Allogeneic Ocular Surface Stem Cell Transplantation Outcomes With Decreased or No Systemic Immunosuppression in the Elderly.

PURPOSE: The aim of this study was to report outcomes after allogeneic ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency in the setting of decreased or no systemic immunosuppression (SI) in the elderly. METHODS: A retrospective chart review was performed of all eyes that underwent OSST for limbal stem cell deficiency between 2005 and 2020 at CVP Physicians. Inclusion criteria included patients who were (1) at least 70 years at the time of (2) allogeneic OSST. Postoperative SI regimens were assessed. Outcome measures included improvement in visual acuity, ocular surface stability, and adverse effects. RESULTS: There were 14 eyes of 14 patients that met the inclusion criteria with mean follow-up of 3.0 (range 0.4-7.0) years. SI was run at a lower level for 6 patients, and 8 patients did not receive any SI. Nine eyes underwent keratolimbal allograft, 1 had a living-related conjunctival limbal allograft, and 4 had combined OSST. Most eyes (85.7%) attained improvement in visual acuity during their follow-up. At the last follow-up, 57.1% maintained a stable ocular surface. Six eyes developed acute rejection or late failure. Minimal adverse events were noted. CONCLUSIONS: Elderly patients administered less or no SI exhibit overall favorable outcomes after allogeneic OSST. Although not significantly different, surface stability and duration of improved vision was greater with low SI. No SI may be an option that still achieves improved vision in a high proportion for at least part of their follow-up. Decreasing SI after OSST in this population can improve quality of life while minimizing adverse effects.

Presence of Panel-reactive Antibodies after Penetrating Keratoplasty.

PURPOSE: To evaluate the relationship between penetrating keratoplasty (PK) and postoperative PRA level and number of unacceptable antigens. METHODS: A cross-sectionalstudy was performed on patients with history of PK. Patients with prior solid organ transplantation, pregnancy, or blood transfusion were excluded. These findings were combined with a retrospective review. Patients were grouped by single or multiple PKs. The primary outcome was postoperative PRA level. RESULTS: Incidence of postoperative PRA elevation and mean peak PRA was higher in the multiple PK group (p = .08 and p = .010, respectively). Mean number of unacceptable antigens was elevated in the multiple PK group (p = .024). There was a moderately positive correlation between number of PK grafts and PRA level (r = 0.629, p = .0002). CONCLUSIONS: PRA level may be influenced by PKs, with higher PRA associated with increased prior PKs. Further studies are necessary to determine the potential prognostic value.Abbreviations: PK: penetrating keratoplasty; PRA: panel reactive antibodies; OSST: ocular surface stem cell transplantation; LSCD: limbal stem cell deficiency.

Comparison of Persistent Epithelial Defect Treatment With Sutureless Cryopreserved and Dehydrated Amniotic Membrane.

PURPOSE: To compare cryopreserved sutureless amniotic membrane (C-SAM) and dehydrated SAM (D-SAM) outpatient treatment outcomes for persistent epithelial defects (PEDs), analyze risk factors for treatment failure, and identify adverse events. DESIGN: Retrospective, interventional comparative clinical study. METHODS: This study was a multicenter retrospective interventional cohort from 2 tertiary corneal referral practices from 2016 to 2020. The inclusion criteria were as follows: (1) PEDs treated (2) outpatient with (3) either C-SAM or D-SAM. PEDs were defined as epithelial defects present for ≥7 days after failing prior conservative therapy. The primary outcome measure was the resolution or improvement of a PED. The secondary outcomes included analysis of treatment failures and identification of adverse events. A total of 220 PEDs from 204 eyes (197 patients) treated with either C-SAM or D-SAM met the inclusion criteria. RESULTS: A total of 100 PEDs (45.5%) resolved after single amniotic membrane administration, 46.5% (59 of 127) in the C-SAM group and 44.1% (41 of 93) in the D-SAM group (P = .727). Forty-nine PEDs neither improved nor resolved without a significant difference between the C-SAM (21.3%) and D-SAM groups (23.7%, P = .673). There was no statistically significant difference for PED resolution, PED improvement, PEDs that did not resolve/improve, or those requiring surgery between the 2 groups for initial SAM. CONCLUSIONS: C-SAM and D-SAM were both effective for treating PEDs with comparable outcomes for resolution, improvement, and need for additional surgical intervention. Specific differences in adverse events may help dictate clinical use. Inflammatory disease was a risk factor for nonresolution of all PEDs.

The Scientific Method as a Scaffold to Enhance Communication Skills in Chemistry.

Scientific success in the field of chemistry depends upon the mastery of a wide range of soft skills, most notably scientific writing and speaking. However, training for scientific communication is typically limited at the undergraduate level, where students struggle to express themselves in a clear and logical manner. The underlying issue is deeper than basic technical skills; rather, it is a problem of students' unawareness of a fundamental and strategic framework for writing and speaking with a purpose. The methodology has been implemented for individual mentorship and in our regional summer research program to deliver a blueprint of thought and reasoning that endows students with the confidence and skills to become more effective communicators. Our didactic process intertwines undergraduate research with the scientific method and is partitioned into six steps, referred to as "phases", to allow for focused and deep thinking on the essential components of the scientific method. The phases are designed to challenge the student in their zone of proximal development so they learn to extract and ultimately comprehend the elements of the scientific method through focused written and oral assignments. Students then compile their newly acquired knowledge to create a compelling and logical story, using their persuasive written and oral presentations to complete a research proposal, final report, and formal 20 min presentation. We find that such an approach delivers the necessary guidance to promote the logical framework that improves writing and speaking skills. Over the past decade, we have witnessed both qualitative and quantitative gains in the students' confidence in their abilities and skills (developed by this process), preparing them for future careers as young scientists.

South Texas orbital fracture protocol for emergency department evaluation of orbital fractures.

PURPOSE: Facial trauma and orbital fractures are common reasons for ophthalmology consultation in the emergency department (ED). The purpose of this study is to assess intervention rates and evaluate the acuity of ophthalmology consultation for orbital fractures in the ED. BASIC PROCEDURES: A retrospective chart review of orbital fractures was conducted over a 23-month period. 379 cases of orbital fractures were identified in a single-center study. All patients that received an ophthalmology consultation in the ED were included. Demographics, mechanism and location of orbital fracture, ophthalmic complications, and surgical and non-surgical ophthalmic interventions were recorded. The primary study outcome was the rate of ophthalmic consultation and intervention with and without retrospective application of our proposed South Texas Orbital Fracture Protocol (STOP). RESULTS: Immediate ophthalmic intervention was performed in 18.7% of patients. Statistically significant subjective, radiographic, and physical exam features correlating with ophthalmic intervention were identified and included globe rupture, concern for entrapment, orbital roof fractures, and retrobulbar hematoma. Retrospective application of our proposed South Texas Orbital Fracture Protocol (STOP) would have resulted in 186 of 379 patients requiring ophthalmology consultation, thus reducing consultation rate by 51% with an improved rate of intervention from 18.7% to 37.6%. CONCLUSIONS: Orbital fractures can be associated with severe ocular complications. Most cases, however, do not require emergent evaluation by an ophthalmologist. We propose the South Texas Orbital Fracture Protocol (STOP) for proper assessment and triaging of orbital fractures in the ED. While this clinical decision-making tool requires validation, it may offer improved healthcare efficiency, reduced costs, fewer unnecessary inter-facility transfers, and less burnout for ophthalmology residents.

The Effect of a Novel Platysma Hammock Flap During Extended Deep Plane Facelift on the Signs of Aging in the Neck.

BACKGROUND: Aging changes in the neck, including platysma banding (PB), skin laxity (SL), and submandibular gland visibility (SGV), have a high degree of recurrence after rhytidectomy. OBJECTIVES: The authors sought to assess the long-term improvement in PB, SL, and SGV with addition of aplatysmal hammock flap to the extended deep-plane facelift and assess patient satisfaction. METHODS: This was a prospective study of 123 consecutive patients undergoing extended deep-plane facelift incorporating platysma hammock flap with or without midline platysmaplasty. Standard 2-dimensional patient photographs were employed to assess PB, SL, and SGV preoperative and >12 months postoperative. A 1-year postoperative patient satisfaction survey was conducted. RESULTS: The platysmal hammock flap without midline platysmaplasty cohort had a significant (P < 0.01) reduction in mean preoperative PB, SL, and SGV scores from 1.03, 1.88, and 1.21 to 0.06, 0.03, and 0.15 at 21 months. The platysmal hammock flap with midline platysmaplasty cohort had a significant (P < 0.01) reduction in preoperative PB, SL, and SGV scores from 1.81, 2.43, and 1.81 to 0.10, 0.15, and 0.48 at 18 months. The platysmal hammock flap with and without midline platysmaplasty cohorts had 96.2% and 88.9% satisfaction, respectively. CONCLUSIONS: Extended deep-plane facelift with a platysmal hammock flap achieves long-term, sustained improvements in PB, SL, and SGV; is well-tolerated; and results in substantial patient satisfaction.

Association between mortality and frailty in emergency general surgery: a systematic review and meta-analysis.

PURPOSE: The purpose of this review was to determine the association between frailty and mortality among adults ≥ 65 years old undergoing emergency general surgery (EGS). METHODS: This systematic review followed the PRISMA guidelines (CRD42020172482 on PROSPERO). A search in MEDLINE, PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews was conducted from inception to March 5, 2020. Studies with patients ≥ 65 years undergoing EGS were included. The primary exposure was frailty, measured using the Clinical Frailty Scale or the Modified Frailty Index. The primary outcome was 30-day mortality. Secondary outcomes were 90-day and 1-year mortality, length of stay, complications, change in level of care at discharge, and loss of independence. Two independent reviewers screened articles and extracted data. Risk of bias was assessed according to the Newcastle-Ottawa Scale and quality of evidence was assessed using the GRADE approach. A meta-analysis was performed for 30-day mortality using a random-effects model. RESULTS: Our search yielded 847 articles and six cohort studies were included in the systematic review. There were 1289 patients, 283 being frail. The pooled OR from meta-analysis for frail compared to non-frail patients was 2.91 (95% CI 2.00, 4.23) for 30-day mortality. Frailty was associated with increased odds of all secondary outcomes. CONCLUSION: Frailty is significantly associated with worse outcomes after emergency general surgery in adults ≥ 65 years of age. The Clinical Frailty Scale could be used to improve preoperative risk assessment for patients and shared decision-making between patients and healthcare providers. REGISTRATION NUMBER: CRD42020172482 (PROSPERO).

Use of Panel-Reactive Antibody Testing in the Planning and Management of Ocular Surface Stem Cell Transplantation.

PURPOSE: Panel-reactive antibody (PRA) testing has been widely adopted in solid organ transplantation for risk assessment in potential allograft recipients but has not been studied in the context of ophthalmic transplantation. The purpose of this study is to evaluate outcomes in patients undergoing ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) relative to preoperative PRA level. METHODS: This is retrospective chart review of all eyes with documented PRA level that underwent OSST for LSCD between May 2000 and March 2019 at a single institution. Eyes with stable ocular surface but <1 year of follow-up and eyes without updated PRA before repeat OSST were excluded. Eyes were grouped by PRA <80% and ≥80%. The primary outcome was ocular surface failure, whereas the secondary outcome was clinical allograft rejection. RESULTS: Sixty-nine surgeries met inclusion criteria, consisting of 54 living-related conjunctival limbal allografts, 5 keratolimbal allografts, and 10 combined living-related conjunctival limbal allografts/keratolimbal allografts (Cincinnati procedure). The most common etiologies for LSCD were aniridia (33%), chemical/thermal injury (28%), and contact lens associated (14%). Surface failure occurred in 5 of 12 eyes (58%) with PRA ≥80% versus 12 of 57 eyes (21%) with PRA <80% (P = 0.01). The relative risk for surface failure with PRA ≥80% was 2.8 [confidence interval (CI), 1.38-5.55]. There was no significant difference in acute rejection (P = 1). CONCLUSIONS: Pretransplant PRA level is an important prognostic factor for ocular surface stability in eyes undergoing OSST for LSCD, with implications for donor selection, perioperative management, and systemic immunosuppression.

Lactulose drives a reversible reduction and qualitative modulation of the faecal microbiota diversity in healthy dogs.

Hepatic encephalopathy is a frequent and debilitating complication of liver disorders. Lactulose is an established and reasonably effective treatment, yet with incompletely understood mechanisms of action. The aims of this study were to examine how the faecal microbiota composition changed before, during and after lactulose treatment in a large animal model. Healthy, privately owned dogs (n = 18) completed a prospective cohort study. Faecal samples were collected weekly, while the subjects were either on their usual diet (week 1), or a standardised diet (weeks 2-9), with added oral lactulose in weeks 6-7. DNA extraction and 16S rRNA gene sequencing were undertaken. Faecal samples from week 7 had a significantly lower microbiota richness/diversity, based on observed operational taxonomic units, Shannon/Chao1 indexes and Pielou's Evenness. Beta diversity based on UniFrac distances was significantly different in week 7 compared to weeks 1, 5 and 9. At the phylum level, week 7 was associated with a significant increase of Firmicutes and Actinobacteria, and a decrease of Bacteroidetes and Fusobacteria, when compared to weeks 5 and 9. In summary, we have shown that lactulose induces a reversible qualitative and quantitative change of the faecal microbiota, which may explain its clinical efficacy in the management of hepatic encephalopathy.

Repressed Wnt Signaling Accelerates the Aging Process in Mouse Eyes.

PURPOSE: Ocular aging is a natural process of functional decline in vision. When the process reaches a point that compromised vision affects normal daily activity, it manifests as age-related ocular diseases, such as age-related macular degeneration, cataracts, glaucoma, and pseudoexfoliation syndrome. We previously reported that repressed Wnt signaling accelerated the maturation of corneal epithelium during tissue development. Here, we explore the hypothesis that repressed Wnt signaling is associated with accelerated aging in mouse eyes. METHODS: Wnt ligand antagonist secreted frizzled-related protein 1 (sFRP1) was expressed in the corneal stroma by a tissue-specific, inducible, bitransgenic system. Tissue structure was analyzed for signs of aging. Signal transduction analysis was performed to determine the cellular response to sFRP1. RESULTS: Mouse eyes with sFRP1 expression showed signs of accelerated aging, resembling those found in pseudoexfoliation (PEX) syndrome, a known age-related disease. Specific findings include granular deposition on the surface of the anterior lens capsule, pigment loss from the anterior surface of the iris, the presence of fibrillary material in the anterior chamber, and changes in cell size (polymegethism) and shape (pleomorphism) of the corneal endothelial cells. In vitro studies demonstrated that sFRP1 did not inhibit Wnt5a function and that cells responded to sFRP1 and Wnt5a in a very similar manner. CONCLUSION: The expression of sFRP1 accelerates the aging process in mouse eyes and future studies are warranted to elucidate the underlying mechanisms.

Critical illness-related corticosteroid insufficiency in cancer patients.

PURPOSE: Critically ill cancer patients with sepsis represent a high-risk sub-group for the development of critical illness-related corticosteroid insufficiency (CIRCI); however, the incidence of CIRCI in this population is unknown. The purpose of this study was to determine the incidence of CIRCI in cancer patients with severe sepsis or septic shock. METHODS: A single-center, retrospective, observational study was conducted in a 52-bed medical-surgical intensive care unit of a National Cancer Institute-recognized academic oncology institution. Eighty-six consecutive patients with a diagnosis of severe sepsis or septic shock who received a high-dose 250-µg cosyntropin stimulation test were included. CIRCI was identified by a maximum delta serum cortisol of 9 µg/dL or less post cosyntropin. RESULTS: Overall, 59% (95% CI, 48-70%) of cancer patients with severe sepsis or septic shock were determined to have CIRCI. When compared to patients without CIRCI, patients with CIRCI had higher baseline serum cortisol (median, 26.3 versus 14.7 µg/dL; p = 0.002) and lower delta cortisol levels (median, 3.1 versus 12.5 µg/dL; p < 0.001). Mortality did not differ between the two groups. An inverse relationship was identified between baseline serum cortisol and maximum delta cortisol (maximum delta cortisol = -0.27 × baseline cortisol + 14.30; R (2) = 0.208, p < 0.001). CONCLUSIONS: The incidence of CIRCI in cancer patients with severe sepsis or septic shock appears high. Further large-scale prospective trials are needed to confirm these findings.

Closing the divide: diverse populations and cancer survivorship.

Currently, there is a "divide" between cancer survivorship initiatives and minority participation. The level of participation is nearly nonexistent in many cancer support and control initiatives. Cancer survivorship resources that facilitate access to treatment, psychosocial interventions, clinical trials, and research are key components to eliminating this divide. Differences in cancer results among minority populations are caused by several factors, including biologic reactions to environmental activities, socioeconomic status, perceived beliefs and notions of medical professionals, a lack of resources to participate in cancer support groups, and having personal contact with cancer survivors. Health professionals, advocates, and researchers hold the key to opening more opportunities for the improvement of cancer survivorship among minorities. The belief that "one size fits all" is unrealistic. These beliefs can influence participation in innovative clinical trials, decisions about treatment, emotional responses, and social support relationships. To help ensure participation in these programs, researchers and health workers must understand the role of social and psychosocial implications and results of the assessment, strategies, and sustainability that must be included in the development stage of any cancer support and survivorship initiatives. For this article, the authors examined mechanisms that can be used by cancer-control researchers and program staff to limit the divide between cancer survivorship initiatives and minority participation. They identified three strategies that must be used to address this divide effectively: the inclusion of minorities in clinical trials, intervention studies, treatment, and research programs; the development of culturally sensitive environments; and the ability to sustain minority participation. In summary, cancer survivorship includes many components that are developed individually and collectively to formulate sound strategies for including minorities in cancer-control initiatives. These programs should go beyond basic support groups and should include research studies, clinical trials, and alternative treatments for increasing cancer survival rates and quality of life among minorities. The divide can be addressed only through a proactive initiative that brings cancer survivorship initiatives and minority communities together in full partnership.

Are intubation conditions using rocuronium equivalent to those using succinylcholine?

OBJECTIVE: To determine whether the intubation conditions created by rocuronium are equivalent to those of succinylcholine during rapid-sequence induction (RSI). METHODS: Medline, EMBASE, and the Cochrane Controlled Trials Register were searched for randomized clinical trials (RCTs). The search strategy included all generic and trade names for succinylcholine and rocuronium, anesthesia, neuromuscular blockade, and a validated RCT filter. Intubation conditions were a required outcome. Two reviewers assessed studies for eligibility, data extraction, and quality. Intubation conditions were scored with Goldberg's scale (excellent conditions defined as clear vocal cords, easy tube insertion, and no cough). A-priori subgroup analysis was conducted for the sedative, use of opioids, true versus modified RSI, age group, and the dose of rocuronium. Data were analyzed with Metaview 4.1 for relative risk (RR) of achieving excellent intubation conditions. A sample size calculation determined that n = 468 is required for equivalence. RESULTS: Forty articles were identified; ten articles were excluded by the inclusion criteria, two were duplicate publications, and two had insufficient data. Therefore, 26 studies were analyzed. Overall, rocuronium was inferior to succinylcholine, with a RR = 0.87 (95% CI = 0.81 to 0.94) (N = 1,606). However, intubation conditions were similar in the propofol subgroup, with a RR = 0.96 (95% CI = 0.87 to 1.06) (N = 640). Failed intubations (N = 28) were equivalent in the two groups. CONCLUSIONS: Overall, succinylcholine creates excellent intubation conditions more reliably than rocuronium. If a second-line agent is required, rocuronium used with propofol creates intubation conditions equivalent to those with succinylcholine.