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Adult-onset Still’s disease classically presents with high fevers, arthralgias, leukocytosis, and an evanescent eruption. There are, however, a known subset of patients who develop an atypical eruption with persistent erythematous to violaceous papules and plaques. Here, we present the case of a white female in her 40s who presented with 2 years of spiking fevers, arthralgias, and a fixed pruritic eruption with erythematous plaques with overlying scale and linear accentuation. She was initially treated with oral prednisone, anakinra, and methotrexate. Due to persistent symptoms, she was switched to adalimumab with significant relief of symptoms. Prompt recognition of adult-onset Still’s disease with this atypical eruption may help prevent delayed or missed diagnosis and allow for early, appropriate intervention.

Reports of permanent chemotherapy-induced alopecia (PCIA) are increasing in the field of oncodermatology, but there is a dearth of information regarding how it is recognized and managed by health care providers (HCPs) across different medical specialties (dermatology, oncology, and internal medicine). A 25-question survey was designed to elicit general knowledge and awareness of PCIA, as well as attitudes about referral and treatment. Responses were collected via REDCap, a secure online application, and analyzed with descriptive statistics, chi-square, and ANOVA tests. There was a significant difference in the number of subjects who had heard of PCIA prior to starting the survey (Derm 79%, Onc 30%, IM 22%, p 6 months) than IM (42% and 45% vs. 17%) and significantly more had encountered patients with the condition (47% and 45% vs. 17%). More providers in dermatology and IM knew how to diagnose PCIA compared with oncology (84% and 83% vs. 70%). Dermatology HCPs were the only participants who had attempted to treat patients with PCIA, and most providers believed that patients would accept similar types of treatment for PCIA. Dermatology HCPs were more likely to report higher confidence in their abilities to diagnose and manage PCIA than other providers. The results of this survey identify knowledge gaps about PCIA among health care providers. Therefore, education and multidisciplinary engagement should be pursued in order to improve awareness, diagnosis, referral, and management of PCIA as part of survivorship care.

Sclerodermatous graft versus host disease (sclGVHD) is a debilitating complication of hematopoietic stem cell transplant and is characterized by skin thickening and fibrosis that can result in severe contractures. While immunosuppressive therapy remains a mainstay of treatment, the disease course often progresses and, in severe cases, renders patients immobile and wheelchair-bound. Lasers that can target sclerotic lesions to improve tissue pliability and restore range of motion are a promising potential treatment for sclGVHD. Fractional CO2 lasers promote selective collagen remodeling by creating microcolumns of thermal injury that stimulate a wound healing response. Here, we present 2 patients with sclGVHD who underwent treatment with fractional ablative CO2 laser. In this pilot case series demonstrating the novel use of CO2 laser for severe, refractory sclGVHD, two patients were treated with fractional ablative CO2 laser to a focal area of sclerosis. One patient also received clobetasol ointment under occlusion in between treatments. Both patients reported marked subjective improvement in pain and mobility. Objective measurements were recorded for patient 2 who gained roughly 10 degrees of extension and 2 degrees of flexion, as well as a 10% reduction in skin thickness in the treated area. CO2 laser therapy with or without clobetasol ointment under occlusion is a promising treatment modality for sclGVHD.

Sexual and gender minority (SGM) individuals, including lesbian, gay, bisexual, transgender/gender diverse, questioning/queer, intersex, and asexual (LGBTQIA) persons, represent a historically underserved population within the field of medicine, though their unique health needs are increasingly recognized. Part 2 of this two-part review will address unique concerns regarding acne, tanning behavior, sexually transmitted infections, and other health disparities among SGM adolescents. A more comprehensive understanding of the dermatologic needs of SGM youth will better allow pediatric dermatologists to actively and compassionately care for this health disparity population.

Biologic agents such as adalimumab, etanercept, golimumab, certolizumab, ustekinumab, brodalumab, secukinumab, ixekizumab, dupilumab, alefacept, rituximab, omalizumab, tildrakizumab, and guselkumab are now indicated in the treatment of dermatologic disorders. This review reports on current prevention, risk, and management of infection in patients receiving biologic therapy for dermatologic disorders. Although risk of infection in patients receiving biologic agents for management of a dermatologic disorder is well-known, it appears to continue to be a low risk. However, optimal prevention and management of some infection risks remain an unmet need. Although the overall risk for infection during biologic therapy for dermatologic disorders appears to remain low, there remains concern about the level of risk for reactivation of tuberculosis, as well as hepatitis B and C, and the risk for other, often uncommon, serious infection remains unknown. Continued pharmacovigilance serves to mitigate risk as well as promote optimal management of dermatologic disorders with biologic agents.

Background 68Gallium-DOTATATE positron emission tomography–computed tomography (PET CT) has shown superior accuracy in detecting grade 1 and 2 neuroendocrine tumors over previous imaging modalities and was recently included in National Comprehensive Cancer Network guidelines. It remains unclear which patients benefit most from this imaging modality. We therefore reviewed our initial experience with 68Gallium-DOTATATE PET CT to evaluate its usefulness in diagnosing, staging, and surveilling neuroendocrine tumors. Methods Records of patients who underwent 68Gallium-DOTATATE PET CT from March to December 2017 were prospectively evaluated. The primary endpoint was whether 68Gallium-DOTATATE PET CT changes treatment in patients with neuroendocrine tumors. Descriptive statistics, Fisher exact tests, and nested logistic regressions were conducted. Results A total of 50 consecutive patients were included. Of these, 41 patients (82%) had a biopsy-proven neuroendocrine tumor at the time of imaging. The remaining 9 patients (18%) had symptoms or biochemistry suggestive of a neuroendocrine tumor with negative cross-sectional imaging. 68Gallium-DOTATATE PET CT changed management in 33 patients (66%). There were 24 patients with intermodality changes in management and 9 patients with intramodality changes in management. Patients with scans performed for staging had a higher likelihood of a change in management (P = .006). Conclusion Performing 68Gallium-DOTATATE PET CT should be considered for staging and surveillance of neuroendocrine tumors because it is frequently associated with changes in management.

Checkpoint inhibitor immunotherapy is a transformative treatment for advanced malignancies, but can be associated with numerous immune-related adverse events (irAEs). The majority of irAEs include those that closely resemble known cutaneous and neurocutaneous autoimmune or autoinflammatory diseases, such as scleroderma, psoriasis, and dermatomyositis. We present the case of a 63-year-old man with metastatic melanoma undergoing treatment with nivolumab who developed significant motor weakness, paresthesias of both hands, swollen fingers, and a pruritic rash over the face, chest, and upper back after two cycles. Creatine kinase was elevated. Electromyography revealed a myopathic pattern, muscle biopsy of the deltoid revealed an inflammatory myopathy, and skin biopsy showed interface dermatitis. There were no detectable autoantibodies except positive antinuclear antibody. He was diagnosed with immunotherapy-induced dermatomyositis, nivolumab was held, and he was treated with oral prednisone and intravenous immunoglobulin with overall improvement in myopathic and cutaneous symptoms. Dermatomyositis is an inflammatory myopathy with a characteristic dermatologic presentation that can occur spontaneously, as a paraneoplastic phenomenon, or as a drug reaction. This is the second known case of nivolumab-induced dermatomyositis. A review of the literature revealed seven total cases of immunotherapy-induced dermatomyositis. Functionally disabling autoimmune adverse effects of this severity would frequently persuade providers to discontinue immunotherapy in patients with metastatic disease.

Immune checkpoint inhibitors are used to treat numerous malignancies but may be associated with severe adverse events. Bullous dermatoses, chiefly bullous pemphigoid (BP), are potentially progressive adverse events that cause blistering skin lesions and may involve a significant body surface area. Herein, we report an 87-year-old man with urothelial cell carcinoma undergoing atezolizumab treatment who presented with an acute-onset blistering eruption. Biopsy revealed a subepidermal bulla, direct immunofluorescence revealed linear IgG and C3 deposits at the dermal-epidermal junction, and serum studies revealed elevated levels of antibodies to BP180 and BP230. Anti-PD-L1-induced BP was diagnosed, immunotherapy was withheld, and he was treated with oral doxycycline with niacinamide and clobetasol ointment. He restarted atezolizumab and has successfully received four cycles (every 3 weeks) while continuing this BP treatment regimen. A literature review revealed eight other cases of anti-PD-L1-induced bullous disorders. The incidence of bullous dermatoses with anti-PD-1/anti-PD-L1 agents combined is 1%, whereas the reported incidence for anti-PD-L1 agents alone ranges from 1.3-5%, raising concerns for a higher overall risk. In addition to our case, only one other case reported successful resumption of immunotherapy. Early control and management of immunotherapy-induced BP may reduce complications and prevent treatment discontinuation.

Checkpoint inhibitor immunotherapy, including ipilimumab and nivolumab, is associated with numerous immune-related adverse events including dermatitis, pruritus, hepatitis, diarrhea, and hypophysitis. As the number of patients undergoing immunotherapy treatment increases, however, rare and unusual immune-related adverse events are observed. Many of these resemble known autoimmune phenomenon, such as subacute lupus erythematosus and myositis. Herein, we report a patient with metastatic serous ovarian carcinoma undergoing treatment with combination ipilimumab and nivolumab who developed subacute cutaneous lupus erythematosus (SCLE). Recent case reports have documented SCLE as a novel immune-related adverse event. In our case, she was able to successfully restart immunotherapy after a course of oral corticosteroids and maintenance oral hydroxychloroquine and topical corticosteroid therapy.

142 Background: Reports of permanent chemotherapy-induced alopecia (PCIA) are increasing in the field of oncodermatology, but there is a dearth of information regarding how it is recognized and managed by health care providers (HCPs) across different medical specialties. Methods: An electronic survey was distributed to HCPs (resident physicians, attending physicians, and nurse practitioners) in the departments of dermatology, oncology, and general internal medicine (GIM) within one Midwestern hospital system. Results: Of the 62 participants (response rate: 13%), there were 19 from dermatology, 20 from oncology, and 23 from GIM. Responses were analyzed with descriptive statistics, and chi-square and ANOVA tests. There was a significant difference in the number of subjects that had heard of PCIA prior to starting the survey (Derm: 79%, Onc: 30%, GIM: 22%, p6 months) than GIM (42% and 45% vs. 17%) and significantly more had encountered patients with the condition (47% and 45% vs. 17%). More providers in dermatology and GIM knew how to diagnose PCIA compared to oncology (84% and 83% vs. 70%). Dermatology HCPs were the only participants who had attempted to treat patients with PCIA. Most providers across the three specialties believed that patients would accept PCIA treatment that was topical, oral, injectable, and required frequent administration or monitoring, but not treatment that was expensive or high risk. A majority of HCPs surveyed (94%) agreed that the diagnosis of PCIA is important. However, there was a significant difference in the confidence of HCPs in diagnosing and managing PCIA. A minority of dermatology providers (2/19) specified that they would refer to an alopecia or oncodermatology specialist, while the majority of oncology and GIM providers would refer to dermatology. Conclusions: The results of this survey identify knowledge gaps about PCIA amongst health care providers. Therefore, education and multidisciplinary engagement should be pursued in order to improve awareness, diagnosis, referral, and management of PCIA as part of survivorship care.

Bis zum heutigen Zeitpunkt existieren fur das Transitionalzellkarzinom der Harnblase (TCC) keine Marker. Fibronektin (FN) spielt eine Rolle im Bereich der Progression und Invasion von Malignomen. Ziel dieser Studie war es, nach ersten viel versprechenden Untersuchungen die Wertigkeit von zellularem FN (cFN), eine spezifischere Subform des produzierten FN, in verschiedenen TCC-Stadien zu evaluieren.

BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

Modifications of the Child-Pugh classification of liver cirrhosis by incorporation of hyaluronan were tested to improve the prognostic power for long term evaluation of liver cirrhosis in 126 patients observed over a period of 10 years.Serum concentrations of HA were determined at study entry. Statistical analysis included Kaplan-Meier life tables and stepwise multivariant Cox-regression analysis for each parameter of Child-Pugh classification and hyaluronan. Prognostic models were developed by exchanging prothrombin time, albumin and encephalopathy by HA in different combinations.Based on a good single correlation between hyaluronan (0.62) and clinical course (P0.01) we conclude that models with hyaluronan instead of albumin or encephalopathy and with or without shifted threshold values of bilirubin and albumin are superior for the prediction of the long term prognosis. In Cox-regression analysis, apart from hyaluronan and bilirubin, no other parameters contributed to an improvement.We conclude that a modification of the Child-Pugh classification of liver cirrhosis by inclusion of HA significantly improves the predictive power of CP, especially in alcoholic etiology. A prospective validation of the newly defined scores needs to be done in the future.

Experiments on saponin-permeabilized bovine and porcine coronary arteries were performed to examine whether fluoride-induced contractile mechanisms are retained after permeabilization and whether they modulate muscle tension without a change in cytoplasmic Ca2+. Fluoride induced reversible contractions in skinned coronary smooth muscle and shifted the apparent Ca2(+)-sensitivity of the contractile system to lower Ca2+ values. Force development to fluoride required exogenous ATP and a minimum Ca2+ concentration (pCa less than 8) of the bathing medium. Force development occurred when the concentration of free Ca2+ available to the contractile apparatus seemed to be sufficiently controlled by a Ca2(+)-EGTA buffering system. The effects of fluoride were enhanced by Al3+ and imitated by both guanylyl-imidodiphosphate and 4 beta-phorbol-12,13-dibutyrate which suggests the involvement of both GTP-binding protein(s) and of the C-kinase pathway. Under conditions of sufficiently controlled Ca2+ buffering, saponin-skinned arteries responded to histamine or carbachol with an increase in muscle tension which was inhibited by specific receptor blocking agents (diphenhydramine, atropine), and which required the presence of both exogenous ATP and a low concentration of Ca2+ (pCa 7) which per se did not result in a contractile response. It is concluded that agents acting on different steps of membrane-associated signal transduction pathways are able to induce contractile responses of saponin-skinned vascular smooth muscle without a change in cytosolic Ca2+ concentration.

Introduction: The dimeric form of pyruvate kinase type M2 is overexpressed in tumor cells (TuM2-PK). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (TCC) and prostate cancer (PCA) by using a commercially available enzyme-linked immunosorbent assay for detection of TuM2-PK in plasma. Material and Methods: The TuM2-PK concentration in EDTA plasma was determined quantitatively and immunologically using an ELISA (ScheBo®Tech, Germany). We measured the TuM2-PK plasma levels of 83 patients with RCC, 30 patients with TCC and 30 patients with PCA before any therapy. 100 patients with various non-malignant urological disorders were recruited as the control group. Results: Only patients with RCC showed significantly elevated plasma levels of TuM2-PK compared to the control group (p < 0.01). We found a sensitivity of 42.6% and a specificity of 80.4% using a cut-off value of 15 U/ml (manufacturer’s recommendation). During follow-up, only 50% showed increasing plasma levels of TuM2-PK in case of metastases. Significant differences could not be detected in either TCC or PCA. Conclusions: Our data suggest that TuM2-PK is not a useful marker for TCC and PCA. Due to low sensitivity and specificity, TuM2-PK is not suitable for the diagnosis of RCC. Whether TuM2-PK may be useful in advanced RCC to control success of palliative treatment regimens is still unclear.

In experiments on anaesthetized dogs the arterial blood pressure and the left ventricular pressure were enhanced by intraarterial blood transfusion. The circumflex branch of the left coronary artery was perfused by constant blood pressure at 65, 100 or 200 mm Hg. After elimination of the sinus node the heart rate was kept constant at 150 beats per minute by electrical stimulation of the right auricle. The metabolically regulated component of coronary resistance of the circumflex branch was kept constant by a maximal pharmacological dilatation. On this condition the coronary blood flow decreases with increasing left intraventricular systolic pressure. The coronary resistance increases. The increasing coronary resistance with increasing intraventricular blood pressure is caused by an enhancement of the extravascular component because the perfusion pressure and hematocrit were constant, and the coronary vessel maximal dilated. The rise of coronary resistance with increasing intraventricular blood pressure depends on the height of perfusion pressure. Low perfusion pressure is combined with a marked increase, while the increase is small in the experiments with high perfusion pressure. The pathophysiological significance of the results has been discussed.

The effect of heart rate, left intraventricular end-diastolic pressure and maximal rate of left intraventricular pressure rise on the extra-vascular resistance to coronary blood flow was evaluated in 19 anesthetized dogs during maximal dilatation of the coronary arteries. The heart was externally stimulated after elimination of the sinus node. It was found that extravascular support increases with increases in heart rate, end-diastolic pressure and maximal rate of rise of left intraventricular pressure.

(1964). The In-Plant Nurse. Archives of Environmental Health: An International Journal: Vol. 9, No. 2, pp. 247-251.

Bei elektrischer Reizung des Herzens (rechtes Herzohr) nach Ausschaltung des Sinusknotens finden sich in dem untersuchten Frequenzbereich von 60–220 Schlagen in der Minute normale Systolen- und Diastolenzeiten. Wird durch eine maximale pharmakologische Coronardilatation die intravasale Komponente des Coronarwiderstandes konstant gehalten, so last sich mit steigender Frequenz in allen Experimenten eine Zunahme der extravasalen Komponente des Coronarwiderstandes nachweisen. Diese Zunahme wird durch die relative Zunahme der Systolenzeit auf Kosten der Diastolenzeit hervorgerufen. Die Zunahme der extravasalen Komponente der Coronarwiderstandes ist relativ gering, weil eine Abnahme des systolischen Einstromwiderstandes die Wirkung der Systolenverlangerung vermindert. Die extravasale Komponente des diastolischen Einstromwiderstandes ist frequenzunabhangig.

In Experimenten an narkotisierten Hunden wurde durch i.v. Injektionen eines Barbiturates bei gleichzeitigen Bluttransfusionen, die den arteriellen Blutdruck konstant hielten, der enddiastolische Druck im linken Ventrikel erhoht. Die Herzen wurden nach Ausschalten des Sinusknotens uber das rechte Herzohr elektrisch mit 150 Impulsen in der Minute stimuliert. Die metabolische Komponente des Einfluswiderstandes wurde durch eine pharmakologische, maximale Dilatation der Coronargefase konstant gehalten. Die Coronardurchblutung bei maximaler pharmakologischer Dilatation sinkt mit steigendem end-diastolischen Druck ab. Die extravasale Komponente des Einfluswiderstandes steigt mit zunehmendem enddiastolischen Druck wahrend der Systole, der Diastole und des Gesamtcyclus an. Die Systolendauer nimmt mit steigendem enddiastolischen Druck zu.

The effects of coronary dilatators were studied in isolated, isovolumetrically beating guinea pig hearts at different Ca++-concentrations of the perfusion fluid. In all experiments hypoxic dilatation of the vessels was absent because the coronary venous partial pressure of oxygen was higher than 50 mm Hg. The coronary dilatation caused by six of the investigated substances—Nifedipine, Prenylamin, Verapamil, Lidoflazin, Dipyridamol and Hexobendin—could be suppressed by increasing of the Ca++-concentration of the perfusion fluid. Therefore the mechanism of action on the smooth muscles of the coronary vessels has to be explained by a calcium antagonistic effect of these substances. The contractility of the myocardium is influenced in different ways. Nifedipine, Verapamil and Prenylamin show negative inotropic effects, which are also compensated by increasing the Ca++-concentration. In contrast Hexobendin, Lidoflazin and Dipyridamol show no negative or even a small positive inotropic effect. The effects of nitroglycerine and carbochromen are not affected by changes of the extracellular Ca++-concentration.

In 9 dogs the heart rate was kept constant by electrical stimulation of the right auricle after elimination of the sinus node. Hypercapnia was induced by increasing inspiratory carbonic acid concentration at constant oxygen concentration. The mean arterial carbonic acid partial pressure increased from 40.5 to 70.5 mm Hg. The mean pH decreased from 7.30–7.14. Under these conditions the coronary flow did not change. Systolic and diastolic aortic pressure, left ventricular pressure, and the maximal rate of pressure rise in the left ventricle remained unchanged. Alterations of coronary blood flow caused by increased carbonic acid concentrations as described by other authors can be explained by a change of hemodynamic conditions.

The influence of increasing perfusion pressure in the coronary arteries on cardiac contractility and oxygen consumption was studied in isovolumetrically working, empty beating, and potassium arrested guinea-pig hearts. Raising the coronary perfusion pressure from 60 to 80 cm H2O increased left ventricular peak systolic pressure by 19.4±2.8%, coronary flow by 47.7±8.0% and oxygen consumption by 32.7±6.2% (N=17). At a constant perfusion pressure hypoxia increased the coronary flow by 111.8±16.4% (N=19), but did not alter the contractility of the heart or its oxygen consumption. Increasing pressure without changing flow, raised pressure in the left ventricle by 26.5±4.8% and myocardial oxygen consumption by 20.3±3.4% (N=14). The end-diastolic pressure and the heart rate remained unchanged in all experiments. From these findings it may be concluded that the pressure in the coronary vessels — independent of the flow rate — exercises a positive inotropic effect, thereby increasing metabolism. This can be explained by increased fibre tension, caused by an extension of the coronary vessels, the so-called “garden-hose-effect”.