Outpatient Antipsychotic Use and Severe COVID-19: Avoiding the Impact of Age in a Real-World Data Study.

BACKGROUND: The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence regarding their effect in the nongeriatric population. We aim to assess the association between antipsychotic use and risk of disease progression and hospitalization due to COVID-19 among the general population, stratifying by age. METHODS: We conducted a population-based, multiple case-control study to assess risk of hospitalization, with cases being patients with a PCR(+) test who required hospitalization and controls being individuals without a PCR(+) test; and risk of progression to hospitalization, with cases being the same as those used in the hospitalization substudy and controls being nonhospitalized PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. RESULTS: Antipsychotic treatment in patients younger than 65 years was not associated with a higher risk of hospitalization due to COVID-19 (aOR 0.94 [95%CI = 0.69-1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI = 0.70-1.33]). For patients aged 65 years or older, however, there was a significant, increased risk of hospitalization (aOR 1.58 [95% CI = 1.38-1.80]) and disease progression (aOR 1.31 [95% CI = 1.12-1.55]). CONCLUSIONS: The results of our large-scale real-world data study suggest that antipsychotic use is not associated with a greater risk of hospitalization due to COVID-19 and progression to hospitalization among patients younger than 65 years. The effect found in the group aged 65 years or older might be associated with off-label use of antipsychotics.

Photophysical properties of DAPI in PVA films. Possibility of room temperature phosphorescence.

We studied the spectral properties of 4'-6-diamidino-2-phenylindole (DAPI) in poly (vinyl alcohol) (PVA) films. Absorption and fluorescence spectra, emission and excitation spectra, quantum yield, and fluorescence lifetime have been characterized. An efficient room temperature phosphorescence (RTP) of DAPI has been observed with UV and blue light excitations. A few hundred millisecond phosphorescence lifetime enables a gated detection with sufficient background reduction. We found the phosphorescent Quantum Yield of DAPI in PVA Film to be 0.0009.

How Much Protection Does a Collar Provide? Assessing Risk of Early Periprosthetic Femur Fractures Following Total Hip Arthroplasty in Elderly Patients.

BACKGROUND: Periprosthetic fractures (PPFs) account for approximately 25% of early revisions following total hip arthroplasty (THA). Cemented femoral fixation is associated with a lower-risk of PPF, and collared-cementless stems may reduce the risk as well. The objective of this study was to compare early-PPF rates between cemented, collared-cementless, and non-collared cementless stems in elderly patients. METHODS: A consecutieve-series of 11,522 primary THAs performed between 2016 and 2021 at our institution in patients >65 years of age was identified. Stem types used were categorized as cemented, collared-cementless, or non-collared cementless. Patients undergoing THA who had cemented-stems were older, more commonly women, and more likely to have a posterior-approach. To reduce confounding of patient characteristics, we matched patients in the 3 stem-categories according to age, sex, and body mass index. This generated 3-groups (cemented, collared-cementless, and non-collared cementless) consisting of 936 patients per group. The mean age of these 2,808 patients was 73 years, the mean body mass index was 27, and 67% were women. Logistic regressions were used to evaluate risk-factors for early-PPF. In the entire cohort of primary THA in elderly patients, there were 85 early PPFs (0.7%) over the study period. RESULTS: Non-collared cementless stems were associated with an increased risk of early PPF (OR: 3.11; P = .03) compared to collared-cementless stems. There were no early PPFs in the matched cemented cohort, 6 early PPFs in the matched collared-cementless cohort, and 16 early-PPFs in the matched non-collared cementless cohort (0% versus 0.64% versus 1.71%, P < .001). CONCLUSIONS: In this large-series of patients >65 years of age undergoing primary THA, cemented stem fixation had the lowest incidence of early PPF, but collared-cementless stems had a nearly 3-fold decrease in risk for early PPF compared to non-collared cementless stems.

Dislocation Following Anterior and Posterior Total Hip Arthroplasty in the Setting of Spinal Deformity and Stiffness: Evolving Trends Using a High-Risk Protocol at a Single Tertiary Center.

BACKGROUND: Patients who have spinal stiffness and deformity are at the highest risk for dislocation after total hip arthroplasty (THA). Previous reports of this cohort are limited to antero-lateral and postero-lateral (PL) approaches. We investigated the dislocation rate after direct anterior (DA) and PL approach THA with a contemporary high-risk protocol to optimize stability. METHODS: We investigated patients undergoing THA who had preoperative biplanar imaging from January-December 2019. Patients were identified using radiographic criteria of spinal-stiffness (<10-degree change in sacral slope from standing to seated) and deformity (flatback deformity with >10-degree difference in pelvic incidence and lumbar lordosis). There were 367 patients identified (181 DA, 186 PL). The primary outcome was dislocation rate at 2-years postoperatively. Risk-factors for dislocation were evaluated using logistic regressions (significance level of 0.05). RESULTS: There were 6 (1.6%) dislocations in the entire cohort, with low dislocation rates for both DA (0.6%) and PL-THA (2.7%). We observed increased utilization of dual mobility with larger outer head bearings (>38 mm) with PL-THA (34.4 versus 5.0%, P < .01) and conversely increased utilization of 32-mm femoral-heads with DA-THA (39.4 versus 7.0%, P < .001). Surgical approach (PL) was not a significant risk-factor for dislocation (odds ratio: 5.03, P = .15). Patients who had a history of lumbar-fusion had 8-times higher odds for dislocation (OR: 8.20, P = .020). CONCLUSIONS: To the best of our knowledge, this is the largest series to date evaluating DA and PL-THA in the hip-spine 2B-group. Our results demonstrate lower dislocation rate than expected with either surgical approach using a high-risk protocol.

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient.

OBJECTIVES: To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. METHODS: We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. RESULTS: ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]). CONCLUSION: This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Outpatient glucocorticoid use and COVID-19 outcomes: a population-based study.

INTRODUCTION: Owing to controversy information surrounds effect of glucocorticoids on the evolution of COVID-19, we evaluate the effects of outpatient glucocorticoid use on the severity and progression of COVID-19 and risk of infection and analyse the effect of window of exposure and dose. METHODS: We conducted a population-based case - control study, involving 4 substudies: (i) Hospitalisation; (ii) Mortality, using subjects hospitalised with a PCR + as cases and subjects without a PCR + as controls; (iii) Progression, including subjects with a PCR + (hospitalised versus non-hospitalised); and (iv) Susceptibility, with all subjects with a PCR + and subjects without a PCR + . Adjusted odds ratios (ORa) and their 95% confidence intervals (95% CI) were calculated. RESULTS: The outpatient glucocorticoid use was associated with an increased risk of hospitalisation (aOR 1.79; 95% CI 1.56-2.05), mortality (aOR 2.30; 95% CI 1.68-3.15), progression (aOR 1.69; 95% CI 1.43-2.00) and susceptibility (aOR 1.29, 95% CI 1.19-1.41). Furthermore, the effects was observed to be greater at higher doses and the closer that drug use approached the outcome date, with an almost fourfold increase in mortality among users in the previous month (aOR 3.85; 95% CI 2.63-5.62). CONCLUSIONS: According to the results of this real-world data study, outpatient glucocorticoid use should be considered in making decisions about intrahospital treatment.

Outpatient atorvastatin use and severe COVID-19 outcomes: A population-based study.

Evidence of the effect of statins on patients with coronavirus disease (2019) COVID-19 is inconsistent. The aim of this study was to evaluate the association between chronic use of statins-both overall and by active ingredient-and severe outcomes of COVID-19 (risk of hospitalization and mortality), progression to severe outcomes, and susceptibility to the virus. We conducted a population-based case-control study with data from electronic records to assess the risk of (1) hospitalization: cases were patients admitted due to COVID-19 and controls were subjects without COVID-19; (2) mortality: cases were hospitalized patients who died due to COVID-19 and controls were subjects without COVID-19; (3) progression: cases were hospitalized COVID-19 subjects and controls were nonhospitalized COVID-19 patients; and (4) susceptibility: cases were patients with COVID-19 (both hospitalized and nonhospitalized) and controls were subjects without COVID-19. We collected data on 2821 hospitalized cases, 26 996 nonhospitalized cases, and 52 318 controls. Chronic use of atorvastatin was associated with a decreased risk of hospitalization (adjusted odds ratios [aOR] = 0.83; 95% confidence interval [CI]: 0.74-0.92) and mortality (aOR = 0.70; 95% CI: 0.53-0.93), attributable in part to a lower risk of susceptibility to the virus (aOR = 0.91; 95% CI: 0.86-0.96). Simvastatin was associated with a reduced risk of mortality (aOR = 0.59; 95% CI: 0.40-0.87). The wide degree of heterogeneity observed in the estimated odds ratios (ORs) of the different statins suggests that there is no class effect. The results of this real-world study suggest that chronic use of atorvastatin (and to a lesser degree, of simvastatin) is associated with a decrease in risk of severe COVID-19 outcomes.

Reasons and Risk Factors for Failed Same-Day Discharge After Primary Total Knee Arthroplasty.

BACKGROUND: As ambulatory total knee arthroplasty (TKA) becomes increasingly common, unplanned admission after surgery presents a challenge for the health care system. Studies evaluating the reasons and risk factors for this occurrence are limited. We sought to evaluate the reasons for unplanned admission after surgery and identify risk factors associated with this occurrence. METHODS: Patients registered in an institutional ambulatory joint arthroplasty program who underwent a TKA from 2017-2020 were retrospectively reviewed. The criteria for enrollment include candidates for unilateral TKA between the ages of 18 and 70 years, with a body mass index (BMI) of less than 35, and appropriate social and material support at home. Patients who had certain comorbidities including coronary artery disease, valvular heart disease, and opioid dependence were not eligible. A total of 274 patients who underwent TKA with planned same-day discharge (SDD) were identified in the medical record and reviewed. In this cohort, 140 patients (51.1%) were discharged on the day of surgery and 134 patients (48.9%) required a minimum 1-night admission. Demographics, comorbidities, and perioperative data were collected. Factors associated with failed SDD were identified using multivariate logistic regression. RESULTS: The most common reasons for failed SDD were failure to meet ambulation goals (25%) and logistical issues related to a late-day case (19%). Risk factors for failed SDD include general anesthesia (odds ratio (OR) 12.60, P = .047), procedure start time after 11:00 am (OR 5.16, P < .001), highest postoperative pain score >8 (visual analogue scale, OR 5.78, P = .001). Willingness to accept a higher pain threshold before discharge (visual analogue scale 4 to 10) was associated with successful SDD (OR 3.0, P < .001). Age and American Society of Anesthesiologists (ASA) classification were not associated with failed SDD. CONCLUSIONS: The most common reasons for failed SDD were related to logistical issues and postoperative mobilization. Risk factors for failed SDD involve case timing and pain control. Modifiable perioperative factors may play an important role in successful SDD after TKA.

Cemented Femoral Fixation in a High-Risk Cohort Diminishes Risk of Early Postoperative Periprosthetic Fracture.

BACKGROUND: Early periprosthetic fractures (PPFx) following primary total hip arthroplasty (THA) create significant morbidity. Established risk factors for early PPFx include age, gender, body mass index, surgical approach, and implant fixation. We investigated the role of femoral fixation on early PPFx (<90 days postoperatively) in a high-risk cohort undergoing direct anterior approach (DAA) THA. METHODS: The final cohort comprised 344 consecutive patients (390 hips) with risk factors for PPFx (age >68 years and body mass index <25 kg/m2) who underwent primary DAA THA between May 4, 2009 and December 31, 2019 and had 90-day follow-up. Noncemented fixation was used in 229-hips, while cemented fixation was used in 161 hips. The primary outcome was early PPFx. Fisher's exact test was used for categorical variables, while t-tests were used to compare continuous variables. RESULTS: We observed 8 early PPFx (2.1%), all fractures occurring in the noncemented group. Baseline demographics were similar but not equal, with the cemented group being older (78.0 versus 76.3 years; P = .004) with a greater proportion of females (91.9% versus 69.4%; P < .001). The rate of early PPFx was significantly higher with noncemented fixation compared to cemented fixation (3.5% versus 0.0%; P = .023). A post hoc power analysis confirmed sufficient power (1-ß = 0.81). CONCLUSION: Although baseline risk factors for early PPFx are not easily modifiable, surgical factors can be modified. Cemented fixation has the potential to markedly reduce the risk of early PPFx in high-risk patients undergoing DAA THA.

Predicting Total Knee Arthroplasty Outpatient Discharge: Surgeons versus Insurance Companies.

BACKGROUND: Insurance companies are increasingly making unilateral determinations of admission status for primary total knee arthroplasty (TKA). These determinations may differ from those based on surgeon-derived criteria for outpatient knee replacement. The goal of this study is to determine if insurance company determinations of outpatient status are as reliable as surgeon-derived criteria in predicting outpatient discharge after TKA. METHODS: We retrospectively reviewed 709 patients who were preoperatively authorized for outpatient TKA. Patients were stratified into 2 groups: "outpatient per surgeon" (appropriate for outpatient surgery per institutional protocols) or "outpatient per insurance" (appropriate for inpatient surgery per institutional protocols but denied inpatient status by insurance). The primary endpoint of this study was the conversion rate of outpatient to inpatient stay. Univariate logistic regression was performed to compare the odds of conversion to inpatient stay between outpatient per surgeon and outpatient per insurance procedures and other covariates. RESULTS: The cohort included 434 outpatient per insurance (61.2%) and 275 outpatient per surgeon (38.8%) patients. Surgeons accurately predicted outpatients' discharge 92.0% of the time, while insurance companies did so 81.3% of time (P < .001). Outpatient per insurance procedures (odds ratio [OR] 2.20, P = .003) and body mass index >35 kg/m2 (OR 1.82, P = .026) had higher odds of being converted to inpatient. Males had higher odds (OR 1.52, P < .001) of being discharged as outpatient. CONCLUSION: Determining inpatient versus outpatient status is a complex decision involving both clinical and social factors. Surgeons accurately predicted outpatient discharge 92% of the time. Moreover, outpatient per insurance procedures were twice as likely to be converted to inpatient status. Therefore, insurance companies should leave deciding admission status up to both the patient and surgeon.

Use of Bedside Entertainment and Relaxation Theater (BERT) to Reduce Fear and Anxiety Associated With Outpatient Procedures in Pediatric Orthopaedics.

BACKGROUND: The aim of the present study was to evaluate the effectiveness of the Bedside Entertainment and Relaxation Theater (BERT) on fear, anxiety, and pain outcomes in pediatric orthopaedic patients associated with cast removal and/or pin removal in the outpatient clinic setting. METHODS: A total of 66 pediatric patients between the ages of 2 and 6 undergoing clinic procedures were recruited for this study and randomized into the control group or the intervention (BERT) group. Patients in the control group received standard of care during the cast room procedure; patients in the BERT group were given headphones and watched a movie on a projector during the procedure. Fear, anxiety, and pain were measured before and after the procedure. Procedures included cast removal, pin removal, or a combination of the 2. RESULTS: Patients in the BERT group reported less fear and anxiety overall after the procedure than patients in the control group (P=0.009, 0.015). Adjusting for procedure type (ie, pin removal), patients in the BERT group reported a 0.67 point decrease (95% confidence interval: 0.04, 1.30) on the fear scale after the procedure (P=0.039) and a 1.81 point decrease (95% confidence interval: 0.04, 3.59) on the anxiety scale associated with the procedure (P=0.045), compared with the control group. Patients and caregivers reported high satisfaction with BERT. CONCLUSION: This randomized, controlled trial demonstrates an evidence-based distraction tool that can be implemented across medical centers for pediatric patients undergoing office based orthopaedic procedures. BERT can be used to reduce fear and anxiety associated with these procedures, and increase patient and parent satisfaction. LEVEL OF EVIDENCE: Level I.

Virtual Reality Reduces Fear and Anxiety During Pediatric Orthopaedic Cast Room Procedures: A Randomized Controlled Trial.

BACKGROUND: Virtual Reality (VR) has been used as a distraction tool in various medical settings to reduce pain and anxiety associated with procedures. This study evaluates the effectiveness of VR as a distraction tool for decreasing fear, anxiety, and pain in pediatric patients undergoing common outpatient orthopaedic procedures. METHODS: A total of 210 patients were recruited from a single orthopaedic clinic between October 2017 and July 2019. Patients were randomized to the VR group or to the control group (standard of care). Outpatient procedures included cast and/or pin removals. Primary outcome measures were collected preprocedure and postprocedure using validated surveys, and included: fear (Children's Fear Scale), anxiety (Children's Anxiety Meter-State), and pain (Numerical Rating Scale). Patients and caregivers in the VR group completed a satisfaction survey at the end of their appointment. Fear, anxiety, and pain scores between the 2 groups were analyzed using multivariable linear regression models, and the satisfaction survey was analyzed using descriptive statistics. RESULTS: One hundred twenty nine patients were included in the final analysis, with 85 patients in the VR group and 44 patients in the control group. During the procedure, patients in the VR group reported significantly lower average fear scores ( P <0.001) and anxiety scores ( P =0.003) as compared with controls. There were no differences between the groups in fear and anxiety scores before and after the procedure, or pain scores before, during, or after the procedure. Overall, patients and caregivers in the VR group reported high satisfaction scores, with 97% of patients and 95% of caregivers recommending this intervention to others. CONCLUSION: VR technology was found to be an effective distraction tool to improve fear and anxiety during cast removal procedures. Findings build on a body of evidence that supports the use of distraction tools in clinics, specifically pediatric orthopaedics, to improve fear and anxiety. The distraction tools can be easily translated into current practices. LEVEL OF EVIDENCE: Level I.

The effects of necrostatin-1 on the in vitro development and function of young porcine islets over 14-day prolonged tissue culture.

BACKGROUND: Necrostatin-1 (Nec-1) supplementation to tissue culture media on day 3 has recently been shown to augment the insulin content, endocrine cellular composition, and insulin release of pre-weaned porcine islets (PPIs); however, its effects were only examined for the first 7 days of tissue culture. The present study examined whether the addition of Nec-1 on day 3 could further enhance the in vitro development and function of PPIs after 14 days of tissue culture. METHODS: PPIs were isolated from 8- to 15-day-old, pre-weaned Yorkshire piglets and cultured in an islet maturation media supplemented with Nec-1 on day 3. The recovery, viability, insulin content, endocrine cellular composition, GLUT2 expression in beta cells, differentiation and proliferation potential, and glucose-stimulated insulin secretion of PPIs were assessed on days 3, 7, and 14 of tissue culture (n = 5 on each day). RESULTS: Compared with day 7 of tissue culture, islets on day 14 had a lower recovery, GLUT2 expression in beta cells, proliferation capacity of endocrine cells, and glucose-induced insulin stimulation index. Prolonging the culture time to 14 days did not affect islet viability, insulin content, proportion of endocrine cells, and differentiation potential. CONCLUSION: The growth-inducing effects of Nec-1 on PPIs were most effective on day 7 of tissue culture when added on day 3. Our findings support existing evidence that the in vitro activities of Nec-1 are short-lived and encourage future studies to explore the use of other novel growth factors during prolonged islet tissue culture.

Leveraging Virtual Reality and Augmented Reality to Combat Chronic Pain in Youth: Position Paper From the Interdisciplinary Network on Virtual and Augmented Technologies for Pain Management.

BACKGROUND: Virtual reality (VR) and augmented reality (AR) interventions are emerging as promising tools in the treatment of pediatric chronic pain conditions. However, in this young field, there is little consensus to guide the process of engaging in the development and evaluation of targeted VR-based interventions. OBJECTIVE: The INOVATE-Pain (Interdisciplinary Network on Virtual and Augmented Technologies for Pain management) consortium aims to advance the field of VR for pediatric chronic pain rehabilitation by providing guidance for best practices in the design, evaluation, and dissemination of VR-based interventions targeting this population. METHODS: An interdisciplinary meeting of 16 academics, clinicians, industry partners, and philanthropy partners was held in January 2020. RESULTS: Reviewing the state of the field, the consortium identified important directions for research-driven innovation in VR and AR clinical care, highlighted key opportunities and challenges facing the field, and established a consensus on best methodological practices to adopt in future efforts to advance the research and practice of VR and AR in pediatric pain. The consortium also identified important next steps to undertake to continue to advance the work in this promising new area of digital health pain interventions. CONCLUSIONS: To realize the promise of this realm of innovation, key ingredients for success include productive partnerships among industry, academic, and clinical stakeholders; a uniform set of outcome domains and measures for standardized evaluation; and widespread access to the latest opportunities, tools, and resources. The INOVATE-Pain collaborative hopes to promote the creation, rigorous yet efficient evaluation, and dissemination of innovative VR-based interventions to reduce pain and improve quality of life for children.

Small surgeries, big smiles: using virtual reality to reduce the need for sedation or general anesthesia during minor surgical procedures.

PURPOSE: Children often require anesthesia for simple diagnostic and therapeutic procedures. The aim of this study was to evaluate the feasibility of using virtual reality (VR) to reduce sedation in children undergoing minor surgical procedures. METHOD: In this prospective, non-randomized clinical trial, pediatric patients at a free-standing children's hospital undergoing hormone implant placement, removal, or exchange were recruited to use VR and local anesthesia instead of procedural sedation or general anesthesia (GA). Patients were enrolled between November 2017 and March 2020, and were compared to historic controls who underwent similar procedures without VR between April 2016 and February 2020. Primary outcome measure was successful procedure completion without sedation or GA. Secondary measures included assessments of pain, fear and anxiety, patient compliance, procedural and recovery times. RESULTS: Twenty-eight patients underwent 29 procedures with VR. Hormone implants (72%), removals (7%), or exchanges (21%) were completed without GA, sedation or IV placement. Procedure lengths and pain scores were similar between VR patients and historic controls, but recovery times were significantly shorter in VR patients (18 vs 65 min, p < 0.001). Participant satisfaction scores were high, with 95% recommending VR to others. CONCLUSIONS: VR is a feasible alternative to sedation or GA for select pediatric patients undergoing minor surgical procedures.

Necrostatin-1 Supplementation to Islet Tissue Culture Enhances the In-Vitro Development and Graft Function of Young Porcine Islets.

Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8-15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.

Virtual reality for pediatric periprocedural care.

PURPOSE OF REVIEW: Commercial availability of virtual reality headsets and software has exponentially grown over the last decade as it has become more sophisticated, less expensive, and portable. Although primarily used by the general public for entertainment, virtual reality has been adopted by periprocedural clinicians to improve patient experiences and treatments. The purpose of this review is to explore recently reported evidence for virtual reality effectiveness for pediatric periprocedural care and discuss considerations for clinical implementation. RECENT FINDINGS: In the preprocedure setting, practitioners use virtual reality to introduce children to periprocedural environments, distract attention from preprocedural vascular access, and increase cooperation with anesthesia induction. Intraprocedure, virtual reality decreases sedation requirements, and in some instances, eliminates anesthesia for minor procedures. Virtual reality also augments pain reduction therapies in the acute and extended rehabilitation periods, resulting in faster recovery and improved outcomes. Virtual reality seems to be well treated for pediatric use, given close clinical care and carefully curated content. SUMMARY: Given the multiple clinical applications of virtual reality to supplement pediatric periprocedural care, practitioners should consider developing clinical programs that reliably provide access to virtual reality. Future research should focus on identification of patient characteristics and types of software that yield optimal patient outcomes.

Virtual Reality Facilitates Engagement in Physical Therapy in the Pediatric CVICU.

PURPOSE: The purpose of this report is to demonstrate the successful application of virtual reality to improve physical therapy in the pediatric cardiovascular intensive care unit. Early mobilization and cognitive stimulation improve morbidity of critically ill children. However, maintaining child engagement with these therapies can be challenging, especially during extended intensive care stays. SUMMARY OF KEY POINTS: While virtual reality has been successfully used as an analgesic and anxiolytic in the cardiovascular intensive care unit, this report demonstrates its novel use as a tool to augment physical therapy for a child who had been debilitated after heart transplantation. Virtual reality encouraged the child to engage in physical therapy sessions, participate for greater durations, and directly address barriers to discharge. CONCLUSIONS AND RECOMMENDATIONS FOR CLINICAL PRACTICE: While further studies are needed to define best practice, this report demonstrates that virtual reality can be safely used for carefully selected and monitored children in critical care.

The diabetic microenvironment causes mitochondrial oxidative stress in glomerular endothelial cells and pathological crosstalk with podocytes.

BACKGROUND: In the setting of diabetes mellitus, mitochondrial dysfunction and oxidative stress are important pathogenic mechanisms causing end organ damage, including diabetic kidney disease (DKD), but mechanistic understanding at a cellular level remains obscure. In mouse models of DKD, glomerular endothelial cell (GEC) dysfunction precedes albuminuria and contributes to neighboring podocyte dysfunction, implicating GECs in breakdown of the glomerular filtration barrier. In the following studies we wished to explore the cellular mechanisms by which GECs become dysfunctional in the diabetic milieu, and the impact to neighboring podocytes. METHODS: Mouse GECs were exposed to high glucose media (HG) or 2.5% v/v serum from diabetic mice or serum from non-diabetic controls, and evaluated for mitochondrial function (oxygen consumption), structure (electron microscopy), morphology (mitotracker), mitochondrial superoxide (mitoSOX), as well as accumulation of oxidized products (DNA lesion frequency (8-oxoG, endo-G), double strand breaks (γ-H2AX), endothelial function (NOS activity), autophagy (LC3) and apoptotic cell death (Annexin/PI; caspase 3). Supernatant transfer experiments from GECs to podocytes were performed to establish the effects on podocyte survival and transwell experiments were performed to determine the effects in co-culture. RESULTS: Diabetic serum specifically causes mitochondrial dysfunction and mitochondrial superoxide release in GECs. There is a rapid oxidation of mitochondrial DNA and loss of mitochondrial biogenesis without cell death. Many of these effects are blocked by mitoTEMPO a selective mitochondrial anti-oxidant. Secreted factors from dysfunctional GECs were sufficient to cause podocyte apoptosis in supernatant transfer experiments, or in co-culture but this did not occur when GECs had been previously treated with mitoTEMPO. CONCLUSION: Dissecting the impact of the diabetic environment on individual cell-types from the kidney glomerulus indicates that GECs become dysfunctional and pathological to neighboring podocytes by increased levels of mitochondrial superoxide in GEC. These studies indicate that GEC-signaling to podocytes contributes to the loss of the glomerular filtration barrier in DKD. Video abstract.

Characterization of chelator-mediated recovery of pancreatic islets from barium-stabilized alginate microcapsules.

INTRODUCTION: Islet recovery from within alginate-based microcapsules is necessary for certain analytical assays like flow cytometry; however, this technology has not been widely characterized. In this study, we explore the ability of EDTA, EGTA, and sodium citrate to induce reverse alginate polymerization via chelation and assess the toxicity of each chelator on pancreatic islets. METHODS: EDTA, EGTA, and sodium citrate were used to dissolve single-layered Ba2+ alginate encapsulated islets and the rate of capsule breakdown calculated from analysis of imaging data. The effect of chelator exposure on islet viability and recovery was assessed using flow cytometry, while glucose-stimulated insulin release (GSIR) assay was used to measure effects on islet function. RESULTS: EGTA demonstrated the most rapid microcapsule dissolving rate followed by EDTA and sodium citrate. Islet recovery was significantly better when encapsulated islets were treated with EDTA than EGTA and Na+ citrate. A decrease in viability and increase in apoptotic cells were observed when encapsulated islets were treated with Na+ citrate compared to islets treated with EDTA and EGTA. Islets treated with EDTA and EGTA demonstrated comparable stimulation index values to non-treated control. Conversely, islets treated with Na+ citrate exhibited significantly decreased SI values compared to control. All chelator groups showed significantly lower insulin secretion than non-treated islets. CONCLUSION: Islet recovery from alginate microcapsule is possible using common chelators like Na+ citrate, EDTA, and EGTA. Chelation of encapsulated islets using EDTA demonstrated the most efficient dissolving capabilities with the least toxicity toward islet recovery and health.