Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

Maximizing patient comfort during hyaluronic acid gel injection is a common concern that is usually addressed by selecting fillers with lidocaine. Two randomized, double-blinded, split-face trials aimed to demonstrate noninferiority of specific hyaluronic acid fillers incorporating mepivacaine (RHA-M) versus their lidocaine controls, at providing pain relief. Thirty subjects per trial received injections of RHA R -M versus RHA R , and RHA4-M versus RHA4, respectively, in the perioral rhytids (PR) and nasolabial folds (NLF). Pain was assessed on a visual analog scale; aesthetic effectiveness was evaluated with validated scales, and safety was monitored based on common treatment responses (CTRs) and adverse events (AEs). RHA-M fillers proved as effective as their lidocaine counterparts at reducing pain (noninferior, p < .0002 and p < .0001). Bilateral wrinkle improvement was measured both in the PR (-1.5 ± 0.6 points on each side) and in the NLF (-1.8 ± 0.6 and -1.9 ± 0.5 points) trials at one month, with virtually identical responder rates (≥96.7%). Common treatment responses and AEs were similar between treated sides, and none was clinically significant. Resilient hyaluronic acid fillers with either mepivacaine or lidocaine are equally effective at reducing pain during treatment and equally performant and safe for correction of dynamic facial wrinkles and folds.

BackgroundOnabotulinumtoxinA 20 U reduces glabellar line (GL) severity at maximum frown for approximately 3 to 4 months. Small studies have suggested that >20-U doses may increase the efficacy and duration of response for GLs.ObjectivesThe aim of this study was to evaluate safety, pharmacodynamic response, and treatment satisfaction with onabotulinumtoxinA doses ≥20 U for GLs.MethodsThis 48-week, double-blind study compared 40, 60, and 80 U onabotulinumtoxinA vs 20 U and placebo in women with moderate or severe dynamic GLs on the Allergan Facial Wrinkle Scale. The following parameters were evaluated: the percentage of subjects with investigator-assessed ≥1-grade Facial Wrinkle Scale improvement from baseline at maximum frown (responders) at Week 24; the estimated median duration of response; the proportion of mostly/very satisfied responders on the Facial Line Satisfaction Questionnaire follow-up Items 1 to 5; and treatment-emergent adverse events.ResultsThe modified intent-to-treat population (N = 226) had a mean age of 48.0 years, with similar baseline GL severity between treatment groups. Week 24 responder rates were 0% for placebo and 16.0%, 32.0%, 30.6%, and 38.5% for onabotulinumtoxinA 20, 40, 60, and 80 U, with significant (P < 0.05) differences for 40 and 80 U vs 20 U. Median duration of response was longer with all higher doses vs 20 U (≥24.0 vs 19.7 weeks; P < 0.05 vs 20 U at Week 24). Facial Line Satisfaction Questionnaire results indicated high subject satisfaction. The incidence and severity of treatment-emergent adverse events did not exhibit a dose-response effect.ConclusionsGL treatment with onabotulinumtoxinA doses >20 U demonstrated longer duration of response and higher patient-reported satisfaction vs the on-label 20-U dose with no apparent impact on safety variables.Level of Evidence: 2

Neuraxial opioids are well known to cause itching, which may be challenging to treat. Neuraxial morphine has been demonstrated to cause recrudescent herpes simplex viruses (HSV-1), especially in women during labor and childbirth with neuraxial analgesia, and may be an occult etiology of refractory itching. This educational review summaries the clinical and epidemiological characteristics associated with recrudescent HSV-1 in patients treated with neuraxial opioids, especially morphine

The use of medicinal leeches in modern reconstructive surgery is well-described. Leech therapy after rhinoplasty has not been previously well-characterized. The medical records of all patients who underwent open rhinoplasty by a single surgeon over a 4-year period were reviewed. Patient demographics, including age, sex, medical comorbidities, number of previous rhinoplasty surgeries, time to utilization of leech therapy, adjunct therapies used, resolution of skin changes, and smoking status, were recorded. Operative reports were reviewed for pertinent information, including number of tip grafts used, graft materials used, and placement of septal extension grafts or "unicorn" grafts. Between April of 2016 and March of 2020, 545 patients underwent rhinoplasty performed by the senior author (P.S.N.). Of these patients, 39 (7.2 percent) underwent leech therapy postoperatively. The mean age of included patients was 47.4 years. Of the patients who required leech therapy, 34 (87.2 percent) had undergone revision rhinoplasty. The mean number of previous rhinoplasties was 3.4. The mean number of tip grafts used was 2.6. Thirty-three patients (84.6 percent) had either a traditional septal extension graft or unicorn graft placed. Nine patients (23.1 percent) were former smokers. Complete resolution of skin color changes was seen in 38 patients (97.4 percent). There were no major complications after leech therapy. Leech therapy is a useful tool for the rhinoplasty surgeon, particularly in the setting of complex revision rhinoplasty, in patients who have undergone multiple previous nasal surgical procedures, or in patients who require significant cartilage grafting to reconstruct the nasal tip or lengthen the nose. Therapeutic, IV.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, involving approximately 25% of the general population and increasing in prevalence in patient populations afflicted with metabolic syndrome and type 2 diabetes. This article discusses the complex interplay between NAFLD and chronic kidney disease (CKD), as well as the underlying pathogenesis and mechanisms through which NAFLD and CKD are linked. Exploration of these sophisticated relationships and causative factors is essential to accurately assessing kidney function in patients with NAFLD, recommending pharmacologic treatment of disease, and identifying favorable avenues for future investigation.

BackgroundValidated, objective clinical scales are needed to assess aesthetic improvement of the lips after augmentation with dermal fillers.ObjectiveTo develop a lip fullness rating scale and establish its reliability for grading subjects in clinical trials or routine practice, and sensitivity for detecting clinically meaningful changes.MethodsThe Teoxane Lip Fullness Scale (TLFS), a proprietary, 5‐grade photonumeric scale, was developed by clinical experts based on real subject photographs and was validated through both photographic and live subjects' evaluation.ResultsClinician intra‐ and inter‐rater agreement for the TLFS was substantial to almost perfect. Mean intra‐rater weighted Kappa score between the two rounds of photographic validation was 0.92, and inter‐rater agreement was substantial with an ICC of 0.93 for the combined rounds. Average intra‐rater weighted Kappa score and inter‐rater ICC for the live validation were equally high, reaching 0.91 and 0.89 respectively. Additionally, evaluators identified clinically significant differences between photographs of subjects presenting a 1‐grade or 2‐grade difference on the scale in 90% and 98% of cases, respectively.ConclusionsThe intra‐rater Kappa scores and inter‐rater ICC met their pre‐determined acceptance criteria of >0.70 in the photographic and live validation. The TLFS was shown to be a repeatable and reproducible Clinician Reported Outcome (Clin‐RO) for healthcare providers to classify lip fullness both in clinical trials and in routine patient care. A 1‐grade difference on the TLFS can detect a clinically meaningful difference in lip fullness.

The perioral region is highly mobile and subject to multifactorial changes during aging. Resilient Hyaluronic Acid Redensity (RHAR), an RHA filler, was developed with the aim of optimizing outcomes in dynamic facial areas. This randomized, blinded, multicenter clinical study aimed to demonstrate superiority of RHAR over no-treatment control for correction of moderate-to-severe dynamic perioral rhytides. Blinded live evaluator assessments of efficacy included improvement in perioral rhytides severity using a proprietary scale (Perioral Rhytids Severity Rating Scale [PR-SRS]) and the Global Aesthetic Improvement Scale. Subjects self-assessed their results with FACE-Q, a validated patient-reported outcome measure, and satisfaction scales. Safety was monitored throughout the study based on common treatment responses (CTRs) and adverse events (AEs). The primary efficacy end point was achieved, with the treatment group showing statistically significant superiority over the control group at Week 8 (80.7% vs 7.8% responder rate by PR-SRS, p < .0001). Most patients (66%) were still responders at Week 52 (study completion). Most AEs were CTRs after perioral injection of a dermal filler, and none was a clinically significant treatment-related AE. Resilient Hyaluronic Acid Redensity is effective and safe for the correction of dynamic perioral rhytides in all Fitzpatrick phototypes, with marked durability.

Digitally customized abutments are increasingly used in contemporary implant prosthodontics. This systematic review and meta-analysis aimed at comparing the peri-implant clinical outcomes of digitally customized and prefabricated abutments. The search strategies included electronic databases (PubMed, Embase, Scopus, and Cochrane clinical trials database) and related journals up to September, 2020. A qualitative and quantitative synthesis was performed on data extracted from the included studies. Three RCTs (number of patients = 120; number of dental implants = 120) and two prospective cohort studies (number of patients = 144; number of dental implants = 144) with one to three-year follow-up periods were included. The quantitative analyses did not demonstrate a significant difference between digitally customized and prefabricated abutments for peri-implant pocket depth (P = 0.62), plaque index (P = 0.67), bleeding on probing (P = 0.43), keratinized mucosa width (P = 0.75), and pink aesthetic score (P = 0.30) at one-year follow-up visit. The qualitative analyses for marginal bone level change, calculus accumulation, implant survival rate, implant success rate, white aesthetic score, and patient-reported outcomes did not demonstrate a significant difference between two groups during 1 to 3-year follow-up visits. The current data do not provide evidence of significant differences between two abutment fabrication methods in terms of peri-implant clinical outcomes within short-term period (CRD42020170807).