Tuberculosis screening in outpatient healthcare workers: lessons from a high-income, low TB burden country.

SETTING: Early diagnosis of latent tuberculous infection (LTBI) should be pursued in healthcare workers (HCWs). While HCWs in hospitals are screened for LTBI, HCWs in outpatient settings are usually not. In 2017, in Italy, a tuberculosis (TB) infected paediatrician working in an outpatient vaccination service infected 15 adults and nine children. The investigation involved 2490 children and 151 adults. Among children, nine were tuberculin skin test-positive, and four developed active TB. Among 123 adult contacts with longer exposure, seven were interferon-gamma release assay (IGRA) positive and none had active TB. Among 28 close contacts, eight had a positive IGRA, and three had pulmonary TB. The total outbreak cost €1 017 903.OBJECTIVE: To compare the outbreak cost with those of potential screening programme strategies.RESULTS: Regular screening of paediatric outpatient HCWs would have cost between €2592 and €11 373. Extending the screening to all outpatient HCWs (caring for adults and children) would have cost between €66 384 and €155 043. Investigating only close contacts would have cost €42 857.CONCLUSION: Each of these screening strategies would have been cost-effective compared with the outbreak investigation occurring in real life with a cut-off of 474 for the maximum number of tested outpatient HCWs needed for the screening strategy to be cost-saving.

Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

Out-patient high-dose-rate endobronchial brachytherapy for palliation of lung cancer: an observational study.

BACKGROUND AND AIM: Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. METHODS: Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. RESULTS: 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. CONCLUSIONS: This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.

Respiratory intensive care units in Italy: a national census and prospective cohort study.

BACKGROUND: In Italy, respiratory intensive care units (RICUs) provide an intermediate level of care between the intensive care unit (ICU) and the general ward for patients with single organ respiratory failure. Because of the lack of official epidemiological data in these units, a two phase study was performed with the aim of describing the work profile in Italian RICUs. METHODS: A national survey of RICUs was conducted from January to March 1997 using a questionnaire which comprised over 30 items regarding location, models of service provision, staff, and equipment. The following criteria were necessary for inclusion of a unit in the survey: (1) a nurse to patient ratio ranging from 1:2.5 to 1:4 per shift; (2) availability of adequate continuous non-invasive monitoring; (3) expertise for non-invasive ventilation (NIV) and for intubation in case of NIV failure; (4) physician availability 24 hours a day. Between November 1997 and January 1998 a 3 month prospective cohort study was performed to survey the patient population admitted to the RICUs. RESULTS: Twenty six RICUs were included in the study: four were located in rehabilitation centres and 22 in general hospitals. In most, the reported nurse to patient ratio ranged from 1:2 to 1:3, with 36% of units reporting a ratio of 1:4 per shift. During the study period 756 consecutive patients of mean (SD) age 68 (12) years were admitted to the 26 RICUs. The highest proportion (47%) were admitted from emergency departments, 19% from other medical wards, 18% were transferred from the ICU, 13% from specialist respiratory wards, and 2% were transferred following surgery. All but 32 had respiratory failure on admission. The reasons for admission to the RICU were: monitoring for expected clinical instability (n=221), mechanical ventilation (n=473), and weaning (n=59); 586 patients needed mechanical ventilation during their stay in the RICU, 425 were treated with non-invasive techniques as a first line of treatment (374 by non-invasive positive pressure, 51 by iron lung), and 161 underwent invasive mechanical ventilation (63 intubated, 98 tracheostomies). All but 48 patients had chronic respiratory disease, mainly chronic obstructive pulmonary disease (COPD; n=451). More than 70% of patients (n=228) had comorbidity, mainly consisting of heart disorders. The median APACHE II score was 18 (range 1--43). The predicted inpatient mortality risk rate according to the APACHE II equation was 22.1% while the actual inpatient mortality rate was 16%. The mean length of stay in the RICU was 12 (11) days. The outcome in most patients (79.2%) admitted to RICUs was favourable. CONCLUSIONS: Italian RICUs are specialised units mainly devoted to the monitoring and treatment of acute on chronic respiratory failure by non-invasive ventilation, but also to weaning from invasive mechanical ventilation. The results of this study provide a useful insight into an increasingly important field of respiratory medicine.

Induced sputum cellularity. Reference values and distribution in normal volunteers.

Sputum induction has recently been proposed as the only direct noninvasive method for measuring airway inflammatory indices. The reference values and the distribution of cells in induced sputum in a control population have not yet been well defined. We therefore evaluated data from a large number of healthy volunteers. One hundred fourteen healthy, nonatopic, nonsmoking volunteers without airway hyperreactivity were enrolled (age: 38 +/- 13 yr [mean +/- SD]; FEV(1): 105 +/- 10% predicted; provocative dose of methacholine inducing a 20% decrease FEV(1) > 3,200 microgram). Ninety-six subjects (84%) produced adequate analysis samples. The subjects had a normal age distribution. Their induced sputum was rich in macrophages (69.2 +/- 13%) and neutrophils (27.3 +/- 13%), and poor in eosinophils (0.6 +/- 0.8%), lymphocytes (1.0 +/- 1.2%), and epithelial cells (1.5 +/- 1.8%). Only macrophages and neutrophils showed a normal distribution; total and differential counts of other cells did not. We propose that these data be used in comparison of the induced sputum cells of normal subjects and those of patients with airway inflammation.

[Surgical treatment of varicocele with inguinal microligation technique. 6-year experience]. / Il trattamento chirurgico del varicocele con tecnica di microlegatura inguinale. Sei anni di esperienza.

BACKGROUND: Varicocele is found approximately in 15% of the male population and is considered a major cause of infertility. Varicocele management include surgical (traditional or laparoscopic) or conservative techniques (sclerotherapy). The authors present their experience on microsurgical inguinal varicocelectomy. This technique has been adopted since 1992 to decrease the incidence of recidives of high spermatic vein ligation; it also permitted to use local or loco-regional anesthesia, reducing time of hospitalization and realizing a minimally invasive approach. METHODS: From 1992 to 1997, 433 microsurgical inguinal varicocelectomy with artery and lymphatic sparing have been performed at the Militar Hospital of Milan in 409 young men with idiopathic varicocele. All patients were discharged 24 hours after operation. Only those who lived particularly far from the hospital remained for 48 hours. RESULTS: Clinical controls were performed I, III, VI months after operation. At the third control (VI month), a new semen analysis was performed, and 65% of patients had an improvement of seminal characteristics. In 394 patients, a complete resolution of varicocele was observed; 4 patients had a recurrence of the pathology and 11 had a recidive. Seventy-three patients who presented a concomitant homolateral inguinal hernia were treated at the same time. CONCLUSIONS: The conclusion is drawn that microsurgical ligation of spermatic veins represents a good surgical option in the treatment of varicocele. It is a quite simple technique that guarantees a low risk of recidives, permits using local or loco-regional anesthesia and can be performed in day-surgery with good results, few complications and good short and long term results.

Gas exchange response to exercise in patients with chronic heart failure.

The objective of the study was investigate the pulmonary gas exchange response to exercise in 16 male patients with chronic heart failure (CHF) due to previous myocardial infarction and left ventricular dysfunction (ejection fraction < 45%). All patients underwent a symptom-limited exercise test during which cardiac frequency (fC), tidal volume (VT), respiratory frequency (fR), minute ventilation (V'E), oxygen consumption (V'O2) and carbon dioxide production (V'CO2) were measured on a breath-by-breath basis. Ventilatory equivalent for carbon dioxide (V'E/V'CO2) and lactate threshold (LT) were calculated. Arterial blood gas levels were measured at rest and at peak exercise. The dead space (VD) to tidal volume ratio (VD/VT) and alveolar-arterial oxygen gradient (PA-a,O2) were computed. Two subgroups of patients were identified according to peak V'O2 (V'O2,peak), group A (n = 7), V'O2,peak > 14 mL.kg-1.min-1 (17.2 +/- 2.5 SEM, range 14.5-20.8), and group B (n = 9), V'O2,peak < 14 mL.kg-1.min-1 (11.9 +/- 1.8, range 9.2-13.6). Arterial oxygen tension (Pa,O2) increased from rest to peak exercise in both groups (group A: 12.2 +/- 0.94 to 13.4 +/- 0.82 kPa (91.4 +/- 7.1 to 100.4 +/- 6.2 mmHg), p < 0.05; group B: 11.7 +/- 1.0 to 13.4 +/- 1.1 kPa (88.0 +/- 7.8 to 100.9 +/- 8.2 mmHg), p < 0.01), while a significant reduction in arterial carbon dioxide tension (Pa,CO2), from rest to peak exercise, was observed in group B only (4.64 +/- 0.39 to 4.08 +/- 0.36 kPa (34.9 +/- 2.8 to 30.7 +/- 2.7 mmHg), p < 0.005). Maximal V'E and maximal power (Powermax) were significantly lower in group B compared to group A (V'E 37.6 +/- 8.4 versus 52.1 +/- 13.8 L.min-1, p < 0.05; Powermax 64.4 +/- 12 versus 82.8 +/- 14.1 W, p < 0.01). fC was not significantly different at peak exercise, although the work load was significantly higher in group A. VD/VT failed to decrease significantly at maximal exercise in both groups. In group B, V'E/V'CO2 tended to be higher than in group A. In chronic heart failure patients, measurements of arterial blood gas levels during exercise might help to identify those subjects with a more pronounced depression of left ventricular function. At peak exercise, high ventilatory demand and respiratory alkalosis were observed in group B patients, suggesting an increased responsiveness of the respiratory centre that might be one major factor contributing to this excessive ventilatory response to exercise; vice versa, a combination of ventilation-perfusion mismatch, wasted ventilation and unpaired peripheral blood circulation seem to play only a minor role.

Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease.

BACKGROUND: Airways inflammation is a feature of chronic obstructive pulmonary disease (COPD), but the role of corticosteroids in the management of clinically stable patients has yet to be established. A randomised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate (BDP) administered for two months to patients with stable, smoking related COPD. Sputum induction was used to evaluate bronchial inflammation response. METHODS: 34 patients (20 men and 14 women) were examined on three separate occasions. At the initial clinical assessment (visit 0), spirometry and blood gas analysis were performed. On visit 1 (within one week of visit 0) sputum induction was performed and each patient was randomised to receive either BDP 500 micrograms three times daily (treated group) or nothing (control group). After two months (visit 2), all patients underwent repeat clinical assessment, spirometry, and sputum induction. RESULTS: There were no differences in sputum cell counts between the groups at baseline. After two months of treatment, induced sputum samples from patients in the treated group showed a reduction in both neutrophils (-27%) and total cells (-42%) with respect to baseline, while the control group did not (neutrophils +9%, total cells +7%). Macrophages increased in the treated group but not in the control group. The mean final value of sputum neutrophils was 52% in the treated group and 73.3% in the control group (95% confidence interval (CI) -27.2 to -15.4). The mean final value of sputum macrophages was 35.8% in treated group and 19.3% in control group (95% CI 10.3 to 22.8). The differences between the treated and control groups for neutrophils (-21.3%), macrophages (+16.5%), and total cells (-65%) were significant. Spirometry and blood gas data did not change from baseline in either patient group. CONCLUSIONS: A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation.

Study of release of eosinophil cationic proteins (ECP and EPX) in the hypereosinophilic syndrome (HES) and other hypereosinophilic conditions.

BACKGROUND: Up to date, the etiology and the pathogenesis of HES are still unknown and particularly it is unclear why eosinophils in HES are more aggressive towards tissues than in other eosinophilic conditions. METHODS: We assessed the cationic proteins ECP and EPX serum concentrations, their in vitro release from polymorphonuclear cell culture, and the monoclonal antibodies EG1 and EG2 in 3 patients with HES, 6 patients with other hypereosinophilic conditions and 20 healthy control subjects. RESULTS: Serum ECP and EPX concentrations were higher in eosinophilic patients than in healthy subjects. Hypereosinophilic patients had more EG2+ cells than healthy subjects, but EG2+ rate failed to differentiate HES from other hypereosinophilic conditions (p = 0.074). Moreover, the release in vitro of ECP and EPX was significantly higher in HES patients (p < 0.05). CONCLUSIONS: Our preliminary results seem to suggest the importance of functional data, such as ECP and EPX release, in differentiating HES from other hypereosinophilic diseases. Particularly, ECP and EPX release in vitro is higher in cell cultures from HES patients than from patients with other hypereosinophilic conditions.

Prevention of delayed emesis with metoclopramide and dexamethasone in patients receiving moderately emetogenic cytotoxic treatment.

Forty-three untreated cancer patients receiving moderately emetogenic polychemotherapy entered a phase II trial in order to evaluate the effectiveness of the combination of metoclopramide (40 mg every 6 hrs) and dexamethasone (8 mg every 12 hrs) in the prevention of delayed emesis (days 2-3). For the control of acute emesis all patients received on day 1 ondansetron 8 mg for 3 times. Results of antiemetic treatment were as follows: complete/major protection from acute emesis (day 1) was observed in 72%/88% of patients. Worst day analysis of delayed emesis (days 2 and 3) showed that complete/major protection was obtained in 93%/95% of cases, respectively. Delayed nausea was not as well controlled: complete/major protection was observed in 44%/79% of patients. Extrapyramidal reactions occurred in 3 patients and moderate epigastric pain was reported by 3 patients. Since control of acute emesis could be one of the most important factors influencing delayed emesis, the absence of acute symptoms in 72% of our patients may be partially responsible for the excellent control of delayed emesis. The combination of metoclopramide and dexamethasone is a feasible and effective treatment for delayed emesis in outpatients receiving moderately emetogenic chemotherapy.

Benign idiopathic hypereosinophilia: a feeble masquerader or a smouldering form of the hypereosinophilic syndrome?

In a patient with long-standing idiopathic hypereosinophilia with no apparent organ damage we measured serum eosinophil cationic protein (ECP) and eosinophil protein X (EPX) titers, activated circulating eosinophil rates (by means of monoclonal antibodies EG1 and EG2), and the release of ECP and EPX in vitro by leukocytes at different cultures stages in order to detect possible functional abnormalities associated with hypereosinophilia. Our patient had elevated serum levels of both ECP and EPX, together with a high EG2 count, which would suggest eosinophil activation. However, serum levels of ECP and EPX were not significantly high in relation to the total number of eosinophil cells, although they were more numerous than in healthy controls. Moreover, the release of intracytoplasmic basic proteins by the patient's eosinophils was poor even after in vitro stimulation. Since hypereosinophilic syndrome (HES) with organ damage can appear as long as 8-9 years after the presence of a hypereosinophilic state, the absolutely benign nature of our patient's condition still cannot be defined. Thus, there is the possibility it could be slow-onset or smoldering HES.

Efficacy and tolerability of nasally administered compared to parenterally administered metoclopramide in the symptomatic treatment of chemotherapy-induced emesis in cancer outpatients. A controlled clinical study.

The clinical efficacy and tolerability of a new nasal spray formulation of metoclopramide (MTC) was evaluated in terms of its ability to prevent the nausea and vomiting induced by a moderately emetic chemotherapy (cisplatin 20 mg/m2 weekly as radioenhancer+radiotherapy for a fractionated total of 60 Gy) in 12 patients with non-small-cell lung cancer, stage IIIB. The first chemotherapy cycle was administered without any prophylaxis in order to identify those patients who experienced grade 2 nausea and/or vomiting. As prophylaxis during the second cycle, these patients were given MTC 20 mg i.v. at time zero, and MTC 20 mg i.m. after 4 h and 8 h; during the third cycle, they received MTC 40 mg by nasal spray 2 h before chemotherapy, followed by the same dose at 4 h and 8 h. The two prophylactic treatments (parenteral injections and nasal spray) proved to be therapeutically equivalent: complete protection, 6 and 6 patients respectively; major protection, 2 and 3 patients; minor protection, 1 and 1 patient; no protection, 3 and 2 patients. The control of nausea was satisfactory, with 7 and 9 patients respectively experiencing grade 0-1 nausea. Comparative analysis of individual responses confirmed the similar anti-emetic efficacy of the two regimens. No adverse reactions were observed at any time during the course of the study, and all 12 patients judged the acceptability of the new formulation as optimal. It can thus be concluded that the use of metoclopramide nasal spray represents an effective, safe, easily managed and low-cost therapeutic alternative for the prophylaxis and treatment of emesis induced by low-dose chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Histoplasmosis in an HIV-negative Italian man with mycosis fungoides.

The authors deal with a case of Histoplasmosis in a 50 yr old Italian man without any history of risk exposure to HIV infection and suffering from mycosis fungoides. Although this infection is rare in Europe and particularly in Italy, this case suggests the possibility that soils capable of supporting the saprophytic fungus growth are present even out of the endemic areas.