The DES-OSA Score for Identifying Patients with Sleep Apnea: A Validation Study and Suggestions for Improvement.

BACKGROUND: The DES-obstructive sleep apnea (DES-OSA) score uses morphological characteristics to predict the presence and severity of obstructive sleep apnea syndrome (OSAS). OBJECTIVES: To validate DES-OSA scores on the Israeli population. To identify patients requiring treatment for OSAS. To evaluate whether additional parameters could improve the diagnostic value of DES-OSA scores. METHODS: We performed a prospective cohort study on patients attending a sleep clinic. Polysomnography results were examined independently by two physicians. DES-OSA scores were calculated. STOP and Epworth questionnaires were administered, and data on cardiovascular risk was extracted. RESULTS: We recruited 106 patients, median age 64 years, 58% male. DES-OSA scores were positively correlated with apnea-hypopnea index (AHI) (P < 0.001) and were significantly different between the OSAS severity groups. Interobserver agreement for calculating DES-OSA was very high between the two physicians (intraclass correlation coefficient 0.86). DES-OSA scores ≤ 5 were associated with high sensitivity and low specificity (0.90 and 0.27, respectively) for moderate to severe OSAS. In univariate analysis, only age was significantly correlated with the presence of OSAS (OR 1.26, P = 0.01). Age older than 66 years as a single point in the DES-OSA score slightly improved the sensitivity of the test. CONCLUSIONS: DES-OSA is a valid score based solely on physical examination, which may be useful for excluding OSAS requiring therapy. DES-OSA score ≤ 5 effectively ruled out moderate to severe OSAS. Age older than 66 years as an extra point improved the sensitivity of the test.

Pulmonary capillary surface area in supine exercising humans: demonstration of vascular recruitment.

In exercising humans, cardiac output (CO) increases, with minor increases in pulmonary artery pressure (PAP). It is unknown if the CO is accommodated via distention of already perfused capillaries or via recruitment of nonconcomitantly perfused pulmonary capillaries. Ten subjects (9 female) performed symptom-limited exercise. Six had resting mean PAP (PAPm) <20 mmHg, and four had PAPm between 21 and 24 mmHg. The first-pass pulmonary circulatory metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) was measured at rest and at peak exercise, and functional capillary surface area (FCSA) was calculated. Data are means ± SD. Mean pulmonary arterial pressure rose from 18.8 ± 3.3 SD mmHg to 28.5 ± 4.6 SD mmHg, CO from 6.4 ± 1.6 to 13.4 ± 2.9 L/min, and pulmonary artery wedge pressure from 14 ± 3.3 to 19.5 ± 5 mmHg (all P ≤ 0.001). Percent BPAP metabolism fell from 74.7 ± 0.1% to 67.1 ± 0.1%, and FCSA/body surface area (BSA) rose from 2,939 ± 640 to 5,018 ± 1,032 mL·min-1·m-2 (all P < 0.001). In nine subjects, the FCSA/BSA-to-CO relationship suggested principally capillary recruitment and not distention. In subject 10, a marathon runner, resting CO and FCSA/BSA were high, and increases with exercise suggested distention. Exercising humans demonstrate pulmonary capillary recruitment and distention. At moderate resting CO, increasing blood flow causes principally recruitment while, based on one subject, when exercise begins at high CO, further increases appear to cause distention. Our findings clarify an important physiologic question. The technique may provide a means for further understanding exercise physiology, its limitation in pulmonary hypertension, and responses to therapy.

Reduction of exposure to tacrolimus trough level variability is associated with better graft survival after kidney transplantation.

PURPOSE: High tacrolimus trough drug level variability was found to be associated with reduced graft survival. The primary goal of this study was to find whether reduction of exposure to high tacrolimus trough level variability in patients in which previously had high variability was associated with better graft survival. METHODS: All tacrolimus drug level values in patients that underwent kidney transplantation at our center between 2006 and 2015 were collected. Exposure to variability was calculated using a time-weighted coefficient of variability (TWCV). Time-dependent univariate and multivariate Cox proportional hazard models were used to analyze the primary outcome of graft survival and to determine a cutoff value for TWCV as a predictor of this outcome. RESULTS: A total of 878 patients were included in the study with a median follow-up of 1263 days. TWCV above 25% was significantly associated with reduced graft survival (HR3.66, 95% CI 2.3-5.8, p < 0.001). Of the 480 patients (54.7%) who had a cumulative TWCV of > 25% at a certain time during the follow-up, 110 (22.9%) later returned to a cumulative TWCV of less than 25%. Reduction of TWCV to values below 25% was associated with a hazard of graft loss that was not different from patients who had cumulative TWCV of less than 25% during the entire follow-up period (HR 1.81, 95% CI 0.71-4.62, p = 0.218 and HR 1.08, 95% CI 0.39-2.99, p = 0.780) in univariate and multivariate analyses, respectively. CONCLUSIONS: Monitoring TWCV can help detect the high-risk patients. Interventions intended to reduce variability on long-term graft survival may have a positive effect on graft survival.

IPF patients are limited by mechanical and not pulmonary-vascular factors - results of a derivation-validation cohort study.

BACKGROUND: During cardiopulmonary exercise testing (CPET), Idiopathic Pulmonary Fibrosis (IPF) patients do not reach their direct maximum voluntary ventilation (MVV) and have deranged gas exchange. Their exercise limitation is therefore attributed to a pulmonary vascular mechanism. METHODS: We studied two cohorts (derivation and validation) of IPF patients with lung function testing and CPET. Maximal ventilation at exercise (VEpeak) was compared to direct MVV by Bland-Altman analysis. RESULTS: In the derivation cohort (n = 101), direct MVV over-estimated VEpeak by a factor of 1.51, driven by respiratory rate during MVV that was 1.99 times higher at rest as compared to VEpeak at exercise. The formula (FEV1 × 20.1) + 15.4 was shown to predict VEpeak (r2 = 0.56) in the derivation cohort. In the validation cohort of 78 patients, VEpeak was within a factor of 1.27 (6.8 l/min) of predicted according to the novel formula. According to the novel prediction formula the majority of patients (58%) in the entire cohort have VEpeak within 85% of their predicted MVV, which would indicate a mechanical respiratory limitation to exercise. CONCLUSION: Estimation of direct MVV performed at rest leads to significant over-estimation of the breathing reserve in IPF patients. This may lead to over-diagnosis of pulmonary vascular limitation in these patients. Expected maximal ventilation at exercise may be accurately predicted indirectly by an IPF-specific formula.

The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation.

PURPOSE: Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. METHODS: We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. RESULTS: Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. CONCLUSION: Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

Survival following lung transplantation for artificial stone silicosis relative to idiopathic pulmonary fibrosis.

BACKGROUND: Silicosis is a progressive lung disease resulting from the inhalation of respirable crystalline silica. Lung transplantation is the only treatment for end-stage silicosis. The aim of this study was to analyze the survival experience following lung transplantation among patients with silicosis. METHODS: We reviewed data for all patients who underwent lung transplantation for silicosis and a matched group undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF) at a single medical center between March 2006 and the end of December 2013. Survival was followed through 2015. RESULTS: A total of 17 lung transplantations were performed for silicosis among 342 lung transplantations (4.9%) during the study period. We observed non-statistically significant survival advantage (hazard ratio 0.6; 95%CI 0.24-1.55) for those undergoing lung transplantation for silicosis relative to IPF patients undergoing lung transplantation during the same period. CONCLUSIONS: Within the limits of a small sample, survival in silicosis patients following lung transplantation was not reduced compared to IPF. Am. J. Ind. Med. 60:248-254, 2017. © 2017 Wiley Periodicals, Inc.

Evaluation of the Microstat™ sublingual PCO2 monitor in ambulatory patients.

Physicians often need to measure arterial PCO2 in clinical practice. Arterial blood gas sampling is typically available only in hospitals and may be unpleasant for patients. Minimally invasive techniques for measuring PCO2 offer the potential for overcoming these limitations. The MicroStat monitor non-invasively measures PCO2 in the sublingual tissues, which should track arterial PCO2 in hemodynamically stable patients. This was a prospective observational study. Patients undergoing routine cardiac catheterization were recruited. Following arterial cannulation, two sequential sublingual PCO2 measurements were taken and a contemporaneous arterial sample was sent for blood gas analysis. For each subject we calculated the mean sublingual-arterial CO2 gradient and the test-retest sublingual PCO2 difference. Twenty-five patients were studied. Mean sublingual-arterial PCO2 gradient was +6.8 mmHg (95 % limits of agreement -3.0 to 16.6 mmHg). Test-retest difference was 3.4 mmHg (95 % limits of agreement -1.1 to 7.9 mmHg), p = 0.11 (Wilcoxon test), repeatability was 11 mmHg. The MicroStat sublingual PCO2 monitor over-estimates arterial PCO2 with wide limits of agreement. Test-retest repeatability was poor. Use of sublingual PCO2 monitoring with the MicroStat monitor cannot currently replace blood gas sampling.

Effect of Jewish-Arab Ancestry and Gender Matching on Clinical Outcome of Lung Transplantation in Israel.

BACKGROUND: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor-recipients lead to a decrease in survival of the recipient. OBJECTIVES: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch. METHODS: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). RESULTS: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012-1.037). CONCLUSIONS: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

Evaluation of tearing in oculoplastics assisted by tear osmolarity measurement.

PURPOSE: To determine the tear osmolarity in patients with tearing secondary to dry eye and other pathologies, and to determine the prevalence of dry eye disease among patients with tearing in an oculoplastics setting. METHODS: 108 eyes of 54 patients with a chief complaint of tearing were prospectively recruited. Subjects were excluded if they used eye drops or contact lenses within 2 hours of assessment, had a history of refractive surgery, an active ocular allergy, or evidence of a systemic disease which affects tear production. A full medical and ocular history was taken with a complete eye exam pertinent to dry eye. Tear osmolarity was measured using the TearLab device. A clinical diagnosis of dry eye was made based on findings, without reference to tear osmolarity. RESULTS: Among 86 eyes symptomatic for tearing, 32 eyes had dry eye disease (37%). Patients with dry eye had a significantly higher median tear osmolarity compared to that in patients with other diagnoses (308 mOsm/L vs. 294 mOsm/L, p < 0.0001). At a cut-off of 308 mOsm/L, tear osmolarity resulted in a sensitivity of 50% and a specificity of 88% for the diagnosis of dry eye. CONCLUSIONS: A significant proportion of patients with tearing in an oculoplastics practice had dry eye disease. The high specificity of tear osmolarity may render it a useful tool to rule in dry eye disease and may assist the oculoplastic surgeon in more accurately determining the cause of tearing.

High prevalence of occult left heart disease in scleroderma-pulmonary hypertension.

Our study aimed to determine the prevalence of occult left-heart disease in patients with scleroderma and pulmonary hypertension. In patients with pulmonary hypertension (mean pulmonary artery pressure (mean PAP)≥25 mmHg), differentiation between pre- and post-capillary pulmonary hypertension has been made according to pulmonary artery wedge pressure (PAWP) less than or more than 15 mmHg, respectively. We performed a retrospective chart review of 107 scleroderma patients. All patients with suspected pulmonary hypertension had routine right or left heart catheterisation with left ventricular end-diastolic pressure (LVEDP) measurement pre-/post-fluid challenge. We extracted demographic, haemodynamic and echocardiographic data. Patients were classified into one of four groups: haemodynamically normal (mean PAP<25 mmHg); pulmonary venous hypertension (PVH) (mean PAP≥25 mmHg, PAWP>15 mmHg); occult PVH (mean PAP≥25 mmHg, PAWP≤15 mmHg, LVEDP>15 mmHg before or after fluid challenge); and pulmonary arterial hypertension (PAH) (mean PAP≥25 mmHg, PAWP≤15 mmHg and LVEDP≤15 mmHg before or after fluid challenge). 53 out of 107 patients had pulmonary hypertension. Based on the PAWP-based definition, 29 out of 53 had PAH and 24 out of 53 had PVH. After considering the resting and post-fluid-challenge LVEDP, 11 PAH patients were reclassified as occult PVH. The occult PVH group was haemodynamically, echocardiographically and demographically closer to the PVH group than the PAH group. PVH had high prevalence in our scleroderma-pulmonary hypertension population. Distinguishing PAH from PVH with only PAWP may result in some PVH patients being misclassified as having PAH.

Pulmonary arterial hypertension in the elderly-clinical characteristics and long-term survival.

BACKGROUND: Recent registries describe a significant prevalence of pulmonary arterial hypertension (PAH) in the elderly, but little is known of their characteristics. We aimed to examine the features and prognostic factors of long-term survival in elderly (≥65 years) PAH patients. METHODS: Clinical, echocardiographic, angiographic, hemodynamic, treatments, and survival data were reviewed in consecutive patients over the course of 20 years. Elderly PAH patients (n = 47) were compared to younger PAH patients (n = 107). RESULTS: At presentation, elderly patients were more likely to have hypertension, diabetes, dyslipidemia, coronary disease, and PAH associated with scleroderma (42.6 vs. 24.3 %; p = 0.02) than younger patients. Prior to PAH therapy, elderly patients had better right ventricular myocardial performance index (RV-MPI; 0.48 ± 0.20 vs. 0.62 ± 0.23, p = 0.006) and lower mean pulmonary arterial pressure (PAP; 45.0 ± 11.1 vs. 49.2 ± 11.8 mmHg, p = 0.04). Elderly patients were treated less often with epoprostenol (8.5 vs. 29 %, p = 0.006) or trepostinil (8.5 vs. 23.4 %, p = 0.04). The 1, 3, and 5 year survival rates of elderly patients were estimated to be 76.4, 50.5, and 37.6 %, respectively. In comparison, younger patients had survival estimates of 92.2, 74.2 and 64.0 % (p = 0.002). Baseline right atrial pressure, mean PAP, cardiac index, and RV-MPI were associated with survival in elderly patients; however in these patients, survival was not affected by any PAH subgroup or age (per year) by itself. CONCLUSIONS: The diagnosis of PAH in elderly patients is associated with poorer survival which is in part explained by a greater vulnerability to the hemodynamic disturbances of PAH.

Pulmonary capillary recruitment and distention in mammalian lungs: species similarities.

Pulmonary arterial pressure rises minimally during exercise. The pulmonary microcirculation accommodates increasing blood flow via recruitment of pulmonary capillaries and, at higher flows, by distention of already perfused capillaries. The flow transition range between recruitment and distention has not been studied or compared across mammalian species, including humans. We hypothesised that the range would be similar. Functional pulmonary capillary surface area (FCSA) can be estimated using validated metabolic techniques. We reviewed data from previous studies in three mammalian species (perfused rabbit lungs and dog lung lobes, and exercising humans) and generated blood flow-FCSA curves over a range of flows. We noted where the curves diverged from the theoretical line of pure recruitment (Recruitment) and determined the flow where the curve slope equalled 50% that of Recruitment, or equalled that of a theoretical curve representing full capillary distention (Distention). The three mammalian species have similar flow ranges for the transition from predominantly recruitment to predominantly distention, with dogs having the highest transition point. Within the physiological range of most daily activity, the species are similar and accommodate increasing blood flow mainly via recruitment, with progressive distention at higher flows. This is highly relevant to pulmonary physiology during exercise.

The Paradox of Pulmonary Vascular Resistance: Restoration of Pulmonary Capillary Recruitment as a Sine Qua Non for True Therapeutic Success in Pulmonary Arterial Hypertension.

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials.

Ambulatory rehabilitation improves exercise capacity in patients with pulmonary hypertension.

BACKGROUND: Rehabilitation is a central treatment modality for patients with chronic cardiopulmonary disease. Physical exertion for patients with pulmonary arterial hypertension (PAH) has typically been discouraged. Inpatient pulmonary rehabilitation has been shown to improve exercise capacity in patients with PAH. The present study aimed to evaluate outpatient pulmonary rehabilitation for patients with PAH. METHODS AND RESULTS: Twenty-two patients with PAH or chronic pulmonary thromboembolic disease were allocated to ambulatory rehabilitation (n = 11) or to the control group (n = 11). All patients were stable on PAH-specific medication. The rehabilitation group underwent 24 1-hour sessions of exercise training/rehabilitation over 12 weeks. Primary end points were change in 6-minute walking distance (6MWD) and peak oxygen uptake (VO(2)) on cardiopulmonary exercise testing. All of the patients assigned to rehabilitation and 9 control subjects completed the study. In the rehabilitation group, 6MWD increased by 32 m, and in the control group 6MWD decreased by 26 meters (P = .003). Peak VO(2) increased in the rehabilitation group by 1.1 mL kg(-1) min(-1) and decreased by 0.5 mL kg(-1) min(-1) in the control group (P < .05). Peak work rate during cardiopulmonary exercise test also increased in the rehabilitation group, with borderline significance (P = .051). Echocardiography and blood N-terminal pro-brain natriuretic peptide levels were unchanged. No adverse events occurred due to the rehabilitation program. CONCLUSIONS: Ambulatory rehabilitation is a safe and efficacious treatment for patients with pulmonary hypertension already on medical therapy. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov ID: NCT00544726.

Non-tuberculous, adenosine deaminase-positive lymphocytic pleural effusion: Consider immunoglobulin G4-related disease.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a recently described systemic disorder. Pleural effusion is considered an uncommon manifestation of the disease. We describe a case series of patients with IgG4-RD and clinically significant pleural effusions. METHODS: A retrospective analysis of patients with histologically proven IgG4-RD treated for pleural effusion in our clinic. RESULTS: We identified 4 male patients with pleural effusion caused by IgG4-RD. The effusions were lymphocytic exudates, with especially high protein concentrations. All patients had hyperglobulinemia, elevated serum immunoglobulin G (IgG) levels and elevated levels subclasses IgG1 and IgG4. In two patients, levels of adenosine deaminase (ADA) were measured in the effusion and were elevated (309 and 108 IU/L). Tuberculosis was excluded in both cases by pleural biopsy. Involvement of other organs by IgG4-RD was the rule, especially thoracic lymphadenopathy which was prominent in all patients. In all cases, effusion responded to corticosteroids therapy. One patient developed radiological findings compatible with rounded atelectasis during remission. CONCLUSIONS: IgG4-RD may cause an ADA-positive, lymphocytic exudate with a high protein concentration, characteristics resembling tuberculous effusion. Thoracic lymphadenopathy, hyperglobulinemia, and an increased total IgG, IgG1, IgG4 may suggest the diagnosis. Not previously described, IgG4-RD pleural inflammation may result in rounded atelectasis. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 225-230).

Surgical management of metastatic sarcoma to the brain.

OBJECT: Metastatic sarcoma to the brain is rare and represents a therapeutic challenge due to its relative resistance to radio- and chemotherapy. Resection has traditionally been the mainstay of treatment. The authors reviewed a series of patients with metastatic sarcoma to the brain treated surgically to determine outcomes and identify predictors of survival in these patients. METHODS: A retrospective review of prospectively collected data was undertaken on patients undergoing surgery between 1993 and 2005 for metastatic sarcoma to the brain at The University of Texas, M.D. Anderson Cancer Center. RESULTS: During the study period, 62 patients underwent 84 operations for metastatic sarcoma to the brain. The median postoperative overall and progression-free survival rates were 7.5 and 4.7 months, respectively. Fifty-nine (95%) of 62 patients had a gross-total resection. The 30-day mortality rate was 4.2%. The Karnofsky Performance Scale scores at discharge from the hospital and 3 months postoperatively were the same or improved in 50 (85%) of 59 and 26 (51%) of 51, respectively. Overall postcraniotomy survival was 62% at 6 months, 39% at 1 year, 21% at 2 years, and 8% at 5 years. In multivariate and univariate analysis, control of systemic disease, and sarcomas originating from bone, cartilage, or soft tissue were predictors of survival. Patients with control of systemic disease had survival advantage when compared with those who did not. In patients with alveolar soft-part sarcoma, there was a significantly increased survival advantage compared with all other histological subgroups. CONCLUSIONS: The authors' results suggest that in selected patients, resection of metastatic sarcoma to the brain is associated with a relatively low risk of operative death and results in improvement in neurological function. Patients with systemic control of their primary disease and certain histological subtypes (specifically alveolar soft-part sarcoma) have improved overall and progression-free survival.

Stereotactic radiosurgery for metastatic brain tumors: a comprehensive review of complications.

OBJECT: Stereotactic radiosurgery (SRS) is commonly used to treat brain metastases. Complications associated with this treatment are underreported. The authors reviewed a large series of patients who underwent SRS for brain metastases to identify complications and factors predicting their occurrence. METHODS: Prospectively collected clinical data from 273 patients undergoing SRS for 1 or 2 brain metastases at The University of Texas M. D. Anderson Cancer Center between June 1993 and December 2004 were reviewed. Patients who had received prior treatment for their tumor, including whole-brain radiation, SRS, or surgery, were excluded from the study. Data on adverse neurological and nonneurological outcomes following treatment were collected. RESULTS: Three hundred sixteen lesions were treated. Complications were associated with 127 (40%) of 316 treated lesions. New neurological complications were associated with 101 (32%) of 316 lesions. The onset of seizure was the most common complication, occurring in 41 (13%) of 316 SRS cases. On multivariate analysis, progressing primary cancer (hazard ratio [HR]=2.4, 95% CI 1.6-3.6, p<0.001), tumor location in eloquent cortex (HR=2.3, 95% CI 1.6-3.4, p<0.001), and lower (<15 Gy) SRS dose (HR=2.1, 95% CI 1.1-4.2, p=0.04) were significantly associated with new complications. On multivariate analysis, a tumor location in the eloquent cortex (HR=2.5, 95% CI 1.6-3.8, p<0.001) and progressing primary cancer (HR=1.6, 95% CI 1.1-2.5, p=0.03) were significantly associated with new neurological complications. CONCLUSIONS: The authors showed that new neurological and nonneurological complications were associated with 40% of SRS treatments for brain metastases. Patients with lesions in functional brain regions have a significantly increased risk of treatment-related complications.

The QuantiFERON-TB-GOLD assay for tuberculosis screening in healthcare workers: a cost-comparison analysis.

The aim of this study was to assess the costs of screening healthcare workers (HCWs) for tuberculosis (TB) using the novel interferon-gamma release assay QuantiFERON((R))-TB Gold In-tube (QFT) versus the tuberculin skin test (TST). We used a prospective observational study with a cost-comparison analysis. The study was conducted at a regional center for ambulatory TB treatment. The study included 100 Israeli HCWs who were referred for routine TB screening. The participants were tested with both TST and QFT. For the TST, induration of 10 mm or more was considered a positive test. For the QFT, a threshold of 0.35 IU/ml interferon-gamma above background levels was a positive test. We developed a computerized model of the present TST-only screening method versus the QFT either alone (instead of the TST) or as a confirmatory test for a positive TST. Of the 100 subjects, 34 had a positive TST result and 17 had a positive QFT result. There was poor agreement between the TST and the QFT (kappa = 0.19). Assuming adherence to treatment of 50%, costs were minimized by using the QFT to confirm a positive TST (4155). The QFT-only model was cheaper than the TST-only model (7280 vs. 8217, respectively). The QFT-only method required the fewest clinic visits (121) compared to the TST (344). Adherence to treatment in the QFT-positive group was 47% compared with 12% for the TST-positive group. Screening HCWs with the QFT test compared to the TST resulted in fewer possible cases being identified, lower costs, and increased adherence to treatment. Costs were minimized by using the QFT to confirm a positive TST. A QFT-based screening program for HCWs is feasible and should be evaluated systematically.