Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species.

The CCR5-specific antibody Leronlimab is being investigated as a novel immunotherapy that can suppress HIV replication with minimal side effects. Here we studied the virological and immunological consequences of Leronlimab in chronically CCR5-tropic HIV-1 infected humans (n = 5) on suppressive antiretroviral therapy (ART) and in ART-naïve acutely CCR5-tropic SHIV infected rhesus macaques (n = 4). All five human participants transitioned from daily combination ART to self-administered weekly subcutaneous (SC) injections of 350 mg or 700 mg Leronlimab and to date all participants have sustained virologic suppression for over seven years. In all participants, Leronlimab fully occupied CCR5 receptors on peripheral blood CD4+ T cells and monocytes. In ART-naïve rhesus macaques acutely infected with CCR5-tropic SHIV, weekly SC injections of 50 mg/kg Leronlimab fully suppressed plasma viremia in half of the macaques. CCR5 receptor occupancy by Leronlimab occurred concomitant with rebound of CD4+ CCR5+ T-cells in peripheral blood, and full CCR5 receptor occupancy was found in multiple anatomical compartments. Our results demonstrate that weekly, self-administered Leronlimab was safe, well-tolerated, and efficacious for long-term virologic suppression and should be included in the arsenal of safe, easily administered, longer-acting antiretroviral treatments for people living with HIV-1. Trial Registration: ClinicalTrials.gov Identifiers: NCT02175680 and NCT02355184.

Listening Sessions to Shape the Innovative NIH ComPASS Common Fund Program to Advance Health Equity.

The National Institutes of Health (NIH) recognized the need for a research program to address the underlying structural factors that impact health. To inform the development of the NIH Common Fund Community Partnerships to Advance Science for Society (ComPASS) Program, NIH obtained input through community listening sessions. Through its design, ComPASS recognizes the essential role of community organizations as the lead in addressing persistent structural and social challenges to accelerate progress toward advancing health equity. (Am J Public Health. 2024;114(7):685-689. https://doi.org/10.2105/AJPH.2024.307656).

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain. OBJECTIVES: To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10), which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the WHO ICTRP. The date of the most recent search was 10 October 2021. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared iridotomy with no iridotomy in primary angle-closure suspects, people with primary angle-closure, or people with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS: We identified four studies (3086 eyes of 1543 participants) that compared iridotomy with no iridotomy in participants (range of mean age 59.6 to 62.9 years) who were primary angle-closure suspects from China, Singapore, or the UK. Study investigators randomized one eye of each participant to iridotomy and the other to no iridotomy. Two studies provided long-term (five or more years) results. We judged the certainty of the evidence as moderate to low across the prespecified outcomes, downgrading for high risk of bias (e.g. performance and detection biases) and imprecision of results. Meta-analyses of data from two studies suggest that iridotomy probably results in little to no difference in IOP compared with no iridotomy at one year (mean difference (MD) 0.04 mm Hg, 95% confidence interval (CI) -0.17 to 0.24; I2 = 65%; 2598 eyes of 1299 participants; moderate certainty evidence) and five years (MD 0.12 mm Hg, 95% CI -0.11 to 0.35; I2 = 0%; 2016 eyes of 1008 participants), and in best-corrected visual acuity measured as logMAR at one year (MD 0.00, 95% CI -0.01 to 0.01; I2 = 69%; 2596 eyes of 1298 participants; moderate certainty evidence) and five years (MD 0.01, 95% CI -0.01 to 0.03; I2 = 0%; 2002 eyes of 1001 participants). In terms of gonioscopic findings, eyes treated with iridotomy likely had wider angles in Shaffer grading scale (MD 4.93 units, 95% CI 4.73 to 5.12; I2 = 59%; 2598 eyes of 1299 participants at one year; MD 5.07, 95% CI 4.78 to 5.36; I2 = 97%; 2016 eyes of 1008 participants at five years; moderate certainty evidence) and experienced fewer peripheral anterior synechiae (PAS) than eyes that received no iridotomy at five years (risk ratio (RR) 0.41, 95% CI 0.24 to 0.67; I2 = 28%; 2 studies, 2738 eyes of 1369 participants), but the evidence was less conclusive at one year (RR 0.62, 95% CI 0.25 to 1.54; I2 = 57%; 3 studies, 2896 eyes of 1448 participants; low certainty evidence). No studies reported data on the proportion of participants with progressive visual field loss during follow-up (the primary outcome of this review), mean number of medications to control IOP, or quality of life outcomes. Low certainty evidence suggests that iridotomy may result in little to no difference in the incidence of acute angle-closure (RR 0.29, 95% CI 0.07 to 1.20; I2 = 0%; 3 studies, 3006 eyes of 1503 participants). Other ocular adverse events (e.g. eye pain, dry eye, redness of eyes, and ocular discomfort), although rare, were more common in eyes treated with iridotomy than in eyes in the control group.  AUTHORS' CONCLUSIONS: We did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. No study reported on progressive visual field loss, the primary outcome of this review. Although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits.

Assessing bidirectional associations between cognitive impairment and late age-related macular degeneration in the Age-Related Eye Disease Study 2.

INTRODUCTION: We aimed to investigate bidirectional associations between cognitive impairment and late age-related macular degeneration (AMD). METHODS: Participants in the Age-Related Eye Disease Study 2 (AREDS2) received annual eye examinations and cognitive function testing (e.g., Modified Telephone Interview for Cognitive Status [TICS-M]). We examined bidirectional associations between cognitive impairment (e.g., a TICS-M score < 30) and late AMD at 5 and 10 years. RESULTS: Five thousand one hundred eighty-nine eyes (3157 participants; mean age 72.7 years) were analyzed and followed for a median of 10.4 years. Eyes of participants with cognitive impairment at baseline were more likely to progress to late AMD at 5 years (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.08-1.43) and 10 years (HR, 1.20; 95% CI, 1.05-1.37) than eyes of participants without cognitive impairment. Worse baseline AMD severity was not associated with developing cognitive impairment. DISCUSSION: Cognitive impairment is associated with late AMD progression in AREDS2. Our finding highlights the importance of eyecare for people with cognitive impairment.

Photosensitizer delivery by fibrin glue: potential for bypassing the blood-brain barrier.

Fibrin glue (FG) has potential as a delivery vehicle for photosensitizer directly to the resection cavity, so it may bypass the blood-brain barrier (BBB) and increase the concentration of successfully delivered photosensitizer. A specialized form of photodynamic therapy (PDT), photochemical internalization (PCI), which involves both photosensitizer and chemotherapeutic agent internalization, can locally inhibit the growth of cells. This will allow the reduction of recurrence of malignant gliomas around surgical resection. This study will look at the efficacy of FG loaded with drugs in mediating both PDT and PCI in inhibiting 3-dimensional tumor spheroid growth in vitro. Experiments were conducted on spheroids comprised of F98 glioma cells using photosensitizer AlPcS2a and chemotherapeutic drug bleomycin (BLM). At 2-, 24-, 48-, and 72-h increments, supernatant covering an FG layer within a well was collected and replaced by fresh medium, then added to spheroid-containing wells, which contained the respective chemicals for PDT and PCI. The wells were then exposed to light treatment from a diode laser, and after, spheroid growth was monitored for a period of 14 days. Significant spheroid growth inhibition was observed in both PDT and PCI modalities, but was far greater in PCI. Additionally, complete growth suppression was achieved via PCI at the highest radiant exposure. Achieving a slow photosensitizer release, significant F98 spheroid inhibition was observed in FG-mediated PDT and PCI. The present study showed BLM-PCI was the most efficacious of the two modalities.

Tea tree oil for Demodex blepharitis.

BACKGROUND: Demodex blepharitis is a chronic condition commonly associated with recalcitrant dry eye symptoms though many people with Demodex mites are asymptomatic. The primary cause of this condition in humans is two types of Demodex mites: Demodex folliculorum and Demodex brevis. There are varying reports of the prevalence of Demodex blepharitis among adults, and it affects both men and women equally. While Demodex mites are commonly treated with tea tree oil, the effectiveness of tea tree oil for treating Demodex blepharitis is not well documented. OBJECTIVES: To evaluate the effects of tea tree oil on ocular Demodex infestation in people with Demodex blepharitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 6); Ovid MEDLINE; Embase.com; PubMed; LILACS; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no date or language restrictions in the electronic search for trials. We last searched the databases on 18 June 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared treatment with tea tree oil (or its components) versus another treatment or no treatment for people with Demodex blepharitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts and then full text of records to determine their eligibility. The review authors independently extracted data and assessed risk of bias using Covidence. A third review author resolved any conflicts at all stages. MAIN RESULTS: We included six RCTs (1124 eyes of 562 participants; 17 to 281 participants per study) from the US, Korea, China, Australia, Ireland, and Turkey. The RCTs compared some formulation of tea tree oil to another treatment or no treatment. Included participants were both men and women, ranging from 39 to 55 years of age. All RCTs were assessed at unclear or high risk of bias in one or more domains. We also identified two RCTs that are ongoing or awaiting publications. Data from three RCTs that reported a short-term mean change in the number of Demodex mites per eight eyelashes contributed to a meta-analysis. We are uncertain about the mean reduction for the groups that received the tea tree oil intervention (mean difference [MD] 0.70, 95% confidence interval [CI] 0.24 to 1.16) at four to six weeks as compared to other interventions. Only one RCT reported data for long-term changes, which found that the group that received intense pulse light as the treatment had complete eradication of Demodex mites at three months. We graded the certainty of the evidence for this outcome as very low. Three RCTs reported no evidence of a difference for participant reported symptoms measured on the Ocular Surface Disease Index (OSDI) between the tea tree oil group and the group receiving other forms of intervention. Mean differences in these studies ranged from -10.54 (95% CI - 24.19, 3.11) to 3.40 (95% CI -0.70 7.50). We did not conduct a meta-analysis for this outcome given substantial statistical heterogeneity and graded the certainty of the evidence as low. One RCT provided information concerning visual acuity but did not provide sufficient data for between-group comparisons. The authors noted that mean habitual LogMAR visual acuity for all study participants improved post-treatment (mean LogMAR 1.16, standard deviation 0.26 at 4 weeks). We graded the certainty of evidence for this outcome as low. No RCTs provided data on mean change in number of cylindrical dandruff or the proportion of participants experiencing conjunctival injection or experiencing meibomian gland dysfunction. Three RCTs provided information on adverse events. One reported no adverse events. The other two described a total of six participants randomized to treatment with tea tree oil who experienced ocular irritation or discomfort that resolved with re-educating the patient on application techniques and continuing use of the tea tree oil. We graded the certainty of the evidence for this outcome as very low. AUTHORS' CONCLUSIONS: The current review suggests that there is uncertainty related to the effectiveness of 5% to 50% tea tree oil for the short-term treatment of Demodex blepharitis; however, if used, lower concentrations may be preferable in the eye care arena to avoid induced ocular irritation. Future studies should be better controlled, assess outcomes at long term (e.g. 10 to 12 weeks or beyond), account for patient compliance, and study the effects of different tea tree oil concentrations.

Development, implementation and evaluation of an online course on evidence-based healthcare for consumers.

BACKGROUND: Evidence-based healthcare (EBHC) principles are essential knowledge for patient and consumer ("consumer") engagement as research and research implementation stakeholders. The aim of this study was to assess whether participation in a free, self-paced online course affects confidence in explaining EBHC topics. The course comprises six modules and evaluations which together take about 6 h to complete. METHODS: Consumers United for Evidence-based Healthcare (CUE) designed, tested and implemented a free, online course for consumers, Understanding Evidence-based Healthcare: A Foundation for Action ("Understanding EBHC"). The course is offered through the Johns Hopkins Bloomberg School of Public Health. Participants rated their confidence in explaining EBHC topics on a scale of 1 (lowest) to 5 (highest), using an online evaluation provided before accessing the course ("Before") and after ("After") completing all six course modules. We analyzed data from those who registered for the course from May 31, 2007 to December 31, 2018 (n = 15,606), and among those persons, the 11,522 who completed the "Before" evaluation and 4899 who completed the "After" evaluation. Our primary outcome was the overall mean of within-person change ("overall mean change") in self-reported confidence levels on EBHC-related topics between "Before" and "After" evaluations among course completers. Our secondary outcomes were the mean within-person change for each of the 11 topics (mean change by topic). RESULTS: From May 31, 2007 to December 31, 2018, 15,606 individuals registered for the course: 11,522 completed the "Before" evaluation, and 4899 of these completed the "After" evaluation (i.e., completed the course). The overall mean change in self-reported confidence levels (ranging from 1 to 5) from the "Before" to "After" evaluation was 1.27 (95% CI, 1.24-1.30). The mean change by topic ranged from 1.00 (95% CI, 0.96-1.03) to 1.90 (95% CI, 1.87-1.94). CONCLUSION: Those who seek to involve consumer stakeholders can offer Understanding EBHC as a step toward meaningful consumer engagement. Future research should focus on long-term impact assessment of online course such as ours to understand whether confidence is retained post-course and applied appropriately.

Gender and Editorial Authorship in High-Impact Epidemiology Journals.

Women comprise about half of senior epidemiologists, but little is known about whether they are also viewed as leaders (i.e., authorities) in the field. We believe editorial roles are markers of leadership in a field. Our objective was to describe the distribution of gender across authorship of editorials published in 5 high-impact epidemiology journals over the past 8 years. We included editorials and commentaries published in American Journal of Epidemiology, European Journal of Epidemiology, Epidemiology, International Journal of Epidemiology, and Journal of Clinical Epidemiology between 2010 and 2017. We classified genders of all authors as woman, man, or unknown and computed the proportions of women editorial authors over all journals and according to position (e.g., first author). Only 31% (682/2,228) of all editorial authors and 36% (524/1,477) of unique editorial authors (i.e., counting each editorial author name only once) were women. We identified 1,180 editorials; 594 had sole authors, 24% (141/594) of whom were women, and 586 had 2 or more authors, 31% (184/586) of which had women as first authors. If women are underrepresented as editorial authors across epidemiology journals (e.g., as a marker of epidemiology leadership), the situation merits immediate correction.

Ab interno trabecular bypass surgery with iStent for open-angle glaucoma.

BACKGROUND: Glaucoma is a leading cause of irreversible blindness worldwide. In early stages, glaucoma results in progressive loss of peripheral (side) vision; in later stages, it results in loss of central vision leading to blindness. Elevated intraocular pressure (IOP) is the only known modifiable risk factor for glaucoma. Minimally invasive glaucoma surgical (MIGS) techniques, such as ab interno trabecular bypass surgery with iStent (Glaukos Corporation, Laguna Hills, CA, USA), have been introduced as a new treatment modality for glaucoma. However, the effectiveness of MIGS on keeping people 'drop-free' (i.e. not having to use eye drops to control IOP) and other outcomes is uncertain. OBJECTIVES: To assess the effectiveness and safety of ab interno trabecular bypass surgery with iStent (or iStent inject) for open-angle glaucoma in comparison to conventional medical, laser, or surgical treatment. SEARCH METHODS: Cochrane Eyes and Vision's Information Specialist searched the following databases on 17 August 2018: the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register; 2018, Issue 7), MEDLINE Ovid, Embase Ovid, the ISRCTN registry, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We applied no date or language restrictions. We searched the reference lists of reports from included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that had compared iStent or iStent inject to medical therapy, laser treatment, conventional glaucoma surgery (trabeculectomy), or other MIGS procedures. We included RCTs that had compared iStent or iStent inject in combination with phacoemulsification to phacoemulsification alone. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened search results, assessed risk of bias, and extracted data from reports of included RCTs using an electronic data collection form. MAIN RESULTS: We included seven RCTs (765 eyes of 764 participants; range per study 33 to 239 participants) that evaluated iStent in people with open-angle glaucoma. We also identified 13 studies that are ongoing or awaiting publications of results. Most participants in the included studies were women (417/764 (55%) participants) and older age (age range: 49 to 89 years). We assessed most trials at unclear or high risk of bias: four trials did not clearly report the method of generating the random sequence or concealing allocation; five were unmasked, open-label studies, which we assessed at high risk of bias for performance and detection bias. All seven trials were funded by the Glaukos Corporation. We graded the certainty of evidence as very low.Four RCTs compared iStent in combination with phacoemulsification to phacoemulsification alone. The summary estimate which we derived from two of the four RCTs suggested that participants in the iStent in combination with phacoemulsification group were 1.38 times more likely to be drop-free between six and 18 months than those in the phacoemulsification alone group (risk ratio (RR) 1.38, 95% confidence interval (CI) 1.18 to 1.63, I2 = 67%). Data from two RCTs also suggested that iStent in combination with phacoemulsification compared to phacoemulsification alone may have offered a small reduction in number of IOP-lowering drops (mean difference (MD) -0.42 drops, 95% CI -0.60 to -0.23). It is uncertain whether there was any difference in terms of mean reduction in IOP from baseline (no meta-analysis).Two RCTs compared treatment with iStent to medical therapy; one of the two trials used the iStent inject. We determined the two trials to be clinically and methodologically heterogeneous and did not conduct a meta-analysis; however, the investigators of both trials reported that over 90% of participants in the treatment groups were drop-free compared to no participants in the medical therapy groups at six to 18 months.One RCT compared treatment with one versus two versus three iStents. There was no difference in terms of participants who were drop-free at 36 months or less; however, at longer follow-up (i.e. at 42 months) participants in the one iStent treatment were less likely to be drop-free than those in the two iStent (RR 0.51, 95% CI 0.34 to 0.75) or three iStent (RR 0.49, 95% CI 0.34 to 0.73) treatment groups. The study did not report the mean change in number of IOP-lowering drops.The type and timing of complications reported varied by RCTs. Similar proportions of participants who underwent treatment with iStent in combination with phacoemulsification and who underwent phacoemulsification alone needed secondary glaucoma surgery. None of RCTs reported findings related to quality of life. AUTHORS' CONCLUSIONS: There is very low-quality evidence that treatment with iStent may result in higher proportions of participants who are drop-free or achieving better IOP control, in the short, medium, or long-term. Results from the 13 studies with results not yet available may clarify the benefits of treatment of people with iStent. Additionally, future MIGS studies should consider measuring quality of life and outcomes that reflect people's ability to perform vision-dependent activities.

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy (often just called 'iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber through use of a laser to create a hole in the iris. It is commonly used to treat patients with primary angle-closure glaucoma, patients with primary angle closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). The effectiveness of iridotomy on slowing progression of visual field loss, however, is uncertain. OBJECTIVES: To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle closure, and primary angle-closure suspects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 9) which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the ICTRP. The date of the search was 18 October 2017. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared iridotomy to no iridotomy in primary angle-closure suspects, patients with primary angle closure, or patients with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS: Two authors worked independently to extract data on study characteristics, outcomes for the review, and risk of bias in the included studies. We resolved differences through discussion. MAIN RESULTS: We identified two trials (2502 eyes of 1251 participants) that compared iridotomy to no iridotomy. Both trials recruited primary angle suspects from Asia and randomized one eye of each participant to iridotomy and the other to no iridotomy. Because the full trial reports are not yet available for both trials, no data are available to assess the effectiveness of iridotomy on slowing progression of visual field loss, change in IOP, need for additional surgeries, number of medications needed to control IOP, mean change in best-corrected visual acuity, and quality of life. Based on currently reported data, one trial showed evidence that iridotomy increases angle width at 18 months (by 12.70°, 95% confidence interval (CI) 12.06° to 13.34°, involving 1550 eyes, moderate-certainty evidence) and may be associated with IOP spikes at one hour after treatment (risk ratio 24.00 (95% CI 7.60 to 75.83), involving 1468 eyes, low-certainty evidence). The risk of bias of the two studies was overall unclear due to lack of availability of a full trial report. AUTHORS' CONCLUSIONS: The available studies that directly compared iridotomy to no iridotomy have not yet published full trial reports. At present, we cannot draw reliable conclusions based on randomized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy. Full publication of the results from the studies may clarify the benefits of iridotomy.

Pre-kidney transplant lower extremity impairment and transplant length of stay: a time-to-discharge analysis of a prospective cohort study.

BACKGROUND: Few objective tests can be performed at admission for kidney transplantation [KT] to discern risk of increased length of stay [LOS], which is important for patient counseling and is associated with increased costs and mortality. The short physical performance battery [SPPB] is an easily administered, potentially modifiable, 3-part test of lower extremity function. SPPB score is associated with longer hospital LOS in older adults, and may provide similar utility in KT recipients given that ESRD is a disease of accelerated aging. The aim of this study was to characterize the association between SPPB-derived lower extremity function and LOS. METHODS: The SPPB was administered at KT admission in a prospective cohort of 595 recipients (8/2009-6/2016). The independent association between SPPB impairment (score ≤ 10) and LOS was tested with an adjusted conventional generalized gamma parametric survival model. RESULTS: Impaired recipients experienced longer LOS (median: 10 vs. 8 days; P <  0.001) with the greatest difference in percent discharged on day 10 (impaired: 54.5%, unimpaired: 73.3%). Discharge typically took 13% longer in the impaired group (relative time = 1.13; 95%CI: 1.05, 1.21, P = 0.001). Discharge for impaired recipients compared to unimpaired was least likely at day 5 (hazard ratio = 0.71; 95% CI:0.68, 0.74, P <  0.001). No differences in the SPPB impairment-LOS relationship were found by age (interaction P = 0.74). CONCLUSIONS: Pre-KT SPPB impairment was independently associated with longer LOS regardless of age, indicating that it is a useful, objective tool for pre-KT risk assessment in younger and older recipients that may help inform discharge planning.

Iridotomy to slow progression of angle-closure glaucoma.

This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective is to assess the role of iridotomy-compared with observation-in the prevention of visual field loss for individuals who have primary angle closure or primary angle-closure glaucoma in at least one eye. We will also examine the role of iridotomy in the prevention of elevated intraocular pressure (IOP) in individuals with narrow angles (primary angle-closure suspect) in at least one eye.

Implementation and early outcomes with Pathogen Reduced Cryoprecipitated Fibrinogen Complex.

OBJECTIVES: Cryoprecipitated antihemophilic factor (cryo) has been used for fibrinogen replacement in actively bleeding patients, dysfibrinogenemia, and hypofibrinogenemia. Cryo has a shelf life of 4 to 6 hours after thawing and a long turnaround time in issuing the product, posing a major limitation of its use. Recently, the US Food and Drug Administration approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex [IFC]) for the treatment of bleeding associated with fibrinogen deficiency, which can be stored at room temperature and has a shelf life of 5 days after thawing. METHODS: We identified locations and specific end users with high cryoprecipitate utilization and waste. We partnered with our blood supplier to use IFC in these locations. We analyzed waste and turnaround time before and after implementation. RESULTS: Operative locations had a waste rate that exceeded nonoperative locations (16.7% vs 3%) and were targeted for IFC implementation. IFC was added to our inventory to replace all cryo orders from adult operating rooms, and waste decreased to 2.2% in these locations. Overall waste of cryoprecipitated products across all locations was reduced from 8.8% to 2.4%. The turnaround time for cryoprecipitated products was reduced by 58% from 30.4 minutes to 14.6 minutes. CONCLUSIONS: There has been a substantial decrease in waste with improved turnaround time after IFC implementation. This has improved blood bank logistics, improved efficiency of patient care, and reduced costly waste.

Analysis of neuronal injury transcriptional response identifies CTCF and YY1 as co-operating factors regulating axon regeneration.

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons in vivo and that all neuronal subtypes are represented. This eDRG neuronal culture does not contain other non-neuronal cell types. Next, we performed RNA sequencing at different time points after in vitro axotomy. Analysis of differentially expressed genes revealed upregulation of known regeneration associated transcription factors, including Jun, Atf3 and Rest, paralleling the axon injury response in vivo. Analysis of transcription factor binding sites in differentially expressed genes revealed other known transcription factors promoting axon regeneration, such as Myc, Hif1α, Pparγ, Ascl1a, Srf, and Ctcf, as well as other transcription factors not yet characterized in axon regeneration. We next tested if overexpression of novel candidate transcription factors alone or in combination promotes axon regeneration in vitro. Our results demonstrate that expression of Ctcf with Yy1 or E2f2 enhances in vitro axon regeneration. Our analysis highlights that transcription factor interaction and chromatin architecture play important roles as a regulator of axon regeneration.

Minimally Invasive Glaucoma Surgical Techniques for Open-Angle Glaucoma: An Overview of Cochrane Systematic Reviews and Network Meta-analysis.

IMPORTANCE: Glaucoma affects more than 75 million people worldwide. Intraocular pressure (IOP)-lowering surgery is an important treatment for this disease. Interest in reducing surgical morbidity has led to the introduction of minimally invasive glaucoma surgeries (MIGS). Understanding the comparative effectiveness and safety of MIGS is necessary for clinicians and patients. OBJECTIVE: To summarize data from randomized clinical trials of MIGS for open-angle glaucoma, which were evaluated in a suite of Cochrane reviews. DATA SOURCES: The Cochrane Database of Systematic Reviews including studies published before June 1, 2021. STUDY SELECTION: Reviews of randomized clinical trials comparing MIGS with cataract extraction alone, other MIGS, traditional glaucoma surgery, laser trabeculoplasty, or medical therapy. DATA EXTRACTION AND SYNTHESIS: Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines by one investigator and confirmed by a second. Methodologic rigor was assessed using the AMSTAR 2 appraisal tool and random-effects network meta-analyses were conducted. MAIN OUTCOMES AND MEASURES: The proportion of participants who did not need to use medication to reduce intraocular pressure (IOP) postsurgery (drop-free). Outcomes were analyzed at short-term (<6 months), medium-term (6-18 months), and long-term (>18 months) follow-up. RESULTS: Six eligible Cochrane reviews were identified discussing trabecular bypass with iStent or Hydrus microstents, ab interno trabeculotomy with Trabectome, subconjunctival and supraciliary drainage devices, and endoscopic cyclophotocoagulation. Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained. Addition of a CyPass microstent improved drop-free glaucoma control compared with cataract surgery alone (RR, 1.3; 95% CI, 1.1 to 1.5) but was associated with an increased risk of vraision loss. Network meta-analyses supported the direction and magnitude of these results. CONCLUSIONS AND RELEVANCE: Based on data synthesized in Cochrane reviews, some MIGS may afford patients with glaucoma greater drop-free disease control than cataract surgery alone. Among the products currently available, randomized clinical trial data associate the Hydrus with greater drop-free glaucoma control and IOP lowering than the iStent; however, these effect sizes were small.