Optic neuropathy after COVID-19 vaccination: a report of two cases.

PURPOSE: We report two cases of optic nerve pathology after the administration of the Pfizer-BioNTech and AstraZeneca-Oxford COVID-19 vaccines, respectively, and describe the implications for management of post-vaccination central nervous system (CNS) inflammation. CASE REPORTS: A 69-year-old woman presented with bilateral optic nerve head oedema, 16 days after the second dose of the Pfizer-BioNTech vaccine. She was diagnosed with post-vaccination CNS inflammatory syndrome and was treated for five days with intravenous methylprednisolone at a dose of 1 gram per day. Her optic disc swelling improved, and her vision stabilised. A 32-year-old woman presented six days after her first dose of the AstraZeneca-Oxford vaccine with two days of sudden onset of progressive blurring of vision in her left eye. Posterior segment examination revealed left optic disc swelling, and an MRI of the brain, orbit, and cervical spine was significant for left optic nerve enhancement. The patient was diagnosed with a unilateral post-vaccination optic neuritis. She was treated with a three-day course of intravenous methylprednisolone followed by oral prednisone. Her optic disc swelling and visual field improved, and she recovered 6/6 vision. CONCLUSIONS: Clinicians and patients should be aware of the potential for post-vaccination CNS inflammatory syndromes associated with COVID-19 vaccine administration. Neuroimaging and cerebrospinal fluid analysis may aid in the diagnosis of the cause of vision loss. Further studies are needed to evaluate the spectrum and frequency of optic nerve involvement associated with COVID-19 vaccination.

Preoperative Intravenous Ketorolac Safely Reduces Postoperative Pain in Levator Advancement Surgery.

PURPOSE: To assess the impact of intravenous ketorolac (IVK) on self-reported pain scores, requirements for opioid analgesic and anti-emetic medications, and bleeding complications in the setting of levator advancement surgery METHODS:: A prospective randomized controlled trial was performed among adult patients undergoing levator advancement surgery. Pain scores were measured immediately after surgery, prior to discharge from the surgical facility, and on the first postoperative day. The requirements for postoperative analgesic and anti-emetic medications were recorded. Statistical comparisons were performed via a dedicated computerized software package. RESULTS: Fifty patients (20 males, 30 females, mean age = 65.7 years, standard deviation = 11.9 years) underwent levator advancement without IVK and acted as controls. An additional 50 patients received IVK (19 males, 31 females, mean age = 64.6 years, standard deviation = 12.0 years). As compared with control patients, IVK resulted in statistically significant reductions in pain score immediately after surgery (4.62 vs. 1.44, p = 0.0001) and on postoperative day 1 (3.22 vs. 1.24, p = 0.0001). Fourteen patients (28%) in the control and 4 patients (8%) in the group that received IVK required opioid analgesics (p = 0.017). Seven patients (14%) in the control group and 1 patient in the group that received IVK required anti-emetic medications (p = 0.059). No patient experienced a hemorrhagic complication. CONCLUSIONS: In the setting of levator advancement surgery, IVK results in a dramatic reduction in self-reported pain score immediately after surgery and on postoperative day 1 and the requirement for opioid analgesics. This medication may be safely utilized for ptosis repair.

Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer.

The interaction of programmed cell death-1 and its ligand is widely studied in cancer. Monoclonal antibodies blocking these molecules have had great success but little is known about them in thyroid cancer. We investigated the role of PD-L1 in thyroid cancer with respect to BRAF mutation and MAP kinase pathway activity and the effect of anti PD-L1 antibody therapy on tumor regression and intra-tumoral immune response alone or in combination with BRAF inhibitor (BRAFi). BRAFV600E cells showed significantly higher baseline expression of PD-L1 at mRNA and protein levels compared to BRAFWT cells. MEK inhibitor treatment resulted in a decrease of PD-L1 expression across all cell lines. BRAFi treatment decreased PD-L1 expression in BRAFV600E cells, but paradoxically increased its expression in BRAFWT cells. BRAFV600E mutated patients samples had a higher level of PD-L1 mRNA compared to BRAFWT (p=0.015). Immunocompetent mice (B6129SF1/J) implanted with syngeneic 3747 BRAFV600E/WT P53-/- murine tumor cells were randomized to control, PLX4720, anti PD-L1 antibody and their combination. In this model of aggressive thyroid cancer, control tumor volume reached 782.3±174.6mm3 at two weeks. The combination dramatically reduced tumor volume to 147.3±60.8, compared to PLX4720 (439.3±188.4 mm3, P=0.023) or PD-L1 antibody (716.7±62.1, P<0.001) alone. Immunohistochemistry analysis revealed intense CD8+ CTL infiltration and cytotoxicity and favorable CD8+:Treg ratio compared to each individual treatment. Our results show anti PD-L1 treatment potentiates the effect of BRAFi on tumor regression and intensifies anti tumor immune response in an immunocompetent model of ATC. Clinical trials of this therapeutic combination may be of benefit in patients with ATC.

Sensorineural hearing loss in congenital diaphragmatic hernia survivors is associated with postnatal management and not defect size.

BACKGROUND/PURPOSE: We determined the incidence of sensorineural hearing loss (SNHL; >20dB at any frequency) in a contemporary cohort of congenital diaphragmatic hernia (CDH) survivors at a single tertiary care center and identified potential risk factors for SNHL. METHODS: From 2000 through 2011, clinical and audiologic data were collected on 122 surgically-repaired Bochdalek CDH patients. CDH defect size, duration of ventilation, and cumulative aminoglycoside treatment were used for multivariate logistic regression. RESULTS: Incidence of SNHL was 7.4% (9/122). We identified one significant independent predictor of SNHL: cumulative length of aminoglycoside treatment (P<.001; OR 1.44, 95% CI: 1.13-1.83). CONCLUSIONS: Over the last decade, the incidence of SNHL in our CDH patients is low compared to previous reports in the literature (7.4%) and is not associated with CDH defect size or the need for extracorporeal membrane oxygenation. Prolonged duration of aminoglycoside treatment increases the risk of SNHL independent of defect size and duration of ventilation.

Prenatally-counseled congenital diaphragmatic hernia parents exhibit positive well-being before and after surgical repair.

BACKGROUND/PURPOSE: The purpose of this paper was to examine the effect of prenatal counseling in the Advanced Fetal Care Center (AFCC) on the well-being of parents of infants with congenital diaphragmatic hernia (CDH). METHODS: From 2008 through 2012, 26 mothers and fathers of surgically repaired CDH patients who received prenatal counseling at our institution, and 15 who received no prenatal counseling, each completed the Short-Form 36 version 1 (SF-36v1) at the appropriate time points: prenatal, two weeks, and six months post-surgery. RESULTS: Parents in both groups did not differ by demographic characteristics. Patients who received prenatal counseling had significantly longer ventilatory time and length of stay (LOS) in the ICU and in the hospital compared to those who did not receive prenatal counseling (all P<.01). Mothers and fathers had similar SF-36v1 mental and physical component summary (MCS, PCS) post-surgery scores when compared by counseling status. Prenatal MCS scores for mothers and fathers (47 vs. 41; P=.24) were similar to those at six months post-surgery (47 vs. 47; P=.90). CONCLUSIONS: When hospital LOS was controlled between groups stratified by AFCC counseling status, MCS scores were comparable prenatally and were sustained at six months post-surgery for both parents. These findings may reflect the support services parents received beginning in the prenatal period.

Ultrasonography-guided bilateral rectus sheath block vs local anesthetic infiltration after pediatric umbilical hernia repair: a prospective randomized clinical trial.

IMPORTANCE: Regional anesthetic techniques can be used to alleviate postoperative pain in children undergoing pediatric surgical procedures. Use of ultrasonographic guidance for bilateral rectus sheath block (BRSB) has been shown to improve immediate pain scores and reduce use of postoperative analgesia in the postanesthesia care unit (PACU). OBJECTIVE: To compare efficacy of ultrasonography-guided BRSB and local anesthetic infiltration (LAI) in providing postoperative analgesia after pediatric umbilical hernia repair. DESIGN: Prospective, observer-blinded, randomized clinical trial. SETTING: Tertiary-referral urban children's hospital. PARTICIPANTS: Eligible children 3 to 12 years of age undergoing elective umbilical hernia repair from November 16, 2009, through May 31, 2011. INTERVENTIONS: Ropivacaine hydrochloride administered at the conclusion of surgery as LAI by the surgeon (n = 25) or as ultrasonography-guided BRSB by the anesthesiologist (n = 27). MAIN OUTCOMES AND MEASURES: Scores on the FACES Pain Rating Scale measured at 10-minute intervals and all use of analgesic medications in the PACU. RESULTS: Median FACES scores in the PACU were lower in the BRSB group compared with the LAI group at 10 minutes (0 vs 1; P = .04), 30 minutes (0 vs 1; P = .01), and 40 minutes or later (0 vs 1; P = .03). Fewer doses of opioid and nonopioid medications were given to the BRSB group compared with the LAI group (5 vs 11 doses for opioids; 5 vs 10 for nonopioids). CONCLUSIONS AND RELEVANCE: In the PACU, ultrasonography-guided BRSB after umbilical hernia repair in children is associated with lower median FACES scores and decreased use of opioid and nonopioid medications compared with LAI. Future studies could examine the use of longer-acting anesthetic agents with ultrasonography-guided BRSB. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01015053.

Impact on family of management strategies for perforated appendicitis in children.

BACKGROUND/PURPOSE: The purpose of this study was to examine the impact on the family of immediate appendectomy compared with initial nonoperative management for perforated appendicitis in children. METHODS: Sixty-six prospectively identified families of children with perforated appendicitis completed a daily activity journal and the Impact on Family Scale at presentation and at completion of therapy. RESULTS: There were no significant differences in postoperative surgical site infections or number of missed school or employment days between the immediate appendectomy group (n = 40) and the initial nonoperative management group (n = 26). Impact on Family Scale total scores decreased over time for both groups, but this improvement over time was significant only in the initial nonoperative management group (P < .01). CONCLUSIONS: Immediate appendectomy or initial nonoperative management can effectively manage perforated appendicitis in children with no statistically significant differences in the number of missed school or employment days. Greater improvements in family impact are associated with initial nonoperative management as measured by the Impact on Family Scale at completion of therapy.

Treatment of perforated appendicitis in children: what is the cost?

BACKGROUND/PURPOSE: We compared direct hospital costs and indirect costs to the family associated with immediate appendectomy or initial nonoperative management for perforated appendicitis in children. METHODS: From June 2009 through May 2010, 61 prospectively identified families completed a cost diary, documenting the numbers of missed school days for the child and missed employment days for the adult caregiver(s) over the treatment course. Hospital costs were obtained from hospital financial databases. Mann-Whitney U tests and Fisher exact tests were used to compare outcome measures for each treatment strategy. RESULTS: Patients treated by initial nonoperative management had a significantly longer median length of stay (9 days vs 7 days, P = .02) and a significantly greater median total hospital cost per patient ($31,349 vs $21,323, P = .01) when compared with those treated by immediate appendectomy. There was no significant difference in median number of missed school days (9 days vs 10 days, P = .23) or missed employment days for adult caregiver(s) (5 days vs 7 days, P = .18) between treatment strategies. CONCLUSIONS: Patients with perforated appendicitis treated by initial nonoperative management had a greater length of stay and a significantly greater total hospital cost but were not burdened by significantly greater indirect costs compared with those treated by immediate appendectomy.