Intercostal cryonerve block versus elastomeric infusion pump for postoperative analgesia following surgical stabilization of traumatic rib fractures.

OBJECTIVE: Patients with blunt thoracic trauma requiring surgical stabilization of rib fractures (SSRF) frequently experience severe pain. Further, a rising prevalence of opioid-tolerant patients sustain traumatic injuries. The optimal pain management adjunct for concurrent use with SSRF remains uncertain. This study compared outcomes in patients undergoing SSRF with concomitant cryonerve block (CryoNB) or ropivacaine 0.2% elastomeric infusion pump (EIP). METHODS: A single-center retrospective comparative analysis was performed at a level II trauma center. A query of our institution's trauma registry of consecutive patients undergoing SSRF from October 2017 to November 2020 with either intercostal CryoNB or ropivacaine 0.2% EIP was conducted. Opioid consumption in oral morphine equivalents (OME), patient-reported pain scores by numerical rating scale, and pulmonary function measured by incentive spirometry effort (mL) were collected at baseline and on postoperative days 1-3. Results were analyzed using a linear-mixed-effects model. Length of stay (LOS), complications, and hospital charges were assessed as secondary outcomes. RESULTS: Twenty-six patients meeting inclusion criteria were evaluated. Patient demographics, injury, and surgical variables were similar between groups. The estimated effect for patients treated with CryoNB (n = 14) compared to EIP (n = 12) demonstrated a 25% (estimated -1.37 OME, 95% CI, -2.411 to -0.335, p = 0.01) reduction in hospital opioid requirements, fewer discharge opioids (41.3 mg (37.5-45) versus 175 mg (150- 200), p = 0.03), 22% (estimated -1.506, 95% CI, -2.722 to -0.290, p = 0.02) reduction in pain scores, and shorter postoperative LOS (4 days (4-5) versus 6 days (5-9.5), p = 0.04). Pulmonary function (estimated -48.8 mL, 95% CI, -312.74 to 215.05, p = 0.71), total hospital costs (CryoNB: $90,224 ± 34,633; EIP: $131,498 ± 73,072, p = 0.07), and complications were no different between cohorts. CONCLUSION: The addition of intercostal CryoNB as an adjunct to multimodal pain management in trauma patients undergoing surgical fixation of rib fractures may be of benefit. Based on our early data, this technique appears to be promising in reducing opioid requirements and providing an extended duration of pain control without increased costs or complications.

Electrocatalytic alcohol oxidation by covalently immobilized ruthenium complex on carbon.

A dearth of discrete immobilized metal complexes exist that electrocatalytically oxidize methanol. Reported here is the covalent immobilization of a tris(2-pyridylmethyl)amine ruthenium complex [RuII(Cl)(DMSO)(ethynyl-TPA)]+ (ethynyl-TPA = (5-ethynyl-2-pyridylmethyl)bis(2-pyridylmethyl)amine) to a glassy carbon (GC) electrode through a CuI catalyzed azide-alkyne cycloaddition (click) reaction between the ethynyl-TPA ligand and an azide derivatized carbon surface forming [RuII(Cl)(DMSO)(GC-click-TPA)]+. Following water substitution for DMSO and proton coupled electron transfer, [RuIV(O)(Cl)(GC-click-TPA)]+ electrooxidizes alcohols, including methanol, efficiently relative to other immobilized metal complexes. A primary kinetic isotope effect suggests rate-limiting Cα-H bond cleavage of benzyl alcohol. Approximately 40% of the [RuII(Cl)(DMSO)(GC-click-TPA)]+ undergoes the DMSO for water exchange to form an active oxidant, consistent with the 40% distribution of the more labile Cl-cis-amine isomer before immobilization. Using the benchmark of benzyl alcohol electrocatalytic oxidation, [RuIV(O)(Cl)(GC-click-TPA)]+ operates at ca. 250 mV lower overpotential, with a 15% increase in faradaic efficiency, and at least an order of magnitude increase in average turnover frequency (0.7 s-1 TOFavg) compared to the previously best immobilized discrete ruthenium complexes.

Infection by dsRNA viruses is associated with enhanced sporulation efficiency in Saccharomyces cerevisiae.

Upon starvation diploid cells of the facultative sexual yeast Saccharomyces cerevisiae undergo sporulation, forming four metabolically quiescent and robust haploid spores encased in a degradable ascus. All endosymbionts, whether they provide net benefits or costs, utilize host resources; in yeast, this should induce an earlier onset of sporulation. Here, we tested whether the presence of endosymbiotic dsRNA viruses (M satellite and L-A helper) correspond with higher sporulation rate of their host, S. cerevisiae. We find that S. cerevisiae hosting both the M and L-A viruses (so-called "killer yeasts") have significantly higher sporulation efficiency than those without. We also found that the removal of the M virus did not reduce sporulation frequency, possibly because the L-A virus still utilizes host resources with and without the M virus. Our findings indicate that either virulent resource use by endosymbionts induces sporulation, or that viruses are spread more frequently to sporulating strains. Further exploration is required to distinguish cause from effect.

Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from CardiAMP heart failure roll-in cohort.

AIM: Heart failure following myocardial infarction (MI) is a potentially lethal problem with a staggering incidence. The CardiAMP Heart Failure trial represents the first attempt to personalize marrow-derived cell-based therapy to individuals with cell characteristics associated with beneficial responses in prior trials. Before the initiation of the randomized pivotal trial, an open-label "roll-in cohort" was completed to ensure the feasibility of the protocol's procedures. METHODS: Patients with chronic post-MI heart failure (NYHA class II-III) receiving stable, guideline-directed medical therapy with a left ventricular ejection fraction between 20 and 40% were eligible. Two weeks prior to treatment, a ~ 5 mL bone marrow aspiration was performed to examine "cell potency". On treatment day, a 60 mL bone marrow aspiration, bone marrow mononuclear cell (BM MNC) enrichment and transendocardial injection of 200 million BM MNC's was performed in a single, point of care encounter. Patients were then followed to assess clinical outcomes. RESULTS: The cell potency small volume bone marrow aspirate, the 60 mL bone marrow aspirate, and transendocardial injections were well tolerated in 10 patients enrolled. There were no serious adverse events related to bone marrow aspiration or cell delivery. Improvement in 6-min walk distance was observed at 6 months (+47.8 m, P = 0.01) and trended to improvement at 12 months (+46.4, P = 0.06). Similarly, trends to improved NYHA heart failure functional class, quality of life, left ventricular ejection fraction and recruitment of previously akinetic left ventricular wall segments were observed. CONCLUSION: All CardiAMP HF protocol procedures were feasible and well tolerated. Favorable functional, echo and quality of life trends suggest this approach may offer promise for patients with post MI heart failure. The randomized CardiAMP Heart Failure pivotal trial is underway to confirm the efficacy of this approach. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02438306.

The Impact of Supplemental Intraoperative Air Decontamination on the Outcome of Total Joint Arthroplasty: A Pilot Analysis.

BACKGROUND: During the early era of arthroplasty, the concept of ultraclean operating room (OR) was introduced based on the principle that the number of airborne particles in the OR directly influences incidence of device-related infections. The hypothesis of this pilot study was that use of an innovative UV-C air decontamination technology would lead to a reduction in the incidence of periprosthetic joint infection (PJI) following total joint arthroplasty. METHODS: A retrospective, observational, surveillance study was conducted with a consecutive series of patients who underwent total joint arthroplasty (n = 496) between January 2016 and August 2017. All perioperative and postoperative care protocols were identical for both groups, only study variable was that in 231 arthroplasty patients (OR B), an innovative supplemental UV-C air decontamination technology was used, whereas in the remaining 265 patients, arthroplasty was performed with standard turbulent HVAC (OR A). RESULTS: There was no significant difference between patient groups regarding age, body mass index, diabetes diagnosis, smoking status, length of surgery, or revision status. The rate of PJI was documented to be 1.9% in the turbulent air group, and no infections were documented in the cohorts operated under UV-C air decontamination, which was statistically significant (P < .044). CONCLUSION: While PJI is multifactorial in nature, the present retrospective pilot study suggests that use of an intraoperative supplemental air decontamination significantly reduced the overall risk of PJI. The findings of this study are encouraging and should be examined in a larger-scale, prospective, multicenter study.

The CardiAMP Heart Failure trial: A randomized controlled pivotal trial of high-dose autologous bone marrow mononuclear cells using the CardiAMP cell therapy system in patients with post-myocardial infarction heart failure: Trial rationale and study design.

BACKGROUND: Heart failure following myocardial infarction is a common, disabling, and deadly condition. Direct injection of autologous bone marrow mononuclear cells into the myocardium may result in improved functional recovery, relieve symptoms, and improve other cardiovascular outcomes. METHODS: CardiAMP-HF is a randomized, double-blind, sham-controlled, pivotal trial designed to investigate the safety and efficacy of autologous bone marrow mononuclear cells treatment for patients with medically refractory and symptomatic ischemic cardiomyopathy. The primary end point is change in 6-minute walk distance adjusted for major adverse cardiovascular events at 12 months following treatment. Particularly novel aspects of this trial include a cell potency assay to screen subjects who have bone marrow cell characteristics that suggest a favorable response to treatment, a point-of-care treatment method, a high target dose of 200 million cells, and an efficient transcatheter intramyocardial delivery method that is associated with high cell retention. CONCLUSIONS: This novel approach may lead to a new treatment for those with ischemic heart disease suffering from medically refractory heart failure.

William R. Shadish (1949-2016).

Presents an obituary for William R. Shadish who passed away on March 27, 2016, after a long, arduous battle with prostate cancer. Shadish was a distinguished professor for the University of California, Merced. He was elected president of three organizations: American Evaluation Association (1996), Society for Research Synthesis Methodology (2013), and Society for Multivariate Experimental Psychology (2014), and received numerous national awards. (PsycINFO Database Record

Next Generation Mesh Fixation Technology for Hernia Repair.

Laparoscopic ventral hernia repair (LVHR) remains a safe, reproducible, and popular method employed by surgeons to repair abdominal wall hernias. Patient selection, operative technique, instrumentation, and implant choice all remain surgeon dependent. Inherent in the technique is the option of using mesh. The decision of where to place the mesh and how to optimally fixate the mesh in the onlay, sublay, or intraabdominal positions also remain surgeon dependent and has been the subject of ongoing debates for the past two decades. In an ongoing effort to develop new methods for securing mesh to minimize pain without increased recurrence rates, novel mesh fasteners and mesh textiles have been developed. With increasing surgeon responsibility to improve value, surgeons should concentrate more on choosing the novel options that not only improve outcomes, but also reduce overall costs. This chapter reviews some of the emerging markets for these technologies.

The Ponseti Method in Low and Middle Income Countries: Challenges and Lessons Learned.

Diffusing a health care innovation like the Ponseti method in low and middle income countries requires more than the application of the traditional continuing medical education approach of providing lectures on the topic. Challenges include limited personnel, competing priorities, inadequate medical supplies, and limited resources. Experience has indicated that the best chances of success in establishing such a program include identifying and advising in-country "champions" to provide the leadership, energy, and direction to build the program.

Early effects of a 'train the trainer' approach to Ponseti method dissemination: a case study of Sri Lanka.

BACKGROUND: The Ponseti method has been established as the standard of care for the treatment of clubfoot in many developed countries for its utility, cost-effectiveness, and efficiency. However, despite its being described as the gold-standard for clubfoot treatment, there are still many areas of the world bereft in formal training in the Ponseti method. This is especially important since 80% of patients with clubfoot are born in developing countries where the need is the greater for experienced providers. This study analyzes a 'Train the Trainer' approach, specifically in the island nation of Sri Lanka, as a model for future dissemination of the Ponseti method throughout the developing world. METHODS: A rapid ethnographic study design that included interviews, focus groups, and direct observation of 162 patients and healthcare practitioners directly involved with clubfoot care was conducted. RESULTS: The average age of the patients at the time of the interview was 75.4 weeks old (SD = 149.2), traveled 45.2 kilometers (SD = 49.8) to receive their care, and received 4 casts (SD = 2.2) for correction of the deformity. Since the initiation of the 'Train the Trainer' educational program, clubfoot clinics reportedly grew from 6-7 patients per week to over 60 patients per week. The majority of this patient population growth was attributed to word of mouth. Major barriers to the method included casting materials, bracing materials, and a lack of a dedicated area of the clinic to conduct tenotomies under local anesthesia. Of note, cost was not cited as a major barrier. CONCLUSION: Early evaluation suggests great utility of the 'Train the Trainer' method - especially regarding an increased patient demand for treatment. However, further studies are necessary to understand the long-term utility of this training methodology.

Descriptive epidemiology of clubfoot in Peru: a clinic-based study.

congenital clubfoot is the most common birth defect of the musculoskeletal system and affects 1 in every 1000 live births each year.(1) Although there have been numerous studies of investigation, the etiology and pathogenesis of clubfoot remains unknown. To date, no epidemiological studies have been conducted in Peru to assess possible genetic and environmental risk factors associated with this deformity. The purpose of this study was to evaluate specific environmental and socioeconomic factors that may increase the risk of clubfoot. A descriptive clinic-based study was conducted using structured questionnaires given to biological mothers of clinically confirmed clubfoot patients (n=72) and biological mothers of children between ages 0-18 with no first or second degree family history of clubfoot as controls (n=103). Phenotypic data from clubfoot subjects were also collected. We found that males were twice as likely to have clubfoot as females, and half of all clubfoot patients had bilateral clubfoot. There was no significant difference in the rate of left vs. right clubfoot. Infant birth in the winter months correlated with an increased risk of clubfoot (p=0.01476). Maternal characteristics found to be significantly associated with increased risk of clubfoot were young maternal age at conception (p=0.04369) and low maternal education (p=0.003245). Young paternal age also had a correlation with increased risk of clubfoot in the child (p=0.0371). Both paternal smoking (p=0.00001) and the presence of any household smoking (p=0.00003) were strongly associated with an increased risk of clubfoot.

Barriers to the Ponseti method in Peru: a two-year follow-up.

Idiopathic clubfoot affects approximately 100,000 children each year and is one of the leading causes of disability worldwide. The Ponseti method is an inexpensive, non-surgical treatment that, when executed correctly, is more than 95% effective; however, in Peru, a developing country where a low-cost alternative is greatly needed, physicians report up to 30% of patients do not complete treatment. This study involved semi-structured interviews with 25 physicians who practice the Ponseti Method in Peru to discuss obstacles for the method in their country. The most frequent obstacles to the Ponseti method in Peru reported by physicians included lack of physicians trained in the Ponseti method in the country, patient transportation and distance to treatment centers, and lack of parental knowledge of the Ponseti method. These data suggest the need to train more physicians in Peru, particularly in the provinces. Increasing access to trained physicians in provincial areas may reduce the financial and travel burden of parents to help increase compliance with treatment.

Exercise testing in asymptomatic patients after revascularization: are outcomes altered?

BACKGROUND: Although exercise echocardiography (ExE) of asymptomatic patients early (2 years after percutaneous coronary intervention [PCI] or 5 years after coronary bypass graft surgery [CABG]) after revascularization is considered inappropriate, the appropriateness of later testing is indeterminate. Treatment responses to positive test results in either setting have uncertain outcome implications. We sought to identify whether predictors of increased risk by ExE could lead to interventions that change outcome in asymptomatic patients with previous coronary revascularization. METHODS: Exercise echocardiography was performed in 2105 asymptomatic patients (mean [SD] age, 64 [10] years; 310 [15%] were women; 845 [40%] had a history of myocardial infarction; 1143 [54%] had undergone PCI and 962 [46%] had undergone CABG 4.1 [4.7] years prior to the ExE). Ischemia was identified as a new or worsening wall motion abnormality. Patients were followed for a mean (SD) period of 5.7 (3.0) years for cardiac mortality. The association of ischemia during ExE with survival was assessed using Cox proportional hazard models, and an interaction with revascularization was sought. RESULTS: Of 262 patients with ischemia (13%), only 88 (34%) underwent subsequent revascularization. Mortality (97 patients [4.6%]) was associated with ischemia (hazard ratio, 2.10; 95% CI, 1.05-4.19; P=.04) in groups tested both early (P=.03) and late (≥2 years after PCI or ≥ 5 years after CABG) (P=.001). However, the main predictors of outcome were clinical and stress testing findings rather than echocardiographic features. Subgroup analysis showed that asymptomatic patients without diabetes mellitus, with normal ejection fraction (≥50%), and normal exercise capacity (>6 METs [metabolic equivalent for task]) were unlikely to have a positive test result or events. Even high-risk patients did not seem to benefit from repeated revascularization. CONCLUSIONS: Asymptomatic patients who undergo ExE after coronary revascularization may be identified as being at high risk but do not seem to have more favorable outcomes with repeated revascularization. From a health economic standpoint, appropriateness of such testing must be carefully reviewed.

Evaluation of the progress and challenges facing the Ponseti method program in Vietnam.

INTRODUCTION: In 2003, an ICRC-SFD Ponseti program was introduced in southern Vietnam. Additional programs were introduced by the Prosthetics Outreach Foundation and independently by physicians trained at our center. The purpose of this study was to evaluate the impact, progress and challenges facing Ponseti practitioners and patients' family members in Vietnam. In addition, web-conferencing (Ponseti Virtual Forum) for continued medical education in the method was also assessed. METHODS: Multiple questionnaires were developed to conduct face-to-face practitioner interviews, focus group interviews, and parental interviews. Observation was done at multiple site clinics to determine or confirm additional challenges faced by practitioners. Web conferencing was introduced to sites in Ho Chi Minh City and Da Nang City. RESULTS: The number of clubfoot patients treated with the Ponseti method has increased over time with approximately 1,252 infants treated between 2003 and 2010. Specific challenges were identified relating to communication, networking, distance and transportation, and finances for both practitioners and parents. The PVF was not only found to facilitate rapid, relevant dissemination of medical knowledge--thus increasing physician and patient satisfaction--but it may also be found to act as an interface in which medical culture, insight, and compassion are shared benefiting all virtual forum participants. CONCLUSION: The identified progress and challenges mirrored that of similar studies done in other countries with several factors affecting progress. Focusing on improving communication channels and networking while working with the ministry of health may improve the facilitation of the Ponseti method in Vietnam. Further implementation and evaluation of the PVF may act as a guide for current and future programs in Vietnam or other countries.

Qualitative assessment of the challenges to the treatment of idiopathic clubfoot by the Ponseti method in urban India.

The Ponseti method of clubfoot treatment has been shown to be a very safe, effective and minimally invasive technique when performed in medical centers in Europe and North America. However, only a limited number of studies have helped identify the challenges for effective treatment with the Ponseti method in India. In this study a qualitative approach was used through distribution of questionnaires, personal interviews and focus groups with orthopedic surgeons (in urban centers) and parents of patients with clubfoot. The following factors were evaluated: (i) physician education, (ii) alternative methods of treatment/modification of the Ponseti technique, (iii) compliance by parents, (iv) treatment in underserved areas, (v) culture, (vi) community knowledge of clubfoot, and (vii) the health care system in India. The results showed that all of the factors evaluated hindered outcomes for patients; however, parent's compliance with bracing, lack of proper rural clubfoot treatment clinics, poverty and physician education were the most prominent challenges. The results of this study can be used to implement specific strategies to improve the diffusion and implementation of the Ponseti method for treating clubfoot throughout India.

The Ponseti method in Latin America: initial impact and barriers to its diffusion and implementation.

The Ponseti method for correcting clubfoot is a safe, effective, and minimally invasive treatment that has recently been implemented in Latin America. This study evaluates the initial impact and unique barriers to the diffusion of the Ponseti method throughout this region. Structured interviews were conducted with 30 physicians practicing the Ponseti method in three socioeconomically diverse countries: Chile, Peru and Guatemala. Since learning the Ponseti method, these physicians have treated approximately 1,740 clubfoot patients, with an estimated 1,705 (98%) patients treated using the Ponseti method, and 35 (2%) patients treated using surgical techniques. The barriers were classified into the following themes: physician education, health care system of the country, culture and beliefs of patients, physical distance and transport, financial barriers for patients, and parental compliance with the method. The results yielded several common barriers throughout Latin America including lack of physician education, physical distance to the treatment centers, and financial barriers for patients. Information from this study can be used to inform, and to implement and evaluate specific strategies to improve the diffusion of the Ponseti method for treating clubfoot throughout Latin America.

Simultaneous determination of sulforaphane and its major metabolites from biological matrices with liquid chromatography-tandem mass spectroscopy.

A simple, sensitive and specific LC-MS/MS method for the simultaneous determination of sulforaphane (SFN) and its major metabolites, the glutathione (SFN-GSH) and N-acetyl cysteine conjugates (SFN-NAC) from biological matrices was developed and validated. The assay procedure involved solid-phase extratcion of all three analytes from rat intestinal perfusate using C2 extraction cartridges, whereas from rat plasma, metabolites were extracted by solid-phase extraction and SFN was extracted by liquid-liquid extraction with ethyl acetate. Chromatographic separation of SFN, SFN-GSH and SFN-NAC was achieved on a C8 reverse phase column with a mobile phase gradient (Mobile Phase A: 10mM ammonium acetate buffer, pH: 4.5 and Mobile Phase B: acetonitrile with 0.1% formic acid) at a flow rate of 0.3 mL/min. The Finnigan LCQ LC-MS/MS was operated under the selective reaction monitoring mode using the electrospray ionization technique in positive mode. The nominal retention times for SFN-GSH, SFN-NAC and SFN were 8.4, 11.0, and 28.2 min,, respectively. The method was linear for SFN and its metabolites with correlation coefficients >0.998 for all analytes. The limit of quantification was 0.01-0.1 microm depending on analyte and matrix, whereas the mean recoveries from spiked plasma and perfusate samples were approximately 90%. The method was further validated according to U.S. Food and Drug Administration guidance in terms of accuracy and precision. Stability of compounds was established in a battery of stability studies, i.e., bench top, auto-sampler and long-term storage stability as well as freeze/thaw cycles. The utility of the assay was confirmed by the analysis of intestinal perfusate and plasma samples from single-pass intestinal perfusion studies with mesenteric vein cannulation in rats.

Surface cementation of stemmed tibial components in primary total knee arthroplasty: minimum 5-year follow-up.

Cement remains the "gold standard" for fixation in total knee arthroplasty. Between 1991 and 1998, 128 consecutive knees in 109 patients underwent primary cemented total knee arthroplasty using a surface cementation technique. The average follow-up was 95 (range, 63-155) months. Preoperative range of motion (ROM) averaged 5 degrees to 111 degrees which improved to 1 degrees to 116 degrees postoperatively. Modified Hospital for special surgery score (HSS) scores improved from 61 (range, 47-76) to 97 (range, 81-100) and the corresponding Knee Society Scores from 122 (range, 94-152) to 195 (range, 162-200). No osteolytic lesions were found; however, 3 tibias had radiolucent lines which were asymptomatic, nonprogressive, and not associated with implant failure. The average depth of penetration of cement was 2.7 mm. One knee (1%) required revision surgery for femoral loosening, and 1 required revision of the polyethylene liner. The present cementation technique provides excellent durable results at midterm follow-up.