Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases

Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.

Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome

AIM：To compare the clinical manifestation of cytomegalovirus（CMV）retinitis and microvascular retinopathy（MVR）in patients with acquired immunodeficiency syndrome（AIDS）in China.METHODS：A total of 93 consecutive patients with AIDS,including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed.Highly active antiretroviral therapy（HAART）status was recorded.HIV and CMV immunoassay were also tested.CD4＋T-lymphocyte count and blood CMV-DNA test were performed in all patients.Aqueous humor CMV-DNA test was completed in 39patients.Ophthalmological examinations including best corrected visual acuity（BCVA,by International Standard Vision Chart）,intraocular pressure（IOP）,slit-lamp biomicroscopy,indirect ophthalmoscopy were performed.RESULTS：In MVR group,the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13.Blood CMV-DNA was 0（0,269 000）and 42 patients（80.77%）did not receive HAART.In CMV retinitis group,13 patients（31.71%）had anterior segment abnormality.The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470（0,1 450 000）.Nineteen patients（46.34%）had not received HAART.MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%,respectively.Two patients with MVR progressed to CMV retinitis during the follow-up period.CONCLUSION：In comparison of CMV,patients with MVR have relatively mild visual function impairment.Careful ophthalmological examination and close follow-up are mandatory,especially for patients who have systemic complications,positive CMV-DNA test and without received HAART.

Human immunodeficiency virus/acquired immune deficiency syndrome: Using drug from mathematical perceptive

Entry of acquired immune deficiency syndrome virus into the host immune cell involves the participation of various components of host and viral cell unit. These components may be categorized as attachment of the viral surface envelope protein subunit, gp120, to the CD4+ receptor and chemokine coreceptors, CCR5 and CXCR4, present on T cell surface. The viral fusion protein, gp41, the second cleaved subunit of Env undergoes reconfiguration and the membrane fusion reaction itself. Since the CD4+ T cell population is actively involved; the ultimate outcome of human immunodeficiency virus infection is total collapse of the host immune system. Mathematical modeling of the stages in viral membrane protein-host cell receptor-coreceptor interaction and the effect of antibody vaccine on the viral entry into the susceptible host cell has been carried out using as impulsive differential equations. We have studied the effect of antibody vaccination and determined analytically the threshold value of drug dosage and dosing interval for optimum levels of infection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that systematic drug dosage of the immune cells leads to longer and improved lives.

Drug-induced erythroderma in patients with acquired immunodeficiency syndrome

BACKGROUND: To explore the clinical manifestations, diagnosis, and treatment of patients with acquired immunodeficiency syndrome(AIDS) complicated with drug-induced erythroderma.METHODS: The clinical data of 12 AIDS patients with drug-induced erythroderma in our hospital were retrospectively analyzed. The general information, offending medications, complications, modified severity-of-illness score for toxic epidermal necrolysis(SCORTEN) scores, and disease outcome spectrums were analyzed.RESULTS: Drug-induced erythroderma was mostly caused by antiviral drugs, antituberculosis drugs, antibiotics, traditional Chinese medicine, and immune checkpoint inhibitors. The spectrum of sensitizing drugs was broad, the clinical situation was complex, and infections were common. The affected areas were greater than 40% body surface area in all patients. The modified SCOTERN score averaged 3.01±0.99. All patients were treated with glucocorticoids, and nine patients were treated with intravenous immunoglobulin(IVIG) pulse therapy at the same time. The average time to effectiveness was 7.08±2.23 days, and the average hospital stay was 17.92±8.46 days. Eleven patients were cured, and one patient died of secondary multiple infections, who had a modified SCORTEN score of 5 points. The mortality rate in this study was 8.3%.CONCLUSIONS: The clinical situation of AIDS patients with drug-induced erythroderma in hospitalized patients is complex and the co-infection rate is high. The use of modified SCORTEN score may objectively and accurately assess the conditions, and the use of glucocorticoid combined with IVIG therapy may improve the prognosis.

Chronic hepatitis B-associated liver disease in the context of human immunodeficiency virus co-infection and underlying metabolic syndrome

Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.

Identification of novel biomarkers for adult-onset-immunodeficiency(AOID)syndrome using serum proteomics

Objective:To identify the candidate protein biomarkers of adult-onset-immunodeficiency(AOID) syndrome using serum proteomics. Methods:Screening and verification phases were performed in the study. A total of 97 serum samples were classified into three groups:AOID patients with opportunistic infections(active AOID),AOID patients without opportunistic infections(inactive AOID),and healthy control. In the screening phase,pooled sera collected from patients and healthy control in each group were separated by 2D-gel electrophoresis,analyzed for differentially expressed proteins and identified for biomarkers using LC/MS. In the verification phase,the protein candidates were selected for confirmation by western blotting. Results:The analysis revealed 35 differentially expressed proteins. Three proteins including haptoglobin,gelsolin,and transthyretin,were selected for verification. The results showed that the levels of haptoglobin in both active and inactive AOID groups were significantly higher than that in the control group,while the levels of gelsolin in the active AOID group were significantly lower than that in the inactive AOID group. The level of transthyretin in the active AOID group was also significantly lower than that in the control group. Conclusions:The comparison of serum proteins between the three groups revealed three candidates which are related to chronic inflammatory diseases. Haptoglobin and transthyretin biomarkers could be applied in clinical assessment for monitor of disease outcome,including for the study of AOID pathogenesis.

An Evans Syndrome Case Expressing Anti-Jk^aAutoantibody under Condition of Primary IgA Immunodeficiency

Autoimmune haemolytic anaemia is a haemolytic disease resulting from an autoimmune reaction to the surface of red blood cells. A part of autoantibody is known to react with the blood type antigen. This is the case of a 14 years old female with Evans syndrome in which autoimmune haemolysis may cause from anti-Jka autoantibody reaction. As this case is complicated with primary IgA immunodeficiency syndrome, anti-Jka autoantibody may occur under the condition of primary immunodeficiency status, in which autoantibody production is accelerated. Considering the co-occurrence of autoimmune haemolytic anaemia and primary IgA immunodeficiency syndrome, analysis focusing on specificity for red blood cells antigens will be required in IgA immunodefi-ciency syndrome patients.

Differential Diagnosis and Association of Acquired Immunodeficiency Syndrome and Systemic Erythematous Lupus: A Brief Review

Acquired immunodeficiency syndrome and lupus erythematosus are multisystem diseases that can affect several organs and systems at different stages of disease evolution. Both diseases share common clinical manifestations, which may lead to diagnostic difficulties, especially at the onset of the disease. Another additional challenge is when there is an association of the two pathologies. The objective of this brief review is to describe the clinical manifestations of the diseases and to make considerations regarding the moment of onset of symptoms. Knowledge of these common manifestations and their peculiarities may alert clinicians to possible diagnoses and avoid errors in the evaluation and conduction of these patients.

Improvement in human immunodeficiency virus-1/acquired immune deficiency syndrome patients' well-being following administration of “Phyto V7”

AIM:To corroborate the capacity of Phyto V7,a complex of phytochemicals,to improve the physical well-being of human immunodeficiency virus-1(HIV-1) infected and acquired immune deficiency syndrome(AIDS) patients not undergoing antiretroviral treatment.METHODS:Two hundred and thirty nine HIV-1 seropositive male and female voluntary inmates were recruited through the Uruguay National Program of AIDS.The study participants received for 90 consecutive days every eight hours two tablets(760 mg/each) of Phyto V7,containing a mix of the following phytochemicals:flavonols(Kaempferol,Quercetin),flavones(Apigenin,Luteolin),hydroxycinnamic acids(ferrulic acid),carotenoids(Lutein,Lycopene,Beta carotene) and organosulfur compounds,all from vegetal origin.The participants did not receive any antiretroviral treatment during the study.At days 0,30,60 and 90(± 2 d) the participants were evaluated for body mass index(BMI),tolerance to Phyto V7 and Index of Quality of Life based on the Karfnosky scale.ANOVA,Tukey Post-test,χ2 test and Wilcoxon Signed Rank test were used to analyze the effect of treatment.RESULTS:One hundred and nighty nine study participants finished the study.Already after 30 d of Phyto V7 consumption,the weight,BMI and Karnofsky score statistically significantly improved(P < 0.001),and continued to improve until the end of the study.The mean weight gain per participant during the 90 d wasof 1.21 kg(approximately 2% of body weight).The overall increase in the mean Karnofsky score after 90 d was 14.08%.The lower the BMI and Karnofsky score of the participants were at the beginning of the study,the more notorious was the improvement over time.For example,the mean increment of Index of Quality of Life,among the participants with an initial Karnofsky score of 5 or below(n = 33) from day 0 to day 90,was of 35.67%(0.476 ± 0.044 vs 0.645 ± 0.09; P < 0.001).The tolerability to Phyto V7 was very good and no adverse reactions were recorded or reported.CONCLUSION:Administration of the Phyto V7 can be an important tool to improve the well-being of HIV-1 seropositive individuals and AIDS patients,not undergoing antiretroviral treatment.

Investigation of perceived stigma among people living with human immunodeficiency virus/ acquired immune deficiency syndrome in Henan Province, China

Purpose:To investigate the level of and factors influencing perceived stigma and discrimination among people living with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(PLWHA)in Henan Province.Methods:In total,161 PLWHA from Zhengzhou and Zhenping were investigated using the Berger HIV stigma scale.Results:The mean Berger stigma scale score was 105.70±15.20,indicating a middle stigma level.Among the four subscales of the Berger stigma scale,the disclosure concerns score was highest,while the negative self-image score was lowest.Multivariate analyses showed that factors influencing perceived HIV stigma included the level of education and route of infection.Conclusion:The level of perceived HIV stigma and discrimination among PLWHA in Henan Province is moderate and was affected by the level of education and route of infection.Special intervention should be established to address this problem.

Salivary gland disease in human immunodeficiency virus/acquired immunodeficiency syndrome: A review

The effect of human immunodeficiency virus(HIV) infection on salivary glands has diagnostic and prognostic significance. HIV-salivary gland disease(HIV-SGD) is comprehensively ascertained amongst the major critical acquired immunodeficiency syndrome(AIDS)-relatedoral manifestation and causes substantial morbidity. Parotid gland swelling due to sicca syndrome, parotid lipomatosis, sialadenitis, diffuse infiltrative lymphocytosis syndrome, benign lymphoepithelial lesions, neoplasms(benign or malignant) of salivary gland, parotid gland inflammation, diminished flow rates of saliva and xerostomia have been documented that also affects the health- associated characteristics of life in subjects infected with HIV. There is a necessity for health care researchers to diagnose it, particularly as it might worsen if left undiagnosed. The precise characteristic of alterations in dynamics of salivary gland structure and functionality with long-standing usage of highly active anti-retroviral therapy still remains unknown. HIV positive children also present with bilateral parotid enlargement and the syndrome state with classical clinical and cytological features of predominated lymphoid hyperplasia. Though various case reports and studies have been extensively published on different aspects of HIV-SGD, it has not been described solely, thus leading to occasional confusion of nomenclature and clinical presentation of HIV-SGD. This article reviews the pathogenesis of HIV-related SGD and its components and various other miscellaneous disorders affecting the salivary glands in HIV/AIDS.

Epidemiological characterization and geographic distribution of human immunodeficiency virus/acquired immunodeficiency syndrome infection in North African countries

BACKGROUND Human immunodeficiency virus(HIV)infection is a major global public health concern.North African countries carry a disproportionate burden of HIV representing one of the highest rates in Africa.AIM To characterize the epidemiological and spatial trends of HIV infection in this region.METHODS A systematic review was carried out on all the published data regarding HIV/acquired immunodeficiency syndrome in North African countries over ten years(2008-2017)following the PRISMA guidelines.We performed a comprehensive literature search using Medline PubMed,Embase,regional and international databases,and country-level reports with no language restriction.The quality,quantity,and geographic coverage of the data were assessed at both the national and regional levels.We used random-effects methods,spatial variables,and stratified results by demographic factors.Only original data on the prevalence of HIV infection were included and independently evaluated by professional epidemiologists.RESULTS A total of 721 records were identified but only 41 that met the criteria were included in the meta-analysis.There was considerable variability in the prevalence estimates of HIV within the countries of the region.The overall prevalence of HIV ranged from 0.9%[95%confidence interval(CI)0.8-1.27]to 3.8%(95%CI 1.17-6.53).The highest prevalence was associated with vulnerable groups and particularly drug abusers and sexually promiscuous individuals.The dense HIV clustering noted varied from one country to another.At least 13 HIV subtypes and recombinant forms were prevalent in the region.Subtype B was the most common variant,followed by CRF02_AG.CONCLUSION This comprehensive review indicates that HIV infection in North African countries is an increasing threat.Effective national and regional strategies are needed to improve monitoring and control of HIV transmission,with particular emphasis on geographic variability and HIV clustering.

^(99m)Tc-ECD brain SPECT imaging in patients with acquired immunodeficiency syndromes

In order to investigate the changes of regional cerebral blood flow(rCBF) in patients with acquired immunodeficiency syndromes (AIDS), 99mTc-ECDbrain SPECT imaging was performed in 5 patients with AIDS and 16 sex and agematched normal controls, and the rCBF percentages compared to the cerebellum werecalculated using a semi-quantitative processing software. Hypoperfusions in the rightand left frontal, temporal, porietal lobe, basal ganglia and left thalamus were seen in1 patient with dementia. Hypoperfusions in the right and left frontal and temporallobe were seen in 4 asymptomatic patients. The rCBF in the right and left frontal.temporal, porietal lobe, basal ganglia and thalamus, front and pons were decreasedsignificantly in patients with AIDS than those of the control subjects (p ＜0.005). Itis concluded that there exists reduced cortico-subcortical rCBF in AIDS patients.

Human immunodeficiency virus patients with low CD4 counts are more likely to have precancerous polyps identified during index colonoscopy

BACKGROUND Antiretroviral treatment(ART)has improved the life expectancy of patients living with human immunodeficiency virus(HIV).As these patients age,they are at increased risk for developing non-acquired immunodeficiency syndrome defining malignancies(NADMs)such as colon cancers.AIM To determine which factors are associated with the development of precancerous polyps on screening colonoscopy in patients with HIV and to investigate whether HIV disease status,measured by viral load and CD4 count,might influence precancerous polyp development.METHODS A retrospective review of records at two urban academic medical centers was performed for HIV patients who had a screening colonoscopy between 2005-2015.Patients with a history of colorectal cancer or polyps,poor bowel preparation,or inflammatory bowel disease were excluded.Demographic data such as sex,age,race,and body mass index(BMI)as well as information regarding the HIV disease status such as CD4 count,viral load,and medication regimen were collected.Well-controlled patients were defined as those that had viral load<50 copies,and poorly-controlled patients were those with viral load≥50.Patients were also stratified based on their CD4 count,comparing those with a low CD4 count to those with a high CD4 count.Using colonoscopy reports in the medical record,the size,histology,and number of polyps were recorded for each patient.Precancerous polyps included adenomas and proximal serrated polyps.Data was analyzed using Fisher’s exact tests and logistic regression through SAS 3.8 software.RESULTS Two hundred and seven patients met our inclusion criteria.The mean age was 56.13 years,and 58%were males.There were no significant differences in terms of age,race or ethnicity,insurance,and smoking status between patients with CD4 counts above or below 500.BMI was lower in patients with CD4 count<500 as compared to those with count>500(P=0.0276).In patients with CD4>500,53.85%of patients were female,and 70.87%of patients with CD4<500 were male(P=0.0004).Only 1.92%of patients with CD4≥500 had precancerous polyps vs 10.68%of patients with CD4<500(P=0.0102).When controlled for sex,BMI,and ART use,patients with CD4<500 were 9.01 times more likely to have precancerous polyps[95%confidence interval(CI):1.69-47.97;P=0.0100].Patients taking non-nucleoside reverse transcriptase inhibitors were also found to be 10.23 times more likely to have precancerous polyps(95%CI:1.08-97.15;P=0.0428).There was not a significant difference noted in precancerous polyps between those that had viral loads greater or less than 50 copies.CONCLUSION Patients with low CD4 counts were more likely to have precancerous polyps on their screening colonoscopy although the etiology for this association is unclear.We also found an increased risk of precancerous polyps in patients taking non-nucleoside reverse transcriptase inhibitors,which is contradictory to prior literature showing ART has decreased the risk of development of NADMs.However,there have not been studies looking at colorectal cancer and ART by drug class,to our knowledge.Further prospective studies are needed to determine the effect of HIV control and therapies on polyp development.

The default mode network is affected in the early stage of simian immunodeficiency virus infection:a longitudinal study

Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.

Intracranial infection accompanied sweet’s syndrome in a patient with anti-interferon-γautoantibodies:A case report

BACKGROUND Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma(IFN-γ)autoantibodies(AIGAs).However,it is rare to find AIGAs with intracranial infections.CASE SUMMARY In this case study,we report a case of an AIGAs with intracranial infection and hand rashes considered Sweet’s syndrome.The patient presented to our hospital with a persistent cough,a fever that had been going on for 6 mo,and a rash that had been going on for a week.The patient started losing consciousness gradually on the fourth day after admission,with neck stiffness and weakened limb muscles.The upper lobe of the left lung had a high-density mass with no atypia and a few inflammatory cells in the interstitium.Brain magnetic resonance imaging and cerebrospinal fluid suggest intracranial infection.The pathology of the skin damage on the right upper extremity revealed an infectious lesion that was susceptible to Sweet’s disease.It has an anti-IFN-γautoantibody titer of 1:2500.She was given empirical anti-non-tuberculous mycobacterial and antifungal treatments.The patient had no fever,obvious cough,headache,or rash on the hand.She got out of bed and took care of herself following hospitalization and discharge with medicine.CONCLUSION Adults with severe and recurrent infections of several organs should be considered for AIGAs if no other known risk factors exist.AIGAs are susceptible to subsequent intracranial infections and Sweet’s syndrome.

An Experimental Model for Screening Anti-AIDS Drugs with Bovine Immunodeficiency Virus

The assays for bovine immunodeficiency virus (BIV) induced syncytium formation and BIV long terminal repeat (LTR) directed luciferase (Luc) gene expression were applied to screen and evaluate anti AIDS drugs. Frequency of the syncytium formation and BIV LTR directed Luc activity were in proportion to the number of input BIV infected cells. AZT inhibited the syncytium formation and the BIV LTR directed Luc gene expression level. Its inhibitory effects were dosedependent with the IC 50 being 0.24 and 0.052 mmol / L, respectively.

Treatment of Pneumocystis jirovecii pneumonia in non-human immunodeficiency virus-infected patients using a combination of trimethoprim-sulfamethoxazole and caspofungin

BACKGROUND Pneumocystis jirovecii pneumonia(PJP)is an infectious disease common in immunocompromised hosts.However,the currently,the clinical characteristics of non-HIV patients with PJP infection have not been fully elucidated.AIM To explore efficacy of trimethoprim–sulfamethoxazole(TMP-SMX)and caspofungin for treatment of non-human immunodeficiency virus(HIV)-infected PJP patients.METHODS A retrospective study enrolled 22 patients with non-HIV-infected PJP treated with TMP-SMX and caspofungin from 2019 to 2021.Clinical manifestations,treatment and prognosis of the patients were analyzed.RESULTS Five patients presented with comorbidity of autoimmune diseases,seven with lung cancer,four with lymphoma,two with organ transplantation and four with membranous nephropathy associated with use of immunosuppressive agents.The main clinical manifestations of patients were fever,dry cough,and progressive dyspnea.All patients presented with acute onset and respiratory failure.The most common imaging manifestation was ground glass opacity around the hilar,mainly in the upper lobe.All patients were diagnosed using next-generation sequencing,and were treated with a combination of TMP-SMX and caspofungin.Among them,17 patients received short-term adjuvant glucocorticoid therapy.All patients recovered well and were discharged from hospital.CONCLUSION Non-HIV-infected PJP have rapid disease progression,high risk of respiratory failure,and high mortality.Combination of TMP-SMX and caspofungin can effectively treat severe non-HIVinfected PJP patients with respiratory failure.

Childhood-onset inflammatory bowel diseases associated with mutation of Wiskott-Aldrich syndrome protein gene

AIM To screen primary immunodeficiency,Wiskott-Aldrich syndrome(WAS),and chronic granulomatous disease(CGD) among children with inflammatory bowel disease(IBD).METHODS This was a single-center retrospective study. Eighteen children with IBD were investigated. We analyzed their expression of Wiskott-Aldrich syndrome protein(WASP) in lymphocytes and superoxide generation in phagocytes using flow cytometry. When the expression of WASP or superoxide generation was low or absent,we performed genetic analysis to determine the cause of this. RESULTS Eighteen patients were classified as having ulcerative colitis(n = 10),Crohn's disease(n = 5),or IBDunclassified(n = 3). In total,three patients revealed low expression of WASP associated with a WAS gene c.1378 C>T p.Pro460 Ser mutation,which has previously been reported as a pathogenic mutation in WAS and X-linked thrombocytopenia. However,with respect to the major symptoms of WAS,none of these three patients showed either thrombocytopenia or increased susceptibility to infection,but one patient showed generalized eczema. No CGD patients were discovered in this study.CONCLUSION Despite the lack of typical clinical manifestations of WAS,low expression of WASP could be associated with the pathogenesis of a subtype of IBD patients.

Human Immunodeficiency Virus Infection-Associated Mortality during Pulmonary Tuberculosis Treatment in Six Provinces of China

Objective To investigate the risk factors attributable to tuberculosis-related deaths in areas with human immunodeficiency virus（HIV） infection epidemics. Methods A prospective cohort study of newly registered patients in tuberculosis（TB） dispensaries in six representative Chinese provinces was conducted from September 1, 2009 to August 31, 2011. Risk factors for TB-associated death were identified through logistic regression analysis. Results Of 19,103 newly registered pulmonary TB patients, 925（4.8%） were found to be HIV-positive. Miliary TB and acid-fast bacillus smear-negative TB were more common among these patients. Out of a total of 322（1.7%） deaths that occurred during TB treatment, 85（26%） of the patients were co-infected with HIV. Multivariate analysis revealed that HIV infection was the strongest predictor of death [adjusted odds ratio（aO R） 7.86]. Other significant mortality risk factors included presentation with miliary TB（aO R 4.10; 95% confidence interval： 2.14-7.88）, ≥35 years of age（aO R 3.04）, non-Han ethnicity（aO R 1.67）, and farming as an occupation（aO R 1.59）. For patients with TB/HIV co-infection, miliary TB was the strongest risk factor for death（aO R 5.48）. A low CD4 count（≤ 200 cells/μL）（aO R 3.27） at the time of TB treatment initiation and a lack of antiretroviral therapy（ART） administration（aO R 3.78） were also correlated with an increased risk of death. Conclusion Infection with HIV was independently associated with increased mortality during TB treatment. Offering HIV testing at the time of diagnosis with TB, early TB diagnosis among HIV/acquired immunodeficiency syndrome patients, and the timely provision of ART were identified as the key approaches that could reduce the number of HIV-associated TB deaths.