Elisa Carretta

Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases

Background Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. Objectives To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. Method Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features. Results Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94–76.25). Diagnostic yield: among adequate TBLC the pathologists were confident (“high confidence”) that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis–interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident (“low confidence”). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69–0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable. Conclusions TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.

Bronchoscopic Lung Cryobiopsy Increases Diagnostic Confidence in the Multidisciplinary Diagnosis of Idiopathic Pulmonary Fibrosis

RATIONALE Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable. OBJECTIVES To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF. METHODS In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels. MEASUREMENTS AND MAIN RESULTS We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF. CONCLUSIONS BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.

Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment

BACKGROUND Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis. METHODS One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality. RESULTS RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS [intermittent (I-RLS) vs continuous (C-RLS)]. Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality. CONCLUSIONS This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Hip fracture: effectiveness of early surgery to prevent 30-day mortality

To estimate the effect of delay to surgery for hip fracture on 30-day mortality using a risk adjustment strategy to control for the effect of demographic and clinical confounders. This observational study was carried out on all patients admitted with a hip fracture and discharged between January 2004 and December 2007 from a teaching hospital. Gender, age, time to surgery, mortality and medical comorbidities were derived from hospital discharge records (SDO), while International Normalised Ratio (INR) and American Society of Anaesthesiologists (ASA) score were retrieved from clinical records. Backward stepwise logistic regression was used to identify potential confounders in the relationship between time to surgery and mortality. A final multivariate logistic regression analysis was carried out controlling for the effect of confounders. In the 1320 patients who underwent surgery (mean age = 83 years, % female = 76.8%), time to surgery was two days or less in 746 (56.5%) patients and 30-day mortality was 3.5%. The interventions included partial or total hip replacement (N=820, 62.1%) and reduction and internal fixation (N=500, 37.9%). Multivariate logistic regression analysis showed that patients with a time to surgery greater than two days had a 2-fold increase in 30-day mortality after adjusting for age, gender, and comorbidity (OR=1.992, 95% CI 1.065-3.725). In a second model also including ASA score the odd ratio decreased to 1.839 (95% CI 0.971-3.486). Patients with a hip fracture should have surgery within two days from admission in order to reduce 30-day mortality.

PSA flare with abiraterone in patients with metastatic castration-resistant prostate cancer.

BACKGROUND The aim of this study was to assess early serum prostate-specific antigen (PSA) changes in patients treated with abiraterone and to correlate those changes with clinical outcome. PATIENTS AND METHODS We retrospectively evaluated 103 patients with castrate-resistant prostate cancer (CRPC) treated with compassionate use of abiraterone in Romagna, Italy. In these patients, serum PSA levels were monitored every 4 weeks, and a time course of serum PSA levels was obtained. The PSA flare phenomenon was evaluated. The log-rank test was applied to compare survival between groups of patients according to early PSA level changes. RESULTS Of 103 patients, 43 (41.7%) had an immediate PSA response, whereas 9 (8.7%) had an initial PSA flare. Of the 9 patients with PSA flare, 5 attained a subsequent PSA response. The temporary PSA flare exceeded baseline values by a median of 19.7% (range, 5%-62.9%). The median PFS of the 9 patients in the PSA-flare group was higher compared with patients without the PSA flare (10.5 vs. 6.4 months; P = .0999) but was similar to the subgroup of patients with immediate PSA response (10.5 vs. 10.7 months; P = .7019). In the multivariate analysis, only the PSA response remained as a predictor of progression-free survival (PFS) (P < .0001) and overall survival (OS) (P = .0003), respectively. CONCLUSION PSA flare occurs not infrequently in patients with CRPC who respond to abiraterone. Patients should be informed of this possible PSA flare phenomenon.

Chromogranin A predicts outcome in prostate cancer patients treated with abiraterone.

In this retrospective study, we evaluated the chromogranin A (CgA) baseline value as a predictor of clinical outcome in patients with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone 1000 mg per day, whose disease progressed after docetaxel chemotherapy. In the 48 evaluable patients, serum CgA level was normal when <120  ng/ml (group A, n=16), within three times the upper normal value (UNV) when between 120 and 360 (group B, n=16), more than three times the UNV when ≥360  ng/ml (group C, n=16). Decline in PSA level ≥50% or more (PSA RR) was observed in 26 of 48 (54%) patients. PSA response rate did not correlate with the CgA groups. CgA levels more than three times the UNV predicted an early radiological progressive disease in eight of 11 cases (73%). The median progression-free survival (PFS) among the CgA groups A, B, and C was 9.2, 9.2, and 4.8 months respectively, P=0.0459. The median overall survival (OS) among the CgA groups was 19.0, 18.8, and 10.8 months respectively, P=0.2092. In the multivariate analysis, PSA RR (nonresponsive vs responsive) and CgA levels (group 3 vs groups 1+2) were predictors of PFS (P=0.0002 and P=0.0047 respectively), whereas PSA RR only was significantly associated with OS (P=0.0024), while CgA levels remained of borderline significance (P=0.0919). A serum CGA level more than three times the UNV predicted PFS and showed a trend vs OS prediction, independently from PSA response, in CRPC patients treated with abiraterone.

Air pollution from incinerators and reproductive outcomes: a multisite study.

Background: The few studies that have investigated the relationship between emissions from municipal solid-waste incinerators and adverse pregnancy outcomes have had conflicting results. We conducted a study to assess the effects of air emissions from the eight incinerators currently in operation in the Emilia-Romagna Region of Italy on reproductive outcomes (sex ratio, multiple births, preterm births, and small for gestational age [SGA] births). Methods: We considered all births (n = 21,517) to women residing within a 4-km radius of an incinerator at the time of delivery during the period 2003–2010 who were successfully linked to the Delivery Certificate database. This source also provided information on maternal characteristics and deliveries. Each newborn was georeferenced and characterized by a specific level of exposure to incinerator emissions, categorized in quintiles of PM10, and other sources of pollution (NOx quartiles), evaluated by means of ADMS-Urban system dispersion models. We ran logistic regression models for each outcome, adjusting for exposure to other pollution sources and maternal covariates. Results: Incinerator pollution was not associated with sex ratio, multiple births, or frequency of SGA. Preterm delivery increased with increasing exposure (test for trend, P < 0.001); for the highest versus the lowest quintile exposure, the odds ratio was 1.30 (95% confidence interval = 1.08–1.57). A similar trend was observed for very preterm babies. Several sensitivity analyses did not alter these results. Conclusions: Maternal exposure to incinerator emissions, even at very low levels, was associated with preterm delivery.

Role of the hemodialysis vascular access type in inflammation status and monocyte activation

Purpose The aim of this study was to ascertain the role of different vascular access types in inflammatory status, monocyte activation, and senescence in hemodialysis patients. Methods We recruited 126 hemodialysis patients, including 51 with arterovenous fistula (AVF), 32 with arterovenous graft (AVG), and 43 with tunneled cuffed catheters (TCC). In dialysis patients enrolled in the study and in a control group of 40 healthy subjects, we measured the serum levels of albumin, CRP, IL-6, and TNF-α, the expression of CD14, CD44, and CD32 on monocyte surface, and the percentage of monocytes exhibiting a senescent phenotype (CD14+CD32+). Results The patients with AVG compared to those with AVF had: a) higher levels of CRP and TNF-α; b) increased expression of CD14 and CD32 on monocyte surface, with no difference in CD44 expression; c) no difference in the percentage of CD14+CD32+ monocytes. In the comparison of TCC vs. AVF group, we observed significantly higher values of: a) circulating inflammatory markers (CRP, IL-6, TNF-α); b) monocyte surface expression of cellular activation markers (CD14, CD44 and CD32); c) relative count of CD14+CD32+ monocytes. When comparing TCC vs. AVG group, we found: a) no difference in serum levels of CRP, IL-6, and TNF-α; b) no difference in the expression of CD14, CD44, and CD32 on monocyte surface; c) no difference in the percentage of CD14+CD32+ monocytes. Conclusions These results suggest that the use of AVG and TCC for dialysis vascular access is associated with serological and cellular indexes of inflammatory reaction, also resulting in a higher degree of monocyte activation and senescence.

Risk adjustment models for interhospital comparison of CS rates using Robson’s ten group classification system and other socio-demographic and clinical variables

BackgroundCaesarean section (CS) rate is a quality of health care indicator frequently used at national and international level. The aim of this study was to assess whether adjustment for Robson’s Ten Group Classification System (TGCS), and clinical and socio-demographic variables of the mother and the fetus is necessary for inter-hospital comparisons of CS rates.MethodsThe study population includes 64,423 deliveries in Emilia-Romagna between January 1, 2003 and December 31, 2004, classified according to theTGCS. Poisson regression was used to estimate crude and adjusted hospital relative risks of CS compared to a reference category. Analyses were carried out in the overall population and separately according to the Robson groups (groups I, II, III, IV and V–X combined). Adjusted relative risks (RR) of CS were estimated using two risk-adjustment models; the first (M1) including the TGCS group as the only adjustment factor; the second (M2) including in addition demographic and clinical confounders identified using a stepwise selection procedure. Percentage variations between crude and adjusted RRs by hospital were calculated to evaluate the confounding effect of covariates.ResultsThe percentage variations from crude to adjusted RR proved to be similar in M1 and M2 model. However, stratified analyses by Robson’s classification groups showed that residual confounding for clinical and demographic variables was present in groups I (nulliparous, single, cephalic, ≥37 weeks, spontaneous labour) and III (multiparous, excluding previous CS, single, cephalic, ≥37 weeks, spontaneous labour) and IV (multiparous, excluding previous CS, single, cephalic, ≥37 weeks, induced or CS before labour) and to a minor extent in groups II (nulliparous, single, cephalic, ≥37 weeks, induced or CS before labour) and IV (multiparous, excluding previous CS, single, cephalic, ≥37 weeks, induced or CS before labour).ConclusionsThe TGCS classification is useful for inter-hospital comparison of CS section rates, but residual confounding is present in the TGCS strata.

Urinary neutrophil gelatinase-associated lipocalin at birth predicts early renal function in very low birth weight infants.

Preterm infants are exposed to conditions that can impair renal function. We evaluated the ability of serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL) to predict renal function in the first weeks of life. From September 2008 to July 2009, infants weighing ≤1500 g at birth with no major congenital anomalies or sepsis were eligible. We measured sNGAL and uNGAL levels at birth. To evaluate renal function, we determined changes in serum creatinine (sCreat) and estimated GFR (eGFR) from birth to d 21. Forty neonates (mean GA, 27 ± 2 wk) completed the study. Renal function improved in 32 of 40 (80%) infants (normal renal function, NRF group) (sCreat, from 0.97 ± 0.2 to 0.53 ± 0.13 mg/dL; eGFR, from 15.3 ± 4.1 to 28.6 ± 7.9 mL/min), whereas renal function worsened in 8 of 40 (20%) infants (impaired renal function, IRF group) (sCreat, from 0.71 ± 0.27 to 0.98 ± 0.43 mg/dL; eGFR from 23 ± 14.7 to 16.4 ± 9.1 mL/min). The uNGAL/urinary creatinine (uCreat) ratio at birth was higher in the IRF group (31.05 ng/mg) than the NRF group (6.0 ng/mg), and uNGAL was significantly higher in IRF group, detecting IRF with a cutoff of 100 ng/mL. uNGAL levels at birth may have a predictive role in very LBW (VLBW) infants.