P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas.

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.

Wound Debridement in Pyoderma Gangrenosum.

BACKGROUND: Wound debridement improves healing in a variety of acute and chronic ulcers. However, there is concern that debridement may trigger pathergy and worsen pyoderma gangrenosum (PG). OBJECTIVE: To determine whether published evidence supports conservative wound debridement for PG. DATA SOURCES: The authors reviewed the literature published in MEDLINE through January 2023 using the search germs "pyoderma gangrenosum" and "debridement." STUDY SELECTION: Articles reporting sharp surgical debridement or maggot debridement for PG were included in the review. The authors also searched the reference sections of the reviewed articles for additional reports on debridement for PG. DATA EXTRACTION: Clinical data regarding patient status, procedures performed, and patient outcomes were extracted from the selected articles. DATA SYNTHESIS: There are multiple reports of uncontrolled, active-phase PG wounds worsening after aggressive excisional debridement of viable inflamed tissues. In contrast, there is no evidence indicating that conservative debridement of nonviable necrotic tissue worsens PG wounds, regardless of the disease activity. There are multiple reports of successful debridement and surgical grafting for PG in remission. CONCLUSIONS: There is no evidence in favor of or against using conservative debridement of nonviable necrotic tissue for a PG wound. Therefore, it should not be considered contraindicated, even in the active phase of the disease.

Trichoblastic carcinosarcoma: A case report and literature review.

Trichoblastic carcinosarcoma is a rare biphasic adnexal neoplasm. This case report chronicals the eighth occurrence of this tumor published in the English literature and provides a review of the prior publications. Clinically, this tumor presents as an isolated, rapidly growing lesion in elderly patients and is usually cured by complete surgical excision, with no evidence of recurrence or metastasis at follow-up (7/8 cases). Histopathologically, trichoblastic carcinosarcoma is dermal-based, with an epithelial component of basal cells and a mesenchymal component of spindle cells, both of which display malignant features. In addition to a morphologic description of trichoblastic carcinosarcoma, a discussion of the differential diagnoses, including other biphasic neoplasms, is also included. The small number of cases of trichoblastic carcinosarcoma is most likely secondary to under-recognition and underreporting and a larger case volume is needed to more accurately assess the clinical course and treatment strategies.

Successful Treatment of Painful Cutaneous Vasculopathy With Rivaroxaban in a Patient With Systemic Lupus Erythematosus.

Novel oral anticoagulant (NOAC) medications have revolutionized hematology and cardiology. Recently, NOACs have demonstrated additional promise in dermatology. Specifically, rivaroxaban, a direct factor Xa inhibitor NOAC, has been shown to be successful in the treatment of livedoid vasculopathy. Herein, we describe a patient with systemic lupus erythematosus who presented with painful cutaneous vasculopathy, demonstrated on biopsy with occlusive microvascular fibrin thrombi without evidence of concurrent vasculitis. Interestingly, imaging and laboratory studies did not show evidence of hypercoagulability, arterial disease, or embolic disease. The patient’s vasculopathy and pain progressed despite antiplatelet therapy, often considered first-line in cases of microvascular occlusive disease. However, with rivaroxaban therapy, the patient experienced complete regression of her painful lesions, thereby supporting a further role for NOACs in cutaneous vasculopathy treatment. J Drugs Dermatol. 2020;19(5) doi:10.36849/JDD.2020.4684.

T-Lymphoblastic Leukemia/Lymphoma With Annular Skin Rash and Epidermotropism.

Leukemia cutis is uncommon in patients with acute lymphoblastic leukemia. It typically presents with dermal papules or subcutaneous nodules, with no epidermal or upper papillary dermal involvement on histopathology. We present an unusual clinical presentation of leukemia cutis, with annular plaques and epidermotropism.

How Frequency of Electrosurgical Current and Electrode Size Affect the Depth of Electrocoagulation.

BACKGROUND: Many factors affect the depth of electrocoagulation. OBJECTIVE: To evaluate the effect of current frequency and electrode size on the depth of electrocoagulation. METHODS AND MATERIALS: In this in vitro study, 4 cylindrical electrodes (2, 2.3, 3, and 4 mm) were used to apply 3 electrosurgical currents (0.4, 1.5, and 3 MHz) to bovine liver. Each electrode was placed at different points on the surface of the liver, and energy at various levels and frequencies was delivered to the tissue. Subsequently, cross-sections of the liver were analyzed. RESULTS: Coagulation started at the periphery of the electrode-tissue contact area. With higher energy levels, coagulation spreads to involve the remainder of the contact area. Neither the frequency nor the electrode size had any effect on this coagulation pattern. The frequency of the current also did not show any relation with depth of coagulation; however, there was a direct correlation between the size of the electrode and the depth of coagulation. CONCLUSION: Larger-tip electrodes provided deeper coagulation compared with finer-tip electrodes.

Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary.

CONTEXT: It is now clear that oxidative stress (OS) and chronic low-grade inflammation are two main pathways involved in polycystic ovary syndrome (PCOS) pathogenesis. Therefore, simultaneous targeting of these pathways by means of carvedilol and Semelil (ANGIPARS™), as established medicines with dual anti-cytokine and anti-oxidant potential may be a therapeutic alternative approach to the current treatments. OBJECTIVE: The objective of this study is to study the protective effects of carvedilol and ANGIPARS™ on inflammatory and oxidative response in hyperandrogenism-induced polycystic ovary (PCO). MATERIALS AND METHODS: The murine model of PCO was induced by letrozole (1 mg/kg/d; orally) and effective doses of carvedilol (10 mg/kg/d; orally) and ANGIPARS™ (2.1 mg/kg/d; orally) were administrated for 21 d in PCO and non-PCO healthy rats. Ovarian folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic biomarkers were assessed in serum and ovaries. RESULTS: PCO rats exhibited ovarian cystogenesis which was preserved by the application of carvedilol and ANGIPARS™. In comparison with controls, decreased level of the total antioxidant power (TAP) and higher levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in serum and ovaries (2.41 ± 0.67 versus 0.72 ± 0.11; and 0.17 ± 0.04 versus 0.05 ± 0.01; 5.48 ± 1.30 versus 10.56 ± 0.77; and 7.06 ± 1.94 versus 17.98 ± 0.98; p < 0.05, respectively) were detected in PCO rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold increase in serum testosterone concentration (35.04 ± 3.17 versus 131.09 ± 13.24; p < 0.05) along with a 2.98-fold decrease in serum progesterone (6.19 ± 0.40 versus 18.50 ± 1.03; p < 0.05) and 5.2-fold decrease in serum estradiol (9.30 ± 0.61 versus 48.3 ± 2.10; p < 0.05) when compared with those of the control group. However, similar to the control group, normal levels of OS markers and sex hormones were detected in ANGIPARS™ and carvedilol co-treated PCO rats. Besides, when compared with controls, increased levels of TNF-α (770.75 ± 42.06 versus 477.14 ± 28.77; p < 0.05) and insulin (1.27 ± 0.10 versus 0.36 ± 0.05; p < 0.05) in PCO rats were significantly inhibited by carvedilol and ANGIPARS™ co-treatment. DISCUSSION AND CONCLUSION: We evidenced the beneficial effects of carvedilol and ANGIPARS™ in PCO, which underpin the new alternative approach in using these kinds of medicines in female reproductive disorders.

Is Tumor of Follicular Infundibulum a Reaction to Dermal Scarring?

Tumor of follicular infundibulum (TFI) is currently believed to be a benign epithelial neoplasm with follicular differentiation. It has been suggested that TFI is associated with dermal scarring, but further investigation is needed to confirm this correlation. To approach this question, a retrospective study was presented, a total of 67 cases (64 lesions) were found in a search covering cases over a 10-year period. Overall, the presence of histological dermal scarring was noted in 34 of 64 (53.13%) cases. Of the cases where TFI was an incidental finding, the presence of dermal scarring was noted in 13 of 18 (72.22%) cases. Meanwhile, of the cases where TFI was the main diagnosis, the presence of dermal scarring was noted in 12 of 34 (35.29%) cases. This suggests that TFI may, in some cases, represent an epidermal reaction pattern to dermal scarring.

Electrosurgery: part I. Basics and principles.

The term electrosurgery (also called radiofrequency surgery) refers to the passage of high-frequency alternating electrical current through the tissue in order to achieve a specific surgical effect. Although the mechanism behind electrosurgery is not completely understood, heat production and thermal tissue damage is responsible for at least the majority--if not all--of the tissue effects in electrosurgery. Adjacent to the active electrode, tissue resistance to the passage of current converts electrical energy to heat. The only variable that determines the final tissue effects of a current is the depth and the rate at which heat is produced. Electrocoagulation occurs when tissue is heated below the boiling point and undergoes thermal denaturation. An additional slow increase in temperature leads to vaporization of the water content in the coagulated tissue and tissue drying, a process called desiccation. A sudden increase in tissue temperature above the boiling point causes rapid explosive vaporization of the water content in the tissue adjacent to the electrode, which leads to tissue fragmentation and cutting.

Electrosurgery: part II. Technology, applications, and safety of electrosurgical devices.

Electrosurgical currents can be delivered to tissue in monopolar or bipolar and monoterminal or biterminal modes, with the primary difference between these modes being their safety profiles. A monopolar electrosurgical circuit includes an active electrode and a dispersive (return) electrode, while there are 2 active electrodes in bipolar mode. In monoterminal mode, there is an active electrode, but there is no dispersive electrode connected to the patient's body and instead the earth acts as the return electrode. Biterminal mode uses a dispersive electrode connected to the patient's body, has a higher maximum power, and can be safer than monoterminal mode in certain situations. Electrosurgical units have different technologies for controlling the output power and for providing safety. A thorough understanding of these technologies helps with a better selection of the appropriate surgical generator and modes.

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization.

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.

Setting national research priorities for difficult-to-treat depression in the UK between 2021-2026.

Background: Difficult-to-treat depression (DTD) presents a substantial health care challenge, with around one-third of people diagnosed with a depressive episode in the UK finding that their symptoms persist following treatment. This study aimed to identify priority research questions (RQs) that could inform the development of new and improved treatments, interventions, and support for people with DTD. Methods: Using an adapted Child Health and Nutrition Research Initiative (CHNRI) method, this national prioritisation exercise engaged 60 leading researchers and health care professionals in the UK, as well as 25 wider stakeholders with relevant lived experience to produce a ranked list of priority RQs in DTD. The final list of 99 distinct RQs was independently scored by 42 individuals against a list of five criteria: answerability, effectiveness, impact on health, deliverability, and equity. Results: Highly ranked RQs covered a range of novel and existing treatments. The three highest scoring RQs included evaluation of psychological and pharmacological therapies (eg, behavioural activation, and augmentation therapies), as well as social interventions to reduce loneliness or increase support for people with DTD. Conclusions: This exercise identified and prioritised 99 RQs that could inform future research and funding decisions over the next five years. The results of this research could improve treatment and support for people affected by DTD. It also serves as an example of ways in which the CHNRI method can be adapted in a collaborative manner to provide a more active role for patients, carers, and health care professionals.

A comparison of three times vs. five times weekly narrowband ultraviolet B phototherapy for the treatment of chronic plaque psoriasis.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is an effective treatment for psoriasis. OBJECTIVES: To compare the effects of three and five times weekly NB-UVB phototherapy in the treatment of chronic plaque psoriasis. METHODS: Sixty-five patients with chronic plaque psoriasis were allocated to receive three or five times weekly NB-UVB, starting at low dose. RESULTS: Among the patients who completed the study, clearance was achieved in 18 out of 23 patients (78%) in the three times weekly group and in 15 out of 22 patients (68%) in the five times weekly group. The difference was not statistically significant (P=0.44). No statistically significant differences were found between the two groups in the number of treatments (P=0.95), cumulative UVB dose (P=0.51), and rate of side-effects. Length of the treatment period was significantly shorter in the five times weekly group (P<0.001). At the end of treatment, the mean psoriasis area and severity index score was lower in the three times weekly group (P=0.02). CONCLUSIONS: We recommend three times weekly NB-UVB for chronic plaque psoriasis; however, the more rapid clearance of psoriasis with five times weekly phototherapy may justify using this method in some patients.

Controlling depth of electrosurgery after curettage of skin tumors-an in vitro study.

BACKGROUND: Depth of tissue injury in electrosurgery depends on generator power, electrode size, speed of electrode movement on tissue, and current delivery method. We sought to evaluate the depth of tissue injury associated with different methods of electrocoagulation in an effort to make electrocoagulation more reproducible. METHODS: A knife-shaped electrode was used to apply an electrosurgical current to the surface of a piece of bovine liver. Different electrosurgical methods were performed. Cross sections of the liver were then studied for tissue effect. RESULTS: Fulguration provided only superficial coagulation. Contact electrocoagulation and electrodesiccation using the flat side of the electrode provided significantly deeper levels of coagulation and were associated with less smoke than fulguration. Desiccation provided the deepest tissue effect. CONCLUSIONS: Electrofulguration can be used for superficial tissue destruction. For deeper coagulation, a relatively larger electrode can be used in contact mode. Slower movement of the electrode on tissue in contact mode is associated with desiccation and the deepest level of tissue destruction.

Management of fluid status and cardiovascular function in patients with diffuse skin inflammation.

Background: Skin inflammation causes vasodilation and increased vascular permeability, which may result in decreased blood pressure and peripheral edema. Patients with erythroderma usually compensate for low blood pressure with fluid retention and increased cardiac output. However, if the heart cannot support increased cardiac output, blood pressure will stay low, resulting in severe compensatory fluid retention, which leads to decompensated congestive heart failure, and pulmonary edema. Treatment for high-output congestive heart failure focuses on the primary pathology, which is skin inflammation. However, aggressive treatment of the inflammation with glucocorticoids may result in rapid resorption of extravascular fluid into the intravascular space and occurrence or aggravation of pulmonary edema. Erythrodermic patients with no clinical heart failure are also at risk for developing pulmonary edema if they receive glucocorticoids and/or intravascular fluids. Most hospitalists and dermatologists are not familiar with fluid administration and ways to manage cardiovascular function and blood pressure in patients with skin inflammation. Objectives and methods: In this article, we discuss the pathophysiology of vascular and fluid changes in the context of diffuse skin inflammation and provide some basic guidelines that can be presented to hospitalists by dermatologists. Limitations: Most of the recommendations and guidelines in the article are based on basic science and on the personal experience of the authors and are not supported by controlled trials. Capsule summary Diffuse skin inflammation causes major changes in the cardiovascular system and in the perfusion of internal organs. We provide guidelines for management of fluid status and cardiovascular function in patients with diffuse skin inflammation. Dermatologists can provide hospitalists or primary care providers with these guidelines to help them with creating better treatment plans.