Nanoparticle-Mediated Delivery of Tetrahydrobiopterin Restores Endothelial Function in Diabetic Rats.

Endothelial dysfunction, underlying the vascular complications of, may result from uncoupling of endothelial nitric oxide synthase (eNOS) activity due to decreased levels of tetrahydrobiopterin (BH4), a critical co-factor for eNOS. Some clinical trials attempting to deliver exogenous BH4 as a potential therapeutic strategy in vascular disease states have failed due to oxidation of BH4 in the circulation. We sought to develop a means of protecting BH4 from oxidation while delivering it to dysfunctional endothelial cells. Polymeric and solid lipid nanoparticles (NPs) loaded with BH4 were delivered by injection or oral gavage, respectively, to streptozotocin-induced diabetic rats. BH4 was measured in coronary endothelial cells and endothelium-dependent vascular reactivity was assessed in vascular rings. Lymphatic uptake of orally delivered lipid NPs was verified by sampling mesenteric lymph. BH4-loaded polymeric NPs maintained nitric oxide production by cultured endothelial cells under conditions of oxidative stress. BH4-loaded NPs, delivered via injection or ingestion, increased coronary endothelial BH4 concentration and improved endothelium-dependent vasorelaxation in diabetic rats. Pharmacodynamics assessment indicated peak concentration of solid lipid NPs in the systemic bloodstream 6 hours after ingestion, with disappearance noted by 48 hours. These studies support the feasibility of utilizing NPs to deliver BH4 to dysfunctional endothelial cells to increase nitric oxide bioavailability. BH4-loaded NPs could provide an innovative tool to restore redox balance in blood vessels and modulate eNOS-mediated vascular function to reverse or retard vascular disease in diabetes.

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

A Case Series on the Use of Brentuximab Vedotin for the Treatment of Mycosis Fungoides.

BACKGROUND: Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that appears to be more effective against CD30-expressing cutaneous T-cell lymphoma (CTCL) compared to current standard-of-care treatments.   Objective: To determine the real-world efficacy and adverse effects of BV use in patients with mycosis fungoides (MF) who were treated with BV at Atrium Health Wake Forest Baptist Medical Center. METHODS: Study staff performed a retrospective chart review of patients diagnosed with MF who were prescribed BV at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. RESULTS:   Regardless of their response to BV, all patients in our cohort had higher CD30 positivity on subsequent biopsies compared to their initial skin biopsy.  Conclusions: Improved understanding of appropriate CD30 testing and evaluation will allow for quicker invention of patients with BV responsive CTCL.  J Drugs Dermatol. 2023;22(12):e33-e34.    doi:10.36849/JDD.6981e.

Topical Moisturizer Meaningfully Reduces Disease Severity in Atopic Patients With Xerosis.

BACKGROUND: Repairing the epidermal barrier is critically important in atopic dermatitis (AD), but the effect of moisturizer on quality of life (QOL) is not well characterized.  Objective: To assess whether the use of a moisturizer improves QOL in atopic patients with xerosis.  Methods: Thirty-five (35) adults with xerosis and AD received a moisturizer designed for AD to apply daily for three months. Adherence was assessed with electronic monitors. Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI) at baseline and follow-up.  Results: Mean adherence to the moisturizer was 46%. Dryness improved from 1.9 at baseline to 1.4 at follow-up (P=0.02). DLQI improved from 3.3 at baseline to 1.5 at 3 months (P=0.005). The "feeling self-conscious or embarrassed due to their skin condition" DLQI item improved from 0.79 at baseline to 0.14 at 3 months (P=0.0009).  Conclusion: Moisturizers are the foundation of AD treatment. Even non-medicated topical emollients can improve QOL in patients with AD.  J Drugs Dermatol. 2023;22(12):e51-e52.     doi:10.36849/JDD.7036e.

The role of traditional social determinants of health in referral patterns, timing of surgery, and Chiari Health Index for Pediatrics-determined quality of life in children with symptomatic Chiari type I malformation.

OBJECTIVE: Understanding the impact of the social determinants of health on the utilization of healthcare resources is an important step in eliminating inequalities. The goal of this study was to determine the role of social determinants of health in referral patterns, timing of consultation/intervention, and quality of life in children with Chiari malformation type I (CM-I). METHODS: A retrospective study was conducted of children aged 0 to 18 years who underwent surgical treatment for CM-I at a single pediatric facility from 2015 to 2019. The variables included demographic and socioeconomic characteristics, referral patterns, timing, and quality of life data based on the Chiari Health Index for Pediatrics (CHIP). RESULTS: The cohort consisted of 103 surgically treated CM-I patients. No differences were seen in race, sex, insurance, or household income when evaluating referral source (community, specialist, or emergency department) or when comparing patients with incidental versus symptomatic findings. In the evaluation of timing from initial evaluation to surgery, no statistical differences were seen between racial, sex, insurance status, or income groups. Children from households of lower median family income were significantly more likely to report pain at the time of consultation (pain group median [interquartile range] $46,660 [$41,004-$50,367] vs nonpain group $53,604 [$41,427-$59,828], p = 0.004). Those in the lower-income group also reported lower CHIP scores corresponding to increased symptomatology in the nonpain physical symptoms (p = 0.004) and psychosocial domains (p = 0.018). CONCLUSIONS: There was no evidence of a difference in referral patterns or a delay in time from clinic presentation to surgery based on the traditional social determinants of health categories. Children from households in the lower-income group were associated with increased severity of pain and nonpain symptoms.

Topical Ivermectin Is Associated With Improved Erythematotelangiectatic, Papulopustular, and Phymatous Rosacea in a Secondary Analysis.

Rosacea has variable clinical presentation consisting of four overlapping phenotypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1 Rosacea's pathogenesis involves increased cutaneous density of Demodex folliculorum mites, which drive inflammation through activation of Toll-like receptor-2.1,2 Thus, topical ivermectin (IVM) 1.0% cream's anti-inflammatory and acaricidal activity provides an effective and targeted treatment for moderate-to-severe rosacea. However, literature assessing IVM is limited to efficacy in treating the papulopustular presentation, limiting generalizability.1,3,4 Although our primary endpoint was to assess patient adherence, the objective of this secondary analysis was to assess IVM efficacy in rosacea, regardless of clinical presentation.

The Patient-Physician Relationship and Adherence: Observations From a Clinical Study.

Improved patient-physician relationships (PPR) are associated with better patient satisfaction and disease outcomes, however, there is limited literature assessing how PPR affects adherence in dermatology. We recruited 30 subjects with a clinical diagnosis of rosacea. Subjects were instructed to use ivermectin 1% cream once daily for 3 months and adherence was measured using the Medication Event Monitoring System cap. The Patient-Doctor Relationship Questionnaire (PDRQ-9), a validated questionnaire assessing patients’ perceived strength of the relationship with their doctor, was completed. Mean adherence for all subjects over three months of the study was 62%. PDRQ-9 scores positively correlated with adherence rates for 3 months of treatment (r(26)=0.52; P=0.006). The perceived strength of the PPR may have a role in patients’ adherence to their medications. Improving the PPR, through empathy and effective communication, may facilitate better medication adherence and treatment outcomes. Perche PO, Singh R, Cook MK, et al. The patient-physician relationship and adherence: observations from a clinical study. J Drugs Dermatol. 2023;22(8):838-839. doi:10.36849/JDD.7103.

Perception of accountability decreases with age: observations from a clinical study of patients with rosacea.

Patient adherence to medications usually increases with age, however, it can also be impacted by other factors. Accountability is a psychosocial construct that is defined as the expectation for an individual to account for their actions. Accountability may also influence patients' motivation to adhere to their treatments. We assessed the relationship between age and perception of accountability as well as efficacy of interventions to improve accountability in a clinical study of 30 rosacea patients. Accountability was assessed using the validated Accountability Measurement Tool. Interventions to improve accountability included a digital interaction group and a digital skin analysis group. All patients were given ivermectin cream 1% and informed to apply it daily for 3-months. There was a negative association between age and AMT scores in all intervention groups, including the control group. Younger patients have a baseline greater perception of accountability that responded more to our interventions.

Full-endoscopic spine surgery diminishes surgical site infections - a propensity score-matched analysis.

BACKGROUND CONTEXT: Surgical site infections (SSI) are one the most frequent and costly complications following spinal surgery. The SSI rates of different surgical approaches need to be analyzed to successfully minimize SSI occurrence. PURPOSE: The purpose of this study was to define the rate of SSIs in patients undergoing full-endoscopic spine surgery (FESS) and then to compare this rate against a propensity score-matched cohort from the National Surgical Quality Improvement Program (NSQIP) database. DESIGN: This is a retrospective multicenter cohort study using a propensity score-matched analysis of prospectively maintained databases. PATIENT SAMPLE: A total of 1277 noninstrumented FESS cases between 2015 and 2021 were selected for analysis. In the nonendoscopic NSQIP cohort we selected data of 55,882 patients. OUTCOME MEASURES: The occurrence of any SSI was the primary outcome. We also collected any other perioperative complications, demographic data, comorbidities, operative details, history of smoking, and chronic steroid intake. METHODS: All FESS cases from a multi-institutional group that underwent surgery from 2015 to 2021 were identified for analysis. A cohort of cases for comparison was identified from the NSQIP database using Current Procedural Terminology of nonendoscopic cervical, thoracic, and lumbar procedures from 2015 to 2019. Trauma cases as well as arthrodesis procedures, surgeries to treat pathologies affecting more than 4 levels or spine tumors that required surgical treatment were excluded. In addition, nonelective cases, and patients with wounds worse than class 1 were also not included. Patient demographics, comorbidities, and operative details were analyzed for propensity matching. RESULTS: In the nonpropensity-matched dataset, the endoscopic cohort had a significantly higher incidence of medical comorbidities. The SSI rates for nonendoscopic and endoscopic patients were 1.2% and 0.001%, respectively, in the nonpropensity match cohort (p-value <.011). Propensity score matching yielded 5936 nonendoscopic patients with excellent matching (standard mean difference of 0.007). The SSI rate in the matched population was 1.1%, compared to 0.001% in endoscopic patients with an odds ratio 0.063 (95% confidence interval (CI) 0.009-0.461, p=.006) favoring FESS. CONCLUSIONS: FESS compares favorably for risk reduction in SSI following spinal decompression surgeries with similar operative characteristics. As a consequence, FESS may be considered the optimal strategy for minimizing SSI morbidity.

Stigmatization, a social perception which may have a debilitating impact on hidradenitis suppurativa patients: an observational study.

Hidradenitis suppurativa (HS) is a debilitating disease and patients are prone to feelings of stigmatization. In our cohort, we assessed how feelings of stigmatization may relate to patient quality of life (QOL), depression, and social anxiety. Participants completed the Dermatology Life Quality Index (DLQI) to assess QOL, Patient Health Questionnaire 9 (PHQ-9) to assess depression, the Brief Fear of Negative Evaluation (BFNE) to assess social anxiety, and an adapted version of the Feelings of Stigmatization (FoS) to assess stigmatization. The FoS also correlated with DLQI (R = 0.68), PHQ-9 (R = 0.42), and BFNE (R = 0.52). Participants with greater FoS were also more likely to have worse QOL (18.1), higher levels of depression (11.1), and higher social anxiety (30.1), as compared to those with less FoS (6.7, P < 0.001; 4.9, P < 0.001; 23.2, P < 0.001, respectively). HS is a chronic disease with no definitive treatment. Effective screening protocols, coupled with pharmacological and nonpharmacological interventions, may help patients with HS's psychosocial burden.

Real-world outcomes following switching from anti-TNF reference products to biosimilars for the treatment of psoriasis.

Tumor necrosis factor (TNF) inhibitors improved clinical outcomes for patients with psoriasis but are limited by their high cost. There are several biosimilar options approved for the treatment of psoriasis which provides a lower-cost alternative and the potential to increase treatment availability for both biologically naïve and bioexperienced patients. Numerous phase III randomized controlled trials (RCTs) have investigated the effects of switching from biologics to biosimilars; biosimilars had comparable safety and efficacy to their reference products. Real-world evidence may provide complementary information on the expected performance of biosimilars. In this literature review, we analyzed data from real-world studies on switching from biologics for psoriasis to their biosimilars. Effectiveness and safety profiles were comparable when switching from biologics to biosimilars of adalimumab, etanercept, and infliximab. These studies are limited by their sample sizes, duration of follow-up, and single-arm designs without control groups. Based on available real-world evidence, patients may safely and effectively undergo switching to biosimilar therapies for the treatment of psoriasis.

Protocolized management of isolated linear skull fractures at a level 1 pediatric trauma center.

OBJECTIVE: Isolated linear skull fractures without intracranial findings rarely require urgent neurosurgical intervention. A multidisciplinary fracture management protocol based on antiemetic usage was implemented at our American College of Surgeons-verified level 1 pediatric trauma center on July 1, 2019. This study evaluated protocol safety and efficacy. METHODS: Children younger than 18 years with an ICD-10 code for linear skull fracture without acute intracranial abnormality on head CT were compared before and after protocol implementation. The preprotocol cohort was defined as children who presented between July 1, 2015, and December 31, 2017; the postprotocol cohort was defined as those who presented between July 1, 2019, and July 1, 2020. RESULTS: The preprotocol and postprotocol cohorts included 162 and 82 children, respectively. Overall, 57% were male, and the median (interquartile range) age was 9.1 (4.8-25.0) months. The cohorts did not differ significantly in terms of sex (p = 0.1) or age (p = 0.8). Falls were the most common mechanism of injury (193 patients [79%]). After protocol implementation, there was a relative increase in patients who fell from a height > 3 feet (10% to 29%, p < 0.001) and those with no reported injury mechanism (12% to 16%, p < 0.001). The neurosurgery department was consulted for 86% and 44% of preprotocol and postprotocol cases, respectively (p < 0.001). Trauma consultations and consultations for abusive head trauma did not significantly change (p = 0.2 and p = 0.1, respectively). Admission rate significantly decreased (52% to 38%, p = 0.04), and the 72-hour emergency department revisit rate trended down but was not statistically significant (2.8/year to 1/year, p = 0.2). No deaths occurred, and no inpatient neurosurgical procedures were performed. CONCLUSIONS: Protocolization of isolated linear skull fracture management is safe and feasible at a high-volume level 1 pediatric trauma center. Neurosurgical consultation can be prioritized for select patients. Further investigation into criteria for admission, need for interfacility transfers, and healthcare costs is warranted.

Therapeutic Potential of Tralokinumab in the Treatment of Atopic Dermatitis: A Review on the Emerging Clinical Data.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that greatly impacts patient quality of life. Type 2 cytokine interleukin (IL)-13 is integral to the pathogenesis of AD. Tralokinumab is a fully human IgG4 monoclonal antibody that specifically targets IL-13, preventing downstream signaling of inflammatory pathways that may contribute to AD. Tralokinumab was US Food and Drug administration (FDA) recently approved for the treatment of moderate to severe AD on December 28, 2021. In our review, we will explore the efficacy and adverse effects (AEs) of tralokinumab for the treatment of patients with moderate to severe AD. A PubMed search for key articles on the emerging clinical data of tralokinumab was performed. Six randomized controlled trials of tralokinumab identified improvements in disease severity measures, including Investigator's Global Assessment (IGA) scores and Eczema Area Severity Index 75 (EASI75) scores. Four of these studies demonstrated improvements in quality of life measures with tralokinumab, including pruritus scores, sleep interference scores, Dermatology Life Quality Index, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure, and The Short Form 36 Health Survey (SF-36v2) scores. One study identified a similar immune response in patients taking tralokinumab to those taking the Tdap and meningococcal vaccines. Upper respiratory infection, conjunctivitis, and headaches were the most common adverse events. The varying criteria to assess changes in AD disease severity across different studies is a limitation of this review. Tralokinumab is another promising biologic option for the treatment of moderate to severe AD, which may reduce disease burden and improve patient quality of life.

Comparing available JAK inhibitors for treating patients with psoriasis.

INTRODUCTION: Cytokine blockers have revolutionized the management of psoriasis. While efficacious, not all patients respond, and treatment may lose efficacy over time. Janus kinase (JAK) inhibitors target the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) transduction cascade from transmitting cytokine signals in psoriasis. AREAS COVERED: A PubMed search of phase I, II, and III clinical trials published between 2012 and 2021 utilizing the key terms: Janus kinase and psoriasis. Our search was expanded from clinical trials to further investigate the pathophysiology, standard of care, and safety and efficacy of JAK inhibitors in psoriasis. EXPERT OPINION: Current treatments for psoriasis include topicals, phototherapy, and systemic therapy. The subcutaneous or intravenous route of biologic administration presents a challenge as patients often prefer oral medications over injections and because of anti-drug antibody development. Tofacitinib is effective and has an overall mild-to-moderate safety profile but includes an FDA black box warning for increased risk of cardiovascular events and malignancy. Other JAK inhibitors have an acceptable safety profile and are effective in early clinical trials. Poor topical medication adherence should be considered when evaluating JAK inhibitors. Oral JAK inhibitors may provide a preferable route of administration and improved clinical outcomes.

Full Endoscopic Ligamentum Flavum Sparing Unilateral Laminotomy for Bilateral Recess Decompression: Surgical Technique and Clinical Results.

OBJECTIVE: Interlaminar endoscopic spine surgery has been introduced and utilized for lumbar lateral recess decompression. We modified this technique and utilized it for bilateral lateral recess stenoses without significant central stenosis. Here we present the surgical details and clinical outcome of ligamentum flavum sparing unilateral laminotomy for bilateral recess decompression (ULBRD). METHODS: Prospectively collected registry for full-endoscopic surgeries was reviewed retrospectively. One hundred eighty-two consecutive cases from a single center between September 2015 and March 2021 were reviewed and 57 of them whom underwent ULBRD were enrolled for analysis. Basic patient demographic data, perioperative details, surgeryrelated complications, and clinical outcome were reviewed. The detailed surgical technique is presented as well. RESULTS: Among the 57 patients enrolled, 37 were males while the other 20 were females. The mean age was 58.53 ± 14.51 years, and a bimodal age distribution at the age of mid-fifties and mid-sixties or older was noted. The later age-peak was related to coexistence of degenerative scoliosis. The average operative time per lamina was 70.34 ± 20.51 minutes and mean length of stay was 0.56 ± 0.85 days. Four perioperative complications were reported (7.0%) and the overall reoperation rate at the index level within 1 year was 8.8%. The preoperative back/leg visual analogue scale scores and functional outcome scales including EuroQol-5 dimension questionnaire, Oswestry Disability Index presented significant improvement immediately after surgery and were maintained until final follow-up. CONCLUSION: ULBRD for bilateral lateral recess stenoses without significant central stenosis resulted in good clinical outcomes with acceptably low perioperative complications rates. Sufficient decompression was achieved with the central ligamentum flavum being preserved.