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A 63-year-old man was admitted to our hospital with sore throat and fever. He was diagnosed with Coronavirus Disease 2019(COVID-19), and on the 3rd day after diagnosis, he started on ventilatory management. On the 25th day, the patient presented with over 3 L of watery diarrhea, which continued daily. When the diarrhea did not improve with various treatments, on the 98th day, a double-balloon endoscopy of the small intestine was performed, and diffuse loss of villi structure in the jejunum was noted. Due to massive pleural effusion, the patient succumbed to circulatory and respiratory failure 111 days after admission to the hospital. The pathological autopsy revealed that the mucosal epithelium had been exfoliated from the entire small intestine. As this case shows, some COVID-19 cases are associated with severe diarrhea;further investigation is needed to elucidate the pathogenesis of COVID-19-associated diarrhea.Copyright © 2023 Authors. All rights reserved.
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Background: Risankizumab (RZB), a p19-anti-interleukin-23 monoclonal antibody, has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (CD). This post hoc analysis evaluates the efficacy of induction and maintenance RZB therapy by baseline clinical, biochemical, and endoscopic disease severity. Method(s): In the ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) studies, patients with moderately to severely active CD and intolerance/inadequate response to >= 1 biologic (both studies) and/or conventional therapy (ADVANCE) were randomized to receive intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving stool frequency and/or abdominal pain score clinical response to 12 weeks of induction therapy were rerandomized in the FORTIFY (NCT03105102) study to receive subcutaneous (SC) maintenance RZB (180 mg or 360 mg) or PBO (withdrawal). Clinical and endoscopic endpoints were evaluated by baseline disease characteristics (Crohn's Disease Activity Index [CDAI: <= 300, > 300], highsensitivity C-reactive protein [hs-CRP: < 10 mg/L, >= 10 mg/L], and Simple Endoscopic Score for Crohn's Disease [SES-CD: 6-15, > 15]). Induction analyses included patients who received RZB 600 mg or PBO;data from the ADVANCE and MOTIVATE studies were pooled. Nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used. Result(s): The induction analysis included 527 patients who received RZB 600 mg IV and 362 patients who received PBO. Patients treated with RZB 600 mg IV achieved significantly higher response rates vs PBO at week 12, regardless of subgroup (P < .05 for all;Figure 1). In the maintenance study, patients treated with SC RZB continued to achieve higher response rates vs the PBO (withdrawal) group at week 52 regardless of subgroup (P was not < .05 for all;Figure 2). Improvements in clinical and endoscopic outcomes were generally observed from weeks 12 to 52 with RZB treatment across all subgroups. Response rates were generally similar across subgroups in both induction and maintenance studies;endoscopic remission and ulcer-free endoscopy (resolution of ulcer) rates were numerically lower for patients with increased inflammation (hs-CRP > 10 mg/mL) and higher endoscopic activity (SES-CD > 15). Conclusion(s): RZB induction therapy resulted in higher response rates for clinical and endoscopic outcomes compared with PBO at week 12, regardless of baseline clinical, biochemical, and endoscopic disease severity. RZB also showed durable efficacy with continued RZB maintenance therapy, supporting the long-term use of RZB for patients across a range of baseline disease severity and activity.
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Purpose: To evaluate the seroconversion rate in kidney transplant recipients (KTR), compared to two non-transplanted groups of patients, and identify predictors of seroconversion in COVID-19 convalescent patients. Method(s): A retrospective cohort study enrolled RT-PCR COVID-19 diagnosed patients (Mar/20 and Oct/2020) of three groups: 601 KTR, 211 health care workers (HCW), and 170 non-transplanted inhabitants (INH) in a countryside city in the state of Sao Paulo - Brazil. At least 14 days after diagnosis, all survivors underwent antibody testing by chemiluminescent microparticle immunoassay (titter expressed in RLU). The primary outcome was seroconversion. The group-adjusted multivariable model for the probability of seroconversion was built by generalized linear mixed models with binary logistic regression and the discrimination performance by AUC-ROC. Result(s): Several differences were observed among groups regarding demographic data and COVID-19 clinical presentation. Of note, KTR were older (54.0 years old vs. 37.0 in HCW vs. 42.0 in INH, P<0.001), more frequently had comorbidities (P<0.001), and severe COVID-19 (P<0.001). Compared to HCW and INH, respectively, admission to ICU (44.9% vs. 0% vs. 1.8%), MV requirement (32.3% vs. 0% vs. 1.8%), and death (28.8% vs. 0% vs. 1.2%) were significantly more frequent in KTR (P<0.001). On the other hand, the seroconversion rate was not different among survivors: 76.2% for KTR, 74.9% for HCW, and 82.2% for INH (P=0.35). The IgG anti-SARS-CoV-2 was slightly higher among INH: 5.8 RLU vs. 5.4 for KTR and 4.4 for HCW (P=0.009). Seroconversion was associated with a shorter time between infection and blood sample collection (OR for each day= 0.986;P<0.001) and increased by 64% if the fever was a COVID-19 symptom (OR=1.737;P=0.017), 78% if the cough was present (OR=1.785;P=0.005) and 98% if the ventilatory support was required (OR=1.981;P=0.017). This predictive model achieved an AU-ROC of 0.730 (P<0.001). Conclusion(s): As expected, the rates of clinical deterioration to ICU admission, MV requirement, and death were significantly higher among KTR. However, among the survivors, KTR had a similar rate of seroconversion, associated with clinical severity parameters and a shorter time of blood sample collection.
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Purpose: This study aims to compare the immunogenicity of a third dose of the heterologous BNT262b2 mRNA vaccine versus the homologous inactivated wholevirion CoronaVac vaccine in adult kidney transplant recipients (KTR). Method(s): This prospective, single-center, phase 4 interventional study included KTR aged 30-69 years, with more than 30days of transplantation, and no previous confirmed COVID-19. The patients received the 3rd heterologous (BNT162b2 mRNA) or homologous dose, at least four weeks after the standard two-dose schedule of CoronaVac vaccine, at the transplant center. Antibody response immediately before and after the 3rd dose was assessed by the AdviseDx SARS-CoV-2 IgG II assay. For those positive assays, neutralizing anti-SARS-CoV-2 antibodies were assessed through the cPassTM SARS-CoV-2 Neutralization Antibody Detection Kit. Result(s): There were 307 patients in the heterologous group and 777 patients in the homologous group. KTR in the heterologous group were older (median age 54 vs. 50 years,p<0.0001), with a lower prevalence of diabetes (7% vs. 11%,p=0.032), lower percentage of deceased donors (60% vs. 68%,p=0.006) and longer time since transplant (median 11 vs. 6 years,p< 0.0001).Immediately before the 3rd dose, seroprevalence for IgG antibodies (36% vs. 34%,p=0.597) and the median antibody titers among those seroprevalent (246 AU/mL vs. 268 AU/mL,p=0.279) were similar. At a median of 25 days after the heterologous and 35 days after the homologous 3rddose vaccine, seroconversion rate was higher in the heterologous group (49% vs. 32%,p<0.0001), resulting in a higher seroprevalence rate (67% vs. 55%,p=0.0003). Overall, 42% remained seronegative after the third dose. The median antibody titers after booster among those seroprevalent patients was higher in those in whom the 3rd heterologous vaccine was administered (7,771 AU/mL vs 599 AU/mL,p<0.0001). The analysis of the neutralizing activity is ongoing. Conclusion(s): This prospective interventional study suggests that a 3rd heterologous dose is associated with a higher seroconversion rate and median antibody titers compared to a homologous dose in kidney transplant recipients fully vaccinated with inactivated whole-virion CoronaVac vaccine. In addition, 42% of subjects did not produce humoral immune response after the third dose, urging the development of alternative strategies.
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Background: Waning levels of anti-SARS-CoV-2 Spike (S) antibodies, particularly neutralizing, are associated with the risk of breakthrough infections. The impact of immunosuppression on antibody decay kinetics is unclear. We have previously reported a strong correlation between total anti-S antibodies and neutralization titers. Here, we report the decay kinetics in anti-S IgG antibodies across various immunosuppressive medications used in patients with CID. Methods: We recruited a volunteer sample of adults with confirmed CID eligible for SARS-CoV-2 vaccination in a prospective observational cohort study at two United States CID referral centers. All study participants received two doses of mRNA vaccine to SARSCoV- 2. To assess the durability of immunogenicity, anti-S IgG were measured at 7 (visit 3), 90 (visit 5), and 120 (visit 6) days after the 2nd dose of mRNA vaccine. The impact of various medications was assessed in repeated measures mixed model with the patient as a random effect, adjusting for gender and age, and using the group of patients on sulfasalazine, NSAIDs, or on no medications as a reference, using STATA. The half-life of anti-S IgG for a 50 percent reduction in titers at visit 3 was calculated for each medication class. Results: A total of 316 CID patients were recruited of which 148 (46.8%) had inflammatory bowel disease (IBD). Durability was assessed in 495 samples obtained in 293 patients. The arithmetic mean of anti-S IgG antibodies for each medication class at visits 3, 5, and 6 is shown in Figure 1. Overall, a 2-fold reduction in titers was observed from 7 to 90 days and 90 to 120 days (Table 1). The strongest decline was observed among patients on B cell depleting/ modulating therapies followed by those on combinations of biologics and/or small molecules and antimetabolites (methotrexate, leflunomide, thiopurines, mycophenolate mofetil, and teriflunomide). There was modest decline seen with TNFi (half-life 430.5 days, -2.15, 95% CI - 4.31 to - 1.07, p = 0.03). There was also a modest, but not significant, decline seen with Janus Kinase inhibitor (JAKi). No decline was seen with anti-IL-23 or anti-integrin medication classes. Conclusions: Antibody decay in patients with CID is not observed in patients on anti-integrins or anti-IL-23 while it is seen among patients on TNFi, JAKi, antimetabolites, and combinations of biologics and/or small molecules. Our data and those from other cohorts may be used to prioritize medication classes for boosting immunogenicity with additional doses of vaccination against SARS-CoV-2. Collection of antibody titers after booster doses is currently ongoing.(Table Presented) (Figure Presented) Figure 1: Durability of anti-spike IgG antibodies after vaccination against SARS-CoV-2 in patients with Chronic Inflammatory Disease
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Background: Cancer patients have been living with some inconvenience and anxiety about recurrence for a longer period while continuing cancer treatment after the initial cancer treatment is completed. In the future, the recuperation period for cancer patients will become longer and more complex. Intractable cancers such as recurrent, metastatic, drug-resistant, and rare cancers are defined as those that do not respond to or are resistant to cancer treatment. In addition, More than 50% of patients with cancer answered “home” as their preferred place to die, and there is a growing need for home treatment that emphasizes their own way of life. Therefore, it is important to encourage the improvement of the quality of home health care nursing related to home treatment cancer patients. Methods: This study has been approved by the Ethical Review Committee of institution. Study 1: A questionnaire was developed from a review of national and international literature, and a pilot web-based questionnaire was administered to visiting nurses. Study 2: An educational program is being planned based on the results obtained in Study 1.Study sessions corresponding to those themes were planned and implemented from May to September 2021 via web-based delivery using ICT. Results: The learning needs for refractory cancer palliative care nursing were included 1. COVID-19 at the home care, 2. ACP and 3. Nutrition Care. Based on our understanding of the above learning needs, nurses participated in the ICT for the intractable cancer nursing study session. Conclusion: As for training opportunities for visiting nurses, home care nursing stations do not have sufficient support systems for learning. In recent years, the number of cancer patients who wish to receive treatment at home has been increasing. The study sessions will be continued in order to obtain outcomes that improve visiting nurses‘ ability to practice cancer nursing through interventions for intractable cancer.
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Background: A novel coronavirus (SARS-CoV-2) has led to the worldwide spread of pandemic proportions and currently no effective therapy is available. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG), and phosphatidylinositol (PI), are potent regulators of inflammatory processes, and are effective as anti-viral agents for multiple respiratory viruses including Respiratory syncytial virus (RSV), Influenza A virus (IAV) and Rhinoviruses (RVs). Objective: The primary objectives of this study are to determine whether POPG or PI are potent against SARS-CoV-2 in vitro, using human airway epithelial cells, and examine the potency of PI against SARS-CoV-2 in vivo, in a hamster model. Methods: We examined efficacies of POPG or PI against SARS-CoV-2 (USA WA/2020) in human bronchial epithelial cells, and nasal epithelial cells from healthy control subjects differentiated by ALI cultures. We quantified SARS-CoV-2 replication by quantitative plaque assays and qRT-PCR. We determined the potency of PI against SARS-CoV- 2 in golden Syrian hamster as in vivo model for SARS-CoV-2 infection. Results: We examined the efficacies of POPG and PI using primary human tracheal and nasal epithelial cells, differentiated in ALI culture. Cells were treated with POPG (10mg/ml) and PI (4mg/ml) added to apical media alone for 16hrs. Subsequently, cells were infected with SARS-CoV-2 at m.o.i = 0.02, for 48hrs, harvested for RNA extraction and qRT-PCR. SARS-CoV-2 replicated in tracheal cells with a 106-fold increase in mRNA. POPG and PI reduced viral mRNA expression by 70% and 85%, respectively (subject numbers n=3). In nasal epithelia, SARS-CoV-2 mRNA expression increased 105 -fold compared to sham infected cultures. Both POPG and PI attenuated the increase in viral mRNA expression by 70% - 82% (subject numbers n=6). We determined the PI effect in an in vivo study in hamsters. Hamsters were challenged with 103 pfu of SARS-CoV-2, either with, or without PI (2mg/hamster) administered intranasally. Hamsters were harvested at Day 3, and lungs were processed for histopathology. Pharyngeal swabs were used to examine viral burden by plaque assays. PI reduced plaque numbers compared to viral infection alone groups at day1 (Virus alone: 2.4±2.7(X104pfu/ml), Virus+PI: 0.9±2.1(X106pfu/ml), p<0.05). PI reduced lung histopathology score at day 3 (Virus alone: 28.0±15.6, Virus+PI: 6.7±7.0, p<0.05). Conclusions: POPG and PI significantly reduced SARS-CoV2 replication in human differentiated airway epithelial cells. PI inhibited SARS-CoV-2 infection in vivo in hamsters. These findings suggest that inhalation of POPG, or PI might be effective as novel anti-viral compounds for treating and preventing SARSCoV- 2 infection.
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Recent years have witnessed the rapid development of artificial intelligence (AI) in different fields, including biomedical, in which timely detection of anomalies can play a vital role in patients' health monitoring. COVID-19, a contagious disease caused by the Severe Acute Respiratory Syndrome Corona-Virus 2 (SARS-CoV-2), has become a global epidemic. The key to combating this and other epidemics is detecting and isolating the infected patients in time. Therefore, there is an urgent need for a timely, practical detection approach. This paper proposes an AI-enabled pneumonia detection system, AIRBiS, to detect pneumonia (i.e., COVID-19) efficiently. AIRBiS is based on a high-performance Artificial Neural Network and an interactive user interface for effective operation and monitoring. The evaluation results demonstrate that the proposed system achieved 94.4% detection accuracy of pneumonia (i.e., COVID-19) over the collected test data. © 2022 IEEE.
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In this paper, we describe NL-Beep, which is a novel ranging method between multiple smartphones using acoustic sensing in non-line-of-sight (NLOS) environments. We need to know the distance between people to maintain social distancing because of the COVID-19 pandemic. Acoustic-based ranging methods that use a smartphone built-in speaker and microphone represent one approach to high-accuracy ranging methods. These methods can be used in line-of-sight (LOS) environments where there are no obstacles between the smartphones. However, in daily life, there are usually many obstacles, including pedestrians, and NLOS environments are the norm rather than the exception. Therefore, we propose the NL-Beep system for NLOS environments. To measure the distance between two smartphones without using a direct signal, NL-Beep efficiently uses a reflected signal from the ceiling in an indoor environment. It can also detect LOS and NLOS environments based on the profile of the received signal, and adapt the method used to estimate the distance between the smartphones. In our experiments, we used two smartphones in a room and estimated the distance between them for several placement configurations. In our results, we obtained 90th-percentile errors of less than 11.97 cm for the distances between the smartphones. In this paper, we also mention the effectiveness and limitations of NL-Beep.
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Background. Most adolescents (age 12-17 years) with COVID-19 have mild disease. However, certain comorbidities may be risk factors for disease progression, and hospitalization rates for this age group have increased. Adolescents and adults with mild to moderate COVID-19 are eligible for monoclonal antibody therapy. To identify subgroups likely to benefit from this intervention, we evaluated the relationship between comorbidities and need for hospitalization in US adolescents presenting with mild to moderate COVID-19. Methods. We analyzed presence of comorbidities and need for hospitalization within 28 days of diagnosis for adolescents in the PIDTRAN registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes (DM), immunosuppressive disease or treatment (IS), sickle cell disease (SCD), congenital/ acquired heart disease (CHD), neurologic disease/neurodevelopmental disorders (ND), medical-related technology dependence (MTD), and pulmonary disease requiring daily inhaled corticosteroids (PD). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization. Results. 1574 patients met inclusion criteria, of whom 180 (11.4%) were hospitalized within 28 days of COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: IS (OR 10.8 [95%CI 5.4 - 21.7]);CKD (OR 5.1 [95%CI 1.0 -25.6]);DM (OR 4.2 [95%CI 1.7 - 10.6]);SCD (OR 3.4 [95%CI 1.1 - 10.6]). ND (OR 3.0 [95%CI 1.7 - 5.4]);and obesity (OR 2.0 [95%CI 1.1 - 3.9]). Notably, CHD, MTD, and PD were not independently associated with hospitalization. There was no effect modification of race/ethnicity on the association between obesity or DM and hospitalization. Conclusion. IS, CKD, DM, SCD, ND, and obesity were associated with increased odds of hospitalization in adolescents presenting with mild to moderate COVID-19. Adolescents with these comorbidities should be prioritized for consideration of treatment with monoclonal antibodies.
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In this study, we conducted a multifaceted analysis of heatstroke cases using the emergency transported big data in Kobe City, and discovered the characteristics of heatstroke incidents in Kobe City in 2020 that differed from previous years. As a result of the analysis, it was found that the peak period of WBGT in 2020 was later than usual, and it was found that the peak period of WBGT is later than usual in 2020, and the occurrences of heatstroke in 2020 is characterized by an increase in the occurrences of heatstroke in people over 65 years old and outdoors, and a decrease in the occurrences of heatstroke in people under 65 years old and indoors. © 2021 IEEE.
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Background: To clarify the impact of the COVID-19 pandemic on the policies and practices of delivery facilities in Japan from April 2020 to March 2021. Methods: We conducted an online survey of midwives working in obstetric wards nationwide between May 15, 2021, and July 31, 2021. We analyzed the 376 valid responses. Results: With the COVID-19 pandemic, most facilities have barred or partially restricted families and other visitors from being present (patient companions) in outpatient clinics, prenatal classes, during delivery, inpatient care, and inpatient visits. These changes were implemented nationwide, regardless of regional differences in the pandemic state of COVID-19. Meanwhile, by facility classification, prenatal classes, companion at birth, and inpatient visits were more likely to be canceled at perinatal centers than at clinics. The acceptance of “satogaeri deliveries” (a custom in Japan where pregnant women return to their natal homes for labor and childbirth) was partially restricted to about 40% of facilities, although this rate was lower in the four Kanto prefectures (Tokyo, Kanagawa, Saitama, and Chiba). Conclusions: With the COVID-19 pandemic, the differences in Japan’s policies and practices of delivery facilities were attributed more to the role played by facilities in the regional perinatal system than to regional pandemic status. © 2022 S.O.G. CANADA Inc.. All rights reserved.