Physicians' knowledge of invasive fungal disease in China.

BACKGROUND: Invasive fungal disease (IFD) is associated with high morbidity and mortality. Data are lacking regarding physicians' perspectives on the diagnosis and management of IFD in China. OBJECTIVES: To evaluate physicians' perspectives on the diagnosis and management of IFD. METHODS: Based on current guidelines, a questionnaire was designed and administered to 294 physicians working in haematology departments, intensive care units, respiratory departments and infectious diseases departments in 18 hospitals in China. RESULTS: The total score and subsection scores for invasive candidiasis, invasive aspergillosis (IA), cryptococcosis and invasive mucormycosis (IM) were 72.0 ± 12.2 (maximum = 100), 11.1 ± 2.7 (maximum = 19), 43.0 ± 7.8 (maximum = 57), 8.1 ± 2.0 (maximum = 11) and 9.8 ± 2.3 (maximum = 13), respectively. Although the perspectives of the Chinese physicians were in good overall agreement with guideline recommendations, some knowledge gaps were identified. Specific areas in which the physicians' perspectives and guideline recommendations differed included use of the ß-D-glucan test to facilitate the diagnosis of IFD, relative utility of the serum galactomannan test and bronchoalveolar lavage fluid galactomannan test in patients with agranulocytosis, use of imaging in the diagnosis of mucormycosis, risk factors for mucormycosis, indications for initiating antifungal therapy in patients with haematological malignancies, when to start empirical therapy in mechanically ventilated patients, first-line drugs for mucormycosis and treatment courses for IA and IM. CONCLUSION: This study highlights the main areas that could be targeted by training programs to improve the knowledge of physicians treating patients with IFD in China.

Case Report: Visceral Leishmaniasis-associated Hemophagocytic Lymphohistiocytosis in Adults: A Case Series and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal complication of visceral leishmaniasis (VL). To provide a basis for early and correct diagnosis and to improve prognosis in the future, we describe a case series of VL-associated HLH in adults in our center in the past decade after review of all reported cases of adult VL-associated HLH in English through May 2022. In our case series, a total of 111 patients were diagnosed with VL. Among these patients, only six cases were diagnosed with VL-associated HLH. All patients tested positive for serology. Leishmania was detected for the first time by bone marrow aspiration (BMA) in three of the six patients and in the other three patients after three or four BMAs. It took more than 1 month from onset to diagnosis of VL for all the six cases, and the longest time was 6 months. Five of the six patients recovered after receiving sodium stibogluconate. VL-associated HLH is rare but potentially life-threatening in adults and predisposes to early delays in diagnosis. However, diagnostic techniques are not complicated or difficult, so it is more important to consider that it is not recognized by physicians. Although guidelines recommend liposomal amphotericin B as the most effective therapy, our experience suggests that sodium stibogluconate can be an alternative option when liposomal amphotericin B is unavailable or unaffordable.

Disseminated alveolar echinococcosis in a patient diagnosed by metagenomic next-generation sequencing: A case report.

Background: Alveolar echinococcosis (AE) is a parasitic zoonosis with high mortality and disability rates. Diverse clinical manifestations and mimicking of differential diagnoses such as tuberculosis and malignancy pose a diagnostic dilemma. With the rapid development of molecular diagnostic techniques in recent years, metagenomic next-generation sequencing (mNGS) has become an attractive approach for the etiological diagnosis of infectious diseases. Case presentation: we report a case of 51-year-old Chinese Tibetan male presented with 3-year low-back pain and 4-month discomfort in the right upper quadrant of the abdomen. He had been in good health. He was diagnosed with tuberculosis and was given anti-tuberculosis treatment a month prior to the visit, but the symptoms were not relieved. Abdominal computerized tomography (CT) revealed a hypodense lesion with uneven enhancement in the liver, and two ring-enhancing cystic lesions in the right abdominal wall. Lumbar spine enhanced MRI showed lesions of mixed density with uneven enhancement in the L1 vertebra and paraspinal tissue. The pathological results of the liver biopsy revealed parasitic infection and possibly echinococcosis. The metagenomic next-generation sequencing (mNGS) of the puncture fluid of abdominal cysts using Illumina X10 sequencer revealed 585 sequence reads matching Echinococcus multilocularis. Disseminated AE was diagnosed. Albendazole (400 mg, twice daily) was used, and the patient was in stable condition during follow-up. Conclusions: mNGS may be a useful tool for the diagnosis of AE. The case would help clinicians to improve their diagnostic skills.

Preoperative and postoperative nomograms for predicting early recurrence of hepatocellular carcinoma without macrovascular invasion after curative resection.

BACKGROUND: Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion. METHODS: Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort. RESULTS: In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively. CONCLUSIONS: The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.

The utility of cerebrospinal fluid white cell count during the prognostic assessment for cryptococcal meningitis patients: a retrospective study.

BACKGROUND: The incidence of cryptococcal meningitis (CM) has gradually increased in recent years. Cerebrospinal fluid (CSF) cytology and cell count are very important for CM on etiology diagnosis and assessment of disease status and therapeutic response. However, the clinical significance of CSF white cell count (WCC) in CM patients is not fully understood. Using longitudinal data of CSF WCC and its relationship with clinical outcomes in CM patients, we aimed to elucidate the clinical significance of this test. METHODS: We retrospectively analyzed the medical records of 150 CM patients admitted to our hospital between January 2008 and December 2018. RESULTS: CM patients with lower baseline CSF WCC, CSF protein concentration or CD4/CD8 ratio, and those with altered mentation or HIV coinfection were more likely to have poor clinical outcome (P<0.05). CM patients with triple therapy during the induction period presented with a better clinical outcome (P<0.05). Baseline CSF WCC had a moderate positive correlation with peripheral CD4+ T lymphocyte count (r = 0.738, P < 0.001) and CD4+ T lymphocyte percentage (r = 0.616, P < 0.001). The best cut-off value to predict a poor clinical outcome was 40 cells/µL during baseline CSF WCC. The predictive model incorporating longitudinal data of CSF WCC had better sensitivity, specificity, and accuracy than a model incorporating only baseline CSF WCC data. CONCLUSIONS: Our results indicated that baseline CSF WCC and changes in CSF WCC over time could be used to assess the prognosis of CM patients.

Retrospective analysis of 1,641 cases of classic fever of unknown origin.

BACKGROUND: Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3 °C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory investigations. It is a special type of fever and a common disease in internal medicine. However, due to its complex etiology, lack of characteristic clinical manifestations, and insufficient laboratory examination indicators, it often baffles clinicians in diagnosis. We herein present a study of the etiological factors and clinical features of classic fever of unknown origin (FUO) to provide help for related clinical diagnosis and treatment. METHODS: A total of 1,641 cases of patients with classic FUO hospitalized in West China Hospital of Sichuan University between January 1, 2011 and December 31, 2017, were collected, and the etiological factors of classic FUO were analyzed. A special effort was made to explore and screen the laboratory indicators related to infectious diseases, and the above data were compared with the clinical features of tuberculosis and lymphoma, which are difficult to diagnose. RESULTS: Among the 1,641 patients, 1,504 were finally diagnosed through various types of examination or diagnostic methods, and the diagnosis rate was 91.65%. Among all the causes of the 1,641 cases of FUO, 48.69% [799] were infectious diseases, of which tuberculosis was the most common, accounting for 19.50% [320]. Connective tissue diseases were responsible for 19.26% [316] of cases, of which adult-onset Still's disease (AOSD) was the most common, comprising 89 (5.42%) of the cases; 16.94% [278] were neoplastic diseases, and lymphoma (143, 8.71%) cases, was the most common malignant tumor; 6.76% [111] were other diseases; and in 8.35% [137] of cases, the cause was unclear. Through comparative analysis of tuberculosis and lymphoma, no significant differences were found between the symptoms, signs, and non-specific routine examination results of the two diseases. The diagnosis of these diseases was more dependent on tuberculosis-related examinations and pathological examinations. CONCLUSIONS: Infectious diseases are the principal cause of classic FUO, in which tuberculosis accounts for a large proportion. Non-infectious diseases that cause FUO are mainly connective tissue diseases and malignant tumors. Of the various causes of classic FUO, tuberculosis and lymphoma are relatively difficult to diagnose. In most cases, the causes of classic FUO can be ascertained.

Clinical analysis in immunocompetent and immunocompromised patients with pulmonary cryptococcosis in western China.

Cryptococcosis is a systemic infection and it may occur in immunocompromised and immunocompetent hosts. In order to better understand the clinical characteristics of patients with PC in different immune status, we retrospectively investigated the clinical, radiological, and treatment profiles of immunocompetent and immunocompromised patients with PC during a 10-year period (2008-2017). As a result, out of 136 patients, 94 (69.1%) were immunocompromised hosts. For the PC patients without CNS involvement, higher percentage of immunocompetent patients (39.5%, 15/38) had asymptomatic presentation than immunocompromised patients (6.3%, 3/48) (P < 0.05). Multiple pulmonary nodules (72.7%, 56/77), ground-glass attenuation/interstitial changes (94.4%, 17/18) and cavitation (88.6%, 31/35) were significantly frequent in immunocompromised patients (P < 0.05). A total of 47 patients were misdiagnosed as tuberculosis or tumors based on CT signs. PC was likely to be misdiagnosed as tuberculosis in immunocompromised patients (88.2%, 15/17), and tumor was more likely to be considered in immunocompetent patients (43.3%, 13/30). Immunocompetent patients accounted for 80% (24/30) of patients with definite diagnosis on surgical lung biopsy. Fluconazole monotherapy can achieve good clinical outcome in most PC patients without central nervous system (CNS) involvement (91.5%, 54/59). After 3 months of treatment, 92.7% (38/41) patients have improved imaging findings. In conclusion, PC has diverse imaging manifestations and it is easily misdiagnosed. Lobectomy should be carefully selected in immunocompetent patients with a single lung lesion. Fluconazole monotherapy is preferred for PC patients without CNS involvement.

RAPIDLY PROGRESSIVE PULMONARY CRYPTOCOCCOSIS WITH CAVITATION IN AN IMMUNOCOMPETENT WOMAN: A CASE REPORT AND LITERATURE REVIEW.

Pulmonary cryptococcosis with pulmonary cavitation is rare, especially in immunocompetent cryptococcosis patients. We describe here a case of rapidly progressive pulmonary with cavitation in an immunocompetent woman. A 29-year-old woman had a routine chest X-ray as part of a routine examination. The chest X-ray showed pulmonary nodules. She was diagnosed as having bacterial pneumonia even though she had no symptoms and was treated with ampicillin orally. A chest X-ray was repeated 12 days later as follow-up which showed an increase in the nodules. She continued to be asymptomatic and had a normal lung examination. Her complete blood count revealed a normal white blood cell count and her anti-human immunodeficiency virus test was normal, as were her immunoglobulin levels and CD4 counts. She had a computed tomography (CT) scan of the lungs that showed two pulmonary nodules, one with cavitation. She then underwent a CT guided needle biopsy of the cavitary lesion which revealed pulmonary cryptococcosis. A serum latex cryptococcal antigen test revealed a titer of 1:32. She was treated with fluconazole 400 mg IV daily for 7 days, followed by oral fluconazole 200 mg daily for a year. The cavitary lesion gradually disappeared and the nodules decreased in size. A follow-up CT 1 year later was normal. Although rare, cryptococcosis of the lungs with pulmonary cavitation can occur in otherwise healthy patients, requiring long term treatment to improve.

[Clinical Analysis of 94 Patients with Neurocysticercosis in Sichuan Province].

Objective: To analyze the clinical features of neurocysticercosis（NCC） to provide evidence for clinical diagnosis and treatment of the disease. Methods: Medical records of NCC patients in the West China Hospital of Sichuan University received between January 2003 and January 2013 were reviewed retrospectively. The epidemiological data, clinical manifestations, therapeutic procedures and outcomes of the patients were analyzed. Results: A total of 94 NCC patients met the recruiting criteria, of whom 67.0%（63/94） were male, 59.6%（56/94） ranged 30-55 years old, 73.4%（69/94） had a living history in endemic regions such as Aba, Ganzi and Liangshan prefectures, 80.9%（76/94） lived in rural areas. NCC was clinically characterized by epilepsy, headache and intracranial hypertension. The positive rate for anti-T. solium antibodies by ELISA was 96.8%（91/94）, and the total positive scan rate of neuroimaging including CT and MRI was 95.7%（90/94）. In addition, 73 patients were suspected to have NCC at the first diagnosis, with a misdiagnosis rate of 22.3%（21/94）. Seventy-nine of the patients received albendazole treatmentï¼»20 mg/（kg·d）, twice per day for 10 days as one treatment course, 1-3 courses as neededï¼½. Eleven patients received praziquantel（total dose of 120-180 mg/kg, 3 times per day for 3 days as one treatment course, 1-3 courses）, and 4 received a combination of albendazole and praziquantel. Symptoms improved in 77 cases（81.9%）, but 12 of them（12/77, 15.6%） relapsed. The improvement rate of the albendazole group（6/11, 84.8%） was significantly higher than that of the praziquantel group（54.6%）（P<0.05）. Conclusion: NCC more commonly occurs in young males and lacks specific clinical manifestations. Neuroimaging combined with serum specific antibody tests is crucial for diagnosis. Albendazole has better therapeutic effects than praziquantel.

Analysis of cerebrospinal fluid protein concentrations of patients with cryptococcal meningitis treated with antifungal agents.

BACKGROUND: Many neurological diseases are accompanied by an increase in the cerebrospinal fluid (CSF) protein concentration, which indicates dysfunction of the blood-CSF/blood-brain barrier. However, the significance CSF protein concentration of patients with cryptococcal meningitis (CM) is not fully understood. The aim of the present was to determine whether CSF protein concentrations correlated with the responses of patients to treatment with antifungal drugs. METHODS: We conducted a retrospective study of the analytical data of 623 lumbar punctures of 46 patients with CM who were treated at West China Hospital. We divided the patients into groups with good or poor responses to antifungal treatment. We used a generalized linear mixed model (GLMM) to evaluate the significance of the differences between the two groups. RESULTS: The baseline CSF protein concentrations of the good antifungal response group (GR-group) (median = 0.97 g/L) were higher compared with those of the poor antifungal response group (PR-group) (median = 0.72 g/L). Analysis using the GLMM indicated that the CSF protein concentration of the GR-group decreased at a rate of 1.8 mg/L per day after antifungal treatment started and was 2.1 mg/L higher compared with that of the PR-group. CONCLUSIONS: Compared with poor responders, we found that the baseline CSF protein concentrations of good responders were higher and decreased at faster rate after the initiation of antifungal treatment.

[Clinical analysis of 137 patients with visceral leishmaniasis].

OBJECTIVE: To analyze the clinical and epidemiological characteristics of visceral leishmaniasis cases in Sichuan. METHODS: The medical records of 137 patients with visceral leishmaniasis were reviewed between January 2000 and April 2012 in West China Hospital. The epidemiological data, clinical manifestations, laboratory features, diagnosis, therapeutic procedures and outcome of the patients were retrospectively analyzed. RESULTS: Eighty-eight (64.2%) out of 137 cases were the residents in the endemic area of Sichuan Province and adjacent areas, and 49 (35.8%) were non-endemic area residents with a history of visiting endemic area. Patients living in rural areas accounted for 84.7% (116/137), in town for 15.3% (21/137). Visceral leishmaniasis should be strongly suspected in a patient with prolonged fever, marked hepatosplenomegaly, lymphadenectasis, cytopenia and hypergammaglobulinemia. All patients showed positive in rk39 dipstick test, and were treated with antimony sodium gluconate. Among these patients, 86.1% (118/137) were cured by drug, 2.9% (4/137) received splenectomy, and 6.6% (9/137) relapsed. The misdiagnosis rate was 23.4% (32/137). CONCLUSION: Bone marrow smear staining and biopsy, combined with rk39 antibody detection and epidemiological history are crucial for early diagnosis and treatment of visceral leishmaniasis. Antimonials is still an effective therapeutic choice.

[Impact of misuse of antimicrobial therapies on inpatient costs].

OBJECTIVE: To evaluate the impact of inappropriate antibiotic use on inpatients' cost during hospitalization. METHODS: 1 000 cases with antibiotic treatment were extracted from 10 hospitals of 5 provinces in China in 2005. We created multivariate linear regression model for hospital cost and Logistic regression model for evaluation of rationality in antibiotic use. RESULTS: We collected 946 valid cases. Rate of inappropriate antibiotic use was 58.4%. Costs of inpatients with inappropriate antibiotic use was 1.55 times of the ones with appropriate use (P<0.001). Risk factors included antibiotic prophylaxis (OR=2.929), medication for surgery (OR=2.44), long hospital stay (OR=1.021 for every prolonged day) and regional factors. Protection factor was in tertiary hospital (OR=0.510). CONCLUSION: Inappropriate antibiotic use could add 55% unnecessary cost on inpatients. Efforts to control misuse of antibiotics such as regulating antibiotic prophylaxis and medication for surgery, and decreasing length of stay should be pursued.

Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population.

BACKGROUND: Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003-2004 among CAP of adult Chinese urban populations. METHODS: Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed. RESULTS: Non-viral pathogens were found in 324/610 (53.1%) patients among whom M. pneumoniae was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of S. pneumoniae to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with beta-lactam antibiotics alone and with combination of a beta-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed M. pneumoniae and/or C. pneumoniae infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a beta-lactam plus a macrolide, or a fluoroquinolone) than with beta-lactam alone (75.8% vs. 42.9%, p = 0.045). CONCLUSION: In Chinese adult CAP patients, M. pneumoniae was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With S. pneumoniae, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.