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort. Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.

The first reported pulmonary nocardiosis caused by Nocardia gipuzkoensis resisted to trimethoprim/sulfamethoxazol (TMP-SMZ) in an immunocompetent patient.

OBJECTIVES: Nocardia gipuzkoensis was first described as a novel and distinct species in 2020 by Imen Nouioui and pulmonary nocardiosis associated with N. gipuzkoensis was once reported in two bronchiectasis patients. Noteworthy, both reported N. gipuzkoensis cases showed sensitivity to trimethoprim/sulfamethoxazol (TMP-SMZ), which are usually recommended for empirical therapy. METHODS: We reported the third case of N. gipuzkoensis infection in a 16-year-old girl with chief complaints of cough and persistent chest and back pain. No underlying immuno-suppressive conditions and glucocorticoid use was revealed. Patchy lesions next to the spine and located in the posterior basal segment of the lower lobes of the left lung were seen in thorax computed tomography (CT), but no pathogenic bacteria were detected according to routine laboratory testings. RESULTS: Metagenomic next-generation sequencing (mNGS) combined with whole-genome sequencing (WGS) was used to classified our isolate from bronchoalveolar lavage fluid (BALF) as N. gipuzkoensis. It is worth mentioning that drug susceptibility testing of our isolate showed resistance to TMP-SMZ, which was never reported before. The patient improved remarkably both clinically and radiographically according to the treatment with imipenem-cilastatin infusion alone. CONCLUSION: mNGS and WGS showed excellent performance in identifying the Nocardia genus to the species level and improving the detection rate of N. gipuzkoensis ignored by traditional culture. Different from previously reported cases, the N. gipuzkoensis infection case showed resistance to TMP-SMZ, which is an unprecedented finding and a crucial addition to our understanding of the antibacterial spectrum of N. gipuzkoensis. The successful treatment with imipenem-cilastatin infusion alone in this case is a testament to the importance of precise identification and tailored antibiotic therapy.

Risk factors, outcomes, and epidemiological and etiological study of hospitalized COVID-19 patients with bacterial co-infection and secondary infections.

BACKGROUND: As a common complication of viral respiratory tract infection, bacterial infection was associated with higher mortality and morbidity. Determining the prevalence, culprit pathogens, outcomes, and risk factors of co-infection and secondary infection occurring in hospitalized patients with coronavirus disease 2019 (COVID-19) will be beneficial for better antibiotic management. METHODS: In this retrospective cohort research, we assessed clinical characteristics, laboratory parameters, microbiologic results, and outcomes of laboratory-confirmed COVID-19 patients with bacterial co-infection and secondary infection in West China Hospital from 2022 December 2nd to 2023 March 15th. RESULTS: The incidence of bacterial co-infection and secondary infection, as defined by positive culture results of clinical specimens, was 16.3% (178/1091) and 10.1% (110/1091) respectively among 1091 patients. Acinetobacter, Klebsiella, and Pseudomonas were the most commonly identified bacteria in respiratory tract samples of COVID-19 patients. In-hospital mortality of COVID-19 patients with co-infection (17.4% vs 9.5%, p = 0.003) and secondary infection (28.2% vs 9.5%, p < 0.001) greatly exceeded that of COVID-19 patients without bacterial infection. Cardiovascular disease (1.847 (1.202-2.837), p = 0.005), severe COVID-19 (1.694 (1.033-2.778), p = 0.037), and critical COVID-19 (2.220 (1.196-4.121), p = 0.012) were proved to be risk factors for bacterial co-infection, while only critical COVID-19 (1.847 (1.202-2.837), p = 0.005) was closely related to secondary infection. CONCLUSIONS: Bacterial co-infection and secondary infection could aggravate the disease severity and worsen clinical outcomes of COVID-19 patients. Notably, only critical COVID-19 subtype was proved to be an independent risk factor for both co-infection and secondary infection. Therefore, standard empirical antibiotics was recommended for critically ill COVID-19 rather than all the inpatients according to our research.

Prognostic Value of Neutrophil to Lymphocyte Ratio for Predicting 90-Day Poor Outcomes in Hospitalized Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Objective: This study aimed to evaluate the predictive value of neutrophil to lymphocyte ratio (NLR) for poor outcomes within 90-day in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A retrospective study including 503 AECOPD patients was performed, and the subjects' clinical characteristics were collected. Binary logistic regression analysis was used to identify risk factors for 90-day poor outcomes in patients with AECOPD. Receiver-operating characteristic curves (ROC) and areas under the curves (AUC) were used to assess the ability of different biomarkers to predict the risk of 90-day mortality, readmission and re-exacerbation in patients with AECOPD. Results: During the follow-up, 188 patients (38.4%) redeveloped exacerbations, 112 patients (22.9%) were readmitted, and 20 patients (4.1%) died directly resulted from COPD or COPD-related causes. Multivariate analysis demonstrated that age>72 years (OR: 14.817, 95% CI: 1.561-140.647), NLR>14.17 (OR: 9.611, 95% CI: 2.303-40.113), EOS<0.15% (OR: 8.621, 95% CI: 3.465-34.913) and BNP>2840ng/L (OR: 5.291, 95% CI: 1.367-20.474) at discharge were independent risk factors for 90-day mortality in AECOPD patients. NLR was the optimal biomarker for predicting 90-day mortality with an AUC of 0.802 (95% CI: 0.631-0.973). Using 14.17 as the critical value of NLR, the sensitivity was 76.7%, and the specificity was 88.9%. Compared with mortality, NLR had no significant advantage in predicting risk of short-term re-exacerbation (AUC=0.580, 95% CI:0.529-0.632, p=0.001) and readmission (AUC=0.555, 95% CI:0.497-0.614, p=0.045), with AUCs less than 0.6. In contrast, the predictive value of EOS (AUC=0.561, 95% CI:0.502-0.621, p=0.038) was slightly better than NLR in terms of readmission within 90 days. CRP did not serve as a well predictive biomarker for the risk of readmission and re-deterioration (p>0.05). Conclusion: NLR is of great value in predicting the risk of poor outcomes, especially COPD associated mortality, in hospitalized patients with AECOPD within 90 days after discharge.

The Impact of Lung Cancer in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE).

Given the high risk of lung cancer (LC) in patients with combined pulmonary fibrosis and emphysema (CPFE), and the difficulty of early diagnosis, it is important to understand the impact of LC in these patients. The effect of LC on the development of acute exacerbation (AE) as a natural course of CPFE is still unknown. We retrospectively reviewed medical records of patients at the West China Hospital and enrolled 59 patients with CPFE combined with LC and 68 CPFE patients without LC for initial diagnosis matched in the same period. We compared the clinical characteristics and imaging features of CPFE patients with LC and without LC, and analyzed the associated factors for the prevalence of LC using binary logistic regression. Cox proportional hazards regression analysis was performed to explore risk factors of AE as a natural course of CPFE. Patients with CPFE combined with LC were more common among elderly male smokers. The most common pathological type of tumor was adenocarcinoma (24/59, 40.7%) and squamous cell carcinoma (18/59, 30.5%). Compared with those in the without LC group, the proportions of men, and ex- or current smokers, and the levels of smoking pack-years, serum CRP, IL-6, fibrinogen, complement C3 and C4 in patients with LC were significantly higher (p < 0.05). There was no significant difference in the proportion of natural-course-related AE (10.2% vs. 16.2%, p > 0.05) between the two groups. Logistic regression analysis demonstrated that pack-years ≥ 20 (OR: 3.672, 95% CI: 1.165-11.579), family history of cancer (OR: 8.353, 95% CI: 2.368-10.417), the level of fibrinogen > 4.81 g/L (OR: 3.628, 95% CI: 1.403-9.385) and serum C3 > 1.00 g/L (OR: 5.299, 95% CI: 1.727-16.263) were independently associated with LC in patients with CPFE. Compared to those without AE, CPFE patients with AE had significantly higher levels of PLR and serum CRP, with obviously lower DLCO and VC. The obviously increased PLR (HR: 3.731, 95% CI: 1.288-10.813), and decreased DLCO%pred (HR: 0.919, 95% CI: 0.863-0.979) and VC%pred (HR: 0.577, 95% CI: 0.137-0.918) rather than the presence of LC independently contributed to the development of natural-course-related AE in patients with CPFE. Pack-years, family history of cancer, the levels of fibrinogen and serum C3 were independently associated with LC in patients with CPFE. The presence of LC did not significantly increase the risk of AE as a natural course of CPFE. Clinicians should give high priority to CPFE patients, especially those with more severe fibrosis and systemic inflammation, in order to be alert for the occurrence of AE.

Clinical features and treatment outcomes of 14 patients with hepatosplenic γ δ T-cell lymphoma.

BACKGROUND: Hepatosplenic γ δ T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma (PTCL) with aggressive clinical behavior. To date, no standard therapy for HSTCL has been established. This study analyzed the clinical features, treatment, and prognosis for patients with HSTCL to determine the best therapeutic approach. METHODS: We reviewed the clinical characteristics, treatments, and responses to treatment of patients in our center between January 2001 and June 2021, and also reviewed related literature. RESULTS: Median patient age was 38 years (range 16-60 years) and the patients included eight males and six females. HSTCL in these patients typically presented with B symptoms (71.4%), splenomegaly (100%), and hepatomegaly (50.0%), but lymphadenopathy was extremely rare. In these patients, routine laboratory testing showed elevated lactate dehydrogenase (71.4%), liver dysfunction (42.9%), and decreased fibrinogen (35.7%). In the induction phase, five of the 14 patients received chemotherapy regimens containing anthracycline (CHOP, or CHOP plus bortezomib or Chidamide), and six were treated with non-CHOP chemotherapy. Seven patients responded to induction treatment, four of whom received allogeneic hematopoietic cell transplantation and then achieved a complete response in the consolidation phase. survival time of patients who received alloHCT range from 10 to 27 months. CONCLUSION: Hepatosplenic γ δ T-cell lacks a standard therapy and is often refractory to conventional chemotherapy regimens. Intensive induction chemotherapy followed by hematopoietic cell transplantation may improve the prognosis of HSTCL.

A near-infrared fluorescent probe with large Stokes shift for visualizing and monitoring mitochondrial viscosity in live cells and inflammatory tissues.

Mitochondria are cellular energy factory, having an essential role in cellular metabolism. Furthermore, abnormal changes in mitochondrial viscosity have been confirmed to be closely related to many diseases. Therefore, the development of probe that responsive to mitochondrial viscosity and its application in mitochondrial viscosity measurement is considered to be a new tool for understanding diseases. In this paper, a mitochondrial viscosity probe (DICB) with a large Stokes shift (214-253 nm) was designed and synthesized by modifying the structure of the carbazole fluorophore. The probe DICB has a favorable responsive to viscosity in the near-infrared (NIR) region (703 nm). In the water-glycerol system (0.893 cP -945 cP), the fluorescence intensity of DICB at 703 nm has a 74 times increase; in the range of 5.041 cP-856.0 cp, it has a well linear fitting relationship. Meantime, the probe has excellent sensitivity to viscosity. The probe (DICB) has been confirmed to be able to detect changes of mitochondrial viscosity in cell models induced by nystatin, carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and lipopolysaccharide (LPS); it has also been validated that DICB can be used in the process of autophagy to monitor mitochondrial viscosity. More importantly, DICB can be applied to the detection of abnormal mitochondrial viscosity in inflammatory tissues at the biological level. The outstanding characteristics of DICB for mitochondrial viscosity detection are not only of great importance to the development of viscosity probes, but also provides a universal strategy to study the relationship between inflammatory and mitochondrial viscosity.

Severe Influenza With Invasive Pulmonary Aspergillosis in Immunocompetent Hosts: A Retrospective Cohort Study.

Background: Influenza was an independent risk factor for invasive pulmonary aspergillosis (IPA). In light of increasing incidence and mortality of influenza associated aspergillosis, our study summarized risk factors, clinical characteristics, and prognostic factors of developing aspergillosis in immunocompetent hosts with influenza to further screen high-risk population and improve outcome. Methods: We reviewed the patient characteristics, laboratory examinations, radiological imaging, and microbiology data of 72 influenza patients with IPA and 84 influenza patients without IPA admitted to West China Hospital. Result: Our study shown that aspergillosis co-infection increased overall mortality of severe influenza from 22.6 to 52.8%, along with higher white blood count (WBC) (10.9 ± 5.0 vs. 8.4 ± 3.3, P = 0.016), Neutrophiles (9.5 ± 5.0 vs. 7.0 ± 3.8, P = 0.023), procalcitonin (PCT) (8.6 ± 15.9 vs. 1.2 ± 2.1, P = 0.009), and a lower CD4+ T cell count (189.2 ± 135.3 vs. 367.1 ± 280.0, P = 0.022) in death group. No impact of age, gender, underlying diseases, immunosuppressive agents and steroids use, CD4+ T cell count on incidence of influenza associated aspergillosis was observed. But influenza associated aspergillosis cases mostly accompanied with more H1N1 subtype (91.7 vs. 79.8%, P = 0.037) and higher level of C-reactive protein (CRP) (117.6 ± 88.1 vs. 78.5 ± 75.2, P = 0.017) and interleukin 6 (IL-6) (133.5 ± 149.2 vs. 69.9 ± 100.0, P = 0.021) than those without aspergillosis. Conclusion: Aspergillosis co-infection in severe influenza patients can lead to a significant increased mortality, which was associated with severe respiratory failure due to mixed infection and immunosuppression. Pulmonary excessive inflammatory response was related with IPA co-infection.

[The complete and extant editions of Jinguiyaolue (Synopsis of Prescriptions of the Golder Chamber).].

The extant Jinguiyaolue (Synopsis of Prescriptions of the Golder Chamber) is less likely to originate directly from the section on miscellaneous diseases in the 16-volume Shanghanzabinglun (Treatise on Cold Pathogenic and Miscellaneous Diseases) of ZHANG Zhong-jing which was complied in the early third century. It was, in fact, compiled in the Northern Song dynasty. All the extant editions of Jinguiyaolue, including Japanese editions, were derived from the five editions system complied from the Yuan dynasty to the Ming dynasty, belongs to the large character version. The small character version of Wu Qian's transcript that was recently discovered in the shanghai Library is different from the original system, and this is worthy of attention to. By comparison of Deng Zhen's version with We Qian's version, it was realized that the Northern Song government had not simply converted the large character version into the small character version, but revised it as large-scale for the second time.