Utilization of Point-of-Care Ultrasound as an Imaging Modality in the Emergency Department: A Systematic Review and Meta-Analysis.

Point-of-care ultrasound (POCUS) is an imaging modality that has become a fundamental part of clinical care provided in the emergency department (ED). The applications of this tool in the ED have ranged from resuscitation, diagnosis, and therapeutic to procedure guidance. This review aims to summarize the evidence on the use of POCUS for diagnosis and procedure guidance. To achieve this, CrossRef, PubMed, Cochrane Library, Web of Science, and Google Scholar databases were extensively searched for studies published between January 2000 and November 2023. Additionally, the risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 (for studies on the diagnostic role of POCUS) and Cochrane Risk of Bias tool (for studies on the use of POCUS for procedure guidance). Furthermore, diagnostic accuracy outcomes were pooled using STATA 16 software (StatCorp., College Station, TX, USA), while outcomes related to procedure guidance were pooled using the Review Manager software. The study included 81 articles (74 evaluating the diagnostic application of POCUS and seven evaluating the use of POCUS in guiding clinical procedures). In our findings sensitivities and specificities for various conditions were as follows: appendicitis, 65% and 89%; hydronephrosis, 82% and 74%; small bowel obstruction, 93% and 82%; cholecystitis, 75% and 96%; retinal detachment, 94% and 91%; abscess, 95% and 85%; foreign bodies, 67% and 97%; clavicle fractures, 93% and 94%; distal forearm fractures, 97% and 94%; metacarpal fractures, 94% and 92%; skull fractures, 91% and 97%; and pleural effusion, 91% and 97%. A subgroup analysis of data from 11 studies also showed that the two-point POCUS has a sensitivity and specificity of 89% and 96%, while the three-point POCUS is 87% sensitive and 92% specific in the diagnosis of deep vein thrombosis. In addition, the analyses showed that ultrasound guidance significantly increases the overall success rate of peripheral venous access (p = 0.02) and significantly reduces the number of skin punctures (p = 0.01) compared to conventional methods. In conclusion, POCUS can be used in the ED to diagnose a wide range of clinical conditions accurately. Furthermore, it can be used to guide peripheral venous access and central venous catheter insertion.

Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors.

Cooperativity and antagonism between transcription factors (TFs) can drastically modify their binding to regulatory DNA elements. While mapping these relationships between TFs is important for understanding their context-specific functions, existing approaches either rely on DNA binding motif predictions, interrogate one TF at a time, or study individual TFs in parallel. Here, we introduce paired yeast one-hybrid (pY1H) assays to detect cooperativity and antagonism across hundreds of TF-pairs at DNA regions of interest. We provide evidence that a wide variety of TFs are subject to modulation by other TFs in a DNA region-specific manner. We also demonstrate that TF-TF relationships are often affected by alternative isoform usage and identify cooperativity and antagonism between human TFs and viral proteins from human papillomaviruses, Epstein-Barr virus, and other viruses. Altogether, pY1H assays provide a broadly applicable framework to study how different functional relationships affect protein occupancy at regulatory DNA regions.

Blue Nevus-Like Metastasis of a Cutaneous Melanoma Identified by Fluorescence In Situ Hybridization.

A blue nevus-like melanoma is a rare melanoma variant arising from or histologically similar to a blue nevus. It can be challenging to distinguish a cellular blue nevus from a blue nevus-like melanoma, particularly in cases of blue nevus-like melanoma lacking a transition from a clearly benign component. We present a case of a 78-year-old man who refused treatment for a previously existing melanoma and subsequently developed a gray nodule near the site of the previous melanoma. After fluorescence in situ hybridization revealed copy number gains in RREB1, this was diagnosed as a blue nevus-like metastatic melanoma. Blue nevus-like metastatic melanoma is most commonly seen near the site of the primary cutaneous melanoma. This entity should be considered in a patient with a history of melanoma and a new blue nevus-like lesion.

Disseminated cutaneous histoplasmosis in newly diagnosed HIV.

We present a woman with a widespread severe papulopustular eruption, fever, and fatigue of 5 weeks' duration. HIV infection was diagnosed, with an absolute CD4(+) count of 3 cells/µL. The eruption was consistent with disseminated cutaneous histoplasmosis. The clinical manifestations and management of cutaneous histoplasmosis are reviewed.

Use of tumor necrosis factor alpha (TNF α) antagonists in a patient with psoriasis and Chagas disease.

There are several studies on the benefits of using TNFα antagonists in the treatment of psoriasis, but few studies addressing the interaction of these drugs with chronic infections. We report the case of a 52-year-old patient diagnosed with psoriasis refractory to traditional systemic agents, who was treated with biologic therapies. After one year of treatment with biologic agents, the patient was diagnosed with Chagas Disease.

Use of tumor necrosis factor alpha (TNF α) antagonists in a patient with psoriasis and Chagas disease

There are several studies on the benefits of using TNFα antagonists in the treatment of psoriasis, but few studies addressing the interaction of these drugs with chronic infections. We report the case of a 52-year-old patient diagnosed with psoriasis refractory to traditional systemic agents, who was treated with biologic therapies. After one year of treatment with biologic agents, the patient was diagnosed with Chagas Disease.

Genital psoriasis is associated with significant impairment in quality of life and sexual functioning.

BACKGROUND: Genital involvement has significant psychosexual implications for psoriasis patients. OBJECTIVE: This study was designed to ascertain factors associated with the development of genital psoriasis and its impact on quality of life and sexual functioning. METHODS: This was an observational, multicenter study of 354 consecutive psoriasis patients. RESULTS: One hundred thirty-four patients (38%) had current genital involvement while 224 (63%) had a current and/or previous history of genital involvement. Eighty-seven percent reported itch, 39% pain, 42% dyspareunia, 32% a worsening of their genital psoriasis after intercourse, and 43% a decreased frequency of intercourse. Younger age of onset of psoriasis, male sex, more severe disease, and involvement of the scalp, flexures, and nails were associated with the presence of genital disease. There was no association with circumcision or obesity. Patients with genital psoriasis had more impairment in quality of life and sexual health as determined by the Dermatology Life Quality Index (P < .0001), the Center for Epidemiological Studies-Depression Scale (P = .01), and the Relationship and Sexuality Scale (P < .0001). LIMITATIONS: This was a descriptive study from 2 tertiary referral centers where patients were likely to have more severe psoriasis. CONCLUSION: This study highlights the high prevalence of genital psoriasis and its profound impact on quality of life and sexual health.

Myocardial Infarction Related to Trauma.

Myocardial infarction (MI) secondary to acute coronary occlusion related to trauma is rare. A previously healthy man developed acute MI shortly after a motor vehicle accident. This case illustrates the feasibility of primary percutaneous coronary intervention for acute MI due to complete coronary artery occlusion related to trauma, including the use of manual thrombectomy, stents, and dual antiplatelet therapy. This approach requires the intervention of a multidisciplinary team in a Level 1 trauma center that can rapidly evaluate the patient and rule out other life-threatening injuries that could preclude antiplatelet therapy.

Angiolymphoid hyperplasia with eosinophilia.

A patient with multiple erythematous nodules on her posterior scalp presented to our dermatology clinic. Biopsy confirmed the diagnosis of angiolymphoid hyperplasia with eosinophilia. The etiology of this disorder is unclear. Several cases have been treated in the past with complete surgical excision, although the recurrence rate remains relatively high.

Ustekinumab treatment for psoriasis in 119 patients maintained on therapy for a minimum of one year: a review.

Ustekinumab is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit shared by both the interleukin-12 and interleukin-23 cytokines. This study reviews clinical response and adverse events in 119 psoriasis patients who have received ustekinumab for a minimum of 1 year. The medical records of 119 psoriasis patients treated with ustekinumab at our referral clinic in Dallas between 2009 and 2013 were reviewed for response rates, side effects, and concomitant therapies. Of 119 patients, 117 (98%) had plaque type psoriasis, with 40 (34%) patients having psoriasis affecting either their palms and/or soles. Forty-four (37%) patients had psoriatic arthritis. The median follow-up period was 31 months. Fifty-six (47%) of the 119 patients obtained near complete clearance (response of more than 90% of initial body surface area involvement) upon the final follow-up visit or at the time of ustekinumab treatment discontinuation. Concomitant systemic treatments, primarily methotrexate, were given to 59 (50%) patients. Twenty-three (19%) patients discontinued treatment, primarily for sub-optimal response or loss of response. Fifty (42%) patients required either an increase in the dose of ustekinumab to 90 mg and/or administration more frequently than every 12 weeks to achieve and maintain psoriasis clearance.

A retrospective analysis of 72 patients on prior efalizumab subsequent to the time of voluntary market withdrawal in 2009.

BACKGROUND: Efalizumab was voluntarily withdrawn from the market in April 2009 after four cases of progressive multifocal leukoencephalopathy. OBJECTIVE: To review the baseline characteristics and psoriasis phenotypes of patients with prior excelled response to efalizumab, and to determine the response of these patients to prior as well as subsequent therapies. By defining this subgroup of patients, particularly relating to palmoplantar psoriasis, future therapeutic considerations could be improved. DESIGN: A retrospective review of 72 patients who were on efalizumab at the time of market withdrawal was conducted. Data was obtained through chart review of patients at a specialty psoriasis clinic in Dallas, TX. MAIN OUTCOMES AND MEASURES: Patient characteristics, details of efalizumab use, and efficacy of efalizumab compared with other psoriasis treatment modalities. RESULTS: Of the 72 patients, 24 (33%) were found to have palmoplantar disease. As a group, these patients were older, more likely to be female, and less likely to have a family history of psoriasis. 48 patients (67%) were on one or more systemic and/or biologic medication prior to starting efalizumab. Their BSA improved from 5.45 to 0.8 as a group. Six patients were identified as having failed TNF alpha antagonist treatment prior to starting efalizumab. All responded well to the medication with an average BSA of 0.54. Five of these six patients had evidence of palmoplantar disease prior to starting efalizumab and five of these six patients were female. Eleven patients (15%) experienced neurologic side effects and 13 (18%) had infections while on efalizumab treatment. LIMITATIONS: This was a retrospective review. Quality of life issues could not always be fully assessed from the data available. CONCLUSIONS AND RELEVANCE: Efalizumab was effectively utilized in our clinical practice to treat patients with palmoplantar psoriasis, including six patients who had failed prior treatment with one or more TNF alpha antagonist agents.

The spectrum of oculocutaneous disease: Part II. Neoplastic and drug-related causes of oculocutaneous disease.

There are a multitude of diseases that commonly affect both the skin and the eye. Part II of this 2-part series reviews the oculocutaneous manifestations of neoplasms, both benign and malignant, and adverse drug reactions affecting the skin and the eye. Though rare, a number of neoplasms that primarily involve the skin, such as melanoma and basal cell carcinoma, can metastasize to the eye, leading to permanent damage if not properly treated. In addition, periocular neoplasms can irritate the conjunctiva and lid, reducing a patient's ability to see clearly. Neoplastic diseases, such as xeroderma pigmentosum, Sturge-Weber syndrome, and multiple myeloma, can also lead to permanent changes in the eye if not discovered and managed promptly. Furthermore, there are a multitude of drugs, including those commonly used by dermatologists, which can result in permanent damage to the eye. With proper knowledge of the ocular manifestations and treatment recommendations described in this 2-part series, dermatologists with the assistance of their ophthalmology colleagues can help avoid the complications, including permanent blindness, associated with infectious, inflammatory, genetic, neoplastic, and drug-related conditions.

Emerging topical treatments for psoriasis.

INTRODUCTION: Psoriasis is an immune-mediated chronic inflammatory skin disease which classically presents as erythematous, scaly plaques affecting extensor surfaces of the limbs, scalp and trunk. Approximately 80% of patients have a mild-to-moderate form routinely treated with topical medications, whereas phototherapy, systemic and biological therapies are typically reserved for treatment of moderate-to-severe psoriasis. AREAS COVERED: The major advances in psoriasis therapy in the past 15 years have been in new immunomodulatory and biological molecules, with a significant unmet need to have new, efficient and safe topical treatment options for the large percentage of patients for whom systemic therapy is not indicated. The available topical therapies (corticosteroids and vitamin D3 analogs) have remained relatively unchanged over the past several decades. This article reviews emerging topical drugs and formulations currently under evaluation in clinical trials. EXPERT OPINION: The time is right for a revolution in our topical therapy armamentarium. It has lagged significantly behind the systemic biological evolution of new drug development. Our large psoriasis population with mild-to-moderate psoriasis certainly deserves potent but safe and innovative topical agents with a new mode of action as well as with long-lasting clinical efficacy.

Biological therapies for psoriasis.

INTRODUCTION: Biological therapies have revolutionized moderate-to-severe psoriasis treatment. Increased understanding of disease pathogenesis has yielded multiple therapeutic targets involving the IL-23/Th17 pathway, while current therapies continue to be monitored for long-term efficacy and safety. AREAS COVERED: This review details current understanding of psoriasis immunopathogenesis specifically related to therapeutic targets. Approved and emerging biological psoriasis therapies targeting TNF-α, IL-12/23p40, IL-17 and IL-23p19 are covered. Biological agent uses in special circumstances are reviewed together with the emerging debate on biosimilar therapies and their potential future role in psoriasis and other inflammatory diseases. EXPERT OPINION: Psoriasis treatment has expanded and has become more effective due to increased understanding of disease pathogenesis. However, lack of efficacy in select psoriasis patients, safety concerns and limited treatment efficacy in psoriasis variants (e.g., pustular) are areas which still need improvement. As such, pharmacogenomics will be of vital importance in future for individualized psoriasis care. Further, a better understanding of the multiple psoriasis comorbidities, especially cardiovascular disease, continues to be of significant interest in the psoriasis community. Last, the emergence of biosimilar agents has the potential to change psoriasis treatment, especially as it relates to better access for the psoriasis community worldwide.

Cutaneous manifestations of gastrointestinal disease: part II.

The gastrointestinal (GI) and cutaneous organ systems are closely linked. In part I of this continuing medical education article, the intricacies of this relationship were explored as they pertained to hereditary polyposis disorders, hamartomatous disorders, and paraneoplastic disease. Part II focuses on the cutaneous system's links to inflammatory bowel disease and vascular disorders. An in-depth analysis of inflammatory bowel disease skin findings is provided to aid dermatologists in recognizing and facilitating early consultation and intervention by gastroenterologists. Cutaneous signs of inflammatory bowel disease include fissures and fistulae, erythema nodosum, pyoderma gangrenosum, pyostomatitis vegetans, oral aphthous ulcers, cutaneous polyarteritis nodosa, necrotizing vasculitis, and epidermolysis bullosa acquisita. Additional immune-mediated conditions, such as diverticulitis, bowel-associated dermatosis-arthritis syndrome, Henoch-Schönlein purpura, dermatitis herpetiformis, and Degos disease, in which the skin and GI system are mutually involved, will also be discussed. Genodermatoses common to both the GI tract and the skin include Hermansky-Pudlak syndrome, pseudoxanthoma elasticum, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia, and blue rubber bleb nevus syndrome. Kaposi sarcoma is a neoplastic disease with lesions involving both the skin and the gastrointestinal tract. Acrodermatitis enteropathica, a condition of zinc deficiency, likewise affects both the GI and dermatologic systems. These conditions are reviewed with updates on the genetic basis, diagnostic and screening modalities, and therapeutic options. Finally, GI complications associated with vascular disorders will also be discussed.

Cutaneous manifestations of gastrointestinal disease: part I.

Cutaneous findings are not uncommonly a concomitant finding in patients afflicted with gastrointestinal (GI) diseases. The dermatologic manifestations may precede clinically evident GI disease. Part I of this 2-part CME review focuses on dermatologic findings as they relate to hereditary and nonhereditary polyposis disorders and paraneoplastic disorders. A number of hereditary GI disorders have an increased risk of colorectal carcinomas. These disorders include familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Each disease has its own cutaneous signature that aids dermatologists in the early diagnosis and detection of hereditary GI malignancy. These disease processes are associated with particular gene mutations that can be used in screening and to guide additional genetic counseling. In addition, there is a group of hamartomatous syndromes, some of which are associated with phosphatase and tensin homolog (PTEN) gene mutations, which present with concurrent skin findings. These include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Cronkhite-Canada syndrome. Finally, paraneoplastic disorders are another subcategory of GI diseases associated with cutaneous manifestations, including malignant acanthosis nigricans, Leser-Trélat sign, tylosis, Plummer-Vinson syndrome, necrolytic migratory erythema, perianal extramammary Paget disease, carcinoid syndrome, paraneoplastic dermatomyositis, and paraneoplastic pemphigus. Each of these disease processes have been shown to be associated with an increased risk of GI malignancy. This underscores the important role of dermatologists in the diagnosis, detection, monitoring, and treatment of these disorders while consulting and interacting with their GI colleagues.

Emerging therapies for the treatment of psoriasis.

Psoriasis is an immune-mediated disease that affects 1%-2% of the European and North American population. While topical agents such as corticosteroids and vitamin D derivatives are prescribed for mild disease, they are generally unable to adequately control patients with more severe disease. Over the past decade, research into the immunopathogenesis of psoriasis, including investigations into the role of tumor necrosis factor-alpha and more recently interleukins (IL) 12/23, has led to the advent of targeted biologic therapies based on the central role of a new subset of T cells, Th17. Because of their increased specificity, biologic agents have revolutionized short- to medium-term treatment outcomes and safety profiles for moderate to severe disease over previously gold standard systemic agents. The immunopathogenesis of the disease is still a focus for researchers and novel targets for future agents are being discovered and investigated in clinical trials. In particular, specifically targeting the IL-23/Th17 pathway has given rise to IL-23p19 and IL-17 antagonists, both of which have shown significant promise in clinical trials. IL-22 is involved in keratinocyte proliferation and is being studied as a treatment target for psoriasis. New small molecule oral agents, including Janus kinase and phosphodiesterase inhibitors are currently in phase 2 and 3 clinical trials.

Widespread dermal ulcerations and bullae.

Bullous pemphigoid is an autoimmune disease of the skin characterized by large, tense bullae resulting in significant morbidity in affected individuals. The diagnosis of bullous pemphigoid may present challenges due to clinical similarities with various other bullous eruptions. Frequently, epidemiological features can provide clues to the diagnosis of bullous pemphigoid, with histologic analysis commonly required for definitive diagnosis. This case study illustrates the typical clinical and histologic findings seen in bullous pemphigoid patients and briefly discusses the differential diagnosis. An in-depth understanding of the intricate pathophysiology is essential in order to educate patients. After diagnosis and appropriate workup, an array of treatment approaches, including topical and systemic corticosteroids, immunosuppressive agents, antibiotics, chemotherapeutic agents, and even monoclonal antibodies, may be utilized individually or in combination to achieve an optimal therapeutic response.

Current investigational drugs in psoriasis.

INTRODUCTION: The advent of biologic therapies has revolutionized the treatment of psoriasis. Increased understanding of immunogenetic pathways has allowed for the development of more selective targeted biologic therapies. Multiple new treatments are currently in development for the treatment of psoriasis. Preliminary data for many of these agents, particularly with regard to agents targeting the IL-23/Th17 pathway, are promising. Proven long-term safety, however, is an absolute necessity with newly developed drugs, and should, therefore, still be considered second-line agents to current established treatments with long-term safety data. AREAS COVERED: This review details the mechanisms of action of drugs currently in development or in clinical trials for the treatment of psoriasis, using clinical trial registries and associated publications. Readers will gain a comprehensive overview about the mechanism of action of emerging treatments targeting various immune pathways deeply involved in psoriasis. Pathogenesis, clinical efficacy and safety data for these treatments are discussed where available. EXPERT OPINION: Psoriasis remains a heavily undertreated systemic immune-mediated disease despite increased understanding of immunopathogenesis of the disease and advent of a multitude of novel therapeutic agents with potentially improved bioavailability and safety profiles. Limitations, however, remain in the realm of topical agents for treatment of mild to moderate psoriasis, which has seen little progress over the years. A concerted effort will need to be made among researchers, clinicians and patient advocacy groups to ensure new therapeutic agents are developed and gain proper exposure.