Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected patients in the HAART era?

Purpose

The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors.

Methods

We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry.

Results

We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89–32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13–17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77–19.96). HAART receipt was not associated with respiratory symptoms nor with COPD.

Conclusions

We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.     

Hypogonadism in patients with sickle cell disease: central or peripheral?

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism.     

Hepatitis E: an emerging infectious disease in Germany?

Increased frequencies of HEV infections have been reported in several industrialized countries. We suggest that this finding might be explained by a better awareness of the disease and not by an increased incidence. Although reported HEV infections increased more than 6-fold in Germany in recent years, the seroprevalence remained unchanged (2 %).     

Peripheral T-cell lymphoma with a T follicular-helper phenotype: A different entity? Results of the Spanish Real-T study

Nodal peripheral T-cell lymphoma (PTCL) with a T follicular helper phenotype (PTCL-TFH) is a new type of PTCL. We aimed to define its clinical characteristics and prognosis compared to PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). This retrospective observational study included 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. Patient diagnosis was centrally reviewed, and patients were reclassified according to the World Health Organization (WHO) 2016 criteria: 21 patients as PTCL-NOS, 55 as AITL and 23 as PTCL-TFH. Median follow-up was 56.07 months (95% CI 38.7–73.4). Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with PTCL-TFH than in those with PTCL-NOS and AITL (PFS, 24.6 months vs. 4.6 and 7.8 months, respectively, p = 0.002; OS, 52.6 months vs. 10.0 and 19.3 months, respectively, p < 0.001). Histological diagnosis maintained an independent influence on both PFS (hazard ratio [HR] 4.1 vs. PTCL-NOS, p = 0.008; HR 2.6 vs. AITL, p = 0.047) and OS (HR 5.7 vs. PTCL-NOS, p = 0.004; HR 2.6 vs. AITL, p = 0.096), regardless of the International Prognostic Index. These results suggest that PTCL-TFH could have more favourable features and prognosis than the other PTCL subtypes, although larger series are needed to corroborate these findings.     

Peripheral blood stem cell contamination in mantle cell non-Hodgkin lymphoma: the case for purging?

Intensification using peripheral blood stem cells collected after chemotherapy followed by growth factors is being increasingly investigated as an alternative to conventional chemotherapy for mantle cell non-Hodgkin lymphoma. We investigated 14 grades III-IV, t(11;14)-positive cases for contamination of PBSC collected after a polychemotherapy regimen followed by G-CSF. Patients were first treated with a polychemotherapy regimen. There were four CR, seven PR, two refractory and one early death. Seven patients have been transplanted, in whom PBSC were mobilized, using either cyclophosphamide/VP16 or Dexa-BEAM followed by G-CSF. For all patients, whether actually autografted or not, PB cells were tested at the time of regeneration on G-CSF after the first polychemotherapy or after the mobilizing regimen. PCR evaluation of contamination was performed first by a semi-quantitative approach, using serial dilutions of initial DNA, then confirmed using a limiting-dilution analysis. Two patients were not informative (one early death and one without an available molecular marker). PB cells collected at regeneration contained at least one log more lymphoma cells than steady-state blood or marrow, apart from in two cases. Moreover, where a mobilizing treatment diminished tumor burden in the patient, at the same time it increased PB contamination in most cases. We conclude that advanced mantle cell NHL appears to be largely resistant to significant in vivo purging by conventional chemotherapy. Where treatment brings benefits by reducing tumor load, it may at the same time negate it by mobilizing malignant cells into the collections used to intensify. Although the clonogenic potential of this massive infiltration is unknown (only gene marking studies could provide a definitive answer regarding the source of relapses), strategies aimed at reducing the level of contamination in the graft should be considered when designing future protocols.     

Is there an increased risk for cardiovascular disease in HIV-infected patients on antiretroviral therapy?

There is a growing concern about an increased risk for cardiovascular disease in HIV infected patients receiving antiretroviral therapy (ART). This risk could be related to metabolic abnormalities associated with long-term use of antiretroviral drugs. In fact, well recognized cardiovascular risk factors such as hypertension, dyslipidaemia, diabetes mellitus and central fat deposition are increasingly seen in HIV patients on ART. These factors can also be associated with non reversible risk factors, such as male sex, age greater than 40 years and family history of premature coronary artery disease. In addition, cigarette smoking and sedentary lifestyle may predispose these patients to significant cardiovascular disease. A direct atherogenic effect of HIV infection itself or antiretroviral drugs is unlikely. Epidemiological studies have suggested an increased risk for coronary artery disease in HIV infected persons; nevertheless, only long term follow-up could confirm this statement. Despite these uncertainties, it seems reasonable to identify and manage cardiovascular risk factors in HIV infected patients.     

Should HIV-positive patients with lymphoma be offered stem cell transplants?

Advances in effective antiretroviral therapy for HIV infection have made high-dose therapy and autologous stem cell transplantation possible in patients with HIV-associated lymphomas. Regimen-related toxicity is not significantly increased when antiretroviral therapy is combined with high-dose chemoradiotherapy. Durable engraftment can be seen with autologous stem cell rescue. Infectious complications can be managed with a combination of surveillance and prophylaxis. Long-term remissions of these high-risk lymphomas can be achieved with this approach. This suggests that patients with HIV-associated lymphomas should be considered for autologous transplantation in a manner similar to HIV-negative lymphoma patients.     

The subclinic autonomic dysfunction in patients with Beh?et disease: an electrophysiological study

Studies that have evaluated autonomic nervous system (ANS) function in Beh?et disease (BD) are rare and have indicated conflicting results with different degrees of involvement. The aim of this study was to investigate ANS function by using electrophysiological tests in patients with BD and to determine the relationship between the disease activity parameters and the indicators of autonomic activity. We included 70 BD patients and 50 healthy controls. Demographic characteristics including age, sex, and disease duration were recorded. A detailed neurological examination was performed, and clinical autonomic symptoms were recorded. The Beh?et Disease Current Activity Form (BDCAF) was used to determine the disease activity. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were determined for laboratory activity. The electrophysiological assessments of ANS function were performed by sympathetic skin response (SSR) and R-R interval variation (RRIV) tests. The mean values of sympathetic (SSR latency and amplitude) and parasympathetic (RRIV at rest [R%] and deep breathing [D%], D% − R%, and D%/R%) parameters were compared, and any correlations between ANS parameters and clinical disease characteristics were determined. Seventy BD patients (23 males, 47 females) with a mean age of 41.2 ± 10.01 years and 50 control subjects (18 males, 32 females) with a mean age of 39.5 ± 8.94 years were included in the study. All the subjects were totally symptom free with respect to ANS involvement, and the subjects in both groups had normal neurological examination findings. The demographic characteristics were similar between the groups. The mean latency of SSR was increased (1.4 ± 0.4 vs 0.7 ± 0.8), and R% (0.3 ± 0.3 vs 0.5 ± 0.4) and D% (0.3 ± 0.3 vs 0.6 ± 0.5) values were decreased in BD patients compared to control subjects. No correlation was found between BDCAF scores and ANS variables. However, there was a significant correlation between SSR latency and ESR and CRP values (p < 0.01, r = −0.25, r = −0.31, respectively) in the patient group, indicating a more sympathetic dysautonomia in patients with active laboratory parameters. In conclusion, our study indicates a subclinical sympathetic and parasympathetic autonomic dysfunction in patients with BD, which may be related with disease activity. As the early recognition of abnormalities in ANS may be very important in order to prevent excessive morbidity, simple electrophysiological methods are suggested to identify Beh?et patients at high risk for symptomatic dysautonomia.     

Cholesterol crystal embolism syndrome in dialysis patients: an emerging clinical diagnosis?

BACKGROUND: Cholesterol crystal embolism syndrome (CCE) is an increasing end-stage renal disease cause. Few cases have been described on dialysis, despite the high prevalence of the predisposing factors. METHODS: The diagnostic criteria of the present study were: skin lesions, myalgia, fatigue, fever and acute inflammatory serologic signs, in the presence of severe vasculopathy. The precipitating factors were: anticoagulation, endovascular intervention and ulcerated atherosclerotic plaque. RESULTS: Between October 2003 and September 2005, CCE was diagnosed in 6 dialysis patients (of 200-210 on chronic treatment): 5 males, 1 female, median age 59.5 years (47-70) and end-stage renal disease follow-up 11.5 years (3-25). All had severe vasculopathy, 5 cardiopathy, and 4 were failed graft recipients. The treatment included: peritoneal dialysis, daily dialysis, 'conventional' hemodialysis (2 cases) and hemodiafiltration. The diagnosis was based on the clinical-laboratory picture in 1 patient. In the 5 others clues were present (dicumarol therapy, angioplasty, femoral artery thrombosis, CCE predialysis and ulcerated aortic plaque). The therapeutic approach consisted of corticosteroids (5 cases), statins (4 cases) and prostaglandin analogues (4 cases). CONCLUSION: The differential diagnosis of CCE should also be considered in dialysis patients (necrotic lesions, limb pain and vasculitis-like signs).     

Is chemotherapy scoring useful to predict progenitor cell mobilisation in patients with non-Hodgkin's lymphoma?

About 10-30% of patients with non-Hodgkin's lymphoma (NHL) intended to receive high-dose therapy are difficult to mobilise. Damage to the stem cell pool caused by previous chemotherapy may be an important factor in predicting progenitor cell mobilisation. We have analysed associations between chemotherapy score and efficiency of progenitor cell mobilisation in 120 consecutive NHL patients mobilised with intermediate-dose cyclophosphamide (4 g/m(2)) plus G-CSF. The original chemotherapy scoring system proposed by Drake et al was applicable in only 27% of our patients and was not predictive for mobilisation outcome. Therefore we made an improved scoring system for previous chemotherapy by adding new drugs. Altogether, 111 patients (93%) could be scored. Our chemotherapy score showed an inverse correlation with the peak blood CD34(+) count measured after the mobilisation (r=-0.214, P=0.024) and with the number of CD34(+) cells collected (r=-0.234, P=0.02). However, in the receiver operating characteristics curve, no threshold value could be detected for chemotherapy score predicting mobilisation failure. Thus, both the original scoring system as well as our more widely applicable scoring system seem to be of limited value in predicting progenitor cell mobilisation in patients with NHL.     

Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson disease

AIM:To determine the mutational characterization of P-type ATP7B gene and to explore the correlation of ATP7Bgenotype to phenotype in Chinese patients with Wilsondisease(WD).METHODS:Seventy-five patients with WD from 72 no-kinshipfamilies,44 males and 31 females,were enrolled in this study.The age of onset ranged from 4 to 39 years,≤18 years in72 patients.Some exons of ATP7B gene mutations wereanalyzed in patients with WD by using biochemical methods,polymerase chain reaction-single strand configurationpolymorphism(PCR-SSCP)and DNA sequence analysis.Atotal of 778 coding regions were identified with restrictionenzyme Msp I.The activity of Cu-ATPase was assessed bymeasuring inorganic phosphorus.RESULTS:Sixty-six of 75 patients(88%)had with hepaticmanifestations,39 of them had only hepatic manifestations,27 patients had hepatic and neurological manifestations orother symptoms at the same time(16 patients had associatedneurological manifestation,3 patients had osteopathy,8patients had other symptoms).Eight of the 75 patients(10.7%)had only neurological symptoms,one patient(5 yearsold)had no symptom.Twelve changing patterns were detectedin ATP7B gene by DNA sequencing,including seven mutations(R778L,C656X,G943D,V1140A,V1106I V1216M and1384del17),six polymorphisms(IVS4-5t/c,A2495G,C2310G,IVS18 6c/t and IVS20 5a/g).R778L occurred in 49/66patients(74%)with hepatic manifestations,homozygosisof R778L in 16 patients,heterozygosity of R778L in 33patients.V1106I mutation of ATP7B gene occurred in 2patients with delaying onset of clinical symptoms.Cu-ATPaseactivity of three patients with known mutations(R778L/V1106I/A2495G,R778L/V1216M and R778L/R778L)weredetermined;and the activity of Cu-ATPase was decreasedby 44.55%,88.23% and 69.49% respectively.CONCLUSION:1384de117bp is a novel mutation found in WD patients.R778L is the most common mutation of ATP7Bgene.There is a correlation between R778L and hepaticmanifestations in WD patient.     

Impaired B-cell reconstitution in lymphoma patients undergoing allogeneic HSCT: an effect of pretreatment with rituximab?

Allogeneic hematopoietic SCT (HSCT) is increasingly considered an option in refractory or relapsing lymphoma. Today, most patients with B-cell lymphoma are treated with the monoclonal anti-CD20 antibody rituximab before HSCT. We hypothesized that prior therapy with rituximab might alter immune reconstitution after allogeneic transplantation due to in vivo depletion of B cells at the time of graft infusion. We studied B-cell immune reconstitution in 12 patients with lymphoma receiving rituximab 1-12 months before HSCT. Compared to an age- and sex-matched population of patients transplanted for myeloid malignancies, lymphoma patients with rituximab pretreatment showed significantly reduced B-cell counts at time of HSCT at +3, +6 and +12 months; B-cell counts reached values comparable to controls only 24 months after HSCT. In parallel, levels of immunoglobulins were markedly reduced for up to 2 years post transplant in patients with prior rituximab treatment. Two patients suffered from severe late bacterial infections to which the impaired humoral immunity may have contributed. In contrast, T- and NK-cell reconstitution was not different compared to control patients.In conclusion, B-cell reconstitution can be significantly delayed in allogeneic HSCT recipients with prior rituximab treatment. Rituximab appears to have clinical consequences beyond the immediate early post-transplant period.     

Peripheral neuropathy in Behçet disease: an electroneurophysiological study

The aim of this study was to determine the peripheral nerve involvement electrophysiologically in Behçet patients without clinically evident neurological signs and symptoms. Sixty-three patients who fulfilled the International Study Group Classification Criteria for Behçet’s disease (BD) and 49 healthy control subjects were enrolled to the study. Conventional electrophysiological studies of peripheral nerves including F latencies were performed to all subjects. Thirty-one male and 32 female Behçet patients with a mean age of 33.6?±?11.1 years and (22 male and 27 female healthy control subjects with a mean age of 35.8?±?9.9 years were included to the study. All but four of the patients were active. In the BD group, electrophysiologically diagnosed neuropathy was detected in nine (14.28%) patients. One (1.58%) patient had sensorimotor polyneuropathy, one patient (1.58%) had sural and ulnar sensorimotor neuropathy, three (4.75%) patients had median and one patient (1.58%) had ulnar sensorimotor neuropathy. Sural nerve sensorial action potential was unobtainable in two (3.17%) patients and prolonged F latencies were observed in two (3.17%) patients. In the control group only one subject (2.4%) had low sural sensorial conduction velocity. The frequency of neuropathy was higher in the patients with BD when compared with the control subjects. Sensory nerves were affected more prominently than motor nerves. There was no relationship between the clinical and laboratory characteristics of the patients and the electrophysiologic findings. No significant difference was observed between the clinical parameters of the patients with and without electrophysiologically detected neuropathy, except the levels of disease duration (8.8?±?5.1 vs 5.28?±?4.3 years, respectively, p?相似文献   

(18)F-deoxyglucose PET: useful in the management of patients with stem cell transplantation for lymphoma?

(18)F-deoxyglucose (FDG) positron emission tomography (PET) and more recently FDG PET/computed tomography (CT) has become an important tool in the management of patients with Hodgkin and non-Hodgkin lymphoma. It adds metabolic and functional information to conventional anatomical imaging, mainly assessed by CT. Especially for the detection of early response to treatment and prognostic considerations, this type of information seems better suited than anatomical information. Consequently, the ability of FDG PET to predict the outcome in patients with stem cell transplantation (SCT) for lymphoma has been tested in several studies. Results in patients with autologous SCT have been promising, and pretransplant FDG PET is likely to become routine in this group of patients. The evaluated study investigates, for the first time, the predictive value of pretransplant FDG PET in allogeneic SCT, as well as the utility of FDG PET for the follow-up of these patients. All 80 patients included in the prospective study had reduced-intensity conditioning. In contrast to FDG PET before autologous SCT, there was no correlation at all between pretransplant FDG PET results and the outcome after allogeneic SCT. This reflects the fact that other or additional reasons, especially the graft-versus-leukemia effect, are substantial for the outcome of allogeneic SCT in comparison with autologous SCT. Follow-up with FDG PET after reduced-intensity allogeneic SCT was significantly more sensitive than CT to detect disease progression or relapse, and was useful in guiding treatment in the situation of disease relapse.