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Michael Kaiser,1 Rama Abdin,2 Simonetta I Gaumond,1 Naiem T Issa,3,4 Joaquin J Jimenez1 1Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; 2Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA; 3Forefront Dermatology, Vienna, VA, USA; 4Issa Research and Consulting, LLC, Springfield, VA, USACorrespondence: Joaquin J Jimenez, Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA, Tel +1 305-243-6586, Email j.jimenez@med.miami.eduAbstract: Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women. Traditionally, topical minoxidil and oral finasteride have been the standard of care yielding mixed results. New treatments such as Low-Level Laser Therapy (LLLT), microneedling, platelet-rich plasma (PRP), and others have been extensively studied in the literature, and the purpose of this review is to provide a comprehensive discussion of the latest treatment methods and their efficacy in treating AGA. Novel therapies such as oral minoxidil, topical finasteride, topical spironolactone, botulinum toxin, and stem cell therapy offer interesting alternatives to standard of care therapies for patients. In this review, we present data from recent studies on the clinical efficacy of these treatments. Furthermore, as new treatments have emerged, clinicians have tested combination therapies to assess whether there may be a synergistic relationship between multiple modalities. While there has been a great increase in the treatments available for AGA, the quality of evidence varies greatly and there is still a great need for randomized double blinded clinical trials to adequately assess the clinical efficacy of some treatments. While PRP and LLLT have demonstrated encouraging results, standardized treatment protocols are needed to adequately inform clinicians on how to use such therapies. Given the abundance of new therapeutic options, clinicians and patients must weigh the benefits and risks of each treatment option for AGA.Keywords: androgenetic alopecia, minoxidil, finasteride, platelet rich plasma, microneedling

Nadia Peyravian,1 Sapna Deo,1 Sylvia Daunert,1 Joaquin J Jimenez1,2 1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA; 2Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USACorrespondence: Joaquin J Jimenez, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA, Tel +1 305 243 6586, Email j.jimenez@med.miami.eduAbstract: Acne is the most common skin condition in the United States and affects approximately 85% of people ages 12– 24. As a multifactorial disease, the pathogenesis of acne involves overproduction of sebum, irregular shedding of the cutaneous cells, accretion of Cutibacterium acnes at the pilosebaceous unit, and inflammation. To date, conventional therapies for acne include topical retinoids, over-the-counter bactericidal agents, and systematic treatments, such as oral antibiotics and isotretinoin. However, the potential for significant side effects and risk of antibiotic resistance remain limitations in these therapies, in turn reducing patient compliance and adherence to acne treatment regimens. Therefore, the use of natural plant-derived treatments or phytotherapeutics as an alternative or adjuvant to conventional treatments is attractive to patients due to their safety and minimal risk for side effects. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid of the Cannabis sativa (hemp) plant. The therapeutic use of CBD has been implicated in many diseases with an inflammatory aspect, including cancers, neurodegeneration, immunological disorders, and dermatological diseases. However, the use of CBD for acne treatment remains a novel window of opportunity. Herein, we summarize the available and relevant data, highlighting the potential use of CBD in acne for its anti-inflammatory properties. To that extent, CBD and other cannabis constituents such as cannabis seeds were found to reduce inflammation and expression of inflammatory cytokines including TNF-α and IL-1β when evaluated in acne-like conditions. Treatment with these cannabis extracts was also found to be safe and well tolerated, further strengthening the prospect of CBD as an anti-inflammatory therapeutic for acne.Keywords: cannabidiol, CBD, acne, inflammation, therapeutic

Sharon M Hudson,1,2 Bobeck S Modjtahedi,2– 4 Danielle Altman,2 Jennifer J Jimenez,2 Tiffany Q Luong,2 Donald S Fong2,3 1Keck School of Medicine of USC/Children’s Hospital Los Angeles, Los Angeles, CA, USA; 2Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA, USA; 3Eye Monitoring Center, Kaiser Permanente Southern California, Baldwin Park, CA, USA; 4Department of Clinical Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USACorrespondence: Bobeck S Modjtahedi, Eye Monitoring Center, Kaiser Permanente Baldwin Park Medical Center, 1011 Baldwin Park Blvd, Baldwin Park, CA, 91706, USA, Email BobModj@gmail.comPurpose: The purpose of this study was to understand individual-, social-, and system-level factors that affect compliance with recommended diabetic retinopathy (DR)-evaluations, and how these factors vary between English and Spanish speakers.Patients and Methods: We conducted a qualitative study using semi-structured interviews. Study subjects included Kaiser Permanente Southern California members with type II diabetes mellitus at least aged 26 years who spoke English or Spanish. Patients were divided into groups based on their adherence with DR evaluations. Our main outcome measure was the major themes expressed by patients that explained their compliance with DR evaluation.Results: Fifty-one participants were enrolled: 30 English speakers (11 nonadherent, 19 adherent) and 21 Spanish speakers (8 nonadherent, 13 adherent). Adherent patients were more likely to have had experience with diabetes and identify as being responsible for their own care. Substantially more non-adherent patients suggested that beliefs and attitudes were the reasons people missed retinopathy appointments. More English-speaking participants tended to be self-directed in managing their healthcare, whereas more Spanish speakers relied on others for help. English speakers also noted better relationships with their physicians. Spanish speakers outlined problems with insurance coverage and costs as barriers.Conclusion: These data suggest two specific intervention strategies that eye care providers could implement to improve adherence with diabetic retinopathy screening and follow up: incorporating a person with DR-related visual loss into the team of staff delivering diabetes support programs and communication campaigns including specific messaging to address fears related to vision loss.Keywords: diabetes, diabetic retinopathy, screening, adherence, language

Nadia Peyravian,1,2 Sapna Deo,1,2 Sylvia Daunert,1– 3 Joaquin J Jimenez1,2,4 1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA; 2Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute of the University of Miami, Miami, FL, USA; 3University of Miami Clinical and Translational Science Institute, Miami, FL, USA; 4Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USACorrespondence: Joaquin J Jimenez; Sylvia DaunertDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 1011 NW 15th Street, Miami, FL 33136, USATel +1 305 243 6586Email j.jimenez@med.miami.edu; sdaunert@med.miami.eduAbstract: The immune-suppressive effects of cannabidiol (CBD) are attributed to the modulation of essential immunological signaling pathways and receptors. Mechanistic understanding of the pharmacological effects of CBD emphasizes the therapeutic potential of CBD as a novel immune modulator. Studies have observed that the antagonists of CB1 and CB2 receptors and transient receptor potential vanilloid 1 reverse the immunomodulatory effects of CBD. CBD also inhibits critical activators of the Janus kinase/signal transducer and activator of transcription signaling pathway, as well as the nucleotide-binding oligomerization domain-like receptor signaling pathway, in turn decreasing pro-inflammatory cytokine production. Furthermore, CBD protects against cellular damage incurred during immune responses by modulating adenosine signaling. Ultimately, the data overwhelmingly support the immunosuppressive effects of CBD and this timely review draws attention to the prospective development of CBD as an effective immune modulatory therapeutic.Keywords: cannabidiol, CBD, immune modulation, CB1 and CB2 receptors, TRPV1, JAK/STAT, inflammasome

Nadia Peyravian,1 Sapna Deo,1 Sylvia Daunert,1 Joaquin J Jimenez1,2 1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA; 2Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USACorrespondence: Joaquin J JimenezDepartment of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, 1011 NW 15th Street, Miami, FL 33136, USATel +1 305 243 6586Email j.jimenez@med.miami.eduAbstract: Male and female pattern hair loss (MPHL and FPHL, respectively), is the most common cause of hair loss affecting nearly 80 million people in the US, yet treatment options remain limited and lacking. As the need for more effective therapeutics remains unmet, this perspective offers a unique angle by directing attention to the inflammatory aspect of MPHL and FPHL. Evidence and implications of inflammation as a characteristic feature of MPHL and FPHL are highlighted through evaluation of clinical and quantitative data. Comparable results suggest the presence of significant perifollicular inflammatory infiltrates, such as lymphocytes and histiocytes, as well as the involvement of inflammatory genes, such as CASP7 and TNF, in the presentation of MPHL and FPHL. Resurfacing of the inflammatory aspect in MPHL and FPHL pathogenesis will advance future developments in MPHL and FPHL therapeutic options.Keywords: hair loss, inflammation, male pattern baldness, female pattern baldness

Acute myeloid leukemia (AML) is the most aggressive and prevalent form of leukemia in adults. The gold-standard intervention revolves around the use of chemotherapy, and in some cases hematopoietic stem cell transplantation. Drug resistance is a frequent complication resulting from treatment, as it stands there are limited clinical measures available for refractory AML besides palliative care. The goal of this review is to renew interest in a novel targeted hormone therapy in the treatment of AML utilizing growth hormone-releasing hormone (GHRH) antagonism, given it may provide a potential solution for current barriers to achieving complete remission post-therapy. Recapitulating pre-clinical evidence, GHRH antagonists (GHRH-Ant) have significant anti-cancer activity across experimental human AML cell lines in vitro and in vivo and demonstrate significant inhibition of cancer in drug resistant analogs of leukemic cell lines as well. GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation., (© 2024. The Author(s).)

Acne has a prevalence of over 90% among adolescents, and subsequently progresses to acne scarring in approximately 47% of cases. Due to the severe psychological and social ramifications acne scarring has on patients, there is a need for more effective treatments. Platelet-rich plasma (PRP), an autologous preparation enriched with growth factors, cytokines, and chemokines, has shown efficacy in promoting wound healing and tissue remodeling in dermatology. Recent evidence suggests that the efficacy of PRP may be enhanced when combined with laser therapy, which induces controlled tissue damage through photo-thermolysis thereby promoting tissue remodeling and epidermal regeneration. The microchannels created by laser treatments are thought to allow deeper penetration of PRP into the skin, potentially increasing its therapeutic effects. This review aims to analyze the combined use of PRP and laser therapy for treating acne scarring by examining randomized control trials from the past decade indexed on PubMed. Six studies met our inclusion criteria and were included in this review. The findings of this review support the hypothesis that combining PRP with laser therapy offers superior clinical results compared to monotherapy, providing a more effective approach to managing acne scarring., (© 2024. The Author(s).)

Background: Food insecurity is associated with poor glycemic control and increased risk for diabetes-related complications. The clinical benefit of addressing these challenges through a medically supportive grocery prescription (GRx) program in patients with type 2 diabetes mellitus (T2D) remains unclear. We report the aims and design of a randomized clinical trial to evaluate the effectiveness of a 6-month GRx intervention on hemoglobin A1c (HbA1c) levels among low-income adults with T2D., Methods: The Kaiser Permanente Evaluating Nutritional Interventions in Food-Insecure High-Risk Adults (KP ENRICH) Study is a pragmatic randomized trial enrolling 1100 participants within Kaiser Permanente Northern California and Southern California, two integrated health care delivery systems serving >9 million members. Medicaid-insured adults with T2D and baseline HbA1c ≥7.5% will be randomized at a 1:1 ratio to either GRx, delivered as $100 per month for select items from among a curated list of healthful food groups in an online grocery ordering and home-delivery platform along with biweekly digital nutrition educational materials, or control, consisting of free membership and deliveries from the online grocery platform but without curated food groups or purchasing dollars. The primary outcome is 6-month change in HbA1c. Secondary outcomes include 12-month change in HbA1c, and 6- and 12-month change in medical resource utilization, food security, nutrition security, dietary habits, diabetes-related quality of life, and dietary self-efficacy., Conclusions: The results of this large randomized clinical trial of GRx will help inform future policy and health system-based initiatives to improve food and nutrition security, disease management, and health equity among patients with T2D., Competing Interests: Declaration of competing interest Dr. Mozaffarian reports research funding from the National Institutes of Health, Gates Foundation, Kaiser Permanente Fund, National Association of Chain Drug Stores Foundation, and Rockefeller Foundation; personal fees from Acasti Pharma (ended); scientific advisory board, Beren Therapeutics, Brightseed, Calibrate, Elysium Health, Filtricine, HumanCo, Instacart Health, January Inc., Season Health, Validation Institute (ended: Perfect Day, Tiny Organics); an unrestricted gift from Google; stock ownership in Calibrate and HumanCo; and chapter royalties from UpToDate. Others at the Food is Medicine Institute have received research funding or gifts for investigator-initiated research from About Fresh, the American Diabetes Association, Kroger, and family foundations. The remaining authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Complementary and alternative medicine (CAM) use has become a field of growing interest in dermatology. However, the prevalence of CAM use is difficult to quantify as it varies based on many factors. Given the exploratory nature of the topic, a scoping review was conducted to identify studies that quantify biologically based CAM use in skin cancer patients. A comprehensive search of Embase, PubMed, and Web of Science databases from inception to August 28th, 2023, was performed. A total of 3,150 articles were identified through the database search. After article screening, 6 studies were suitable for inclusion in this review. Articles included were all questionnaire, survey, or interview style. Biologically based CAM use is prevalent in skin cancer patients. It can be associated with many factors such as location, stage of cancer, and age. CAM use can interact with conventional therapy; therefore, physicians should employ a culturally competent approach to inquiring about CAM use in order to improve patient outcomes and identify patterns and predictors of use.J Drugs Dermatol. 2024;23(5):322-326. doi:10.36849/JDD.8077.

Acute myeloid leukemia (AML) is characterized by the rapid proliferation of mutagenic hematopoietic progenitors in the bone marrow. Conventional therapies include chemotherapy and bone marrow stem cell transplantation; however, they are often associated with poor prognosis. Notably, growth hormone-releasing hormone (GHRH) receptor antagonist MIA-602 has been shown to impede the growth of various human cancer cell lines, including AML. This investigation examined the impact of MIA-602 as monotherapy and in combination with Doxorubicin on three Doxorubicin-resistant AML cell lines, KG-1A, U-937, and K-562. The in vitro results revealed a significant reduction in cell viability for all treated wild-type cells. Doxorubicin-resistant clones were similarly susceptible to MIA-602 as the wild-type counterpart. Our in vivo experiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602.

Competing Interests: The authors declare no conflicts of interest.

Autoimmune connective tissue disorders, including systemic lupus erythematosus, systemic sclerosis (SSc) and dermatomyositis (DM), often manifest with debilitating cutaneous lesions and can result in systemic organ damage that may be life-threatening. Despite recent therapeutic advancements, many patients still experience low rates of sustained remission and significant treatment toxicity. While genetic predisposition plays a role in these connective tissue disorders, the relatively low concordance rates among monozygotic twins (ranging from approximately 4% for SSc to about 11%-50% for SLE) have prompted increased scrutiny of the epigenetic factors contributing to these diseases. In this review, we explore some seminal studies and key findings to provide a comprehensive understanding of how dysregulated epigenetic mechanisms can contribute to the development of SLE, SSc and DM., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: We examined whether a combined measure of neighborhood greenspace and neighborhood median income was associated with white matter hyperintensity (WMH) and ventricle size changes., Methods: The sample included 1260 cognitively normal ≥ 65-year-olds with two magnetic resonance images (MRI; ≈ 5 years apart). WMH and ventricular size were graded from 0 (least) to 9 (most) abnormal (worsening = increase of ≥1 grade from initial to follow-up MRI scans). The four-category neighborhood greenspace-income measure was based on median neighborhood greenspace and income values at initial MRI. Multivariable logistic regression tested associations between neighborhood greenspace-income and MRI measures (worsening vs. not)., Results: White matter grade worsening was more likely for those in lower greenspace-lower income neighborhoods than higher greenspace-higher income neighborhoods (odds ratio = 1.73; 95% confidence interval = 1.19-2.51)., Discussion: The combination of lower neighborhood income and lower greenspace may be a risk factor for worsening white matter grade on MRI. However, findings need to be replicated in more diverse cohorts., Highlights: Population-based cohort of older adults (≥ 65 years) with greenspace and MRI dataCombined measure of neighborhood greenspace and neighborhood income at initial MRIMRI outcomes included white matter hyperintensities (WMH) and ventricular sizeLongitudinal change in MRI outcomes measured approximately 5 years apartWorsening WMH over time more likely for lower greenspace-lower income neighborhoods., Competing Interests: Lilah Besser, Gina Lovasi, Joyce Jimenez Zambrano, Simone Camacho, Devi Dhanekula, Yvonne L. Michael, Parveen Garg, Jana Hirsch, David Siscovick, Philip M. Hurvitz, Mary Lou Biggs, James Galvin, and Traci Bartz have no conflicts of interest. Will Longstreth serves as a co‐PI for the NIH‐funded ARCADIA trial, which receives in‐kind study drug from the BMS‐Pfizer Alliance and ancillary funding from Roche Diagnostics. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Dysmenorrhea is a condition that manifests itself in women before, during, and after menstruation, and it is accompanied by very intense pelvic pain. Moreover, women experience moderate to intense menstrual cramps year after year, decreasing their quality of life. The purpose of the study was to establish semiological differences associated with primary dysmenorrhea. Women who start their menstrual cycles with this symptomatology assume that it is normal and that they do not need specialized medical assistance. Medical professionals have established general practice guidelines on clinical disorders. However, there are no specific recommendations for the menstrual cycle that can effectively support the prompt diagnosis and treatment of primary dysmenorrhea, particularly at 3870 msnm. The uniqueness of our research is that semiological distinctions can change depending on height., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2023 The Authors.)

Cryotherapy has recently been examined as a potential treatment for alopecia areata (AA). AA is classically managed with intralesional or systemic steroids but relapse rates among those with longstanding disease are high. This narrative review serves to describe the existing studies evaluating cryotherapy for the treatment of AA and examine studies comparing cryotherapy with intralesional steroid injection for the treatment of AA. A review of the literature from 1990 to 2022 was conducted looking for keywords such as “alopecia areata” and “cryotherapy". A total of 8 studies were identified. Three studies assessed the efficacy of liquid nitrogen cryotherapy for the treatment of AA and found approximately 60% of patients responded to treatment and achieved hair regrowth. Three studies compared cryotherapy with intralesional corticosteroid injection, and 2 studies compared cryotherapy with topical corticosteroid therapy. There was no statistically significant difference in efficacy, but there is some evidence to suggest that relapse rates were lower in the cryotherapy group. Treatment protocols differed between studies regarding the number of cycles used for cryotherapy, dosage of intralesional steroids, and patient populations used. Some studies examined cases of recalcitrant AA while other studies examined all cases of AA. More research with larger sample sizes and with similar experimental procedures is necessary to assess the clinical efficacy of cryotherapy.Kaiser M, Issa N, Yaghi M, et al. Review of superficial cryotherapy for the treatment of alopecia areata. J Drugs Dermatol. 2023;22(8):802-809. doi:10.36849/JDD.7431.

Facial hair is an important social and psychologic aspect of clinical appearance for men. The purpose of this review is to provide a comprehensive overview of the causes of alopecia of the beard including the prevalence, pathophysiology, clinical presentation, and treatment. In this review, we highlight more common causes of beard alopecia including alopecia areata and pseudofolliculitis barbae, infectious causes such as tinea barbae and herpes simplex folliculitis, and rare causes including dermatopathia pigmentosa reticularis and frontal fibrosing alopecia. This review serves as an important resource for clinicians when faced with patients suffering from beard alopecia.

Androgenetic alopecia (AGA) is the most common cause of alopecia in males and females. Minoxidil and finasteride are the only FDA-approved treatments for AGA. New treatments including Platelet Rich Plasma (PRP) and microneedling have shown promising results. The purpose of this literature review was to highlight recent studies examining the effects of topical minoxidil combined with PRP to minoxidil or PRP monotherapy. The method used for this paper includes a systematic review of the literature from 2010 to 2022 using the PubMed, EMBASE, and MEDLINE databases examining studies evaluating combination therapies for AGA. Three randomized control trials compared combination PRP + topical 5% minoxidil to either no treatment, 5% minoxidil, or PRP only. Two studies found increased hair growth at five months and at six months following combined therapy. Another study found an increase in hair density and improved patient satisfaction with combination therapy compared to monotherapy. A prospective study revealed that patients treated with combined 5% minoxidil, PRP, and microneedling reported the highest patient and physician satisfaction compared to minoxidil monotherapy. An observational study evaluating topical 5% minoxidil with PRP reported an increase in hair diameter after one year of combination treatment compared to minoxidil monotherapy. PRP therapy combined with minoxidil and microneedling in a retrospective study was shown to increase hair growth compared to PRP with minoxidil as well as PRP or minoxidil monotherapy. In conclusion, a variety of studies demonstrated superior treatment response with a combination of PRP and minoxidil therapy in patients with AGA. Limitations to this study include different PRP preparation protocols, few randomized control studies, and small sample sizes., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cutaneous and Aesthetic Surgery.)

GHRH is a hypothalamic peptide shown to stimulate the proliferation of malignant cells in humans. We have previously shown that the use of GHRH antagonist MIA-602 successfully suppressed the growth of many human cancer cell lines, spanning more than 20 types of cancers. In this study, we demonstrate the presence of GHRH-R in the NB4, NB4-RAA, and K-562 model cell lines. Furthermore, we demonstrate the inhibited proliferation of all three cell lines in vitro after incubation with MIA-602. The treatment of xenografts of human APL cell lines with MIA-602 led to a significant reduction in tumor growth. Additionally, combination therapy with both doxorubicin (DOX) and MIA-602 showed a marked synergistic effect in reducing the proliferation of the K-562 AML cell line. These findings suggest that MIA-602 could be utilized to address resistance to all- trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapies, as well as in augmenting anthracycline-based regimens.

Introduction: We analyzed randomized clinical trials (RCTs) evaluating the efficacy of combined therapy with low-level light therapy (LLLT) and topical minoxidil for treatment of androgenetic alopecia (AGA)., Methods: A literature search within PubMed identified RCTs evaluating hair regrowth following LLLT and minoxidil. Selection criteria were 600-1,100 nm wavelengths, treatment time ≥16 weeks, and objective evaluation for hair regrowth., Results: Five RCTs compared LLLT with minoxidil (2% or 5%) to 5% minoxidil treatment or LLLT treatment. One study showed combination therapy of LLLT, and 5% minoxidil improved hair density more than monotherapy. Another found combination LLLT with 2% minoxidil induced hair regrowth equivalent to 5% minoxidil. Similarly, another study described LLLT with 5% minoxidil versus minoxidil monotherapy to increase the number of hairs with no statistical difference between groups. One trial found that combination group increased hair regrowth in the first 2 months. The last study found a statistically significant increase in hair density with combined therapy compared to monotherapy., Conclusion: The studies describe either superiority or equivalence of combination therapy to minoxidil monotherapy for AGA. Early outcomes appear to support the superiority of combination therapy, but this advantage wanes at the end of the study periods., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)

Introduction: Global clinical trials in rheumatoid arthritis (RA) often do not recruit enough patients from diverse racial and ethnic backgrounds to identify any potential differences in treatment outcome across such groups. To overcome this limitation, using data from five previous clinical trials and two ongoing trial extensions, this study aimed to assess the efficacy and safety of filgotinib in patients with RA across geographic regions., Methods: This was a post hoc, exploratory analysis of data from male and female patients with RA meeting the 2010 RA criteria as defined by the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology. Data were analyzed from phase 2 (DARWIN 1-2) and phase 3 (FINCH 1-3) clinical trials, as well as two long-term extension studies (DARWIN 3, FINCH 4), of filgotinib. Efficacy endpoints included ACR 20%/50%/70% improvement (ACR20/50/70) responses, disease activity score in 28 joints using C-reactive protein [DAS28(CRP)], Clinical Disease Activity Index scores, Boolean remission, and change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety data were presented as exposure-adjusted incidence rates per 100 patient-years of exposure of treatment-emergent adverse events., Results: Compared with placebo, at week 12 a greater proportion of patients receiving filgotinib 200 mg (FIL200) or 100 mg (FIL100) achieved ACR20 (p < 0.01), with similar outcomes in most regions. Overall, the reduction in HAQ-DI with FIL200 or FIL100 was greater than with placebo (p < 0.05) at week 12. Compared with placebo, at week 24 the proportions of patients achieving DAS28(CRP) ≤ 3.2 were greater for both doses of FIL, as seen in most regions (p < 0.01). Safety outcomes did not indicate regional or ethnic differences in the safety profile of filgotinib., Conclusion: Filgotinib efficacy and safety in patients with RA were generally consistent across geographic regions., Gov Trial Registration Numbers: NCT02889796; NCT02873936; NCT02886728; NCT03025308; NCT01888874; NCT01894516; NCT02065700., (© 2022. The Author(s).)

Women who have had a Cesarean Section (CS) frequently report severe pain and pain-related interference. One reason for insufficient pain treatment might be inconsistent implementation of evidence-based guidelines. We assessed the association between implementing three elements of care recommended by guidelines for postoperative pain management and pain-related patient-reported outcomes (PROs) in women after CS. The analysis relied on an anonymized dataset of women undergoing CS, retrieved from PAIN OUT. PAIN OUT, an international perioperative pain registry, provides clinicians with treatment assessment methodology and tools for patients to assess multi-dimensional pain-related PROs on the first postoperative day. We examined whether the care included [i] regional anesthesia with a neuraxial opioid OR general anesthesia with wound infiltration or a Transvesus Abdominis Plane block; [ii] at least one non-opioid analgesic at the full daily dose; and [iii] pain assessment and recording. Credit for care was given only if all three elements were administered (= “full”); otherwise, it was “incomplete”. A “Pain Composite Score-total” (PCStotal), evaluating outcomes of pain intensity, pain-related interference with function, and side-effects, was the primary endpoint in the total cohort (women receiving GA and/or RA) or a sub-group of women with RA only. Data from 5182 women was analyzed. “Full” care was administered to 20% of women in the total cohort and to 21% in the RA sub-group. In both groups, the PCStotal was significantly lower compared to “incomplete” care (p < 0.001); this was a small-to-moderate effect size. Administering all three elements of care was associated with better pain-related outcomes after CS. These should be straightforward and inexpensive for integration into routine care after CS. However, even in this group, a high proportion of women reported poor outcomes, indicating that additional work needs to be carried out to close the evidence-practice gap so that women who have undergone CS can be comfortable when caring for themselves and their newborn.

Chemotherapy induces hair loss in most cancer patients who undergo treatment, which causes them significant psychosocial trauma. Scalp cooling has demonstrated some efficacy in attenuating chemotherapy-induced alopecia, but response rate varies between patients and chemotherapy class. Here, we showcase in rats a proof-of-concept treatment of using subcutaneous hydrogen peroxide and cumene hydroperoxide injections to provide total protection from hair loss against multiple classes of chemotherapy. We found that subcutaneous peroxides induce cell cycle arrest via P53 activation, thereby protecting hair follicles from the cytotoxic effects of chemotherapy on actively dividing cells. This treatment represents a highly effective and accessible way for cancer patients to maintain quality of life while undergoing treatment for cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang and Jimenez.)

Laser-induced photodamage is a robust method for investigating retinal pathologies in small animals. However, aiming of the photocoagulation laser is often limited by manual alignment and lacks real-time feedback on lesion location and severity. Here, we demonstrate a multimodality OCT and SLO ophthalmic imaging system with an image-guided scanning laser lesioning module optimized for the murine retina. The proposed system enables targeting of focal and extended area lesions under OCT guidance to benefit visualization of photodamage response and the precision and repeatability of laser lesion models of retinal injury., Competing Interests: 7Conflict of Interest The authors have no relevant financial interests nor any potential conflicts of interest to disclose related to this work.

Significance: Coronary heart disease has the highest rate of death and morbidity in the Western world. Atherosclerosis is an asymptomatic condition that is considered the primary cause of cardiovascular diseases. The accumulation of low-density lipoprotein triggers an inflammatory process in focal areas of arteries, which leads to the formation of plaques. Lipid-laden plaques containing a necrotic core may eventually rupture, causing heart attack and stroke. Lately, intravascular optical coherence tomography (IV-OCT) imaging has been used for plaque assessment. The interpretation of the IV-OCT images is performed visually, which is burdensome and requires highly trained physicians for accurate plaque identification., Aim: Our study aims to provide high throughput lipid-laden plaque identification that can assist in vivo imaging by offering faster screening and guided decision making during percutaneous coronary interventions., Approach: An A-line-wise classification methodology based on time-series deep learning is presented to fulfill this aim. The classifier was trained and validated with a database consisting of IV-OCT images of 98 artery sections. A trained physician with expertise in the analysis of IV-OCT imaging provided the visual evaluation of the database that was used as ground truth for training and validation., Results: This method showed an accuracy, sensitivity, and specificity of 89.6%, 83.6%, and 91.1%, respectively. This deep learning methodology has the potential to increase the speed of lipid-laden plaques identification to provide a high throughput of more than 100 B-scans/s., Conclusions: These encouraging results suggest that this method will allow for high throughput video-rate atherosclerotic plaque assessment through automated tissue characterization for in vivo imaging by providing faster screening to assist in guided decision making during percutaneous coronary interventions.

In this study, we present a time-efficient protocol for thoracic volume calculation as a proxy for total lung volume. We hypothesize that lung volume can be calculated indirectly from this thoracic volume. We compared the measured thoracic volume with manually segmented and automatically thresholded lung volumes, with manual segmentation as the gold standard. A linear regression formula was obtained and used for calculating the theoretical lung volume. This volume was compared with the gold standard volumes. In healthy animals, thoracic volume was 887.45 mm 3 , manually delineated lung volume 554.33 mm 3 and thresholded aerated lung volume 495.38 mm 3 on average. Theoretical lung volume was 554.30 mm 3 . Finally, the protocol was applied to three animal models of lung pathology (lung metastasis and transgenic primary lung tumor and fungal infection). In confirmed pathologic animals, thoracic volumes were: 893.20 mm 3 , 860.12 and 1027.28 mm 3 . Manually delineated volumes were 640.58, 503.91 and 882.42 mm 3 , respectively. Thresholded lung volumes were 315.92 mm 3 , 408.72 and 236 mm 3 , respectively. Theoretical lung volume resulted in 635.28, 524.30 and 863.10.42 mm 3 . No significant differences were observed between volumes. This confirmed the potential use of this protocol for lung volume calculation in pathologic models.

Androgenetic alopecia ("AGA") is the most prevalent type of progressive hair loss, causing tremendous psychological and social stress in patients. However, AGA treatment remains limited in scope. The pathogenesis of androgenetic alopecia is not completely understood but is known to involve a hair follicle miniaturization process in which terminal hair is transformed into thinner, softer vellus-like hair. This process is related to the dysregulation of the Wnt/β-catenin signaling pathway, which causes premature termination of the anagen growth phase in hair follicles. Historically used for wound healing, platelet rich plasma ("PRP") has recently been at the forefront of potential AGA treatment. PRP is an autologous preparation of plasma that contains a high number of platelets and their associated growth factors such as EGF, IGF-1, and VEGF. These factors are known to individually play important roles in regulating hair follicle growth. However, the clinical effectiveness of PRP is often difficult to characterize and summarize as there are wide variabilities in the PRP preparation and administration protocols with no consensus on which protocol provides the best results. This study follows the previous review from our group in 2018 by Cervantes et al. to analyze and discuss recent clinical trials using PRP for the treatment of AGA. In contrast to our previous publication, we include recent clinical trials that assessed PRP in combination or in direct comparison with standard of care procedures for AGA such as topical minoxidil and/or oral finasteride. Overall, this study aims to provide an in-depth analysis of PRP in the treatment of AGA based on the evaluation of 17 recent clinical trials published between 2018 and October 2021. By closely examining the methodologies of each clinical trial included in our study, we additionally aim to provide an overall consensus on how PRP can be best utilized for the treatment of AGA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdin, Zhang and Jimenez.)

There are currently several commercialized products approved by the Food and Drug Administration and the European Medicines Agency based on the use of recombinant human BMP-2 for the treatment of non-unions long fractures and spinal fusion. However, the adverse effects recorded with the use of BMPs suggest the need for drug delivery carriers that allow reducing the required doses and improve their cost-effectiveness. Herein, we have developed a new osteoconductive scaffold that reduces the required doses of BMP-2 for promoting bone regeneration in an osteoporotic defect model. The composite is, in brief, a gelatin-based 3D scaffold reinforced with either calcium sulfate or hydroxyapatite as an inorganic osteoconductive biomaterial. To this end, the organic/inorganic composite systems showed high hydration capacity and good in vitro degradability. The incorporation of 7.5% (m/v) ceramic compounds resulted in scaffolds with stiffer Young modulus (179 and 75 kPa for CaSO 4 &#95;7 and HA&#95;7, respectively) than bare gelatin hydrogels (48 kPa). Studies with human bone-marrow derived mesenchymal stem cells (hBM-MSCs) revealed that the 3D scaffolds promote cell adhesion and proliferation along with osteogenic differentiation capabilities. Specifically, downregulation of stemness (Nanog, Oct4) genes and upregulation of osteogenic markers (ALP, Col1a1, Fmod) by two fold were observed over 10 days under basal culture conditions. Promisingly, the sustained in vitro release of BMP-2 observed from the porous reinforced scaffolds allowed us to address the critical-sized osteoporotic mice calvarial defects with a relatively low growth factor doses (600 ng BMP-2/scaffold) compared to conventional doses at 2-15 micrograms. Overall, this study demonstrates the promising potential of osteoconductive gelatin/calcium bioceramics composites as osteogenic growth factors delivery carriers for bone-regeneration via ultra-low growth factor doses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Optical coherence tomography (OCT) has become the gold standard for ophthalmic diagnostic imaging. However, clinical OCT image-quality is highly variable and limited visualization can introduce errors in the quantitative analysis of anatomic and pathologic features-of-interest. Frame-averaging is a standard method for improving image-quality, however, frame-averaging in the presence of bulk-motion can degrade lateral resolution and prolongs total acquisition time. We recently introduced a method called self-fusion, which reduces speckle noise and enhances OCT signal-to-noise ratio (SNR) by using similarity between from adjacent frames and is more robust to motion-artifacts than frame-averaging. However, since self-fusion is based on deformable registration, it is computationally expensive. In this study a convolutional neural network was implemented to offset the computational overhead of self-fusion and perform OCT denoising in real-time. The self-fusion network was pretrained to fuse 3 frames to achieve near video-rate frame-rates. Our results showed a clear gain in peak SNR in the self-fused images over both the raw and frame-averaged OCT B-scans. This approach delivers a fast and robust OCT denoising alternative to frame-averaging without the need for repeated image acquisition. Real-time self-fusion image enhancement will enable improved localization of OCT field-of-view relative to features-of-interest and improved sensitivity for anatomic features of disease., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for activating receptors, such as MHC Class I peptide A/B (MICA/B) and ULBPs. Here, we describe the use of a blood-brain barrier (BBB) permissive supramolecular cationic drug vehicle comprising an inhibitor of the chaperone heat shock protein 90 (Hsp90), which sustains a cytotoxic effect on GBM cells, boosts the expression of MICA/B and ULBPs on the residual population, and augments the activity of clinical-grade aNK cells (GTA002). First, we identify Hsp90 mRNA transcription and gain of function as significantly upregulated in GBM compared to other central nervous system tumors. Through a rational chemical design, we optimize a radicicol supramolecular prodrug containing cationic excipients, SCI-101, which displays >2-fold increase in relative BBB penetration compared to less cationic formulations in organoids, in vitro . Using 2D and 3D biological models, we confirm SCI-101 sustains GBM cytotoxicity 72 h after drug removal and induces cell surface MICA/B protein and ULBP mRNA up to 200% in residual tumor cells compared to the naked drug alone without augmenting the shedding of MICA/B, in vitro . Finally, we generate and test the sequential administration of SCI-101 with a clinical aNK cell therapy, GTA002, differentiated and expanded from healthy umbilical cord blood CD34 + hematopoietic stem cells. Using a longitudinal in vitro model, we demonstrate >350% relative cell killing is achieved in SCI-101-treated cell lines compared to vehicle controls. In summary, these data provide a first-of-its-kind BBB-penetrating, long-acting inhibitor of Hsp90 with monotherapy efficacy, which improves response to aNK cells and thus may rapidly alter the treatment paradigm for patients with GBM., Competing Interests: AV, A-MG, JS, and AD were employees of Glycostem Therapeutics B.V. AG and CC was employed by Xsphera Biosciences and/or hold equity. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saha, van Vliet, Cui, Macias, Kulkarni, Pham, Lawler, Spanholtz, Georgoudaki, Duru and Goldman.)

Purpose: To assess the Pediatric Vision Scanner (PVS), a handheld vision screening device designed to test for amblyopia and strabismus, in a general pediatric population., Methods: In this prospective study, trained research staff screened 300 eligible children 24-72 months of age with no known eye conditions for amblyopia and strabismus using the PVS. A pediatric ophthalmologist masked to PVS screening results then performed a comprehensive eye examination. Sensitivity and specificity of the PVS was calculated with a 95% confidence interval., Results: Based on the gold standard eye examination, 6 children (2%) had amblyopia and/or strabismus. The PVS detected all 6 cases, yielding a sensitivity rate of 100% (95% CI, 54%-100%). The PVS referred 45 additional children (15%) who had normal ophthalmic findings, yielding a specificity rate of 85% (95% CI, 80%-89%). The median acquisition time for the PVS was 28 seconds., Conclusions: The PVS detected amblyopia with high sensitivity in a nonenriched pediatric population. The device would allow children with amblyopia and/or strabismus to be referred to an eye care specialist as early as 2 years old. Given its short acquisition time, the PVS can be implemented in a pediatric clinic with minimal impact on workflow., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)