Psychosocial stress differentially affects emotional empathy in women with borderline personality disorder and healthy controls.

OBJECTIVE: Deficits in empathy, an important part of social cognition, have been described in patients with borderline personality disorder (BPD). Importantly, psychosocial stress enhances emotional empathy in healthy participants. However, it remains unknown whether stress affects empathy in BPD. METHOD: We randomized 47 women with BPD and 47 healthy women to either the Trier Social Stress Test or a control condition. Subsequently, all participants underwent the Multifaceted Empathy Test (MET), a measure of cognitive and emotional facets of empathy. RESULTS: Across groups, stress resulted in a significant increase in cortisol and stress ratings. There was a significant stress × group interaction for emotional empathy (Fdf1,92 = 5.12, P = 0.04, ηp2 = 0.05). While there was no difference between patients with BPD and healthy participants after the control condition, patients with BPD had significantly lower emotional empathy scores after stress compared to healthy individuals. There were no effects for cognitive empathy. CONCLUSION: The current finding provides first evidence that stress differentially affects emotional empathy in patients with BPD and healthy individuals such that patients with BPD showed reduced emotional empathy compared to healthy women after stress. Given the strong impact of stress on acute psychopathology in patients with BPD, such a response may exacerbate interpersonal conflicts in stress contexts and may be an important target for therapeutic interventions.

Biomechanical strength and failure mechanism of different tubercula refixation methods within the framework of an arthroplasty for shoulder fracture.

BACKGROUND: Tuberosity repair in shoulder fracture prosthesis implantation still remains a challenge often leading to poor functional outcomes, despite a variety of materials and suggested suture patterns. We aimed to evaluate, which forces currently used suture and cerclage materials withstand and to assess whether they are useful with regard to stability of reconstruction of tuberosities and which failure modes they display. MATERIAL AND METHODS: Using sheep infraspinatus tendons with attached tuberosities three different suture materials (suture 1: Ethibond size 2; suture 2: Orthocord size 2; suture 3: Fiberwire size 5) and a 0.8mm titanium cerclage wire were investigated. For each suture material as well as the cerclage wire 6 tests were carried out. A material testing machine was used to perform cyclic loading tests (20mm/min, Fmin=50N, Fmax=100N, respectively after 50 cycles: Fmax+50N until failure). Outcome measures and thus comparison criteria were the maximum holding force, number of cycles reached, total elongation of the system (tendon and suture) and qualitative appraisal and documentation of the mechanism of failure. RESULTS: Overall average maximum forces between the fixation materials differed significantly (P=0.003), especially suture 3 (braided polyethylene coating, non-resorbable polyfile UHMW core) displayed superior results in comparison to the cerclage wire (P=0.016). Although, primary elongation of the cerclage technique was significantly lower compared to the suture materials (P=0.002). All tests showed a high initial lengthening and caused incision-like defects in the bone or tendon and led to failure and huge displacement of the tuberosities. DISCUSSION: Currently used suture and cerclage materials have a limited usefulness for refixation of tuberosities due to an increased risk of obstruction for bony consolidation. LEVEL OF EVIDENCE: Basic science, Biomechanics.

High and low vitamin D level is associated with cardiovascular autonomic neuropathy in people with Type 1 and Type 2 diabetes.

AIM: To investigate the possible association between vitamin D deficiency and cardiovascular autonomic neuropathy in people with diabetes. METHODS: A total of 113 people with Type 1 or Type 2 diabetes [mean (interquartile range) diabetes duration 22.0 (12-31) years, mean (sd) age 56.2 (13.0) years, 58% men] underwent vitamin D (D2 and D3) assessment, and were screened for cardiovascular autonomic neuropathy using three cardiovascular reflex tests [heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva manoeuvre] and assessment of 5-min resting heart rate and heart rate variability indices. RESULTS: We found an inverse U-shaped association between serum vitamin D level and E/I ratio, 30/15 ratio and three heart rate variability indices (P < 0.05). Vitamin D level was non-linearly associated with cardiovascular autonomic neuropathy diagnosis (P < 0.05 adjusted for age and sex). Linear regression models showed that an increase in vitamin D level from 25 to 50 nmol/l was associated with an increase of 3.9% (95% CI 0.1;7.9) in E/I ratio and 4.8% (95% CI 4.7;9.3) in 30/15 ratio. Conversely, an increase from 125 to 150 nmol/l in vitamin D level was associated with a decrease of 2.6% (95% CI -5.8;0.1) and 4.1% (95% CI -5.8;-0.5) in the respective outcome measures. CONCLUSIONS: High and low vitamin D levels were associated with cardiovascular autonomic neuropathy in people with diabetes. Future studies should explore this association and the efficacy of treating dysvitaminosis D to prevent cardiovascular autonomic neuropathy.

Does the implant make the difference ? - Prospective comparison of two different proximal femur nails.

The aim of this study was to compare two proximal femur nails with regard to the complication rate and midterm clinical outcome : the InterTAN nail (ITN) versus the third generation gamma nail (GN). 78 patients older than 60 years with an unstable intertrochanteric femoral fracture (AO/OTA 31 A2/A3) were randomised over a 20 month period into either ITN (n = 39) or GN (n = 39). The outcomes of interest were the perioperative implant-related complications and the functional status (Harris Hip Score) at 6 months postoperatively. In 14 of the ITN and in two of the GN procedures the surgeons rated the implant as cumbersome (p = 0.002). Functional outcome and complication rate did not differ between both groups. The mechanical failure correlated with the positioning of the lag screw independent on the used implant. The surgeon's technique (closed reduction, positioning of lag screw) and not implant configuration, is of crucial importance in achieving successful outcome.

Model of anisotropic nonlinearity in self-defocusing photorefractive media.

We develop a phenomenological model of anisotropy in self-defocusing photorefractive crystals. In addition to an independent term due to nonlinear susceptibility, we introduce a nonlinear, non-separable correction to the spectral diffraction operator. The model successfully describes the crossover between photovoltaic and photorefractive responses and the spatially dispersive shock wave behavior of a nonlinearly spreading Gaussian input beam. It should prove useful for characterizing internal charge dynamics in complex materials and for accurate image reconstruction through nonlinear media.

The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy: the ADDITION Denmark study.

AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form (n = 882). RESULTS: No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing. CONCLUSION: Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes.

Objective measurements of activity patterns in people with newly diagnosed Type 2 diabetes demonstrate a sedentary lifestyle.

AIMS: To evaluate physical activity in people with newly diagnosed Type 2 diabetes using objective measures. METHODS: We analysed data from a study aimed at assessing carotid femoral pulse wave velocity in which a piezoelectric accelerometer was worn by 100 people with newly diagnosed Type 2 diabetes and by 100 age- and sex-matched control subjects. Differences in physical activity patterns were investigated. RESULTS: Compared with the control group, the people with Type 2 diabetes spent significantly more time engaged in sedentary or lower level activities during the day, with a mean (sd) time of 926 (44) vs 898 (70) min, P < 0.001). This difference remained significant after correction for differences in BMI between the two groups. CONCLUSIONS: Using objective measurements, our findings demonstrate that people with newly diagnosed Type 2 diabetes have a more sedentary lifestyle compared with well-matched controls.

Impact of early detection and treatment of diabetes on the 6-year prevalence of cardiac autonomic neuropathy in people with screen-detected diabetes: ADDITION-Denmark, a cluster-randomised study.

AIMS/HYPOTHESIS: There is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. Cardiac autonomic neuropathy (CAN) in people with diabetes indicates widespread damage to the autonomic nervous system, which may severely affect health and quality of life. We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-randomised parallel group trial. METHODS: One hundred and ninety general practices were randomised to deliver either intensive multifactorial treatment (IT) or routine care (RC) as recommended by national guidelines to patients with type 2 diabetes, identified through a stepwise screening programme in the primary care setting. 1533 people (IT, n = 910; RC, n = 623) were identified and included. At the 6-year follow-up examination, measures of CAN were applied in an unselected subsample of 777 participants using heart rate variability analysis and standard tests of CAN. RESULTS: At the 6-year follow-up examination, the prevalence of early CAN was 15.1% in the RC group and 15.5% in the IT group, while manifest CAN was present in 7.1% and 7.3%, respectively. We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care. CONCLUSIONS/INTERPRETATION: In the Danish arm of the ADDITION Study, signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes. Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care. However, at follow-up the level of medication was also high in the RC group.

Premenopausal women with idiopathic low-trauma fractures and/or low bone mineral density.

INTRODUCTION: In men, idiopathic osteoporosis (IOP) is often associated with low serum insulin-like growth factor (IGF-1) and reduced bone formation. The characteristics of premenopausal women with IOP are not well defined. We aimed to define the clinical, reproductive, and biochemical characteristics of premenopausal women with unexplained osteoporosis. METHODS: This is a cross-sectional study of 64 women with unexplained osteoporosis, 45 with fragility fractures, 19 with low bone mineral density (BMD; Z-score less than or equal to -2.0) and 40 normal controls. The following are the main outcome measures: clinical and anthropometric characteristics, reproductive history, BMD, gonadal and calciotropic hormones, IGF-1, and bone turnover markers (BTMs). RESULTS: Subjects had lower BMI and BMD than controls, but serum and urinary calcium, serum estradiol, vitamin D metabolites, IGF-1, and most BTMs were similar. Serum parathyroid hormone (PTH) and the resorption marker, tartrate-resistant acid phosphatase (TRAP5b), were significantly higher in both groups of subjects than controls and directly associated in all groups. Serum IGF-1 and all BTMs were directly associated in controls, but the association was not significant after controlling for age. There was no relationship between serum IGF-1 and BTMs in subjects. There were few differences between women with fractures and low BMD. CONCLUSIONS: Higher serum TRAP5b and PTH suggest that increased bone turnover, possibly related to subclinical secondary hyperparathyroidism could contribute to the pathogenesis of IOP. The absence of differences between women with fractures and those with very low BMD indicates that this distinction may not be clinically useful to categorize young women with osteoporosis.

[Biomechanical investigation on refixation of tuberosities on shoulder prostheses. Does refixation with different suture materials offer enough stability?]. / Biomechanische Untersuchung zur Refixation der Tuberkula an Frakturschulterendoprothesen. Bietet die Rekonstruktion der Tuberkula mittels unterschiedlicher Nahtmaterialien eine ausreichende Stabilität?

BACKGROUND: Elderly patients suffering from complex, non-reconstructable fractures of the proximal humerus are commonly treated by primary implantation of a shoulder endoprosthesis. One of the most critical factors for success or failure of treatment is still the refixation of the tuberosities. METHOD: Using sheep infraspinatus tendons with attached tuberosities three different suture materials were investigated. For 2 of the suture materials 4 tests were accomplished and 5 tests were carried out for the third suture material. A material testing machine was used to perform cyclic loading tests (20 mm/min, Fmin=50 N, Fmax=100 N, respectively after 50 cycles: Fmax+50 N until failure). RESULTS: The results showed large variations in the average maximum forces (152.4 N for suture 1, 219.9 N for suture 2 and 452.3 N for suture 3). All tests showed a high initial lengthening and caused incision-like defects in the bone or tendon and led to failure and high displacement of the tuberosities. CONCLUSION: Due to these results suture materials have a limited usefulness for refixation of tuberosities as an increased risk of obstruction for bony consolidation can result.

Cardiac structure and diastolic function in mild primary hyperparathyroidism.

CONTEXT: Data on the presence, extent, and reversibility of cardiovascular disease in primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: To evaluate the heart in PHPT, we assessed cardiac structure and diastolic function in patients with mild PHPT compared with age- and sex-matched controls. DESIGN: This was a case-control study. SETTINGS: The study was conducted in a university hospital Metabolic Bone Diseases Unit. PARTICIPANTS: Fifty-four men and women with PHPT and 76 controls without PHPT participated in the study. OUTCOME MEASURES: We measured left ventricular mass index (LVMI), the presence of mitral annular calcification, the ratio of early to late diastolic mitral inflow velocities (E/A), and early diastolic velocity of the lateral mitral annulus using Doppler tissue imaging (tissue Doppler e'). RESULTS: Patients had mild disease with mean (+/-sd) serum calcium 10.5 +/- 0.5 mg/dl and PTH 96 +/- 45 pg/ml. LVMI and diastolic function were normal in PHPT. There was no difference in LVMI (98 +/- 23 vs. 96 +/- 24 g/m(2), P = 0.69) or the frequency of mitral annular calcification between PHPT cases and controls. Diastolic function variables (E/A and tissue Doppler e') were higher (better) in cases compared with controls, although both were within the reference range. PHPT patients with low E/A had higher serum PTH (121 +/- 36 vs. 89 +/- 46 pg/ml, P = 0.03) and calcium (10.8 +/- 0.4 vs. 10.5 +/- 0.5 mg/dl, P = 0.05) than those with normal values. Finally, we found LVMI to be inversely associated with serum 25-hydroxyvitamin D in PHPT (r = -0.29, P < 0.05). All findings persisted after adjustment for group differences in cardiovascular risk factors. CONCLUSIONS: Patients with biochemically mild PHPT do not have evidence of increased left ventricular mass, diastolic dysfunction, or increased valvular calcifications. However, the data support an association between low vitamin D levels and the development of left ventricular hypertrophy in this disorder. Finally, the increased serum calcium and PTH levels in those with diastolic dysfunction suggest that disease severity may determine the presence of cardiac manifestations in PHPT.

[Obligatory vaccination reporting in Saxony-Anhalt. Possibilities and limitations of establishing a computerized vaccination registry]. / Impfmeldepflicht in Sachsen-Anhalt. Möglichkeiten und Grenzen der Entwicklung eines elektronischen Impfregisters.

Vaccination registries are databases intended to assess and manage complete vaccination data of as many individuals as possible in a population under survey. The task of these registries is to identify low vaccination rates on the individual and population level, to enable systems of reminding individuals, to focus vaccination campaigns and to maximize overall vaccination coverage. Saxony-Anhalt is the only federal state of Germany to have a law that prescribes the reporting of vaccinations. Vaccinations of children up to the age of 7 are reported to the regional public health services. However, as the law provides no regulations as to how the data should be registered and processed, the development of a vaccination registry depends entirely on the initiative and cooperation of the "players in vaccination". The key players in vaccination in Saxony-Anhalt have recently created a Vaccination-Committee, which set out to develop the theoretical standards and a software prototype for the establishment of a computerized vaccination registry. Recent developments in the public health reporting system of Saxony-Anhalt (which strives to modernize its computerized assessment of child and adolescent health) are now opening the possibility to integrate the vaccination registry into the commercially available child health software.

Carotid vascular abnormalities in primary hyperparathyroidism.

CONTEXT: Data on the presence, extent, and reversibility of cardiovascular disease in primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: This study evaluated carotid structure and function in PHPT patients compared with population-based controls. DESIGN: This is a case-control study. SETTING: The study was conducted in a university hospital metabolic bone disease unit. PARTICIPANTS: Forty-nine men and women with PHPT and 991 controls without PHPT were studied. OUTCOME MEASURES: We measured carotid intima-media thickness (IMT), carotid plaque presence and thickness, and carotid stiffness, strain, and distensibility. RESULTS: IMT, carotid plaque thickness, carotid stiffness, and distensibility were abnormal in PHPT patients, and IMT was higher in patients than controls (0.959 vs. 0.907 mm, P < 0.0001). In PHPT, PTH levels, but not calcium concentration, predicted carotid stiffness (P = 0.04), strain (P = 0.06), and distensibility (P = 0.07). Patients with increased carotid stiffness had significantly higher PTH levels than did those with normal stiffness (141 +/- 48 vs. 94.9 +/- 44 pg/ml, P = 0.002), and odds of abnormal stiffness increased 1.91 (confidence interval = 1.09-3.35; P = 0.024) for every 10 pg/ml increase in PTH, adjusted for age, creatinine, and albumin-corrected calcium. CONCLUSIONS: Mild PHPT is associated with subclinical carotid vascular manifestations. IMT, a predictor of cardiovascular outcomes, is increased. Measures of carotid stiffness are associated with extent of PTH elevation, suggesting that those with more severe PHPT may have impaired vascular compliance and that PTH, rather than calcium, is the mediator.

The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss.

CONTEXT: Bariatric surgery is common and may be associated with deleterious effects on the skeleton. OBJECTIVE: Our objective was to assess bone metabolism and bone mineral density (BMD) after Roux-en-Y gastric bypass. DESIGN AND SETTING: We conducted a 1-yr prospective longitudinal study at a university hospital bariatric surgery practice and metabolic bone disease unit. PARTICIPANTS: Participants included 23 obese (mean body mass index 47 kg/m(2)) men and women, aged 20-64 yr. MAIN OUTCOME MEASURES: Serum PTH, 25-hydroxyvitamin D, osteocalcin, and urinary N-telopeptide, and BMD were assessed. RESULTS: Patients lost 45 +/- 2 kg 1 yr postoperatively (P < 0.01). PTH increased early (3 months, 43-50 pg/ml; P < 0.001) and urinary calcium dropped (161-92 mg/24 h; P < 0.01), despite doubling of calcium intake (1318-2488 mg/d; P < 0.001). Serum 25-hydroxyvitamin D concentrations were unchanged (23-26 ng/ml), although vitamin D intake increased by 260% (658 IU/d at baseline to 1698 IU/d at 12 months; P < 0.05). Markers of bone remodeling rose (P < 0.01 for both urinary N-telopeptide and osteocalcin), whereas BMD decreased at the femoral neck (9.2%, P < 0.005) and at the total hip (8.0%, P < 0.005). These declines were strongly associated with the extent of weight loss (femoral neck: r = 0.90, P < 0.0001; and total hip: r = 0.65, P = 0.02). Lumbar spine and distal radius sites did not change. CONCLUSIONS: After Roux-en-Y gastric bypass, there was evidence of calcium and vitamin D malabsorption. Bone turnover increased, and hip bone density rapidly declined. The decline in hip BMD was strongly associated with weight loss itself. Vigilance for nutritional deficiencies and bone loss in patients both before and after bariatric surgery is crucial.

Incoherent white-light solitons in nonlinear periodic lattices.

We predict the existence of lattice solitons made of incoherent white light: lattice solitons made of light originating from an ordinary incandescent light bulb. We find that the intensity structure and spatial power spectra associated with different temporal frequency constituents of incoherent white-light lattice solitons (IWLLSs) arrange themselves in a characteristic fashion, with the intensity structure more localized at higher frequencies, and the spatial power spectrum more localized at lower frequencies; the spatial correlation distance is larger at lower frequency constituents of IWLLSs. This characteristic shape of incoherent white-light lattice solitons reflects the fact that diffraction is stronger for lower temporal frequency constituents, while higher frequencies experience stronger effective nonlinearity and deeper lattice structure.

The sense of smell: multiple olfactory subsystems.

The mammalian olfactory system is not uniformly organized but consists of several subsystems each of which probably serves distinct functions. Not only are the two major nasal chemosensory systems, the vomeronasal organ and the main olfactory epithelium, structurally and functionally separate entities, but the latter is further subcompartimentalized into overlapping expression zones and projection-related subzones. Moreover, the populations of 'OR37' neurons not only express a unique type of olfactory receptors but also are segregated in a cluster-like manner and generally project to only one receptor-specific glomerulus. The septal organ is an island of sensory epithelium on the nasal septum positioned at the nasoplatine duct; it is considered as a 'mini-nose' with dual function. A specific chemosensory function of the most recently discovered subsystem, the so-called Grueneberg ganglion, is based on the expression of olfactory marker protein and the axonal projections to defined glomeruli within the olfactory bulb. This complexity of distinct olfactory subsystems may be one of the features determining the enormous chemosensory capacity of the sense of smell.

Design and evaluation of a handheld impedance plethysmograph for measuring heart rate variability.

Heart rate variability (HRV) analysis from 10s ECGs has been shown to be reliable. However, the short examination time warrants a user-friendly system that can be used for ad-hoc examinations without normal preparation, unlike ECG. A handheld device has been developed that can measure ultra-short HRV from impedance plethysmographic recordings of the pulse wave in distal superficial arteries. The prototype device was made user-friendly through a compact, pen-like design and the use of integrated metal electrodes that were especially designed for dry operation. The main signal processing was performed by a digital signal processor, where the discrete heart beats were detected using a correlation algorithm that could adapt to individual pulse wave shapes to account for biological variation. The novel device was evaluated in 20 mainly young volunteers, using 10 s time-correlated ECG recordings as the reference method. Agreement between the two methods in measuring heart rate and root mean square of successive differences in the heart beat interval (RMSSD) was analysed using correlation coefficients (Pearson's R2), mean differences with 95% confidence intervals and 95% limits of agreement, and Bland-Altman plots. The correlation between the two methods was R2 = 1.00 and R2 = 0.99 when heart rate and RMSSD were measured, respectively. The Bland-Altman plots showed suitable agreement between the novel device and standard 10 s ECGs, which was substantiated by 95% limits of agreement of the difference of +/- 0.1 beats min(-1) and approximately +/- 10 ms for heart rate and RMSSD, respectively. Therefore the evaluation showed no significant systematic error of the novel device compared with ECG.

Random-phase solitons in nonlinear periodic lattices.

We predict the existence of random phase solitons in nonlinear periodic lattices. These solitons exist when the nonlinear response time is much longer than the characteristic time of random phase fluctuations. The intensity profiles, power spectra, and statistical (coherence) properties of these stationary waves conform to the periodicity of the lattice. The general phenomenon of such solitons is analyzed in the context of nonlinear photonic lattices.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.