Procedure Refinement Research Articles

Ultrasensitive Detection of Alzheimer's Amyloids on a Plasmonic-Gold Platform.

More than 55 million people live with dementia worldwide in 2021, and there are nearly 10 million new cases every year. Alzheimer's disease (AD) is the most common cause of dementia. Despite urgent need, early detection of AD and long-term monitoring of AD progression have been challenging. This is due to the limited availability of brain imaging facilities and the highly invasive procedure with the cerebrospinal fluid assay to assess the level of AD biomarkers, such as beta-amyloid (Aβ). Reliable measurements of AD biomarkers in blood samples are still difficult because of their very low abundance. Here, we develop a rapid, specific, and ultrasensitive immunoassay using plasmonic-gold nanoisland (pGOLD) chips with near-infrared fluorescence-enhanced detection for Aβ1-40 and Aβ1-42. We show step-by-step processes and results during the platform establishment, including antibody specificity and sensitivity tests, antibody pair examination, condition optimization, and procedure refinement. Finally, we demonstrate the platform performance with detection sensitivity at the subpicogram per milliliter level. This platform, therefore, has a great application potential for early detection of AD using blood samples.

Laparoscopic hepatectomy for hepatocellular carcinoma: A study on the adoption at a large academic center

Presenter: Xavier Pereira MD | Montefiore Medical Center Background: Laparoscopic Hepatectomy (LH) for hepatocellular carcinoma (HCC) represents a major change in surgical practice for the established liver surgeon. LH has gradually evolved through the steps of surgical innovation: proof of concept, procedure development, procedure refinement, and now phasing into widespread adoption at most academic centers. However, technical challenges impacting operative outcomes and effects on R0 resection have slowed the adoption of laparoscopy in liver surgery. While landmark studies have confirmed the safety of laparoscopy to early adopters, they often fail to capture the efficacy, safety, and comparable oncologic outcomes that can be seen with the widespread adoption of LH at most academic centers. We sought to describe the adoption of LH for HCC at our institution with an emphasis on early patient selection, a safe and gradual increase in case complexity, and it effects on procedural and oncologic outcomes. Methods: Patients undergoing hepatectomy for HCC between July 2016 to December 2018 were reviewed. Patient demographics, indications for surgery, hepatic disease burden, co-morbidities, intraoperative and postoperative data were reviewed retrospectively. Open (OH) vs. laparoscopic procedures (LH) were matched for comparison od endpoints using Chi square, Student’s T-test, and Mann-Whitney U tests. Results: Comparative distribution of 177 cases on a quarterly timeline is presented (Figure 1), highlighting a steady adoption of LH. Of the 56 patients matched for analysis, 27 underwent open hepatectomy (OH) while 26 underwent LH. These cohorts were well matched without notable difference in the Charlson Comorbidities Index (CCI) (p-value 0.943) or Childs class (p-value 0.077). The LH group showed less tumor burden (p<0.0639) less segments involved (p<0.0063) and less complex resections based on the Iwate difficulty scoring (p<0.0013) indicating an expected bias in patient selection, more conservative for LH. The average LOS, EBL, and intraoperative transfusions were lower in the laparoscopic group vs. the open group (P < 0.0115 and p<0.0483). The proportion of R0/R1 resections was no different between both groups (p<0.2771) achieving R0 resections in 92% of LLRs vs. 80% of OLRs. The median recurrence-free survival and median patient survival was not different between groups. As the study period went on, progression in the learning curve of LH correlated with an increase in the proportion of CCI score >70% and the Iwate difficulty scoring per case, as well as an increase in operative time and a rate of conversions with more challenging cases. Conclusion: Widespread adoption of LH on diseased livers with HCC relies on progressive patient selection reassuring the surgical team on taking more challenging cases. Even with increasingly difficult cases, the complication rate and oncologic outcomes remain comparable to open surgery.

Exploration of robotic-assisted surgical techniques in vascular surgery.

Robotic-assisted surgical approaches for vascular surgery are feasible regarding minimally invasive exposure, dissection, ligation and skeletonization for varicose vein ligation, anterior spine exposure, femoral-popliteal bypass, femoral vein harvest and aortic aneurysm repair. The authors performed a cadaveric exploration to demonstrate proof of concept and feasibility for a robotic-assisted approached. Surgeon autonomy over endoscopic vision, robotic instrumentation and retraction were noted as key benefits over existing open vascular approaches. Robotic-assisted approaches for vascular surgery enable innovative minimally invasive approaches to disease states not amenable to endovascular repair. Potential reductions in paresthesia through nerve identification were noted during a cadaveric exploration for varicose vein ligation in the setting of chronic venous insufficiency. Minimally invasive femoral artery exposure via a retroperitoneal approach could potentially reduce the morbidity associated with the traditional groin incision. Further exploration and procedure refinement are warranted.

Transapical NeoChord mitral valve repair.

Transapical off-pump mitral valve repair (MVr) with NeoChord implantation has become widely applied in Europe for patients presenting with severe mitral regurgitation due to leaflet prolapse or flail. The procedure is performed under real-time 2D- and 3D-transesophageal echocardiography (TEE) for both implantation and neochordae tension adjustment allowing real-time monitoring of hemodynamic recovery. Preoperative anatomic and echocardiographic selection criteria, procedure refinement, as well as innovative ex-vivo surgical simulator training have been developed and strategically employed in the past few years, to generate a robust precision-based procedural framework with significantly enhanced operator use, patient safety and clinical outcomes. The procedure has evolved into a reproducibly successful and safe approach, which complements existing surgical treatment strategies available to eligible patients with chronic severe degenerative mitral regurgitation.

Endoscopic sutured gastroplasty: procedure evolution from first-in-man cases through current technique

Endoscopic sutured gastroplasty (ESG) has evolved over time. With the advent of full-thickness endoscopic suturing, an efficient technique for ESG was developed and refined. This prospective first-in-man trial started in April 2012 and represents the first use of full-thickness endoscopic suturing for primary obesity therapy. The trial focused on procedure development, reproducibility, safety, and short-term efficacy. The trial was performed at centers in five countries, in three phases. Phase I was evaluation of safety and technical feasibility of various procedure techniques; stitch patterns and sequences were assessed for efficiency, safety, and feasibility. Phase II entailed continued procedure refinement to establish a standardized technique. Phase III entailed evaluation of technical feasibility and weight loss outcomes in 77 patients; the procedure was performed using the standardized technique, and there was no procedure development. Data were prospectively collected into a registry. In Phase I, the procedure was created and modified to improve time efficiency. Safety and technical feasibility were established, and short-term weight loss was demonstrated. In Phase II, a number of stitch patterns were attempted, and the stitch pattern was modified and finalized. 22 patients were included, and 1-year total weight loss was 17.3 ± 2.6%. In Phase III, conformity with the final technique was high. 77 patients were included, with a mean BMI of 36.1 ± 0.6kg/m2. Mean weight loss was 16.0 ± 0.8% at 6months and 17.4 ± 1.2% at 12months (n = 44). Postprocedural nausea, vomiting, and epigastric pain were frequently reported; there were no reported significant adverse events post-procedure or during the follow-up period. Following a methodical procedure development phase, ESG demonstrated safety and short-term efficacy in this trial. The procedure also achieved meaningful weight loss during the follow-up period.

Evaluation of gastroscopy and biopsy of the proventriculus and ventriculus in pigeons (Columba livia)

OBJECTIVE To evaluate the efficacy and safety of gastroscopy and biopsy of the proventriculus and ventriculus in pigeons (Columba livia). ANIMALS 15 adult pigeons. PROCEDURES Each pigeon was anesthetized, and the upper gastrointestinal tract (from the cervical portion of the esophagus to the ventriculus) was endoscopically evaluated by use of a rigid endoscope inserted orally. Saline (0.9% NaCl) solution was orally infused to achieve lumen dilation and visibility. Two mucosal biopsy specimens were collected from each of the proventriculus and ventriculus, histologically evaluated, and graded for crush artifacts and depth. Pigeons were monitored for adverse effects for 3 to 6 days after the procedure, after which they were euthanized for necropsy. RESULTS Gastroscopy via the oral approach provided excellent visibility of the lumen and mucosal surfaces of the proventriculus and cranial portion of the ventriculus and was safe provided that appropriate precautions were taken. Two intraoperative deaths occurred at the beginning of the study; following procedure refinement, no additional deaths occurred. No major adverse effects of the procedure were detected in the remaining 13 pigeons during the postoperative monitoring period or at necropsy. Diagnostic quality of proventriculus specimens was adequate for 10 of 13 pigeons. Eight of 13 ventriculus specimens were of inadequate quality, and only 3 were of adequate quality. CONCLUSIONS AND CLINICAL RELEVANCE Gastroscopy was useful for evaluating the lumen and mucosal surface of the proventriculus and ventriculus in pigeons, and biopsy of those organs was safely performed with the appropriate technique. Further evaluation of these techniques is needed in birds with clinical disease and birds of other species.

Refinement of habituation procedures in diet-induced obese mice.

Orogastric gavage, while a common method for delivering experimental substances in mice, has been shown to induce stress. To minimize the associated stress with this procedure, sham gavage prior to the start of experiment is a common method for habiutating mice. We investigated whether handling and restraint could replace sham treatment in the acclimatization protocol. Mice were either undisturbed, hand-restrained for 10 s or sham-gavaged daily for six days prior to eight days of twice daily gavage. The results showed that repetitive restraint and gavage had no differences in body weight after eight days of treatment compared with the body weights at the start of treatment, whereas animals left undisturbed lost significant weight once treatment began. These data suggest that procedure refinement by replacing sham treatment with hand restraint is sufficient to acclimatize mice to the stress associated with gavage.

Endovascular Aneurysm Sealing for Infrarenal Abdominal Aortic Aneurysms: 30-Day Outcomes of 105 Patients in a Single Centre

Endovascular aneurysm sealing (EVAS) has been proposed as a novel alternative to endovascular aneurysm repair (EVAR) in patients with infrarenal abdominal aortic aneurysms (AAA). The early clinical experience, technical refinements, and learning curve of EVAS in the treatment of AAA at a single institution are presented. One-hundred and five patients were treated with EVAS between March 2013 and November 2014. Prospective data were recorded on consecutive patients receiving EVAS. Data included demographics, preoperative aneurysm morphology, and 30-day outcomes, including rates of endoleak, limb occlusion, reintervention, and death. Postoperative imaging consisted of duplex ultrasound and computed tomographic angiography. The mean age of the cohort was 76 ± 8 years and 12% were female. Adverse neck morphology was present in 72 (69%) patients, including aneurysm neck length <10 mm (20%), neck diameter >32 mm (18%), β-angulation >60° (21%), and conical aneurysm neck (51%). There was one death within 30 days. The incidence of Type 1 endoleak within 30 days was 4% (n = 4); all were treated successfully with transcatheter embolisation. All four proximal endoleaks were associated with technical issues that resulted in procedure refinement, and all were in patients with adverse proximal aortic necks. The persistent Type 1 endoleak rate at 30 days was 0% and there were no Type 2 or Type 3 endoleaks. Angioplasty and adjunctive stenting were performed for postoperative limb stenosis in three patients (3%). EVAS appears to be associated with reasonable 30-day outcomes despite the necessity of procedural evolution in the early adoption of this technique. EVAS appears to be applicable to patients with challenging aortic morphology and endoleak rates should reduce with procedural experience. The utility of EVAS will be defined by the durability of the device in long-term follow-up, although the absence of Type 2 endoleaks is encouraging.

Endovascular Aneurysm Sealing for Infrarenal Abdominal Aortic Aneurysms: 30-Day Outcomes of 105 Patients in a Single Centre

Endovascular aneurysm sealing (EVAS) has been proposed as a novel alternative to endovascular aneurysm repair (EVAR) in patients with infrarenal abdominal aortic aneurysms (AAA). The early clinical experience, technical refinements, and learning curve of EVAS in the treatment of AAA at a single institution are presented. One-hundred and five patients were treated with EVAS between March 2013 and November 2014. Prospective data were recorded on consecutive patients receiving EVAS. Data included demographics, preoperative aneurysm morphology, and 30-day outcomes, including rates of endoleak, limb occlusion, reintervention, and death. Postoperative imaging consisted of duplex ultrasound and computed tomographic angiography. The mean age of the cohort was 76±8 years and 12% were female. Adverse neck morphology was present in 72 (69%) patients, including aneurysm neck length <10mm (20%), neck diameter >32mm (18%), β-angulation >60° (21%), and conical aneurysm neck (51%). There was one death within 30 days. The incidence of Type 1 endoleak within 30 days was 4% (n=4); all were treated successfully with transcatheter embolisation. All four proximal endoleaks were associated with technical issues that resulted in procedure refinement, and all were in patients with adverse proximal aortic necks. The persistent Type 1 endoleak rate at 30 days was 0% and there were no Type 2 or Type 3 endoleaks. Angioplasty and adjunctive stenting were performed for postoperative limb stenosis in three patients (3%). EVAS appears to be associated with reasonable 30-day outcomes despite the necessity of procedural evolution in the early adoption of this technique. EVAS appears to be applicable to patients with challenging aortic morphology and endoleak rates should reduce with procedural experience. The utility of EVAS will be defined by the durability of the device in long-term follow-up, although the absence of Type 2 endoleaks is encouraging.

Thirty Years of Hyperthermic Isolated Limb Perfusion for Melanoma Demonstrates the Importance of Patient Selection

Introduction: Since its inception almost four decades ago, hyperthermic isolated limb perfusion (HILP) has been the most common and studied method for treating advanced melanoma confined to an extremity. This study evaluates the importance of patient selection as well as procedure refinement in the evolution of this treatment over a 30-year period at a major academic medical center. Methods: After approval from our institutional IRB, a retrospective chart review of 85 patients treated with HILP at a single tertiary academic medical center from 1980 to 2009 was performed evaluating patients on several parameters including perfusion time, chemotherapeutics utilized, patient demographics, and length of hospital stay.

Critical review of the efficacy and safety of cryotherapy of the prostate

Modern cryoablation of the prostate is a procedure that has evolved since the early 1990s into a safer and more successful treatment of adenocarcinoma of the prostate. The improvement of this technique has taken place secondary to advancement in engineering, procedure refinement, temperature monitoring, and a better understanding of physiologic events during the freezing process. Long-term results are available that demonstrate durable efficacy equivalent to other therapies in low-risk groups. In moderate to high risk groups, results point toward equal to superior results than other standard therapies. New ideas on potency preservation using vacuum erection devices have improved men's return to function over the course of the postoperative year. Early morbidity issues, such as fistula formation and incontinence, have become much less problematic, with results between 0% and 1% in some series. Cryoablation of the prostate now offers significantly improved outcomes with a parallel decrease in morbidity.

An algebraic treatment of procedure refinement to support mechanical verification

Abstract. We introduce a new algebraic model for program variables, suitable for reasoning about recursive procedures with parameters and local variables in a mechanical verification setting. We give a predicate transformer semantics to recursive procedures and prove refinement rules for introducing recursive procedure calls, procedure parameters, and local variables. We also prove, based on the refinement rules, Hoare total correctness rules for recursive procedures, and parameters. We introduce a special form of Hoare specification statement which alone is enough to fully specify a procedure. Moreover, we prove that this Hoare specification statement is equivalent to a refinement specification. We implemented this theory in the PVS theorem prover.

Discovery of a Novel Series of DHODH Inhibitors by a Docking Procedure and QSAR Refinement.

A novel series of DHODH inhibitors was developed based on a lead which was obtained by a docking procedure and a medicinal chemistry exploration. The activity of the initial lead was improved by a QSAR method to yield low nanomolar inhibitors.