Japan has experienced five waves of the COVID-19 pandemic so far. Four states of emergency were declared, and the Tokyo 2020 Olympic (July 23-August 8, 2021) and Paralympic Games (August 24-September 5, 2021) were held during the fifth wave of the pandemic. Although a record 5,773 new cases were reported in Tokyo on August 13, the number abruptly decreased afterwards, and only 9 new cases were confirmed in Tokyo on November 1, 2021. The high vaccination rates (79.2% of the total population has received the first dose and 77.8% has received the second dose as of December 24, 2021) and behavioral changes (such as mask wearing rate in public places remains close to 100%) are considered to be important factors in curbing the spread of the virus. However, the new Omicron variant poses future challenges due to its uncertainty. A cumulative total of 231 cases of the Omicron variant were reported in Japan between November 30 and December 25, 2021. Preliminary data indicated that the Omicron variant could be more contagious but less deadly than the Delta variant. Since mankind may be forced to coexist with COVID-19, efforts such as vaccination campaigns will need to continue and behavioral changes will become increasingly important as the "new normal" to reduce population density and contact with people. This is evinced at least in Japan's successful practices in fighting the past five waves of the pandemic.
In China, cardiovascular disease (CVD) has surpassed malignant tumours to become the disease with the highest mortality rate, and atherosclerosis (AS) is an important pathological cause of CVD. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in circulating human blood and is a precursor of estrogen and androgen. DHEA is converted into a series of sex hormones in local peripheral tissues where its acts physiologically. DHEA also acts therapeutically, thereby avoiding the adverse systemic reactions to sex hormones. DHEA inhibits AS, thus inhibiting the development of CVD, and it improves the prognosis for CVD. The incidence of CVD in postmenopausal women is substantially higher than that in premenopausal women, and that incidence is believed to be related to a decrease in ovarian function. The current review analyzes the mechanisms of postmenopausal women's susceptibility to AS. They tend to have dyslipidemia, and their vascular smooth muscle cells (VSMCs) proliferate and migrate more. In addition, oxidative stress and the inflammatory response of endothelial cells (ECs) are more serious in postmenopausal women. This review also discusses how DHEA combats AS by countering these mechanisms, which include regulating the blood lipid status, protecting ECs (including coping with oxidative stress and inflammatory reactions of the vascular endothelium, inhibiting apoptosis of ECs, and inducing NO production) and inhibiting the proliferation and migration of VSMCs. As a result, DHEA has great value in preventing AS and inhibiting its progression in postmenopausal women.
The effectiveness of neoadjuvant therapy (NAT) remains controversial in the treatment of pancreatic cancer (PC). Therefore, this meta-analysis aimed to investigate the clinical differences between NAT and upfront surgery (US) in resectable pancreatic cancer (RPC). Eligible studies were retrieved from PubMed, Embase, and Cochrane Library. The endpoints assessed were R0 resection rate, pathological T stage < 2 rate, positive lymph node rate, and overall survival. A total of 4,588 potentially relevant studies were identified, and 13 studies were included in this study. In patients with RPC, this meta-analysis showed that NAT presented an increased R0 resection rate, pathological T stage < 2 rate, and a remarkably reduced positive lymph node rate compared to US. However, patients receiving NAT did not result in a significantly increased overall survival. These findings supported the application of NAT, especially as a patient selection strategy, in the management of RPC. Additional large clinical studies are needed to determine whether NAT is superior to US.
Lung injury caused by cardiopulmonary bypass (CPB) increases the mortality after cardiac surgery. Previous studies have shown that regulatory T cells (Tregs) play a protective role during CPB, but the correlation between Tregs and CPB-induced lung injury remains unclear. Here, we conducted a prospective study about Treg cells in patient receiving CPB. Treg cells were collected from patients before the CPB operation (pre-CPB Tregs), and the effect of pre-CPB Tregs on the occurrence of CPB-induced lung injury was evaluated. Data showed that the baseline level of Treg cells in peripheral blood were lower in patients who developed lung injury after CPB, compared to those who did not develop lung injury after CPB. Function analyses revealed that pre-CPB Tregs from CPB-induced lung injury patients presented decreased ability in suppressing the proliferation and IFN-γ production of CD4 and CD8 T cell. Also, pre-surgery levels of TGF- β and IL-10 were markedly lower in lung injury patients than in non-lung injury patients. In addition, PD-1 and Tim-3 expression on pre-CPB Tregs were significantly lower in CPB-induced lung injury patients than the CPB patients without lung injury. Above all, we found impaired peripheral Treg responses in CPB-induced lung injury patients, indicating a potential role of Treg cells in the early diagnosis of CPB-induced lung injury.
The occurrence of peritoneal sarcomatosis (PS) in patients with retroperitoneal sarcoma (RPS) indicates a poor prognosis. However, the appropriate treatment modality remains unclear. This study aimed to identify its prognostic factors and further explore the role of macroscopically complete excision (CE) in the management of PS. A retrospective database was established to evaluate patients with RPS who underwent resection between January 2011 and January 2019. Univariate and multivariate survival analyses were performed to analyze the prognostic factors and identify the population that will optimally benefit from CE. This study included a total of 49 patients with PS from 211 patients with RPS, and 34 (69.4%) patients of whom with PS underwent CE successfully. The median follow-up time was 36.0 months. There were 8 patients excluded because of loss to follow-up (n = 4) or death from complications within 90 days postoperatively (n = 4). The CE group had a marginally better prognosis compared to the macroscopically incomplete excision (IE) group (median disease-specific survival: 20 months vs. 8 months). Multivariate survival analysis demonstrated that completeness of operation (CE vs. IE) was the only independent prognostic factor in PS patients (P = 0.042). There was no significant difference in the overall complications between the CE and IE groups (P = 0.205). In conclusion, completeness of macroscopical excision is an independent prognostic predictor of PS. If technically possible, CE is a feasible strategy to improve the prognosis of selected patients with PS.
It remains unknown whether and to what extend the angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can play a role in the development of atrial fibrillation (AF) after pacemaker implantation in very old patients. Therefore, we aimed to investigate the association between oral ACEIs or ARBs and the risk of developing AF in very old patients after pacemaker implantation. Patients above 80 years old with pacemaker implantation and without baseline history of AF were included and their real-world information about ACEIs or ARBs use was extracted from electronic medical records. New AF cases were confirmed via the records of outpatient visits. The multivariable Cox proportional-hazards model was used to evaluate the associations between oral ACEIs or ARBs and risk of AF after pacemaker implantation. Among a total of 388 identified patients aged 80 to 98 years, 118 used ACEIs, 174 had ARBs therapy, and 115 AF were identified after pacemaker implantation during a median follow-up time of 3.1 years. After adjustment for potential confounders, patients with daily use of ARBs had a relatively lower risk of AF after pacemaker implantation (HR: 0.627, 95% CI: 0.425, 0.926; P = 0.019) compared with those non-users, whereas ACEIs therapy didn't show a significant relation with AF risk (HR: 1.335, 95% CI: 0.894, 1.995; P = 0.157). In conclusion, for very old patients with a permanent pacemaker, daily use of oral ARBs was associated with a relative lower risk of AF after pacemaker implantation, however, daily use of ACEIs was not related with AF risk.
We explored the prognostic value of preoperative CA19-9 in α-fetoprotein (AFP)-positive and -negative HCC with hepatitis B virus (HBV) background (HBV-HCC), and explored the underlying mechanism. Recurrence-free survival (RFS) and overall survival (OS) were assessed in HBV-HCC patients who underwent curative resection (Cohort 1). Immunohistochemical staining of CA19-9 in HCC and liver parenchyma were quantified in another cohort of 216 patients with resected HCC (Cohort 2). Immunohistochemical staining of CA19-9 and serum CA19-9 level was also compared between patients with HCC and intrahepatic cholangiocarcinoma (ICC) (Cohort 3). In Cohort 1, CA19-9 ≥ 39 U/mL was an independent risk factor for RFS (HR = 1.507, 95% CI = 1.087-2.091, p = 0.014) and OS (HR = 1.646, 95% CI = 1.146-2.366, p = 0.007). CA19-9 ≥ 39 U/mL was also associated with significantly higher incidence of macrovascular invasion (MaVI) compared with CA19-9 < 39 U/mL (23.0% vs. 7.2%, p = 0.002), and elevated aminotransferase and aspartate aminotransferase to platelet ratio index (APRI), and lower albumin. Immunohistochemical staining of CA19-9 revealed that CA19-9 expression was found exclusively in the background liver but not in HCC tumor cells. In contrast, tumor tissue was the main source of CA19-9 in ICC patients. CA19-9 ≥ 39 U/mL was associated with worse OS and RFS in both AFP-positive and negative HCC patients. CA19-9 indicated more severe inflammation and cirrhosis in the liver of HCC patients.
Both cytomegalovirus (CMV) viremia and disseminated nontuberculous mycobacterial (NTM) disease are common opportunistic infections in AIDS patients. Whether concurrent CMV viremia is associated with mortality in patients with AIDS and disseminated NTM disease is unknown. Subjects were patients with AIDS and disseminated NTM disease seen at a single center from January 2015 to April 2021. Data were retrospectively collected. Differences in demographics and clinical characteristics and hospitalization survival rates were compared between patients with disseminated NTM and with CMV viremia or not. Subjects were 113 AIDS patients with disseminated NTM who were seen at this Hospital from January 2015 to April 2021. Twenty-six of the patients had CMV viremia and 87 did not. The median age was 36 years (interquartile range [IQR] 29-42) and 108 patients were male (96%). The median CD4 count was 7 cells/µL (IQR 3-17). The median plasma CMV viral load was 9,245 IU/mL (IQR 3147-45725). The serum albumin of patients with CMV viremia was significantly lower than that of patients without CMV viremia (P = 0.03). Compared to patients without CMV viremia (81.6%), patients with CMV viremia had a significantly poorer prognosis (P = 0.01). Cox regression analysis indicated that the risk of a poor prognosis in patients with CMV viremia was 4.7 times higher than that in patients without CMV viremia (P = 0.003), and patients with CD8 more than 250/μL had a better prognosis (P = 0.02). CMV viremia increases the risk of a poor prognosis in patients with AIDS and a disseminated NTM infection. A routine CMV DNA test should be performed on patients with AIDS and disseminated NTM disease in order to reduce the risk of death.
Since the first edition of the guidelines for the diagnosis and treatment of AIDS was published in 2005, the AIDS Specialists Group of the Society of Infectious Diseases has updated the guidelines three more times to include more thorough, practical, standardized, and specific content. The latest edition (the 2021 version) has recently been updated in China in accordance with clinical practice nationwide and results of the latest research. Compared to the four previous editions, the 2021 edition references the latest information on the epidemiology of HIV, the prevention of HIV transmission, standardized lab diagnosis, and clinical management. First, the guidelines highlight the concept of "enhancing the combination of early intervention, prevention, and treatment". The guidelines specify more detailed clinical phases (three clinical stages), the clinical staging and progression of AIDS, and patient prognosis. The guidelines also specify diagnostic criteria – HIV antibodies, HIV RNA tests, CD4 cell counts, and the patient's epidemiological history – to use in conjunction with symptoms to confirm an HIV infection. In addition, the guidelines summarize more advanced HIV/AIDS research in China by describing the different circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in Chinese patients, by summarizing the most prevalent strains in the Chinese population, and by comparing disease progression by route of transmission and by the CD4+T cell count. Lastly, this edition describes ways to optimize programs to prevent mother-to-child transmission, strategies for diagnosis and treatment of opportunistic infections, the aging patient population, and specialized ART treatment programs for different populations living with HIV. The guidelines should not only help to prolong the life of people living with HIV and improve their quality of life but also encourage successful collaboration between scientific researchers and physicians in the area of HIV.
The COVID-19 pandemic has been the biggest public health crisis in a century. Since it was initially reported in 2019, the duration and intensity of its impacts are still in serious question around the world, and it is about to enter its third year. The first public health revolution failed to achieve its ultimate targets, as previously contained infectious diseases seem to have returned, and new infectious diseases continue to emerge. The prevention and control of infectious diseases is still a public health priority worldwide. After SARS, China adjusted a series of its infectious disease policies. In order to ensure the effectiveness and implementation of prevention and control interventions, the government should integrate the concept of public health. Perhaps we need a global public health system at the government level to fight the potential threat of infectious disease. This system could include multifaceted strategies, not just specific prevention and control interventions, and it could also be a comprehensive system to ensure unimpeded communication and cooperation as well as sustainable development.