The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are responsible for the devastating coronavirus disease 2019 (COVID-19) pandemic with more than 6.5 million deaths since 2019.Although a number of vaccines significantly reduced the mortality rate, a large number of the world population is yet being infected with highly contagious omicron variants/subvarints. Additional therapeutic interventions are needed to reduce hospitalization and curb the ongoing pandemic. The activity of the SARS-CoV-2 enzyme; chymotrypsin-like main protease (Mpro) is essential for the cleavage of viral nonstructural polypeptides into individual functional proteins and therefore Mpro is an attractive drug target. The aim of this review is to summarize recent progress toward the development of therapeutic drugs against Mpro protease.
The occurrence of immune-related adverse events (irAEs) after immune checkpoint inhibitors (ICIs) is unpredictable. Profiles of peripheral blood mononuclear cells (PBMCs) represent the host immune system and have the potential to predict irAEs. We analyzed PBMC subsets using multicolor flow cytometry before and at weeks 2 and 8 after the start of ICIs in patients with non-small cell lung cancer. Sixteen eligible patients were evaluated. The irAEs occurred in 6 patients (37.5%): diarrhea in 2, diarrhea and a rash in 1, pituitary dysfunction in 1, cholangitis in 1, and pneumonitis in 1. Patients experiencing irAEs had higher levels of CD86+plasmacytoid dendritic cells (pDCs) at the baseline and weeks 2 and 8 after the ICIs than those not experiencing irAEs (p = 0.005, 0.038, and 0.050, respectively). In patients experiencing irAEs, the levels of CD86+pDCs significantly decreased at weeks 2 and 8 compared to the baseline (p = 0 .034 and 0.025, respectively) but did not change in those not experiencing irAEs. The levels of other PBMC subsets were not significantly associated with irAEs. Higher levels of natural killer (NK) cells were significantly associated with an overall objective response (p = 0.024). In conclusion, higher levels of CD86+pDCs at the baseline and a reduction in those levels 2 and 8 weeks after ICIs were associated with the occurrence of irAEs. Higher levels of NK cells were associated with an objective response to ICIs. Evaluation of PBMCs may help to predict the efficacy and safety of ICIs.
The number of the human immunodeficiency virus (HIV)-positive patients are increasing worldwide, and more HIV-positive patients are undergoing urgent or elective cholecystectomy. There is still insufficient evidence on the relationship between surgical complications of cholecystectomy and antiviral status in HIV-positive patients. The purpose of the present study is to evaluate surgical outcomes after cholecystectomy in HIV-positive patients. Records of consecutive HIV-positive patients who underwent cholecystectomy between January 2010 and December 2020 were reviewed retrospectively. Patients were divided into urgent and elective surgery groups. Urgent surgery was defined as surgery within 48 hours of admission. Postoperative complications were evaluated according to the Clavien-Dindo classification. A total of 30 HIV-positive patients underwent urgent (n = 7) or elective (n = 23) cholecystectomy. Four complications (13.3%) occurred, and the rate was significantly higher in the urgent group than in the elective group (p = 0.008). However, all complications were minor (3 cases of grade I and one case of grade II), and there were no severe postoperative complications. There was no significant difference in CD4+ lymphocyte status in all patients and between the 2 groups before and after surgery (p = 0.133). No cases of postoperative deterioration in the control of HIV infection were observed. In conclusion, cholecystectomy in HIV-positive patients with controlled HIV under recent antiretroviral therapy may be performed safely even in an emergency situation.
Bronchial artery embolization (BAE) is the first choice treatment for hemoptysis. With advances in endovascular treatment, various embolic materials have become available. However, the optimal embolic material for the treatment of cryptogenic hemoptysis has not been determined. This study aimed to investigate the short- and long-term efficacy of BAE using a gelatin sponge in the treatment of patients with cryptogenic hemoptysis. The clinical characteristics, angiographic findings, and short- and long-term outcomes of BAE were retrospectively analyzed in 22 consecutive patients who underwent BAE for control of cryptogenic hemoptysis between January 2010 and September 2018. Selective angiography and super-selective BAE were successfully performed for all patients. A gelatin sponge was used in all patients. Further, polyvinyl alcohol was mixed with the gelatin sponge in 11 patients (50%). Angiography showed that the bronchial artery was responsible for hemoptysis in all patients, along with the intercostal artery in one patient (4.5%) and the inferior phrenic artery in one patient (4.5%). Immediate hemostasis was achieved in all patients. The recurrence-free rate was 100% for 1 month, 94.1% for 3 months, 94.1% for 12 months, and 87.4% for 24 months. Of two patients with recurrent hemoptysis, one underwent bronchoscopic hemoptysis and the other received intravenous hemostatic agents. No patient underwent BAE for recurrence. No severe complications occurred. In conclusion, BAE using a gelatin sponge has short- and long-term hemostatic efficacy for treating cryptogenic hemoptysis without any severe complications. A gelatin sponge is a suitable embolic material for patients with cryptogenic hemoptysis.
Although Omicron appears to cause less severe acute illness than the original strain, the potential for large numbers of patients to experience long COVID is a major concern. Little is known about the recovery phase in cases of Omicron, highlighting the importance of dynamically monitor long COVID in those patients. Subjects of the current study were patients available for a three-month follow-up who were admitted from January 13 to May 22, 2020 (period of the original strain) and from January 1 to May 30, 2022 (period of Omicron). Twenty-eight-point-four percent of patients infected with the original strain had long-term symptoms of COVID-19 and 5.63% of those infected with the Omicron strain had such symptoms. The most common symptom was a cough (18.5%), followed by tightness in the chest (6.5%), in patients infected with the original strain. Fatigue (2.4%) and dyspnea (1.7%) were the most commonly reported symptoms in patients infected with the Omicron strain. The respiratory system is the primary target of SARSCoV-2. Supportive treatment is the basis for the treatment of respiratory symptoms in patients with COVID-19. Quality sleep and good nutrition may alleviate fatigue and mental issues. Further knowledge about a long-term syndrome due to Omicron needs to be discussed and assembled so that healthcare and workforce planners can rapidly obtain information to appropriately allocate resources.
Japan has faced seven waves of the COVID-19 pandemic since 2020. Due to the less severe Omicron variant and the high rate of vaccination nationwide, the death rate has declined compared to that due to previous variants. In early 2022, current Prime Minister Fumio Kishida devised a new concept entitled "Living with COVID-19", encouraging a new lifestyle of living with SARS-CoV-2. Although treatment and prevention options have increased, the Omicron variant still causes deaths among the most vulnerable population. Before accepting life with SARS-CoV-2, challenges remain, especially with regard to communication, the healthcare system, and vaccination. A society-wide strategy involving multiple stakeholders should be adopted to mitigate the damage and achieve a true world where we are "Living with COVID-19".
At the beginning of the COVID-19 pandemic in 2020, many hospitals around the world recommended stopping elective surgery as a precaution to stop the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The number of elective surgeries was reduced in Japan due to several waves of the pandemic. This work describes the management of COVID-19 and actual polymerase chain reaction (PCR) screening in operating theaters at the National Center for Global Health and Medicine (NCGM), a designated hospital for specified infectious diseases in Japan. The following three steps for COVID-19 infection control were taken to maintain the operating theater: i) Do not bring COVID-19 into the operating theater, ii) Infection control for all medical staff, and iii) Surgical management of surgical patients with COVID-19. We introduced checklists for surgical patients, simulations of surgery on infected patients, screening PCR tests for all surgical patients, and use of a negative pressure room for infective or suspected cases. We determined the flow and timing of surgery for patients with COVID-19. However, many aspects of COVID-19 infection control measures in the operating theater are still unclear. Therefore, infection control measures require further advances in the future to manage new infections.
In patients with severe coronavirus disease 2019 (COVID-19) with diabetes, glycemic control is essential for a better outcome, however, we face difficulty controlling hyperglycemia induced by high-dose glucocorticoids. We report five cases of severe COVID-19 patients with diabetes, whose glycemic control was managed using an intermittently scanned continuous glucose monitoring (isCGM) system during methylprednisolone therapy. Patients using isCGM showed significantly lower average blood glucose levels and significantly higher total daily insulin dose during the methylprednisolone therapy, compared to patients under regular blood glucose monitoring. The use of isCGM enables remote glucose monitoring, and this can reduce the risks of healthcare workers who have frequent contact with the patients. Thus, we suggest that using isCGM should be considered in hospitalized patients with diabetes under the COVID-19 pandemic to achieve better glycemic control and to minimize the possible risks of healthcare workers.
Language barriers negatively affect patient outcomes, and linguistic assistance is essential for adequate healthcare. The adoption of face-to-face medical interpretating is believed to have been rendered more challenging by the implementation of hospital admission restrictions following the outbreak of novel coronavirus disease (COVID-19). On the other hand, remote interpretating can be implemented using merely equipment, enabling it to be introduced without being impacted by the transmission of illness, and its use may have spread globally. To comprehend how COVID-19 has impacted remote interpreting utilization and what issues have arisen, we conducted a systematic review of two databases, PubMed and Ichushi-web (Japanese medical literature) with "remote interpreting" and "COVID-19" as keywords in June, 2022. Five references were included in the review. The research supported an increase in remote interpreting during COVID-19 to limit the risk of infection. This change in the trend of medical interpreting has the potential of promoting remote medical interpreting for places lacking sufficient linguistically skilled human resources, regardless of the pandemic status. There have also been accounts of novel methods of remote medical interpretation in which neither the healthcare professional nor the interpreter was face-to-face with the patient, and difficulty was acknowledged by both the healthcare professional and the patient with remote interpreting. To fully take advantage of the possibilities of remote interpreting, additional training and support would be required. Further studies are also required to determine the best way to employ this technology.
January 2020 marked the very early period of SARS-CoV-2's arrival in Japan. At the time, we immediately and strictly adopted the use of enhanced PPE, including a N95, gown, gloves, eye protection, and an apron, during every endoscopic procedure for every patient, with or without COVID-19. One reason why we use enhanced PPE for every patient is because all endoscopic procedures should be considered aerosol-generating procedures, and another reason is that asymptomatic patients with COVID-19 cannot be identified during a pandemic. The volume of endoscopic screening/surveillance endoscopies decreased markedly, but therapeutic endoscopies did not decrease. In contrast, urgent endoscopic hemostasis has increased more than ever. The most common reason for the increase might be that the lack of protective equipment and the need for medical staff to deal with an unknown virus, creating a pandemic panic in emergency medicine.