Variation in blubber cortisol levels in a recovering humpback whale population inhabiting a rapidly changing environment.

Glucocorticoids are regularly used as biomarkers of relative health for individuals and populations. Around the Western Antarctic Peninsula (WAP), baleen whales have and continue to experience threats, including commercial harvest, prey limitations and habitat change driven by rapid warming, and increased human presence via ecotourism. Here, we measured demographic variation and differences across the foraging season in blubber cortisol levels of humpback whales (Megaptera novaeangliae) over two years around the WAP. Cortisol concentrations were determined from 305 biopsy samples of unique individuals. We found no significant difference in the cortisol concentration between male and female whales. However, we observed significant differences across demographic groups of females and a significant decrease in the population across the feeding season. We also assessed whether COVID-19-related reductions in tourism in 2021 along the WAP correlated with lower cortisol levels across the population. The decline in vessel presence in 2021 was associated with a significant decrease in humpback whale blubber cortisol concentrations at the population level. Our findings provide critical contextual data on how these hormones vary naturally in a population over time, show direct associations between cortisol levels and human presence, and will enable comparisons among species experiencing different levels of human disturbance.

Outcomes of a quality improvement project aimed at improving delivery of new anticancer drug education to nursing in an academic-community hybrid model

Background: Educating staff on new anticancer medications is imperative for patient safety. Infusion nurses at Dana Farber Cancer Institute (DFCI) satellite infusion centers were surveyed on their comfort level administering newer oncology drugs. Results revealed only 57% of nurses were extremely comfortable or somewhat comfortable, while 32% of nurses were somewhat uncomfortable or very uncomfortable. This project aimed to increase percentage of nurses at the satellites indicating they are extremely comfortable or somewhat comfortable from baseline of 57% to >=75%. Method(s): An interdisciplinary team including pharmacy, medical oncology, and nursing was formed to analyze workflows around new drug onboarding, staff education, and satellite communication. The team utilized Plan-Do-Study-Act (PDSA) cycle methodology. Tools included process maps and fishbone to identify areas of improvement. Intervention development tools included a Pareto chart and a priority matrix. Results were analyzed using statistical process control charts. Result(s): PDSA cycle 1 consisted of making the pharmacy driven education sheet, At-A-Glance (AAG), more accessible for new drugs. AAGs for drugs approved by the FDA in the previous 18 months were posted on the DFCI pharmacy intranet page. Nurses were educated on how to access AAG weekly. For PDSA cycle 2, the survey was modified to target individual nurses administering new drugs rather than all nurses. A Nursing consideration section was added to the AAG template and workflow developed;Navigation and review of AAG was added to nursing competency. Monthly nursing/pharmacy huddles were established to optimize communication. These interventions increased the percentage of nurses indicating they are extremely comfortable or somewhat comfortable to >=75% which was sustainable through PDSA cycle 2 (see Table). Conclusion(s): Making an easy-to-use nursing education resource accessible improved nursing comfort level. There were challenges with nursing survey due to COVID-19 surge and staff shortages. Routine huddles are essential for sustainability.

Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial.

PURPOSE: Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . METHODS: We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . RESULTS: Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2; 1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). CONCLUSIONS: We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

SARS-CoV-2 Placentitis with Intraparenchymal Thrombohematomas: Association with Intrauterine Fetal Demise, Perinatal Morbidity, and Ultrasonographic Findings

Background: SARS-CoV-2 placentitis is defined by the triad of histiocytic or mixed inflammatory intervillositis, increased perivillous fibrin deposition, and villous trophoblastic necrosis. We have observed multiple cases of intrauterine fetal demise (IUFD) or perinatal morbidity with intraparenchymal thrombohematomas, a feature not previously linked to poor outcomes associated with SARS-CoV-2-placentitis. Here we present 17 cases with such findings and provide a possible point of intervention as these lesions can be identified by ultrasonography. Design: A retrospective study, approved by the Institutional Review Board, was performed by searching the terms SARS-CoV-2 placentitis or SARS-CoV-2 infection or COVID in our pathology database for all in-house deliveries and cases from the consult practice of the authors between 1/1/21 and 9/24/21. Clinical data was obtained via the electronic medical records or through contacting the consulting pathologists. Results: Twenty-three cases were retrieved and reviewed for the presence of thrombohematomas in the maternal space. Seventeen cases had thrombohematomas, intervillous thrombi, or intervillous hemorrhage in addition to classic SARS-CoV-2 placentitis, and 12 of those cases (71%) were associated with IUFD. The period between a positive maternal COVID test and loss was less than 14 days in all but three cases of IUFD (75%). The non-IUFD cases were all associated with other perinatal morbidity. In 8 of 17 cases (47%), thrombohematomas were noted grossly. The presence of multiple placental lakes were identified in three cases where placental imaging was available. Representative gross and histologic findings and an ultrasound displaying placental lakes are presented in Figures 1 and 2, respectively. Clinical data associated with each case is in Table 1. Conclusions: We identify a novel feature present in placentas with SARS-CoV-2 placentitis associated with poor outcomes. The often grossly identifiable thrombohematomas were present in 17 cases of SARS-CoV-2 placentitis, the majority of which were associated with IUFD, suggesting that their presence is a marker for increased perinatal morbidity and mortality. We also show that these thrombohematomas can be identified by ultrasound, demonstrating that imaging the placenta is critical in pregnancies affected by COVID-19 independent of maternal symptoms as it may identify markers of severe placental damage that can be associated with IUFD or significant perinatal morbidity.

The COVID-19 pandemic may force the world to reflect on the pre-pandemic style of life

Introduction: The COVID-19 pandemic has caused a lot of changes on an individual and societal level. The current study was designed to investigate the impact of the isolation/social distancing period on people's sense of Being, Belonging, and Becoming at the early stages of the COVID-19 measures.

Hyperimmune immunoglobulin for people with COVID-19

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. Using a living systematic review approach, to assess whether hyperimmune immunoglobulin therapy is effective and safe in the treatment of people with COVID-19; and to maintain the currency of the evidence.

Vasovagal reactions reported in COVID-19 convalescent plasma donors-NHSBT experience

Safety and efficacy of COVID-19 Convalescent Plasma (CCP) was tested as part of two large randomised controlled trials in UK (REMAP-CAP and RECOVERY). CCP collections by apheresis were started across NHSBT from early in the pandemic to support the trials. Data from CCP donors who had donated at least once in the period between April 2020 and March 2021 (inclusive) was reviewed. Of the 57 213 attendances during this period, 6908 (12.1%) resulted in at least one adverse event, reported within seven days of attendance. Donors experiencing an adverse event were more likely to be first-time donors than donors with no adverse event were. The risk of having any adverse event reduced from 14% for first-time donors to 7% for repeat donors. Bruising was seen in58%and vasovagal events were the second most commondonor adverse events accounting for 37% (2570/6908). Most (2373/2570, 92%) were mild with no loss of consciousness. CCP donors experienced lower rates of mild vasovagal events to new/returning whole blood donors overall but appear to be at higher risk after stratifying by sex and age. They are significantlymore likely to feel faint than new/returning apheresis donors. Differences between new/returning whole blood and CCP donors are statistically significant (p < 0.05) in both men and women in all age groups from 35 years upwards. In all cases where there is a significant difference, the rate was higher for CCP donors. When compared with new/returning apheresis donors, the rate in CCP donors was higher overall. One serious adverse event of donation was recorded in a new male CCP donor in his mid-40s who had severe immediate vasovagal reaction with hypotensive seizure requiring hospitalisation following his first CCP donation. He recovered subsequently and was withdrawn from donation. Donating CCP was largely safe but complications were seen following donation in 12% with vasovagal events, bruising and arm pain being the most reported donor adverse events. Vasovagal events could be multifactorial with increased anxiety, new/first time donors, vascular dysregulation or subclinical cardiac dysfunction secondary to recent COVID-19 infection possibly contributory. It is encouraging to see that the risk of having any adverse event halved with repeat donations.

Impact of COVID-19 pandemic on stroke care at the university of rochester medical center

Introduction: The impact of the COVID-19 pandemic response on medical care for stroke is unknown. Methods: We used local “Get With The Guidelines” stroke data for patients with ischemic stroke (IS), transient ischemic attack (TIA), and intracerebral hemorrhage/subarachnoid hemorrhage (ICH/SAH) from March 20-April 14, 2020 (study period) and January 1-March 19, 2020 (control period #1) and March 20-April 14, 2019 (control period #2). We examined daily admission rates, transfers, tPA administration, thrombectomy, and time from last well to hospital arrival. Results: There were 349 patients (n=40 study period, n=225 control period #1, n=84 control period #2);263 with IS, 37 with TIA, and 49 with ICH/SAH. Overall, 46% were female, 82% white, with median age 70 years (IQR 58-82 years). Daily admission rates were 1.4 IS/day for the study period compared to 2.1 IS/day (Incident rate ratio [IRR] 1.49 95% CI 1.05-2.13, p=0.027) and 2.2 IS/day (IRR 1.57 1.04-2.37, p=0.033) for control periods #1 and #2 (Table), respectively. There was only one admission for TIA in the study period compared to approximately one every 4 days in control period #1 (IRR 7.2 95% CI 1.0-53.7, p=0.053) and one every 2 days in control period #2 (IRR 14.0 95% CI 1.8-106.5, p=0.011). ICH/SAH admissions were fewer in the study period. Transfers were less common with approximately one transfer every four days in the study period compared to one each day of the control periods. Rates of tPA, thrombectomy, and time from last well to first hospital contact did not differ across the epochs. Conclusions: Our data suggest the COVID-19 pandemic response has led to reduced admissionvolumes for all stroke types in the University of Rochester Medical Center catchment area, partlydue to decreases in hospital transfers. These data raise the question whether fewer patients soughtcare for stroke symptoms at the height of the COVID-19 pandemic.

Persistence of respiratory and non-respiratory symptoms among COVID-19 patients seeking care at an ambulatory COVID-19 center

Background: While hospitalized COVID-19 patients are well described in the literature, studies of the natural history and ambulatory cases are limited. We aim to describe the symptoms and clinical course of COVID-19 among ambulatory patients seen at the Emory University multidisciplinary Acute Respiratory Clinic (ARC) developed to care for patients with confirmed or suspected COVID-19. Methods: PCR-confirmed COVID-19 cases seen at ARC from 4/3-5/16/2020 were included in a retrospective chart review. Encounters were classified as acute, subacute, or convalescent depending on the duration since illness onset (< 1, 1-4, or >4 weeks, respectively). Demographic, clinical, physical exam, diagnostic test, and disposition data were abstracted and analyzed with standard descriptive statistics. Results: Among 404 visits at ARC, 127 (31.4%) were for confirmed COVID-19 illness (107 unique patients with 1-4 visits). The majority (75.7%) of patients were female, and the median age was 55 years (range 24-89). Patients presented during acute, subacute, and convalescent phases of illness (15.7%, 58.3%, and 26.0%, respectively;Table). Prevalent co-morbidities included hypertension (39.3%), obesity (27.1%), diabetes (20.6%), and asthma (21.5%). While measured or subjective fever was reported in the majority of acute visits (60.0%), it was less common in subacute and convalescent encounters (27.0% and 30.3%). Cough was commonly reported in acute, subacute, and convalescent visits (70.0%, 79.7%, 66.7%), as were dyspnea on exertion (45.0%, 70.3%, 66.7%) and chest tightness (40.0%, 40.5%, 60.6%). Although smell or taste alteration was present in almost half of acute and subacute patients, it was only reported in a quarter of convalescent patients. Among the three stages of illness, transfers from ARC to the ED or direct hospitalizations occurred in 15.0%, 23.0%, and 12.1% of acute, subacute and convalescent visits, respectively. Conclusion: Following acute illness, COVID-19 patients can experience persistent symptoms, primarily respiratory symptoms, which can be severe enough to warrant hospitalization. Clinics evaluating recovering patients should prepare to manage these symptoms. Further study of the pathophysiology and treatment of persistent pulmonary symptoms in COVID-19 is needed. (Table Presented).

Convalescent plasma and hyperimmune immunoglobulin to prevent infection with SARS-CoV-2

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe to prevent infection with SARS-CoV-2 and development of COVID-19; and to maintain the currency of the evidence, using a living systematic review approach.

The placental protein expression pattern of the SARS-COV-2 receptor ACE2 and serine proteinase TMPRSS2 suggest a protective mechanism against infection

Background: The rarity of placental infection by SARSCoV- 2 suggests the presence of protective measures. SARS-CoV-2 requires coexporession of its receptor, ACE2, and the serine proteinase TMPRSS2 for cellular infection. Both are expressed in the placenta but their protein expression pattern has not been demonstrated to date. Methods: 19 placentas from women with PCR proven SARS-CoV-2 infection were examined for SARS-CoV-2 expression by RNAish and immunohistochemistry (IHC) and for ACE2 and TMPRSS2 by IHC. Gross and histopathology were also reviewed. Two sets of controls were used: 'normal controls' - 122 placentas examined solely for GBS exposure (no other indication for examination) delivered from 2000-2004;and 'abnormal controls' - 130 placentas from neonates with a clinical diagnosis of HIE delivered from 2000-2019. The control placentas were reviewed for gross and histopathology. Results: 2 cases showed placental infection with viral RNA the villous syncytiotrophoblast (ST) and cytotrophoblast (CT) in a patchy distribution in 1 and only focally in the other. The infant with the patchy infection was SARSCoV- 2 PCR positive at 24 hours, the infant with only focal infection was PCR negative. None of the other placentas showed viral infection. All placentas showed robust expression of ACE2 in the trophoblast. The ST and CTexpression was membranous and In most cases ST expression was polarized-strongest, and in many cases only present, on the villous stromal side of the ST. TMPRSS2 was weakly expressed in the placental endothelial cells. Hofbauer cells were negative for both. We did not find a an increase in maternal or fetal vascular malperfusion (MVM or FVM) over controls. We saw MVM at 25%, FVM at 20%, acute chorioamnionitis at 30%, inflammatory pathologies (1 case each of ungradable VUE, intervillositis, Hofbauer cell hyperplasia) at 15%, all within published prevalences and similar to our controls. Conclusion:We did not find increased prevalence of MFM, FVM, infectious, or inflammatory pathology above published our our sets of controls as other have, perhaps due to small sample size. SARS-CoV-2 infection of the placenta is rare and vertical transmission, if it occurs, is even rarer. One mechanism for this is the rare occurrence of maternal SARS-CoV-2 viremia. Another mechanisms might be the unfavorable expression ACE2 and TMPRSS2. We show that their expression is uniquely distinct: ACE2 in the tropohobast and TMPRSS2 in the endothelium. Although we did not detect coexpression we cannot rule out that the vascular-syncytial membranes might coexpress ACE2 and TMPRSS2. We also show that ACE2 expression is polarized in most cases away from the maternal vascular space thereby perhaps limiting SARS-CoV-2 access to ST infection.