The role of laser and energy-assisted drug delivery in the treatment of alopecia.

It has been recently established that laser treatment can be combined with topical or intralesional medications to enhance the delivery of drugs and improve overall results in a variety of different dermatological disorders. The aim of this review is to evaluate the use of laser and energy-assisted drug delivery (LEADD) for the treatment of alopecia with a specific focus on ablative fractional lasers (AFL), non-ablative fractional lasers (NAFL), and radiofrequency microneedling (RFMN). A comprehensive PubMed search was performed in December 2022 for "laser-assisted drug delivery" as well as "laser" and "alopecia." The evidence regarding LEADD for alopecia treatment is limited to two specific alopecia subtypes: alopecia areata (AA) and androgenetic alopecia (AGA)/pattern hair loss (PHL). LEADD with minoxidil and platelet-rich plasma (PRP) were evaluated for efficacy in both treatments of AA and AGA. LEADD with topical corticosteroids and intralesional methotrexate were studied for the treatment of AA, while LEADD with growth factors and stem cells were studied for the treatment of AGA. Multiple RCTs evaluated LEADD for topical corticosteroids with ablative fractional lasers for the treatment of AA. There is evidence in the literature that supports the use of topical minoxidil in combination with all devices for the treatment of AGA/PHL. All the reviewed studies show a positive treatment effect with LADD; however, some trials did not find LEADD to be superior to monotherapy or microneedling-assisted drug delivery. LEADD is a rapidly emerging treatment modality for the treatment of AGA and AA.

Laser-Assisted Drug Delivery in the Treatment of Scars, Rhytids, and Melasma: A Comprehensive Review of the Literature.

Although broad reviews on laser-assisted drug delivery (LADD) have been published in the past, an updated focused examination of its utility in the context of common, treatment-resistant, dermatologic conditions has not been published. This article reports a comprehensive scoping review of the potential benefits of LADD compared to laser or drug monotherapy for the treatment of 3 such conditions: scars, rhytids, and melasma. A PubMed (National Institutes of Health; Bethesda, MD) search was conducted for keywords including "laser-assisted drug delivery," "scar," "rhytid," and "melasma." Out-of-scope studies were excluded. To evaluate the efficacy of LADD for the treatment of scars, relevant articles were categorized by scar type: hypertrophic/keloid, atrophic, and hypopigmented. LADD, with both ablative and nonablative laser types, was studied in combination with corticosteroids, botulinum toxin-A (BTX-A), 5-fluorouracil, 5-aminolevulinic acid photodynamic therapy, stem cells, platelet-rich plasma, and prostaglandin analogs for the treatment of scars. Some randomized controlled trials demonstrated the efficacy of LADD, whereas others showed no significant differences in clinical outcomes but demonstrated reduced adverse effects. Regarding rhytids, laser treatment has been combined with various cosmeceuticals, including poly-L-lactic acid, topical retinaldehyde, and topical BTX-A. The studies reviewed supported the use of LADD with these drugs over monotherapy. Some studies showed that LADD was effective for the absorption of drugs such as poly-L-lactic acid and BTX-A which are often not effective topically. For melasma treatment, LADD with tranexamic acid and hydroquinone was superior in some studies, but not significantly different than monotherapy in other studies. LADD with certain drugs could be considered to treat scars, rhytids, and melasma.

Intravenous vs Oral Acetaminophen as a Component of Multimodal Analgesia After Total Hip Arthroplasty: A Randomized, Blinded Trial.

BACKGROUND: Multimodal analgesia including acetaminophen is increasingly popular for analgesia after total hip arthroplasty (THA). Intravenous (IV) administration of acetaminophen has pharmacokinetic benefits, but unclear clinical advantages. The authors hypothesized that IV acetaminophen would reduce pain with activity, opioid usage, or opioid-related side effects, compared to oral acetaminophen. METHODS: In this double-blinded, randomized, controlled trial, 154 THA patients received either IV or oral acetaminophen as part of a comprehensive opioid-sparing multimodal analgesia strategy. Primary outcomes were pain with physical therapy on postoperative day (POD) 1, opioid side effects (POD 1), and cumulative opioid use. RESULTS: There was no difference in opioid side effects, pain scores, or opioid use between the groups. CONCLUSION: Patients in both groups had low pain scores, minimal opioid side effects, and limited opioid usage (corresponding to 6 doses of tramadol 100 mg over 3 days). This highlights multimodal analgesia as an effective method of pain control for THA.

Bacterial Decolonization for Prevention of Radiation Dermatitis: A Randomized Clinical Trial.

Importance: Evidence-based approaches for the prevention of acute radiation dermatitis (ARD) are limited, and additional strategies are necessary to optimize care. Objective: To determine the efficacy of bacterial decolonization (BD) to reduce ARD severity compared with standard of care. Design, Setting, and Participants: This phase 2/3 randomized clinical trial was conducted from June 2019 to August 2021 with investigator blinding at an urban academic cancer center and enrolled patients with breast cancer or head and neck cancer receiving radiation therapy (RT) with curative intent. Analysis was performed on January 7, 2022. Interventions: Intranasal mupirocin ointment twice daily and chlorhexidine body cleanser once daily for 5 days prior to RT and repeated for 5 days every 2 weeks through RT. Main Outcomes and Measures: The primary outcome as planned prior to data collection was the development of grade 2 or higher ARD. Based on wide clinical variability of grade 2 ARD, this was refined to grade 2 ARD with moist desquamation (grade 2-MD). Results: Of 123 patients assessed for eligibility via convenience sampling, 3 were excluded, and 40 refused to participate, with 80 patients in our final volunteer sample. Of 77 patients with cancer (75 patients with breast cancer [97.4%] and 2 patients with head and neck cancer [2.6%]) who completed RT, 39 were randomly assigned BC, and 38 were randomly assigned standard of care; the mean (SD) age of the patients was 59.9 (11.9) years, and 75 (97.4%) were female. Most patients were Black (33.7% [n = 26]) or Hispanic (32.5% [n = 25]). Among patients with breast cancer and patients with head and neck cancer (N = 77), none of the 39 patients treated with BD and 9 of the 38 patients (23.7%) treated with standard of care developed ARD grade 2-MD or higher (P = .001). Similar results were observed among the 75 patients with breast cancer (ie, none treated with BD and 8 [21.6%] receiving standard of care developed ARD grade ≥2-MD; P = .002). The mean (SD) ARD grade was significantly lower for patients treated with BD (1.2 [0.7]) compared with patients receiving standard of care (1.6 [0.8]) (P = .02). Of the 39 patients randomly assigned to BD, 27 (69.2%) reported regimen adherence, and only 1 patient (2.5%) experienced an adverse event related to BD (ie, itch). Conclusions and Relevance: The results of this randomized clinical trial suggest that BD is effective for ARD prophylaxis, specifically for patients with breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03883828.

The Role of Fat Reducing Agents on Adipocyte Death and Adipose Tissue Inflammation.

Deoxycholic Acid (DCA), which is an FDA-approved compound for the reduction of submental fat, has evolved through an unanticipated and surprising sequence of events. Initially, it was used as a solvent for Phosphatidylcholine (PDC), which was thought to promote lipolysis, but it was later proven to be the bioactive component of the formula and is currently widely used as Kybella. It has also been used off-label to treat other types of fat deposits like lipomas, HIV lipodystrophy, and excess orbital fat. Despite widespread clinical use, there has been no consensus clarifying the mechanisms of DCA and PDC alone or in combination. Furthermore, despite PDC's removal from the FDA-approved formula, some studies do suggest it plays an important role in fat reduction. To provide some clarity, we conducted a PubMed search and reviewed 41 articles using a comprehensive list of terms in three main categories, using the AND operator: 1) Phosphatidylcholines 2) Deoxycholic Acid, and 3) Lipoma. We isolated articles that studied PDC, DCA, and a PDC/DCA compound using cell biology, molecular and genetic techniques. We divided relevant articles into those that studied these components using histologic techniques and those that utilized specific cell death and lipolysis measurement techniques. Most morphologic studies indicated that PDC/DCA, DCA, and PDC, all induce some type of cell death with accompanying inflammation and fibrosis. Most morphologic studies also suggest that PDC/DCA and DCA alone are non-selective for adipocytes. Biochemical studies describing PDC and DCA alone indicate that DCA acts as a detergent and rapidly induces necrosis while PDC induces TNF-α release, apoptosis, and subsequent enzymatic lipolysis after at least 24 hours. Additional papers have suggested a synergistic effect between the two compounds. Our review integrates the findings of this growing body of literature into a proposed mechanism of fat reduction and provides direction for further studies.

Exosome therapy in hair regeneration: A literature review of the evidence, challenges, and future opportunities.

BACKGROUND: Alopecia is a common chief complaint and is challenging to treat. As such, regenerative treatments to promote hair growth are an emerging area of research. Exosomes, which are extracellular vesicles involved in cell communication, homeostasis, differentiation, and organogenesis, have been shown to play a central role in hair morphogenesis and regeneration with potential for use as alopecia treatment. AIMS: This review summarizes and assesses the body of literature surrounding exosomes as regenerative therapeutics for alopecia and identifies areas for improvement in future research. METHODS: A review was conducted using a comprehensive list of keywords including "exosome," "alopecia," and "hair loss" on PubMed, EMBASE, and Google Scholar databases published from inception to February 2022. Reference lists of identified articles were included. 47 studies were included. Clinical trial databases were searched using the term "exosome"; however, no trials relevant to hair growth were identified. RESULTS: Our updated and comprehensive review details the history of exosome use in medicine, postulated underlying mechanisms in treating hair loss, and current clinical studies. Preclinical studies demonstrate clear benefits of exosome therapeutics in regenerative medicine and for hair loss treatment. Clinical trials demonstrate safety of exosome use in medicine, but data showing efficacy and safety of exosome therapy for alopecia are lacking. We identified several gaps in knowledge required for effective clinical translation including safety, exosome source, and optimal treatment delivery mechanism and dosage. CONCLUSION: Exosomes are on the horizon as an exciting therapeutic for the treatment of alopecia. Further studies and clinical trials are required.

Immune Checkpoint Inhibitor-Induced Psoriasiform, Spongiotic, and Lichenoid Dermatitis: A Novel Clinicopathological Pattern.

Immune checkpoint inhibitors (ICIs), a class of anticancer agents that upregulate T-cell response to tumor cells, are associated with immune-related adverse events (irAEs), and the skin is one of the most commonly affected organs. We report the first two cases of a unique ICI-induced clinicopathological entity. A psoriasiform-appearing eruption with psoriasiform, spongiotic, and lichenoid dermatitis pattern on histopathology. A 73-year-old male with stage IV melanoma treated with nivolumab and a 63-year-old female with stage IV colorectal cancer treated with pembrolizumab and TAK-981 separately presented to our clinic with a psoriasiform rash. In both patients, punch biopsy revealed an unusual combination of psoriasiform, spongiotic, and lichenoid dermatitis. Treatment with apremilast in the first patient yielded some improvement, while treatment with ixekizumab in the second patient yielded a complete resolution of the eruption. Our cases add to the growing body of reported immune toxicities related to ICI use and illustrate the utility of targeted immune suppression of pathways in disease phenotype to allow for ICI continuation and optimization of cancer treatment.

Verruca Vulgaris Eruption Arising in the Setting of a Tyrosine Kinase Inhibitor.

A 71-year-old female with breast cancer presented with a generalized papular rash that began following the initiation of rebastinib. Examination revealed scattered pink to skin-colored verrucous papules on the forehead, extremities, and back. A biopsy showed hyperkeratosis, hypergranulosis, digitated epidermal hyperplasia, and dilated blood vessels at the tips of dermal papillae consistent with verruca vulgaris. The patient discontinued rebastinib due to muscle weakness and the lesions resolved. Rebastinib is an antineoplastic agent that targets several tyrosine kinases. Tyrosine kinase inhibitors (TKI) frequently cause cutaneous adverse events, but to date, there have been no reported cases of a verruca vulgaris eruption arising in the setting of TKI treatment. Recent studies indicate that TKIs can have immunosuppressive effects by decreasing T-cell levels. We postulate that rebastinib induced an immunosuppressive state in our patient which permitted human papillomavirus (HPV) proliferation. To our knowledge, this is the first report describing a verruca vulgaris eruption with TKI therapy.

Design Modifications of the Posterior-Stabilized Knee System May Reduce Anterior Knee Pain and Complications Following Total Knee Replacement.

BACKGROUND: In total knee arthroplasty (TKA), advances in posterior-stabilized (PS) knee implant designs address patellofemoral mechanics and cam-post engagement in an effort to reduce patellofemoral pain and improve knee kinematics. Such modifications may include improved femoral rollback, improved femoral dislocation resistance, minimized wear, and improved longevity. QUESTIONS/PURPOSES: In this study, we compared a newer PS knee design that incorporates a left and right specific femoral component and smoother trochlear groove to improve patellofemoral mechanics with an older PS design in order to assess patellofemoral pain, manipulation rates, and revision rates. METHODS: Using an institutional database, we retrospectively identified TKAs performed by the same surgeon using the Logic® PS knee system and the older Optetrak PS knee system (Exactech Inc., Gainesville, FL, USA), with a minimum 2-year follow-up. Clinical outcomes for each cohort were measured using the Knee Society Clinical Rating System, University of California Los Angeles Activity Scale, pain visual analog scale (VAS), Veterans Rand 12-Item Health Survey, and Western Ontario and McMaster Universities Osteoarthritis Index. In addition, rates of anterior knee pain, manipulation, and revision were compared between the two knee systems, and a Kaplan-Meier survivorship curve defining failure as need for revision was calculated to allow comparison between the cohorts. RESULTS: From 2000 to 2018, there were 1482 TKAs performed using the Logic PS (not counting 12 patients who had died) and 445 in the Optetrak PS group (not counting 20 patients who had died). In the Logic PS and Optetrak PS groups, respectively, the average age at operation was 66.7 years and 68.6 years and the average body mass index was 30.8 and 31.2. Pain VAS scores were significantly lower in the Logic PS group than in the Optetrak group (1.72 vs. 2.75 out of 10, respectively). There was also a significant difference in the percentages of patients reporting anterior knee pain in the Logic group, as compared with the Optetrak group (5.6% vs. 11.8%, respectively). In addition, manipulation rates differed significantly between the Logic and Optetrak groups (0.34% vs. 10.70%, respectively). The revision rates were 1.15% for the Logic group and 2.0% for the Optetrak group. However, there was a significant difference in rates of revision performed because of osteolysis, favoring the Logic group (0.07% vs. 0.6%). The Kaplan-Meier survivorship curve shows a significant difference in time until revision between the Logic and Optetrak groups. CONCLUSION: Design modifications to improve patellofemoral mechanics demonstrated significant improvements in overall pain and patellofemoral pain and reduced manipulation rates post-operatively.

Multiacquisition Variable-Resonance Image Combination Magnetic Resonance Imaging Used to Study Detailed Bone Apposition and Fixation of an Additively Manufactured Cementless Acetabular Shell.

BACKGROUND: The ability to utilize magnetic resonance imaging (MRI) to assess bony fixation in 3 dimensions may allow a better understanding of the implant design and bony integration. We hypothesized that a new 3-dimensionally printed cementless highly porous acetabular component (Stryker Trident II TritaniumTM) would show better fixation than an earlier cup from the same manufacturer as assessed by the noninvasive technique of multispectral MRI. METHODS: Multiacquisition variable-resonance image combination selective metal suppression MRI was performed in 19 patients implanted with a new 3-dimensionally printed cup and 20 patients who had received a previous-generation cup from the same manufacturer at 1-year follow-up. Each cup was graded globally as well as by 9 specific zones. Integration grades were performed for each zone: 0, full bone integration; 1, fibrous membrane present; 2, osteolysis; and 3, fluid present. A mixed-effects logistic regression model was used to compare fixation between the 2 groups. RESULTS: All cups in both cohorts showed greater than 90% estimated global bony integration (3-dimensionally printed cups, 99.4%; regular cups 91.6%) with no osteolysis or fluid observed in any cup. The 3-dimensionally printed cup had 1 of 171 zones (0.6%) graded as fibrous membrane present, while the 2-dimensional group had 15 of 180 zones (8.3%) graded as fibrous. Of note, screw hole regions were omitted but may be read as fibrous membrane areas. CONCLUSION: Using multiacquisition variable-resonance image combination selective MRI, our analysis showed greater osteointegration and less fibrous membrane formation in the 3-dimensionally printed cups than the control group at 1-year follow-up.

Five-Year Follow-Up of Clinical Outcomes with an Anatomic Dual-Mobility Acetabular System: A Multicenter Study.

BACKGROUND: The dual-mobility implant system has been shown to increase impingement-free range of motion and decrease dislocation risk by increasing the effective head size. In addition, the anatomic dual-mobility (ADM) cup offers relief between the acetabular shell rim and the iliopsoas tendon. This study was designed to review a series of hips implanted with the ADM acetabular cup to examine clinical outcomes after 5 years of implantation at multiple orthopaedic centers. METHODS: We retrospectively queried our prospectively collected total joint arthroplasty registry for patients who underwent total hip arthroplasty with an ADM cup from January 2008 to December 2012 at 4 different orthopaedic institutions and who had minimum 5-year follow-up. Harris Hip Scores and visual analog scale scores were evaluated. Postoperative complications, dislocations, and revisions for any reason were recorded. RESULTS: A total of 142 patients had a mean follow-up of 5.7 years (range: 5.0 to 8.0 years). Radiographic analysis showed no radiolucent lines, osteolysis, or acetabular loosening. There were no dislocations in this patient series. Two (1.2%) hips required a revision because of adverse local tissue reactions related to corrosion from a recalled modular neck stem, but this was unrelated to the ADM cup. The mean Harris Hip pain scores increased from 17 points preoperatively to 39 points at the most recent follow-up (P < .001). The mean Harris Hip function score increased from an average of 29 points preoperatively to 38 points at the most recent follow-up (P < .001). The mean visual analog scale score showed patient improvement from 6.5 preoperatively to 1.2 postoperatively (P < .001). CONCLUSIONS: ADM prostheses were designed to reduce the risk of dislocation by increasing the size of the effective femoral head. In this multicenter study of ADM cups used in primary total hip arthroplasty, we demonstrated good clinical and radiographic outcomes, no dislocations, and no revisions at midterm 5-year minimum follow-up. Patient-reported outcome measures were also improved, supporting the use of this implant.