Lung cancer in HIV-infected patients

Purpose: Several studies have shown that HIV patients are at higher risk of lung cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV-infected patients. Methods: The clinical charts of 4,721 HIV-infected patients seen in three hospitals of southeast Spain (study period 1992-2012) were reviewed, and all patients with a lung cancer were analysed. Results: There were 61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%), and smokers (96.6%; mean pack-years 35.2), with a median age of 48.0 (41.7-52.9) years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty-four (56.7%) patients were Aids cases, and 29 (47.5%) had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42-232), the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85-397), and 66.1% <350/mm3. 66.7% were on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0%) and 23 (38.3%) cases, respectively. There were 49 (80.3%) cases with advanced stages (III and IV) at diagnosis. The distribution of treatments was: only palliative 23 (39.7%), chemotherapy 14 (24.1%), surgery and chemotherapy 8 (13.8%), radiotherapy 7 (12.1%), surgery 4 (6.9%), and other combined treatments 2 (3.4%). Forty-six (76.7%) patients died, with a median survival time of 3 months. The Kaplan-Meier survival rate at 6 months was 42.7% (at 12 months 28.5%). Conclusions: The prevalence of lung cancer in this cohort of HIV-patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis. Adenocarcinoma is the most frequent histological type. The diagnosis is usually made at advanced stages of the neoplasm, and mortality is high.

Coccidioidomycosis in armadillo hunters from the state of Ceará, Brazil

Coccidioidomycosis is a systemic mycosis with a variable clinical presentation. Misdiagnosis of coccidioidomycosis as bacterial pneumopathy leads to inappropriate prescription of antibiotics and delayed diagnosis. This report describes an outbreak among armadillo hunters in northeastern Brazil in which an initial diagnosis of bacterial pneumonia was later confirmed as coccidioidomycosis caused by Coccidioides posadasii. Thus, this mycosis should be considered as an alternative diagnosis in patients reporting symptoms of pneumonia, even if these symptoms are only presented for a short period, who are from areas considered endemic for this disease.

Bacterial-induced protection against allergic inflammation through a multicomponent immunoregulatory mechanism.

Background Airborne microbial products have been reported to promote immune responses that suppress asthma, yet how these beneficial effects take place remains controversial and poorly understood. Methods We exposed mice to the bacterium Escherichia coli and subsequently induced allergic airway inflammation through sensitization and intranasal challenge with ovalbumin. Results Pulmonary exposure to the bacterium Escherichia coli leads to a suppression of allergic airway inflammation. This immune modulation was neither mediated by the induction of a T helper 1 (Th1) response nor regulatory T cells; however, it was dependent on Toll-like receptor 4 (TLR4) but did not involve TLR desensitisation. Dendritic cell migration to the draining lymph nodes and activation of T cells was unaffected by prior exposure to E.coli, while dendritic cells in the lung displayed a less activated phenotype and had impaired antigen presentation capacity. Consequently, in situ Th2 cytokine production was abrogated. The suppression of airway hyper-responsiveness was mediated through the recruitment of gd T cells; however, the suppression of dendritic cells and T cells was mediated through a distinct mechanism that could not be overcome by the local administration of activated dendritic cells, or by the in vivo administration of tumour necrosis factor a. Conclusion Our data reveal a localized immunoregulatory pathway that acts to protect the airways from allergic inflammation.

Respiratory infection in congenital cardiac disease. Hospitalizations in young children in Spain during 2004 and 2005: the CIVIC Epidemiologic Study.

OBJECTIVES To evaluate the rate of hospitalization for acute respiratory tract infection in children less than 24 months with haemodynamically significant congenital cardiac disease, and to describe associated risk factors, preventive measures, aetiology, and clinical course. MATERIALS AND METHODS We followed 760 subjects from October 2004 through April 2005 in an epidemiological, multicentric, observational, follow-up, prospective study involving 53 Spanish hospitals. RESULTS Of our cohort, 79 patients (10.4%, 95% CI: 8.2%-12.6%) required a total of 105 admissions to hospital related to respiratory infections. The incidence rate was 21.4 new admissions per 1000 patients-months. Significant associated risk factors for hospitalization included, with odds ratios and 95% confidence intervals shown in parentheses: 22q11 deletion (8.2, 2.5-26.3), weight below the 10th centile (5.2, 1.6-17.4), previous respiratory disease (4.5, 2.3-8.6), incomplete immunoprophylaxis against respiratory syncytial virus (2.2, 1.2-3.9), trisomy 21 (2.1, 1.1-4.2), cardiopulmonary bypass (2.0, 1.1-3.4), and siblings aged less than 11 years old (1.7, 1.1-2.9). Bronchiolitis (51.4%), upper respiratory tract infections (25.7%), and pneumonia (20%) were the main diagnoses. An infectious agent was found in 37 cases (35.2%): respiratory syncytial virus in 25, Streptococcus pneumoniae in 5, and Haemophilus influenzae in 4. The odds ratio for hospitalization due to infection by the respiratory syncytial virus increases by 3.05 (95% CI: 2.14 to 4.35) in patients with incomplete prophylaxis. The median length of hospitalization was 7 days. In 18 patients (17.1%), the clinical course of respiratory infection was complicated and 2 died. CONCLUSIONS Hospital admissions for respiratory infection in young children with haemodynamically significant congenital cardiac disease are mainly associated with non-cardiac conditions, which may be genetic, malnutrition, or respiratory, and to cardiopulmonary bypass. Respiratory syncytial virus was the most commonly identified infectious agent. Incomplete immunoprophylaxis against the virus increased the risk of hospitalization.

Risk for Pneumocystis carinii transmission among patients with pneumonia: a molecular epidemiology study.

We report a molecular typing and epidemiologic analysis of Pneumocystis carinii pneumonia (PCP) cases diagnosed in our geographic area from 1990 to 2000. Our analysis suggests that transmission from patients with active PCP to susceptible persons caused only a few, if any, PCP cases in our setting.

Estudio de los exitus con diagnóstico secundario de desnutrición en un hospital de tercer nivel.

BACKGROUND: Malnutrition is a major public health problems, according to WHO, is the leading cause of death, when it affects the group of hospitalized patients, making denominating separate entity "hospital malnutrition". OBJECTIVES: The overall objective is to quantify the main diagnoses frequently high, causing exitus, with secondary diagnosis of malnutrition. METHODS: This is a descriptive study, which included all hospital discharges in 2011 and first half of 2012, which have been exitus and whose secondary diagnosis of malnutrition, with the total of 33. We performed a descriptive analysis, effected the Mann-Whitney nonparametric test (p < 0.05). RESULTS: The most frequent main diagnoses among 33 analyzed are high sepsis (12.1%), liver metastases (9.1%), pneumonia (6.1%), acute respiratory failure (6.1%) and renal acute renal (6.1%). CONCLUSIONS: Although the most frequent primary diagnosis of sepsis, by grouping the diagnoses, the most frequent DRG is respiratory disease, so it has to make comprehensive and quality coding to adjust the relative weight of the same reality. It is essential to specify the source of clinical information used for coding, the degree of malnutrition, for greater specificity in the data.

Seasonal fluctuations of bacterial community diversity in agricultural soil and experimental validation by laboratory disturbance experiments.

Natural fluctuations in soil microbial communities are poorly documented because of the inherent difficulty to perform a simultaneous analysis of the relative abundances of multiple populations over a long time period. Yet, it is important to understand the magnitudes of community composition variability as a function of natural influences (e.g., temperature, plant growth, or rainfall) because this forms the reference or baseline against which external disturbances (e.g., anthropogenic emissions) can be judged. Second, definition of baseline fluctuations in complex microbial communities may help to understand at which point the systems become unbalanced and cannot return to their original composition. In this paper, we examined the seasonal fluctuations in the bacterial community of an agricultural soil used for regular plant crop production by using terminal restriction fragment length polymorphism profiling (T-RFLP) of the amplified 16S ribosomal ribonucleic acid (rRNA) gene diversity. Cluster and statistical analysis of T-RFLP data showed that soil bacterial communities fluctuated very little during the seasons (similarity indices between 0.835 and 0.997) with insignificant variations in 16S rRNA gene richness and diversity indices. Despite overall insignificant fluctuations, between 8 and 30% of all terminal restriction fragments changed their relative intensity in a significant manner among consecutive time samples. To determine the magnitude of community variations induced by external factors, soil samples were subjected to either inoculation with a pure bacterial culture, addition of the herbicide mecoprop, or addition of nutrients. All treatments resulted in statistically measurable changes of T-RFLP profiles of the communities. Addition of nutrients or bacteria plus mecoprop resulted in bacteria composition, which did not return to the original profile within 14 days. We propose that at less than 70% similarity in T-RFLP, the bacterial communities risk to drift apart to inherently different states.

High bacterial load in negative pressure wound therapy (NPWT) foams used in the treatment of chronic wounds.

No earlier study has investigated the microbiology of negative pressure wound therapy (NPWT) foam using a standardized manner. The purpose of this study is to investigate the bacterial load and microbiological dynamics in NPWT foam removed from chronic wounds (>3 months). To determine the bacterial load, a standardized size of the removed NPWT foam was sonicated. The resulting sonication fluid was cultured, and the colony-forming units (CFU) of each species were enumerated. Sixty-eight foams from 17 patients (mean age 63 years, 71% males) were investigated. In 65 (97%) foams, â0/00¥âeuro0/001 and in 37 (54%) â0/00¥2 bacterial types were found. The bacterial load remained high during NPWT treatment, ranging from 10(4) to 10(6) CFU/ml. In three patients (27%), additional type of bacteria was found in subsequent foam cultures. The mean bacterial countâeuro0/00±âeuro0/00standard deviation was higher in polyvinyl alcohol foam (6.1âeuro0/00±âeuro0/000.5 CFU/ml) than in polyurethane (5.5âeuro0/00±âeuro0/000.8 CFU/ml) (pâeuro0/00=âeuro0/000.02). The mean of log of sum of CFU/ml in foam from 125âeuro0/00mmHg (5.5âeuro0/00±âeuro0/000.8) was lower than in foam from 100âeuro0/00mmHg pressure (5.9âeuro0/00±âeuro0/000.5) (pâeuro0/00=âeuro0/000.01). Concluding, bacterial load remains high in NPWT foam, and routine changing does not reduce the load.

Preparation of bacterial DNA template by boiling and effect of immunoglobulin G as an inhibitor in real-time PCR for serum samples from patients with brucellosis.

Real-time PCR is a widely used tool for the diagnosis of many infectious diseases. However, little information exists about the influences of the different factors involved in PCR on the amplification efficiency. The aim of this study was to analyze the effect of boiling as the DNA preparation method on the efficiency of the amplification process of real-time PCR for the diagnosis of human brucellosis with serum samples. Serum samples from 10 brucellosis patients were analyzed by a SYBR green I LightCycler-based real-time PCR and by using boiling to obtain the DNA. DNA prepared by boiling lysis of the bacteria isolated from serum did not prevent the presence of inhibitors, such as immunoglobulin G (IgG), which were extracted with the template DNA. To identify and confirm the presence of IgG, serum was precipitated to separate and concentrate the IgG and was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. The use of serum volumes above 0.6 ml completely inhibited the amplification process. The inhibitory effect of IgG in serum samples was not concentration dependent, and it could be eliminated by diluting the samples 1/10 and 1/20 in water. Despite the lack of the complete elimination of the IgG from the template DNA, boiling does not require any special equipment and it provides a rapid, reproducible, and cost-effective method for the preparation of DNA from serum samples for the diagnosis of brucellosis.

Pancreatic stone protein: a marker of organ failure and outcome in ventilator-associated pneumonia.

Background: Ventilator-associated pneumonia (VAP) is the most common hospital-acquired, life-threatening infection. Poor outcome and health-care costs of nosocomial pneumonia remain a global burden. Currently, physicians rely on their experience to discriminate patients with good and poor outcome. However, standardized prognostic measures might guide medical decisions in the future. Pancreatic stone protein (PSP)/regenerating protein (reg) is associated with inflammation, infection, and other disease-related stimuli. The prognostic value of PSP/reg among critically ill patients is unknown. The aim of this pilot study was to evaluate PSP/reg in VAP.Methods: One hundred one patients with clinically diagnosed VAP were assessed. PSP/reg was retrospectively analyzed using deep-frozen serum samples from VAP onset up to day 7. The main end point was death within 28 days after VAP onset.Results: Serum PSP/reg was associated with the sequential organ failure assessment score from VAP onset (Spearman rank correlation coefficient 0.49 P < .001) up to day 7. PSP/reg levels at VAP onset were elevated in nonsurvivors (n = 20) as compared with survivors (117.0 ng/mL [36.1-295.3] vs 36.3 ng/mL [21.0-124.0] P = .011). The areas under the receiver operating characteristic curves of PSP/reg to predict mortality/survival were 0.69 at VAP onset and 0.76 at day 7. Two PSP/reg cutoffs potentially allow for identification of individuals with a particularly good and poor outcome. Whereas PSP/reg levels below 24 ng/mL at YAP onset were associated with a good chance of survival, levels above 177 ng/mL at day 7 were present in patients with a very poor outcome.Conclusions: Serum PSP/reg is a biomarker related to organ failure and outcome in patients with VAP.

Experimental bacterial endocarditis after dental extractions in rats with periodontitis.

The development of bacterial endocarditis was analyzed after dental extractions in rats with or without periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars and placing the animals on a high sucrose diet for 14 weeks. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hr later the maxillary first molars were extracted. The animals were killed 72 hr after the extractions. In rats with periodontal disease, extractions resulted in a 48% (14 of 29) incidence of bacterial endocarditis, most cases of which were due to Streptococcus spp. (one was caused by Staphylococcus aureus). In contrast, when the teeth with a healthy periodontium were extracted, only 6% (one of 15) of the rats developed endocarditis. When catheters were placed in animals with periodontal disease but no extractions were performed, no endocarditis occurred.

AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be.

INTRODUCTION: According to reports from observational databases, classic AIDS-defining opportunistic infections (ADOIs) occur in patients with CD4 counts above 500/µL on and off cART. Adjudication of these events is usually not performed. However, ADOIs are often used as endpoints, for example, in analyses on when to start cART. MATERIALS AND METHODS: In the database, Swiss HIV Cohort Study (SHCS) database, we identified 91 cases of ADOIs that occurred from 1996 onwards in patients with the nearest CD4 count >500/µL. Cases of tuberculosis and recurrent bacterial pneumonia were excluded as they also occur in non-immunocompromised patients. Chart review was performed in 82 cases, and in 50 cases we identified CD4 counts within six months before until one month after ADOI and had chart review material to allow an in-depth review. In these 50 cases, we assessed whether (1) the ADOI fulfilled the SHCS diagnostic criteria (www.shcs.ch), and (2) HIV infection with CD4 >500/µL was the main immune-compromising condition to cause the ADOI. Adjudication of cases was done by two experienced clinicians who had to agree on the interpretation. RESULTS: More than 13,000 participants were followed in SHCS in the period of interest. Twenty-four (48%) of the chart-reviewed 50 patients with ADOI and CD4 >500/µL had an HIV RNA <400 copies/mL at the time of ADOI. In the 50 cases, candida oesophagitis was the most frequent ADOI in 30 patients (60%) followed by pneumocystis pneumonia and chronic ulcerative HSV disease (Table 1). Overall chronic HIV infection with a CD4 count >500/µL was the likely explanation for the ADOI in only seven cases (14%). Other reasons (Table 1) were ADOIs occurring during primary HIV infection in 5 (10%) cases, unmasking IRIS in 1 (2%) case, chronic HIV infection with CD4 counts <500/µL near the ADOI in 13 (26%) cases, diagnosis not according to SHCS diagnostic criteria in 7 (14%) cases and most importantly other additional immune-compromising conditions such as immunosuppressive drugs in 14 (34%). CONCLUSIONS: In patients with CD4 counts >500/ µL, chronic HIV infection is the cause of ADOIs in only a minority of cases. Other immuno-compromising conditions are more likely explanations in one-third of the patients, especially in cases of candida oesophagitis. ADOIs in HIV patients with high CD4 counts should be used as endpoints only with much caution in studies based on observational databases.

The microbiological signature of human cutaneous leishmaniasis lesions exhibits restricted bacterial diversity compared to healthy skin

Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions.