Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials

Background:The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19.Methods:Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.Results:Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20–0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75–0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60–2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05–1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18–8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38–0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20–5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02–7.08) vs. SOC with very low quality were associated with an increased risk.Conclusions:COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.     

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis: a 2-year retrospective analysis

Background:Cryptococcal meningitis (CM) is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus (HIV)-infected patients, and is complicated with significant morbidity and mortality. This study retrospectively analyzed the clinical features, characteristics, treatment, and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.Methods:Data from all patients (n = 101) of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.Results:Of the 101 patients, 86/99 (86.9%) of patients had CD4 count <50 cells/mm³, 57/101 (56.4%) were diagnosed at ≥14 days from the onset to diagnosis, 42/99 (42.4%) had normal cerebrospinal fluid (CSF) cell counts and biochemical examination, 30/101 (29.7%) had concomitant Pneumocystis (carinii) jiroveci pneumonia (PCP) on admission and 37/92 (40.2%) were complicated with cryptococcal pneumonia, 50/74 (67.6%) had abnormalities shown on intracranial imaging, amongst whom 24/50 (48.0%) had more than one lesion. The median time to negative CSF Indian ink staining was 8.50 months (interquartile range, 3.25–12.00 months). Patients who initiated antiretroviral therapy (ART) before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients (7 vs. 12 months, χ² = 15.53, P < 0.001). All-cause mortality at 2 weeks, 8 weeks, and 2 years was 10.1% (10/99), 18.9% (18/95), and 20.7% (19/92), respectively. Coinfection with PCP on admission (adjusted odds ratio [AOR], 3.933; 95% confidence interval [CI], 1.166–13.269, P = 0.027) and altered mental status (AOR, 9.574; 95% CI, 2.548–35.974, P = 0.001) were associated with higher mortality at 8 weeks.Conclusion:This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data. Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.     

Functional mitral regurgitation combined with increased early diastolic transmitral velocity to early mitral annulus diastolic velocity ratio is associated with a poor prognosis in patients with shock

Background:Functional mitral regurgitation (FMR) is common in critically ill patients and may cause left atrial (LA) pressure elevation. This study aims to explore the prognostic impact of synergistic LA pressure elevation and FMR in patients with shock.Methods:We retrospectively screened 130 consecutive patients of 175 patients with shock from April 2016 to June 2017. The incidence and impact of FMR and early diastolic transmitral velocity to early mitral annulus diastolic velocity ratio (E/e’) ≥ 4 within 6 h of shock on the prognosis of patients were evaluated. Finally, the synergistic effect of FMR and E/e’ were assessed by combination, grouping, and trend analyses.Results:Forty-four patients (33.8%) had FMR, and 15 patients (11.5%) had E/e’ elevation. A multivariate analysis revealed FMR and E/e’ as independent correlated factors for 28-day mortality (P = 0.043 and 0.028, respectively). The Kaplan-Meier survival analysis revealed a significant difference in survival between patients with and without FMR (χ² = 7.672, P = 0.006) and between the E/e’ ≥ 14 and E/e’ < 14 groups (χ² = 19.351, P < 0.010). Twenty-eight-day mortality was significantly different among the four groups (χ² = 30.141, P < 0.010). The risk of 28-day mortality was significantly higher in group 4 (E/e’ ≥ 14 with FMR) compared with groups 1 (E/e’ < 14 without FMR) and 2 (E/e’ < 14 with FMR) (P = 0.001 and 0.046, respectively).Conclusions:Patients with shock can be identified by the presence of FMR. FMR and E/e’ are independent risk factors for a poor prognosis in these patients, and prognosis is worst when FMR and E/e’ ≥ 14 are present. It may be possible to improve prognosis by reducing LA pressure and E/e’.Trial Registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03082326","term_id":"NCT03082326"}}NCT03082326.     

Retrospective analysis of sentinel lymph node biopsy using methylene blue dye for early breast cancer

BackgroundMethylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses.MethodsWe retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves.ResultsBetween January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ² = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ² = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ² = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224−0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006).ConclusionOur single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.     

A double-blind,double-dummy,randomized controlled,multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

Background:Clinical observational studies revealed that ⁹⁹Tc-methylene diphosphonate (⁹⁹Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of ⁹⁹Tc-MDP plus methotrexate (MTX) vs. MTX alone or ⁹⁹Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.Methods:Eligible patients with moderate to severely active RA were randomized to receive ⁹⁹Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or ⁹⁹Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.Results:At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + ⁹⁹Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or ⁹⁹Tc-MDP group (47.5%) (P = 0.03 for MTX + ⁹⁹Tc-MDP vs. MTX, and MTX + ⁹⁹Tc-MDP vs.⁹⁹Tc-MDP, respectively). The participants in the MTX + ⁹⁹Tc-MDP group and the ⁹⁹Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + ⁹⁹Tc-MDP vs. MTX: P = 0.03, ⁹⁹Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.Conclusions:This study demonstrated that the combination of ⁹⁹Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and ⁹⁹Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of ⁹⁹Tc-MDP therapy in patients with RA are warranted.Trial Registration:Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.     

Clinical features of acute kidney injury in patients with nephrotic syndrome and minimal change disease: a retrospective,cross-sectional study

Background:Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome.Methods:Patients from Chinese People''s Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis.Results:A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ² = 41.063, P < 0.001). The percentage of AKI increased with age in the MCD patients. The percentage of AKI in patients aged 50 years or older was 52.9% (46/87), which was significantly higher than that [22.5% (63/280)] in patients under 50 years (χ² = 6.347, P = 0.013). We observed statistically significant differences in age (43 [27, 59] years vs. 28 [20, 44] years, Z = 5.487, P < 0.001), male (78.0% vs. 51.4%, χ² = 22.470, P < 0.001), serum albumin (19.9 ± 6.1 g/L vs. 21.5 ± 5.7 g/L, t = 2.376, P = 0.018), serum creatinine (129.5 [105.7, 171.1] μmol/L vs. 69.7 [57.7, 81.9] μmol/L, Z = 14.190, P < 0.001), serum urea (10.1 [6.2, 15.8] mmol/L vs. 4.7 [3.6, 6.4] mmol/L, Z = 10.545, P < 0.001), IgE (266.0 [86.7, 963.0] IU/ml vs. 142.0 [35.3, 516.5] IU/ml, Z = 2.742, P = 0.007), history of diabetes (6.4% vs. 1.2%, P = 0.009), and history of hypertension (23.9% vs. 5.1%, χ² = 28.238, P < 0.001) between the AKI group and the non-AKI group. According to multivariate linear regression analysis, among the renal pathological features analyzed, renal tubular epithelial cell damage (β = 178.010, 95% CI: 147.888−208.132, P < 0.001) and renal interstitial edema (β = 28.833, 95% CI: 11.966−45.700, P = 0.001) correlated with serum creatinine values.Conclusions:The percentage of AKI in MCD patients is significantly higher than that in MN patients. Patients over 50 years old are more likely to develop AKI. Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.     

Comparable efficacy of 100 mg aspirin twice daily and rivaroxaban for venous thromboembolism prophylaxis following primary total hip arthroplasty: a randomized controlled trial

Background:Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.Methods:Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications.Results:We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ² = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ² = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5–1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4–1740.6mL]) (χ² = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8–83.0], Rivaroxaban: 81.0 [79.3–83.0], χ² = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0–92.0], Rivaroxaban: 91.5 [88.3–92.8], χ² = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ² = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ² = 1.13, P = 0.29).Conclusion:In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.Trial Registration:Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284     

Clinical and epidemiological characteristics of COVID-19 mortality in Saudi Arabia

Objectives:To analyze the clinical and epidemiological characteristics for 224 of in-hospital coronavirus disease 2019 (COVID-19) mortality cases. This study’s clinical implications provide insight into the significant death indicators among COVID-19 patients and the outbreak burden on the healthcare system in the Kingdom of Saudi Arabia (KSA).Methods:A multi-center retrospective cross-sectional study conducted among all COVID-19 mortality cases admitted to 15 Armed Forces hospitals across KSA, from March to July 2020. Demographic data, clinical presentations, laboratory investigations, and complications of COVID-19 mortality cases were collected and analyzed.Results:The mean age was 69.66±14.68 years, and 142 (63.4%) of the cases were male. Overall, 30% of the COVID-19 mortalities occurred in the first 24 hours of hospital admission, while 50% occurred on day 10. The most prevalent comorbidities were diabetes mellitus (DM, 73.7%), followed by hypertension (HTN, 69.6%). Logistic regression for risk factors in all mortality cases revealed that direct mortality cases from COVID-19 were more likely to develop acute respiratory distress syndrome (odds ratio [OR]: 1.75, confidence intervel [CI: 0.89-3.43]; p=0.102) and acute kidney injury (OR: 1.01, CI: [0.54-1.90]; p=0.960).Conclusion:Aging, male gender and the high prevalence of the underlying diseases such as, DM and HTN were a significant death indicators among COVID-19 mortality cases in KSA. Increases in serum ferritin, procalcitonin, C-reactive protein (CRP), and D-dimer levels can be used as indicators of disease progression.     

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China

Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n = 72) or allo-HSCT (n = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2–143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.     

Occult Andersson lesions in patients with ankylosing spondylitis: undetectable destructive lesions on plain radiographs

Background:Andersson lesions (ALs) are not uncommon in ankylosing spondylitis (AS). Plain radiography (PR) is widely used for the diagnosis of ALs. However, in our practice, there were some ALs in AS patients that could not be detected on plain radiographs. This study aimed to propose the concept of occult ALs and evaluate the prevalence and radiographic characteristics of the occult ALs in AS patients.Methods:A total of 496 consecutive AS patients were admitted in the Affiliated Drum Tower Hospital, Medical School of Nanjing University between April 2003 and November 2019 and they were retrospectively reviewed. The AS patients with ALs who met the following criteria were included for the investigation of occult ALs: (1) with pre-operative plain radiographs of the whole-spine and (2) availability of pre-operative computed tomography (CT) and/or magnetic resonance imaging (MRI) of the whole-spine. The occult ALs were defined as the ALs which were undetectable on plain radiographs but could be detected by CT and/or MRI. The extensive ALs involved the whole discovertebral junction or manifested as destructive lesions throughout the vertebral body. Independent-samples t test was used to compare the age between the patients with only occult ALs and those with only detectable ALs. Chi-square or Fisher exact test was applied to compare the types, distribution, and radiographic characteristics between detectable and occult ALs as appropriate.Results:Ninety-two AS patients with a mean age of 44.4 ± 10.1 years were included for the investigation of occult ALs. Twenty-three patients had occult ALs and the incidence was 25% (23/92). Fifteen extensive ALs were occult, and the proportion of extensive ALs was significantly higher in detectable ALs (97% vs. 44%, χ² = 43.66, P < 0.001). As assessed by PR, the proportions of osteolytic destruction with reactive sclerosis (0 vs. 100%, χ² = 111.00, P < 0.001), angular kyphosis of the affected discovertebral units or vertebral body (0 vs. 22%, χ² = 8.86, P = 0.003), formation of an osseous bridge at the intervertebral space adjacent to ALs caused by the ossification of the anterior longitudinal ligament (38% vs. 86%, χ² = 25.91, P < 0.001), and an abnormal height of the affected intervertebral space were all significantly lower in occult ALs (9% vs. 84%, χ² = 60.41, P < 0.001).Conclusions:Occult ALs presented with more subtle radiographic changes. Occult ALs should not be neglected, especially in the case of extensive occult ALs, because the stability of the spine might be severely impaired by these lesions.     

Increased risk of cardio-cerebrovascular disease after hematopoietic cell transplantation in patients with previous history

Background:The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes.Methods:A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs).Results:The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88–40.30, P < 0.001), which was an independent risk factor for increased NRM (HR: 10.29, 95% CI: 3.84–27.62, P < 0.001) and inferior OS (HR: 10.29, 95% CI: 3.84–27.62, P < 0.001).Conclusions:These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure, leading to a risk of post-CCVD. Post-CCVD was a powerful predictor for high NRM and inferior OS. Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.     

Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma

BackgroundThe mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC.MethodsWe performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III–IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS).ResultsThe expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=−2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=−2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = −2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = −2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019).ConclusionsCD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.     

Performance and comparison of assessment models to predict 30-day mortality in patients with hospital-acquired pneumonia

BackgroundHospital-acquired pneumonia (HAP) is the most common hospital-acquired infection in China with substantial morbidity and mortality. But no specific risk assessment model has been well validated in patients with HAP. The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.MethodsThis study was a single-center, retrospective study. In total, 223 patients diagnosed with HAP from 2012 to 2017 were included in this study. Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index (PSI); consciousness, urea nitrogen, respiratory rate, blood pressure, and age ≥65 years (CURB-65); Acute Physiology and Chronic Health Evaluation II (APACHE II); Sequential Organ Failure Assessment (SOFA); and Quick Sequential Organ Failure Assessment (qSOFA) scores. The discriminatory power was tested by constructing receiver operating characteristic (ROC) curves, and the areas under the curve (AUCs) were calculated.ResultsThe all-cause 30-day mortality rate was 18.4% (41/223). The PSI, CURB-65, SOFA, APACHE II, and qSOFA scores were significantly higher in non-survivors than in survivors (all P < 0.001). The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores (ROC AUC: APACHE II vs. CURB-65, 0.863 vs. 0.744, Z = 3.055, P = 0.002; APACHE II vs. qSOFA, 0.863 vs. 0.767, Z = 3.017, P = 0.003; SOFA vs. CURB-65, 0.856 vs. 0.744, Z = 2.589, P = 0.010; SOFA vs. qSOFA, 0.856 vs. 0.767, Z = 2.170, P = 0.030). The cut-off values we defined for the SOFA, APACHE II, and qSOFA scores were 4, 14, and 1.ConclusionsThese results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments. The qSOFA score may be a simple tool that can be used to quickly identify severe infections.     

Association between serum bilirubin concentration and Parkinson's disease: a meta-analysis

Background:The antioxidant effects of bilirubin in Parkinson''s disease (PD) have recently gained much attention from the research community. However, results from these studies have been conflicting. This meta-analysis is conducted to assess the relationship between the serum bilirubin concentration and the risk of PD.Methods:Two reviewers performed a systematic literature search across five databases (MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials). The case-control studies regarding bilirubin levels in PD patients published up to April 2020 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the standard mean difference (SMD) and the 95% confidence interval (CI), which were analyzed using the Stata V.12.0 statistical software.Results:A total of eight studies which included 1463 PD cases and 1490 controls were incorporated into our meta-analysis. SMD analysis showed that there was a higher total bilirubin (TBIL) and direct bilirubin (DBIL) levels in PD patients compared with controls (for TBIL, SMD: 0.300, 95% CI: 0.050–0.549, P = 0.018; for DBIL, SMD: 0.395, 95% CI: 0.102–0.688, P = 0.008). However, no significant relationship was found between the serum indirect bilirubin and PD patients (SMD: −0.223, 95% CI: −0.952–0.505, P = 0.548). A subgroup analysis based on ethnicity indicated that the serum TBIL was higher in PD patients of Caucasian descent in contrast to matched healthy controls (SMD: 0.511, 95% CI: 0.324–0.698, P = 0.000, I² = 58.0%).Conclusion:Higher serum bilirubin levels in PD patients suggest that bilirubin might play a role in the pathogenesis of PD and have the potential to be utilized as a biochemical marker for PD diagnosis and treatment.     

Risk factors associated with osteoporosis and fracture in psoriatic arthritis

Background:Although there are few studies mentioned there may be some relationship between psoriatic arthritis (PsA) and osteoporosis, clinical data in real world still need to be clarified in China. The aim of this study was to assess the areal and volumetric bone mineral density (BMD), frequency of fracture, and risk factors in patients with PsA.Methods:A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age- and sex-matched healthy controls with DXA data were enrolled in the study. Patients with clinical fractures confirmed by X-ray during follow-up were also recorded. Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group, as well as between the fracture and non-fracture groups. Risk factors for fracture and low BMD were analyzed.Results:Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls (0.809 ± 0.193 vs. 0.901 ± 0.152 g/cm², P = 0.041; 0.780 ± 0.146 vs. 0.865 ± 0.166 g/cm², P = 0.037, respectively). Moreover, lumbar spine BMD was negatively correlated with psoriasis duration, swollen joint count and DAS28-CRP (r = –0.503, –0.580, –0.438; P < 0.05). Total hip BMD and femoral neck BMD were negatively correlated with HAQ (r = –0.521, –0.335; P < 0.05). Fractures occurred in 29 patients during the follow-up period. Logistic regression analysis showed that older age (OR 1.132 [95%CI: 1.026–1.248), P < 0.05], higher HAQ score (OR 1.493, 95%CI: 1.214–1.836, P < 0.01), higher disease activity index for psoriatic arthritis (OR 1.033, 95% CI: 1.002–1.679, P < 0.05) and hip joint involvement (OR 6.401, 95% CI: 4.012–44.180, P < 0.05) were risk factors for fracture in the multivariate model.Conclusions:Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls. Besides age, high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.     

Risk factors for gastric cancer: a large-scale,population-based case-control study

Background:Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC.Methods:Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI).Results:A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219–0.599, P < 0.001), overweight/obesity (BMI ≥24 kg/m²; OR = 0.489, 95% CI = 0.329–0.726, P < 0.001), cigarette smoking (OR = 3.069, 95% CI = 1.700–5.540, P < 0.001), alcohol consumption (OR = 1.661, 95% CI = 1.028–2.683, P = 0.038), history of stomach disease (OR = 6.917, 95% CI = 4.594–10.416, P < 0.001), and family history of GC in first-degree relatives (OR = 4.291, 95% CI = 1.661–11.084, P = 0.003) were significantly correlated with the occurrence of GC. Subgroup analyses by age and gender indicated that GC risk was still increased in the presence of a history of stomach disease. A history of chronic gastritis, gastric ulcer, or gastric polyposis was positively associated with GC, with adjusted ORs of 4.155 (95% CI = 2.711–6.368), 1.839 (95% CI = 1.028–3.288), and 2.752 (95% CI = 1.197–6.326).Conclusions:Subjects who smoke, drink, with history of stomach disease and family history of GC in first-degree relatives are the high-risk populations for GC. Therefore, attention should be paid to these subjects for GC screening.     

In vitro fertilization-embryo transfer in patients with unexplained recurrent pregnancy loss

Background:Empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age. The clinical outcomes of URPL patients who have undergone in vitro fertilization-embryo transfer (IVF-ET) require elucidation. The IVF outcome and influencing factors of URPL patients need further study.Methods:A retrospective cohort study was designed, and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included. By comparing clinical outcomes between these patients and those with tubal factor infertility (TFI), the factors affecting the clinical outcomes of URPL patients were analyzed.Results:The clinical pregnancy rate (35.18% vs. 34.52% in fresh ET cycles, P = 0.877; 34.48% vs. 40.27% in frozen-thawed ET cycles, P = 0.283) and live birth rate (LBR) in fresh ET cycles (27.67% vs. 26.59%, P = 0.785) were not significantly different between URPL group and TFI group. URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group (23.56% vs. 33.56%, P = 0.047), but the cumulative LBRs (34.69% vs. 38.26%, P = 0.368) were not significantly different between the two groups. The increased endometrial thickness (EMT) on the human chorionic gonadotropin day (odds ratio [OR]: 0.848, 95% confidence interval [CI]: 0.748–0.962, P = 0.010) and the increased number of eggs retrieved (OR: 0.928, 95% CI: 0.887–0.970, P = 0.001) were protective factors for clinical pregnancy in stimulated cycles. The increased number of eggs retrieved (OR: 0.875, 95% CI: 0.846–0.906, P < 0.001), the increased two-pronucleus rate (OR: 0.151, 95% CI: 0.052–0.437, P < 0.001), and increased EMT (OR: 0.876, 95% CI: 0.770–0.997, P = 0.045) in ET day were protective factors for the cumulative live birth outcome.Conclusion:After matching ages, no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI. A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles, but a better normal fertilization potential will increase the possibility of a live birth.     

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China

Background:Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.Methods:We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI.Results:The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56–4.52, P < 0.001), low body mass index (BMI) (OR 0.91, 95% CI 0.84–0.98, P = 0.013), not being married (OR 0.29, 95% CI 0.17–0.49, P < 0.001), history of myocardial infarction (MI) (OR 2.59, 95% CI 1.33–5.04, P = 0.005), higher heart rate (HR) (OR 1.02, 95% CI 1.01–1.03, P = 0.002), cardiac shock in the ED (OR 5.03, 95% CI 1.48–17.08, P = 0.010), pre-hospital delay (>12 h) (OR 3.31, 95% CI 1.83–6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27–0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals.Conclusions:Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.     

Safety of early surgery for geriatric hip fracture patients taking clopidogrel: a retrospective case-control study of 120 patients in China

Background:Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal.Methods:Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued <5 days before surgery constituted the clopidogrel group. The control group constituted 60 patients not taking antiplatelet or anticoagulant drugs and matched 1:1 with the clopidogrel group for sex, fracture type, operative procedure, and time from injury to operation (±10 h). The primary outcome was perioperative blood loss and the secondary outcomes were transfusion requirement, complications, and mortality. The Student''s t test or Wilcoxon signed rank sum test was used for continuous variables and the Chi-square test was used for categorical variables.Results:Age, body mass index, American Society of Anesthesiologists score, and percentage undergoing general anesthesia were comparable between the groups (P > 0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P < 0.001) and cerebrovascular disease (45.0% vs. 15.0%; P < 0.010) were significantly higher in the clopidogrel vs. control groups, respectively. The median clopidogrel discontinuation time before operation was 73.0 (range: 3.0–120.0) h. There was no significant difference in the estimated perioperative blood loss between the clopidogrel group (median: 745 mL) and control group (median: 772 mL) (P = 0.866). The intra-operative transfusion rate was higher in the clopidogrel group (22/60, 36.7%) than that in the control group (12/60, 20.0%) (P < 0.050). However, there was no significant difference in the blood transfusion rate during the entire perioperative period (26/60, 43.3% vs. 20/60, 33.3%; clopidogrel group vs. control group, respectively; P > 0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups.Conclusions:Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.