Viruses require the host cellular machinery for protein translation and replication. Upon proliferation, virions damage cells and are released from the infected cells before infecting other cells. Acute inflammation occurs when host cells are damaged by infection. The cell receptors to which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binds, are widely distributed compared to those for other viruses, thereby resulting in various symptoms such as rhinitis, pneumonia, and enteritis. In general, RNA viruses, including SARS-CoV-2, exhibit a high frequency of gene mutations. Antigenic modulation due to genetic mutations of the spike protein causes cytokine storms because of strong activation of the innate immune system, similar to the phenomenon previously observed in highly pathogenic avian influenza. The proportion of severely ill patients due to coronavirus disease 2019 (COVID-19) varies from country to country, and factors that are responsible for the severity of the disease include antibody-dependent enhancement (ADE), Bacillus Calmette-Guérin (BCG) vaccination, and human leukocyte antigen (HLA) type. ADE and HLA types may also influence the protective effect of immunity, including its vaccine response against SARS-CoV-2.
This report is a secondary publication of our previous review report "J Tokyo Wom Med Univ 91: 2-10, 2021."
The December 2019 outbreak in China of a novel coronavirus infection (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus quickly spread globally. In the era of economic globalization, as of February 24, 2021, the cumulative number of people with COVID-19 has reached 110 million worldwide, with more than 24.7 million deaths, with containment of the pandemic not likely to happen soon. Conventional outbreaks have spread in low- and middle-income countries where poverty and immature health systems prevail, resulting in significant human and social inequity. However, middle- and upper-income people account for more than 85% of the total cumulative deaths. The spread of infection in Africa and Asia is relatively limited despite their fragile health systems. These unexpected phenomena are noteworthy when reconsidering the definition of social vulnerability. To prevent direct or indirect mortality associated with the COVID-19 pandemic, society has made efforts to minimize disruptions to health systems and mitigate social, racial, and gender inequity globally. While facing conventional and newly emerged social vulnerabilities, we are standing at a historical turning point to promote our new normal lifestyle of "coexisting with viruses" through a promising paradigm shift that focuses on improving the sustainability of our entire planet.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019. It has been rapidly spreading worldwide ever since. The majority of COVID-19 infections are asymptomatic or mildly symptomatic. However, old age or comorbidities can result in a cytokine storm, which eventually leads to death. To date, no drug has been clinically proven effective to treat COVID-19, and development of effective drugs against SARS-CoV-2 is urgently required. Several drugs used in treating other diseases are being evaluated. Clinical trials on many new antiviral drugs and vaccine candidates are also rapidly ongoing. In this review, we summarized the currently used drugs and newly developed vaccines for the treatment of COVID-19.
This is a secondary publication of "COVID-19 Pandemic: Drug Development and Drug Treatment" published in the Journal of Tokyo Women's Medical University (in Japanese) 91 (1): 19-28, 2021.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a wide range of clinical manifestations, including acute respiratory distress syndrome, severe inflammation, abnormal blood coagulation, and cytokine storm syndrome. SARS-CoV-2 uniquely facilitates its entry and expansion in host cells through the spike protein consisting of S1 (receptor binding domain) and S2 (fusion peptide domain). The S1 binds to angiotensin-converting enzyme 2 (ACE2), the host cell receptor. The cleavage at the boundary of S1 and S2 by Furin protease and subsequent digestion within the S2 by TMPRSS2 activate the S2 fusion peptides, which are necessary for the entry of SARS-CoV-2 into host cells. After infection, SARS-CoV-2 RNA genome encodes viral proteins including structural proteins, RNA polymerases/helicases, and modulators of host- defense system, which inhibit type I interferon-related immune signaling and signal transducer and activator of transcription 1 (STAT1) signaling. In contrast, SARS-CoV-2 infection activates the proinflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor α (TNFα). In severe cases of COVID-19, these alterations in immune signaling may induce a state of systemic immune dysfunction. Recent studies also revealed the involvement of hematopoietic cells and alteration of cellular metabolic state in COVID-19. We here review the pathogenesis of COVID-19, primarily focusing on the molecular mechanism underlying SARS-CoV-2 infection and the resulting immunological and hematological alterations.
This is the secondary publication of "The pathophysiology of COVID-19 (Coronavirus Disease 2019) caused by the infection of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) " published in the Journal of Tokyo Women's Medical University (in Japanese) 91 (1): 11-18, 2021.
Coronavirus disease 2019 (COVID-19) has grown to pandemic levels, making a significant impact on people's physical, mental, and social lives. Along with the direct central nervous system damage caused by the infection, those infected have experienced psychological effects as well, including the stress they experience during treatment, the guilt of infecting others, and the accompanying stigma. For the uninfected public, there are effects on lifestyle changes because of the spread of the infection, along with the anxiety caused by isolation (due to restricted mobility for preventing the spread of the infection). Healthcare workers and other support staff may experience anxiety, depression, and insomnia, which may interfere with their social lives, such as a difficulty in concentrating at work and the development of post-traumatic stress disorder.
The mental health responses in a pandemic are diverse. Responses to infected individuals include dealing with the infection's effects on the central nervous system and the psychological burden of the treatment. Care for non-infected people includes providing accurate information and dealing with the stress of limited mobility; moreover, care for supporters includes organizational support and individual psychological education. Another form of mental health support that should be provided first in the event of a major disaster, regardless of the target population, is psychological first aid. This involves engaging with the affected population, gathering information, providing safety and adequate information, and linking them to available services.
In addition to the Psychiatric Liaison Team, Tokyo Women's Medical University Hospital formed the COVID-19 Mental Health Care Team, which consists of doctors, nurses, and psychologists. This team not only provides a support system for infected patients but also for their families and the healthcare workers at the hospital.
In this paper, we will discuss the impact of COVID-19 on mental health and introduce the mental health support (the Psychiatric Liaison Team & COVID-19 Mental Health Care Team) during the pandemic.
This is a secondary publication of "Mental Health Care on COVID-19 Pandemic: The Role of Psychiatric Team on Pandemic" published in the Journal of Tokyo Women's Medical University (in Japanese) 91 (1): 72-80, 2021.
Background: Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is useful for detecting microperitoneal dissemination in gastric cancer. However, reports on its use in colorectal cancer are sparse. In this study, we performed PDD with 5-ALA to diagnose peritoneal dissemination in colorectal cancer during laparoscopic surgery.
Methods: Between January 2018 and March 2019, we examined six patients scheduled laparoscopic surgery for colorectal cancer (cT3 or deeper) with suspected peritoneal dissemination. A solution of 5-ALA (20 mg/kg) in water was orally administered 3 to 4 hours before surgery. Intraoperatively, the peritoneal cavity was observed with white and fluorescent lights. Nodules suspected as dissemination lesions were resected and the presence or absence of seeding was confirmed histopathologically.
Results: The median time from oral 5-ALA administration to observation was 226 minutes. Peritoneal nodules found in four of six cases using white light were collected. In Case 5, white nodules were observed in white light and luminescence in fluorescent light. Of the nodules collected, only that of Case 5 was pathologically diagnosed as disseminating. No adverse events were observed.
Conclusions: We attempted PDD using 5-ALA during laparoscopic surgery for colorectal cancer. Observing more cases and optimizing observation conditions are required to improve accuracy.
This study was registered at the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN Exam ID: UMIN000030531).
Objective: We analyzed the serum levels of leukotrienes (LTs) to obtain further insight into the pathogenesis of respiratory syncytial virus (RSV) infection in infants.
Methods: The subjects were 22 infants with RSV infection. The serum LT and immunoglobulin E (IgE) levels were measured at admission and at the end of the hospital stay. We investigated the correlations of the serum LT levels with the serum IgE levels and the long-term (3-6 years) prognosis of the infants.
Results: The mean serum LT level was significantly higher at the end of the hospital stay than at admission, particularly in the high-IgE group. The mean serum LT level at the end of the hospital stay was also significantly higher in the poor-prognosis group as compared to that in the good-prognosis group.
Conclusion: In infants with RSV infection, the serum LT levels were significantly elevated, particularly in the high-IgE group and the poor-prognosis group, suggesting a pathogenetic role of LTs of lower respiratory tract inflammation caused by RSV infection.
Background: Zinc (Zn) is highly important for metabolism in humans and its deficiency is associated with various diseases. The present retrospective study has assessed the serum Zn level in cases of acute stroke.
Methods: Study cohort included 47 patients (mean age, 73 years) with minor (N = 27), moderate (N = 13), and severe (N = 7) stroke. The National Institutes of Health Stroke Scale (NIHSS) score at admission varied from 1 to 40 (median, 3).
Results: Serum Zn level ranged from 23 to 102 μg/dL (mean, 68.4 μg/dL). It inversely correlated with the NIHSS score (P = 0.0340), was associated with the stroke severity (P = 0.0133), was significantly lower in patients with thrombotic stroke (P = 0.0434), and inversely correlated with the age of patient (P = 0.0220). In those aged >74 years (N = 23), but not in younger individuals, serum Zn level inversely correlated with the NIHSS score (P = 0.0155) and was associated with the stroke severity (P = 0.0117).
Conclusions: In patients with acute stroke the serum Zn level is frequently decreased. It is associated with the stroke severity, thrombotic type, and older age, and may contribute to more severe clinical course of the disease among the elderly.
Background: We evaluated 12 biomarkers as potential prognostic predictors in Japanese breast cancer patients: EGFR, PTEN, IGF-1R, Bcl-2, c-Kit, c-Met, HIF-1α, PDGFRA, survivin, VEGFR2, VEGF-A, and Ki67.
Methods: A total of 466 surgical patients were divided into six subgroups in accordance with St. Gallen 2017 classification: triple-negative, HER2, triple-positive, luminal-low risk, luminal-intermediate risk, and luminal-high risk. Immunohistochemical staining of the biomarkers was compared among the subgroups in relation to 10-year disease-free survival (DFS) and cancer-specific survival (CSS), calculated by the Kaplan-Meier method and evaluated by Cox regression.
Results: In the triple-negative group, by multivariate analysis of Cox model for DFS, c-Kit (hazard ratio [HR], 5.941; 95% confidence interval [CI], 1.171-30.137; p = 0.0315) and HIF-1α (HR, 5.631; 95%CI, 1.014-31.275; p = 0.0482) emerged as significant. In the CSS model, c-Kit (HR, 8.541; 95%CI, 1.396-52.266; p = 0.0203) and HIF-1α (HR, 11.103; 95%CI, 1.227-100.429; p = 0.0322) were significant. In other subgroups, several biomarkers and clinical factors remained significant with DFS model but none with CSS.
Conclusions: We found c-Kit and HIF-1α with a statistical effect on outcomes in the triple-negative group. A combination of these can be useful in predicting prognoses.
Background: The implementation of clinical information systems (CISs) alone and with hospital electric medical records in intensive care units (ICUs) can lead to numerous errors. This study aimed to investigate errors in an ICU and intermediate medical care unit (IMU) for 9 months after implementing of a CIS.
Methods: A CIS was incrementally implemented in the general ICU and IMU of a university hospital over 3 months and was used for all patients by April 2019. The errors encountered over 9 months were extracted from the hospital's incident reporting system.
Results: Overall, 122 and 140 errors in the ICU and IMU, respectively, during the study period. Incidence rates of the errors in the ICU and IMU were 31.7 (95% confidence interval [CI] 26.3-37.8) and 51.3 (43.2-60.6) events per 1,000 patient-days, respectively. There were 17 (14%) and 15 (11%) CIS-related errors in the ICU and IMU, respectively. The incidence rates of errors in the ICU and IMU were 5.3 (3.1-8.5) and 6.5 (3.6-10.7) events per 1,000 CIS operation patient-days, respectively.
Conclusions: Thirteen percent of the errors in the ICU and IMU were related to the CIS, and the incidence did not vary with the staffing intensity of both care units.
The study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000039402).
Background: Patient registries play an important role in rare disease, particularly for recruitment of clinical trials and clinical research.
Methods: In 2012, we launched a registry for the purpose of clarifying the clinical characteristics of spinal muscular atrophy (SMA) in Japan and with the goal of enrolling patients with SMA into newly started clinical trials. In order to document the current status of SMA in Japan, we conducted a survey based on the data of 277 SMA patients enrolled in the registry from October 2012 to July 2020.
Results: Genetic testing was performed in 95% of patients. Patients with type III SMA experienced the longest onset to genetic diagnosis times, while those with type I had the shortest times. Tongue fasciculation was more common in types I and II SMA, while finger fasciculation was more common in types II and III. The site of fasciculation was thought to be the key to predicting the disease type. Over-the-counter or investigational drugs were administered to 76% of patients as of June 2019.
Conclusion: Our registry is useful for understanding the current status of SMA patients in Japan, and can provide accurate and up-to-date information on the clinical course of patients over their lifetime.
Background: Transcatheter aortic valve implantation (TAVI) is intended to reduce left ventricular afterload and the concomitant left ventricular end-diastolic pressure (LVEDP) change. Currently, two types of prosthetic valves are used in the TAVI procedures: balloon-expandable valves and self-expandable valves. The purpose of the current study was to investigate the effects of these valves on the LVEDP after valve deployment.
Methods: This retrospective study included 181 patients who underwent transfemoral TAVI. The patients were classified into one of two groups according to whether a balloon-expandable prosthetic valve (group B) or self-expandable prosthetic valve (group S) was used in the procedure. The intraoperative LVEDP, measured using an intracardiac catheter, was compared before and after valve deployment.
Results: The LVEDP decrement was significantly greater for group S than for group B (-1.3 ± 6.0 mmHg vs. 0.8 ± 5.1 mmHg). A subgroup analysis of the patients with mild or lower grade aortic regurgitation showed a significantly greater decrement of the LVEDP for subgroup S than for subgroup B (-1.8 ± 5.6 mmHg vs. 0.5 ± 4.8 mmHg).
Conclusion: Self-expandable prosthetic valves are advantageous for preventing LVEDP elevation after TAVI compared to balloon expandable prosthetic valves.
The study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000040255).
Aim: We aimed to compare the low-density lipoprotein cholesterol (LDL-c) values obtained by direct measurement (D) and by the Friedewald equation (F), and examine the validity of the LDL-c + 30 mg/dL value as a non-high-density lipoprotein cholesterol (non-HDL-c) reference value. Additionally, we evaluated the association between the discrepancies between D and F and the clinical background.
Methods: We collected 2,237 samples from patients ≥ 20 year-old, in either fasting or non-fasting state.
Results: The Spearman's correlation coefficient between D and F was 0.964 and there was a correlation between LogD and LogF (R2 = 0.9259). The average of % Bias was -4.94% in TG < 400 mg/dL. A weak correlation between non-HDL-c and D + 30 was observed in TG ≥ 400 mg/dL (R2 = 61%). In the most cases with D lower than F, end-stage liver disease was observed. In the cases with D higher than F, no particular diseases were observed.
Conclusion: In conclusion, a significant correlation was found between D and F. Both D and F could be continuously compared and examined as follow-up data in TG < 400 mg/dL. We proposed to reconsider LDL-c + 30 mg/dL as a reference value of non-HDL-c in TG ≥ 400 mg/dL.
Background: Cryoprecipitate contains high concentrations of fibrinogen (Fib) that is effective for dilutional coagulopathy in massive blood transfusions. The supply of cryoprecipitate by in-house preparation in our hospital began in July 2013. There is heterogeneity in the Fib content of fresh frozen plasma (FFP) and cryoprecipitates. Here, we measured the Fib content of cryoprecipitates prepared in our hospital.
Methods: We measured the Fib content of 2,715 cryoprecipitate bags prepared in our hospital. Four randomly selected bags were used as the basic order unit, and the amount of Fib per four bags was measured for 579 orders. The number of bags and Fib content of cryoprecipitate administered in all 487 surgical cases were examined.
Results: The average amount of Fib per bag was 516.3±166.8 mg/bag. Per four bags, 551 orders (95.2%) contained >1,500 mg and 28 orders (4.8%) contained <1,500 mg, and 6.1±2.0 bags of cryoprecipitate and 3,115.0±1.0 mg of Fib were administered per surgical case.
Conclusion: The Fib content of cryoprecipitates varied widely, reflecting the heterogeneity of Fib concentrations in FFP. A large amount of cryoprecipitate must be administered to deliver sufficient Fib. Therefore, besides cryoprecipitate, the use of Fib preparations should be considered in treating severe dilutional coagulopathy.
Tailgut Cyst is a rare lesion occurring in the retrorectal space. A complete resection is necessary for diagnosis and treatment without morbidity. Here we report a case of a Tailgut Cyst successfully resected using the laparoscopic approach. A 63-year-old woman presented to the orthopedic clinic with a complaint of right coxalgia and was referred to our department for treatment of a suspected Tailgut Cyst demonstrated on magnetic resonance imaging. Laparoscopic surgery was performed in the Trendelenburg position utilizing five ports. The mesorectum was mobilized at the level of the levator ani muscle. Upon confirmation, the tumor in the left posterior mesorectum was excised using laparoscopic coagulation shears for sharp dissection around the tumor. The pathological diagnosis was a Tailgut Cyst with no evidence of malignancy. Her postoperative course was uneventful and she had no signs of recurrence 6 months postoperatively. Thus, laparoscopic resection is a safe and feasible method for complete surgical resection of Tailgut Cyst.