Perceptions, Utilization, and Cost Assessment of Sebaceous Hyperplasia Treatment Modalities: A Pilot Survey.

BACKGROUND: Sebaceous hyperplasia (SH) is a common, benign but cosmetically bothersome skin condition preferentially affecting older adults. Despite multiple treatment options, there is no universally accepted first-line treatment for SH nor standard pricing for said approaches.  Methods: A survey aimed at evaluating treatment approaches and their respective costs was disseminated on the Orlando Dermatology Aesthetic and Clinical Conference email listserv.  Results: Out of 224 dermatologists who participated in the survey (response rate 9.2%), most treated patients with SH (95.98%). In-office procedures were used more than pharmacologic treatments (P=<0.05). Treatments most used by respondents included electrodesiccation (ED; 83.9%), cryosurgery (35.3%), oral isotretinoin (32.6%), and carbon dioxide (CO2) laser (19.2%). Cryosurgery and ED priced between <$200 to $400. Most reported 1 to 2 sessions to achieve lesion clearance for ED, CO2 laser, and cryosurgery. Twenty-one percent reported 3-4 sessions with cryosurgery. Chemical peels, diode lasers, and photodynamic therapy required between 2-4 sessions. Respondents indicated lesions were most unlikely to recur with ED and CO2 laser. Most dermatologists (86.39%) agreed or strongly agreed that they were exposed to new treatments methods for SH through this survey and 86.49% of dermatologists were interested in learning about treatments employed by others. CONCLUSION: SH is a common issue that presents in the dermatologist's office. These data highlight the perception that ED is the most common approach employed, associated with lower costs, and requiring fewer sessions to achieve resolution. More data is needed and wanted to better determine best practices for the management of SH.J Drugs Dermatol. 2024;23(2):29-37.  doi:10.36849/JDD.7734.

Hyperthecosis: an underestimated nontumorous cause of hyperandrogenism.

Hyperthecosis is defined as the presence of nests of luteinized theca cells in the ovarian stroma. Persistent testosterone released by ovarian theca cells is unmasked postmenopausally through the loss of granulosa cell-mediated aromatization of testosterone to estradiol. Ovarian hyperthecosis (OH) usually presents with symptoms of hyperandrogenism and is often described as a severe or extreme form of Polycystic Ovary Syndrome (PCOS). Serum testosterone levels in excess of 150 ng/dl (>5.2 nmol/l) are seen in affected patients and this threshold is used to confirm a diagnosis. Treatment of hyperthecosis is multi-faceted. It addresses the attendant hyperandrogenism (hirsutism and virilization) as well as metabolic complications such as obesity and insulin resistance. Ultimately, laparoscopic bilateral salpingo-oophorectomy is definitive treatment. This remains the treatment of choice in postmenopausal women whereas treatment using GnRH agonists may be used in women of reproductive age, especially younger women. Nevertheless, if serum testosterone remains elevated despite several months of therapy with a GnRH agonist, surgery is often required for biopsy sample collection and further definitive therapy. In order to mitigate the common clinical manifestations of hyperandrogenism, anti-androgen therapy (either cyproterone acetate or spironolactone) may be used to suppress the actions of testosterone on tissues. In patients with impaired glucose metabolism and insulin resistance, Metformin should also be considered as part of treatment. Combined, such a treatment regimen will often lead to decreased ovarian androgen secretion.

Safety and Efficacy of Nanosecond Pulsed Electric Field Treatment of Sebaceous Gland Hyperplasia.

BACKGROUND: Nanosecond pulsed electric field (nsPEF) technology involves delivery of ultrashort pulses of electrical energy and is a nonthermal, drug-free technology that has demonstrated favorable effects on cellular structures of the dermis and epidermis. OBJECTIVE: Determine the tolerability and effectiveness of nsPEF treatment of sebaceous gland hyperplasia (SGH). METHODS: This study was a prospective, randomized, open-label, multisite, nonsignificant risk trial in which each subject served as their own control. After injection of local anesthetic, high-intensity, ultrashort pulses of electrical energy were used to treat 72 subjects resulting in a total of 222 treated lesions. Subjects returned for 3 to 4 follow-up evaluations with photographs. RESULTS: At the final study visit, 99.6% of treated SGH lesions were rated clear or mostly clear and 79.3% of the subjects were satisfied or mostly satisfied with the outcome. At 60 days after nsPEF treatment, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild post-treatment hyperpigmentation. At the last observation for all lesions, 32% of the 222 lesions were noted as having slight volume loss. CONCLUSION: Nanosecond pulsed electric field procedure is well tolerated and is very effective in the removal of SGHs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03612570.

Dedicator of cytokinesis 2 silencing therapy inhibits neointima formation and improves blood flow in rat vein grafts.

OBJECTIVE: The high rate of vein graft failure due to neointimal hyperplasia is a major challenge for cardiovascular surgery. Finding novel approaches to prevent neointimal hyperplasia is important. Thus, the purpose of this study was to investigate whether dedicator of cytokinesis 2 (DOCK2) plays a role in the development of neointima formation in the vein grafts. METHODS AND RESULTS: We found that DOCK2 levels were significantly elevated in the vein grafts following grafting surgery. In addition, overexpression of DOCK2 promoted venous smooth muscle cell (SMC) proliferation and migration. Conversely, knocking-down endogenous DOCK2 expression in venous SMCs inhibited SMC proliferation and migration. Consistent with this, knocking-down DOCK2 expression in the grafted veins significantly reduced neointimal formation compared with the controls 28 days after vein transplantation. Moreover, DOCK2 silencing treatment improved hemodynamics in the vein grafts. Mechanistically, knockdown of DOCK2 significantly alleviated the vein graft-induced down regulation of SMC contractile protein expression and impeded the vein graft-induction of both Cyclin D1 and PCNA expression. In particular, to ensure high efficiency when transferring the DOCK2 short hairpin RNA (shDOCK2) into the grafted veins, a 30% poloxamer F-127 gel incorporated with 0.25% trypsin was smeared around the vein grafts to increase the adenovirus contact time and penetration. CONCLUSIONS: DOCK2 silencing gene therapy effectively attenuates neointimal hyperplasia in vein grafts. Knock-down of DOCK2 would be a potential therapeutic approach for the treatment of vein graft failure.

Exosomes from mesenchymal stem cells expressing miR-125b inhibit neointimal hyperplasia via myosin IE.

Intercellular communication between mesenchymal stem cells (MSCs) and their target cells in the perivascular environment is modulated by exosomes derived from MSCs. However, the potential role of exosome-mediated microRNA transfer in neointimal hyperplasia remains to be investigated. To evaluate the effects of MSC-derived exosomes (MSC-Exo) on neointimal hyperplasia, their effects upon vascular smooth muscle cell (VSMC) growth in vitro and neointimal hyperplasia in vivo were assessed in a model of balloon-induced vascular injury. Our results showed that MSC-Exo were internalised by VSMCs and inhibited proliferation and migration in vitro. Further analysis revealed that miR-125b was enriched in MSC-Exo, and repressed the expression of myosin 1E (Myo1e) by targeting its 3' untranslated region. Additionally, MSC-Exo and exosomally transferred miR-125b repressed Myo1e expression and suppressed VSMC proliferation and migration and neointimal hyperplasia in vivo. In summary, our findings revealed that MSC-Exo can transfer miR-125b to VSMCs and inhibit VSMC proliferation and migration in vitro and neointimal hyperplasia in vivo by repressing Myo1e, indicating that miR-125b may be a therapeutic target in the treatment of vascular diseases.

Complications of Cryolipolysis: Paradoxical Adipose Hyperplasia (PAH) and Beyond.

BACKGROUND: Cryolipolysis is a fairly popular procedure performed in North America, Europe, and many other countries. Although it is considered a rather safe procedure, there are underreported side effects such as paradoxical adipose hyperplasia (PAH), contour irregularities, skin and soft tissue atrophy, and asymmetries. Our knowledge regarding the prevalence and treatment of such complications is limited. OBJECTIVES: We hereby report a case series of 5 patients treated for various complications of cryolipolysis, including PAH, that persisted for more than 12 months after their last treatment. METHODS: Five patients with various complications of cryolipolysis (4 patients with PAH and 1 with atrophy and indentations) presented in our private office between 2015 and 2018. Three of the 4 patients with PAH were treated at other facilities with ultrasonic liposuction, laser lipolysis, and radiofrequency skin tightening devices respectively. The fourth patient developed PAH after liposuction at another facility. The fifth patient developed several areas of indentations and atrophy and received mesotherapy and lymphatic massages at another facility. All 5 patients were subsequently treated in our office by means of a customized approach specific to their underlying complications. RESULTS: Near-normal results were achieved in all 5 patients. None of our patients showed any recurrences of their initial complication for which they were treated. All 5 patients were extremely satisfied with their results. CONCLUSIONS: Cryolipolysis, just like any other form of lipolysis, has certain specific adverse effects associated with it, including but not limited to PAH. Complications of cryolipolysis must be individually recognized and treated accordingly.

Mild electrical stimulation with heat shock reduces inflammatory symptoms in the imiquimod-induced psoriasis mouse model.

Psoriasis is a chronic skin disease caused by immune disorder. The chronic skin inflammation involves inflammatory molecules that are released from T lymphocytes and keratinocytes. Therefore, developing an anti-inflammatory therapy that is suitable for long-term treatment is needed. Electrical stimulation induces biological responses by modulating intracellular signaling pathways. Our previous studies showed that the optimized combination treatment of mild electrical stimulation (MES, 0.1-millisecond; ms, 55-pulses per second; pps) and heat shock (HS, 42°C) modulates inflammatory symptoms of metabolic disorders and chronic kidney disease in mice models and clinical trials. Here, we investigated the effect of MES+HS treatment on imiquimod-induced psoriasis mouse model. Topical application of imiquimod cream (15 mg) to mice ear induced keratinocyte hyperproliferation and psoriasis-like inflammation. In MES+HS-treated mice, imiquimod-induced skin hyperplasia was significantly decreased. MES+HS treatment reduced the protein expression of IL-17A and the infiltration of CD3-positive cells in lesioned skin. In addition, MES+HS-treated mice had decreased mRNA expression level of antimicrobial molecules (S100A8 and Reg3γ) which aggravate psoriasis. In IL-17A-stimulated HaCaT cells, MES+HS treatment significantly lowered the mRNA expression of aggravation markers (S100A8, S100A9 and ß-defensin2). Taken together, our study suggested that MES+HS treatment improves the pathology of psoriasis via decreasing the expression of inflammatory molecules.

Management of Barrett's esophagus with low-grade dysplasia.

Barrett's esophagus progresses to esophageal adenocarcinoma in a stepwise histological fashion of no dysplasia, low grade dysplasia, high grade dysplasia and cancer. Hence the progression to cancer from various histological stages is different. Progression to cancer from low grade dysplasia is highly variable in the literature due to high inter-observer variability between pathologists in diagnosing it. Studies have shown the utility of having confirmation of low grade dysplasia by expert pathologists or documenting its persistence on two subsequent endoscopies in order to unify the diagnosis. The treatment of low grade dysplasia is variable. In this article we summarize the diagnosis, evaluation and management of low grade dysplasia in Barrett's Esophagus.

[Immunotropic reaction onto balneotherapy by mineral water «naftusia¼ of women with hyperplasia of the thyroid gland and non-calcular cholecystitis].

OBJECTIVE: Introduction: Hyperplasia of the thyroid gland is recetly widespread, especially among women, with pathology. At structural changes of a gland there are various types of violations of the hormonal status of the organism - from hyperthyroidism through euthyroidism to hypothermia. The aim: The article aims at investigation of the peculiarities of the influence of mineral water "Naftusia" on the immunological status of women with non-calcular cholecystitis and hyperplasia of the thyroid gland, as well as the substantiation of the possibilities of using balneotherapy in the treatment of this pathology on the basis of the obtained data. PATIENTS AND METHODS: Materials and methods: Object of investigation- hyperplasia of the thyroid gland in the presence of women's non calcular cholecystitis. Subject of research -hormonal and immune status and their changes under the influence of mineral water "Naftusia". Methods of investigation: general clinical, standard laboratory methods of examination, special clinical and laboratory methods: physiological, biochemical, statistical. The evaluation of the immune system was carried out by determining the serum total blood levels of total immunoglobulins G, M, A. The level of immunoglobulins in the blood serum was determined by radial immune diffusion according to Mancini. RESULTS: Results and conclusions: The analysis of obtained results, makes it possible to characterize fully the positive influence of such a non-medicamentous item, as the use of mineral water "Naftusia" for the treatment of noncalcular cholecystitis. Under the influence of water "Naftusia", in one way or another, the cellular and phagocytic links of immunity are normalized. It can be assumed that a positive effect on the immune system is realized through the normalization of the processes of division and differentiation of cells of the immune system, in particular on the membrane level.

Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin's antiphotodamage and antiphotoinflammation activities.

A Porphyrin-Based Conjugated Polymer for Highly Efficient In Vitro and In Vivo Photothermal Therapy.

Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor-acceptor (D-A) structured porphyrin-containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D-A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state-of-art porphyrin-based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 × 104 m-1 cm-1 at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer-based photothermal therapeutic materials for potential personalized theranostic nanomedicine.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia of the Lung (DIPNECH): Current Best Evidence.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is recognized as a preneoplastic condition by the World Health Organization. We reviewed our experience with 30 patients and performed a systematic review of the English literature to collect best evidence on the clinical features and disease course in 169 additional patients. Some patients presented with one or more carcinoid tumors associated with multiple small pulmonary nodules on imaging studies and showed DIPNECH as a somewhat unexpected pathologic finding. Others presented with multiple small pulmonary nodules that raised suspicion of metastatic disease on imaging. A third subset was presented with previously unexplained respiratory symptoms. In most patients, DIPNECH was associated with a good prognosis, with chronological progression into a subsequent carcinoid tumor noted in only one patient and death attributed directly to DIPNECH in only two patients. There is no best evidence to support the use of octreotide, steroids, or bronchodilators in DIPNECH patients.

Light and laser therapies for the treatment of sebaceous gland hyperplasia a review of the literature.

Sebaceous gland hyperplasia (SGH) is a benign cutaneous condition that presents primarily on the face and increases with UVB exposure and ageing. These lesions are a common cosmetic concern but are difficult to treat, as the entire sebaceous gland needs to be destroyed to prevent recurrence. Traditional methods of treatment include: cryosurgery, electrodessication, curettage, shave excision and topical trichloroacetic acid. These methods have an increased risk of skin discoloration and scarring to the area of treatment that may lead to inferior cosmetic outcomes. Alternatively, oral isotretinoin can treat SGH, but is a known teratogen in pregnancy and has high relapse rates with discontinuation. A systematic review of the literature was performed to look at photodynamic therapy (PDT) and laser treatment for SGH. According to the results of this study, PDT, lasers and combinations of the two treatments were found to offer alternatives to the more conventional techniques with better outcomes. In particular, the use of wavelength-specific laser for the sebaceous gland of 1720 nm were found to have better outcomes and provide minimal damage to surrounding tissues. Additionally, combination PDT with aminolevulinic acid and pre-treatment with carbon dioxide laser ablation or pulse-dyed laser offered higher cure rates over stand-alone laser or PDT treatments in a shorter number of sessions with similar transient side-effects. However, further large-scale prospective studies with adequate follow-up are required to confirm these findings and those for sebaceous gland-specific lasers.

Prolonged exposure of cholestatic rats to complete dark inhibits biliary hyperplasia and liver fibrosis.

Biliary hyperplasia and liver fibrosis are common features in cholestatic liver disease. Melatonin is synthesized by the pineal gland as well as the liver. Melatonin inhibits biliary hyperplasia of bile duct-ligated (BDL) rats. Since melatonin synthesis (by the enzyme serotonin N-acetyltransferase, AANAT) from the pineal gland increases after dark exposure, we hypothesized that biliary hyperplasia and liver fibrosis are diminished by continuous darkness via increased melatonin synthesis from the pineal gland. Normal or BDL rats (immediately after surgery) were housed with light-dark cycles or complete dark for 1 wk before evaluation of 1) the expression of AANAT in the pineal gland and melatonin levels in pineal gland tissue supernatants and serum; 2) biliary proliferation and intrahepatic bile duct mass, liver histology, and serum chemistry; 3) secretin-stimulated ductal secretion (functional index of biliary growth); 4) collagen deposition, liver fibrosis markers in liver sections, total liver, and cholangiocytes; and 5) expression of clock genes in cholangiocytes. In BDL rats exposed to dark there was 1) enhanced AANAT expression/melatonin secretion in pineal gland and melatonin serum levels; 2) improved liver morphology, serum chemistry and decreased biliary proliferation and secretin-stimulated choleresis; and 4) decreased fibrosis and expression of fibrosis markers in liver sections, total liver and cholangiocytes and reduced biliary expression of the clock genes PER1, BMAL1, CLOCK, and Cry1. Thus prolonged dark exposure may be a beneficial noninvasive therapeutic approach for the management of biliary disorders.

Hepatopulmonary syndrome associated with nodular regenerative hyperplasia after liver transplantation in a child.

HPS is a significant complication of portal hypertension in children with chronic liver disease and is an established indication for LT. It is characterized clinically by the triad of pulmonary vascular dilatation causing hypoxemia in the setting of advanced liver disease. NRH, a cause of non-cirrhotic portal hypertension, is characterized by diffuse benign transformation of the hepatic parenchyma into small regenerative nodules with minimal or no fibrosis. Development of NRH and HPS in pediatric LT recipients has not been reported, although occasional cases have been reported in adult LT recipients. In this report, we discuss a case of a three-yr-old male who developed HPS, two yr after LT. Pulmonary and cardiac causes for hypoxemia were ruled out by appropriate investigations including a chest X ray, echocardiogram, cardiac catheterization, and a CT angiographic study. The diagnosis of HPS was confirmed via bubble echocardiogram that demonstrated intrapulmonary shunting. Open liver biopsy revealed marked NRH. The patient underwent liver retransplantation that resulted in complete reversal of his pulmonary symptoms and normal oxygen saturations within three months after LT.

Early treatment of unilateral temporomandibular joint ankylosis: a multidisciplinary approach.

Ankylosis of temporomandibular joint is a condition in which partial or complete immobilization of mandible occurs because of fusion between mandibular condyle and skull base. This condition can be treated orthodontically, surgically, or therapeutically or by prosthodontic rehabilitation. A 10-year-old female patient presented to the Department of Oral and Maxillofacial Surgery, Gazi University Faculty of Dentistry, with limited mouth opening. She got injury in the face when she was 5 years old. Extraoral and intraoral examination findings were facial asymmetry on the left side, micrognathic mandible, and 19-mm mouth opening. After radiographic examination, ankylosis (Shawney type I) on the left side was revealed, and the patient was referred to Department of Orthodontics. After orthodontic clinical examination, we create following multidisciplinary treatment approach: (1) acrylic posterior bite block with spring application, (2) interpositional arthroplasty operation, and (3) physiotherapy (passive mouth-opening exercises). After the follow-up of 9 months, significant improvement (5 mm) was noticed in the opening of the mouth, and we decided to remove appliance and operate on the patient. Surgical procedure was performed under general anesthesia via blinded nasotracheal intubation. To prevent postoperative relapse, temporal fascia was interpositioned and sutured. Passive mouth-opening exercises were started 10 days after the surgery. Thirty-one-millimeter mouth opening was reached after the surgery and passive mouth-opening exercises. Patient's routine controls have been continued for 2 years.