Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multicenter Study.

PURPOSE: To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. PARTICIPANTS: Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab. METHODS: Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The primary outcomes measure was AE incidence and onset. Secondary outcome measures included AE severity, AE reversibility, AE duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of patients (101/131), with average proptosis improvement of 3.0 ± 2.1 mm and average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 ± 38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about AE risk, properly screen patients before treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Breakthrough invasive fungal infections on isavuconazole prophylaxis in hematologic malignancy & hematopoietic stem cell transplant patients.

BACKGROUND: Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side-effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported. METHODS: In this single-center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs. RESULTS: We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21-91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%). Nineteen patients (17.9%) developed bIFIs-nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8-253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 µg/mL) were comparable to industry-sponsored clinical trials. All-cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co-infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups. CONCLUSION: ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side-effect and drug-interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs.

Changes in low-acuity patient volume in an emergency department after launching a walk-in clinic.

Objective: Unscheduled low-acuity care options are on the rise and are often expected to reduce emergency department (ED) visits. We opened an ED-staffed walk-in clinic (WIC) as an alternative care location for low-acuity patients at a time when ED visits exceeded facility capacity and the impending flu season was anticipated to increase visits further, and we assessed whether low-acuity ED patient visits decreased after opening the WIC. Methods: In this retrospective cohort study, we compared patient and clinical visit characteristics of the ED and WIC patients and conducted interrupted time-series analyses to quantify the impact of the WIC on low-acuity ED patient visit volume and the trend. Results: There were 27,211 low-acuity ED visits (22.7% of total ED visits), and 7,058 patients seen in the WIC from February 26, 2018, to November 17, 2019. Low-acuity patient visits in the ED reduced significantly immediately after the WIC opened (P = 0.01). In the subsequent months, however, patient volume trended back to pre-WIC volumes such that there was no significant impact at 6, 9, or 12 months (P = 0.07). Had WIC patients been seen in the main ED, low-acuity volume would have been 27% of the total volume rather than the 22.7% that was observed. Conclusion: The WIC did not result in a sustained reduction in low-acuity patients in the main ED. However, it enabled emergency staff to see low-acuity patients in a lower resource setting during times when ED capacity was limited.

Melphalan on day -1 versus day -2 in patients with plasma cell disorders undergoing autologous stem cell transplant.

High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the literature surrounding the timing of melphalan administration to avoid potential cytotoxic effects, although the administration has been safely proposed when given at least 8 hours prior to stem cell infusion. The objectives of this study were to assess differences in safety and efficacy outcomes between day -1 and day -2 single-dose melphalan administration in patients undergoing ASCT for PCDs. A retrospective chart review was performed at our institution comparing patients receiving melphalan on day -1 to an equal number of patients receiving melphalan on day -2. The primary endpoint was time to neutrophil engraftment from stem cell infusion. Univariate analyses were performed. Mean time to neutrophil engraftment from stem cell infusion was identical at 10.7 days for both cohorts (p = 0.88). Mean time to platelet engraftment from stem cell infusion was shorter with day -1 administration (17.4 vs. 18.6 days, p = 0.06). Mean time to neutrophil and platelet engraftment from melphalan infusion were significantly shorter with day -1 administration. Similar outcomes were observed for length of hospitalization, infection- and mucositis-related toxicities, hematologic response, transplant-related mortality, and overall survival. Our findings show no difference in time to neutrophil engraftment from stem cell infusion and a trend toward shorter time to platelet engraftment with day -1 administration. Based on our study, day -1 melphalan administration is an acceptable and safe practice.

#CosmeticsTwitter: Predicting Public Interest in Nonsurgical Cosmetic Procedures Using Twitter Data.

BACKGROUND: The utilization of social media in plastic surgery is expanding. The Twitter Academic Research Product Tract (TARPT) database provides plastic surgeons the opportunity to monitor public interest in plastic surgery procedures. Previously, TARPT was shown to be effective in tracking public interest in surgical cosmetic facial and body procedures. OBJECTIVES: The authors sought to determine the ability of the TARPT tool to track and predict public interest in nonsurgical cosmetic procedures and to examine temporal public interest trends in nonsurgical cosmetic procedures. METHODS: The authors employed the TARPT tool to calculate the total number of tweets containing keywords related to 15 nonsurgical cosmetic procedures from 2010 to 2020. Annual case volumes were obtained for each of the 15 procedures from annual reports provided by the American Society of Plastic Surgeons. Univariate linear regression was employed to compare tweet volumes and procedure volumes, with P < 0.05 as a threshold for significance. RESULTS: Univariate linear regression revealed significant positive correlations between tweet volumes and American Society of Plastic Surgeons procedure volumes for 10 search terms representing 6 nonsurgical cosmetic procedures: "xeomin," "microdermabrasion," "facial filler," "fat filler," "fat injections," "fat transfer," "hyaluronic acid filler," "hyaluronic acid injection," "HA filler," and "PRP filler." Thirty-two search terms did not demonstrate a significant relationship. CONCLUSIONS: The TARPT tool is an informative data source for plastic surgeons with the potential to guide marketing and advertising strategies, and monitor public interest in nonsurgical cosmetic procedures, helping surgeons respond to patients' evolving needs.

A Common Outer Retinal Change in Retinal Degeneration by Optical Coherence Tomography Can Be Used to Assess Outcomes of Gene Therapy.

Identifying early disease hallmarks in animal models with slow disease progression may expedite disease detection and assessment of treatment outcomes. Using optical coherence tomography, a widely applied noninvasive method for monitoring retinal structure changes, we analyzed retinal optical sections from six mouse lines with retinal degeneration caused by mutations in different disease-causing genes. While images from wild-type mice revealed four well-separated hyper-reflective bands in the outer retina (designated as outer retina reflective bands, ORRBs) at all ages, the second band (ORRB2) and the third band (ORRB3) were merged in retinas of five mutant mouse lines at early ages, suggesting the pathological nature of this alteration. This ORRB change appeared to be degenerating photoreceptor related, and occurred before obvious morphological changes that can be identified on both hematoxylin and eosin-stained sections and electron microscopic sections. Importantly, the merging of ORRB2 and ORRB3 was reversed by treatment with adeno-associated viral vector-mediated gene replacement therapies, and this restoration occurred much earlier than measurable functional or structural improvement. Our data suggest that the ORRB change could be a common hallmark of early retinal degeneration and its restoration could be used for rapid and noninvasive assessment of therapeutic effects following gene therapy or other treatment interventions.

Clostridium difficile infection, a descriptive analysis of solid organ transplant recipients at a single center.

Clostridium difficile is a bacterial enteric pathogen, which causes clinical disease among solid organ transplant (SOT) recipients. This large, single-center, retrospective study describes incidence, demographics, and impact of C. difficile infection (CDI) among adult SOT recipients, cardiac (n=5), lung (n=14), liver (n=9), renal (n=26), and multiorgan (n=9) patients transplanted and diagnosed with CDI (geneB PCR) between 9/2009 and 12/2012. The overall incidence of CDI in our population during the 40-month period of study was 4%. CDI incidence among cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and 3.2%, respectively (P=0.03 between organ-types). Median time from transplant to CDI for all was 51 (14-249) days, with liver recipients having the shortest time to infection, median 36 (15-101) days, and lung recipients having a longer time to infection, median 136 (29-611) days. Antibiotic exposure within 3 months of CDI was evident in 45 of the 63 (71%) patients in this study, 80%, 79%, 100%, 58%, and 67% of cardiac, lung, liver, renal, and multiorgan transplant recipients, respectively. Most patients (83%) were hospitalized within the 3 months preceding CDI. Recipients were followed for a median time of 23 (16-31) months; at the time of last follow-up, 83% of allografts were functioning, and 86% of patients were alive. One death and 1 graft failure were causally related to CDI. CDI had an overall incidence of 4%; clinicians should have heightened awareness for CDI, especially among patients receiving antibiotics, with increased monitoring and aggressive management of CDI.

A case series using famciclovir in stem cell transplant recipients with valacyclovir hypersensitivity reactions.

BACKGROUND: Herpes simplex virus and varicella zoster virus reactivation can occur in up to 32% and 40% of patients, respectively in the first year post-transplant without prophylaxis. Antiviral therapy consisting of acyclovir or valacyclovir is recommended for at least 1 year post stem cell transplant per evidence-based guidelines. OBJECTIVE: In the event of a contraindication or hypersensitivity reaction to either drug, an alternative is essential based on the proven efficacy in reducing clinically significant herpes simplex virus and varicella zoster virus reactivations. We report two cases of successful initiation of famciclovir in stem cell transplant recipients experiencing hypersensitivity to valacyclovir or acyclovir. DISCUSSION: In both cases, there were no hypersensitivity reactions or breakthrough viral infections after famciclovir initiation but this observation is limited by a small patient population. CONCLUSION: Due to the limited data available, famciclovir appears to be a reasonable option in immunocompromised patients with a mild valacyclovir or acyclovir hypersensitivity reaction.

Ectopic intraocular lens: an unusual complication of cataract surgery.

We wish to report an unusual complication of intraocular lens (IOL) insertion following uneventful phacoemulsification. After successful phacoemulsification surgery, a hydrophobic acrylic IOL was loaded in the injector for insertion into the capsular bag. During insertion, the IOL inadvertently extended into the corneal stromal lamella. The complication was recognized at a late stage, and the foldable acrylic lens was retrieved and reinserted correctly in the bag. The anterior chamber was made viscoelastically taut and was maintained in this state for 10 min, followed by a routine viscoelastic wash and air bubble injection. Cornea was slightly edematous with stromal haze, and the corneal thickness was 908 µm. At the 1-month follow-up visit, the patient's vision was 20/40, the stromal haze had subsided, the corneal thickness was 572 µm, and the patient was comfortable. Though it was unknown complication, following proper management patient recovered satisfactorily.