Three-dimensional volumetric evaluation of root resorption in maxillary anteriors following en-masse retraction with varying force vectors - a randomized control trial.

BACKGROUND: Root resorption in orthodontics is associated with direction and magnitude of force application as primary etiological factors. Well-controlled trials that utilize three-dimensional segmentation to detect volumetric changes in tooth structure are required to assess the quantitative nature of root resorption. OBJECTIVE: To assess the severity of root resorption (RR) during retraction of maxillary anteriors with three different force vectors (with and without skeletal anchorage) via cone-beam computed tomography (CBCT) superimpositions. TRIAL DESIGN: Three-arm parallel randomized clinical trial (RCT). MATERIALS AND METHODS: Forty-two (16 males, 26 females) patients, (17-28 years), in permanent dentition with bimaxillary protrusion were randomly allocated to three groups of 14 patients each using block randomization (1:1:1 ratio) and allocation concealment. En-masse anterior retraction post first premolar extractions was carried out with modified force vectors in the three groups based on anchorage type [Molar, Mini-implant and Infrazygomatic crest (IZC) bone screws]. Volumetric root loss and linear dimensional changes were blindly assessed on initial (T0) and final (T1, end of space closure) CBCT scans. Normality distribution of values was done using Shapiro-Wilk's test. ANOVA and Post-hoc Tukey HSD test were done to compare measurements between groups at significance levels (P < .05). RESULTS: Forty patients were analysed (14, 14, and 12 in three groups). Significant volumetric loss was noted in all groups. Central incisors demonstrated a significant reduction in IZC group (81.5 ± 21.1 mm3 ) compared to conventional (50.1 ± 26.5 mm3 ) and mini-implant groups (76.1 ± 27.6 mm3 ). Canines demonstrated a significant reduction in mini-implant group (108.9 ± 33.9 mm3 ) compared to conventional (68.8 ± 42.5 mm3 ) and IZC groups (103.1 ± 29.1 mm3 ). Regarding linear parameters, central incisors and canines revealed significant root length reduction in both skeletal anchorage groups. Lateral incisors showed no significant changes between groups. CONCLUSIONS: Intrusive force vectors generated during skeletally anchored retraction can predispose anteriors to an increased risk of resorption. Greater loss of root volume was noted in the centrals and canines when retracted with skeletal anchorage. LIMITATIONS: Small sample size and variations during CBCT acquisition. HARMS: Low-dose CBCT scans were taken at T0 and T1 treatment intervals.

A review study on early detection of pancreatic ductal adenocarcinoma using artificial intelligence assisted diagnostic methods.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, chemo-refractory and recalcitrant cancer and increases the number of deaths. With just around 1 in 4 individuals having respectable tumours, PDAC is frequently discovered when it is in an advanced stage. Accordingly, ED of PDAC improves patient survival. Subsequently, this paper reviews the early detection of PDAC, initially, the work presented an overview of PDAC. Subsequently, it reviews the molecular biology of pancreatic cancer and the development of molecular biomarkers are represented. This article illustrates the importance of identifying PDCA, the Immune Microenvironment of Pancreatic Cancer. Consequently, in this review, traditional and non-traditional imaging techniques are elucidated, traditional and non-traditional methods like endoscopic ultrasound, Multidetector CT, CT texture analysis, PET-CT, magnetic resonance imaging, diffusion-weighted imaging, secondary signs of pancreatic cancer, and molecular imaging. The use of artificial intelligence in pancreatic cancer, novel MRI techniques, and the future directions of AI for PDAC detection and prognosis is then described. Additionally, the research problem definition and motivation, current trends and developments, state of art of survey, and objective of the research are demonstrated in the review. Consequently, this review concluded that Artificial Intelligence Assisted Diagnostic Methods with MRI images can be proposed in future to improve the specificity and the sensitivity of the work, and to classify malignant PDAC with greater accuracy.

Severe lower respiratory tract infections associated with human parainfluenza viruses 1-3 in children infected and noninfected with HIV type 1.

The aim of this study was to compare the clinical course of severe lower respiratory tract infections associated with human parainfluenza virus types 1-3 (HPIV 1-3) in hospitalised children infected with the human immunodeficiency virus type 1 (HIV-1) versus that in hospitalised children not infected with HIV-1. Children were enrolled prospectively as part of a broader study that evaluated the aetiology of lower respiratory tract infections in HIV-1-infected and -noninfected children from March 1997 through March 1999. HPIV types 1-3 were isolated from nasopharyngeal aspirate samples that were analysed using immunofluorescein monoclonal antibody assays. Thirty percent (24 of 80) of the children from whom HPIV was isolated were infected with HIV-1. Sixty-six percent (47 of 62) and 22% (14 of 62) of the HPIV isolates that were typed were subtypes 3 and 1, respectively. The clinical presentation of severe lower respiratory tract infection was similar in both HIV-1-infected and -noninfected children, except that the former were less likely to have wheezing (4.2% vs. 28.6%, P=0.01). Furthermore, the duration of hospitalisation was longer in HIV-1-infected children than in HIV-1-noninfected children (median 11.5 days [range 1-15 days] vs. median 7.5 days [range 1-22 days]; P=0.02), and mortality was higher (5 of 24 [20.8%] infected children vs. 0 of 56 noninfected children; P=0.001). Importantly, four of five (80%) of the HIV-1-infected children who died had other concurrent illnesses or predisposing factors for severe HPIV-associated disease. HPIV-associated lower respiratory tract infection causes greater morbidity and mortality in HIV-1-infected children than in HIV-1-noninfected children; however, this may be due to other concurrent illnesses in HIV-1-infected children.

Improved outcomes with an implantable left ventricular assist system: a multicenter study.

BACKGROUND: Cumulative experience with the Novacor wearable electric left ventricular assist system (LVAS) now exceeds 850 recipients. The pump inflow conduit (IFC) has been implicated in embolic complications. METHODS: Clinical outcomes were compared for two IFC designs in a retrospective, nonrandomized, multicenter study. The original IFC (woven, unsupported, crimped polyester: control group) and an alternative IFC (knitted, gelatin-sealed, integrally supported, uncrimped polyester: test group) were utilized upon availability in North American and European centers. Differences in cerebral embolism to 180 days postimplant were analyzed. RESULTS: Four hundred ninety patients implanted between August 1996 and August 1999, were studied. Two hundred eighty-eight received the control IFC and 202 received the test IFC. The groups (control, test) were well matched for age (48, 49 years), etiology (idiopathic 53%[152 of 288], 55% [112 of 202]; ischemic 34% [97 of 288], 33% [66 of 202]) and mean observation time (97, 91 days). The incidence of embolic cerebrovascular accidents (CVA) was 21% (60 of 288) in the control and 12% (24 of 202) in the test group (p = 0.010). Independent risk factors for embolic CVA were found to be preimplant acute myocardial infarction (odds ratio 4.3), age above 50 years (odds ratio 2.1), and ischemic etiology (odds ratio 1.7). There was no difference in survival between the groups (71% [205 of 288], 68% [137 of 202]). CONCLUSIONS: The alternative (test) IFC has significantly reduced the incidence of embolic CVA. This improvement is likely due to increased resistance to deformation at implant, improved neointimal adhesion, and more favorable blood flow characteristics within the conduit.

Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Device explant protocol.

An explant protocol was developed to investigate the effects of implantation of a left ventricular assist system (LVAS) manufactured by Novacor Division, Baxter Healthcare Corporation on the function of end organs (such as the brain, the kidney, the liver), with particular interest in examining possible complications due to LVAS support. Emphasis was placed on an analysis at the time of device removal and/or autopsy of 1) the local LVAS-host interface; 2) remote cardiovascular and end-organ effects; and 3) the impact of chronic circulatory support on the native heart. To accomplish these objectives, tissue and device samples must be obtained in an appropriate fashion to ensure photographic documentation, microscopic examination, microbiologic and biochemical assays, and compliance with regulatory and manufacturer requirements. This article describes the techniques and protocol that were proposed to ensure the quality of device explant and tissue analysis.

Initial clinical experience with a wearable controller for the Novacor left ventricular assist system.

The Novacor left ventricular assist system (LVAS), an implanted electromechanically driven blood pump, has been used in an ongoing clinical trial as a bridge to cardiac transplantation since 1984. The initial configuration included a console based extracorporeal controller. Because patients supported by the device usually become rehabilitated and highly mobile, a wearable control system was developed for the ambulatory patient. Ergonomically designed for portability, comfort, and appearance, it offers the recipient greater mobility, improved self-image, and an enhanced quality of life. This wearable control system consists of a microprocessor based compact controller that drives the implanted pump/drive unit in synchronous counterpulsation to the native heart. Main and reserve rechargeable power packs, each incorporating a "smart" monitoring circuit with charge-level display and alarm, are capable of supporting the pump for as long as 7 hr. An LVAS monitor can be connected to the controller for device monitoring and adjustment or as a power supply in lieu of the main power pack. Clinical evaluation in patients with end-stage heart disease followed the same protocol as the console study. By April 4, 1994, 41 patients had been supported by the wearable system, including 9 patients currently being supported. Mean duration of use was 51 days (range, 1.5-143+ days), compared with 42 days for 170 console patients (range, 0-370 days). Survival to transplant was 66%, which was similar to the survival (60%) for the patients using the console. Post-transplant survival was 100%, compared with 90% for console patients (not significantly different). After recovering from implant surgery and pre-implant morbidity, device recipients had considerable freedom and mobility and were able to move freely within and outside the hospital. Recipients could readily switch between monitored and untethered operation and could manage power pack replacement and recharging.

Clinical experience with the Novacor ventricular assist system. Bridge to transplantation and the transition to permanent application.

At Stanford University, a Novacor left ventricular assist system (Baxter Healthcare Corporation, Novacor Division, Oakland, Calif.) was placed as a bridge to heart transplantation in 13 patients. During the hospitalization preceding device implantation, all patients were receiving inotropic support for biventricular failure, 11 had pulmonary edema, 6 had life-threatening ventricular arrhythmias, 5 had liver dysfunction with coagulopathy, and 2 had renal failure necessitating artificial support. The mean cardiac index before implantation of the Novacor system was 1.5. All survivors with the Novacor device had a dramatic increase in cardiac output (mean cardiac index = 3.1). One patient with cardiac allograft rejection died during implantation of the left ventricular assist system. Two patients died of pulmonary sepsis and multiorgan failure after the device was implanted. All patients who had the Novacor device implanted for more than 7 days were able to walk and ride stationary bicycles while awaiting transplantation. Ten patients (77%) underwent successful heart transplantation after a mean of 18 days' support with the Novacor device. One patient died of presumed sepsis 2 days after transplantation. Nine patients (90%) are alive 4 months to 6 years after transplantation. In the overall United States experience, 68 patients (as of May 1990) have had a Novacor left ventricular assist device implanted. Five were still being supported, 39 had received a transplant (62%), and 35 patients (90%) survived the transplant hospitalization (1 died later). No instances of device failure have occurred. Overall, the Novacor assist system provided effective bridging to transplantation, with posttransplant survival similar to results after routine transplantation. Modifications and improvements based on this clinical experience have been made in the areas of patient selection, techniques of operative placement, postoperative management, and design of the assist system. Isolated left heart support with a fully implantable left ventricular assist system will be offered as an alternative to heart transplantation for selected patients by 1992.

Clinical evaluation of the Novacor totally implantable ventricular assist system. Current status.

The totally implantable Novacor left ventricular assist system (LVAS) is currently approaching clinical evaluation. In vivo testing and production are underway with National Institutes of Health (NIH) support. Activity over the past year has focused on manufacturing engineering, preproduction quality assurance, and in vivo experiment completion. Subsequent to successful completion of the NIH-sponsored, 2-year preclinical device readiness test (DRT), a number of refinements were identified and approved by the NIH technical/data review board. Most of these were necessitated by obsolescence or unavailability of electronic components and the decision to use only high reliability military (MIL) qualified electronic components and processes. A few additional refinements were identified to increase design margins, all of which were qualified by accelerated testing. The development of production processes, automated test programs, and MIL compliant environmental stress screening procedures was completed. Production of LVAS subsystems, including core electronic components (hybrids, application-specific integrated circuits, and surface mount boards), was initiated. Animal studies are underway. The clinical trial, at Presbyterian-University Hospital of Pittsburgh and St. Louis University Medical Center, awaits completion of in vivo experiments, protocol development, and Food and Drug Administration approval.

Chronic ovine evaluation of a totally implantable electrical left ventricular assist system.

The totally implantable Novacor left ventricular assist system (LVAS) comprises a pump/drive unit (VAD), electronic control and power subsystem (ECP), variable volume compensator (VVC), and belt skin transformer (BST). The system is now undergoing chronic in vivo evaluation. Cumulative animal testing of VAD, VVC, and BST subsystems are 12.1, 4.9, and 43 years, respectively. The longest implants were 279 days for the VAD, 767 days for the VVC, and 1,148 days for the BST. A chronic implant of the total system was electively terminated at 260 days. The LVAS was powered via the BST. Continuously monitored hemodynamic and pump parameters have demonstrated normal hemodynamics and LVAS operation. Periodic VVC determinations suggest a 0.8 ml/day diffusive gas loss. Tether-free operation has been demonstrated with an Ag-Zn battery backpack. The animal was healthy and free of infection as indicated by routine hematologic, biochemical and serum enzyme determinations. Hemolysis is minimal (plasma free hemoglobin less than 5 mg%). Pump output ranged from 7 to 8 L/min. Severe valve calcification was the reason for elective termination at 260 days. This preclinical in vivo experience, and in vitro reliability studies, demonstrate efficacy of the total system.

Implantable electrical left ventricular assist system: bridge to transplantation and the future.

An implantable left ventricular assist system (LVAS) utilizing an electromechanically driven dual pusher-plate blood pump has been employed in a multiinstitutional trial as a bridge to cardiac transplantation. Under development for permanent circulatory support in patients with end-stage heart disease, the LVAS, in this application, derives power and control from an external console via a percutaneous lead. The LVAS was implanted in 20 patients (16 men, 4 women) who were hemodynamically unstable or in refractory cardiogenic shock. The mean age was 44.9 years (range, 25 to 63 years). Preoperative diagnosis was evenly divided between end-stage ischemic disease, cardiomyopathy, and acute myocardial infarction. Implanted in the left upper quadrant within the anterior abdominal wall, the blood pump was connected between the left ventricular apex and ascending aorta. Total support of the systemic circulation and substantial left ventricular unloading were achieved with synchronous counterpulsation for periods up to 90 days (mean, 22.7 days). All patients were stabilized hemodynamically. The mean preoperative cardiac index of 1.5 L/min/m2 increased by a factor of 2. Pulmonary arterial pressures decreased substantially. Serious complications occurred in 16 patients, precluding cardiac transplantation in 10. Most complications (greater than 70%) were in patients who did not receive transplants; the most common complication was bleeding. Twelve of 13 patients with LVAS implants for more than seven days were mobilized, and 4 were fully ambulatory and completely rehabilitated. Orthotopic cardiac transplantation was performed in 10 patients after implants ranging from two to 90 days (mean, 30.3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro and in vivo testing of a totally implantable left ventricular assist system.

The totally implantable Novacor LVAS is being tested under NIH auspices to demonstrate safety and efficacy before clinical trials. Twelve complete systems (submerged in saline at 37 degrees C) are being tested, with an NIH goal of demonstrating 80% reliability for 2 year operation with a 60% confidence level. The systems, which are continuously monitored, are diurnally cycled between two output levels by automatically varying preload and afterload. Currently, 14.3 years of failure-free operation have been accumulated, with a mean duration of 14 months. Using an exponential failure distribution model, the mean time to failure (MTTF) is greater than 8.8 years, corresponding to a demonstrated reliability (for a 2 year mission time) of 80% (80% confidence level). Recent ovine experiments with VAS subsystems include a 767 day volume compensator implant, a 279 day pump/drive unit implant and a 1,448 day BST implant. The last 12 chronic pump/drive unit experiments had a mean duration of 153 days (excluding early postoperative complications). This compares favorably with the NIH goals for complete systems (5 month mean duration). Complete system experiments are currently underway.

Bioprosthetic valve calcification and pseudoneointimal proliferation in bovine and ovine models.

Both porcine (PX) and bovine pericardial (BP) valves have been used in the implantable Novacor left ventricular assist system (LVAS). Results from 58 chronic LVAS implants of greater than 7 days in calves and adult sheep are presented: the PX valve was used in 41 and the BP in 17. With PX valves, the maximum and mean assist durations were 161 and 54 days, respectively, in the calf and 279 and 129 days, respectively, in the sheep. The maximum and mean durations for BP valves were 93 and 38 days (calf) and 153 and 69 days (sheep). In bovine studies with PX valves, severe obstructive pseudoneointimal (PNI) proliferation in the Dacron inflow conduit was the primary cause for termination; valves exhibited moderate calcification. With BP valves, both PNI proliferation and severe valve calcification contributed to a declining pump output, leading to termination. In contrast to the bovine experience, PNI proliferation was not observed in ovine implants. BP valves still became calcified, as evidenced by a progressive decline in pump output (from about twelve weeks) and confirmed at termination. Valve calcification was minimal with the PX valves, even at 236 days. These results favor the adult ovine animal model for extended implants.

Isolated left ventricular assist as bridge to cardiac transplantation.

The electrically driven Novacor implantable left ventricular assist device has been implanted in six patients (four men and two women) since Sept. 7, 1984. In four of the six patients (67%) the device was a successful bridge to cardiac transplantation. One patient died of multiple organ failure and Candida sepsis after 16 days of support with the device. One patient died in the operating room of uncontrollable hemorrhage and biventricular failure caused by severe cardiac rejection. Three patients are alive with cardiac transplants 38, 17, and 10 months after transplantation. One patient died after cardiac transplantation of presumed sepsis. The Novacor left ventricular assist device performed in all cases without mechanical or electrical failure. Excluding the intraoperative death, assist duration ranged from 2 to 16 days. The cardiac index (synonymous with device output) ranged from 2.4 to 3.4 L/min/m2. No embolic events (cerebrovascular or systemic) occurred during assistance with the device. Minimal red cell hemolysis was documented during the period of support. The Novacor left ventricular assist device is a safe and effective bridge to cardiac transplantation in patients with refractory cardiogenic shock.

The blood interface at artificial surfaces within a left ventricular assist system.

A left ventricular assist system presents a very complex set of interfaces to the blood. The interactions of the various components, their junctions, and fluid dynamic effects have been discussed at a macroscopic, cellular and molecular level. Failure of any part of the system can seriously compromise LVAS function or host response whether due to gross thrombosis with occlusion, proliferative PNI formation, or thromboembolic events. It has been stated that: "When artificial hearts are designed properly, nearly any surface goes." Unfortunately, the blood interface within any circulatory support system, and indeed in much simpler systems, is a much more complex function than design, which includes the surface, materials and many other factors (Table 6).

Long-term function of NCGT vascular conduits in a multicenter trial: evaluation of physical chemical parameters.

Our experience with the NCGT graft has now encompassed 12 years in experimental animals and 4.5 years clinical experience with 134 grafts in man. It has previously been suggested that vessel wall structure, interface-charge, electric potential, and polarity of the blood intimal interface appear critical in the prevention of intravascular thrombosis in all vascular prosthetic bypass grafts. This concept has now been confirmed using ferritin, colloidal iron and fluorescamine intimal labelling. These provide a quantitative special characterization of the surface charges of several grafts, including the NCGT graft. Study indicates that each step in the production of the NCGT graft results in a cumulative increase in the structured negative charge of the vascular interface. The more dense the structured negative charge of the prosthesis, the more resistant is the graft to short and long-term thrombosis in experimental animals and man. The experience has been confirmed with a comparative analysis of implantation results in 105 patients up to 4.5 years with 65 to 70% patency rate over that time interval. Statistical analysis of parameters confirm again that the polarity and structure of the vascular interface is important in the effective function and patency rate of the grafts.

Hormonal steroids: effects on the vascular system.

An increase in the incidence of thromboembolic disorders has been associated with oral contraceptive use, though the causative mechanisms remain unclear. Our studies indicate that the contraceptive steroids, irrespective of the intermediary metabolic processes involved, cause changes in the surface charge characteristics of the blood vessel wall and blood cells in the following cases: (i) in experiments using dogs, the hormonal steroids result in a greater reduction in the pore surface charge of veins than in arteries; (ii) in rats, the current induced mesenteric occlusion times are significantly lowered following administration of combined contraceptives steroids; (iii) in humans, the electrophoretic mobilities of erythrocytes and platelets from women taking Ovral and Demulen are lower than in controls, and (iv) there is no significant alteration of plasma coagulation times of women who are on injectable progestin therapy. Demulen and Ovral appear to result in a slight decrease in activated partial thromboplastin times compared to controls.

PIP: The effects of hormonal contraceptive agents on the vascular system were studied in rats, dogs, and 34 women taking oral or injectable steroid contraceptive agents. Changes in the surface charge characteristics of the blood vessel wall and blood cells were observed. In dogs, the reduction in pore surface charge was greater in veins than in arteries. In rats, the induced mesenteric occlusion times were significantly reduced (p less than .001). However, Provera did not significantly reduce induced occlusion time in these animals (p greater than .01). Ov ral and Demulen lowered the mobilities of erythrocytes and platelets in women. Plasma coagulation times were not markedly altered in women receiving injectable progestin. Acitivated partial thromboplastin times were slightly decreased by Ovral and Demulen. The results suggest an increased tendency toward thrombosis in women taking steroid hormone contraceptive agents.