Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

RATIONALE: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction which can impact other solid organs. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied. OBJECTIVES: We aimed to identify underlying patterns of liver injury in a cohort of PAH and CTEPH patients enrolled in 15 randomized clinical trials conducted between 1998 and 2014. METHODS: We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity. MEASUREMENTS AND MAIN RESULTS: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin data. Using k-means clustering, we identified phenotypes with no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns. Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and the highest risk of mortality. The cholestatic injury group also experienced the greatest placebo-corrected treatment effect on six-minute walk distance. Randomization to the experimental arm transitioned patients to a healthier liver status. CONCLUSIONS: Liver injury was associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment had beneficial effects on liver health compared to placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

Laparoscopy and thoracoscopy in small animal surgery: A 2020 survey of small animal diplomate and resident veterinary surgeons.

OBJECTIVE: To document the utilization and training of laparoscopic and thoracoscopic minimally invasive surgery (MIS) techniques within the American, European, Australian and New Zealand Colleges of Small Animal Veterinary Surgeons (ACVS, ECVS, and ANZCVS) in 2020. STUDY DESIGN: Observational study. SAMPLE POPULATION: Diplomates and residents of the ACVS, ECVS, and FANZCVS. METHODS: An electronic survey was sent using veterinary list servers. Questions were organized into categories evaluating (1) the demographics of the study population and the caseload, (2) comfort level with specific procedures, (3) motivating factors and limitations, and (4) surgical training and the role of the governing bodies. RESULTS: Respondents included 111 practicing surgeons and 28 residents. Respondents' soft-tissue MIS caseloads had increased since they first started performing MIS; however, most respondents were only comfortable performing basic laparoscopy. Over half of the respondents agreed on the patient benefits and high standard of care provided by MIS. Perceived adequate soft-tissue training in MIS during residency was strongly associated with perceived proficiency at the time of survey response. Most respondents agreed that the specialty colleges should take a more active role in developing standards for soft-tissue MIS, with residents agreeing that a required standardized course would be beneficial. CONCLUSION: Soft-tissue MIS is widely performed by diplomates and residents. Perceived adequate soft-tissue MIS training was strongly associated with perceived proficiency. CLINICAL SIGNIFICANCE: There is substantial underutilization of advanced MIS techniques in veterinary specialty surgical practice, which might be improved by a stronger focus on MIS training during residency.

Complications and outcomes of thoracoscopic-assisted lung lobectomy in dogs.

OBJECTIVE: To describe complications and outcomes of dogs undergoing thoracoscopic-assisted (TA) lung lobectomy. STUDY DESIGN: Multi-institutional, retrospective study. ANIMALS: Client-owned dogs (n = 30). METHODS: Medical records of dogs that underwent TA lung lobectomy were reviewed. Signalment, bodyweight, clinical signs, imaging findings, surgical variables, complications, and short-term/long-term outcome were assessed. Thoracoscopic-assisted lung lobectomy was performed with a mini-thoracotomy. RESULTS: Twelve intraoperative complications were recorded in 11 dogs, 6 requiring conversion to open thoracotomy. Reasons for conversion were reported in 5/6 dogs and included adhesions (2), difficultly manipulating the lesion through the mini-thoracotomy (2), and acute oxygen desaturation (1). One lung ventilation was successful in 4 of the 7 dogs in which this was attempted. A linear stapling device (DST series Medtronic, Minneapolis, Minnesota) was used for lung lobe ligation in 14 dogs. Twenty-three dogs underwent surgery for a neoplastic lesion, with 19 of these being carcinoma. The median lesion size was 4.3 cm (range 1-10 cm); margins were clean, except in 1 dog. Complications were documented in 8 dogs prior to discharge, 5 of these being classified as mild. Twenty-nine dogs were discharged at a median of 47 h postoperatively (range 24-120 h). Death was reported in 9 dogs, with a median survival time of 168 days (range 70-868 days). CONCLUSION: Thoracoscopic-assisted lung lobectomy was achieved with few major complications in the population reported here. Dogs were able to be discharged from hospital quickly, with most surviving beyond the follow-up period. CLINICAL SIGNIFICANCE: Thoracoscopic-assisted lung lobectomy may be considered to facilitate the excision of larger pulmonary lesions or to treat smaller dogs, in which a thoracoscopic excision may be technically more challenging.

Enrichment Benefits of Risk Algorithms for Pulmonary Arterial Hypertension Clinical Trials.

Rationale: Event-driven primary endpoints are increasingly used in pulmonary arterial hypertension clinical trials, substantially increasing required sample sizes and trial lengths. The U.S. Food and Drug Administration advocates the use of prognostic enrichment of clinical trials by preselecting a patient population with increased likelihood of experiencing the trial's primary endpoint.Objectives: This study compares validated clinical scales of risk (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, the French score, and Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management [REVEAL] 2.0) to identify patients who are likely to experience a clinical worsening event for trial enrichment.Methods: Baseline data from three pulmonary arterial hypertension clinical trials (AMBITION [a Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects with Pulmonary Arterial Hypertension], SERAPHIN [Study of Macitentan on Morbidity and Mortality in Patients with Symptomatic Pulmonary Arterial Hypertension], and GRIPHON [Selexipag in Pulmonary Arterial Hypertension]) were pooled and standardized. Receiver operating curves were used to measure each algorithm's performance in predicting clinical worsening within the pooled placebo cohort. Power simulations were conducted to determine sample size and treatment time reductions for multiple enrichment strategies. A cost analysis was performed to illustrate potential financial savings by applying enrichment to GRIPHON.Measurements and Main Results: All risk algorithms were compared using area under the receiver operating curve and substantially outperformed prediction per New York Heart Association Functional Class. The REVEAL 2.0's risk grouping provided the greatest time and sample size savings in AMBITION and GRIPHON for all enrichment strategies but lacked appropriate inputs (i.e., N-terminal-proB-type natriuretic peptide) to perform as well in SERAPHIN. Cost analysis applied to GRIPHON demonstrated the greatest financial benefit by enrolling patients with a REVEAL score ≥8.Conclusions: This preliminary study demonstrates the feasibility of risk algorithms for pulmonary arterial hypertension trial enrichment and a need for further investigation.

Understanding the role of religion in shaping cross-national and domestic attitudes and interest in abortion, homosexuality, and pornography using traditional and Google search data.

Over the last 20 years, internet usage has increased substantially, providing an inexpensive source of data that may be less prone to bias and could provide a greater number of meso and macro units. However, validating big data and their usefulness has been challenging. This study uses established sources to validate Google Trends' search interest in the "Bible" across US Designated Market Areas and "Ramadan" across nations, establishing a potential new source of religion data. We then use these measures to show that people from religiously conservative US areas and countries are more likely to disapprove of homosexuality, abortion and pornography. Conversely, Americans from conservative religious areas are also more likely to search for these topics; and cross-national interest in Islam is associated with increased interest in pornography. Our study offers insight into Google Trends' potential for social science research and a roadmap on how to use these data.

Risk stratification in pulmonary arterial hypertension using Bayesian analysis.

BACKGROUND: Current risk stratification tools in pulmonary arterial hypertension (PAH) are limited in their discriminatory abilities, partly due to the assumption that prognostic clinical variables have an independent and linear relationship to clinical outcomes. We sought to demonstrate the utility of Bayesian network-based machine learning in enhancing the predictive ability of an existing state-of-the-art risk stratification tool, REVEAL 2.0. METHODS: We derived a tree-augmented naïve Bayes model (titled PHORA) to predict 1-year survival in PAH patients included in the REVEAL registry, using the same variables and cut-points found in REVEAL 2.0. PHORA models were validated internally (within the REVEAL registry) and externally (in the COMPERA and PHSANZ registries). Patients were classified as low-, intermediate- and high-risk (<5%, 5-20% and >10% 12-month mortality, respectively) based on the 2015 European Society of Cardiology/European Respiratory Society guidelines. RESULTS: PHORA had an area under the curve (AUC) of 0.80 for predicting 1-year survival, which was an improvement over REVEAL 2.0 (AUC 0.76). When validated in the COMPERA and PHSANZ registries, PHORA demonstrated an AUC of 0.74 and 0.80, respectively. 1-year survival rates predicted by PHORA were greater for patients with lower risk scores and poorer for those with higher risk scores (p<0.001), with excellent separation between low-, intermediate- and high-risk groups in all three registries. CONCLUSION: Our Bayesian network-derived risk prediction model, PHORA, demonstrated an improvement in discrimination over existing models. This is reflective of the ability of Bayesian network-based models to account for the interrelationships between clinical variables on outcome, and tolerance to missing data elements when calculating predictions.

Optimization of surgical approach for thoracoscopic-assisted pulmonary surgery in dogs.

OBJECTIVE: To determine the optimal intercostal space (ICS) to perform thoracoscopic-assisted lung lobectomy. STUDY DESIGN: Cadaveric study. ANIMALS: Six mature, medium-sized canine cadavers. METHODS: Cadavers were placed in right or left lateral recumbency. A 15-mm thoracoscopic cannula was inserted in the middle third of the 9th or 10th ICS. A wound retraction device was placed into a 7-cm minithoracotomy incision created in the middle third of the 4th-7th ICS on the left side and the 4th-8th ICS on the right side. The pulmonary ligaments were sectioned by using a combined intracorporeal and extracorporeal technique. Each lung lobe was sequentially withdrawn from the wound retraction device at the respective ICS and side. A thoracoabdominal stapler was positioned to simulate lung lobectomy, and the distance from the stapler anvil to the hilus was measured. RESULTS: Simulated thoracoscopic-assisted lung lobectomy performed at left or right ICS 4 and 5, compared with other ICS evaluated, resulted in a significantly shorter median distance from the stapler anvil to the pulmonary hilus of the left cranial and caudal lung lobes and right cranial and middle lung lobes, respectively (all P < .05). Lobectomy at right ICS 5 or 6 resulted in a significantly shorter median distance from the stapler anvil to the pulmonary hilus of the right caudal and accessory lung lobes, respectively (both P < .05). CONCLUSION: These data may inform minithoracotomy positioning to optimize tumor margin excision during thoracoscopic-assisted lung lobectomy for treatment of pulmonary neoplasia in dogs. CLINICAL SIGNIFICANCE: Complete lung lobectomy is possible by using the described thoracoscopic-assisted technique in normal, cadaveric lungs.

Healing of canine skin incisions made with monopolar electrosurgery versus scalpel blade.

OBJECTIVE: To determine the influence of monopolar electrosurgery in cutting mode set at 10, 20, or 30 W on surgery time, hemostasis, and healing of cutaneous wounds compared to scalpel incisions. STUDY DESIGN: Randomized blinded control trial. ANIMALS: Dogs (n = 15). METHODS: Four skin incisions were created on either side of the dorsal midline with a scalpel, or monopolar electrosurgery at 10, 20, and 30 W. Surgical time and incisional bleeding were measured. Each incision was assessed daily for edema, erythema and discharge, and complications. Healing was evaluated via histology at 7 days. Results were analyzed for significance at P ≤ .05. RESULTS: Surgical time and hemostasis were improved in all electrosurgery groups. Erythema was reduced in all electrosurgical incisions for days 1-4, but was greater in wounds created via electrosurgery at 20 W than those made with a scalpel blade by day 7. No difference was noted in the degree of edema or presence of wound discharge. All histologic variables of tissue healing were lower in electrosurgical incisions than scalpel incisions (P < .001). Ten incisional complications occurred, all associated with electrosurgery. CONCLUSIONS: The use of monopolar electrosurgery at 10, 20, and 30 W in a cutting waveform improved hemostasis and surgical time when incising canine skin, but delayed healing and increased complications within the first 7 days compared to scalpel incisions.

Video-assisted thoracic surgery for the management of pyothorax in dogs: 14 cases.

OBJECTIVE: To report the perioperative findings and outcome of dogs undergoing video-assisted thoracic surgery (VATS) for the management of pyothorax. DESIGN: Multi-institutional, retrospective study. ANIMALS: Client-owned dogs (n = 14). METHODS: Medical records of dogs with pyothorax managed via VATS were reviewed for signalment, history, clinical signs, clinicopathological findings, diagnostic imaging results, surgical variables, bacterial culture and sensitivity results, post-operative management and outcome. VATS was performed after placing a paraxyphoid endoscopic portal and 2-3 intercostal instrument portals. VATS exploration was followed by one or more of the following: mediastinal debridement, tissue sampling, pleural lavage, and placement of a thoracostomy tube. RESULTS: Two dogs (14%) required conversion from VATS to an open thoracotomy to completely resect proliferative mediastinal tissue. These dogs had severe pleural effusion on preoperative thoracic radiographs and one had severely thickened contrast-enhancing mediastinum on preoperative computed tomography (CT). The cause of pyothorax was identified as a penetrating gastric foreign body (n = 2), migrating plant material (n = 2), and idiopathic (n = 10). The median follow-up time was 143 days (range, 14-2402 days). All dogs were discharged from the hospital and their clinical signs resolved. One patient had recurrence of a pyothorax requiring revision surgery 17 months postoperatively. CONCLUSION: VATS allows minimally invasive treatment of uncomplicated canine pyothorax. Preoperative thoracic CT may help identify candidates for VATS among dogs with pyothorax.

Perioperative Complications and Outcome of Laparoscopic Cholecystectomy in 20 Dogs.

OBJECTIVE: To report the complications and outcome of dogs undergoing laparoscopic cholecystectomy for uncomplicated gall bladder disease. STUDY DESIGN: Multi-institutional case series. ANIMALS: Client-owned dogs (n=20). METHODS: Medical records of dogs that underwent laparoscopic cholecystectomy were reviewed and signalment, history, clinical and ultrasound examination findings, surgical variables, and complications were collated. Laparoscopic cholecystectomy was performed using a multiport approach. Data were compared between dogs with successful laparoscopic cholecystectomy and dogs requiring conversion to open cholecystectomy. RESULTS: Six dogs (30%) required conversion from laparoscopic to open cholecystectomy due to inability to ligate the cystic duct (3), evidence of gall bladder rupture (1), leakage from the cystic duct during dissection (1), and cardiac arrest (1). Cystic duct dissection was performed in 19 dogs using an articulating dissector (10), right angle forceps (7), and unrecorded (2). The cystic duct was ligated in 15 dogs using surgical clips (5), suture (6), or a combination (4). All dogs were discharged from the hospital and had resolution of clinical signs, although 1 dog developed pancreatitis and 1 dog required revision surgery for bile peritonitis. There was no significant difference in preoperative blood analysis results, surgical technique, or duration of hospitalization between dogs undergoing laparoscopic cholecystectomy and cases converted to open cholecystectomy. CONCLUSION: Laparoscopic cholecystectomy can be performed successfully for uncomplicated gall bladder disease in dogs after careful case selection. The surgeon considering laparoscopic cholecystectomy should be familiar with a variety of methods for cystic duct dissection and ligation to avoid difficulties during the procedure.

Novel Liver Injury Phenotypes and Outcomes in Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are disorders of the pulmonary vasculature that cause right ventricular dysfunction. Systemic consequences of right ventricular dysfunction include damage to other solid organs, such as the liver. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied. Methods: We aimed to identify underlying patterns of liver injury in a cohort of PAH and CTEPH patients enrolled in 15 randomized clinical trials conducted between 1998 and 2012. We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity. Results: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with complete liver laboratory panels (serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin). Using k-means clustering paired with factor analysis, we identified four unique liver phenotypes (no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns). Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and highest chance of worsening World Health Organization functional class. Randomization to the experimental arm was associated with a transition to healthier liver clusters compared to randomization to the control arm. The cholestatic injury group experienced the greatest placebo-corrected treatment benefit in terms of six-minute walk distance. Conclusions: Liver injury patterns were associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment of pulmonary hypertension in these clinical trials had beneficial effects on liver health compared to placebo. The independent role of liver disease (often subclinical) in determining outcomes warrants prospective studies of the clinical utility of liver phenotyping for PAH prognosis and contribution to clinical disease.

Right ventricular myocardial energetic model for evaluating right heart function in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) increases right ventricular (RV) workload and decreases myocardial oxygen reserve, eventually leading to poor cardiac output. This study created and assessed a novel model of RV work output based on RV hemodynamics and oxygen supply, allowing new insight into causal mechanisms of RV dysfunction. METHODS: The RV function model was built upon an earlier, left ventricular model and further adjusted for more accurate clinical use. The model assumes that RV total power output (1) is the sum of isovolumic and stroke power and (2) is linearly related to its right coronary artery oxygen supply. Thus, when right coronary artery flow is limited or isovolumic power is elevated, less energy is available for producing cardiac output. The original and adjusted models were validated via data from patients with idiopathic PAH (n = 14) and large animals (n = 6) that underwent acute pulmonary banding with or without hypoxia. RESULTS: Both models demonstrated strong, significant correlations between RV oxygen consumption rate and RV total power output for PAH patients (original model, R2  = 0.66; adjusted model, R2  = 0.78) and sheep (original, R2  = 0.85; adjusted, R2  = 0.86). Furthermore, the models demonstrate a significant inverse relationship between required oxygen consumption and RV efficiency (stroke power/total power) (p < 0.001). Lastly, higher NYHA class was indicative of lower RV efficiency and higher oxygen consumption (p = 0.013). CONCLUSION: Right ventricular total power output can be accurately estimated directly from pulmonary hemodynamics and right coronary perfusion during PAH. This model highlights the increased vulnerability of PAH patients with compromised right coronary flow coupled with high afterload.

Complications and outcomes associated with laparoscopic-assisted splenectomy in dogs.

OBJECTIVE: To report the perioperative characteristics and outcomes of dogs undergoing laparoscopic-assisted splenectomy (LAS). ANIMALS: 136 client-owned dogs. PROCEDURES: Multicentric retrospective study. Medical records of dogs undergoing LAS for treatment of naturally occurring splenic disease from January 1, 2014, to July 31, 2020, were reviewed. History, signalment, physical examination and preoperative diagnostic test results, procedural information, complications, duration of hospitalization, histopathologic diagnosis, and perioperative outcomes were recorded. Perioperative complications were defined using the Veterinary Cooperative Oncology Group - Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) guidelines. RESULTS: LAS was performed for treatment of a splenic mass (124/136 [91%]), immune-mediated disease (7/136 [5%]), splenomegaly (4/136 [3%]), or immune-mediated disease in conjunction with a splenic mass (1/136 [1%]). Median splenic mass size was 1.3 cm3/kg body weight. Conversion to open laparotomy occurred in 5.9% (8/136) of dogs. Complications occurred in 78 dogs, with all being grade 2 or lower. Median surgical time was 47 minutes, and median postoperative hospital stay was 28 hours. All but 1 dog survived to discharge, the exception being postoperative death due to a suspected portal vein thrombus. CLINICAL RELEVANCE: In the dogs of this report, LAS was associated with low rates of major complications, morbidity, and mortality when performed for a variety of splenic pathologies. Minimally invasive surgeons can consider the LAS technique to perform total splenectomy in dogs without hemoabdomen and with spleens with modest-sized splenic masses up to 55.2 cm3/kg, with minimal rates of complications, morbidity, and mortality.

Diagnostic and public health investigation of Mycobacterium tuberculosis infection in a dog in Ontario, Canada.

A 4-y-old, female mixed-breed dog was presented to the Ontario Veterinary College for further evaluation of multiple pulmonary and hepatic masses, intrathoracic lymphadenitis, and recent development of a pyogranulomatous pleural effusion. Along with other comprehensive tests, a thoracic lymph node biopsy was performed, and Mycobacterium tuberculosis complex infection was confirmed by real-time PCR. The dog's condition declined post-operatively, and euthanasia was elected. Postmortem examination confirmed severe granulomatous pneumonia, hepatitis, intrathoracic and intraabdominal lymphadenitis, omentitis, and nephritis. Line-probe assays performed on samples collected postmortem confirmed the species as M. tuberculosis. 24-loci MIRU-VNTR genotyping, spoligotyping, and whole-genome sequencing revealed relations to known human isolates, but no epidemiologic link to these cases was investigated. Given the concern for potential human exposure during this animal's disease course, a public health investigation was initiated; 45 individuals were tested for M. tuberculosis exposure, and no subsequent human infections related to this animal were identified. Our case highlights the need for more readily available, minimally invasive testing for the diagnosis of canine mycobacteriosis, and highlights the ability of canid species to act as potential contributors to the epidemiology of M. tuberculosis infections.

Development and Validation of an Abridged Version of the REVEAL 2.0 Risk Score Calculator, REVEAL Lite 2, for Use in Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Achievement of low-risk status is a treatment goal in pulmonary arterial hypertension (PAH). Risk assessment often is performed using multiparameter tools, such as the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator. Risk calculators that assess fewer variables without compromising validity may expedite risk assessment in the routine clinic setting. We describe the development and validation of REVEAL Lite 2, an abridged version of REVEAL 2.0. RESEARCH QUESTION: Can a simplified version of the REVEAL 2.0 risk assessment calculator for patients with PAH be developed and validated? STUDY DESIGN AND METHODS: REVEAL Lite 2 includes six noninvasive variables-functional class (FC), vital signs (systolic BP [SBP] and heart rate), 6-min walk distance (6MWD), brain natriuretic peptide (BNP)/N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and renal insufficiency (by estimated glomerular filtration rate [eGFR])-and was validated in a series of analyses (Kaplan-Meier, concordance index, Cox proportional hazard model, and multivariate analysis). RESULTS: REVEAL Lite 2 approximates REVEAL 2.0 at discriminating low, intermediate, and high risk for 1-year mortality in patients in the REVEAL registry. The model indicated that the most highly predictive REVEAL Lite 2 parameter was BNP/NT-proBNP, followed by 6MWD and FC. Even if multiple, less predictive variables (heart rate, SBP, eGFR) were missing, REVEAL Lite 2 still discriminated among risk groups. INTERPRETATION: REVEAL Lite 2, an abridged version of REVEAL 2.0, provides a simplified method of risk assessment that can be implemented routinely in daily clinical practice. REVEAL Lite 2 is a robust tool that provides discrimination among patients at low, intermediate, and high risk of 1-year mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

Therapeutic Ultrasound Triggered Silk Fibroin Scaffold Degradation.

A patient's capacity for tissue regeneration varies based on age, nutritional status, disease state, lifestyle, and gender. Because regeneration cannot be predicted prior to biomaterial implantation, there is a need for responsive biomaterials with adaptive, personalized degradation profiles to improve regenerative outcomes. This study reports a new approach to use therapeutic ultrasound as a means of altering the degradation profile of silk fibroin biomaterials noninvasively postimplantation. By evaluating changes in weight, porosity, surface morphology, compressive modulus, and chemical structure, it is concluded that therapeutic ultrasound can trigger enhanced degradation of silk fibroin scaffolds noninvasively. By removing microbubbles on the scaffold surface, it is found that acoustic cavitation is the mechanism responsible for changing the degradation profile. This method is proved to be safe for human cells with no negative effects on cell viability or metabolism. Sonication through human skin also effectively triggers scaffold degradation, increasing the clinical relevance of these results. These findings suggest that silk is an ultrasound-responsive biomaterial, where the degradation profile can be adjusted noninvasively to improve regenerative outcomes.

Pneumoperitoneum in Veterinary Laparoscopy: A Review.

Objective: To review the effects of carbon dioxide pneumoperitoneum during laparoscopy, evaluate alternative techniques to establishing a working space and compare this to current recommendations in veterinary surgery. Study Design: Literature review. Sample Population: 92 peer-reviewed articles. Methods: An electronic database search identified human and veterinary literature on the effects of pneumoperitoneum (carbon dioxide insufflation for laparoscopy) and alternatives with a focus on adaptation to the veterinary field. Results: Laparoscopy is the preferred surgical approach for many human and several veterinary procedures due to the lower morbidity associated with minimally invasive surgery, compared to laparotomy. The establishment of a pneumoperitoneum with a gas most commonly facilitates a working space. Carbon dioxide is the preferred gas for insufflation as it is inert, inexpensive, noncombustible, colorless, excreted by the lungs and highly soluble in water. Detrimental side effects such as acidosis, hypercapnia, reduction in cardiac output, decreased pulmonary compliance, hypothermia and post-operative pain have been associated with a pneumoperitoneum established with CO2 insufflation. As such alternatives have been suggested such as helium, nitrous oxide, warmed and humidified carbon dioxide and gasless laparoscopy. None of these alternatives have found a consistent benefit over standard carbon dioxide insufflation. Conclusions: The physiologic alterations seen with CO2 insufflation at the current recommended intra-abdominal pressures are mild and of transient duration. Clinical Significance: The current recommendations in veterinary laparoscopy for a pneumoperitoneum using carbon dioxide appear to be safe and effective.

Home and Community-Based Physical Therapist Management of Adults With Post-Intensive Care Syndrome.

More than 4 million adults survive a stay in the intensive care unit each year, with many experiencing new or worsening physical disability, mental health problems, and/or cognitive impairments, known as post-intensive care syndrome (PICS). Given the prevalence and magnitude of physical impairments after critical illness, many survivors, including those recovering from COVID-19, could benefit from physical therapist services after hospital discharge. However, due to the relatively recent recognition and characterization of PICS, there may be limited awareness and understanding of PICS among physical therapists practicing in home health care and community-based settings. This lack of awareness may lead to inappropriate and/or inadequate rehabilitation service provision. While this perspective article provides information relevant to all physical therapists, it is aimed toward those providing rehabilitation services outside of the acute and postacute inpatient settings. This article reports the prevalence and clinical presentation of PICS and provides recommendations for physical examination and outcomes measures, plan of care, and intervention strategies. The importance of providing patient and family education, coordinating community resources including referring to other health care team members, and community-based rehabilitation service options is emphasized. Finally, this perspective article discusses current challenges for optimizing outcomes for people with PICS and suggests future directions for research and practice.

Determination of optimal location for thoracoscopic-assisted pulmonary surgery for lung lobectomy in cats.

OBJECTIVE: To determine the optimal intercostal space (ICS) for thoracoscopic-assisted pulmonary surgery for lung lobectomy in cats. SAMPLE: 8 cat cadavers. PROCEDURES: Cadavers were placed in lateral recumbency. A 5-cm minithoracotomy incision was made in the middle third of ICS 4 through 7 on the left side and 4 through 8 on the right side, and a wound retractor device was placed. A camera port was made in the middle third of ICS 9. Each lung lobe was sequentially exteriorized at each respective ICS. A thoracoabdominal stapler was placed to simulate a lung lobectomy, and distance from the stapler anvil to the hilus was measured. RESULTS: For the left cranial lung lobe, there was no significant difference in median distance from the stapler anvil to the pulmonary hilus for ICS 4 through 6. Simulated lobectomy of the left caudal lung lobe performed at ICS 5 and 6 resulted in a significantly shorter distance, compared with lobectomy performed at ICS 4 and 7. Simulated lobectomy of the right cranial and right middle lung lobes performed at ICS 4 and 5 resulted in a significantly shorter distance, compared with lobectomy performed at ICS 7. Simulated lobectomy of the accessory and right caudal lung lobes at ICS 5 and 6 resulted in a significantly shorter distance than for lobectomy performed at ICS 8. CONCLUSIONS AND CLINICAL RELEVANCE: An optimal ICS for a minithoracotomy incision was determined for thoracoscopic-assisted lung lobectomy in cats.

The validity of open-source data when assessing jail suicides.

BACKGROUND: The Bureau of Justice Statistics' Deaths in Custody Reporting Program is the primary source for jail suicide research, though the data is restricted from general dissemination. This study is the first to examine whether jail suicide data obtained from publicly available sources can help inform our understanding of this serious public health problem. METHODS: Of the 304 suicides that were reported through the DCRP in 2009, roughly 56 percent (N = 170) of those suicides were identified through the open-source search protocol. Each of the sources was assessed based on how much information was collected on the incident and the types of variables available. A descriptive analysis was then conducted on the variables that were present in both data sources. The four variables present in each data source were: (1) demographic characteristics of the victim, (2) the location of occurrence within the facility, (3) the location of occurrence by state, and (4) the size of the facility. RESULTS: Findings demonstrate that the prevalence and correlates of jail suicides are extremely similar in both open-source and official data. However, for almost every variable measured, open-source data captured as much information as official data did, if not more. Further, variables not found in official data were identified in the open-source database, thus allowing researchers to have a more nuanced understanding of the situational characteristics of the event. CONCLUSIONS: This research provides support for the argument in favor of including open-source data in jail suicide research as it illustrates how open-source data can be used to provide additional information not originally found in official data. In sum, this research is vital in terms of possible suicide prevention, which may be directly linked to being able to manipulate environmental factors.