Right upper lobe 'window' in right main bronchus stenting.

Stent insertion for bronchial stenosis has become common practice in lung transplantation and advanced lung malignancy, and for external compression of the airways for other reasons. Right main bronchus stenting may require blocking the right upper lobe by the stent, placing the patient at risk of recurrent pneumonia and atelectasis. In this study, three patients after insertion of a metal stent to the right main bronchus are described. In all cases, the right upper lobe was covered by the stent, and a laser (Nd:YAG) procedure was used to open a 'window' in the stent toward the right upper lobe with a follow-up of 1 year. We conclude that stent insertion to the right main bronchus may be followed by a laser therapy to open a 'window' toward the right upper lobe.     

Association of elevated levels of vascular endothelial growth factor in obstructive sleep apnea syndrome with patient age rather than with obstructive sleep apnea syndrome severity

BACKGROUND: Although certain studies report high levels of vascular endothelial growth factor (VEGF) in obstructive sleep apnea syndrome (OSAS), the effect of systemic hypoxia on circulating VEGF remains controversial. OBJECTIVES: To study the association of serum VEGF and OSAS in a large group of patients. METHODS: One hundred patients with OSAS (mean age 58.1+/-12.4 years, mean body mass index 30.6+/-5.4 kg/m2) were tested for serum VEGF levels, and the findings were correlated with the severity of OSAS, as determined by the apnea-hypopnea index (AHI) on the basis of polysomnography and background data. RESULTS: The mean AHI was 40.0+/-21.2 (range 10-106). Mean minimal oxygen saturation was 80.6+/-11.7% (range 43-98%) and mean time of oxygen saturation under 90% was 50.0+/-75.0 min (range 0-300 min). The mean VEGF level was 445.2+/-289.8 pg/ml in the study group (vs. 280 pg/ml reported in normal controls). The mean platelet count was 233.8+/-64.4 10(3)/ml and the mean VEGF/platelet ratio was 1.95+/-1.40 pg/10(6). There was no association of VEGF or VEGF/platelets with the severity of OSAS. However, both factors showed a significant correlation with patient age (r=0.224, p=0.01 and r=0.425, p=0.01, respectively). Age was the only parameter to significantly predict VEGF and VEGF/platelets on multivariate analysis (R2=0.713, p=0.001 and R2=0.844, p=0.001, respectively). CONCLUSION: The elevation of serum VEGF in OSAS is not associated with the severity of the disease, but it is associated with patient age. VEGF might be involved in the long-term adaptive mechanism in OSAS, and its age-dependent increase might partly explain the reduced mortality in elderly OSAS patients.     

Risk factors for death while awaiting lung transplantation in Israeli patients: 1997–2006

OBJECTIVE: Patients with end-stage lung disease very frequently die while awaiting lung transplantation. The aim of this study was to identify factors associated with mortality in patients referred for lung transplant assessment. METHODS: The files of all consecutive patients listed for lung transplantation in Israel between 1997 and 2006 were reviewed and the data were compared statistically between those who survived to transplantation. RESULTS: A total of 229 patients were listed for lung transplantation, of whom 42 (18.3%) died while awaiting transplantation. Comparison of the patients who survived to transplantation with those who did not using univariate analysis revealed that the died-waiting group was significantly older, used steroids to a greater extent, had more IPF patients and less emphysematous, and lower mean oxygen saturation at rest (p=0.005). There were no between-group differences in comorbid diseases or pulmonary function measurements. The 6 min walk distance was strongly and inversely correlated with risk of death before transplantation (p=0.005). On multivariate analysis, only oxygen saturation at rest was a significant independent risk factor for death while awaiting transplantation (OR 0.886; C.I. 0.805-0.974). CONCLUSIONS: There are several risk factors for death in the Israeli population listed for LTX, including age, steroid use, emphysematous patients and lower saturation at rest.     

A rise in pain threshold during labor: a prospective clinical trial

To evaluate changes in pain threshold before, during and after labor in a prospective clinical trial. Forty pregnant women at term were included. Pain threshold in 18 specific pressure points was evaluated using a dolorimeter. Woman underwent pain threshold assessment at term before labor, during the active phase of labor and postpartum. Subjective pain intensity was assessed by the parturient using the Verbal Rating Scale (VRS). Pain threshold was significantly higher during active phase of labor. There was a significant decline in pain threshold after labor as compared to pain threshold during labor (2.507+/-0.947 and 2.608+/-1.023, respectively, p=0.01). Pain intensity using the VRS score was higher during labor than before labor (4.8+/-2.7 and 2.4+/-2.6 p<0.001). We found a significant rise in pain threshold during labor in term pregnancies. This rise may have an intended protective effect during the intense labor pain experience.     

Warfarin metabolism and anticoagulant effect: a prospective, observational study of the impact of CYP2C9 genetic polymorphism in the presence of drug-disease and drug-drug interactions

BACKGROUND: Cytocbrome P450 (CYP) 2C9 polymorphism affects the warfarin dosage requirement in stable outpatients. However, it is not known whether the CYP2C9 genotype contributes to the variability in warfarin dosage in the presence of drug-disease and drug-drug interactions. OBJECTIVE: The aim of this study was to examine the effects of CYP2C9 genetic polymorphism on warfarin dosage requirements in patients with severe comorbid conditions and those treated with medications that potentially interact with warfarin. METHODS: This prospective, observational study was conducted at Hadassah University Hospital, Jerusalem, Israel. Data from consecutive patients treated with warfarin for at least 3 months and admitted to the internal medicine ward were eligible for inclusion. Clinical data, international normalized ratio (INR), and warfarin dosage were recorded from medical records. The CYP2C9 genotype was determined using polymerase chain reaction restriction fragment length polymorphism, and plasma concentrations of (S)- and (R)-warfarin were determined by high-performance liquid chromatography using chiral methods. RESULTS: One hundred nineteen subjects (52% women) were studied. Mean age was 65.8 years (95% CI, 63.1-68.4), and weight was 74.9 kg (95% CI, 72.1-77.7). The mean warfarin dosage was 33% lower in patients with the CYP2C9-*1/*3 genotype (mean [SEM], 0.045 [0.006] mg/kg x d(-1)) compared with the CYP2C9-*1/*1 genotype (0.067 [0.004] mg/kg x d(-1)) (P=0.008); an intermediate value was found for the CYP2C9-*1/*2 genotype (0.062 [0.008] mg/kg x d(-1)). However, despite the lower dosage, INR was significantly higher in patients with the *1/*3 genotype (mean [95% CI], 3.29 [2.44-4.14]) (n=18) compared with the *1/*1 genotype (2.52 [2.34-2.71]) (n=64) (P=0.029). In addition to genotype, older age, congestive heart failure (CHF), and treatment with antibiotics were associated with lower warfarin dosages, whereas treatment with drug-metabolism inducers was associated with higher warfarin dosages. In addition, the ratios of (S)- to (R)-warfarin concentrations were significantly higher in patients with *1/*3 compared with those in patients with the *1/*1 genotype. CONCLUSIONS: In this study population of patients with severe comorbid conditions and those treated with medications that potentially interact with warfarin, CYP2C9 *1/*3 genotype, older age, CHF, and the use of antibiotics were associated with lower warfarin dosage requirements. The CYP2C9*1/*3 genotype, compared with CYP2C9 *1/*1, was associated with 33% lower mean warfarin dosage requirements and higher INR values, which were higher than the upper therapeutic range of INR (ie, 3). Genetic CYP2C9 polymorphism contributed to the variability in warfarin dosage requirements in the presence of drug-disease and drug-drug interactions.     

Cognition- and Dementia-Related Adverse Effects With Sacubitril-Valsartan: Analysis of the FDA Adverse Event Report System Database

Background

Because neprilysin is involved in the degradation of amyloid-beta, there is concern that the angiotensin-neprilysin inhibitor sacubitril-valsartan could increase the risk for dementia.

Lung transplantation in patients with scleroderma: case series, review of the literature, and criteria for transplantation

Abstract: Backgrounds: The use of lung transplantation (LTX) to treat respiratory failure because of scleroderma is controversial. We present our experience, review the current literature, and suggest specific criteria for LTX in scleroderma. Of the 174 patients who underwent LTX at our center, seven (4%) had scleroderma‐associated respiratory failure. Patients and methods: A MEDLINE search of the English literature was performed for studies of LTX in patients with scleroderma between 1986 and 2006. A Kaplan–Meier survival curve was calculated over the time of the studies. Results: The MEDLINE search yielded one large review and four small case series. The small case series were included in the review. The review and our series yield a total of 54 patients. Mean patient age was 47.1 yr; 59.3% were female. Pre‐operative lung data were available for 24 patients: 22 (92%) had pulmonary fibrosis and 17 (71%) had pulmonary hypertension. Most patients (69%) underwent single‐lung transplantation. Mean forced expiratory volume at one s after LTX was 67% (range 56–87%). There was no difference in infection and rejection rates between the patients with scleroderma and other LTX recipients. The two‐ and five‐yr survival rates were 72% and 55%, respectively. Conclusions: LTX is a valid option in well‐selected patients with scleroderma and pulmonary fibrosis, yielding good pulmonary function and acceptable morbidity and mortality.