Seasonal activity patterns of a Kalahari mammal community: Trade-offs between environmental heat load and predation pressure.

Mammals in arid zones have to trade off thermal stress, predation pressure, and time spent foraging in a complex thermal landscape. We quantified the relationship between the environmental heat load and activity of a mammal community in the hot, arid Kalahari Desert. We deployed miniature black globe thermometers within the existing Snapshot Safari camera trap grid on Tswalu Kalahari Reserve, South Africa. Using the camera traps to record species' activity throughout the 24-h cycle, we quantified changes in the activity patterns of mammal species in relation to heat loads in their local environment. We compared the heat load during which species were active between two sites with differing predator guilds, one where lion (Panthera leo) biomass dominated the carnivore guild and the other where lions were absent. In the presence of lion, prey species were generally active under significantly higher heat loads, especially during the hot and dry spring. We suggest that increased foraging under high heat loads highlights the need to meet nutritional requirements while avoiding nocturnal activity when predatory pressures are high. Such a trade-off may become increasingly costly under the hotter and drier conditions predicted to become more prevalent as a result of climate change within the arid and semi-arid regions of southern Africa.

Macro- and microscopic changes in veins with short-term central venous catheters: an observational autopsy study.

BACKGROUND: Centrally inserted central catheters (CICCs) are indispensable in modern healthcare, but unfortunately, come with complications. Catheter-related thrombosis is a well-known complication reported to occur in 5-30% of patients with CICC. There is a paucity of studies that report the incidence of catheter-related thrombosis after the introduction of real-time ultrasound insertion guidance as clinical practice. This study aimed to demonstrate any pathological macro- or microscopic changes in the vein wall associated with CICCs. METHODS: The study was approved by the Swedish Ethical Review Authority and was conducted at a large university hospital. The study included 12 patients with a short-term CICC who were subject to autopsies. Vessels with inserted catheters were macroscopically and microscopically examined. RESULTS: In total, seven female and five male patients with a median age of 70 (interquartile range 63-76) were included. With one exception, all patients received routine thromboprophylaxis throughout the period with CICC. Most inserted CICCs were 9.5 French (54%) and were inserted in the internal jugular vein (92%). The median time with CICC was seven days (interquartile range 1.8-20). At autopsy, thrombi were observed in all cases (100%), macroscopically and microscopically, attached to the distal portion of the CICC and/or the adjacent vessel wall. Inflammatory changes in the vessel walls were seen in all cases, and varying degrees of fibrosis were demonstrated in eight cases (67%). CONCLUSIONS: This autopsy study demonstrated that catheter-related thrombus formation with adjacent inflammatory and fibrotic vessel wall thickening was very common, despite a limited period of catheter use. The consequences of these findings are important, as thrombi may cause pulmonary embolism and possibly lead to catheter-related infections, and since inflammatory and fibrotic vessel wall thickening may evolve into chronic venous stenosis. Furthermore, the findings are a cause of concern, as CICCs are indispensable in modern healthcare and complications may be masked by the general disease that was the indication for CICC insertion.

Changes in alpha, theta, and gamma oscillations in distinct cortical areas are associated with altered acute pain responses in chronic low back pain patients.

Introduction: Chronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known. Methods: We compared measured pain responses to peripheral mechanical stimuli applied to a site of chronic pain and at a pain-free site in participants suffering from chronic lower back pain (n = 15) versus pain-free control participants (n = 15) by analyzing behavioral and electroencephalographic (EEG) data. Results: As expected, participants with chronic pain endorsed enhanced pain with mechanical stimuli in both back and hand. We further analyzed electroencephalographic (EEG) recordings during these evoked pain episodes. Brain oscillations in theta and alpha bands in the medial orbitofrontal cortex (mOFC) were associated with localized hypersensitivity, while increased gamma oscillations in the anterior cingulate cortex (ACC) and increased theta oscillations in the dorsolateral prefrontal cortex (dlPFC) were associated with generalized hyperalgesia. Discussion: These findings indicate that chronic pain may disrupt multiple cortical circuits to impact nociceptive processing.

Implementing Telemedicine During the COVID-19 Pandemic: Disparities in Utilization in an Urban Pain Medicine Practice.

Purpose: The COVID-19 pandemic led to a drastic expansion in utilizing telemedicine, circumventing some of the geographical barriers to accessing pain care. However, uncertainties around the impact of telemedicine across various sociodemographic groups still exist, prompting further exploration. Therefore, this study aimed to evaluate the impact of sociodemographic factors in telemedicine utilization during and after the COVID-19 pandemic. Patients and methods: All outpatient non-procedural visits at the pain medicine division of a large academic institution in the epicenter of the pandemic (New York, USA), between March 2019 and October 2021, were retrospectively included. Sociodemographic data including gender, age, ethnicity/race, postal code, and type of health insurance, across three time periods associated with the COVID-19 pandemic - pre-lockdown (in-office visits only), lockdown (telemedicine visits only) and post-lockdown (offering both in-office and telemedicine visits) - were analyzed and compared. Results: In total, 12,615 unique patients - The majority being women (58%) - were seen during the whole study period. In the post-lockdown period, telemedicine was utilized by 42% of all patients. Follow-up visits, younger patients, white patients, patients residing further away from the hospital, and privately insured patients were more likely to utilize telemedicine post-lockdown (p <0.05). Older patients, minorities, Manhattan residents, and Medicare/Medicaid recipients, were more likely to use in-office visits post-lockdown (p <0.05). Conclusion: We identified disparities in the utilization of telemedicine in Pain Medicine, which may be due to socioeconomic factors such as lack of access to reliable internet access, cost of devices, and technological know-how. This emphasizes the need for further studies to better understand the reasons for and barriers to telemedicine use. This could help inform policymaking to safeguard equitable access to telemedicine use for pain care.

In search of a composite biomarker for chronic pain by way of EEG and machine learning: where do we currently stand?

Machine learning is becoming an increasingly common component of routine data analyses in clinical research. The past decade in pain research has witnessed great advances in human neuroimaging and machine learning. With each finding, the pain research community takes one step closer to uncovering fundamental mechanisms underlying chronic pain and at the same time proposing neurophysiological biomarkers. However, it remains challenging to fully understand chronic pain due to its multidimensional representations within the brain. By utilizing cost-effective and non-invasive imaging techniques such as electroencephalography (EEG) and analyzing the resulting data with advanced analytic methods, we have the opportunity to better understand and identify specific neural mechanisms associated with the processing and perception of chronic pain. This narrative literature review summarizes studies from the last decade describing the utility of EEG as a potential biomarker for chronic pain by synergizing clinical and computational perspectives.

Local relapse of soft tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy.

BACKGROUND: The quality of surgical margins is the most important factor affecting local control in soft tissue sarcoma (STS). Despite this, there is no universally accepted consensus on the definition of an adequate surgical margin or on which patients should be offered radiation therapy. This study focuses on local control and its prognostic factors in patients with trunk wall and extremity STS. METHODS: Adult patients with a final diagnosis of trunk wall or extremity STS referred to a single tertiary referral centre between August 1987 and December 2016 were identified from a prospective institutional database. Patients were treated according to a protocol instituted in 1987. The classification of surgical margins and indications for radiation therapy were based on anatomy and strict definition of surgical margins as metric distance to the resection border. Local treatment was defined as adequate if patients received either surgery with wide margins alone or marginal surgery combined with radiation therapy. Margins were considered wide if the tumour was excised with pathological margins greater than 2.5 cm or with an uninvolved natural anatomical barrier. After treatment, patients were followed up with local imaging and chest X-ray: 5 years for high-grade STS, 10 years for low-grade STS. RESULTS: A total of 812 patients were included with a median follow-up of 5.8 (range 0.5-19.5) years. Forty-four patients had a grade 1 tumour: there were no instances of recurrence in this group thus they were excluded from further analysis. Five-year local control in the 768 patients with grade 2-3 STS was 90.1 per cent in patients receiving adequate local treatment according to the protocol. Altogether, 333 patients (43.4 per cent) were treated with wide surgery alone and their 5-year local control rate was 91.1 per cent. Among patients treated with wide surgery alone, deep location was the only factor adversely associated with local relapse risk in multivariable analysis; 5-year local control was 95.3 per cent in superficial and 88.3 per cent in deep-sited sarcomas (hazards ratio 3.154 (95% c.i. 1.265 to 7.860), P = 0.014). CONCLUSION: A high local control rate is achievable with surgery alone for a substantial proportion of patients with STS of the extremities or superficial trunk wall.

The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis.

OBJECTIVE: The type 1 interferon (IFN) pathway is up-regulated in dermatomyositis (DM). We sought to define how organ-specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic type I IFN activity in adult patients with DM. METHODS: RNA sequencing was performed on 355 whole blood samples collected from 202 well-phenotyped DM patients followed up during the course of their clinical care. A previously defined 13-gene type I IFN score was modeled as a function of demographic, serologic, and clinical variables using both cross-sectional and longitudinal data. RESULTS: The pattern of type I IFN-driven transcriptional response was stereotyped across samples with a sequential modular activation pattern strikingly similar to systemic lupus erythematosus. The median type I IFN score was higher or lower in patients with anti-melanoma differentiation-associated protein 5 (anti-MDA-5) or anti-Mi-2 antibodies, respectively, compared to patients without these antibodies. Absolute type I IFN score was independently associated with muscle and skin disease activity, interstitial lung disease, and anti-MDA-5 antibodies. Changes in the type I IFN score over time were significantly associated with changes in skin or muscle disease activity. Stratified analysis accounting for heterogeneity in organ involvement and antibody class revealed high correlation between changes in the type I IFN score and skin disease activity (Spearman's ρ = 0.84-0.95). CONCLUSION: The type I IFN score is independently associated with skin and muscle disease activity as well as certain clinical and serologic features in DM. Accounting for the effect of muscle disease and anti-MDA-5 status revealed that the type I IFN score is strongly correlated with skin disease activity, providing support for type I IFN blockade as a therapeutic strategy for DM.

Sustained low catheter related infection (CRI) incidence in an observational follow-up study of 9924 catheters using automated data scripts as quality assurance for central venous catheter (CVC) management.

Background: To maintain a low incidence of Catheter Related Infections (CRI) and Catheter Related Bloodstream Infections (CRBSI), continuous follow-up studies on catheter management are necessary. The aims of the present study were to investigate the incidence of catheter tip colonisation, CRI and CRBSI in the Region, to further explore the feasibility of automatic data collection and to investigate associations between independent variables and CRI. Methods: Data from electronic patient charts on all documented central venous catheter (CVC) insertions from multiple hospitals in southern Sweden, between March 2019 and August 2020, were automatically extracted. Multivariable regression analyses were used to identify associated risk factors. Results: In total, 9924 CVC insertions were included. The prevalence of CRI and CRBSI were 0.7% (n = 74) and 0.02% (n = 20) with incidences of 1.2/1000 catheter days and 0.3/1000 catheter days, respectively. Conclusions: We found a sustained low incidence of CRI and CRBSI in the Region. Catheter tips were less likely to be colonised when the subclavian route was used compared to the internal jugular route and male sex as well as increased number of catheter lumens were associated with both catheter tip colonisation and CRI. By using automated scripts, data extraction was efficient and feasible but also demonstrated that real-time quality assurance should be recommended, since this is superior to current standard.

Localised chronic fibrosing vasculitis versus erythema elevatum diutinum.

A woman in her 70s was referred for a painless plaque on the shin, present for 2 years and progressing in thickness. Examination revealed a large erythematous to violaceous indurated plaque with cobblestone appearance. Biopsy revealed an inflammatory infiltrate of neutrophils with scattered histiocytes, lymphocytes, eosinophils and plasma cells interspersed with areas of lamellar fibrosis and focal areas of vascular damage, suggestive of a localised chronic fibrosing vasculitis of the skin. Localised chronic fibrosing vasculitis is a rare dermatosis, typically presenting as ulcerated violet-red nodules, which can appear histologically similar to erythema elevatum diutinum (EED), which typically presents as red-brown annular plaques. EED may have a predominance of neutrophils and granulomas, while chronic fibrosing vasculitis may have a sparse infiltrate of mixed inflammatory cells without granulomas. While dapsone is a first-line treatment for EED, there are no formal guidelines on the treatment of localised chronic fibrosing vasculitis. Given the neutrophils in this sample and similarities with EED, this patient was treated with oral dapsone, resulting in plaque improvement.

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma.

Background: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma. Patients and Methods: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter. Results: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (r Pearson =0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival. Conclusion: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.

Radiation-associated angiosarcoma of the breast: analysis of diagnostic tools in a registry-based population.

BACKGROUND: Radiation-associated angiosarcoma of the breast (RAASB) is a serious late consequence caused by breast cancer treatment. Initial symptoms are often inconspicuous, thus contributing to diagnostic delay. Most previous studies of the diagnostic aspects of RAASB are case reports. PURPOSE: To perform a complete review of the imaging findings and biopsy methods in a nationwide RAASB cohort. MATERIAL AND METHODS: RAASB patients were identified from a national cancer registry and additional patients were included from our hospital. All available information from imaging (mammogram [MGR], ultrasound [US], magnetic resonance imaging [MRI], and computed tomography [CT]) and biopsies was reviewed. The sensitivity of imaging and biopsy methods for detection of RAASB was calculated. RESULTS: Fifty-eight patients with RAASB were found. Fourteen MGR, 30 US, 24 MRI, and 25 CT studies were available for evaluation. The sensitivity of MGR, US, MRI, and CT for detection of RAASB was 43%, 50%, 92%, and 84%, respectively. Superior sensitivity was demonstrated for punch biopsy (84%) and incisional biopsy (93%) compared to fine-needle aspiration cytology (0%) and core needle biopsy (18%). CONCLUSION: MRI and CT have comparable sensitivity for detection of RAASB, while MGR and US are unreliable. However, negative findings in MRI or CT must be interpreted with caution. Punch biopsy and incisional biopsy are the preferred biopsy methods.

Central venous catheter-related complications in hematologic patients: An observational study.

BACKGROUND: The frequency of central venous catheter (CVC)-related complications in hematologic patients has previously been studied but some uncertainty remains. Therefore, this observational cohort study was designed primarily to investigate mechanical and infectious complications related to CVC insertion in hematologic patients and secondarily to identify factors associated with these complications. METHODS: Documented data on CVC insertions in all adult hematologic patients who received a CVC from 2013 to 2019 at a University Hospital in Sweden were retrospectively collected. RESULTS: A total of 589 CVC insertions in 387 patients were included. The prevalence of moderate and severe mechanical complications, predominantly comprising grades 2-4 bleeding, was 11%. Preprocedural coagulopathy, number of needle passes, and arterial puncture were all independently associated with grades 2-4 bleeding. The incidence of suspected catheter-related infections (sCRI) was 3.7/1000 catheter days. Higher body mass index and male gender were independently associated with sCRI. CONCLUSIONS: Patients with hematologic malignancies have a high risk of both grades 2-4 bleeding and sCRI after CVC insertion. This underlines the importance of optimizing the conditions at the insertion and also of daily inspections, evaluation of future needs, and extra precautions to avoid sCRI in these susceptible patients.

[Transgender health and healthcare during the COVID­19 pandemic: a cross-sectional online survey in German-speaking countries]. / Gesundheit und Gesundheitsversorgung von trans Personen während der COVID­19-Pandemie: Eine Online-Querschnittstudie in deutschsprachigen Ländern.

BACKGROUND AND OBJECTIVE: Since spring of 2020, the COVID­19 pandemic has disrupted our day-to-day lives and led to negative consequences in various areas of life, including mental and physical wellbeing. In this article, we take a closer look at the situation of trans people, who - due to experiences with discrimination and marginalization as well as their specific health-related interests - could be characterized by a particular vulnerability. METHODS: Using an online cross-sectional survey, which we designed collaboratively with experts from the trans community, we investigated the mental and physical health of trans people from German-speaking countries and their access to trans-related healthcare during the COVID­19 pandemic in the period from 1 May 2020 to 31 January 2021. RESULTS: Since the beginning of the COVID­19 pandemic, trans people have experienced barriers in access to gender-affirming treatments, mental health services, and COVID­19-related medical care. At the same time, trans people reported being affected by chronic diseases disproportionately more often than the general population, including those leading to a higher risk for poorer outcomes of a COVID­19 infection. Moreover, the participants reported being exposed to many risk factors associated with higher mental distress (e.g., having a chronic illness, belonging to a minority based on a non-heterosexual orientation, or having a low income). DISCUSSION: The results of this survey indicate that prior vulnerabilities with regards to health problems and the restricted access to an informed and qualified transgender healthcare were exacerbated by the COVID­19 pandemic.

Management of a Child vs an Adult Presenting With Acral Lesions During the COVID-19 Pandemic: A Practical Review.

During the coronavirus disease 2019 (COVID-19) pandemic, there has been a rise in the diagnosis of acral lesions, including chilblains-like lesions, ischemia, and retiform purpura. Understanding the differences in presentation and severity of illness between children and adult patients is important for physicians to understand risk stratification and management of these lesions. We reviewed the literature on the acral lesions seen in children and adults with COVID-19 infection to offer guidelines for diagnosis and treatment.

ZebraShare: a new venue for rapid dissemination of zebrafish mutant data.

BACKGROUND: In the past decade, the zebrafish community has widely embraced targeted mutagenesis technologies, resulting in an abundance of mutant lines. While many lines have proven to be useful for investigating gene function, many have also shown no apparent phenotype, or phenotypes not of interest to the originating lab. In order for labs to document and share information about these lines, we have created ZebraShare as a new resource offered within ZFIN. METHODS: ZebraShare involves a form-based submission process generated by ZFIN. The ZebraShare interface (https://zfin.org/action/zebrashare) can be accessed on ZFIN under "Submit Data". Users download the Submission Workbook and complete the required fields, then submit the completed workbook with associated images and captions, generating a new ZFIN publication record. ZFIN curators add the submitted phenotype and mutant information to the ZFIN database, provide mapping information about mutations, and cross reference this information across the appropriate ZFIN databases. We present here examples of ZebraShare submissions, including phf21aa, kdm1a, ctnnd1, snu13a, and snu13b mutant lines. RESULTS: Users can find ZebraShare submissions by searching ZFIN for specific alleles or line designations, just as for alleles submitted through the normal process. We present several potential examples of submission types to ZebraShare including a phenotypic mutants, mildly phenotypic, and early lethal mutants. Mutants for kdm1a show no apparent skeletal phenotype, and phf21aa mutants show only a mild skeletal phenotype, yet these genes have specific human disease relevance and therefore may be useful for further studies. The p120-catenin encoding gene, ctnnd1, was knocked out to investigate a potential role in brain development or function. The homozygous ctnnd1 mutant disintegrates during early somitogenesis and the heterozygote has localized defects, revealing vital roles in early development. Two snu13 genes were knocked out to investigate a role in muscle formation. The snu13a;snu13b double mutant has an early embryonic lethal phenotype, potentially related to a proposed role in the core splicing complex. In each example, the mutants submitted to ZebraShare display phenotypes that are not ideally suited to their originating lab's project directions but may be of great relevance to other researchers. CONCLUSION: ZebraShare provides an opportunity for researchers to directly share information about mutant lines within ZFIN, which is widely used by the community as a central database of information about zebrafish lines. Submissions of alleles with a phenotypic or unexpected phenotypes is encouraged to promote collaborations, disseminate lines, reduce redundancy of effort and to promote efficient use of time and resources. We anticipate that as submissions to ZebraShare increase, they will help build an ultimately more complete picture of zebrafish genetics and development.

Phenotypic heterogeneity of neurofibromatosis type 1 in a large international registry.

Neurofibromatosis type 1 (NF1) is a rare genetic disorder, characterized by the development of benign and malignant nerve tumors. Although all individuals with NF1 harbor genetic alterations in the same gene, the clinical manifestations of NF1 are extremely heterogeneous even among individuals who carry identical genetic defects. In order to deepen the understanding of phenotypic manifestations in NF1, we comprehensively characterized the prevalence of 18 phenotypic traits in 2051 adults with NF1 from the Children's Tumor Foundation's NF1 registry. We further investigated the coassociation of traits and found positive correlations between spinal neurofibromas and pain, spinal neurofibromas and scoliosis, spinal neurofibromas and optic gliomas, and optic gliomas and sphenoid wing dysplasia. Furthermore, with increasing numbers of cutaneous neurofibromas, the odds ratio of malignant peripheral nerve sheath tumor increased. Phenotypic clustering revealed 6 phenotypic patient cluster subtypes: mild, freckling predominant, neurofibroma predominant, skeletal predominant, late-onset neural severe, and early-onset neural severe, highlighting potential phenotypic subtypes within NF1. Together, our results support potential shared molecular pathogenesis for certain clinical manifestations and illustrate the utility of disease registries for understanding rare diseases.

Differentiation syndrome during ivosidenib treatment with immunohistochemistry showing isocitrate dehydrogenase R132H mutation.

We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H-mutated leukemia cutis. A 72-year-old man with IDH1-mutated acute myeloid leukemia (AML), status-post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture-negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase-positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation-specific antibodies such as anti-IDH1 R132H may be useful to help distinguish malignant from non-malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy.

Gamification improves melanoma visual identification among high school students: Results from a randomized study.

Identification of melanoma or worrisome moles is often taught as an important part of routine skin checks. We sought to evaluate the efficacy of gamified education vs. traditional ABCDEs education on melanoma identification and self-confidence in identifying worrisome moles. We report that in our cohort (n = 271), participants randomized to the gamified intervention were more likely to correctly identify melanoma and non-melanoma skin lesions than those randomized to the ABCDE control cohort (74.2% vs 63.5% correct, P < .0001) and perceived confidence in self-identifying worrisome lesions was slightly higher in the gamified group than the traditional group, though the trend was not significant. These novel findings have significant implications on improved ways to educate young patients on the visual identification of melanoma and worrisome moles.