Reduced IFNL1 and/or IFNL2, but not IFNL3 is associated with worse outcome in patients with COVID-19.

The recent pandemic was caused by the emergence of a new human pathogen, SARS-CoV-2. While the rapid development of many vaccines provided an end to the immediate crisis, there remains an urgent need to understand more about this new virus and what constitutes a beneficial immune response in terms of successful resolution of infection. Indeed, this is key for development of vaccines that provide long lasting protective immunity. The interferon lambda (IFNL) family of cytokines are produced early in response to infection and are generally considered anti-viral and beneficial. However, data regarding production of IFNL cytokines in COVID-19 patients is highly variable, and generally from underpowered studies. In this study, we measured all three IFNL1, IFNL2 and IFNL3 cytokines in plasma from a well characterised, large COVID-19 cohort (n=399) that included good representation from patients with a more indolent disease progression, and hence a beneficial immune response. While all three cytokines were produced, they differed in both the frequency of expression in patients, and the levels produced. IFNL3 was produced in almost all patients but neither protein level nor IFNL3/IFNL4 SNPs were associated with clinical outcome. In contrast, both IFNL1 and IFNL2 levels were significantly lower, or absent, in plasma of patients that had a more severe disease outcome. These data are consistent with the concept that early IFNL1 and IFNL2 cytokine production is protective against SARS-CoV-2 infection.

Food Insecurity and Pediatric Nonalcoholic Fatty Liver Disease Severity.

OBJECTIVE: To determine the association between food insecurity and pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: Cross-sectional study of patients < 21 years of age with histologically confirmed NAFLD. The Household Food Security Survey Module was administered to determine food insecurity status. Skin lipidomics were performed to explore pathophysiologic mechanisms. RESULTS: Seventy-three patients with histologically confirmed NAFLD completed the Household Food Security Survey Module. Of these, the majority were male (81%) and non-Hispanic (53%), with a mean age at biopsy of 13 ± 3 years. Food insecurity was seen in 42% (n = 31). Comparison of features between food insecure and food secure subgroups revealed no differences in sex, ethnicity, BMI z-score, aminotransferases, or histologic severity. However, children experiencing food insecurity presented on average 2 years before their food secure counterparts (12.3 ± 3.0 vs 14.4 ± 3.6 years, P = .015). A subset of 31 patients provided skin samples. Skin lipidomics revealed that food insecurity was associated with down-regulated features from the lipoamino acid class of lipids, previously linked to inflammation and adipocyte differentiation. CONCLUSIONS: Food insecurity is highly prevalent in children with NAFLD and is associated with earlier presentation. Lipidomic analyses suggest a possible pathophysiologic link that warrants further exploration.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients.

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Sunscreen: a brief walk through history.

The sunscreens we see today were paved by our ancestors' sun protection methods, followed by scientific discovery in the more recent era and the trials and errors of the sunscreen formulations that followed. This history highlights sun protection methods used over the centuries and the varying degrees of agreeable sensorial properties or comforts in these methods.

Single-Center, Prospective, Double-Blind, Evaluator-Blind, non-Randomized, Vehicle-Controlled Trial With a 1927 Nm Non-Ablative Fractionated Laser and Topical 0.05% Tretinoin Lotion for Facial Dyspigmentation and Photodamage.

BACKGROUND: Dyspigmentation and photodamage are common concerns in patients who seek aesthetic consultation. A number of treatment modalities have been utilized to address this issue. 1927 nm thulium fiber laser is a fractionated non-ablative laser that has been shown to be safe and effective in treatment of photoaging. Topical retinoids have been used for over two decades for photoaging to promote epidermal hyperplasia and collagen synthesis and to decrease melanin production. There has been lack of data to support the combination of topical retinoids with laser treatments in the management of facial dyspigmentation and photodamage. OBJECTIVE: The primary objective of this study is to evaluate the benefits and subject satisfaction resulting from use of a 1927 nm thulium fiber laser with and without 0.05% tretinoin lotion for facial dyspigmentation and photodamage. RESULTS: Both groups showed a significant change in Investigator Assessed Overall Hyperpigmentation and Investigator Assessed Overall Photodamage over time (P<0.001). No statistically significant differences were seen between groups at any time point as measured by investigator reported and subject reported efficacy scales except for Subject Global Aesthetic Improvement Scale and Subject Satisfaction at 30 days after laser treatment, at which patients who received 0.05% tretinoin lotion reported a lower level of improvement (2.8 ± 0.86 in the treatment group vs 2 ± 0.85 in the vehicle group, P=0.009) and lower patient satisfaction when compared to the vehicle group (2.87 ± 1.55 in the treatment groups vs 1.53 ± 0.64 in the vehicle group, P=0.001). CONCLUSION: In our study, patients tolerated the combination of 1927 nm thulium fiber laser and 0.05% tretinoin lotion well. Both groups resulted in significant reduction of hyperpigmentation and photodamage. Subject satisfaction and perceived improvement were temporarily lower at 30 days only when, combining 0.05% tretinoin lotion with 1927 nm thulium fiber laser. Future studies are needed to investigate the impact on efficacy when combining laser procedures with a longer duration of use or a higher concentration of topical tretinoin. J Drugs Dermatol. 2021;20(11):1174-1179. doi:10.36849/JDD.6182.

Updates and Best Practices in the Management of Facial Erythema.

Facial erythema is a common dermatologic complaint. There are many medical and procedure-based treatments to help reduce the appearance of unwanted facial redness. The authors review a variety of treatment options and techniques to reduce facial erythema and prominent facial veins including topical medical therapies, a variety of lasers, light- and energy-based devices as well as the use of neuromodulators and sclerotherapy. The benefits and potential pitfalls of each procedure modality are also highlighted.

Omadacycline for treatment of Mycobacterium chelonae skin infection.

Mycobacterium chelonae can be difficult to treat because of inherent resistance to many available antimicrobials. We present a case of a multidrug-resistant M. chelonae skin infection in a 52-year-old woman who presented with a 3- to 4-week history of painful, erythematous nodules on the bilateral lower extremities. She demonstrated dramatic improvement at her 4-week follow-up on omadacycline.

Retinoschisis: splitting hairs on retinal splitting.

Retinoschisis can be found in the fovea or the retinal periphery, either of which may be present in isolation, or in conjunction with each other. Foveal schisis may be congenital, acquired, or secondary to an associated ocular pathology such as optic pit, glaucoma, or pathological myopia. The visual acuity is dependent on the cause of the schisis and appropriate treatment is variable based on likelihood for progression and visual impact. There are many useful considerations and tools for evaluation and monitoring that can be used to determine the aetiology and prognosis of these retinal findings. Retinoschisis is a diagnosis of exclusion, and pathology must be ruled out to accurately make the diagnosis. A review of two cases and following discussion summarises the various types, manifestations, presentations, and complications of retinoschisis and their evaluation, management, and appropriate monitoring or treatment. These cases lead a dialogue on the presentation and aetiology of retinoschisis, important considerations for differential diagnoses, and appropriate management.

Painful nipple hyperkeratosis secondary to vemurafenib.

Vemurafenib is a selected BRAF kinase inhibitor approved for treating metastatic or unresectable melanoma, which has numerous cutaneous side effects unfortunately, including three previously reported cases of asymptomatic areola and/or nipple hyperkeratosis. We present the first case of painful bilateral nipple hyperkeratosis secondary to vemurafenib in an 84-year-old woman. She was successfully treated with tretinoin 0.05% cream that allowed her to comfortably continue treatment. With increased awareness of this condition, we found a second case of asymptomatic nipple hyperkeratosis secondary to vemurafenib in our clinic. As this medication gains acceptance for treatment of metastatic melanoma, it is imperative that dermatologists are aware of this potentially uncomfortable side effect that can result in decreased compliance and impaired quality of life.

Complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a neurologic disorder that often results in debilitating chronic pain, but the diagnosis may elude providers as it is one of exclusion. A history of trauma may be elucidated. We report a case of CRPS and review the clinical findings, appropriate workup, and treatment options for the patient. The patient we describe went through an extensive workup before receiving the correct diagnosis. Delay in diagnosis leads to prolonged suffering for the patient and, at times, unnecessary invasive debridement procedures. Raising awareness of this entity may help physicians make the correct diagnosis early, as well as initiate a collaborative effort between neurology, anesthesiology, and dermatology to provide the patient the most favorable outcome.

Physical activity in older adults in a combined functional circuit and walking program.

Our study examined the impact of a 16-week functional circuit/walking program on physical activity (PA) in older adults in independent-living facilities. Exploratory goals included examination of associations among self-efficacy, neighborhood and mobility. Participants (N = 13) were female (M = 77.8, SD = 7.44, range = 65-85 years). One third were African-American; the remainder Caucasian; 1/3 used assistive devices. PA increased from 70 min/week (SD = 35.51) at baseline to 81.31 min/week (SD = 34.21) at 16 weeks. PA was associated with self-efficacy for overcoming neighborhood and facility barriers to walking at all measurement points (baseline r = .73, p < .05 and r = .68, p < .05, respectively). At eight weeks, PA was associated with self-efficacy for walking duration (r = .58, p < .05), self-efficacy for individual (r = .66, p < .05), facility (r = .58, p < .05) and neighborhood (r = .70, p < .05) barriers. At sixteen weeks, physical activity was associated with balance confidence (r = .72, p < .05), and self-efficacy for individual (r = .76, p < .05), facility (r = .71, p < .05), and neighborhood (r = .80, p < .01) barriers. Functional circuit/walking interventions can increase PA in older adults. Further examination of self-efficacy, mobility, neighborhoods and PA is needed.

Randomized trial of cesarean vs vaginal delivery for effects on the pelvic floor in squirrel monkeys.

BACKGROUND: Vaginal delivery is a risk factor in pelvic floor disorders. We previously described changes in the pelvic floor associated with pregnancy and parturition in the squirrel monkey, a species with a humanlike pattern of spontaneous age- and parity-associated pelvic organ prolapse. OBJECTIVE: The potential to prevent or diminish these changes with scheduled cesarean delivery (CD) has not been evaluated. In a randomized, controlled trial, we compared female squirrel monkeys undergoing spontaneous vaginal delivery with those undergoing scheduled primary CD for pelvic floor muscle volumes, muscle contrast changes, and dynamic effects on bladder neck position. STUDY DESIGN: Levator ani, obturator internus, and coccygeus (COC) muscle volumes and contrast uptake were assessed by magnetic resonance imaging in 20 nulliparous females examined prior to pregnancy, a few days after delivery, and 3 months postpartum. The position of bladder neck relative to bony reference line also was assessed with abdominal pressure using dynamic magnetic resonance imaging. RESULTS: Baseline measurements of 10 females randomly assigned to scheduled primary CD were not different from those of 10 females assigned to spontaneous vaginal delivery. Levator ani and obturator internus muscle volumes did not differ between groups, while volumes were reduced (P < .05) in the observation immediately after pregnancy. The COC muscles increased (P < .05) immediately after delivery for females in the spontaneous vaginal delivery group, but not for females in the scheduled CD group. Position of the bladder neck descended (P < .05) by 3 months postpartum in both groups. CONCLUSION: Scheduled CD diminishes changes in COC muscle volume and contrast reported to be associated with spontaneous vaginal delivery in squirrel monkeys. However, pelvic support of the bladder was not protected by this intervention suggesting that effects of pregnancy and delivery are not uniformly prevented by this procedure.

High-frequency phosphorus monitoring of the River Kennet, UK: are ecological problems due to intermittent sewage treatment works failures?

The River Kennet in southern England has exhibited excessive benthic algal growth and associated ecological problems, such as loss of macrophytes and invertebrates, since the 1980s. These ecological problems were attributed to regular peaks in phosphorus concentration, which were widely attributed to intermittent failures of the Marlborough sewage treatment works (STW). This study deployed high-frequency phosphorus auto-analysers to monitor the total reactive phosphorus (TRP) concentrations of Marlborough STW final effluent and the downstream River Kennet at hourly and 30 minute resolution respectively, between 2008 and 2009. This monitoring confirmed that the Marlborough STW was operating well within its 1000 µg l⁻¹ annual mean total phosphorus consent limit, with mean total P and soluble reactive P concentrations of 675 and 345 µg l⁻¹ respectively. There were two occasions where effluent TRP concentration exceeded 1000 µg l⁻¹, and only one of these resulted in a peak in TRP concentration of over 100 µg l⁻¹ in the River Kennet at Mildenhall. The other nine peaks of over 100 µg l⁻¹ in the River Kennet during the monitoring period were associated with storm events, indicating that diffuse-source inputs and remobilisation of stored within-channel phosphorus were the cause of the peaks in river concentration, rather than Marlborough STW. The value of high-frequency environmental monitoring and the problems associated with using nutrient auto-analysers in the field are discussed. Seasonal phosphorus consents for STWs could provide a useful and cost effective means to improve both water quality and river ecology in the upper River Kennet.

Inpatient brain MRI for new-onset seizures: utility and cost effectiveness.

Inpatient magnetic resonance imaging for evaluation of new-onset afebrile seizures can extend hospital stay, can add cost, and may not affect acute management. The study was to assess cost and impact on acute management of inpatient brain magnetic resonance imagings performed as part of new-onset seizure evaluation. Retrospective chart review of brain magnetic resonance imagings on pediatric inpatients admitted for new-onset afebrile seizure has been carried out. Seventy-five patients were identified. Seventy-one of the patients (95%) stayed an additional day for the magnetic resonance imaging. Thirteen had abnormal results. No patient had treatment changes based upon the magnetic resonance imaging results. If these magnetic resonance imagings had been done as an outpatient, the savings to the hospital could have been $215,575. Thus, obtaining an inpatient brain magnetic resonance imaging for evaluation of new-onset seizures did not lead to acute changes in management and added to facility costs and length of stay. Scheduling a magnetic resonance imaging as an outpatient could achieve cost savings without compromising care.

The safety of central line placement prior to treatment of pediatric acute lymphoblastic leukemia.

BACKGROUND: Central venous lines are placed in children with acute lymphoblastic leukemia at diagnosis, despite significant cytopenias, to facilitate the administration of chemotherapy and blood sampling. The present study aimed to determine the safety of central line placement in these patients. METHODS: We reviewed the charts of 115 consecutive patients treated during a 10-year period. Data abstracted comprised age, gender, presenting and preoperative blood counts, type of central line, blood products transfused preoperatively, duration of neutropenia (absolute neutrophil count [ANC], <500/microl), treatment, and central line-associated complications. RESULTS: There were 66 male and 49 female patients with a median age of 4 years. Seventy-one patients were classified as standard-risk and 44 as high-risk. Respective median blood counts at diagnosis and prior to surgery were white cell count (microl), 4,200 and 5,550; hemoglobin (g/dl), 7.7 and 9.4; platelet count (microl), 63,000 and 72,000; and ANC (microl), 3,950 and 4,900. The median duration of neutropenia was 15 days in the standard-risk group and 18 days in the high-risk group. Thirty-eight patients were not transfused preoperatively. There were no episodes of bacteremia. Seven patients (7%) with life-ports experienced a complication: in four blood could not be aspirated, two ports needed realignment, and one a wound infection developed without dehiscence. Four patients (27%) with external lines had a complication: one each with line occlusion, accidental removal by patient, line rupture, and line leakage at insertion site. The complication rate between ports and external lines was different (P = 0.045). CONCLUSIONS: Central line placement prior to anti-leukemia treatment is safe. Most complications are mechanical and not due to leukemia, chemotherapy, or cytopenias.