Clinical outcomes of prestripped, prestained, and preloaded Descemet's membrane endothelial keratoplasty ("P3 DMEK").

PURPOSE: Despite faster healing and reduced risk of rejection, some surgeons are hesitant to adopt Descemet membrane endothelial keratoplasty (DMEK) due to difficult intraoperative tissue preparation. Use of eye bank prestripped, prestained, and preloaded (p3) DMEK tissue can reduce the learning curve and risk of complications. MATERIALS AND METHODS: We conducted a prospective study including 167 eyes undergoing p3 DMEK and compared outcomes to a retrospective chart review of 201 eyes that underwent standard DMEK surgery. The primary outcomes were graft failure, detachment, and re-bubbling frequency. The secondary outcomes included baseline and postoperative visual acuity at months 1, 3, 6, and 12. Baseline and postoperative central corneal thickness (CCT) and endothelial cell counts (ECC) were collected. RESULTS: ECC decrease for p3 DMEK at 3, 6, and 12 months were 15.0%, 18.0%, and 21.0%, respectively. Forty (24%) of p3 DMEK and 72 (35.8%) of standard DMEK eyes had at least a partial graft detachment. There was no difference in CCT, graft failures, or re-bubble frequency. At 6 months, mean visual acuity was 20/26 and 20/24 for standard and p3 DMEK, respectively. Mean case time for p3 DMEK with phaco or p3 DMEK alone was 33 and 24 min, respectively. Mean case time for eyes undergoing DMEK with phaco or DMEK alone was 59 and 45 min, respectively. CONCLUSION: P3 DMEK tissue is safe and can provide excellent clinical outcomes that are comparable to standard DMEK tissue. Eyes undergoing p3 DMEK may have lower graft detachment and ECC loss.

Elucidating academic surgical staff perspectives of medical student learning in the operating room: An embedded mixed methods study.

BACKGROUND: The operating room (OR) is a complex environment for medical students. Little is known about the OR staff's perception of medical students. METHODS: We utilized an embedded mixed methods design to characterize surgical staff perceptions of students at an academic institution. We surveyed 408 OR nursing/technician staff with 16 follow-up interviews. RESULTS: 139 respondents. 91.3% reported having daily-to-weekly interactions with medical students. Yet, only 37.9% agreed that "patient care is better when medical students are part of the team." 25.2% felt confident that they knew what a student's education entails outside the OR. 93.5% agreed that interprofessional training between physicians and OR staff should be included in educational programs. 54% agreed that their responsibilities include medical student training in the OR setting. CONCLUSIONS: Despite an overall desire for teamwork, this study highlights a lack of knowledge of each others' roles. To improve OR culture and team dynamics, concerted efforts need to be made around interprofessional training.

Assessment of olfactory fluctuations in a clinical context.

PURPOSE: The aim of the study was to investigate whether olfactory fluctuations (OF) are pronounced in patients with sinonasal olfactory dysfunction (OD). METHODS: The retrospective investigation included patients aged 18 years or older, who consulted a tertiary referral center for olfactory loss. Patients with normal smell function were excluded. Patients answered a structured questionnaire about their olfactory symptoms, with specific questions related to the presence of OF and its average frequency, amplitude, duration, time since most recent OF, and associated symptoms of self-reported OF. Patients also underwent clinical evaluation including a structured medical history and physical examination including nasal endoscopy. In addition, we assessed orthonasal olfactory function using Sniffin' Sticks, and gustatory function using "taste sprays". RESULTS: Participants included 131 men and 205 women (n = 336), aged 18 to 86 years (mean 50, SD 16). Patient-reported fluctuations occurred most frequently in sinonasal (38%), idiopathic (29%), and postviral (29%) OD. Amplitude of OF was highest in postviral OD (p = 0.009). Average frequency, duration, and the time since the most recent fluctuation were not significantly different between groups (all p's > 0.42). Odor discrimination (p = 0.002) and identification (p = 0.017) scores were higher among those individuals with OF. CONCLUSION: Amplitude of OF may help distinguish postviral from other causes of OD, especially in patients presenting with equivocal symptoms of sinonasal disease.

Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation.

Loss-of-function (LOF) variants in SCN1B, encoding the voltage-gated sodium channel ß1/ß1B subunits, are linked to neurological and cardiovascular diseases. Scn1b-null mice have spontaneous seizures and ventricular arrhythmias and die by approximately 21 days after birth. ß1/ß1B Subunits play critical roles in regulating the excitability of ventricular cardiomyocytes and maintaining ventricular rhythmicity. However, whether they also regulate atrial excitability is unknown. We used neonatal Scn1b-null mice to model the effects of SCN1B LOF on atrial physiology in pediatric patients. Scn1b deletion resulted in altered expression of genes associated with atrial dysfunction. Scn1b-null hearts had a significant accumulation of atrial collagen, increased susceptibility to pacing induced atrial fibrillation (AF), sinoatrial node (SAN) dysfunction, and increased numbers of cholinergic neurons in ganglia that innervate the SAN. Atropine reduced the incidence of AF in null animals. Action potential duration was prolonged in null atrial myocytes, with increased late sodium current density and reduced L-type calcium current density. Scn1b LOF results in altered atrial structure and AF, demonstrating the critical role played by Scn1b in atrial physiology during early postnatal mouse development. Our results suggest that SCN1B LOF variants may significantly impact the developing pediatric heart.

Combined Adjuvant Chemotherapy and Radiation Therapy Improves Disease-Free Survival for Uterine Serous Cancer.

PURPOSE: Uterine serous carcinoma (USC) is a rare but aggressive endometrial cancer histology. We reviewed outcomes for patients with USC to identify the best adjuvant treatment strategy. METHODS AND MATERIALS: We retrospectively identified 162 patients with The International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA USC treated at our institution. Baseline characteristics, treatment details, clinical outcomes, and toxicity data were recorded. RESULTS: Median follow-up was 3.4 years (0.3-26 years). A variety of adjuvant therapy strategies were employed: 14% no adjuvant therapy, 28% radiation alone, 15% chemotherapy alone, and 43% combined chemotherapy and radiation. Distant metastasis was the most common type of recurrence (37% at 5 years). For patients with stage I-IVA disease, there were no significant differences in outcomes by treatment type. For patients with stage I-II disease (70% of the cohort), disease-free survival was significantly higher after chemotherapy (alone or with radiation therapy, P = .005) and after combined chemotherapy and radiation compared with all other treatments (P = .025). Toxicity outcomes were favorable, with minimal grade 3 and no grade 4 or 5 events. CONCLUSIONS: Patients with USC experience high rates of recurrence and mortality. Distant metastasis is the most common pattern of failure for all stages. For patients with early-stage disease, combined chemotherapy and radiation improves 5-year disease-free survival compared with either single adjuvant treatment alone or no adjuvant treatment. The relatively large group of patients with USC included in this study may account for our ability to detect this improvement whereas clinical trials have failed to do so, possibly owing to the relatively small percentages of patients with USC enrolled.

A gain of function paradox: Targeted therapy for glioblastoma associated with abnormal NHE9 expression.

Glioblastoma (GBM) is the most frequent and inevitably lethal primary brain cancer in adults. It is recognized that the overexpression of the endosomal Na+ /H+ exchanger NHE9 is a potent driver of GBM progression. Patients with NHE9 overexpression have a threefold lower median survival relative to GBM patients with normal NHE9 expression, using available treatment options. New treatment strategies tailored for this GBM subset are much needed. According to the prevailing model, NHE9 overexpression leads to an increase in plasma membrane density of epidermal growth factor receptors (EGFRs) which consequently enhances GBM cell proliferation and migration. However, this increase is not specific to EGFRs. In fact, the hallmark of NHE9 overexpression is a pan-specific increase in plasma membrane receptors. Paradoxically, we report that this gain of function in NHE9 can be exploited to effectively target GBM cells for destruction. When exposed to gold nanoparticles, NHE9 overexpressing GBM cells accumulated drastically high amounts of gold via receptor-mediated endocytosis, relative to control. Irradiation of these cells with near-infrared light led to apoptotic tumour cell death. A major limitation for delivering therapeutics to GBM cells is the blood-brain barrier (BBB). Here, we demonstrate that macrophages loaded with gold nanoparticles can cross the BBB, deliver the gold nanoparticles and effect the demise of GBM cells. In combination with receptor tyrosine kinase inhibition, we show this approach holds great promise for a new GBM-targeted therapy.