Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute Respiratory Failure: A Multicenter Retrospective Cohort Study.

OBJECTIVES: Extracorporeal carbon dioxide removal (ECCO 2 R) devices are effective in reducing hypercapnia and mechanical ventilation support but have not been shown to reduce mortality. This may be due to case selection, device performance, familiarity, or the management. The objective of this study is to investigate the effectiveness and safety of a single ECCO 2 R device (Hemolung) in patients with acute respiratory failure and identify variables associated with survival that could help case selection in clinical practice as well as future research. DESIGN: Multicenter, multinational, retrospective review. SETTING: Data from the Hemolung Registry between April 2013 and June 2021, where 57 ICUs contributed deidentified data. PATIENTS: Patients with acute respiratory failure treated with the Hemolung. The characteristics of patients who survived to ICU discharge were compared with those who died. Multivariable logistical regression analysis was used to identify variables associated with ICU survival. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 159 patients included, 65 (41%) survived to ICU discharge. The survival was highest in status asthmaticus (86%), followed by acute respiratory distress syndrome (ARDS) (52%) and COVID-19 ARDS (31%). All patients had a significant reduction in Pa co2 and improvement in pH with reduction in mechanical ventilation support. Patients who died were older, had a lower Pa o2 :F io2 (P/F) and higher use of adjunctive therapies. There was no difference in the complications between patients who survived to those who died. Multivariable regression analysis showed non-COVID-19 ARDS, age less than 65 years, and P/F at initiation of ECCO 2 R to be independently associated with survival to ICU discharge (P/F 100-200 vs <100: odds ratio, 6.57; 95% CI, 2.03-21.33). CONCLUSIONS: Significant improvement in hypercapnic acidosis along with reduction in ventilation supports was noted within 4 hours of initiating ECCO 2 R. Non-COVID-19 ARDS, age, and P/F at commencement of ECCO 2 R were independently associated with survival.

Interventions for perinatal borderline personality disorder and complex trauma: a systematic review.

Perinatal borderline personality disorder (BPD) and complex post-traumatic stress disorder (cPTSD) are associated with significant impairment to interpersonal functioning, and risk of intergenerational transmission of psychopathology. Evaluation of interventions, however, is scarce. To date, no systematic review has addressed interventions for perinatal BPD, cPTSD, and associated symptomatology. Given the modest evidence to support informed clinical guidelines, the objective of this systematic review is to synthesise the literature on interventions for perinatal BPD and cPTSD, and to generate future directions for research. A comprehensive literature search following PRISMA guidelines was conducted in PsycInfo, MEDLINE, Emcare, Scopus, and ProQuest Dissertations and Theses Global databases. Seven original studies were included, of which only two were randomised controlled trials, using less intensive comparison conditions. Results suggest an association between Dialectical Behavioural Therapy (DBT) group skills training, a multimodal therapeutic approach at a Mother-Baby Unit (MBU), and Child-Parent Psychotherapy with improved perinatal mental health outcomes and remission of symptoms. MBU admission and home-visiting programs were associated with healthy postpartum attachment relationships. Home-visiting programs and DBT group skills were additionally associated with improved maternal parenting capabilities. Conclusions to inform clinical guidelines are limited by a lack of credible comparison conditions, and low quantity and quality of evidence. The feasibility of implementing intensive interventions in real-world settings is dubious. Hence, it is suggested that future research considers utilising antenatal screening to identify at-risk mothers, and the implementation of early intervention, using robust designs that can inform robust conclusions.

Novel hybrid total artificial heart with integrated oxygenator.

There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable cardiopulmonary support system that integrates an implantable oxygenator with a hybrid, dual-support, continuous-flow total artificial heart (TAH). The TAH has a centrifugal flow pump that is rotating about an axial flow pump. By attaching the hollow fiber bundle of the oxygenator to the base of the TAH, we establish a new cardiopulmonary support technology that permits a patient to be ambulatory during usage. In this study, we investigated the design and improvement of the blood flow pathway from the inflow-to-outflow of four oxygenators using a mathematical model and computational fluid dynamics (CFD). Pressure loss and gas transport through diffusion were examined to assess oxygenator design. The oxygenator designs led to a resistance-driven pressure loss range of less than 35 mmHg for flow rates of 1-7 L/min. All of the designs met requirements. The configuration having an outside-to-inside blood flow direction was found to have higher oxygen transport. Based on this advantageous flow direction, two designs (Model 1 and 3) were then integrated with the axial-flow impeller of the TAH for simulation. Flow rates of 1-7 L/min and speeds of 10,000-16,000 RPM were analyzed. Blood damage studies were performed, and Model 1 demonstrated the lowest potential for hemolysis. Future work will focus on developing and testing a physical prototype for integration into the new cardiopulmonary assist system.

Time course of red blood cell intracellular pH recovery following short-circuiting in relation to venous transit times in rainbow trout, Oncorhynchus mykiss.

Accumulating evidence is highlighting the importance of a system of enhanced hemoglobin-oxygen (Hb-O2) unloading for cardiovascular O2 transport in teleosts. Adrenergically stimulated sodium-proton exchangers (ß-NHE) create H+ gradients across the red blood cell (RBC) membrane that are short-circuited in the presence of plasma-accessible carbonic anhydrase (paCA) at the tissues; the result is a large arterial-venous pH shift that greatly enhances O2 unloading from pH-sensitive Hb. However, RBC intracellular pH (pHi) must recover during venous transit (31-90 s) to enable O2 loading at the gills. The halftimes ( t1/2) and magnitudes of RBC ß-adrenergic stimulation, short-circuiting with paCA and recovery of RBC pHi, were assessed in vitro, on rainbow trout whole blood, and using changes in closed-system partial pressure of O2 as a sensitive indicator for changes in RBC pHi. In addition, the recovery rate of RBC pHi was assessed in a continuous-flow apparatus that more closely mimics RBC transit through the circulation. Results indicate that: 1) the t1/2 of ß-NHE short-circuiting is likely within the residence time of blood in the capillaries, 2) the t1/2 of RBC pHi recovery is 17 s and within the time of RBC venous transit, and 3) after short-circuiting, RBCs reestablish the initial H+ gradient across the membrane and can potentially undergo repeated cycles of short-circuiting and recovery. Thus, teleosts have evolved a system that greatly enhances O2 unloading from pH-sensitive Hb at the tissues, while protecting O2 loading at the gills; the resulting increase in O2 transport per unit of blood flow may enable the tremendous athletic ability of salmonids.

Month-long Respiratory Support by a Wearable Pumping Artificial Lung in an Ovine Model.

BACKGROUND: A wearable artificial lung could improve lung transplantation outcomes by easing implementation of physical rehabilitation during long-term pretransplant respiratory support. The Modular Extracorporeal Lung Assist System (ModELAS) is a compact pumping artificial lung currently under development. This study evaluated the long-term in vivo performance of the ModELAS during venovenous support in awake sheep. Feedback from early trials and computational fluid dynamic analysis guided device design optimization along the way. METHODS: The ModELAS was connected to healthy sheep via a dual-lumen cannula in the jugular vein. Sheep were housed in a fixed-tether pen while wearing the device in a holster during support. Targeted blood flow rate and support duration were 2-2.5 L/min and 28-30 days, respectively. Anticoagulation was maintained via systemic heparin. Device pumping and gas exchange performance and hematologic indicators of sheep physiology were measured throughout support. RESULTS: Computational fluid dynamic-guided design modifications successfully decreased pump thrombogenicity from initial designs. For the optimized design, 4 of 5 trials advancing past early perioperative and cannula-related complications lasted the full month of support. Blood flow rate and CO2 removal in these trials were 2.1 ± 0.3 L/min and 139 ± 15 mL/min, respectively, and were stable during support. One trial ended after 22 days of support due to intradevice thrombosis. Support was well tolerated by the sheep with no signs of hemolysis or device-related organ impairment. CONCLUSIONS: These results demonstrate the ability of the ModELAS to provide safe month-long support without consistent deterioration of pumping or gas exchange capabilities.

Effect of Hematocrit on the CO2 Removal Rate of Artificial Lungs.

Extracorporeal CO2 removal (ECCO2R) can permit lung protective or noninvasive ventilation strategies in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). With evidence supporting ECCO2R growing, investigating factors which affect CO2 removal is necessary. Multiple factors are known to affect the CO2 removal rate (vCO2) which can complicate the interpretation of changes in vCO2; however, the effect of hematocrit on the vCO2 of artificial lungs has not been investigated. This in vitro study evaluates the relationship between hematocrit level and vCO2 within an ECCO2R device. In vitro gas transfer was measured in bovine blood in accordance with the ISO 7199 standard. Plasma and saline were used to hemodilute the blood to hematocrits between 33% and 8%. The vCO2 significantly decreased as the blood was hemodiluted with saline and plasma by 42% and 32%, respectively, between a hematocrit of 33% and 8%. The hemodilution method did not significantly affect the vCO2. In conclusion, the hematocrit level significantly affects vCO2 and should be taken into account when interpreting changes in the vCO2 of an ECCO2R device.

Blood Recirculation Enhances Oxygenation Efficiency of Artificial Lungs.

Ambulating patients on extracorporeal membrane oxygenation (ECMO) or extracorporeal CO2 removal (ECCO2R) improves outcomes. These systems would further simplify ambulation if made more compact. This study investigates blood recirculation to decrease device size by increasing efficiency. The required hollow fiber membrane (HFM) area was determined by numerically modeling gas transfer. An oxygenation device with recirculating blood flow was designed using computational fluid dynamics (CFD). Hydrodynamic performance and shear stresses of the device were analyzed using CFD at 2,000, 2,250 and 2,500 RPM. A prototype (0.38 m) was manufactured for in-vitro oxygenation testing. Oxygenation was measured at a constant 3.5 L/min blood flow while recirculation flow rate varied up to 6.5 L/min. Hemolysis was measured at 3.5 L/min blood flow and 6.5 L/min recirculation flow. A 0.3 m prototype device was used to test in-vitro ECCO2R recirculation at a constant 500 ml/min blood flow rate and recirculation flow rates up to 5.5 L/min. Computational fluid dynamics analysis showed that the oxygenation device could produce over 250 mm Hg while maintaining 3.5 L/min blood flow and 6.5 L/min recirculation flow. The model predicted oxygenation within 8% and overestimated ECCO2R by up to 32%. Measured gas transfer was 180 ml O2/min and 62 ml CO2/min. Normalized index of hemolysis contribution of the HFM was 0.012 gm/100 L.

In vivo testing of the low-flow CO2 removal application of a compact, platform respiratory device.

BACKGROUND: Non-invasive and lung-protective ventilation techniques may improve outcomes for patients with an acute exacerbation of chronic obstructive pulmonary disease or moderate acute respiratory distress syndrome by reducing airway pressures. These less invasive techniques can fail due to hypercapnia and require transitioning patients to invasive mechanical ventilation. Extracorporeal CO2 removal devices remove CO2 independent of the lungs thereby controlling the hypercapnia and permitting non-invasive or lung-protective ventilation techniques. We are developing the Modular Extracorporeal Lung Assist System as a platform technology capable of providing three levels of respiratory assist: adult and pediatric full respiratory support and adult low-flow CO2 removal. The objective of this study was to evaluate the in vivo performance of our device to achieve low-flow CO2 removal. METHODS: The Modular Extracorporeal Lung Assist System was connected to 6 healthy sheep via a 15.5 Fr dual-lumen catheter placed in the external jugular vein. The animals were recovered and tethered within a pen while supported by the device for 7 days. The pump speed was set to achieve a targeted blood flow of 500 mL/min. The extracorporeal CO2 removal rate was measured daily at a sweep gas independent regime. Hematological parameters were measured pre-operatively and regularly throughout the study. Histopathological samples of the end organs were taken at the end of each study. RESULTS: All animals survived the surgery and generally tolerated the device well. One animal required early termination due to a pulmonary embolism. Intra-device thrombus formation occurred in a single animal due to improper anticoagulation. The average CO2 removal rate (normalized to an inlet pCO2 of 45 mmHg) was 75.6 ± 4.7 mL/min and did not significantly change over the course of the study (p > 0.05). No signs of consistent hemolysis or end organ damage were observed. CONCLUSION: These in vivo results indicate positive performance of the Modular Extracorporeal Lung Assist System as a low-flow CO2 removal device.

A Proof of Concept Study, Demonstrating Extracorporeal Carbon Dioxide Removal Using Hemodialysis with a Low Bicarbonate Dialysate.

Extracorporeal carbon dioxide removal (ECCO2R) devices remove CO2 directly from blood, facilitating ultraprotective ventilation or even providing an alternative to mechanical ventilation. However, ECCO2R is not widely available, whereas dialysis is available in most intensive care units (ICUs). Prior attempts to provide ECCO2R with dialysis, by removing CO2 in the form of bicarbonate, have been plagued by metabolic acidosis. We hypothesized that bicarbonate dialysis is feasible, provided the plasma strong ion difference is maintained. We used a mathematical model to investigate the effects of bicarbonate removal on pH and CO2 in plasma, and performed in-vitro experiments to test CO2 removal using three dialysates with different bicarbonate concentrations (0, 16, and 32 mmol·L). Our modeling predicted a reduction in partial pressures of CO2 (PCO2) and increased pH with progressive lowering of plasma bicarbonate, provided strong ion difference and plasma proteins (Atot) were maintained. In our in-vitro experiments, total CO2 removal, scaled up to an adult size filter, was highest with our dialysate containing no bicarbonate, where we removed the equivalent of 94 ml·min (±3.0) of CO2. Under the same conditions, our dialysate containing a conventional bicarbonate concentration (32 mmol·L) only removed 5 ml·min (±4; p < 0.001). As predicted, pH increased following bicarbonate removal. Our data show that dialysis using low bicarbonate dialysates is feasible and results in a reduction in plasma PCO2. When scaled up, to estimate equivalent CO2 removal with an adult dialysis circuit, the amount removed competes with existing low-flow ECCO2R devices.

Acute In Vivo Evaluation of the Pittsburgh Pediatric Ambulatory Lung.

Respiratory failure is a significant problem within the pediatric population. A means of respiratory support that readily allows ambulation could improve treatment. The Pittsburgh Pediatric Ambulatory Lung (P-PAL) is being developed as a wearable pediatric pump-lung for long-term respiratory support and has previously demonstrated positive benchtop results. This study aimed to evaluate acute (4-6 hours) in vivo P-PAL performance, as well as develop an optimal implant strategy for future long-term studies. The P-PAL was connected to healthy sheep (n = 6, 23-32 kg) via cannulation of the right atrium and pulmonary artery. Plasma-free hemoglobin (PfHb) and animal hemodynamics were measured throughout the study. Oxygen transfer rates were measured at blood flows of 1-2.5 L/min. All animals survived the complete study duration with no device exchanges. Flow limitation because of venous cannula occlusion occurred in trial 2 and was remedied via an altered cannulation approach. Blood exiting the P-PAL had 100% oxygen saturation with the exception of trial 4 during which inadequate device priming led to intrabundle clot formation. Plasma-free hemoglobin remained low (<20 mg/dl) for all trials. In conclusion, this study demonstrated successful performance of the P-PAL in an acute setting and established the necessary methods for future long-term evaluation.

Bench Validation of a Compact Low-Flow CO2 Removal Device.

BACKGROUND: There is increasing evidence demonstrating the value of partial extracorporeal CO2 removal (ECCO2R) for the treatment of hypercapnia in patients with acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. Mechanical ventilation has traditionally been used to treat hypercapnia in these patients, however, it has been well-established that aggressive ventilator settings can lead to ventilator-induced lung injury. ECCO2R removes CO2 independently of the lungs and has been used to permit lung protective ventilation to prevent ventilator-induced lung injury, prevent intubation, and aid in ventilator weaning. The Low-Flow Pittsburgh Ambulatory Lung (LF-PAL) is a low-flow ECCO2R device that integrates the fiber bundle (0.65 m2) and centrifugal pump into a compact unit to permit patient ambulation. METHODS: A blood analog was used to evaluate the performance of the pump at various impeller rotation rates. In vitro CO2 removal tested under normocapnic conditions and 6-h hemolysis testing were completed using bovine blood. Computational fluid dynamics and a mass-transfer model were also used to evaluate the performance of the LF-PAL. RESULTS: The integrated pump was able to generate flows up to 700 mL/min against the Hemolung 15.5 Fr dual lumen catheter. The maximum vCO2 of 105 mL/min was achieved at a blood flow rate of 700 mL/min. The therapeutic index of hemolysis was 0.080 g/(100 min). The normalized index of hemolysis was 0.158 g/(100 L). CONCLUSIONS: The LF-PAL met pumping, CO2 removal, and hemolysis design targets and has the potential to enable ambulation while on ECCO2R.

In Vitro Characterization of the Pittsburgh Pediatric Ambulatory Lung.

Acute and chronic respiratory failure are a significant source of pediatric morbidity and mortality. Current respiratory support options used to bridge children to lung recovery or transplantation typically render them bedridden and can worsen long-term patient outcomes. The Pittsburgh Pediatric Ambulatory Lung (P-PAL) is a wearable pediatric blood pump and oxygenator (0.3 m surface area) integrated into a single compact unit that enables patient ambulation. The P-PAL is intended for long-term use and designed to provide up to 90% of respiratory support in children weighing 5-25 kg. Computational fluid dynamics and numerical gas exchange modeling were used to design the P-PAL and predict its performance. A P-PAL prototype was then used to obtain pressure versus flow curves at various impeller rotation rates using a blood analog fluid. In vitro oxygen exchange rates were obtained in blood in accordance with ISO standard 7199. The normalized index of hemolysis (NIH) was measured over a 6 hour period at blood flow rates of 1 and 2.5 L/min. The P-PAL provided blood flows of 1-2.5 L/min against the pressure drop associated with its intended-use pediatric cannulas. The oxygen exchange rate reached a maximum of 108 ml/min at a blood flow rate of 2.5 L/min and met our respiratory support design target. Device-induced hemolysis was low with NIH values of 0.022-0.027 g/100 L in the intended blood flow rate range. In conclusion, the current P-PAL design met our pumping, oxygenation, and hemolysis specifications and has the potential to improve treatment for pediatric respiratory failure.

Extracorporeal CO2 removal by hemodialysis: in vitro model and feasibility.

BACKGROUND: Critically ill patients with acute respiratory distress syndrome and acute exacerbations of chronic obstructive pulmonary disease often develop hypercapnia and require mechanical ventilation. Extracorporeal carbon dioxide removal can manage hypercarbia by removing carbon dioxide directly from the bloodstream. Respiratory hemodialysis uses traditional hemodialysis to remove CO2 from the blood, mainly as bicarbonate. In this study, Stewart's approach to acid-base chemistry was used to create a dialysate that would maintain blood pH while removing CO2 as well as determine the blood and dialysate flow rates necessary to remove clinically relevant CO2 volumes. METHODS: Bench studies were performed using a scaled down respiratory hemodialyzer in bovine or porcine blood. The scaling factor for the bench top experiments was 22.5. In vitro dialysate flow rates ranged from 2.2 to 24 mL/min (49.5-540 mL/min scaled up) and blood flow rates were set at 11 and 18.7 mL/min (248-421 mL/min scaled up). Blood inlet CO2 concentrations were set at 50 and 100 mmHg. RESULTS: Results are reported as scaled up values. The CO2 removal rate was highest at intermittent hemodialysis blood and dialysate flow rates. At an inlet pCO2 of 50 mmHg, the CO2 removal rate increased from 62.6 ± 4.8 to 77.7 ± 3 mL/min when the blood flow rate increased from 248 to 421 mL/min. At an inlet pCO2 of 100 mmHg, the device was able to remove up to 117.8 ± 3.8 mL/min of CO2. None of the test conditions caused the blood pH to decrease, and increases were ≤0.08. CONCLUSIONS: When the bench top data is scaled up, the system removes a therapeutic amount of CO2 standard intermittent hemodialysis flow rates. The zero bicarbonate dialysate did not cause acidosis in the post-dialyzer blood. These results demonstrate that, with further development, respiratory hemodialysis can be a minimally invasive extracorporeal carbon dioxide removal treatment option.

Metabolome-Wide Association Study of Primary Open Angle Glaucoma.

PURPOSE: To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics. METHODS: We used ultra-high resolution mass spectrometry with C18 liquid chromatography for metabolomic analysis on frozen plasma samples from 72 POAG patients and 72 controls. Metabolome-wide Spearman correlation was performed to select differentially expressed metabolites (DEM) correlated with POAG. We corrected P values for multiple testing using Benjamini and Hochberg false discovery rate (FDR). Hierarchical cluster analysis (HCA) was used to depict the relationship between participants and DEM. Differentially expressed metabolites were matched to the METLIN metabolomics database; both DEM and metabolites significantly correlating with DEM were analyzed using MetaboAnalyst to identify metabolic pathways altered in POAG. RESULTS: Of the 2440 m/z (mass/charge) features recovered after filtering, 41 differed between POAG cases and controls at FDR = 0.05. Hierarchical cluster analysis revealed these DEM to associate into eight clusters; three of these clusters contained the majority of the DEM and included palmitoylcarnitine, hydroxyergocalciferol, and high-resolution METLIN matches to sphingolipids, other vitamin D-related metabolites, and terpenes. MetaboAnalyst also indicated likely alteration in steroid biosynthesis pathways. CONCLUSIONS: Global ultrahigh resolution metabolomics emphasized the importance of altered lipid metabolism in POAG. The results suggest specific metabolic processes, such as those involving palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors, may contribute to POAG status and merit more detailed study with targeted methods.

Neuropsychological effects of deep brain stimulation in subjects with early stage Parkinson's disease in a randomized clinical trial.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial. OBJECTIVE: The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. METHODS: Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. RESULTS: Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. CONCLUSIONS: The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD.

Biochemical recurrence-free survival after robotic-assisted laparoscopic vs open radical prostatectomy for intermediate- and high-risk prostate cancer.

OBJECTIVE: To compare biochemical recurrence (BCR)-free survival and predictors of BCR in intermediate-risk (IR) and high-risk (HR) patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) vs open radical prostatectomy (ORP). MATERIALS AND METHODS: We conducted a retrospective study on 1336 men with D'Amico IR or HR prostate cancer who underwent RALP or ORP between 2003 and 2009. Exclusion criteria were use of neoadjuvant therapy, <6 months of follow-up, and insufficient clinicopathologic data. We compared demographic, clinical, and pathologic variables between groups. Kaplan-Meier analysis was performed to compare the 5-year BCR-free survival between groups. Multivariate models were developed to determine whether surgical approach influences BCR. RESULTS: A total of 979 IR and HR patients (237 ORP and 742 RALP patients) met inclusion criteria. Median follow-up was shorter for RALP (43 vs 63 months; P<.001). ORP patients had a higher median prostate-specific antigen level (7.9 vs 6.7 ng/mL; P<.002), significantly more Gleason sum 8-10 tumors, and more adverse pathologic features overall. There was no difference in positive surgical margins between groups. Pathologic features including extraprostatic extension, seminal vesicle involvement, lymph node involvement, pathologic Gleason sum, and positive surgical margin were significant independent predictors of BCR in multivariate analysis. Surgical approach (RALP vs ORP) did not predict BCR when controlling for other known predictors of BCR. CONCLUSION: Among IR and HR prostate cancer patients, the oncologic outcomes are similar between RALP and ORP. Not surprisingly, adverse pathologic features are harbingers of BCR.