Psoas Muscle Area Predicts All-Cause Mortality After Endovascular and Open Aortic Aneurysm Repair.

OBJECTIVE: Psoas muscle area (PMA) is a validated surrogate for muscle mass that can be easily measured from a clinical CT scan. This study sought to determine whether PMA was associated with post-operative mortality after endovascular or open aortic aneurysm repair. METHODS: A retrospective review was undertaken of patients who underwent elective endovascular or open aortic aneurysm repair between 2010 and 2015 at a tertiary vascular center in Montreal, Quebec, Canada. Pre-operative CT scan images were analyzed with the CoreSlicer.com software tool to measure PMA at the axial level of the L4 vertebrae. Measurements were made by two independent observers blinded to clinical data. The primary endpoint was all-cause mortality. RESULTS: The cohort consisted of 149 patients with a mean age of 75.6 ± 8.8 years. The mean PMA was 24.0 ± 5.8 cm2 in males, and 14.3 ± 3.1 cm2 in females. There were 31 deaths over a mean follow-up of 22.4 months. After adjusting for age, sex, revised cardiac risk index, and surgical approach, Cox regression revealed a graded association between PMA and all-cause mortality with a hazard ratio of 0.86 per cm2 (95% CI 0.79-0.93). Addition of PMA to the model with the clinical covariates resulted in an improvement in C-statistic from 0.57 to 0.67, and BIC from 307 to 301 (with lower BIC values preferred). CONCLUSIONS: PMA is independently associated with all-cause mortality after elective endovascular and open aortic aneurysm repair, and may be integrated into the pre-operative risk assessment to optimize care in high-risk frail patients.

Change in Driving Performance following Arthroscopic Shoulder Surgery.

The current study aimed to measure perioperative changes in driving performance following arthroscopic shoulder surgery using a validated driving simulator.21 patients who underwent arthroscopic surgery for rotator cuff or labral pathology were tested on a driving simulator preoperatively, and 6 and 12 weeks postoperatively. An additional 21 subjects were tested to establish driving data in a control cohort. The number of collisions, centerline crossings, and off-road excursions were recorded for each trial. VAS and SPADI scores were obtained at each visit.The mean number of collisions in the study group significantly increased from 2.05 preoperatively to 3.75 at 6 weeks (p<0.001), and significantly decreased to 1.95 at 12 weeks (p<0.001). Centerline crossings and off-road excursions did not significantly change from preoperative through 12 weeks, although centerline crossings were statistically different from the controls at each time point (p<0.001). Surgery on the dominant driving arm resulted in greater collisions at 6 weeks than surgery on the non-dominant driving arm (p<0.001).Preliminary data shows that driving performance is impaired for at least 6 weeks postoperatively, with a return to normal driving by 12 weeks. Driving is more profoundly affected in conditions that require avoiding a collision and when the dominant driving arm is involved.

Unusual Cause of Hemoptysis in a Woman With Cystic Fibrosis.

CASE PRESENTATION: A 20-year-old patient with cystic fibrosis (CF) complicated by pansinusitis, pancreatic insufficiency, and diabetes presented to the local ED after an episode of large-volume hemoptysis at home. At baseline, she had advanced lung disease (FEV1, 0.97 L; 31% predicted) and upper lobe-predominant fibrocavitary changes. She was intermittently followed at a regional lung transplant center. She was previously evaluated for transplant but was not listed at the time of this presentation because of nontuberculous mycobacteria infection. She had never used tobacco, without reports of recreational inhaled drug use. Her mother had CF, and one of her brothers died in 2018 at age 24 of respiratory failure resulting from the disease.

Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double-blind, placebo-controlled phase 1/2 clinical study.

BACKGROUND: MRT5005, a codon-optimized CFTR mRNA, delivered by aerosol in lipid nanoparticles, was designed as a genotype-agnostic treatment for CF lung disease. METHODS: This was a randomized, double-blind, placebo-controlled Phase 1/2 study performed in the US. Adults with 2 severe class I and/or II CFTR mutations and baseline ppFEV1 values between 50 and 90% were randomized 3:1 (MRT5005: placebo). Six dose levels of MRT5005 (4, 8, 12, 16, 20, and 24 mg) or placebo (0.9% Sodium Chloride) were administered by nebulization. The single ascending dose cohort was treated over a range from 8 to 24 mg; the multiple ascending dose cohort received five weekly doses (range 8-20 mg); and the daily dosing cohort received five daily doses (4 mg). RESULTS: A total of 42 subjects were assigned to MRT5005 [31] or placebo [11]. A total of 14 febrile reactions were observed in 10 MRT5005-treated participants, which were mild [3] or moderate [11] in severity; two subjects discontinued related to these events. Additionally, two MRT5005-treated patients experienced hypersensitivity reactions, which were managed conservatively. The most common treatment emergent adverse events were cough and headache. No consistent effects on FEV1 were noted. CONCLUSIONS: MRT5005 was generally safe and well tolerated through 28 days of follow-up after the last dose, though febrile and hypersensitivity reactions were noted. The majority of these reactions resolved within 1-2 days with supportive care allowing continued treatment with MRT5005 and careful monitoring. In this small first-in-human study, FEV1 remained stable after treatment, but no beneficial effects on FEV1 were observed.

Acromial and Scapular Fractures After Reverse Total Shoulder Arthroplasty with a Medialized Glenoid and Lateralized Humeral Implant: An Analysis of Outcomes and Risk Factors.

This article was updated on TK because of a previous error, which was discovered after the preliminary version of the article was posted online. In Table VII, the fracture rate in the study by Walch et al. that had read "4.6% (21 of 457)" now reads "0.9% (4 of 457)." BACKGROUND: Acromial and scapular fractures after reverse total shoulder arthroplasty (rTSA) are rare and challenging complications, and little information is available in the literature to identify patients who are at risk. This study analyzes risk factors for, and compares the outcomes of patients with and without, acromial and scapular fractures after rTSA with a medialized glenoid/lateralized humeral implant. METHODS: Four thousand one hundred and twenty-five shoulders in 3,995 patients were treated with primary rTSA with 1 design of reverse shoulder prosthesis by 23 orthopaedic surgeons. Sixty-one of the 4,125 shoulders had radiographically identified acromial and scapular fractures. Demographic characteristics, comorbidities, implant-related data, and clinical outcomes were compared between patients with and without fractures to identify risk factors. A multivariate logistic regression, 2-tailed unpaired t test, and chi-square test or Fisher exact test identified significant differences (p < 0.05). RESULTS: After a minimum duration of follow-up of 2 years, the rate of acromial and scapular fractures was 1.77%, with the fractures occurring at a mean (and standard deviation) of 17.7 ± 21.1 months after surgery. Ten patients had a Levy Type-1 fracture, 32 had a Type-2 fracture, 18 had a Type-3 fracture, and 1 fracture could not be classified. Patients with acromial and scapular fractures were more likely to be female (84.0% versus 64.5% [p = 0.004]; odds ratio [OR] = 2.75 [95% confidence interval (CI) = 1.45 to 5.78]), to have rheumatoid arthritis (9.8% versus 3.3% [p = 0.010]; OR = 3.14 [95% CI = 1.18 to 6.95]), to have rotator cuff tear arthropathy (54.1% versus 37.8% [p = 0.005]; OR = 2.07 [95% CI = 1.24 to 3.47]), and to have more baseplate screws (4.1 versus 3.8 screws [p = 0.017]; OR = 1.53 [95% CI = 1.08 to 2.17]) than those without fractures. No other implant-related differences were observed in the multivariate analysis. Patients with fractures had significantly worse outcomes than patients without fractures, and the difference in mean improvement between these 2 cohorts exceeded the minimum clinically important difference for the majority of measures. CONCLUSIONS: Acromial and scapular fractures after rTSA are uncommon, and patients with these fractures have significantly worse clinical outcomes. Risk factors, including female sex, rheumatoid arthritis, cuff tear arthropathy, and usage of more baseplate screws were identified on multivariate logistic regression analysis. Consideration of these findings and patient-specific risk factors may help the orthopaedic surgeon (1) to better inform patients about this rare complication preoperatively and (2) to be more vigilant for this complication when evaluating patients postoperatively. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Mechanism for intercalation of kaolinite by alkali acetates.

The relative strengths of the hydrogen bonds in kaolinite-alkali salt-water systems control kaolinite-salt interactions. A new technique for intercalation results in formation of a kaolinite-salt complex free of excess salt.

Preoperative bisphosphonate treatment may adversely affect the outcome after shoulder arthroplasty.

AIMS: The aim of this study was to investigate the effects of preoperative bisphosphonate treatment on the intra- and postoperative outcomes of arthroplasty of the shoulder. The hypothesis was that previous bisphosphonate treatment would adversely affect both intra- and postoperative outcomes. PATIENTS AND METHODS: A retrospective cohort study was conducted involving patients undergoing arthroplasty of the shoulder, at a single institution. Two patients with no previous bisphosphonate treatment were matched to each patient who had received this treatment preoperatively by gender, age, race, ethnicity, body mass index (BMI), and type of arthroplasty. Previous bisphosphonate treatment was defined as treatment occurring during the three-year period before the arthroplasty. The primary outcome measure was the incidence of intraoperative complications and those occurring at one and two years postoperatively. A total of 87 patients were included: 29 in the bisphosphonates-exposed (BP+) group and 58 in the non-exposed (BP-) group. In the BP+ group, there were 26 female and three male patients, with a mean age of 71.4 years (51 to 87). In the BP- group, there were 52 female and six male patients, with a mean age of 72.1 years (53 to 88). RESULTS: Previous treatment with bisphosphonates was positively associated with intraoperative complications (fracture; odds ratio (OR) 39.40, 95% confidence interval (CI) 2.42 to 6305.70) and one-year postoperative complications (OR 7.83, 95% CI 1.11 to 128.82), but did not achieve statistical significance for complications two years postoperatively (OR 3.45, 95% CI 0.65 to 25.28). The power was 63% for complications at one year. CONCLUSION: Patients who are treated with bisphosphonates during the three-year period before shoulder arthroplasty have a greater risk of intraoperative and one-year postoperative complications compared with those without this previous treatment.

2019 Frank Stinchfield Award: A comparison of prosthetic joint infection rates between direct anterior and non-anterior approach total hip arthroplasty.

AIMS: We studied the impact of direct anterior (DA) versus non-anterior (NA) surgical approaches on prosthetic joint infection (PJI), and examined the impact of new perioperative protocols on PJI rates following all surgical approaches at a single institution. PATIENTS AND METHODS: A total of 6086 consecutive patients undergoing primary total hip arthroplasty (THA) at a single institution between 2013 and 2016 were retrospectively evaluated. Data obtained from electronic patient medical records included age, sex, body mass index (BMI), medical comorbidities, surgical approach, and presence of deep PJI. There were 3053 male patients (50.1%) and 3033 female patients (49.9%). The mean age and BMI of the entire cohort was 62.7 years (18 to 102, sd 12.3) and 28.8 kg/m2 (13.3 to 57.6, sd 6.1), respectively. Infection rates were calculated yearly for the DA and NA approach groups. Covariates were assessed and used in multivariate analysis to calculate adjusted odds ratios (ORs) for risk of development of PJI with DA compared with NA approaches. In order to determine the effect of adopting a set of infection prevention protocols on PJI, we calculated ORs for PJI comparing patients undergoing THA for two distinct time periods: 2013 to 2014 and 2015 to 2016. These periods corresponded to before and after we implemented a set of perioperative infection protocols. RESULTS: There were 1985 patients in the DA group and 4101 patients in the NA group. The overall rate of PJI at our institution during the study period was 0.82% (50/6086) and decreased from 0.96% (12/1245) in 2013 to 0.53% (10/1870) in 2016. There were 24 deep PJIs in the DA group (1.22%) and 26 deep PJIs in the NA group (0.63%; p = 0.023). After multivariate analysis, the DA approach was 2.2 times more likely to result in PJI than the NA approach (OR 2.2 (95% confidence interval 1.1 to 3.9); p = 0.006) for the overall study period. CONCLUSION: We found a higher rate of PJI in DA versus NA approaches. Infection prevention protocols such as use of aspirin, dilute povidone-iodine lavage, vancomycin powder, and Gram-negative coverage may have been positively associated with diminished PJI rates observed for all approaches over time. Cite this article: Bone Joint J 2019;101-B(6 Supple B):2-8.

Risk factors for recurrent instability or revision surgery following arthroscopic Bankart repair.

Aims: The factors that predispose to recurrent instability and revision stabilization procedures after arthroscopic Bankart repair for anterior glenohumeral instability remain unclear. We sought to determine the rate and risk factors associated with ongoing instability in patients undergoing arthroscopic Bankart repair for instability of the shoulder. Materials and Methods: We used the Statewide Planning and Research Cooperative System (SPARCS) database to identify patients with a diagnosis of anterior instability of the shoulder undergoing arthroscopic Bankart repair between 2003 and 2011. Patients were followed for a minimum of three years. Baseline demographics and subsequent further surgery to the ipsilateral shoulder were analyzed. Multivariate analysis was used to identify independent risk factors for recurrent instability. Results: A total of 5719 patients were analyzed. Their mean age was 24.9 years (sd 9.3); 4013 (70.2%) were male. A total of 461 (8.1%) underwent a further procedure involving the ipsilateral shoulder at a mean of 31.5 months (sd 23.8) postoperatively; 117 (2.1%) had a closed reduction and 344 (6.0%) had further surgery. Revision arthroscopic Bankart repair was the most common subsequent surgical procedure (223; 65.4%). Independent risk factors for recurrent instability were: age < 19 years (odds ratio 1.86), Caucasian ethnicity (hazard ratio 1.42), bilateral instability of the shoulder (hazard ratio 2.17), and a history of closed reduction(s) prior to the initial repair (hazard ratio 2.45). Revision arthroscopic Bankart repair was associated with significantly higher rates of ongoing persistent instability than revision open stabilization (12.4% vs 5.1%, p = 0.041). Conclusion: The incidence of a further procedure being required in patients undergoing arthroscopic Bankart repair for anterior glenohumeral instability was 8.1%. Younger age, Caucasian race, bilateral instability, and closed reduction prior to the initial repair were independent risk factors for recurrent instability, while subsequent revision arthroscopic Bankart repair had significantly higher rates of persistent instability than subsequent open revision procedures. Cite this article: Bone Joint J 2018;100-B:324-30.

Release of angiotensin converting enzyme by the lung after Pseudomonas bacteremia in sheep.

We studied release of angiotensin-converting enzyme (ACE) by the lung after acute injury associated with an increase in pulmonary vascular permeability. In eight adult sheep with chronic lung lymph fistulas, we measured lymph flow (QL), and both ACE activity and total protein content in lymph and plasma under base-line conditions and during 24 h after an infusion of live pseudomonas organism. Under base-line conditions, ACE activity in plasma was 4.93 +/- 0.43 U/ml (mean +/- SEM). The [lymph]/[plasma] ([L]/[P]) ratio for ACE was 0.93 +/- 0.18, compared with a ratio of 0.79 +/- 0.08 for albumin (mean +/- SD). We estimated the molecular weight of ovine ACE to be 145,000 by gel chromatography. Predicted [L]/[P] ratio for a molecule this size is 0.51. Thus, a substantial fraction of ACE activity detected lung lymph under base-line conditions (11.1 +/- 6.2 U/h; mean +/- SD) originated in the lung, and did not diffuse passively from plasma. After pseudomonas infusion, endothelial injury was demonstrated by a rise in pulmonary vascular clearance for total protein (Crp = QL X [L]/[P]). Crp = 3.1 +/- 0.6 ml/h before pseudomonas bacteremia, and rose to 6.7 +/- 1.2 ml/h by 2 h after onset of the infusion (means +/- SEM, p less than 0.05). Crp remained significantly elevated for at least 10 h after the infusion. Release of ACE into lung lymph doubled after acute lung injury and equaled 22.3 +/- 13.8 U/h at 4 h after onset of the infusion. ACE secretion into lung lymph had returned to baseline levels by 24 h after bacteremia. We did not observe a significant rise in plasma ACE activity after acute lung injury. Pseudomonas bacteremia in sheep results in acute, reversible lung injury associated with increased pulmonary vascular permeability, and increased release of ACE by the lung. Failure to detect a rise in plasma ACE content might result from dilution in the large vascular pool or rapid catabolism of the enzyme at some site distant from the lung.

Gastrin releasing peptide is a selective mitogen for small cell lung carcinoma in vitro.

Human small cell lung carcinoma (SCLC) cells have been shown to contain significant levels of a bombesin-immunoreactive peptide. The 27-amino acid peptide, gastrin releasing peptide (GRP), has recently been shown to be responsible for the bombesin-like immunoreactivity found in SCLC cells. Among four lung cancer cell lines examined in vitro, GRP exhibited mitogenic activity for two SCLC subtypes, but not for a squamous carcinoma or adenocarcinoma lung cell line. The mitogenicity of the GRP molecule has been isolated to the carboxyterminal fragment, designated GRP 14-27, which is in part homologous to bombesin. The aminoterminal fragment, GRP 1-16, is no homologous to bombesin and exhibits no mitogenic activity. Thus, GRP may be an important growth regulating or autocrine factor in human SCLC.

MinK-related peptide 1: A beta subunit for the HCN ion channel subunit family enhances expression and speeds activation.

The HCN family of ion channel subunits underlies the currents I(f) in heart and I(h) and I(q) in the nervous system. In the present study, we demonstrate that minK-related peptide 1 (MiRP1) is a beta subunit for the HCN family. As such, it enhances protein and current expression as well as accelerating the kinetics of activation. Because MiRP1 also functions as a beta subunit for the cardiac delayed rectifier I(Kr), these results suggest that this peptide may have the unique role of regulating both the inward and outward channels that underlie cardiac pacemaker activity. The full text of this article is available at http://www.circresaha.org.

In vitro selection and characterization of a bleomycin-resistant subline of B16 melanoma.

A subline of B16 melanoma cells which is 10-fold resistant to bleomycin (BLM) was developed by exposure of the parental cell line to sequential increases in BLM concentration. This resistance to BLM is stable for over 30 passages in drug-free medium. Neither double minute chromosomes nor homogeneously staining regions were evident in karyotypes of the resistant cells. The subline, B16/BLM-R1, was slightly radioresistant, with a D0 ratio of 1.4 compared to the parental cells. No cross-resistance was observed to a number of cytotoxic drugs, including doxorubicin, melphalan, cisplatin, carmustine, dactinomycin, mitomycin C, and vinblastine. However, slight cross-resistance (2-fold) was noted with etoposide. Marked resistance to BLM also was demonstrated in vivo in mice bearing B16/BLM-R1 implanted s.c. Possible mechanisms of BLM resistance in these cells were explored through examination of the degree of drug inactivation by BLM hydrolase and measurement of single- and double-strand DNA scission, as well as repair of single strand breaks by the alkaline elution technique. The specific activity of BLM hydrolase was 70% higher in the resistant subline, commensurate with a 50% increase in protein content in these cells. Because this is insufficient to account for the 10-fold resistance, BLM hydrolase activity does not appear to be a major determinant of resistance in B16/BLM-R1. The overall number of single and double strand breaks in DNA produced by bleomycin treatment did not differ in the sensitive and resistant cells. The cross-resistance with ionizing radiation and etoposide suggests an enhanced capability of B16/BLM-R1 cells to withstand or repair single strand breaks in DNA. However, this was not evident by measuring repair of single strand scission by alkaline elution.

The influence of a history of clinical depression on peri-operative outcomes in elective total shoulder arthroplasty: a ten-year national analysis.

AIMS: Depression can significantly affect quality of life and is associated with higher rates of medical comorbidities and increased mortality following surgery. Although depression has been linked to poorer outcomes following orthopaedic trauma, total joint arthroplasty and spinal surgery, we wished to examine the impact of depression in elective total shoulder arthroplasty (TSA) as this has not been previously explored. PATIENTS AND METHODS: The United States Nationwide Inpatient Sample (NIS) was used to identify patients undergoing elective TSA over a ten-year period. Between 2002 and 2012, 224 060 patients underwent elective TSA. RESULTS: Among the identified patients who had undergone TSA, 12.4% had a diagnosis of a history of depression. A diagnosis of depression was twice as common in women compared with men (16.0% vs 8.0%, p < 0.001), and more frequent in those with low income and Medicaid insurance (p < 0.001). A diagnosis of depression was an independent risk factor for post-operative delirium (odds ratio (OR) 2.29, p < 0.001), anaemia (OR 1.65, p < 0.001), infection (2.09, p = 0.045) and hospital discharge to a placement other than home (OR 1.52, p < 0.001) CONCLUSION: A history of clinical depression is present in 12.4% of patients undergoing elective TSA and the disease burden is projected to increase further in the future. Depression is often underdiagnosed and pre-operative screening and appropriate peri-operative management of patients is encouraged. TAKE HOME MESSAGE: The awareness that clinical depression is associated with increased complications following total shoulder arthroplasty provides physicians an opportunity for early intervention in this at-risk population. Cite this article: Bone Joint J 2016;98-B:818-24.

Beating the Odds: Successful Establishment of a Phase II/III Clinical Research Trial in Resource-Poor Liberia during the Largest-Ever Ebola Outbreak.

It has been argued that a country such as Liberia, not fully recovered from the devastation of decades of civil unrest, lacked the appropriate ethical and regulatory framework, basic human and health care services, and infrastructure to carry out clinical trials according to international standards of quality during a public health emergency. However, as Liberia, Sierra Leone, and Guinea were being ravaged by the largest and most devastating Ebola Virus Disease (EVD) outbreak ever recorded, the topic of conducting clinical trials of experimental vaccine and treatment candidates in these resource-poor countries generated the keen interest and concern of scientists, researchers, physicians, bioethicists, philanthropists, and even politicians. Decisive action on behalf of the Liberian government, and a timely positive and supportive response from the United States (U.S.) government, led to the formation of PREVAIL (Partnership for Research on Ebola Vaccines in Liberia) - a clinical research partnership between the two governments. Within a span of 12 weeks, this partnership accomplished the unimaginable: the successful initiation of a Phase II/III vaccine clinical trial for EVD in Liberia. This paper will discuss the dynamics of the research collaboration, barriers encountered, breakthroughs realized, key elements of success, and lessons learned in the process.

Deterioration of left ventricular chamber performance after bed rest : "cardiovascular deconditioning" or hypovolemia?

BACKGROUND: Orthostatic intolerance after bed rest is characterized by hypovolemia and an excessive reduction in stroke volume (SV) in the upright position. We studied whether the reduction in SV is due to a specific adaptation of the heart to head-down tilt bed rest (HDTBR) or acute hypovolemia alone. METHODS AND RESULTS: We constructed left ventricular (LV) pressure-volume curves from pulmonary capillary wedge pressure and LV end-diastolic volume and Starling curves from pulmonary capillary wedge pressure and SV during lower body negative pressure and saline loading in 7 men (25+/-2 years) before and after 2 weeks of -6 degrees HDTBR and after the acute administration of intravenous furosemide. Both HDTBR and hypovolemia led to a similar reduction in plasma volume. However, baseline LV end-diastolic volume decreased by 20+/-4% after HDTBR and by 7+/-2% after hypovolemia (interaction P<0.001). Moreover, SV was reduced more and the Starling curve was steeper during orthostatic stress after HDTBR than after hypovolemia. The pressure-volume curve showed a leftward shift and the equilibrium volume of the left ventricle was decreased after HDTBR; however, after hypovolemia alone, the curve was identical, with no change in equilibrium volume. Lower body negative pressure tolerance was reduced after both conditions; it decreased by 27+/-7% (P<0.05) after HDTBR and by 18+/-8% (P<0.05) after hypovolemia. CONCLUSIONS: Chronic HDTBR leads to ventricular remodeling, which is not seen with equivalent degrees of acute hypovolemia. This remodeling leads to a greater decrease in SV during orthostatic stress after bed rest than hypovolemia alone, potentially contributing to orthostatic intolerance.

Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers.

OBJECTIVES: We sought to determine the relationship between different echocardiographic indices and pulmonary capillary wedge pressures (PCWP) in normal volunteers. BACKGROUND: Indices based on tissue Doppler (TDE) and color M-mode (CMM) echocardiography have been proposed to reflect left (LV) ventricular filling pressures. These include the ratio of early diastolic transmitral velocity (E) to early myocardial velocity measured by TDE (E') and the ratio of E to the wave propagation velocity (Vp) measured from CMM images. These indices, however, have not been validated in normal individuals. METHODS: We studied seven volunteers during two phases of preload altering maneuvers, baseline, with two stages of lower body negative pressure, and repeat baseline with two stages of volume loading. The PCWP obtained from right heart catheterization was compared with diastolic indices using pulsed Doppler, TDE and CMM echocardiography. RESULTS: The PCWP ranged from 2.2 to 23.5 mm Hg. During preload alterations, significant changes in E and septal E' (both p < 0.05) but not lateral E' or Vp were observed. Furthermore, E, septal E' and E/Vp correlated with PCWP (all r > 0.80) but not combined E and TDE indices (both r < 0.15). Within individuals, a similar linear relationship was observed among E/Vp, E and septal E' (average r > 0.80). CONCLUSIONS: In subjects without heart disease, E, septal E' and E/Vp correlate with PCWP. Because the influence of ventricular relaxation is minimized, the ratio E/Vp may be the best overall index of LV filling pressures.

Decreasing spine implant costs and inter-physician cost variation: the impact of programme of cost containment on implant expenditure in spinal surgery.

The demand for spinal surgery and its costs have both risen over the past decade. In 2008 the aggregate hospital bill for surgical care of all spinal procedures was reported to be $33.9 billion. One key driver of rising costs is spinal implants. In 2011 our institution implemented a cost containment programme for spinal implants which was designed to reduce the prices of individual spinal implants and to reduce the inter-surgeon variation in implant costs. Between February 2012 and January 2013, our spinal surgeons performed 1493 spinal procedures using implants from eight different vendors. By applying market analysis and implant cost data from the previous year, we established references prices for each individual type of spinal implant, regardless of vendor, who were required to meet these unit prices. We found that despite the complexity of spinal surgery and the initial reluctance of vendors to reduce prices, significant savings were made to the medical centre.

Protease inhibitor and triple-drug therapy: cellular immune parameters are not restored in pediatric AIDS patients after 6 months of treatment.

OBJECTIVE: To assess whether treatment of HIV-positive children by antiretroviral drugs for a 6-month period would improve immune function significantly. DESIGN AND METHODS: Immunological assessment of 89 HIV-positive children who received protease inhibitor monotherapy for 12-16 weeks as part of phase I/II studies, followed by triple antiretroviral therapy for an additional 12 weeks, was conducted. Immunological parameters were assessed in vitro at four time points (at enrollment, at weeks 2-4, at weeks 12-16, and at weeks 24-28). Assessments included: cytokine production by monocytes, T-cell proliferation to mitogen or recall antigens (including an HIV antigen) and apoptotic cell death. Plasma levels of tumor necrosis factor (TNF)-alpha and soluble TNF receptor (sTNF-R) were also measured, in addition to CD4+ T-lymphocyte counts and viral load. In addition, limited analyses were performed on samples from 17 children after 120 weeks of therapy, including 104 weeks of triple therapy. RESULTS: At enrollment, the 89 children exhibited severe immune defects. Antiretroviral therapy raised CD4+ T-lymphocyte counts significantly and decreased viral loads. In contrast, the in vitro immune parameters studied were not improved, except for plasma levels of sTNF-RII which decreased in parallel with the decrease in viral load. In addition, there was a trend towards increased skin test reactivity for the ritonavir-treated children. No differences were seen in the immune parameters whether the patients were treated with mono- or triple therapy. Results obtained after 120 weeks of therapy demonstrated that defective interleukin-12 production was not restored by long-term therapy. CONCLUSIONS: After 6 months of therapy, with the exception of decreased sTNF-RII levels, and a trend towards increased skin test reactivity, restoration of several defective cellular immune responses did not occur despite significantly decreased viral loads and increased CD4+ T-lymphocyte counts.

A phase I study of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator gene to a lung segment of individuals with cystic fibrosis.

A third-generation adenoviral vector containing recombinant human cystic fibrosis transmembrane conductance regulator (CFTR) gene was delivered by bronchoscope in escalating doses to the conducting airway of 11 volunteers with cystic fibrosis. Assessments of dose-limiting toxicity (DLT), efficiency of gene transfer, and cell-mediated and humoral immune responses to vector administration were performed. DLT, manifest by flulike symptoms and transient radiographic infiltrates, was seen at 2.1 x 10(11) total viral particles. A highly specific assay for gene transfer was developed using in situ hybridization with an oligoprobe against unique vector sequence. Detectable gene transfer was observed in harvested bronchial epithelial cells (<1%) 4 days after vector instillation, which diminished to undetectable levels by day 43. Adenovirus-specific cell-mediated T cells were induced in most subjects, although only mild increases in systemic humoral immune response were observed. These results demonstrate that gene transfer to epithelium of the lower respiratory tract can be achieved in humans with adenoviral vectors but that efficiency is low and of short duration in the native CF airway.