[The 506th case: fever of unknown origin, negative PET-CT and hemoperitoneum].

A 48-year-old male was admitted to Peking Union Medical College Hospital presented with intermittent fever for two years. The maximum body temperature was 39 ℃, and could spontaneously relieve. The efficacy of antibacterial treatment was poor. He had no other symptoms and positive signs. He had a significant weight loss, and the serum lactate dehydrogenase increased significantly. It was highly alert to be lymphoma, but bone marrow smear and pathology, and PET-CT had not shown obvious abnormalities. Considering high inflammatory indicators, increased ferritin and large spleen, the patient had high inflammatory status, and was treated with methylprednisolone. Then the patient's body temperature was normal, but the platelet decreased to 33×109/L. During hospitalization, he had suddenly hemoperitoneum and hemorrhagic shock. He was found spontaneous spleen rupture without obvious triggers, and underwent emergency splenectomy. The pathological diagnosis of spleen was diffuse large B-cell lymphoma.

[The 485th case: fever of undetermined origin and hypoxemia].

A 49-year-old male was admitted to Peking Union Medical College Hospital presented with fever for more than half a year. The patient was diagnosed as Sjogren's syndrome at local hospital. After oral prednisone 60 mg per day was given, the fever alleviated, but recurred after prednisone tapered to 40 mg/d. Both blood culture and stool culture were positive for Salmonella enteritidis. Antibiotics including ceftazidime, ceftriaxone, cilastatin-imipenem were sequentially administrated for 4 weeks, yet not effective. Although there were not respiratory symptoms or certain abnormalities on high-resolution chest CT, arterial blood gas indicated hypoxemia. Serum lactate dehydrogenase and ß2 micro-globulin were elevated, and the lung function test demonstrated significant impairment of diffusion function. Positron emission tomography-computed tomography (PET/CT)scan suggested that high fluorodeoxyglucose uptake was diffusely seen in both lungs. The patient was finally diagnosed as pulmonary intravascular large B-cell lymphoma (IVLBCL) by transbronchial lung biopsy. This case aims to emphasize the differentiation diagnoses of pulmonary intravascular lymphoma from common situations.

[The 481st case: fever, rash, and cough].

Talaromyces Marneffei infection is rarely reported in patients with chronic active Epstein-Barr virus (EBV) infection. We reported an old man with chronic fever, pleomorphic rash, cough, EBV viraemia, and secondary hemophagocytic syndrome. Repeated histological biopsy and culture of skin lesions revealed Talaromyces Marneffei. This patient was diagnosed as chronic active EBV infection, and Talaromyces Marneffei infection. After treated with glucocorticoid steroids and anti-fungal therapy, the patient finally recovered. EBV infection is usually seen in immune compromised patients, who are susceptible to opportunistic pathogens rarely as Talaromyces Marneffei in this case.

[A randomized controlled study of peramivir, oseltamivir and placebo in patients with mild influenza].

Objectives: To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza. Methods: This was a randomized, double-blind, double-dummy, placebo and positive control, multicenter clinical trial, comparing peramivir trihydrate with oseltamivir and placebo. The inclusive criteria were 15-70 years old, onset within 48 h, positive rapid influenza antigen test, and febrile (>38℃) accompanied with at least two associated symptoms. The severe cases complicated with chronic pulmonary and cardiac diseases, malignancies, organ transplantation, hemodialysis, uncontrolled diabetes, immunocompromised status, pregnancy and coexistence of bacterium infections were excluded. All patients were randomized 2∶2∶1 to receive peramivir, oseltamivir and placebo respectively. The primary endpoint was the disease duration, the secondary endpoints included time to normal axillary temperature and normal living activities, viral response, and adverse effects. Results: Following informed consent, 133 patients were included in this study. Four patients were exclude due to missing medical records, not fitting inclusion or exclusion criteria and poor compliance. A total of 129 patients were finally analyzed, including 49 cases, 54 cases and 26 cases in peramivir group, oseltamivir group and placebo group. The median disease duration were 96 (76, 120) hours, 105 (90,124) hours, and 124 (104, 172) hours in three groups respectively (P>0.05) . The time to normal axillary temperature, normal living activities and viral response were not significantly different in three groups (P>0.05) . Conclusion: The value of antiviral therapy in patients with mild influenza needs to be further determined.

[The analysis of peripheral blood T lymphocyte subsets in patients with colorectal cancer: a single center cross-section study].

The distribution of peripheral blood lymphocyte subsets were compared between patients with colorectal cancer and healthy controls. The number of natural killer(NK) cells and CD(8)(+)T cells and the percentage of naive CD(4)(+) T cells were all decreased significantly in patients. On the contrary, the percentages of memory CD(4)(+) T cells, HLA-DR(+) CD(8)(+) T cells and CD(38)(+) CD(8)(+) T cells were significantly increased. It suggests that the tumor killing effect of cytotoxic lymphocytes in peripheral blood is impaired in patients with colorectal cancer, whereas the immune response is over stimulated.

[Expert consensus on the diagnosis and treatment of cryptococcal meningitis].

Cryptococcal meningitis is a common and refractory central nervous system infection, with high rates of mortality and disability. The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion. Based on the current situation of cryptococcal meningitis in China, the management of cryptococcal meningitis includes 6 aspects: introduction, microorganism identification, clinical manifestations and diagnosis, principles of antifungal therapy, treatment of refractory and recurrent meningitis, treatment of intracranial hypertension. There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis. This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines. The importance of early diagnosis, combined long-term antifungal therapy, control of intracranial hypertension are emphasized.

[Opportunistic infection in systemic lupus erythematosus patients: the disease spectrum and the characteristics of peripheral lymphocyte subsets].

Objective: To investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (SLE). Methods: From December 2013 to December 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated SLE patients with or without opportunistic infections (OIs) . The lymphocyte subsets in healthy donors were used as normal control group. Results: A total of 145 treated SLE patients were enrolled including 108 with OIs and 37 without OIs. The common OIs were cytomegalovirus (CMV) diseases (66/108), Pneumocystis jirovecii pneumonia (PJP, 16/108), other fungal infections (16/108), Epstein-Barr virus (EBV, 15/108) and tuberculosis (14/108). Compared with treated SLE without OIs, total lymphocyte, CD(4+) T, and CD(8+) T lymphocyte counts were significantly reduced in SLE with OIs [1 260 (780, 1 810) cells/µl vs. 565 (399, 1 043) cells/µl, P<0.001; 485 (280, 811) cells/µl vs. 173 (95, 327) cells/µl, P<0.001; 464 (339, 764) cells/µl vs. 265 (158, 424) cells/µl, P=0.003, respectively]. Conclusions: The common OIs in treated SLE patients were CMV diseases, PJP, other fungi, EBV and tuberculosis. OIs are prone to develop in SLE patients with severe lymphocytopenia, especially CD(4+) T cell depletion.

[A clinical analysis of six patients with Brucella endocarditis and literature review].

Objective: To analyze the epidemiology and clinical characteristics of patients with Brucella endocarditis in order to improve the understanding and treatment of Brucella endocarditis. Methods: The clinical data including demographic characteristics, clinical features, laboratory data, echocardiography, treatment and clinical outcome of 6 patients with Brucella endocarditis were collected and analyzed. Results: In our database consisting of 211 brucellosis patients with positive blood culture, 6 patients (2.8%) with Brucella endocarditis were selected from May 2007 to December 2016 in Peking Union Medical College Hospital.The age range was 25-55 years, among whom 5 patients were men.The majority were farmers and all patients reported the history of closely contact with livestock.All of them had fever and 3 of them had arthralgia.Four patients had aortic involvement (4/6) and 2 of them presented with symptoms of left ventricular failure at admission.Blood culture of Brucella and serum agglutination test of Brucella were positive in all of them.Combined antibiotics treatments were given to all patients.Valve replacement surgery was performed in four patients, among them, three patients well recovered, one lost. Among all the patients, four were followed up continually and other two were lost. Conclusions:Brucella endocarditis has a predominance of aortic involvement and is prone to left ventricular failure.Early antibiotic treatment combined with valve-replacement surgery is effective to improve the prognosis.

[HIV antibody detection results in patients seeking medical care in Peking Union Medical College Hospital, 2003-2014].

Objective: To better understand the infection status of HIV in the patients seeking medical care in Peking Union Medical College Hospital. Methods: The HIV detection data of the patients in the hospital from 2003-2014 were collected for a statistical analysis with software SPSS 19.0. Results: A total of 715 421 patients were screened, and 1 012 (0.14%) patients were HIV positive, and HIV infection were confirmed in 776 (0.11%) patients by Western Blot testing. The detection rate of HIV infection increased from 0.05% in 2003 to 0.17% in 2014 (trend χ(2)=66.83 , P=0.000), and the increase during 2012-2014 was obvious. Of the 776 newly diagnosed HIV-infected individuals, 631 (81.31%) were men and 145 (18.69%) were women. The percentage of the males infected with HIV increased from 50.00% to 90.26% (trend χ(2)=58.41, P=0.000). The median age was 36 years (interquartile range: 27-43), and the age group 18-50 years were mostly affected. In the 776 patients infected with HIV, 634 (81.70% ) were infected through sexual contacts, and the proportion of sexual transmissions increased with year (trend χ(2)=126.38, P=0.000). The proportion of infected men who have sex with men (MSM) increased from 0% in 2003 to 53.90% in 2014 (trend χ(2)=11.96, P=0.001), similar to the trend in western countries. The proportion of infected patients who were not married increased from 18.75% to 42.21% (trend χ(2)=43.74, P=0.000). The top three source departments of HIV/AIDS cases were internal medicine (51.03%), emergency room (18.30%) and dermatology (13.53%). The proportion of the HIV/AIDS patients from department of gynecology and obstetrics declined from 18.75% in 2003 to 2.60% in 2014. No HIV/AIDS patients were detected in department of surgery, department of otorhinolaryngology, department of ophthalmology, department of stomatology and health examination center in 2003, but 14 cases (9.10%), 11 cases (7.14%) and 4 cases (2.60%) were detected in these departments respectively in 2014. Conclusion: The HIV detection rate increased with year in Peking Union Medical College Hospital, suggesting the necessity of strengthened HIV test in general hospitals. MSM are the population at high risk, to whom more attention should be paid.

[Risk factors and prognosis of neurological complications in patients with infective endocarditis].

OBJECTIVE: To identify risk factors of neurological complications (NC) in left-sided infective endocarditis (IE) and to assess its impact on the outcome and cardiac surgery. METHODS: Clinical data, NC, treatment and outcome of patients with definite left-sided IE admitted to our hospital during 2001-2012 were retrospectively analyzed. RESULTS: A total of 308 patients with age of (45.3±15.9) years were enrolled. Among them, 65 (21.1%) experienced at least one NC. Independent risk factors associated with NC were large vegetation (HR=1.681, 95%CI 1.013-2.788, P=0.044), non-neurologic embolism (HR=1.820, 95%CI 1.068-3.100, P=0.028), mitral valve involvement (HR=1.888, 95%CI 1.089-3.274, P=0.024), Staphylococcus aureus infection (HR=2.054, 95%CI 1.097-3.846, P=0.044), and uncontrolled infection (HR=4.680, 95%CI 2.563-8.546, P<0.001). During a median follow-up for 17 months, 70 (22.7%) patients died. NC had a negative impact on long-term outcome (HR=2.292, 95%CI 1.274-4.122, P=0.006). Valve replacement surgery was performed in 156(50.6%)patients, which was associated with a lower rate of 1-year IE-related death (HR=0.160, 95%CI 0.063-0.405, P<0.001). Among patients with NC, valve replacement surgery was associated with lower rates of in-hospital mortality and 1-year IE-related mortality (14.8% vs 5.3%, 18.5% vs 73.7%, respectively, P<0.001). CONCLUSIONS: Independent risk factors of NC include large vegetation, non-neurologic embolism, mitral valve involvement, Staphylococcus aureus infection, and uncontrolled infection. Neurologic complications link to the poor prognosis in patients with left-sided IE. Valve surgery is considered as a safe procedure and improves the survival.

[An analysis of immunophenotyping of peripheral lymphocytes in adult patients with infectious mononucleosis and chronic active Epstein-Barr virus infection].

OBJECTIVE: To determine the immunophenotypic features of peripheral lymphocytes in adult patients with Epstein-Barr virus(EBV)-associated infectious mononucleosis(IM) and chronic active EBV infection (CAEBV). METHODS: Eighteen IM patients, 12 CAEBV patients and 18 healthy donors were included. Lymphocyte subsets including CD3(-)CD19(+) B cells, CD3(-)CD16/56(+) NK cells, CD4(+) and CD8(+) T cells in peripheral blood were measured by flow cytometry. The expression of activation markers (HLA-DR and CD38) on CD8(+) T cells and CD28 expression on T cells were also determined. Kruskal-Wallis H and Mann-Whitney U tests were used to compare variables among groups. RESULTS: IM patients had dramatically increased CD8(+) T cell counts than healthy donors (5.22×10(9)/L vs 0.54×10(9)/L, P<0.001). B cell counts moderately reduced in patients with IM than in healthy donors. No difference was found in absolute CD4(+) T cell and NK cell counts between IM and healthy donors. The levels of HLA-DR and CD38 on CD8(+) T cells significantly increased in IM patients compared with those in healthy controls. The intensity of CD28 on CD8(+) T cells significantly decreased, which was not seen on CD4(+) T cells. The median cell counts of B, NK, CD4(+) T and CD8(+) T subsets in CAEBV patients were 0.02×10(9)/L, 0.06×10(9)/L, 0.26×10(9)/L and 0.21×10(9)/L respectively, which were significantly lower than those in healthy donors (0.22×10(9)/L, 0.38×10(9)/L, 0.78×10(9)/L, 0.54×10(9)/L)and IM patients (0.12×10(9)/L, 0.40×10(9)/L, 0.91×10(9)/L, 5.22×10(9)/L). The positive rates of HLA-DR and CD38 on CD8(+) T cells in CAEBV patients were higher than those in healthy controls, but lower than those in IM patients. CONCLUSIONS: The immunophenotypic pattern in adult patients with IM is characterized by a dramatic increase of extensively activated CD8(+) T cells, a moderate reduction of CD19(+) B cells and no significant change of CD4(+) T cells and CD16/56(+) NK cells. CAEBV is featured by an immunosuppression status as demonstrated by significantly decreased B, NK, CD4(+) T and CD8(+) T subsets.

Optimal ileocolic flap length for a reconstructed voice tube after laryngopharyngectomy.

BACKGROUND: Voice restoration after laryngopharyngectomy can be achieved with an autologous ileocolic flap. We have observed that the length of the flap influences vocal outcome. This investigation aimed to evaluate the association between ileocolic flap length and vocal quality after laryngopharyngectomy. METHODS: The charts of patients who underwent voice rehabilitation with an ileocolic flap after laryngopharyngectomy between 1 January 2011 and 30 December 2012 were abstracted. The length of ileum segment in the ileocolic flap was stratified, and voice outcome was evaluated three months post-operatively, while adjusting for confounding variables. RESULTS: There was a significant association between flap length and loudness, maximum phonation time and sound pressure level (p < 0.05). All three parameters were best in the 10 cm length group. CONCLUSION: Voice rehabilitation after laryngopharyngectomy is possible with an ileocolic flap. The optimal ileocolic flap contains a 10 cm ileum segment. Complications are frequent but amenable to revision surgery.

The influence of tumour resection on angiostatin levels and tumour growth--an experimental study in tumour-bearing mice.

The phenomenon of primary neoplasms inhibiting the growth of their metastatic lesions is thought to be related to endogenous angiogenesis inhibitors. The aim of this experiment was to investigate the influence of tumour resection on angiostatin levels and tumour growth using a tumour-bearing mouse model. A primary Lewis lung cancer tumour model was established in C57BL/6 mice and these mice were divided into two groups 10 days after the tumour cells were inoculated. In the surgical resection group (S group) the tumour was resected, but in the control group (C group) a sham operation was performed. The level of angiostatin in the sera was analysed 5 days after the operation by western blotting. To observe tumour growth, four Lewis lung cancer models were established in these mice from both the S and C groups. An immunohistochemical analysis of the tumour tissues was conducted to estimate the proliferation and apoptotic rates of the tumour cells, as well as the amount of neoangiogenesis in the tumours. Angiostatin was observed in the tumour-bearing mice, but disappeared within 5 days after the tumour had been resected. Increased tumour growth was observed in all of the tumour models in the S group compared with the C group and the differences were significant. A significantly higher intratumour vessel density and proliferation cell index, but a significantly lower apoptotic index were also found in the S group compared with the C group. These findings demonstrated that angiostatin was generated directly from the tumour tissue. Furthermore, tumour resection accelerates the growth of other tumours and this is probably related to multiple factors including increased neoangiogenesis, increased tumour cell proliferation, and decreased apoptosis.

Digitonin enhances the antitumor effect of cisplatin during isolated lung perfusion.

BACKGROUND: The antitumor effect of isolated lung perfusion with cisplatin was limited because the intracellular platinum concentration did not increase sufficiently. To solve this problem, digitonin, a detergent, was chosen to increase cell permeability and enhance intracellular uptake and antitumor effect. This study was designed to investigate toxicity, pharmacokinetics, and efficacy of isolated lung perfusion with the combined use of digitonin and cisplatin in Fischer 344 rats. METHODS: Systemic and local toxicities of isolated lung perfusion treatment were evaluated on the basis of body weight change, survival rate, and histologic findings. The maximal tolerated dose of digitonin was determined by assessing survival on day 21 after contralateral pneumonectomy, body weight change, and histologic findings. Pharmacokinetics were observed in a solitary lung tumor nodule model by measuring platinum concentration in tumor and normal lung tissue. The antitumor effect was evaluated by the number of tumor nodules in the left lung 21 days after isolated lung perfusion. Isolated lung perfusion was performed 7 days after 1.0 x 10(6) methylcholanthrene sarcoma cells were injected into the external jugular vein. RESULTS: The maximal tolerated dose of digitonin was 20 micromol/L. Platinum concentration of tumor nodules in the digitonin-cisplatin-treated rats was 20% higher than in the cisplatin-only group (5.48 +/- 0.64 microg/g tissue versus 4.50 +/- 1.09 microg/g tissue; p = 0.067). The number of pulmonary nodules decreased significantly by digitonin use (1.3 +/- 1.5 versus 9.7 +/- 2; p < 0.0001). CONCLUSIONS: Isolated lung perfusion with digitonin and cisplatin in combination was performed safely and enhanced the antitumor effect. These drugs in combination show promise for enhancing the effect of clinical isolated lung perfusion.

Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results.

A new therapy for severe ischemic heart disease has been developed; therapeutic angiogenesis induced by the local implantation of autologous bone marrow cells (BMC). After confirming that no detrimental changes were induced by this treatment in a canine heart model, a clinical trial was commenced in 1999. Thus far, 5 patients have been given this new treatment concomitant with coronary artery bypass grafting and all have been followed up for at least 1 year. Autologous BMC were implanted into the ungraftable area and postoperative cardiac scintigraphy showed specific improvement in coronary perfusion in 3 of the 5 patients. Postoperative chest radiography, electrocardiography, echocardiography and blood tests did not reveal any detrimental changes. In conclusion, this new therapy appears to be safe and could provide a treatment option for patients with otherwise untreatable ischemic heart disease.

The induction of angiogenesis by the implantation of autologous bone marrow cells: a novel and simple therapeutic method.

BACKGROUND: Bone marrow contains many kinds of primitive cells that could differentiate to endothelial cells and secrete several growth factors. In the current study, we attempted to induce therapeutic angiogenesis by implanting autologous bone marrow cells (BMCs) and using a rat ischemic hind limb model. METHODS: BMCs were prepared by removing red blood cells. A rat ischemic hind limb model was made by the ligation of the left femoral artery and its branches. BMCs were injected into 7 points of the ischemic muscles. To assess angiogenesis, a microangiogram, laser Doppler, and histologic evaluation were performed after the surgical procedure. RESULTS: A microangiogram and histologic evaluation showed that angiogenesis was significantly induced in the ischemic hind limb by the implantation of BMCs. Laser Doppler imaging analysis showed that blood flow was significantly increased after implantation of BMCs. Some implanted BMCs were stained positively with CD31 and vascular endothelial-cadherin (VE-cadherin), which might have been incorporated into the vasculature. The condition of ischemia caused an elevation in the level of basic fibroblast growth factor in the ischemic muscle and also in interleukin-1beta derived from the implanted BMCs, which might contribute to angiogenesis. CONCLUSION: These findings indicate that autologous bone marrow implantation may be a novel and simple method for inducing therapeutic angiogenesis.

Increasing drug concentration in a rat lung tumor model by combining isolated lung perfusion with hypertensive chemotherapy.

Isolated left lung perfusion (ILP) with cisplatin was performed in Fisher 344 rats. Before perfusion, bolus injection with endothelin was given via the pulmonary artery. The vasoconstrictive potency was estimated by monitoring the perfusion pressure. The toxicity was estimated by tracking body weight change, survival rate after right pneumonectomy, arterial blood gas analysis and histological findings. To observe the pharmacokinetic changes, a solitary Methylcholanthrene-induced sarcoma model was established in a rat lung and the total platinum concentration in perfused lung and tumor tissues was measured. Perfusion pressure was increased significantly in a dose-dependent manner. Pulmonary toxicity from ILP with cisplatin was limited by the use of endothelin. Significantly higher levels of total platinum were obtained in tumors but not in normal lung tissues by endothelin injection before ILP than by ILP alone. The combination of ILP and hypertensive chemotherapy should be one of the available treatments for unresectable pulmonary carcinoma.

Digitonin enhances the anti-tumor effect of cisplatin against methylcholanthrene-induced rat sarcoma cells in vitro.

BACKGROUND: This study was designed to evaluate cellular uptake and cytotoxicity of cisplatin in methylcholanthrene (MCA)-induced rat sarcoma cells when used in combination with a detergent, digitonin. MATERIALS AND METHODS: In the cellular intake study, after MCA sarcoma cells (10(7)) were treated with cisplatin alone (50 micrograms/ml) and with cisplatin (50 micrograms/ml) in combination with digitonin at 20 microM and 50 microM, the cells were washed twice with PBS and the platinum levels were measured by flameless atomic spectrometry. For the anti-tumor effect MCA sarcoma cells (10(3)) were seeded in cell culture dishes and loaded for 10 minutes with PBS, digitonin (5 microM), cisplatin (5 micrograms/ml) or a combination of cisplatin (5 micrograms/ml) and digitonin (5 microM). The cells were then washed and incubated for 72 hours. Bromodeoxyuridine uptake was measured with an ELISA system for determining viable cells counts. RESULTS: Cell platinum levels were significantly elevated in proportion to the increase of digitonin (p < 0.0001). The number of viable cells was significantly decreased with, the combined cisplatin (5 micrograms/ml)--digitonin (5 microM) treatment (p < 0.0001 CONCLUSION: Digitonin enhances the antitumor effect of cisplatin against methylcholanthrene-induced rat sarcoma in vitro.