Successful Antifungal Combination Therapy and Surgical Approach for Aspergillus fumigatus Suppurative Thyroiditis Associated with Thyrotoxicosis and Review of Published Reports.

In immunocompromised patients, Aspergillus infections are important causes of morbidity and mortality. We describe a patient with cryoglobulinemic vasculitis who developed disseminated invasive aspergillosis with thyrotoxicosis caused by Aspergillus fumigatus. The diagnosis was based upon radiological, microbiological and pathological findings. The patient was treated successfully with voriconazole and caspofungin treatment followed by total thyroidectomy. We provide an overview of published reports on Aspergillus thyroiditis with an emphasis on therapeutic approaches.

Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series.

PURPOSE: Chronic pulmonary aspergillosis (CPA) is a rare disease that primarily affects subjects with moderate immunodepression and/or structural alterations in the lung. METHODS: Data for patients with probable CPA were collected over 24 months. Patients with probable CPA received oral voriconazole, and clinical, laboratory and radiological follow-up was performed at 3, 6 and 12 months. RESULTS: 21 patients (mean age 52.4 years) were evaluated. Factors predisposing to CPA were tuberculosis (n = 8), chronic obstructive pulmonary disease (n = 7), corticosteroids (n = 14), chemo- or radio-therapy (n = 6), tracheostomy or endotracheal prosthesis (n = 5), smoking (n = 4), asthma (n = 3), and chronic liver disease (n = 3). Sputum or bronchial aspirate cultures were positive for Aspergillus spp. in 14 cases (66.6 %). (1,3)-ß-D-glucan on serum was positive in 16 cases (76.2 %). Excavated pulmonary thickening was evident in 14 patients (66.6 %) and in 9 of these cases (64.2 %) aspergilloma was present. [(18)F]2-fluoro-2-deoxy-D-glucose-PET-CT was positive in 13/15 patients, and simple aspergilloma was diagnosed after surgical excision in one of the negative cases. All patients were treated with oral voriconazole. Therapy was discontinued due to skin toxicity (n = 3), liver toxicity (n = 2) and severe mental disorder (n = 1). At 12 months' follow-up, nine patients (42.9 %) were considered cured or improved. Seven patients (33.3 %) died during follow-up, mainly due to underlying disease. CONCLUSIONS: A reasonable proportion of patients achieved cure or improvement with voriconazole, but 28.5 % of treated patients had to discontinue therapy because of toxicity. The high mortality makes it difficult to fully assess the real efficacy of voriconazole and to establish the correct duration of therapy.

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. METHODS: All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. RESULTS: 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to > or = 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 73%. Sputum smear became negative in 84.4% cases after 60 days and 933% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p < 0.0001) and 90 days (p = 0.038) of hospital-based DOT. CONCLUSIONS: These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status.

Cytofluorimetric evaluation of DNA ploidy in lung cancer: a bronchoscopic study.

The study of the biological characteristics of lung cancer is gaining more and more interest both because of their potential role as prognostic indicators and for therapeutic reasons. The DNA content estimated by flow cytometry in surgical samples of non-small cell lung cancer (NSCLC) has already been demonstrated to be correlated with survival in these patients. From July 1990 to February 1992 we analyzed the DNA distribution of bronchoscopic biopsies from 88 patients with lung cancer (18 small cell lung cancer, SCLC, and 68 NSCLC, two unspecified histology). Twenty-eight tumors (34.6%) had a diploid DNA distribution, while 53 were aneuploid (65.4%). A correlation was found between DNA ploidy and survival. Evaluation of the DNA content in bronchoscopic samples in a large series of patients could determine the role of this analysis prior to surgery in NSCLC and its value as a marker with respect to prognosis and response to therapy in SCLC.

Transbronchial biopsy in the diagnosis of pulmonary infiltrates in immunocompromised patients.

Bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) frequently are performed in the investigation of immunocompromised patients with lung disorders. The risk-benefit ratio of TBB currently is debated, since several authors have found that the less invasive BAL may provide as much information as TBB, with the avoidance of some biopsy-related side effects. We retrospectively evaluated 157 instances of bronchoscopy carried out on 142 immunocompromised patients, with both BAL and TBB performed in every case. Immunosuppressant conditions were HIV infection (79), hematologic malignancies (36), and antirejection therapy in renal transplant recipients (27). Transbronchial biopsy provided a diagnostic yield significantly higher than that obtained by BAL in all categories investigated; diagnostic rates were 77.3% for TBB and 47.6% for BAL (p < 0.001) in patients with HIV infection, 55 and 20% (p < 0.001) in patients with hematologic malignancies, and 57.5 and 27.2% (p < 0.001) in renal transplant recipients. Looking at the whole series, the diagnostic rates of TBB and BAL were 67.5 and 36.3%, respectively (p < 0.001), with a total additional yield of 33% provided by TBB, while in only 2% of cases BAL gave rise to diagnostic information not achieved by TBB. Considering that side effects followed TBB at a negligible rate (2.5%), we believe that TBB should be routinely carried out in these patients once the diagnostic strategy has been oriented to bronchoscopy.

Transmission of HIV-associated tuberculosis to healthcare workers.

OBJECTIVE: A retrospective investigation was made to compare the occupational risk of tuberculosis in personnel assisting human immunodeficiency virus (HIV)-infected and uninfected subjects with active tuberculosis. DESIGN: We retrospectively reviewed 6 years of hospital activity in 3 units where HIV-infected patients with tuberculosis are hospitalized and in 2 units where non-HIV-infected tuberculosis patients are hospitalized. The risk of occupational tuberculosis in healthcare workers who assisted HIV-infected and non-HIV-infected patients with tuberculosis was investigated. PARTICIPANTS: The risk of occupational tuberculosis in healthcare workers was studied by considering the numbers of potential source cases (hospitalized patients with tuberculosis) in the two conditions investigated (HIV-positive and HIV-negative). Both potential source cases and cases of tuberculosis in healthcare workers had to be microbiologically proven in order to be considered. RESULTS: Seven cases of tuberculosis occurred in persons who cared for 85 HIV-infected subjects with tuberculosis, while only 2 cases occurred in staff members who took care of 1,079 HIV-negative tuberculosis patients over the same period (relative risk = 44.4; 95% confidence interval = 8.5-438). CONCLUSIONS: Tuberculosis seems no longer to be a neglectable risk in healthcare workers assisting patients with HIV infection. Further study is urgently needed to see whether such unexpectedly high dissemination of tuberculosis also is demonstrable in the community.

Clinical and demographic aspects of extrathoracic tuberculosis: experience of an Italian university hospital.

OBJECTIVE: The decline of tuberculosis in industrialised countries concerns mainly its pulmonary forms. We have analysed all the cases of non-respiratory tuberculosis admitted to our hospital between January 2000 and June 2002, and compared epidemiological, clinical and diagnostic features in our area with those observed in other industrialised countries with high immigration rates. DESIGN: Patients' records were retrospectively analysed for demographic, clinical, laboratory and instrumental data. Delays in the introduction of treatment were also measured. Characteristics of immigrants were compared with those of native-born persons. We also investigated specific features of extrathoracic tuberculosis affecting different body sites. RESULTS: Forty-eight patients were identified, two thirds of whom were from industrialised countries. Age distribution was characteristically bimodal. Vertebral (n = 18) and lymph node (n = 11) tuberculosis were the most frequently detected forms. The therapeutic delay among individuals from industrialised countries was found to be significantly longer than that of their counterparts from developing countries (P = 0.05). CONCLUSION: We hypothesise that the complex and non-standardised diagnostic approach to the different forms of extrathoracic tuberculosis forms and physicians' lack of awareness of the specific risk of each epidemiological group strongly influence the unacceptably long therapeutic delay. Extrathoracic tuberculosis was more neglected in native-born individuals than in immigrants.

The ParaSight-F rapid dipstick antigen capture assay for monitoring parasite clearance after drug treatment of Plasmodium falciparum malaria.

Three methods for the detection of Plasmodium falciparum infection in peripheral blood were compared during antimalarial treatment and follow-up in 32 Burundian patients: dipstick antigen capture assay, standard (TBF) and prolonged thick blood film examination (PTBF) (3 x 5 min and 3 x 20 min examination respectively). Parasitaemia was determined daily by comparison with total white blood cell counts (determined by Coulter counter) until no parasite was detected on 2 consecutive days by PTBF. Cumulatively, 231 observations were made with each assay: 64 were negative and 167 positive by PTBF (59 had parasite counts < or = 100/microL). Compared to PTBF, the sensitivities of TBF and the dipstick assay were 1.0 for parasite counts > 100/microL and 0.458 and 0.966 respectively for counts < or = 100/microL. Overall, the dipstick assay was significantly more sensitive (0.988 vs. 0.808; P < 0.001) but less specific (P = 0.013) than TBF. The dipstick assay is of potential use for monitoring response to drug treatment and for detecting low parasitaemias.

Invasive pulmonary aspergillosis complicating allergic bronchopulmonary aspergillosis.

Invasive pulmonary aspergillosis is a frequent complication in immunocompromised patients. The role of the prolonged use of steroids in predisposing to invasive aspergillosis has been recognized, but exceptionally described in asthmatic patients. We report the case of a 59-year-old woman with bronchial asthma treated with steroid therapy for a long time, who developed an invasive pulmonary aspergillosis with an unusual combination of invasive and allergic disease. It seems reasonable to think that allergic disease due to allergic bronchopulmonary aspergillosis (ABPA) preceded the terminal invasive process. Adjunctive therapy with antifungal agents in patients with ABPA is considered, since there is the risk of an invasive pulmonary aspergillosis.

Aetiology of pneumonia following isolated closed head injury.

Patients undergoing mechanical ventilation (MV) after an isolated closed head injury (ICHI) have often been found to develop hospital-acquired pneumonia (HAP) well before subjects who require MV for different reasons. In a prospective study of patients receiving MV after an ICHI. 38 subjects (out of 65 with clinically suspected HAP) had a bacteriological diagnosis established on the basis of correspondence between cultures made from bronchoalveolar lavage and protected specimen brush (with quantitative thresholds of 10(4) and 10(3) cfu ml-1, respectively). Patients were separated according to the time of onset of HAP, with 20 subjects who developed HAP within 4 days of the start of MV (early onset pneumonia, EOP) and 18 subjects who developed HAP after the fourth day (late onset pneumonia, LOP). In those who had LOP, an expected spectrum of organisms was found, with Gram-negatives (especially Pseudomonas sp.) accounting for the majority of isolates. However, in EOP cases, Gram-positive bacteria (especially Staphylococcus sp. and Streptococcus pneumoniae) were found to largely predominate (P = 0.0000026). This confirms the high incidence of staphylococcal pneumonia in neurosurgery patients, and also provides evidence that the vast majority of such staphylococcal pneumonia are EOP. Unlike most previous reports, the microbiological findings from the present study suggest that a cut-off point of 4 days successfully distinguishes between EOP and LOP. Since these two clinical entities differ significantly in terms of pathogenesis and aetiology, preventive measures and therapeutical protocols have to be tailored accordingly.

Failure of prophylaxis against PCP in patients with HIV infection.

Since the end of the 1980s, primary anti-Pneumocystis carinii pneumonia (PCP) prophylaxis has become a fundamental part of the global AIDS control strategy in industrialized countries. The widespread adoption of anti-PCP chemoprophylaxis has been a key element in prolonging the survival of patients with AIDS. There is general agreement on the need to begin chemoprophylaxis when individual CD4+ cell counts drop below the value of 200/microL. However, PCP still develops in up to 27% of susceptible HIV-infected patients despite regular prophylaxis intake. Failure of chemoprophylaxis may depend on different factors. The choice of the regimen and the patient's compliance to it have been the first variables to be identified, whereas the importance of the residual cellular immune function as complementary protective mechanism against PCP has emerged in subsequent clinical studies. Albeit of limited general concern, issues such as P. carinii drug resistance and defective drug absorption may play some role in prophylaxis failure in selected patients. Regarding the epidemiology of primary and recurrent episodes of PCP, recent studies based on genetic fingerprinting techniques revealed that interhuman transmission of the organism could be more relevant than so far expected, thus raising some concern of the possibility of nosocomial spread among susceptible individuals. The downgrading tendency of immune competence in HIV infection and the related increasing risk of developing PCP make it possible to envisage a two-step chemoprophylactic strategy, with the most effective compound, cotrimoxazole, to be reserved for the last and most risky disease stage, when immune response no longer provides any support for preventing the development of PCP.

Tentative reference values for some elements in broncho-alveolar lavage fluid.

The concentrations of Fe, Mn, Pb and Cr have been determined in broncho-alveolar lavage (BAL) fluid of 25 subjects without occupational or abnormal environmental exposure to metals, using the AAS method. The numerous factors which can interfere with the results in pre-analytical and in analytical phases are stressed. Metals concentrations in BAL are expressed in micrograms/l. They were not correlated with the volume of fluid recovered, the total cells, alveolar macrophages and erythrocytes. The results were not modified by stratification considering age and sex. Iron concentrations were higher than others, probably due to higher environmental exposure and partly to its essential role in humans. The diagnostic significance of element determination in BAL fluid and the relationship with exposure and lung load is discussed.

[Acute pneumonia and cell-mediated immunity in patients with HIV infection]. / Polmoniti acute e immunità cellulo-mediata in pazienti con infezione da HIV.

The aim of this retrospective study is to evaluate the correlation between T-cell immunity and pulmonary disorders in a group of Italian subjects with HIV infection. HIV-infected patients seen at the Institute of Infectious Diseases, University of Verona, were included in this study if they had a specific acute pneumonia, a CD4+ cell count and a CD4+/CD8+ ratio during the 60 days immediately before the onset of pulmonary disease. Cases receiving any antimicrobial prophylaxis were excluded. Pneumonia was recognized by usual clinical and radiologic abnormalities. The diagnostic procedure included sputum examination, bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. The specimens were processed for bacterial, mycobacterial and fungal stains and cultures. Ziehl-Neelsen, periodic acid-Schiff and silver methenamine stains were performed on the transbronchial biopsy specimens in addition to usual pathologic examinations mononuclear. Determination of percentage of peripheral blood mononuclear cells bearing CD4+ and CD8+ markers was done by conventional fluorescent antibody cell-sorter analysis of the mononuclear cell population. Absolute number of CD4+ lymphocytes was determined by multiplying the total lymphocyte count by the percent of mononuclear cells bearing CD4+ marker. From October 1987 to August 1991, 61 patients, 50 males and 11 females, had 65 episodes of specific pneumonia. The average age of patients was 31.4 years (range 29-59 years). The risk factors for HIV infection included intravenous drug abuse (47 patients), homosexuality (6 patients), bisexuality (3 patients) and heterosexual contact (5 patients). Before the onset of pulmonary disorders, patients were classified in the following clinical HIV-related stages: asymptomatic state (22 episodes), ARC (22 episodes) and AIDS (21 episodes). In decreasing order of frequency diagnosis of pneumonias were PCP (29 episodes), community-acquired bacterial pneumonia (16 episodes), pulmonary tuberculosis (8 episodes), nonspecific interstitial pneumonia (4 episodes), PCP and pulmonary tuberculosis (3 episodes), cytomegalovirus pneumonia (2 episodes), and one of each episode of PCP and pulmonary cryptococcosis, pulmonary candidiasis, pulmonary Kaposi's sarcoma. The mean and the standard deviation of immunologic values regarding the four primary diagnostic groups were: PCP CD4+/CD8+ 0.50 +/- 0.42, CD4+/mm3 196 +/- 190; bacterial pneumonia CD4+/CD8+ 0.53 +/- 0.44, CD4+/mm3 247 +/- 139; pulmonary tuberculosis CD4+/CD8+ 0.62 +/- 0.38, CD4+/mm3 260 +/- 170; nonspecific interstitial pneumonia CD4+/CD8 + 0.57 +/- 0.48, CD4+/mm3 240 +/- 189. No significant statistical differences with respect to CD4+/CD8 ratios and CD4+ cell counts among these diagnostic groups were found by standard analysis of variance.(ABSTRACT TRUNCATED AT 400 WORDS)

[Tracheal sleeve lobectomy in the radical surgery for lung cancer]. / Tracheal sleeve lobectomy nella chirurgia estrema del carcinoma polmonare.

Tracheal sleeve lobectomy is right upper lobectomy extended to include resection of the main bronchus, the carina and a segment of the trachea with end-to-end anastomosi of the trachea and end-to-side anstomosis of the intermediate bronchus on the main left bronchus, or the upper lobe on the trachea. This operation is possible with the aid of high frequency jet ventilation. The surgical indication of this operation is bronchoscopic and functional and guarantees a good oncological radicality in the presence of N0.

Interstitial lung granulomas as a possible consequence of exposure to zirconium dust.

A case of interstitial lung granulomas is described in a worker exposed to zirconium compounds. Chest X-rays revealed diffuse slight reticular interstitial radio-opacities (ILO classification, 1/0 s/t). Histological examination of transbronchial biopsy tissue revealed small interstitial nonconfluent granulomas with epithelioid and giant cells showing no central necrosis, with PAS-positive diastase-resistant small weakly birefringent particles in interstitial histiocytes. These histological and stain findings, which are characteristic of zirconium skin lesions and granulomas, suggest zirconium interstitial lung disease.

Lymphocyte subpopulations in active tuberculosis: association with disease severity and the QFT-GIT assay.

Cell-mediated immune response plays an essential role in the pathogenesis of tuberculosis (TB). We retrospectively evaluated lymphocyte subpopulations in 177 active TB patients compared to 93 healthy controls, finding a relevant decrease in total lymphocytes and CD8+ cells. Conversely, activated human leukocyte antigen (HLA-DR+) and CD4+CD57+ cells were higher in the TB group. B-1a (CD5+CD19+) lymphocytes were reduced in TB subjects, particularly those with extended and cavitary pulmonary forms, suggesting increased compartmentalisation at the infection site. QuantiFERON-TB Gold In-Tube positive results were associated with higher HLA-DR+CD4+ and CD4+CD57+ cells, while interferon-gamma response and total lymphocyte levels were lower in advanced pulmonary TB cases.

[Herpes zoster in general medicine: experience of the Italian group Netaudit]. / Herpes zoster e medicinagenerale: l'esperienza deimedici del gruppo Netaudit.

Herpes zoster is caused by the reactivation of the varicella-zoster virus (VZV) and usually appears many years after primary infection (varicella), induced by immunosuppression due to underlying diseases. Few epidemiological data in Italy are available concerning Herpes zoster, mainly because disease notification is not mandatory. An observational perspective trial was conducted for 12 months by 41 Italian general practitioners belonging to the Netaudit network to determine herpes zoster incidence and its correlation to patients' characteristics (age, gender, educational qualification, co-morbidities), the delay from correct diagnosis to the start of treatment and different drug prescription. In all, the study involved 193 patients with herpes zoster: this population included mostly female (60.6%) and elderly subjects (59.6%) with a mean age of 60.4 years. 46.1% of patients presented underlying diseases (diabetes 13%, solid tumours 5.7%). Correct diagnosis was achieved after a mean delay of 49 hours while therapy was started within 48 hours in most cases (75.1%). Aciclovir (51%) and valaciclovir (24%) were the most commonly used drugs. A significant correlation between educational level and prompt treatment suggests the major role of education in primary health prevention campaigns.