Complete Response to Immunotherapy Using Pembrolizumab in a Patient With Conjunctival Squamous Cell Carcinoma With Nodal Metastasis.

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden. She was treated with pembrolizumab and had complete resolution of the conjunctival mass and the associated parotid metastasis after just 2 cycles of treatment. This case underscores the promising role of immune checkpoint inhibitors in the treatment of conjunctival squamous cell carcinoma, especially when surgery is associated with significant ocular morbidity, in patients who may not be good surgical candidates, or in patients with metastasis.

Successful Treatment of Refractory Orbital Plasmacytoma with Chimeric Antigen Receptor T Cell Therapy: A Case Report and Review of the Literature.

Orbital plasmacytoma is a rare plasma cell tumor that may arise as an aggressive form of extramedullary multiple myeloma. Treatment modalities include surgical excision, radiation, and chemotherapy. Chimeric antigen receptor T cell therapy is currently reserved for refractory disease. The authors present a case of a 69-year-old woman with an extensive orbital plasmacytoma refractory to multimodal therapy who was treated with idecabtagene vicleucel chimeric antigen receptor T cell therapy. Four days after infusion, the patient exhibited grade 1 cytokine release syndrome, which resolved with tocilizumab. The orbital plasmacytoma significantly decreased in size 1 month after treatment and demonstrated complete serological response and sustained tumor burden reduction at 10-month follow-up. This case highlights the efficacy of chimeric antigen receptor T cell therapy for refractory orbital plasmacytoma and calls attention to potential inflammatory toxicities.

Oral Corticosteroids for Teprotumumab-Related Hearing Loss: A Case Report.

Teprotumumab is a novel insulin-like growth factor-1 receptor inhibitor approved for the treatment of thyroid eye disease, but growing reports of hearing loss require further investigation. To date, an effective protocol for managing hearing loss in this setting has not been determined. Here, we present the first report of the resolution of teprotumumab-related hearing loss with prompt oral prednisone. A 70-year-old woman on teprotumumab experienced sudden hearing loss and tinnitus after her first infusion. An audiogram demonstrated a mild down-sloping to moderately severe mixed conductive and sensorineural hearing loss that was promptly treated with prednisone 60 mg for 6 days with a 1-week gradual taper. An audiogram 3 weeks later demonstrated return of hearing to normal thresholds, and the whole teprotumumab treatment course was completed without further issue. This case highlights the importance of audiometric monitoring, prompt identification of hearing symptoms, and the potential for oral steroids to reverse teprotumumab-related hearing loss.

Reduction of Teprotumumab-Induced Hearing Loss With Comparable Efficacy Using Half-Dose Therapy.

Teprotumumab has been shown to be effective in the treatment of thyroid eye disease, a potentially vision-threatening condition. Adverse events, including sensorineural hearing loss, have been associated with teprotumumab. The authors present the case of a 64-year-old female who discontinued teprotumumab due to significant sensorineural hearing loss after 4 infusions, along with other adverse events. The patient was unresponsive to a subsequent course of intravenous methylprednisolone and orbital radiation, during which she experienced worsening thyroid eye disease symptoms. Teprotumumab was restarted 1 year later, at a half dose of 10 mg/kg for 8 infusions. Three months post-treatment, she retains resolution of double vision and orbital inflammatory signs, and significant improvement in proptosis. She tolerated all infusions with an overall reduction in the severity of her adverse events and without return of significant sensorineural hearing loss. The authors conclude that a lower dose of teprotumumab can be effective for patients with active moderate-severe thyroid eye disease who experience significant or intolerable adverse events.

Randomized, double-blind, noninferiority study of diclofenac diethylamine 2.32% gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily in patients with acute ankle sprain.

BACKGROUND: Diclofenac diethylamine (DDEA) gel has demonstrated efficacy for treatment of ankle sprains in both the 1.16% four-times-daily (QID) and 2.32% twice-daily (BID) formulations. The objective of this study was to compare, for the first time, the efficacy of DDEA 2.32% gel BID and DDEA 1.16% gel QID. METHODS: This was a phase 3, randomized, double-blind, multicenter, active-controlled, parallel-group study conducted in China from October 2019 to November 2020, designed to determine the noninferiority of DDEA 2.32% gel BID relative to DDEA 1.16% gel QID for treatment of grade I-II ankle sprain. At study entry, patients must have had pain on movement (POM) ≥50 mm on a 100-mm visual analogue scale (VAS), and not received any pain medication. The primary efficacy endpoint was the noninferiority of DDEA 2.32% gel BID vs DDEA 1.16% gel QID for POM as assessed by the patient using the 100-mm VAS, conducted on day 5. Secondary endpoints included measures of ankle tenderness, joint function, swelling, and patient-reported pain intensity and pain relief. RESULTS: A total of 302 patients were randomized and 95.4% completed the study. The mean (SD) change in POM from baseline to day 5 using the 100-mm VAS was - 42.8 mm (19.7 mm) with DDEA 2.32% gel BID and - 43.1 mm (18.1 mm) with DDEA 1.16% gel QID for the per-protocol population. The least squares mean difference (DDEA gel 2.32% - DDEA gel 1.16%) at this timepoint was 1.11 mm (95% CI - 3.00, 5.22; P = 0.595), and the upper limit (5.22 mm) of the 95% CI was less than the noninferiority margin of 13 mm, demonstrating that DDEA 2.32% gel BID was noninferior to DDEA 1.16% gel QID. Similar trends were seen for the secondary efficacy endpoints. There was no significant difference in the incidence of treatment-emergent adverse events or adverse events adjudicated as being treatment related. All treatment-related adverse events were dermatological; one patient discontinued from the DDEA 2.32% gel BID arm due to application-site inflammation. CONCLUSIONS: DDEA 2.32% gel BID offers a convenient alternative to DDEA 1.16% gel QID, with similar pain reduction and relief, anti-inflammatory effects, and tolerability. TRIAL REGISTRATION: NCT04052620.

Sentiment Analysis Surrounding Blepharoplasty in Online Health Forums.

Background: Upper and lower blepharoplasty are among the most common procedures in aesthetic surgery and are often emotionally laden due to the subjective nature of outcomes and implications with beauty and self-identity. This article capitalizes on the increasing wealth of patient-provided health information online and is the first to analyze the emotions surrounding blepharoplasty discussions in an open internet health forum, MedHelp. Methods: We used Python to scrape MedHelp for threads that contained "blepharoplasty" and then used IBM Watson Natural Language Understanding to perform sentiment analyses, calculating a general sentiment score (-1 to +1) as well as emotion scores for anger, sadness, joy, fear, and disgust (0 to 1) for posts and keywords contained within the posts. Keywords were then manually grouped into five distinct clinical categories: symptoms, doctor, treatment, medication, and body. Results: We collected 52 threads containing "blepharoplasty," yielding 154 posts and 1365 keywords. The average sentiment score was negative among all posts (-0.15) and keywords (-0.30). Among all posts and keywords, sadness had the highest score and disgust had the lowest score. Conclusions: Fear and sadness are the predominant emotions for blepharoplasty patients online, and the most negative symptoms cited are not ones that surgeons typically expect.

Advances in the Treatment of Thyroid Eye Disease Associated Extraocular Muscle Myopathy and Optic Neuropathy.

PURPOSE OF REVIEW: To review emerging treatments for thyroid eye disease (TED) associated extraocular muscle myopathy and dysthyroid optic neuropathy (DON). RECENT FINDINGS: Emerging targeted biologic therapies may alter the disease course in TED. Teprotumumab, a type I insulin-like growth factor receptor inhibitor, is the most recent addition to the treatments available for TED-associated extraocular muscle myopathy causing diplopia. Small studies also suggest a potential therapeutic benefit for DON. Various recent studies have also expanded our knowledge on conventional TED therapies. The therapeutic landscape of TED and its sequelae has evolved in recent years. New targeted therapies have the potential to reduce the extraocular muscle and orbital volume expansion which can lead to diplopia and vision loss from optic nerve compression. Longer term efficacy and durability data is needed to determine the role biologics, such as teprotumumab, should play in the treatment of TED patients compared to the current standard of care.

Reactivation of Herpes Zoster Keratitis Following Shingrix Vaccine.

We present a case of herpes zoster keratitis reactivation shortly following the Shingrix vaccine. In our patient, reactivation of herpes zoster keratitis occurred a few weeks following the herpes zoster subunit (HZ/su) vaccine. The development of herpes zoster ophthalmicus following HZ/su is exceedingly rare, with only one prior reported case found in the literature. Reporting of this potential correlation is important in understanding the full risks of vaccines and can help elucidate the etiology of such responses.

Imaging in neuro-ophthalmology in the context of value-based care.

PURPOSE OF REVIEW: Neuro-ophthalmic imaging is an invaluable tool for clinical decision-making and has evolved rapidly. At the same time, both imaging utilization and healthcare costs have skyrocketed, and concern for imaging overuse has become a salient topic. This article gives an overview of the current state of neuro-ophthalmic imaging from a value-based medicine lens and discusses recent neuro-ophthalmic advancements in OCT with these considerations in mind. RECENT FINDINGS: Neuro-ophthalmology is not immune to the waste prevalent in medical imaging. Recent guidelines recommend against routine imaging for ophthalmic conditions without the presence of symptoms. Although neuro-ophthalmic specialty consults and imaging compare favorably against other specialties, the diagnostic yield depending on imaging indication can vary dramatically. For newer developments such as in OCT, it is particularly difficult to assess cost-effectiveness despite the technology's exciting diagnostic potential. SUMMARY: Familiarity with guidelines to counter misuse, the diagnostic yield of imaging in particular situations, and the limitations of new technology can all help neuro-ophthalmologists make educated tradeoffs and adapt to the new landscape of cost-effective medicine. By helping to decrease costs and efficiently utilize limited resources, the end benefactors will be the increased number of patients who have greater access to affordable care.

A preliminary in vitro evaluation of the bioactive potential of cryogel scaffolds incorporated with Manuka honey for the treatment of chronic bone infections.

Previous studies have identified honey as an agent in bacterial inhibition and a mediator in lowering the pH at the wound site. Manuka honey (MH), indigenous to New Zealand, contains a Unique Manuka Factor that provides an additional antibacterial agent. While there are many potential benefits to incorporating MH into wounds, there is currently no ideal way to deliver the material to the site of injury. Cryogels are a type of scaffold that possess high porosity, mechanical stability, and a sponge-like consistency. This study uniquely incorporates varying amounts of MH into cryogel scaffolds, utilizing its properties in a sustained release fashion to assist in the overall healing process, while using the cryogel structure as a tissue template. All cryogels were evaluated to determine the effects of MH on porosity, swelling potential, mechanical durability, and cell compatibility. The release of MH was also quantified to evaluate bacterial clearance potential, and the scaffolds were mineralized to replicate native bone. It was determined that a 5% MH silk fibroin cryogel has the potential to inhibit bacterial growth while still maintaining adequate porosity, mechanical properties, and cell infiltration. Such a scaffold would have use in a number of applications, including bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1918-1933, 2018.

A comprehensive review of cryogels and their roles in tissue engineering applications.

The extracellular matrix is fundamental in providing an appropriate environment for cell interaction and signaling to occur. Replicating such a matrix is advantageous in the support of tissue ingrowth and regeneration through the field of tissue engineering. While scaffolds can be fabricated in many ways, cryogels have recently become a popular approach due to their macroporous structure and durability. Produced through the crosslinking of gel precursors followed by a subsequent controlled freeze/thaw cycle, the resulting cryogel provides a unique, sponge-like structure. Therefore, cryogels have proven advantageous for many tissue engineering applications including roles in bioreactor systems, cell separation, and scaffolding. Specifically, the matrix has been demonstrated to encourage the production of various molecules, such as antibodies, and has also been used for cryopreservation. Cryogels can pose as a bioreactor for the expansion of cell lines, as well as a vehicle for cell separation. Lastly, this matrix has shown excellent potential as a tissue engineered scaffold, encouraging regrowth at numerous damaged tissue sites in vivo. This review will briefly discuss the fabrication of cryogels, with an emphasis placed on their application in various facets of tissue engineering to provide an overview of this unique scaffold's past and future roles. STATEMENT OF SIGNIFICANCE: Cryogels are unique scaffolds produced through the controlled freezing and thawing of a polymer solution. There is an ever-growing body of literature that demonstrates their applicability in the realm of tissue engineering as extracellular matrix analogue scaffolds; with extensive information having been provided regarding the fabrication, porosity, and mechanical integrity of the scaffolds. Additionally, cryogels have been reviewed with respect to their role in bioseparation and as cellular incubators. This all-inclusive view of the roles that cryogels can play is critical to advancing the technology and expanding its niche within biomaterials and tissue engineering research. To the best of the authors' knowledge, this is the first comprehensive review of cryogel applications in tissue engineering that includes specific looks at their growing roles as extracellular matrix analogues, incubators, and in bioseparation processes.

A Comparison of Tissue Engineering Scaffolds Incorporated with Manuka Honey of Varying UMF.

Purpose. Manuka honey (MH) is an antibacterial agent specific to the islands of New Zealand containing both hydrogen peroxide and a Unique Manuka Factor (UMF). Although the antibacterial properties of MH have been studied, the effect of varying UMF of MH incorporated into tissue engineered scaffolds have not. Therefore, this study was designed to compare silk fibroin cryogels and electrospun scaffolds incorporated with a 5% MH concentration of various UMF. Methods. Characteristics such as porosity, bacterial clearance and adhesion, and cytotoxicity were compared. Results. Pore diameters for all cryogels were between 51 and 60 µm, while electrospun scaffolds were 10 µm. Cryogels of varying UMF displayed clearance of approximately 0.16 cm for E. coli and S. aureus. In comparison, the electrospun scaffolds clearance ranged between 0.5 and 1 cm. A glucose release of 0.5 mg/mL was observed for the first 24 hours by all scaffolds, regardless of UMF. With respect to cytotoxicity, neither scaffold caused the cell number to drop below 20,000. Conclusions. Overall, when comparing the effects of the various UMF within the two scaffolds, no significant differences were observed. This suggests that the fabricated scaffolds in this study displayed similar bacterial effects regardless of the UMF value.

The calcification potential of cryogel scaffolds incorporated with various forms of hydroxyapatite for bone regeneration.

Cryogels are advantageous scaffolds for bone regeneration applications due to their high mechanical stability and macroporous structure. Anatomically, bone is composed of collagen and hydroxyapatite and during remodeling, these structural components are replaced. However, early forms of mineralization include calcium salts which take up to months to be converted to the desired hydroxyapatite form. Thus, it is beneficial to provide a primary source of hydroxyapatite within the scaffold, expediting the process of mineralization during bone regeneration. In this study, chitosan-gelatin (CG) cryogels were incorporated with various forms of hydroxyapatite to evaluate effects on the standard characteristics of cryogels, as well as the potential for increased mineralization. Testing included the comparison of porosity, swelling, mechanical integrity, cellular infiltration, and mineralization potential between all types of cryogels. The addition of bone char to CG cryogels produced scaffolds with appropriate porosity and interconnectivity. Additionally, the bone char cryogels exhibited an adequate swelling potential, suitable mechanical properties, excellent cell attachment, and increased mineralization. These properties support this cryogel for such an application in tissue engineering.

Homebound patients' perspectives on technology and telemedicine: A qualitative analysis.

Telemedicine holds promise in bridging the gap between homebound patients and high quality health care, but uptake of such technology remains limited. Qualitative interviews conducted with 17 homebound patients found two major barriers to telemedicine. First, participants who lack familiarity with technology are hesitant about telemedicine, as baseline use of technology in the home is limited, participants did not feel capable of learning, and the advantages of telemedicine were unclear. Second, homebound patients place a high value on in-office visits due to therapeutic benefit, face-to-face communication, and the social aspect of medical appointments.