Control4Life: A randomized controlled trial protocol examining the feasibility and efficacy of a combined pelvic health rehabilitation and exercise fitness program for individuals undergoing prostatectomy.

BACKGROUND: Urinary incontinence (UI), erectile dysfunction and cardiometabolic conditions are common after prostatectomy for prostate cancer (PCa). Although physical activity could improve overall survival and quality of survivorship, fear of UI can restrict participation in exercise. Individuals with PCa could benefit from therapeutic exercise programming to support continence recovery and cardiometabolic health. AIM: The main objective of this study is to determine the feasibility and the effects of a combined pelvic health rehabilitation and exercise fitness program on UI after prostatectomy. The combined exercise program will be delivered both in-person and virtually. METHODS: This study follows a modified Zelen, two-arm parallel randomized controlled trial design. A total of 106 individuals with PCa will be recruited before prostatectomy surgery. Participants will be randomized between two groups: one receiving usual care and one receiving a combined exercise fitness and intensive pelvic floor muscle training program. Exercise programming will begin 6-8 weeks after prostatectomy and will last 12 weeks. Outcomes include: the 24-h pad test (primary outcome for UI); physical fitness, metabolic indicators, and patient-reported outcomes on erectile function, self-efficacy, severity of cancer symptoms and quality of life. Important timepoints for assessments include before surgery (T0), after surgery (T1), after intervention (T3) and at one-year after surgery (T4). CONCLUSION: This study will inform the feasibility of offering comprehensive exercise programming that has the potential to positively impact urinary continence, erectile function and cardiometabolic health of individuals undergoing prostatectomy for prostate cancer. CLINICALTRIALS REGISTRATION NUMBER: NCT06072911.

Effects of Hyperbaric and Decompression Stress on Blood Coagulation and Fibrinolysis: Comparison of Thromboelastography and Thromboelastometry.

Hyperbaric and decompression stress from diving impairs blood coagulation and fibrinolysis. We hypothesized that thromboelastography (TEG) and rotational thromboelastometry (ROTEM) were suitable to characterize the effects of stress on global hemostatic profiles. We thus conducted a comparative study of the hyperbaric effects on human coagulation using TEG and ROTEM. Maximum clot strength (maximum amplitude [MA]) and clot lysis (lysis index at time 30 minutes [LI30]) were reduced as indicated by TEG MA and EXTEM LI30, respectively. The relative changes in coagulation and fibrinolysis by the hyperbaric effects of diving were indicated by reduced TEG reaction time R at 5 hours, MA at 24 hours postdive, and reduced EXTEM coagulation time at 15 minutes postdive as well as decreased fibrinolysis (EXTEM LI30) at all postdiving time points investigated. Comparison of the parameter values and the diving-induced changes in each parameter between TEG and ROTEM showed both differences and correlations. The discrepancies between the 2 systems may be due to the different assay reagents used. Future studies will seek to further elucidate the changes in blood coagulation and fibrinolysis following varying levels of hyperbaric and decompression stress.

Anatomic surface reconstruction from sampled point cloud data and prior models.

In this paper, we propose an approach for reconstruction of an anatomic surface model from point cloud data using the Screened Poisson Surface Reconstruction algorithm, which requires a collection of points and their normal vectors. Various algorithms exist for estimating normal vectors for point cloud data; however, in this work we describe a novel approach to estimating the normal vectors from a high-resolution prior model. In many medical applications, a preoperative high-resolution scan is acquired for diagnostic and planning purposes, whereas intraoperative, lower fidelity imaging is utilized during the procedure. This approach assumes an already existing registration between intra-operatively acquired data and the preoperative model. We conducted simulation experiments to evaluate the effect of registration error, point sampling rate, and noise levels on the acquired point cloud data samples. In addition, we evaluated the effect of using both the closest point, as well as a neighborhood of closest points on the prior model for estimating the normal. Our results showed that surface reconstruction error increases with higher registration error; however, acceptable performance was achieved with clinically-acceptable registration error. In addition, the best reconstruction was obtained when estimating the normal using only the closest point on the prior model, as opposed to utilizing a neighborhood of points. When combining the effect of all factors (Gaussian sampling noise of zero mean and σ=1.8mm; Gaussian translational error of zero mean and σ=2.0mm; and Gaussian rotational error of zero mean and σ=3°) the overall RMS reconstruction error was 0.88±0.03mm.

Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures.

PURPOSE: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. METHODS: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamic in vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. RESULTS: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved landmark-only registration provided the noise in the surface points is not excessively high. Increased variability on the landmark fiducials resulted in increased registration errors; however, refinement of the initial landmark registration by the surface-based algorithm can compensate for small initial misalignments. The surface-based registration algorithm is quite robust to noise on the surface points and continues to improve landmark registration even at high levels of noise on the surface points. Both the canine and patient studies also demonstrate that combined landmark and surface registration has lower errors than landmark registration alone. CONCLUSIONS: In this work, we describe a model for evaluating the impact of noise variability on the input parameters of a registration algorithm in the context of cardiac ablation therapy. The model can be used to predict both registration error as well as assess which inputs have the largest effect on registration accuracy.

Fast adaptation of pre-operative patient specific models to real-time intra-operative volumetric data streams.

Image-guided catheter ablation therapy is becoming an increasingly popular treatment option for atrial fibrillation. Successful treatment relies on accurate guidance of the treatment catheter. Integration of high-resolution, pre-operative data with electrophysiology data and positional data from tracked catheters improves targeting, but lacks the means to monitor changes in the atrial wall. Intra-operative ultrasound provides a method for imaging the atrial wall, but the real-time, dynamic nature of the data makes it difficult to seamlessly integrate with the static pre-operative patient-specific model. In this work, we propose a technique which uses a self-organizing map (SOM) for dynamically adapting a pre-operative model to surface patch data. The surface patch would be derived from a segmentation of the anatomy in a real-time, intra-operative ultrasound data stream. The method is demonstrated on two regular geometric shapes as well as data simulated from a real, patient computed tomography dataset.

Hyperbaric stress in divers and non-divers: neuroendocrine and psychomotor responses.

This study compared neuroendocrine and psychomotor responses in divers (D, n = 11) and non-divers (ND, n = 9) following 30-minute hyperbaric and decompression stress to 180, 300 and 450 kPa. Venous blood was drawn pre-dive and at 20 and 60 minutes post-dive and analyzed for norepinephrine (NE), epinephrine (E), tryptophan (TRP), cortisol (COR), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and prolactin (PRL). Reaction time was assessed using a psychomotor vigilance task. There was no difference between groups, across time or among levels of hyperbaric stress, for NE, E, TRP or GH. Small decreases over time in COR were noted. ACTH was significantly higher for ND at 20 minutes following 180 kPa and after 60 minutes for 450 kPa exposure. PRL increased significantly more for ND, and changes from baseline following 450 kPa exposure were moderately related (r = 0.52) to the significant slowing of reaction time at 20 minutes (296 +/- 55 msec) and 60 minutes (277 +/- 35 msec) compared with baseline (247 +/- 22 msec), although PRL returned to baseline levels faster than reaction time. It was concluded that for the stress hormones measured, PRL may provide some indication of the adaptation involved with repeated hyperbaric stress, but its relationship to changes in reaction time was weak.

Nitration of the mitochondrial complex I subunit NDUFB8 elicits RIP1- and RIP3-mediated necrosis.

Nitric oxide (NO) and other reactive nitrogen species target multiple sites in the mitochondria to influence cellular bioenergetics and survival. Kinetic imaging studies revealed that NO from either activated macrophages or donor compounds rapidly diffuses to the mitochondria, causing a dose-dependent progressive increase in NO-dependent DAF fluorescence, which corresponded to mitochondrial membrane potential loss and initiated alterations in cellular bioenergetics that ultimately led to necrotic cell death. Cellular dysfunction is mediated by an elevated 3-nitrotyrosine signature of the mitochondrial complex I subunit NDUFB8, which is vital for normal mitochondrial function as evidenced by selective knockdown via siRNA. Overexpression of mitochondrial superoxide dismutase substantially decreased NDUFB8 nitration and restored mitochondrial homeostasis. Further, treatment of cells with either necrostatin-1 or siRNA knockdown of RIP1 and RIP3 prevented NO-mediated necrosis. This work demonstrates that the interaction between NO and mitochondrially derived superoxide alters mitochondrial bioenergetics and cell function, thus providing a molecular mechanism for reactive oxygen and nitrogen species-mediated alterations in mitochondrial homeostasis.

A randomized controlled feasibility trial comparing safety and effectiveness of prehospital pacing versus conventional treatment: 'PrePACE'.

OBJECTIVE: To evaluate the feasibility of a prehospital randomized controlled trial comparing transcutaneous pacing (TCP) with dopamine for unstable bradycardia. METHODS: Unstable bradycardic patients who failed to respond to a fluid bolus and up to 3mg atropine were enrolled. The intervention was dopamine or TCP with crossover to dopamine if TCP failed. The primary outcome was survival to discharge or 30 days. Randomization compliance, safety, follow-up rates, primary outcome, and sample size requirements were assessed. RESULTS: Of 383 patients with unstable bradycardia, 151 (39%) failed to respond to atropine or fluid and were eligible for enrollment and 82 (55%) were correctly enrolled. Fifty-five (36%) of eligible patients could not be enrolled for practical reasons; 3 had advance directives, 32 met inclusion criteria on arrival at hospital and in 20 cases, paramedics chose not to enroll based on the circumstances of the case. The remaining 13 were missed cases; 8 were missing randomization envelopes and in 5, the paramedic forgot. Randomization compliance was 95% (78/82). Forty-two (51%) patients were randomized to TCP and seven of these crossed over to dopamine. Two cases were randomized but did not receive the intervention; either due to lack of time or loss of IV access. Three adverse events occurred in each group. Survival to discharge or 30 days in hospital was 70% (28/40) and 69% (29/42) in the dopamine and TCP groups, respectively with 100% follow up. To detect a 10% relative difference in 30 days survival between treatment arms, a sample size of 690 per group would be required. CONCLUSIONS: It is feasible to conduct a prehospital randomized controlled trial of TCP for unstable bradycardia and a definitive trial would require a multi-centre study.

Risk factors for venous gas emboli after decompression from prolonged hyperbaric exposures.

INTRODUCTION: The physical forces governing gas phase nucleation and growth in a liquid would predict less variation in the development of decompression sickness (DCS) than is known to occur in people. METHODS: In order to gain insight into the causes of biological susceptibility to DCS, we analyzed a dataset containing 250 human steady-state hyperbaric exposures using multivariate ordinal and linear regression analysis for relationships between venous gas emboli (VGE) and exposure parameters and subject characteristics. RESULTS: In both previously published data and new chamber exposure data, we found that the strongest predictor of VGE magnitude after decompression was the duration and depth of the hyperbaric exposure, as predicted. Of the subject factors, only age was significantly associated with VGE; body mass index (BMI) and gender were not. The relationship between age and VGE strengthened with decompression magnitude. DISCUSSION: These results suggest that the physiology of aging interacts with the mechanism of VGE generation, altering the risk of DCS after decompression.

Evaluation of platelet transfusion triggers in a tertiary-care hospital.

BACKGROUND: Our 1100-bed referral hospital uses approximately 12,000 units of random-donor platelets (PLTs) and 1,900 units of single-donor apheresis PLTs per year with a mean of 23 percent outdating. An analysis of patterns of utilization has been undertaken to evaluate practice. STUDY DESIGN AND METHODS: Over a 9-month period, data were collected on a total of 1682 transfusion episodes in 464 patients. When the pretransfusion count was greater than 10 x 10(9) per L an attempt was made to identify the specific indications for PLT transfusions such as bleeding. RESULTS: The majority (78%) of PLTs were transfused when the counts were above 10 x 10(9) per L. The mean pretransfusion counts for different services were: bone marrow transplant (BMT) 17.4 x 10(9) per L, hematology-oncology 14.6 x 10(9) per L, the Heart Institute 3 x 10(9) per L, and other services 36 x 10(9) per L. The percentage of transfusions given to patients with a count greater than 10 x 10(9) per L varied by service with 79 percent in BMT, 60 percent in hematology and oncology, 98 percent at the Heart Institute, and 81 percent in other services. Routine monitoring of counts shows a mean increment of 10.2 x 10(9) per L per transfusion. One hour posttransfusion counts, 24-hour posttransfustion counts, and documentation of clinical justification for transfusions was often not available. CONCLUSIONS: The data show that most patients who receive PLTs have pretransfusion counts of more than 10 x 10(9) per L and more than one-third have pretransfusion counts of greater than 20 x 10(9) per L. The medical literature supports prophylactic PLT transfusion based solely on the count when the PLT number is 10 x 10(9) per L or less. Above this level additional justification is needed although there are different points of view concerning the appropriate triggers. Our data suggest that there is a need for clear hospital transfusion guidelines and ongoing monitoring of PLT use.

Tissue engineering templates using minimal surfaces.

The status quo of tissue engineering can be summarized as "a random walk through the design space". The existing scaffold designs based on computeraided design (CAD) and solid freeform fabrication (SFF) are anti-biomorphic and mechanically weak cubic partitions with sharp edges. We introduce minimal surface based unit cells to create biomorphic scaffolds with optimal stress/strain distribution and superior mechanical strength.

Virtual-reality-assisted interventional procedures.

Observable objects in biology and medicine extend across a range of scale, from individual molecules and cells; through the varieties of tissue and interstitial interfaces; and to complete organs, organ systems, and body parts. These objects include functional attributes of these systems such as biophysical, biomechanical, and physiologic properties. Imaging in three dimensions of such objects and their functions is possible now with the advent of high-resolution tomographic scanners and imaging systems. Medical applications include accurate anatomy and function mapping, enhanced diagnosis, accurate treatment planning and rehearsal, and education and training. Biologic applications include study and analysis of structure-to-function relationships in individual cells and organelles. The potential for revolutionary innovation in the practice of medicine and in biologic investigations lies in direct, fully immersive, real-time multisensory fusion of real and virtual information data streams into online, real-time images available during actual clinical procedures or biologic experiments. Current high-performance computing, advanced image processing and high-fidelity rendering capabilities have facilitated major progress toward realization of these goals. With these advances in hand, there are several important applications of three-dimensional viewing that will have a substantial impact on the practice of medicine.

Out-of-hospital cardiac arrest rectilinear biphasic to monophasic damped sine defibrillation waveforms with advanced life support intervention trial (ORBIT).

BACKGROUND: Although biphasic defibrillation waveforms appear to be superior to monophasic waveforms in terminating VF, their relative benefits in out-of-hospital resuscitation are incompletely understood. Prior comparisons of defibrillation waveform efficacy in out-of-hospital cardiac arrest (OHCA) are confined to patients presenting in a shockable rhythm and resuscitated by first responder (basic life support). This effectiveness study compared monophasic and biphasic defibrillation waveform for conversion of ventricular arrhythmias in all OHCA treated with advance life support (ALS). METHODS AND RESULTS: This prospective randomized controlled trial compared the rectilinear biphasic (RLB) waveform with the monophasic damped sine (MDS) waveform, using step-up energy levels. The study enrolled OHCA patients requiring at least one shock delivered by ALS providers, regardless of initial presenting rhythm. Shock success was defined as conversion at 5s to organized rhythm after one to three escalating shocks. We report efficacy results for the cohort of patients treated by ALS paramedics who presented with an initially shockable rhythm who had not received a shock from a first responder (MDS: n=83; RLB: n=86). Shock success within the first three ascending energy shocks for RLB (120, 150, 200J) was superior to MDS (200, 300, 360J) for patients initially presenting in a shockable rhythm (52% versus 34%, p=0.01). First shock conversion was 23% and12%, for RLB and MDS, respectively (p=0.07). There were no significant differences in return of spontaneous circulation (47% versus 47%), survival to 24h (31% versus 27%), and survival to discharge (9% versus 7%). Mean 24h survival rates of bystander witnessed events showed differences between waveforms in the early circulatory phase at 4-10 min post event (mean (S.D.) RLB 0.45 (0.07) versus MDS 0.31 (0.06), p=0.0002) and demonstrated decline as time to first shock increased to 20 min. CONCLUSION: Shock success to an organized rhythm comparing step-up protocol for energy settings demonstrated the RLB waveform was superior to MDS in ALS treatment of OHCA. Survival rates for both waveforms are consistent with current theories on the circulatory and metabolic phases of out-of-hospital cardiac arrest.

Electronic laboratory reporting for the infectious diseases physician and clinical microbiologist.

BACKGROUND: One important benefit of electronic health information is the improved interface between infectious diseases practice and public health. Electronic communicable disease reporting (CDR), given its legal mandate and clear public health importance, is a significant early step in the sifting and pooling of health data for purposes beyond patient care and billing. Over the next 5-10 years, almost all CDR will move to the internet. METHODS: This paper reviews the components of electronic laboratory reporting (ELR), including sifting through data in a laboratory information management system for reportable results, controlled "vocabularies" (e.g., LOINC, Logical Observation Identifiers Names and Codes [Regenstrief Institute], and SNOMED, Systematized Nomenclature of Medicine [College of American Pathologists]), the "syntax" of an electronic message (e.g., health level 7 [HL7]), the implications of the Health Insurance Portability and Accountability Act for ELR, and the obstacles to and potential benefits of ELR. RESULTS: There are several ways that infectious diseases physicians, infection control professionals, and microbiology laboratorians will participate in electronic CDR, including web-based case reporting and ELR, the direct, automated messaging of communicable disease reports from clinical lab information management systems to the appropriate public health jurisdiction's information system. CONCLUSIONS: ELR has the potential to make a large impact on the timeliness and the completeness of communicable disease reporting, but it does not replace the clinician's responsibility to submit a case report with important demographic and epidemiologic information.

Neuronal nitric oxide synthase and N-methyl-D-aspartate neurons in experimental carbon monoxide poisoning.

We measured changes in nitric oxide (NO) concentration in the cerebral cortex during experimental carbon monoxide (CO) poisoning and assessed the role for N-methyl-d-aspartate receptors (NMDARs), a glutamate receptor subtype, with progression of CO-mediated oxidative stress. Using microelectrodes, NO concentration was found to nearly double to 280 nM due to CO exposure, and elevations in cerebral blood flow, monitored as laser Doppler flow (LDF), were found to loosely correlate with NO concentration. Neuronal nitric oxide synthase (nNOS) activity was the cause of the NO elevation based on the effects of specific NOS inhibitors and observations in nNOS knockout mice. Activation of nNOS was inhibited by the NMDARs inhibitor, MK 801, and by the calcium channel blocker, nimodipine, thus demonstrating a link to excitatory amino acids. Cortical cyclic GMP concentration was increased due to CO poisoning and shown to be related to NO, versus CO, mediated guanylate cyclase activation. Elevations of NO were inhibited when rats were infused with superoxide dismutase and in rats depleted of platelets or neutrophils. When injected with MK 801 or 7-nitroindazole, a selective nNOS inhibitor, rats did not exhibit CO-mediated nitrotyrosine formation, myeloperoxidase (MPO) elevation (indicative of neutrophil sequestration), or impaired learning. Similarly, whereas CO-poisoned wild-type mice exhibited elevations in nitrotyrosine and myeloperoxidase, these changes did not occur in nNOS knockout mice. We conclude that CO exposure initiates perivascular processes including oxidative stress that triggers activation of NMDA neuronal nNOS, and these events are necessary for the progression of CO-mediated neuropathology.

An immersive simulation system for provoking and analyzing cataplexy.

Cataplexy, a sudden loss of voluntary muscle control, is one of the hallmark symptoms of narcolepsy, a sleep disorder characterized by excessive daytime sleepiness. Cataplexy is usually triggered by strong, spontaneous emotions, such as laughter, surprise, fear or anger, and is more common in times of stress. The Sleep Disorders Unit and the Biomedical Imaging Resource at Mayo Clinic are developing interactive display technology for reliably inducing cataplexy during clinical monitoring. The use of immersive displays may help bypass patient defenses, and game-like "unreality" allows introduction of surprising, threatening, or humorous elements, with little risk of offending patients. The project is referred to as the "Cataplexy/Narcolepsy Activation Program", or CatNAP. We have developed an automobile driving simulation to allow the introduction of humorous, surprising, or stress-inducing events and objects as the patient attempts to navigate a simulated vehicle through a virtual town. The patient wears a stereoscopic head-mounted display, by which he views the virtual town through the windows of his simulated vehicle. The vehicle is controlled via a driving simulator steering wheel and pedal cluster. The patient is instructed to drive his vehicle to another location in town, given initial directions and street signs. As he attempts to accomplish the task, various objects, sounds or conditions occur which may distract, startle, frustrate or cause laughter; responses which may trigger a cataplectic episode. The patient can be monitored by reflex tests and EMG recordings during the driving experience. An evaluation phase with volunteer patients previously diagnosed with cataplexy has been completed. The goal of these trials was to gain insight from the volunteers as to improvements that could be made to the simulation. All patients that participated in the evaluation phase have been under a physician's care for a number of years and control their cataplexy with medication. We believe this is a novel and innovative approach to a difficult problem. CatNAP is a compelling example of the potentially effective application of virtual reality technology to an important clinical problem that has resisted previous approaches. Preliminary results suggest that an immersive simulation system like CatNAP will be able to reliably induce cataplexy in a controlled environment. The project is continuing through a final stage of refinement prior to conducting a full clinical study.