scholarly journals Limited thermal acclimation capacity in cave beetles

2018 ◽  
Vol 1 ◽  
Author(s):  
Susana Pallarés ◽  
Ignacio Ribera ◽  
Aitor Montes ◽  
Andrés Millán ◽  
Valeria Rizzo ◽  
...  
Keyword(s):  
Thermal Tolerance ◽  
Video Recording ◽  
Thermal Acclimation ◽  
List Type ◽  
Thermal Limit ◽  
Control Temperature ◽  
Rate Of Increase ◽  
Subterranean Species ◽  
Upper Thermal Limit

Thermal tolerance is a key vulnerability factor for species that cannot cope with changing conditions by behavioural adjustments or dispersal, such as subterranean species. Previous studies of thermal tolerance in cave beetles suggest that these species may have lost some of the thermoregulatory mechanisms common in temperate insects, and appear to have a very limited thermal acclimation ability. However, it might be expected that both thermal tolerance and acclimation ability should be related with the degree of specialization to deep subterranean environments, being more limited in highly specialized species. To test this hypothesis, we use an experimental approach to determine the acclimation capacity of cave beetles within the tribe Leptodirini (family Leiodidae) with different degrees of specialization to the deep subterranean environment. For this, we acclimate groups of individuals at a temperature close to their upper thermal limit (20ºC) or a control temperature (approximately that of the cave in which they were found) for 2 or 10 days (short- vs. long-term acclimation). a temperature close to their upper thermal limit (20ºC) or a control temperature (approximately that of the cave in which they were found) for 2 or 10 days (short- vs. long-term acclimation). Upper thermal limits (heat coma temperature, HC) are then measured for each individual using a ramping protocol (rate of increase of 1ºC/min) combined with infrared thermography and video recording. Preliminary results in a deep subterranean species (Speonomidius crotchi, with an intermediate degree of specialization) showed no significant effect of acclimation temperature in HC at any of the exposure times. Such reduced thermal plasticity could be also expected for other highly specialized subterranean species. The potential implications of these findings for subterranean biodiversity in a climate change context are discussed.

scholarly journals Neural dysfunction at the upper thermal limit in the zebrafish

2020 ◽  
Author(s):  
Anna H. Andreassen ◽  
Petter Hall ◽  
Pouya Khatibzadeh ◽  
Fredrik Jutfelt ◽  
Florence Kermen
Keyword(s):  
Heart Rate ◽  
Heat Stress ◽  
High Temperatures ◽  
Neural Activity ◽  
Thermal Tolerance ◽  
Oxygen Availability ◽  
Adult Zebrafish ◽  
Thermal Limit ◽  
Larval Zebrafish ◽  
Upper Thermal Limit

ABSTRACTUnderstanding animal thermal tolerance is crucial to predict how animals will respond to increasingly warmer temperatures, and to mitigate the impact of the climate change on species survival. Yet, the physiological mechanisms underlying animal thermal tolerance are largely unknown. In this study, we developed a method for measuring upper thermal limit (CTmax) in larval zebrafish (Danio rerio) and found that it occurs at similar temperatures as in adult zebrafish. We discovered that CTmax precedes a transient, heat-induced brain-wide depolarization during heat ramping. By monitoring heart rate, we established that cardiac function is sub-optimal during the period where CTmax and brain depolarization occur. In addition, we found that oxygen availability affects both locomotor neural activity and CTmax during a heat stress. The findings of this study suggest that neural impairment due to limited oxygen availability at high temperatures can cause CTmax in zebrafish.HighlightsLarval zebrafish reach their critical thermal limit (CTmax) at similar temperature as adult zebrafishAcute heat stress causes a brain-wide spreading depolarization near the upper thermal limitCTmax precedes brain-wide depolarizationHeart rate declines at high temperatures but is maintained during CTmax and brain depolarizationNeural activity is impaired prior to CTmax and brain-wide depolarizationOxygen availability in the water affects both CTmax and neural activity

scholarly journals Critical Thermal maximum measurements and its biological relevance: the case of ants

2020 ◽  
Author(s):  
Chi-Man Leong ◽  
Toby P. N. Tsang ◽  
Benoit Guénard
Keyword(s):  
Community Dynamics ◽  
Phylogenetic Signal ◽  
Methodological Approach ◽  
Functional Trait ◽  
List Type ◽  
Critical Thermal Maximum ◽  
Thermal Limit ◽  
Thermal Maximum ◽  
Multiple Species ◽  
Upper Thermal Limit

ABSTRACTUpper thermal limit (UTL) is a key trait in evaluating ectotherm fitness. Critical Thermal maximum CTmax, often used to characterize the UTL of an organism in laboratory setting, needs to be accurate to characterize this significant and field-relevant threshold. The lack of standardization in CTmax assays has, however, introduce methodological problems in its measurement and incorrect estimation of species upper thermal limit; with potential major implications on the use of CTmax in forecasting community dynamics under climate change. In this study we ask if a satisfactory ramping rate can be identified to produce accurate measures of CTmax for multiple species.We first identified the most commonly used ramping rates (i.e. 0.2, 0.5 and 1.0 °Cmin−1) based on a literature review, and determined the ramping rate effects on CTmax value measurements in 27 ant species (7 arboreal, 16 ground, 4 subterranean species) from eight subfamilies using both dynamic and static assays. In addition, we used field observations on multiple species foraging activity in function of ground temperatures to identify the most biologically relevant CTmax value to ultimately develop a standardized methodological approach.Integrating dynamic and static assays provided a powerful approach to identify a suitable ramping rate for the measurements of CTmax values in ants. Our results also showed that among the values tested the ramping rate of 1 °Cmin−1 is optimal, with convergent evidences from CTmax values measured in laboratory and from foraging thermal maximum measured in the field. Finally, we illustrate how methodological bias in terms of physiological trait measurements can also affect the detection of phylogenetic signal (Pagel’s λ and Bloomberg’s K) in subsequent analyses.Overall, this study presents a methodological framework allowing the identification of suitable and standardized ramping rates for the measurement of ant CTmax, which may be used for other ectotherms. Particular attention should be given to CTmax values retrieved from less suitable ramping rate, and the potential biases that functional trait based research may induce on topics such as global warming, habitat conversion or their impacts on analytical interpretations on phylogenetic conservatism.

scholarly journals P044 Can an electronic prescribing system ensure clear anticoagulation discharge communication?

2019 ◽  
Vol 104 (7) ◽  
pp. e2.49-e2
Author(s):  
Susie Gage
Keyword(s):  
Patient Safety ◽  
Discharge Summary ◽  
Electronic Prescribing ◽  
List Type ◽  
Heparin Infusion ◽  
National Patient Safety Agency ◽  
High Dependency ◽  
National Patient ◽  
Discharge Summaries

AimThe National Patient Safety Agency (NPSA)1 identified heparin as a major cause of adverse events associated with adverse incidents, including some fatalities. By ensuring good communication, this should be associated with risk reduction.1 The aim of this study was to ensure there is clear anticoagulation communication on discharge, from the paediatric intensive care unit (PICU) electronic prescribing system (Philips), to the paediatric cardiac high dependency unit and paediatric cardiac ward. To investigate whether the heparin regimen complies with the hospital’s anticoagulant guidelines and if there is any deviation; that this is clearly documented. To find out if there is an indication documented for the heparin regimen chosen and if there is a clear long term plan documented for the patient, after heparin cessation.MethodsA report was generated for all patients who were prescribed a heparin infusion on PICU, between 1st January 2018 and 30th June 2018, from the Philips system. All discharge summaries from the PICU Philips system were reviewed. Only paediatric cardiac patients were included that had a heparin infusion prescribed on discharge, all other discharge summaries were excluded from the study. Each discharge summary was reviewed in the anticoagulant section; for the heparin regimen chosen, whether it complies with the hospital’s anticoagulant guidelines and if there was any deviation whether this was documented. The indication documented of which heparin regimen was chosen and whether a clear long term plan was documented after heparin cessation; for example if the patient is to be transferred onto aspirin, clopidogrel, warfarin or enoxaparin.Results82 discharge summaries were reviewed over the 6 month period between 1st January 2018 and 30th June 2018; 16 were excluded as were not paediatric cardiac, leaving 66 paediatric cardiac discharge summaries that were reviewed. 45 out of 66 (68%) complied with the hospital’s heparin anticoagulation guidelines. Of the 32% that deviated from the protocol; only 33% (7 out of 21) had a reason documented. Only 50% (33) of the summaries reviewed had an indication for anticoagulation noted on the discharge summary and 91% of discharge summaries had a long term anticoagulant plan documented.ConclusionThe electronic prescribing system can help to ensure a clear anticoagulation communication as shown by 91% of the anticoagulation long term plan being clearly documented; making it a more seamless patient transfer. On the Philips PICU electronic prescribing system there is an anticoagulant section on the discharge summary that has 3 boxes that need to be completed; heparin regimen, indication and anticoagulation long term plan. However, despite these boxes; deviations from the anticoagulant protocol were poorly documented as highlighted by only 33% having the reason highlighted in the discharge summary, only 50% of the indications were documented. Despite having prompts for this information on the discharge summary, the medical staffs needs to be aware to complete this information, in order to reduce potential medication errors and risk.ReferenceThe National Patient Safety Agency (NPSA). Actions that make anticoagulant therapy safer. NPSA; March 2007.

scholarly journals Antibiotics at birth and later antibiotic courses: effects on gut microbiota

2021 ◽  
Author(s):  
Sofia Ainonen ◽  
Mysore V Tejesvi ◽  
Md. Rayhan Mahmud ◽  
Niko Paalanne ◽  
Tytti Pokka ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Group ◽  
List Type ◽  
Antibiotic Exposure ◽  
Microbiota Composition ◽  
Long Term Effects ◽  
The Impact ◽  
Antibiotic Courses ◽  
Gut Microbiota Composition

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

429 Long-term analysis of MASTERKEY-265 phase 1b trial of talimogene laherparepvec (T-VEC) plus pembrolizumab in patients with unresectable stage IIIB-IVM1c melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A454-A454
Author(s):  
Georgina Long ◽  
Reinhard Dummer ◽  
Douglas Johnson ◽  
Olivier Michielin ◽  
Salvador Martin-Algarra ◽  
...  
Keyword(s):  
Pigment Cell ◽  
Objective Response ◽  
Stage Iiib ◽  
List Type ◽  
Talimogene Laherparepvec ◽  
Unresectable Stage ◽  
Long Term Follow Up ◽  
Phase 1B

BackgroundPrevious findings from the MASTERKEY-265 phase 1b study showed that the combination of T-VEC and pembrolizumab was well tolerated and produced a high complete response (CR) rate of 43% in patients with advanced melanoma.1 The 3-year progression-free survival (PFS) and overall survival (OS) rates at that time were 53.6% and 71%, respectively. Here, we report the results of the long-term follow-up efficacy analyses.MethodsThe MASTERKEY-265 phase 1b trial (NCT02263508) was an open-label, single-arm study that enrolled patients who had unresectable, stage IIIB-IVM1c melanoma with injectable, measurable lesions and no prior systemic treatment. T-VEC was administered intralesionally at the approved dosing starting day 1 of week 1. Pembrolizumab (200 mg) was administered intravenously Q2W beginning on day 1 of week 6. The maximum treatment period was 2 years. The primary endpoint was dose-limiting toxicities; key secondary endpoints included objective response rate and PFS per modified irRC, OS, and safety.ResultsAs of the data cutoff (Mar 2, 2020), all 21 patients enrolled were off treatment; 6 died and 15 are in long-term follow-up. The median follow-up time was 58.6 months (range: 1.4–61.6). The CR rate remained 43% (9/21 patients). Twelve of the 13 responders (92.3%) are still in response, including all 9 patients with a CR. Median duration of response was not reached (range: 2.8+–54.3+ months). Median PFS and OS were not reached at the data cutoff. KM estimates of 4-year PFS and OS rates were 55.9% and 71.4%, respectively, which have held stable since the 3-year analysis. Patients who achieved a CR or partial response had better OS (p=0.0056) compared to those who did not respond. Median OS for non-responders was 24.4 months and was not reached for responders. No additional safety signals were detected.ConclusionsAt almost 5 years of follow-up, median PFS and OS were not reached for patients treated with the combination of T-VEC and pembrolizumab in this phase 1b study of unresectable metastatic melanoma. 92% of responders remained in response with improved OS observed in responders compared with non-responders. The corresponding randomized phase 3 trial has completed enrollment and is currently ongoing.Trial RegistrationNCT02263508Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.ReferenceLong G, Dummer R, Andtbacka R, et al. Follow-up analysis of MASTERKEY-265 Phase 1b (ph1b) trial of talimogene laherparepvec (T-VEC) in combination (combo) with pembrolizumab (pembro) in patients (pts) with unresectable stage IIIB–IVM1c melanoma (MEL). Pigment Cell Melanoma Res 2019;32:133–134.

#3104 Is dipsogenic diabetes insipidus the same condition as psychogenic polydipsia?

2021 ◽  
Vol 92 (8) ◽  
pp. A11.2-A11
Author(s):  
Ewelina de Leon ◽  
Graeme Yorston
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Literature Review ◽  
Diabetes Insipidus ◽  
Endocrine Disruption ◽  
Psychiatric Disease ◽  
List Type ◽  
Psychogenic Polydipsia

Objectives/AimsTraumatic brain injury is a common cause of permanent or long-term disability,1 and up to 80% of people with moderate to severe brain injury have some degree of pituitary insufficiency. Endocrine disruption has been documented in medical literature since the 1940s,2-4 where central diabetes insipidus has been described as a common transient complication which causes polydipsia (insatiable thirst). However, polydipsia can be caused by other conditions. It is classified into dipsogenic, in a syndrome of disordered thirst-regulating mechanism in patients without psychiatric disease called dipsogenic diabetes insipidus, psychogenic, as a compulsive water drinking in patients with psychiatric conditions referred to as psychogenic polydipsia or psychogenic diabetes insipidus and iatrogenic where large quantities of water are consumed for health benefits. All of which are referred to as primary polydipsia if these conditions cannot be distinguished. Dipsogenic diabetes insipidus and psychogenic polydipsia can be easily mixed up, misdiagnosed or even unrecognised, mainly because their pathophysiology is still unclear. Are these conditions different, or is there anything that can relate them to each other? With this literature review, we are aiming to find the link between subsets of polydipsia after brain trauma, to compare proposed differential diagnosis and their functionality in clinical settings.MethodA literature review was conducted following a search of MEDLINE, CINAHL Plus, APA PsycArticles, APA PsycBooks, APA PsycInfo databases from 1858 onwards.ResultsWe will present our findings from the literature review.ConclusionPolydipsia is a common clinical problem and requires careful evaluation and management to prevent long term neurological sequelae, and there are no evidence-based treatment guidelines.References National Institute of Health and Care Excellence (NICE). (2019). Head Injury. CG176. Retrieved from: https://www.nice.org.uk/guidance/cg176 Escamilla RF, Lisser H. Simmonds disease: A clinical study with revie of the literature; Differentiation from anorexia nervosa by statistical analysis of 595 cases, 101 of which were provided pathologically. The Journal of Clinical Endocrinology & Metabolism 1942;2(2):6596. Porter RJ, Miller RA. Diabetes insipidus following closed head injury. Journal of Neurology, Neurosurgery, and Psychiatry 1946;11:528562. Webb NE, Little B, Loupee-Wilson S, Power EM. Traumatic brain injury and neuro-endocrine disruption: medical and psychosocial rehabilitation. NeuroRehabilitation (Reading, Mass.) 2014;34(4):625636.

scholarly journals Long-term Photometric Monitoring of FUor and FUor-like Objects

2018 ◽  
pp. 240-248
Author(s):  
E. Semkov ◽  
S. Ibryamov ◽  
S. Peneva ◽  
A. Mutafov
Keyword(s):  
Light Curve ◽  
Significant Role ◽  
Stellar Evolution ◽  
Photographic Plate ◽  
Light Curves ◽  
Curve Shape ◽  
Rate Of Increase ◽  
Fu Ori ◽  
Photometric Monitoring

A phenomenon with a significant role in stellar evolution is the FU Orionis (FUor) type of outburst. The first three (classical) FUors (FU Ori, V1515 Cyg and V1057 Cyg) are well-studied and their light curves are published in the literature. But recently, over a dozen new objects of this type were discovered, whose photometric history we do not know well. Using recent data from photometric monitoring and data from the photographic plate archives we aim to study, the long-term photometric behavior of FUor and FUor-like objects. The construction of the historical light curves of FUors could be very important for determining the beginning of the outburst, the time to reach the maximum light, the rate of increase and decrease in brightness, the pre-outburst variability of the star. So far we have published our results for the light curves of V2493 Cyg, V582 Aur, Parsamian 21 and V1647 Ori. In this paper we present new data that describe more accurate the photometric behavior of these objects. In comparing our results with light curves of the well-studied FUors (FU Ori, V1515 Cyg and V1057 Cyg), we conclude that every object shows different photometric behavior. Each known FUor has a different rate of increase and decrease in brightness and a different light curve shape.

scholarly journals Long-term low-dose ketoconazole treatment in bilateral macronodular adrenal hyperplasia

2014 ◽  
Vol 2014 ◽  
Author(s):  
Sophie Comte-Perret ◽  
Anne Zanchi ◽  
Fulgencio Gomez
Keyword(s):  
Medical Therapy ◽  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
List Type ◽  
Adrenal Hyperplasia ◽  
Benign Condition ◽  
Steroid Secretion ◽  
Free Cortisol

Summary Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery. Learning points Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features. Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated. However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.

scholarly journals 934 Biological mechanisms in the different etiologies of Merkel cell carcinoma patients: polyomavirus or UV exposure

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A980-A980
Author(s):  
Domenico Mallardo ◽  
Giosuè Scognamiglio ◽  
Khrystyna North ◽  
Mariaelena Capone ◽  
Michael Bailey ◽  
...  
Keyword(s):  
Informed Consent ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell Polyomavirus ◽  
Uv Exposure ◽  
List Type ◽  
Phase 2 ◽  
Merkel Cell ◽  
Term Survival

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer with neuroendocrine features, and it is associated with elevated mortality. The pathogenesis is associated with presence of clonally integrated Merkel cell polyomavirus (MCPyV) or ultraviolet light (UV) exposure.1 The MCPyV causes up to 80% of MCC tumors in North America and Europe.2–4 Recently immunotherapy is having good results,5 the phase 2 trial JAVELIN Merkel 200 indicated that treatment with Avelumab (PDL1 inhibitor) in patients with metastatic MCC pre-treated have a meaningful long-term survival outcomes respect chemotherapy. Moreover, ORRs were highest in patients with high TMB that were also MCPyV−, PD-L1+ or had a greater CD8+ T cell density at the invasive margin.6 In this study, we investigated the biological signatures in patients with MCPyV or not.MethodsFrom April 2011 to June 2018, we collected retrospectively 50 FFPE (Formalin-Fixed Paraffin-Embed) from 37 patients with metastatic MCC and 13 tissues from a secondary metastatic site. All patients have appropriately signed informed consent. We performed an immunohistochemistry assays (IHC) for MCPyV and PDL1. In addition, through the NanoString GeoMx DSP (Digital Spatial Profiling), we analysed 11 patients (6 MCPyV+; 5 MCPyV-) with cutaneous metastasis using a 44-plex antibody cocktail. For each slide we selected three different areas: Intratumoral, extratumoral and tumour border, in each area we selected CD4+ and CD8+ cells in 4 different ROIs (Region of Interest). Statistical analysis was performed via Bonferroni correction, P< 0.05 was considered statistically significant for median stratification.ResultsThe DSP analysis showed that the tumour border cells have an overexpression of IDO respect intratumoral area (adj. p<0.01). Instead, extratumoral area of MCPyV- patients have a higher expression of B7-H3 respect MCPyV+ as well as FOXP3 is higher in the tumour border of MCPyV+ patients and EpCAM in the intratumoral area (p<0.05). PDL1 is overexpressed in MCPyV+ CD4+ cells respect CD8+ (p<0.05). The IHC assay shown that viral status does not change in multiple metastases and PDL1 is elevated in the tumour border (p<0.05).ConclusionsIn this retrospective study, our preliminary data shown that tumour edge have an important role in the modulations of immune infiltrate and patients with Merkel cell polyomavirus could have a different pathway of immunosuppression compared to patients with non-virus related etiology. Further investigations are needed to get additional information.AcknowledgementsThe study was supported by the Institutional Project ”Ricerca Corrente” of Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli, Italy.ReferencesKaae J, Hansen AV, Biggar RJ, et al. Merkel cell carcinoma: incidence, mortality, and risk of other cancers. J Natl Cancer Inst 2010 June 2;102(11):793–801.Feng H, Shuda M, Chang Y, et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008 February 22;319(5866):1096–100.Garneski KM, Warcola AH, Feng Q, et al. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol 2009 January;129(1):246–8.Goh G, Walradt T, Markarov V, et al. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget 2016 January 19;7(3):3403–15.Bichakjian CK, Olencki T, Aasi SZ, et al. Merkel cell carcinoma, version 1.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2018 June;16(6):742–774.D’Angelo SP, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer 2020 May;8(1):e000674.Ethics ApprovalThe study was approved by internal ethics board of the Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli Italy, approval number of registry 33/17 OSS.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

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