Celsite T202F B. Braun Catheter with Synchromed II Medtronic Pump for Hepatic Artery Infusion Therapy Is a Safe Alternative to Codman Pump Discontinuation: The First Latin-American HAIP Program Early Experience

Introduction: The Codman 3000 pump was the commonest system used in the U.S. for HAIP until 2018 device discontinuation. There are many countries abroad where Codman devices have never been available. The aim is to describe our early experience with the use of Celsite T202F B. Braun catheter-Syncromed II Medtronic pump in the first Latin American HAIP program. Method(s): We describe early outcomes of 6 patients with HAIP that used Celsite T202F, 6.5 Fr B. Braun catheter-Synchromed II Medtronic pump combination. Result(s): 2 patients were female (33.3%). Unresectable colorectal liver metastasis (CRLM) in 3 patients (50%), adjuvant chemotherapy for CRLM in 1 (16.6%) and intrahepatic cholangiocarcinoma in 2 (33.3%). No extra hepatic perfusion was documented. Complications were present in 4 patients (66.6%). 3 (50%) were not related to the hepatic pump: 1 COVID-19 pneumonia, 1 colonic anastomosis leakage and 1 intraabdominal collection. One patient (16.6%) presented a pump pocket seroma. Floxuridine was the intra arterial drug administered in all patients. The median number of cycles administered was 6. All patients have partial response to date. The median follow up was 234 days. No catheter disconnection or dysfunction events occurred. Conclusion(s): The use of the Celsite B Braun catheter-Medtronic pump is a feasible and safe option for HAIP. A HAIP program can be implemented safely in Latin-America. [Formula presented] Figure 1. Celsite T202F B. Braun catheter connection with Synchromed II Medtronic pump. Copyright © 2022

SARS-CoV-2 Spike Protein S1/S2 Antibodies after Vaccination with Sinopharm in Peruvian Physicians

Background. Peru started its national vaccination campaign in February 2021 using Sinopharm vaccine, targeting healthcare personnel on its initial phase. Although the immunogenicity of this vaccine was tested in clinical trials, there are no studies that evaluated the humoral response post vaccination in Peru. Methods. We conducted a cross sectional study, which objective was to evaluate the humoral immunogenicity triggered by the Sinopharm vaccine in Peruvian physicians. We collected demographic and epidemiologic data via an electronic. The SARS-CoV-2 spike protein S1/S2 antibodies were measured by chemiluminescense (Liaison®). A positive test was defined as >15 U/ml, which has correlation of 95% with neutralizing antibodies measured by plaque reduction neutralizing test. Results. 92 participants were enrolled in the study. The epidemiologic characteristics are described in table 1. The mean level of antibodies measured at least 2 weeks from the second vaccine dose was 67.5 ± 70.5 U/ml. 85.7% of the study cohort had positive S1/S2 antibodies. In the univariate analysis, an imperfect negative correlation was found between the level of antibodies and participants' age (r= -0.24;regression F test 5.25;p = 0.0242). A weak negative correlation was observed between the antibody titer and the time elapsed from the second vaccine dose and the day of antibody measurement (r= -0.17). A higher antibody level post vaccine was found in individuals who worked in COVID units (105.5 U / mL vs 58.2 U / mL;p = 0.0125), and in participants with history of COVID (216.5 U / mL vs 81.2 U / mL;p = < 0.0000). Hypertension was associated with lower antibody titers (36.9 U / mL vs. 74.6;p = 0.0464). In the multivariate analysis, working in COVID units, having previous COVID infection and shorter time from second vaccine dose and day of antibody measurement were associated with higher antibody levels post vaccine (table 2). Conclusion. Our study showed that the time elapsed from the second vaccine dose and the day of antibody measurement, having previous COVID-19 infection and working in COVID -19 units may help to predict higher antibody titers post vaccine. Larger studies to evaluate the humoral response post Sinopharm vaccine and its clinical implications are still needed in Peru.

Prognostic Significance of Referral Patterns and Time Trends in Head and Neck Cancer Management

Purpose/Objectives Early diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC) is paramount to improving patient prognosis. The purpose of this study was to analyze the association of patient demographic, clinical, and management variables with time to treatment initiation (TTI) and one-year survival. Additionally, we evaluated the effect of potential areas of delay, such as the COVID-19 pandemic, in association with TTI and one-year survival. Materials/Methods Medical records of patients who were diagnosed with HNSCC from 2018 to 2020 at a tertiary academic medical center were reviewed to extract demographic and clinical information. Univariate and multivariate linear and cox-regression were used to evaluate TTI and one year survival with our study variables. Kaplan Meier (KM) curves were created to evaluate the difference in hazard over time between patients diagnosed in 2019 and 2020. Results A total of 233 patients met eligibility criteria. The median time between symptom onset and presentation to a medical provider was 1 month (Interquartile range [IQR]: 0.5-3). 118 patients (50.9%) were referred to one of our academic head and neck specialists by their PCP, 37 (15.9%) by a dental provider, 32 (13.8%) through the emergency department, 26 (11.2%) by a local ENT, and 20 (8.6%) by other means. Median time for oncologic work-up was 25 days (IQR: 16-38). Median TTI was 37.5 days (IQR: 27-50.75). 21% of patients reported delays in treatment, with the top three reasons cited as concurrent medical problems (34.69%), patient deferrals (16.33%), and delayed dental exams (8.16%). Univariate analysis for TTI found a significant increase in TTI in female patients (p=0.041) and those undergoing salvage therapy (p=0.045), and chemoradiation (p=0.008). Univariate cox-regressions predicting one-year mortality found direct admission status (p=0.005), the use of pre-treatment PEG tubes (p=0.006) and tracheostomies (p=0.025) significantly increased one-year mortality. This association was not significant in a multivariate models. Other demographic and clinical variables, including smoking history, median income by zip code, distance from hospital, tumor subsite, and others, did not significantly impact TTI or one-year mortality. Hazard ratios for one-year mortality and Kaplan-Meier estimates for one-year survival were not significant when adjusted for year of diagnosis (p>0.05) and TTI quartile (p>0.05). Conclusion Our analysis determined that many patient and management variables may not significantly impact TTI and one-year survival. Patients diagnosed in 2020 showed no difference in overall survival compared to prior years, despite COVID-19. The scope for improved HNSCC management may lie in continuing to optimize care in a timely manner for those with characteristics of advanced disease, many of which were found to be predictive of one-year mortality.

Educational intervention on COVID-19 in older adults of the Family Doctor's Office No. 4. Cumanayagua, 2020

Background: the COVID 19 pandemic causes the death of many people, mainly older adults. Knowing about it is one way to prevent it. Objective: to describe the results of an educational intervention on COVId 19, in older adults. Methods: educational intervention carried out in a universe of 230 older adults, from which a sample of 178 dispensed elderly people belonging to the Family Doctor's Office No. 4 in Cumanayagua was selected. A diagnosis was made to identify the level of knowledge about COVID-19, in which aspects about the disease were investigated, such as: symptoms, prevention measures, transmission routes. They were also asked about compliance with prevention measures. On that basis, an educational intervention was developed. Results: The 50 % present risk factors;knowledge about symptoms increased from 10.1% before the intervention to 100% after;on transmission routes from 35.9 % to 83.7 % and that of preventive measures from 53.9 % to 91.7 %. They learned to use the mask correctly. The satisfaction of the elderly with the educational actions was high. Conclusions: after the application of educational actions, there was an increase in knowledge about the disease, which may be favorable for its prevention in this group of elderly.

Risk factors for RRT and mortality in patients with COVID-19-related AKI in São Paulo, Brazil

Background: In COVID-19, as in SARS, the degree of kidney injury can have major implications for the clinical outcomes. Early reports indicate that, among patients with COVID-19, AKI is common and is associated with worse outcomes. However, COVID-19-related AKI among ICU patients in Brazil has not been well described. Methods: This was a retrospective observational study of the electronic health records of patients with COVID-19-related AKI admitted to the Hospital das Clínicas in the city of São Paulo, Brazil, between March and August of 2020. We applied only KDIGO criteria 2 and 3. We used logistic regression to analyze risk factors for the composite outcome of mortality or RRT. Results: Among the 694 patients with COVID-19-related AKI, the mean age was 63 years and mortality was 66.4%;41% needed vasoactive drugs, 66% needed mechanical ventilation, and 72% needed dialysis. Univariate analysis showed the following risk factors for mortality and RRT at admission: male sex;diabetes;CKD;vasoactive drug use;mechanical ventilation;acidemia;elevated lactate, magnesium, potassium, creatinine, C-reactive protein, creatine phosphokinase, total bilirrubin;proteinuria;hematuria;and increased fractional excretion of potassium (n=98) and sodium (n=110). The factors that remained significant in the multivariate analysis were male sex, vasoactive drug use, serum magnesium >2.5 mg/dL and oliguria (24-h urine output <500 mL). Conclusions: In ICU patients with COVID-19-related AKI, in Brazil and elsewhere, in-hospital mortality is high. The exact mechanism by which hypermagnesemia increases mortality in such patients merits further study.

Improving otolaryngology access through telehealth: Cutting no-show rates in half

Introduction: The use of telehealth visits was a necessary adjustment in 2020 due to the COVID-19 pandemic. Even after clinics were either shut down or restricted, synchronous telehealth became an alternative for maintaining essential patient care. As we emerge from the pandemic, further benefits of telehealth services are being discovered, including the reduction in missed-or no-show-visits when compared with in-person visits. The primary aim of this study was to compare the rates of missed visits between telehealth and inperson visits and comment on potential benefits of telehealth. Method: The study was conducted at an otolaryngology department from a quaternary academic medical center. Telehealth visits were rendered as primarily audio and video or audio only. Data were obtained from the institutional electronic financial data system. Overall visits were analyzed from April 2020 to December 2020 for the otolaryngology service by type of visit. The rates were calculated individually from the total number of in-person and telehealth visits. Statistical analysis for the difference in the proportion of encounters between groups was calculated using the prop.test function in R. Results: During the intervention period from April 2020 to December 2020, 25,854 otolaryngologic encounters were seen by the Department of Otolaryngology. The 'no-show' rate for telehealth visits was found to be significantly lower at 9.9% when compared with 18% for in-person visits (P < .001). From those telehealth visits, 57% were rescheduled for another day. Conclusion: The benefits of telehealth in a postpandemic world extend beyond providing an alternative to in-person visits, providing a significant reduction in no-show rates. Reducing missed appointments has multiple benefits, including improved resource utilization in clinics, better access for patients, and productivity for providers. It should be considered as one of the primary benefits when adding telehealth visits to a practice both during and post-pandemic.

Consequences of the pandemic for Brazilian criminal law

Objective: This paper seeks to discuss the criminal institutes which importance is intensified in a period of pandemic, such as currently experienced. The collective legal goods, the blank criminal norms and the crimes of danger, as well as the intention outline the criminal offenses that may arise in cases of non-compliance with measures to contain the spread of the Covid virus. Methodology: The methodology adopted in the research is deductive, with the setting of assumptions. The conclusions presented are extracted following the research, the bibliographic review and the analysis of the relevant normative texts. Results: In a pandemic period there are certain criminal categories which importance is reinvigorated, imposing a new doctrinal understanding about these institutes and also that Criminal Law has definitions of crimes that directly relate to this moment, as the last instance of behavior control (ultima ratio), Contributions: The relevance of this paper is to revisit concepts that are often criticized by the doctrine, such as collective legal goods, blank criminal rules and crimes of danger, as well as the current reflection on the types of crimes that, in a pandemic phase, can be committed if the rules related to this singular moment are not complied with. © 2021, Centro Universitário Curitiba - UNICURITIBA. All rights reserved.

COVID-19, placenta and vertical transmission

The coronavirus that causes COVID-19 is called SARS-CoV-2. This virus belongs to the family Coronaviridae. Pregnant women are not exempt from infection by this new virus. The placenta is a highly specialized pregnancy organ that supports the normal growth and development of the fetus. There is evidence that the placenta is permissive to infection by this coronavirus and of its infection, although at a low frequency. Vertical transmission of this virus does occur, but it is a rare event. During COVID-19, placental involvement can be observed, which frequently leads to placental vascular hypoperfusion, which may have implications for fetal development. © 2021 Academia Nacional de Medicina. All rights reserved.

Prevention of COVID-19 in pregnant women, eventual use of new vaccines

Pregnant women who have COVID-19 have an increased risk of hospitalization and death;however, there are many restrictions for the application of COVID-19 vaccines on pregnant patients, mainly because there is no confirmation of the safety of their use during pregnancy. None of the vaccines approved to date are based on live attenuated SARS-CoV-2, so the possibility of generating an infection in the fetus is nonexistent. Likewise, current evidence does not suggest that COVID-19 vaccines can induce a complication or adverse pregnancy outcome and due to the emergence of new waves of COVID-19, the potential protective benefits of these vaccines far outweigh the possible risks in most patients. A review of the evidence of the safety of COVID-19 vaccines, recommendations, and restrictions for the use of COVID-19 vaccines in pregnant women made by international health organisms and professional associations, as well as prospects and information on clinical trials of these vaccines in pregnant women are presented. © 2021 Academia Nacional de Medicina. All rights reserved.

Fetus as a patient in pregnant women with COVID-19

Introduction: Fetus and placenta are an immunologically privileged unit, whose physiological changes during pregnancy intervenes in the behavior against SARS-CoV- 2, describing a theoretical potential teratogenic damage due to receptors ACE-2 expression, necessary for SARS-CoV-2 intracellular transport in the epiblast, vital in organogenesis, as well as the current pharmacological therapy teratogenic effects, abortions, and fetal demise. Early Chinese reports pointed to the unlikely vertical transmission, however, the diagnostic test’s low sensibility with the serological detection in fetal and neonatal blood samples of IgM Anti- E SARS-CoV-2 and IL-6 caused great controversy. Purpose of the study: To resume current data about fetal risks (real or potential) from a viral agent, pharmacological therapy, or placental damage from a worldwide literature data review. M ethods: Articles in all languages about the SARS-CoV-2 infection in pregnant women and fetuses as a patient searched from LILACS, PUBMED, and Google Scholar from March 2020 to February 2021 were review. Conclusion: A year later, it is seen that the placental damage is maternal and fetal vascular bad perfusion, like preeclampsia and chorioamnionitis, endothelitis, thrombosis, and inflammation, reconsidering fetal surveillance in COVID-19 pregnant women. © 2021 Academia Nacional de Medicina. All rights reserved.

COVID -19 and pregnancy: Epidemiology and clinical evolution

The relationship of COVID-19 and pregnancy implies a novel clinical condition, information regarding the true medical picture is currently being collected. The present work aims to carry out a review of the most prominent publications on COVID-19 and Pregnancy: epidemiology and clinical evolution based on currently available evidence. The risk of infection in the pregnant woman, clinical findings, infection by gestation trimester and risks, risk of perinatal death, cesarean section and delivery, and finally maternal risk of admission to intensive care, mechanical ventilation, and death are summarized. © 2021 Academia Nacional de Medicina. All rights reserved.

Supression of ACE2 function and antiviral immune response by SARS-CoV-2 infection

Background: SARS-CoV-2 receptor angiontensin-conveting-enzyme 2 (ACE2) is also a protective factor that contributes to reduce inflammation and fibrosis in tissues. An active form of ACE2 can be released from the cell surface by host proteases ADAM17 and TMPRSS2, being the latter also necessary for viral entry. Due to its properties, the administration of soluble recombinant ACE2 has been proposed as a SARS-CoV-2 treatment. Here, we assess the role of ACE2 activity and antiviral immune response at the site of infection in nasopharyngeal swabs of SARS-CoV-2 patients, to unravel its effect on inflammation cascade and infection outcome. Methods: Soluble enzymatic activity of ACE2 was measured in nasopharyngeal swabs at the time of PCR positivity (mean time from symptom=4d) and 3 days after in a cohort of mild SARS-CoV-2 patients (n=40, mean age=42y) and in uninfected controls. Gene expression profiles of ACE2, its proteases, ADAM17 and TMPRRS2, and interferon-stimulated genes (ISGs), DDX58, CXCL10 and IL-6 were also evaluated by RT-qPCR. Results: Both ACE2 activity and mRNA expression decreased significantly during infection course in paired samples of SARS-CoV-2 infected subjects (p=0.048 and p<0.001, respectively), although differences between infected and uninfected subjects were only seen at mRNA level (p<0.001) Importantly, both ACE2 activity and mRNA expression showed a positive correlation with viral load (rho=0.352, p-value=0.0259), suggesting that viral infection is influencing ACE2 function. Similarly, infection downregulates TMPRSS2 expression (pvalue< 0.01), but not ADAM17, further indicating the viral-induced regulation of host receptors. In contrast to ACE2 data, a clear induction of IFN stimulated genes, CXCL10, IL-6 and DDX58 (RIG-I), is observed upon infection (p-value<0.05 in all cases), demonstrating that SARS-CoV-2 induces an antiviral response and suggesting that ACE2 is not an ISG. This increased expression of ISGs is directly linked to viral load (rho=0.6177, p-value<0.0001;rho=0.4026, p-value=0.0110;rho=0.3024, p-value=0.0613, respectively) but it is rapidly reversed during infection course. Conclusion: Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 suppress ACE2 expression and function, intracellular viral detection and subsequent ISG induction, offering new insights into ACE2 dynamics and inflammatory response in the human upper respiratory tract that may contribute to understand the early antiviral host response to SARS-CoV-2 infection.

Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 infections has led to a substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS-CoV-2 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID-19. At the time of writing, in vivo studies of SARS-CoV-2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partly model the mechanisms involved in human severe COVID-19. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID-19. These models need to reproduce the key mechanisms of COVID-19 severe acute respiratory distress syndrome and the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS-CoV-2 infection and COVID-19-related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID-19 pathogenesis and for assessing potential treatments. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Adding heparin to citrate in continuous renal replacement therapy may extend filter lifespan in COVID-related AKI

Background: COVID may predispose patients to thrombosis and lower filter lifespan. Association between D-dimer level (DD) and filter clotting in Continuous Renal Replacement Therapy (CRRT) has not been described. Methods: All patients who needed CRRT in Hospital das Clínicas (Brazil) during March to May 2020 (COVID related-AKI (COV+), n=37) and August to September 2019 (COVID unrelated-AKI (COV-), n=18) were studied. Anticoagulation in CRRT in COV+ was done with citrate 3mmol/L (ACD, n=19), or citrate 4mmol/L plus non-fractioned heparin 10U/Kg/h (ACD/Hep, n=18), while in COV- with citrate 3mmol/L only. Data are expressed in median [IQR]. We performed Spearman's correlation between DD and time-free of filter clotting (TFC), and Kaplan-Meier curve to study filter survival by anticoagulation method and DD. Results: ACD/Hep group presented lower filter clotting in 72h when compared to other groups (ACD/Hep: 35% vs ACD: 100% vs COV-: 80%, p< 0.05). Analyzingfilter clotting per patient-day, ACD/Hep also presented less clotting than ACD group (ACD/Hep: 41% vs ACD: 100%, p< 0.05). In COVID patients, median TFC was 33.5 h [17.0;72.0] (ACD: 29.0 h [13.0;68.5], ACD/Hep: 40.0 h [17.0;62.0], p: NS). Clotting time from obese patients did not differ from non obese patients (obese: 31.0 h [18.5;57.2] vs non-obese: 56.0 h [16.8;72.0], p: ns). Median DD in all COVID patients was 3,519 [1420- 13,883]. Patients with DD below median (<3,500) had higher TFC (ACD high DD: 19.0 h [9.00;27.5], ACD/Hep high DD: 34.0 [17.0;62.0], ACD low DD: 57.0 h [27.2;66.8], ACD/Hep low DD: 67.0 h [26.0;72.0];Figure 1). There was statistically significance in correlation between DD and TFC in ACD patients, but not in ACD/Hep group. Conclusions: Heparin may extend filter lifespan in CRRT, and this benefit seem to be greater in high DD patients.

Selective CD8 cell reduction by SARS-CoV-2 is associated with a worse prognosis and systemic inflammation in COVID-19 patients.

The lymphopenia exhibited in patients with COVID-19 has been associated with a worse prognosis in the development of the disease. To understand the factors associated with a worse evolution of COVID-19, we analyzed comorbidities, indicators of inflammation such as CRP and the ratio of neutrophils/lymphocytes, as well as the count of blood cells with T-lymphocyte subtypes in 172 hospitalized patients with COVID-19 pneumonia. Patients were grouped according to their needs for mechanical ventilation (ICU care) or not. Within the comorbidities studied, obesity was the only associated with greater severity and ICU admission. Both the percentage and the absolute number of neutrophils were higher in patients needing ICU care than non-ICU patients, whereas absolute lymphocyte count, and especially the percentage of lymphocytes, presented a deep decline in critical patients. There was no difference between the two groups of patients for CD4 T-lymphocytes, neither in percentage of lymphocyte nor in absolute number, however for CD8 T-cells the differences were significant for both parameters which were in decline in ICU patients. There was a firm correlation between the highest values of inflammation indicators with the decrease in percentage of CD8 T-lymphocytes. This effect was not seen with CD4 cells. Obesity together with lymphopenia, especially whether preferentially affects to CD8 T- lymphocytes, are factors that can predict a poor prognosis in patients with COVID-19.

Neuro-ophthalmological manifestations as complication of an infection with Mycoplasma pneumoniae and subsequent development of disseminated acute encephalitis. / Manifestaciones neuroftalmológicas como complicación de una infección por Mycoplasma pneumoniae y desarrollo posterior de una encefalitis aguda diseminada.

The purpose of this article is to describe two paediatric neuro-ophthalmological clinical cases caused by a systemic infection due to Mycoplasma pneumoniae (M. pneumoniae). The cases are two girls aged 14 and 12 seen in the Emergency Department: The first one had internuclear ophthalmoplegia and second with loss of vision and headache. They had no other neurological foci. Magnetic resonance imaging showed hyperintense plaques in both, suggestive of a demyelinating disease. One month later, the neuro-ophthalmological symptoms resolved, with normal follow-up magnetic resonance imagings. The diagnosis was acute disseminated encephalitis secondary to M. pneumoniae. The diagnosis was made using PCR (gold standard) and/or IgM in serology. It is important to think about this possible aetiology in cases of suggestive demyelinating disease. There is controversy about the role of antibiotics and on whether corticosteroids are contemplated. In conclusion, M. pneumoniae must be a differential diagnosis in acute neuro-ophthalmological disorders in children.