The Effect of 2019 Coronavirus Stay-at-Home Order on Geriatric Trauma Patients in Southern California.

BACKGROUND: California issued stay-at-home (SAH) orders to mitigate COVID-19 spread. Previous studies demonstrated a shift in mechanisms of injuries (MOIs) and decreased length of stay (LOS) for the general trauma population after SAH orders. This study aimed to evaluate the effects of SAH orders on geriatric trauma patients (GTPs), hypothesizing decreased motor vehicle collisions (MVCs) and LOS. METHODS: A post-hoc analysis of GTPs (≥65 years old) from 11 level-I/II trauma centers was performed, stratifying patients into 3 groups: before SAH (1/1/2020-3/18/2020) (PRE), after SAH (3/19/2020-6/30/2020) (POST), and a historical control (3/19/2019-6/30/2019) (CONTROL). Bivariate comparisons were performed. RESULTS: 5486 GTPs were included (PRE-1756; POST-1706; CONTROL-2024). POST had a decreased rate of MVCs (7.6% vs 10.6%, P = .001; vs 11.9%, P < .001) and pedestrian struck (3.4% vs 5.8%, P = .001; vs 5.2%, P = .006) compared with PRE and CONTROL. Other mechanisms of injury, LOS, mortality, and operations performed were similar between cohorts. However, POST had a lower rate of discharge to skilled nursing facility (SNF) (20% vs 24.5%, P = .001; and 20% vs 24.4%, P = .001). CONCLUSION: This retrospective multicenter study demonstrated lower rates of MVCs and pedestrian struck for GTPs, which may be explained by decreased population movement as a result of SAH orders. Contrary to previous studies on the generalized adult population, no differences in other MOIs and LOS were observed after SAH orders. However, there was a lower rate of discharge to SNF, which may be related to a lack of resources due to the COVID-19 pandemic, and thus potentially negatively impacted recovery of GTPs.Keywords.

A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 ocular retardation J mice.

BACKGROUND: A goal of developmental genetics is to identify functional interactions that underlie phenotypes caused by mutations. We sought to identify functional interactors of Vsx2, which when mutated, disrupts early retinal development. We utilized the Vsx2 loss-of-function mouse, ocular retardation J (orJ), to assess interactions based on principles of positive and negative epistasis as applied to bulk transcriptome data. This was first tested in vivo with Mitf, a target of Vsx2 repression, and then to cultures of orJ retina treated with inhibitors of Retinoid-X Receptors (RXR) to target Rxrg, an up-regulated gene in the orJ retina, and gamma-Secretase, an enzyme required for Notch signaling, a key mediator of retinal proliferation and neurogenesis. RESULTS: Whereas Mitf exhibited robust positive epistasis with Vsx2, it only partially accounts for the orJ phenotype, suggesting other functional interactors. RXR inhibition yielded minimal evidence for epistasis between Vsx2 and Rxrg. In contrast, gamma-Secretase inhibition caused hundreds of Vsx2-dependent genes associated with proliferation to deviate further from wild-type, providing evidence for convergent negative epistasis with Vsx2 in regulating tissue growth. CONCLUSIONS: Combining in vivo and ex vivo testing with transcriptome analysis revealed quantitative and qualitative characteristics of functional interaction between Vsx2, Mitf, RXR, and gamma-Secretase activities.

Unnecessary Early Gastrostomy for Trauma Patients.

While early gastrostomy tube placement (GTP) may decrease hospital length of stay and facilitate disposition, GTP may be unnecessary as some patients regain the ability to eat earlier than expected. No guidelines currently exist regarding optimal GTP timing or minimum duration of need indicating appropriateness of GTP. This retrospective (9/2017-12/2019) single center study evaluated the incidence of adequate (>75%) oral caloric intake (ACI) after GTP during index hospitalization and associated characteristics before discharge. Bivariate analyses were performed to compare patients achieving ACI and patients not achieving ACI at discharge. By discharge, 10 (12.5%) patients achieved ACI and 6 (7.5%) had their GT removed prior to discharge suggesting many patients undergo unnecessary GTP. Also, 6 (7.5%) patients suffered GTP-related complications. Future multicenter studies are needed to corroborate these findings and establish GTP guidelines for trauma patients to avoid unnecessary GT procedures and associated morbidities.

Rethinking protocolized completion angiography following extremity vascular trauma: A prospective observational multicenter trial.

BACKGROUND: Completion angiography (CA) is commonly used following repair of extremity vascular injury and is recommended by the Eastern Association for the Surgery of Trauma practice management guidelines for extremity trauma. However, it remains unclear which patients benefit from CA because only level 3 evidence exists. METHODS: This prospective observational multicenter (18LI, 2LII) analysis included patients 15 years or older with extremity vascular injuries requiring operative management. Clinical variables and outcomes were analyzed with respect to with our primary study endpoint, which is need for secondary vascular intervention. RESULTS: Of 438 patients, 296 patients required arterial repair, and 90 patients (30.4%) underwent CA following arterial repair. Institutional protocol (70.9%) was cited as the most common reason to perform CA compared with concern for inadequate repair (29.1%). No patients required a redo extremity vascular surgery if a CA was performed per institutional protocol; however, 26.7% required redo vascular surgery if the CA was performed because of a concern for inadequate repair. No differences were observed in hospital mortality, length of stay, extremity ischemia, or need for amputation between those who did and did not undergo CA. CONCLUSION: Completion angiogram following major extremity injury should be considered in a case-by-case basis. Limiting completion angiograms to those patients with concern for an inadequate vascular repair may limit unnecessary surgery and morbidity. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Advancing DNA Barcoding to Elucidate Elasmobranch Biodiversity in Malaysian Waters.

The data provided in this article are partial fragments of the Cytochrome c oxidase subunit 1 mitochondrial gene (CO1) sequences of 175 tissues sampled from sharks and batoids collected from Malaysian waters, from June 2015 to June 2022. The barcoding was done randomly for six specimens from each species, so as to authenticate the code. We generated barcodes for 67 different species in 20 families and 11 orders. DNA was extracted from the tissue samples following the Chelex protocols and amplified by polymerase chain reaction (PCR) using the barcoding universal primers FishF2 and FishR2. A total of 654 base pairs (bp) of barcode CO1 gene from 175 samples were sequenced and analysed. The genetic sequences were blasted into the NCBI GenBank and Barcode of Life Data System (BOLD). A review of the blast search confirmed that there were 68 valid species of sharks and batoids that occurred in Malaysian waters. We provided the data of the COI gene mid-point rooting phylogenetic relation trees and analysed the genetic distances among infra-class and order, intra-species, inter-specific, inter-genus, inter-familiar, and inter-order. We confirmed the addition of Squalus edmundsi, Carcharhinus amboinensis, Alopias superciliosus, and Myliobatis hamlyni as new records for Malaysia. The establishment of a comprehensive CO1 database for sharks and batoids will help facilitate the rapid monitoring and assessment of elasmobranch fisheries using environmental DNA methods.

Left ventricular aneurysm versus pseudoaneurysm: Diagnosis in the era of multi-modality imaging and 3D-printing.

In this case report, we illustrate the contemporary use of multi-modality cardiac imaging and three-dimensional (3D)-printing in the diagnosis and precise surgical planning of a large ventricular aneurysm with an extensive thrombus burden after myocardial infarction. We further discuss an integrated multimodality approach in the evaluation of ventricular outpouchings.

Reproductive biology, length-weight relationship and diet of co-occurring butterfly rays, Gymnura poecilura and Gymnura zonura, in Malaysian waters.

Recent IUCN assessments had resulted in up listing of the status of butterfly rays due to concerns of overfishing, but inadequate biological understanding of these rays prevents meaningful conservation and management measures. Therefore, this study was undertaken to address knowledge gaps in the reproductive biology and diet of longtail butterfly ray (Gymnura poecilura) and zone tail butterfly ray (Gymnura zonura) in Malaysian waters. From surveys of landing sites and fish markets from years 2017 to 2022, size (disc width, DW), weight and maturity were recorded, and stomachs were collected from 94 G. poecilura (N = 39 females and 55 males) and 20 G. zonura (N = 10 females and 10 males) specimens. The length-weight relationships were significantly different between sexes for G. poecilura. The size at maturity (DW50) was estimated to be 476.0 mm (females), 385.0 mm (males) for G. poecilura and 442.0 mm (combined) for G. zonura. The number of embryos ranged from 1 to 6, and the embryo size was between 73.90 to 130.44 mm DW. Dietary analysis of stomach contents revealed that fish prey was dominant in both G. poecilura [94.4% Index of Relative Importance (IRI)] and G. zonura (100% IRI). Ontogenetic shift was seen in G. poecilura that fed on more variety of prey items, including shrimps, squids and crabs with an increase in body size. Both species co-occur all along coastal Malaysia although G. zonura is rarely encountered from fisheries surveys along the Strait of Malacca. Given similar habitat associations and dietary habits, G. poecilura may be able to outcompete G. zonura across their shared habitat range. The validity of G. japonica and G. micrura records in Malaysia remains questionable and requires future investigation.

Adolescent Trauma During the COVID Pandemic: Just Like Adults, Children, or Someone Else?

COVID-19 stay-at-home (SAH) orders were impactful on adolescence, when social interactions affect development. This has the potential to change adolescent trauma. A post-hoc multicenter retrospective analysis of adolescent (13-17 years-old) trauma patients (ATPs) at 11 trauma centers was performed. Patients were divided into 3 groups based on injury date: historical control (CONTROL:3/19/2019-6/30/2019, before SAH (PRE:1/1/2020-3/18/2020), and after SAH (POST:3/19/2020-6/30/2020). The POST group was compared to both PRE and CONTROL groups in separate analyses. 726 ATPs were identified across the 3 time periods. POST had a similar penetrating trauma rate compared to both PRE (15.8% vs 13.8%, P = .56) and CONTROL (15.8% vs 14.5%, P = .69). POST also had a similar rate of suicide attempts compared to both PRE (1.2% vs 1.5%, P = .83) and CONTROL (1.2% vs 2.1%, P = .43). However, POST had a higher rate of drug positivity compared to CONTROL (28.6% vs 20.6%, P = .032), but was similar in all other comparisons of alcohol and drugs to PRE and POST periods (all P > .05). Hence ATPs were affected differently than adults and children, as they had a similar rate of penetrating trauma, suicide attempts, and alcohol positivity after SAH orders. However, they had increased drug positivity compared to the CONTROL, but not PRE group.

Decreased hospital length of stay and intensive care unit admissions for non-COVID blunt trauma patients during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic overwhelmed hospitals, forcing adjustments including discharging patients earlier and limiting intensive care unit (ICU) utilization. This study aimed to evaluate ICU admissions and length of stay (LOS) for blunt trauma patients (BTPs). METHODS: A retrospective review of COVID (3/19/20-6/30/20) versus pre-COVID (3/19/19-6/30/19) BTPs at eleven trauma centers was performed. Multivariable analysis was used to identify risk factors for ICU admission. RESULTS: 12,744 BTPs were included (6942 pre-COVID vs. 5802 COVID). The COVID cohort had decreased mean LOS (3.9 vs. 4.4 days, p = 0.029), ICU LOS (0.9 vs. 1.1 days, p < 0.001), and rate of ICU admission (22.3% vs. 24.9%, p = 0.001) with no increase in complications or mortality compared to the pre-COVID cohort (all p > 0.05). On multivariable analysis, the COVID period was associated with decreased risk of ICU admission (OR = 0.82, CI 0.75-0.90, p < 0.001). CONCLUSIONS: BTPs had decreased LOS and associated risk of ICU admission during COVID, with no corresponding increase in complications or mortality.

Effects of the COVID-19 pandemic on pediatric trauma in Southern California.

PURPOSE: The COVID-19 pandemic resulted in increased penetrating trauma and decreased length of stay (LOS) amongst the adult trauma population, findings important for resource allocation. Studies regarding the pediatric trauma population are sparse and mostly single-center. This multicenter study examined pediatric trauma patients, hypothesizing increased penetrating trauma and decreased LOS after the 3/19/2020 stay-at-home (SAH) orders. METHODS: A multicenter retrospective analysis of trauma patients ≤ 17 years old presenting to 11 centers in California was performed. Demographic data, injury characteristics, and outcomes were collected. Patients were divided into three groups based on injury date: 3/19/2019-6/30/2019 (CONTROL), 1/1/2020-3/18/2020 (PRE), 3/19/2020-6/30/2020 (POST). POST was compared to PRE and CONTROL in separate analyses. RESULTS: 1677 patients were identified across all time periods (CONTROL: 631, PRE: 479, POST: 567). POST penetrating trauma rates were not significantly different compared to both PRE (11.3 vs. 9.0%, p = 0.219) and CONTROL (11.3 vs. 8.2%, p = 0.075), respectively. POST had a shorter mean LOS compared to PRE (2.4 vs. 3.3 days, p = 0.002) and CONTROL (2.4 vs. 3.4 days, p = 0.002). POST was also not significantly different than either group regarding intensive care unit (ICU) LOS, ventilator days, and mortality (all p > 0.05). CONCLUSIONS: This multicenter retrospective study demonstrated no difference in penetrating trauma rates among pediatric patients after SAH orders but did identify a shorter LOS.

Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination.

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.

Drug and alcohol positivity of traumatically injured patients related to COVID-19 stay-at-home orders.

Background: COVID-19 related stay-at-home (SAH) orders created many economic and social stressors, possibly increasing the risk of drug/alcohol abuse in the community and trauma population.Objectives: Describe changes in alcohol/drug use in traumatically injured patients after SAH orders in California and evaluate demographic or injury pattern changes in alcohol or drug-positive patients.Methods: A retrospective analysis of 11 trauma centers in Southern California (1/1/2020-6/30/2020) was performed. Blood alcohol concentration, urine toxicology results, demographics, and injury characteristics were collected. Patients were grouped based on injury date - before SAH (PRE-SAH), immediately after SAH (POST-SAH), and a historical comparison (3/19/2019-6/30/2019) (CONTROL) - and compared in separate analyses. Groups were compared using chi-square tests for categorical variables and Mann-Whitney U tests for continuous variables.Results: 20,448 trauma patients (13,634 male, 6,814 female) were identified across three time-periods. The POST-SAH group had higher rates of any drug (26.2% vs. 21.6% and 24.7%, OR = 1.26 and 1.08, p < .001 and p = .035), amphetamine (10.4% vs. 7.5% and 9.3%, OR = 1.43 and 1.14, p < .001 and p = .023), tetrahydrocannabinol (THC) (13.8% vs. 11.0% and 11.4%, OR = 1.30 and 1.25, p < .001 and p < .001), and 3,4-methylenedioxy methamphetamine (MDMA) (0.8% vs. 0.4% and 0.2%, OR = 2.02 and 4.97, p = .003 and p < .001) positivity compared to PRE-SAH and CONTROL groups. Alcohol concentration and positivity were similar between groups (p > .05).Conclusion: This Southern California multicenter study demonstrated increased amphetamine, MDMA, and THC positivity in trauma patients after SAH, but no difference in alcohol positivity or blood concentration. Drug prevention strategies should continue to be adapted within and outside of hospitals during a pandemic.

COVID-19 in trauma: a propensity-matched analysis of COVID and non-COVID trauma patients.

PURPOSE: There is mounting evidence that surgical patients with COVID-19 have higher morbidity and mortality than patients without COVID-19. Infection is prevalent amongst the trauma population, but any effect of COVID-19 on trauma patients is unknown. We aimed to evaluate the effect of COVID-19 on a trauma population, hypothesizing increased mortality and pulmonary complications for COVID-19-positive (COVID) trauma patients compared to propensity-matched COVID-19-negative (non-COVID) patients. METHODS: A retrospective analysis of trauma patients presenting to 11 Level-I and II trauma centers in California between 1/1/2019-6/30/2019 and 1/1/2020-6/30/2020 was performed. A 1:2 propensity score model was used to match COVID to non-COVID trauma patients using age, blunt/penetrating mechanism, injury severity score, Glasgow Coma Scale score, systolic blood pressure, respiratory rate, and heart rate. Outcomes were compared between the two groups. RESULTS: A total of 20,448 trauma patients were identified during the study period. 53 COVID trauma patients were matched with 106 non-COVID trauma patients. COVID patients had higher rates of mortality (9.4% vs 1.9%, p = 0.029) and pneumonia (7.5% vs. 0.0%, p = 0.011), as well as a longer mean length of stay (LOS) (7.47 vs 3.28 days, p < 0.001) and intensive care unit LOS (1.40 vs 0.80 days, p = 0.008), compared to non-COVID patients. CONCLUSION: This multicenter retrospective study found increased rates of mortality and pneumonia, as well as a longer LOS, for COVID trauma patients compared to a propensity-matched cohort of non-COVID patients. Further studies are warranted to validate these findings and to elucidate the underlying pathways responsible for higher mortality in COVID trauma patients.

The coronavirus disease 2019 (COVID-19) stay-at-home order's unequal effects on trauma volume by insurance status in Southern California.

BACKGROUND: The rapid spread of coronavirus disease 2019 in the United States led to a variety of mandates intended to decrease population movement and "flatten the curve." However, there is evidence some are not able to stay-at-home due to certain disadvantages, thus remaining exposed to both coronavirus disease 2019 and trauma. We therefore sought to identify any unequal effects of the California stay-at-home orders between races and insurance statuses in a multicenter study utilizing trauma volume data. METHODS: A posthoc multicenter retrospective analysis of trauma patients presenting to 11 centers in Southern California between the dates of January 1, 2020, and June 30, 2020, and January 1, 2019, and June 30, 2019, was performed. The number of trauma patients of each race/insurance status was tabulated per day. We then calculated the changes in trauma volume related to stay-at-home orders for each race/insurance status and compared the magnitude of these changes using statistical resampling. RESULTS: Compared to baseline, there was a 40.1% drop in total trauma volume, which occurred 20 days after stay-at-home orders. During stay-at-home orders, the average daily trauma volume of patients with Medicaid increased by 13.7 ± 5.3%, whereas the volume of those with Medicare, private insurance, and no insurance decreased. The average daily trauma volume decreased for White, Black, Asian, and Latino patients with the volume of Black and Latino patients dropping to a similar degree compared to White patients. CONCLUSION: This retrospective multicenter study demonstrated that patients with Medicaid had a paradoxical increase in trauma volume during stay-at-home orders, suggesting that the most impoverished groups remain disproportionately exposed to trauma during a pandemic, further exacerbating existing health disparities.

Changes in traumatic mechanisms of injury in Southern California related to COVID-19: Penetrating trauma as a second pandemic.

BACKGROUND: The COVID-19 pandemic resulted in a statewide stay-at-home (SAH) order in California beginning March 19, 2020, forcing large-scale behavioral changes and taking an emotional and economic toll. The effects of SAH orders on the trauma population remain unknown. We hypothesized an increase in rates of penetrating trauma, gunshot wounds, suicide attempts, and domestic violence in the Southern California trauma population after the SAH order. METHODS: A multicenter retrospective analysis of all trauma patients presenting to 11 American College of Surgeons levels I and II trauma centers spanning seven counties in California was performed. Demographic data, injury characteristics, clinical data, and outcomes were collected. Patients were divided into three groups based on injury date: before SAH from January 1, 2020, to March 18, 2020 (PRE), after SAH from March 19, 2020, to June 30, 2020 (POST), and a historical control from March 19, 2019, to June 30, 2019 (CONTROL). POST was compared with both PRE and CONTROL in two separate analyses. RESULTS: Across all periods, 20,448 trauma patients were identified (CONTROL, 7,707; PRE, 6,022; POST, 6,719). POST had a significantly increased rate of penetrating trauma (13.0% vs. 10.3%, p < 0.001 and 13.0% vs. 9.9%, p < 0.001) and gunshot wounds (4.5% vs. 2.4%, p = 0.002 and 4.5% vs. 3.7%, p = 0.025) compared with PRE and CONTROL, respectively. POST had a suicide attempt rate of 1.9% and a domestic violence rate of 0.7%, which were similar to PRE (p = 0.478, p = 0.514) and CONTROL (p = 0.160, p = 0.618). CONCLUSION: This multicenter Southern California study demonstrated an increased rate of penetrating trauma and gunshot wounds after the COVID-19 SAH orders but no difference in attempted suicide or domestic violence rates. These findings may provide useful information regarding resource utilization and a target for societal intervention during the current or future pandemic(s). LEVEL OF EVIDENCE: Epidemiological, level IV.

Reduced cardiac function is associated with cardiac injury and mortality risk in hospitalized COVID-19 Patients.

BACKGROUND: Cardiac injury is common in COVID-19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID-19 patients. HYPOTHESIS: The aim of this study was to assess cardiac function among COVID-19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function. METHODS/RESULTS: This retrospective cohort study analyzed 143 consecutive COVID-19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin-I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin-I elevation, 42% with mild troponin increase (0.04-5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in-hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96). CONCLUSIONS: Reduced cardiac function is highly prevalent among hospitalized COVID-19 patients with biomarkers of myocardial injury and is independently associated with mortality.

Light-dependent pathways for dopaminergic amacrine cell development and function.

Retinal dopamine is a critical modulator of high acuity, light-adapted vision and photoreceptor coupling in the retina. Dopaminergic amacrine cells (DACs) serve as the sole source of retinal dopamine, and dopamine release in the retina follows a circadian rhythm and is modulated by light exposure. However, the retinal circuits through which light influences the development and function of DACs are still unknown. Intrinsically photosensitive retinal ganglion cells (ipRGCs) have emerged as a prime target for influencing retinal dopamine levels because they costratify with DACs in the inner plexiform layer and signal to them in a retrograde manner. Surprisingly, using genetic mouse models lacking specific phototransduction pathways, we find that while light influences the total number of DACs and retinal dopamine levels, this effect does not require ipRGCs. Instead, we find that the rod pathway is a critical modulator of both DAC number and retinal dopamine levels.

Supervised exercise training versus usual care in ambulatory patients with left ventricular assist devices: A systematic review.

Implantation of left ventricular assist devices (LVAD) has increased because of improved safety profile and limited availability of heart transplantation. Although supervised exercise training (ET) programs are known to improve exercise capacity and quality of life (QoL) in heart failure (HF) patients, similar data is inconclusive in LVAD patients. Thus, we performed a systematic review on studies that incorporated supervised ET and measured peak oxygen uptake in LVAD patients. A total of 150 patients in exercise and 55 patients in control groups were included from 8 studies selected from our predefined criteria. Our systematic review suggests supervised ET has an inconsistent effect on exercise capacity and QoL when compared to control groups undergoing usual care. A quantitative sub-analysis was performed with 4 studies that provided enough data to compare peak oxygen uptake and QoL at baseline and at follow-up. After at least 6 weeks of training, LVAD patients undergoing supervised ET demonstrated significant improvement in exercise capacity (standardized mean difference [SMD] = 0.735, 95% Confidence Interval-[CI], 0.31-1.15 units of the standard deviation, P = 0.001) and QoL scores (SMD = 1.58, 95% CI 0.97-2.20 units of the standard deviation, P <0.001) when compared to the usual care group, with no serious adverse events with exercise. These results suggest that supervised ET is safe and can improve patient outcomes in LVAD patients when compared to the usual care.

The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity.

The visual responses of vertebrates are sensitive to the overall composition of retinal interneurons including amacrine cells, which tune the activity of the retinal circuitry. The expression of Paired-homeobox 6 (PAX6) is regulated by multiple cis-DNA elements including the intronic α-enhancer, which is active in GABAergic amacrine cell subsets. Here, we report that the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated α-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1-/- mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective Pax6ΔPBS/ΔPBS mutation. Together, we show the antagonistic regulation of the α-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation.