2022年 · 第135卷第02期

Asymptomatic or symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be followed by reinfection. The protection conferred by prior infection among coronavirus disease 2019 (COVID-19) patients is unclear. We assessed the incidence of SARS-CoV-2 reinfection and the protection effect of previous infection against reinfection.

We searched PubMed, EMBASE, Cochrane, Scopus, Web of Science, and ClinicalTrials.gov for publications up until the end date of May 1, 2021. The reinfection rate of recovered patients and the protection against reinfection were analyzed using meta-analysis.

Overall, 19 studies of 1096 reinfection patients were included. The pooled reinfection rate was 0.65% (95% confidence interval [CI] 0.39-0.98%). The symptomatic reinfection rate was a bit lower (0.37% [95% CI 0.11-0.78%], I² = 99%). The reinfection rate was much higher in high-risk populations (1.59% [95% CI 0.30-3.88%], I²= 90%). The protection against reinfection and symptomatic reinfection was similar (87.02% [95% CI 83.22-89.96%] and 87.17% [95% CI 83.09-90.26%], respectively).

The rate of reinfection with SARS-CoV-2 is relatively low. The protection against SARS-CoV-2 after natural infection is comparable to that estimated for vaccine efficacy. These data may help guide public health measures and vaccination strategies in response to the COVID-19 pandemic. High-quality clinical studies are needed to establish the relevant risk factors in recovered patients.

Physical therapy is regarded as an essential aspect in achieving optimal outcomes following total knee arthroplasty (TKA). The coronavirus disease 2019 (COVID-19) pandemic has made face-to-face rehabilitation inaccessible. Virtual reality (VR) is increasingly regarded as a potentially effective option for offering health care interventions. This systematic review and meta-analysis investigate VR-based rehabilitation’s effectiveness on outcomes following TKA.

From inception to May 22, 2021, PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Scopus, PsycINFO, Physiotherapy Evidence Database, China National Knowledge Infrastructure, and Wanfang were comprehensively searched to identify randomized controlled trials (RCTs) evaluating the effect of VR-based rehabilitation on patients following TKA according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions.

Eight studies were included in the systematic review, and seven studies were included in the meta-analysis. VR-based rehabilitation significantly improved visual analog scale (VAS) scores within 1 month (standardized mean difference [SMD]: -0.44; 95% confidence interval [CI]: -0.79 to -0.08, P = 0.02), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) within 1 month (SMD: -0.71; 95% CI: -1.03 to -0.40, P < 0.01), and the Hospital for Special Surgery Knee Score (HSS) within 1 month and between 2 months and 3 months (MD: 7.62; 95% CI: 5.77 to 9.47, P < 0.01; MD: 10.15; 95% CI: 8.03 to 12.27, P < 0.01; respectively) following TKA compared to conventional rehabilitation. No significant difference was found in terms of the Timed Up and Go (TUG) test.

VR-based rehabilitation improved pain and function but not postural control following TKA compared to conventional rehabilitation. More high-quality RCTs are needed to prove the advantage of VR-based rehabilitation. As the COVID-19 pandemic continues, it is necessary to promote this rehabilitation model.

Postoperative chylous ascites is an infrequent condition after colorectal surgery and is easily treatable. However, its effect on the long-term oncological prognosis is not well established. This study aimed to investigate the short-term and long-term impact of chylous ascites treated with neoadjuvant therapy followed by rectal cancer surgery and to evaluate the incidence of chylous ascites after different surgical approaches.

A total of 898 locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery between January 2010 and December 2018 were included. The clinicopathological data and outcomes of the patients with chylous ascites were compared with those of the patients without chylous ascites. The primary endpoint was recurrence-free survival (RFS). To balance baseline confounders between groups, propensity score matching (PSM) was performed for each patient with a logistic regression model.

Chylous ascites was detected in 3.8% (34/898) of the patients. The incidence of chylous ascites was highest after robotic surgery (6.9%, 6/86), followed by laparoscopic surgery (4.2%, 26/618) and open surgery (1.0%, 2/192, P = 0.021). The patients with chylous ascites had a significantly higher number of lymph nodes harvested (15.6 vs. 12.8, P = 0.009) and a 3-day longer postoperative hospital stay (P = 0.017). The 5-year RFS rate was 64.5% in the chylous ascites group, which was significantly lower than the rate in the no chylous ascites group (79.9%; P = 0.007). The results remained unchanged after PSM was performed. The chylous ascites group showed a nonsignificant trend towards a higher peritoneal metastasis risk (5.9% vs. 1.6%, P = 0.120). Univariate analysis and multivariate analysis confirmed chylous ascites (hazard ratio= 3.038, P < 0.001) as an independent negative prognostic factor for RFS.

Considering the higher incidence of chylous ascites after laparoscopic and robotic surgery and its adverse prognosis, we recommend sufficient coagulation of the lymphatic tissue near the vessel origins, especially during minimally invasive surgery.

Acute kidney injury (AKI) is a common and serious complication following lung transplantation (LTx), and it is associated with high mortality and morbidity. This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.

This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019. The outcomes were AKI incidence, risk factors, mortality, and kidney recovery. Multivariate analysis was performed to identify independent risk factors. Survival analysis was presented using the Kaplan-Meier curves.

AKI occurred in 137 of the 191 patients (71.7%), with transient AKI in 43 (22.5%) and persistent AKI in 94 (49.2%). AKI stage 1 occurred in 27/191 (14.1%), stage 2 in 46/191 (24.1%), and stage 3 in 64/191 (33.5%) of the AKI patients. Renal replacement therapy (RRT) was administered to 35/191 (18.3%) of the patients. Male sex, older age, mechanical ventilation (MV), severe hypotension, septic shock, multiple organ dysfunction (MODS), prolonged extracorporeal membrane oxygenation (ECMO), reintubation, and nephrotoxic agents were associated with AKI (P < 0.050). Persistent AKI was independently associated with preoperative pulmonary hypertension, severe hypotension, post-operative MODS, and nephrotoxic agents. Severe hypotension, septic shock, MODS, reintubation, prolonged MV, and ECMO during or after LTx were related to severe AKI (stage 3) (P < 0.050). Patients with persistent and severe AKI had a significantly longer duration of MV, longer duration in the intensive care unit (ICU), worse downstream kidney function, and reduced survival (P < 0.050).

AKI is common after LTx, but the pathogenic mechanism of AKI is complicated, and prerenal causes are important. Persistent and severe AKI were associated with poor short- and long-term kidney function and reduced survival in LTx patients.

Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation.

HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.

In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806).

According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.

In-hospital mortality in patients with coronavirus disease 2019 (COVID-19) is high. Simple prognostic indices are needed to identify patients at high-risk of COVID-19 health outcomes. We aimed to determine the usefulness of the CONtrolling NUTritional status (CONUT) index as a potential prognostic indicator of mortality in COVID-19 patients upon hospital admission.

Our study design is of a retrospective observational study in a large cohort of COVID-19 patients. In addition to descriptive statistics, a Kaplan-Meier mortality analysis and a Cox regression were performed, as well as receiver operating curve (ROC).

From February 5, 2020 to January 21, 2021, there was a total of 2969 admissions for COVID-19 at our hospital, corresponding to 2844 patients. Overall, baseline (within 4 days of admission) CONUT index could be scored for 1627 (57.2%) patients. Patients’ age was 67.3 ± 16.5 years and 44.9% were women. The CONUT severity distribution was: 194 (11.9%) normal (0-1); 769 (47.2%) light (2-4); 585 (35.9%) moderate (5-8); and 79 (4.9%) severe (9-12). Mortality of 30 days after admission was 3.1% in patients with normal risk CONUT, 9.0% light, 22.7% moderate, and 40.5% in those with severe CONUT (P < 0.05). An increased risk of death associated with a greater baseline CONUT stage was sustained in a multivariable Cox regression model (P < 0.05). An increasing baseline CONUT stage was associated with a longer duration of admission, a greater requirement for the use of non-invasive and invasive mechanical ventilation, and other clinical outcomes (all P < 0.05). The ROC of CONUT for mortality had an area under the curve (AUC) and 95% confidence interval of 0.711 (0.676-0746).

The CONUT index upon admission is potentially a reliable and independent prognostic indicator of mortality and length of hospitalization in COVID-19 patients.

Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells (CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells.

BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells. Tumor growth and pulmonary metastasis were assessed. ALDEFLOUR^TM assays were performed to identify aldehyde dehydrogenase^bright (ALDH^br) tumor cells. ALDH^br cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry. The effects of CD8⁺ T cells on ALDH^br tumor cells were assessed in vitro and in vivo. The expression profiles of ALDH^br and ALDH^dim 4T1 tumor cells were determined. The levels of plasma IFN-γ were measured by enzyme-linked immunosorbent assay, and their associations with the percentages of ALDH^br tumor cells were evaluated. The effects of IFN-γ on ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro.

There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice (25.40 vs. 54.67, P < 0.050). CD8⁺ T cells decreased the percentages of ALDH^br 4T1 tumor cells in vitro (control vs. effector to target ratio of 1:1, 10.15% vs. 5.76%, P < 0.050) and in vivo (control vs. CD8⁺ T cell depletion, 10.15% vs. 21.75%, P < 0.001). The functions of upregulated genes in ALDH^br 4T1 tumor cells were enriched in the pathway of response to IFN-γ. The levels of plasma IFN-γ decreased gradually in tumor-bearing BALB/c mice, while the percentages of ALDH^br tumor cells in primary tumors increased. IFN-γ at a concentration of 26.68 ng/mL decreased the percentages of ALDH^br 4T1 tumor cells (22.88% vs. 9.88%, P < 0.050) and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells (0.86 vs. 0.49, P < 0.050) and inhibited the abilities of sphere formation (sphere diameter <200 μm, 159.50 vs. 72.0; ≥200 μm, 127.0 vs. 59.0; both P < 0.050) and invasion (89.67 vs. 67.67, P < 0.001) of 4T1 tumor cells.

CD8⁺ T cells and IFN-γ decreased CSC numbers in a 4T1 mouse model of breast cancer. The application of IFN-γ may be a potential strategy for reducing CSCs in breast cancer.

Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS’s response to SD.

Middle-aged wild-type (WT) C57BL/6 and CX3CR1^-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes.

CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1^-/- S group, the CX3CR1^-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted.

These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

The term of interstitial pneumonia with autoimmune features (IPAF), based on a combination of clinical, serological, and morphological domains (specific chest imaging features, histopathological features, or multi-compartment involvement, including non-specific interstitial pneumonia [NSIP], organizing pneumonia, NSIP with organizing pneumonia overlap and lymphoid interstitial pneumonia), is proposed to describe patients with interstitial lung disease (ILD) and clinical features indicative of connective tissue disease (CTD) but not meeting established CTD classification criteria.^[1]However, the usual interstitial pneumonia (UIP) pattern in chest high-resolution computed tomography (HRCT) is not included in IPAF morphological domain, thereby patients with UIP and positive autoantibodies without one of the seven symptoms in the IPAF clinical domain were excluded from IPAF and presumably are considered to have "idiopathic pulmonary fibrosis (IPF)" .^[1]Long-term follow-up studies are lacking now, particularly, few studies had described clinical characteristics and radiologic appearances of IPF patients with positive antibodies with or without extra-pulmonary syndromes. As autoantibodies are present in about 22% of patients with IPF,^[2]do the positive autoantibodies have clinical significance? Or do IPF patients with positive or negative autoantibodies have similar disease behaviors or survival outcomes? It is necessary to conduct a long-term follow-up study in patients with IPF with or without antibodies. We conducted this 9-year retrospective study in an ILD center of China to compare clinical characteristics, radiological findings, and long-term transplant-free survival between IPF patients with or without autoantibodies.

Allergic rhinitis (AR) is a costly and highly prevalent chronic disease now.^[1]More seriously, many patients with AR also have allergic asthma (AA). The presence of AR is a risk factor for the development of AA.^[2]Moreover, AA is still a significant cause of mortality for all ages.^[3]Therefore, predicting and preventing AA can reduce accidental death, severe health hazards, and the society’s enormous economic burden.

Aneurysmal subarachnoid hemorrhage (aSAH) is a typical neurosurgical emergency. The patient’s prognosis is related to the severity of the initial illness and post-operative complications, especially delayed cerebral ischemia (DCI). DCI, which occurs in up to 30% of patients with subarachnoid hemorrhage (SAH), usually 2 weeks after hemorrhage, is one of the leading causes of death and disability in aSAH. Currently, it is generally accepted that DCI is primarily associated with cerebral vasospasm (CVS). However, after aggressive anti-CVS therapy, a subset of patients still develop DCI, suggesting that CVS is not the entire DCI cause.^[1]

Papillary thyroid carcinoma (PTC) is the most common type (accounting for over 80%) of thyroid cancer.^[1]Although PTC is a well-differentiated endocrine neoplasm, unfortunately, certain PTCs show malignant characteristics such as aggressiveness and metastasis; these characteristics contribute to a poor 5-year survival rate.^[1]However, the fundamental molecular mechanism of extra-thyroid metastasis remains unclear.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a newly discovered coronavirus and has rapidly spread to most of the world and resulted in a global pandemic. However, there is a paucity of information available to characterize the immunodeficient population in the COVID-19 pandemic, especially information that focuses on patients after renal transplantation as the typical representative of this population. Understanding the susceptibility, clinic characteristics, treatment strategy, and prognosis of this population is of substantial importance for the management of immunodeficient patients in the pandemic.

Anterior cruciate ligament (ACL) tear is a common disease among sports-medicine outpatients. To restore static and dynamic stability as well as kinematics in an ACL injured knee, accurate position of the femoral and tibial tunnel plays an important role in ACL reconstruction, especially the femoral tunnel.^[1]Some studies have attempted to maximize functional outcome of anteriomedial (AM) and posterolateral (PL) bundles by reconstructing ACL in the center of the entire femoral footprint^[2,3]; however, instability persists after operation. Therefore, various studies concluded that single bundle and double bundle techniques could yield similar efficacy in ACL reconstruction.^[4]

To the Editor: Due to the immunogenicity of the platelet antigens, especially blood group antigen (such as ABO antigens), human leukocyte antigen (HLA), human platelet antigen (HPA), and CD36 (platelet glycoproteins IV), which can produce corresponding alloantibodies through immune factors such as blood transfusion, pregnancy, and drugs, the immune reaction of the platelet antigens and antibodies in patients will lead to various types of alloimmune thrombocytopenia, including the immune platelet transfusion refractoriness, post-transfusion purpura, and fetal/neonatal alloimmune thrombocytopenia.^[1,2,3,4]Platelet transfusion is an effective approach to treat alloimmune thrombocytopenia. Antigen-negative platelets (platelets lacking certain antigens that do not react with the alloantibodiesin vivo) are the keys to avoid related alloimmune reactions and achieve satisfactory treatment outcomes of platelet transfusion.^[1]To this end, establishing a complete platelet donor database (PDD) that has a suitable number of donors with the known platelet antigens or antigen genotypes and meets the characteristics of platelet immunohematology in the local population is the effective way for the patients with alloimmune thrombocytopenia to quickly find out the antigen-matched platelet donors.

To the Editor:Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory condition. Malignant HLH (M-HLH) is one of the most common types of secondary HLH (sHLH), especially in adults. HLH can occur either as the initial manifestation of malignant disease (here referred to as "malignancy-triggered HLH" ) or in the setting of iatrogenic immunosuppression from chemotherapy ( "HLH during chemotherapy" or Ch-HLH).^[1]In the majority of cases, HLH during chemotherapy develops in association with triggering infections that occur as the result of chemotherapy-induced immunosuppression.^[2]Bacteria, fungi, and viruses can all contribute to it. Patients with M-HLH and Ch-HLH show very poor survival with a median overall survival of 0.9 to 1.2 years and 6-month survival rates of 67% and 63%, respectively, as reported previously.^[3]No consensus has been reached on the treatment of Ch-HLH, which ranges from postponing subsequent chemotherapeutic blocks to aggressive HLH-directed therapy based on etoposide.^[1]The JAK1/2 (Janus Kinase 1/2) inhibitor ruxolitinib exhibits potential effectiveness in the treatment of HLH by suppressing inflammatory factor storms through inhibition of the JAK-signal transducer and activator of transcription (STAT) pathway, and its efficacy has been demonstrated in the HLH mouse model and some clinical cases.^[4]Here, we report a rare case of the use of ruxolitinib in Epstein-Barr virus (EBV)-associated HLH during the treatment course of acute myelocytic leukemia (AML).

To the Editor: Cortisol is closely related to hemostasis.^[1]In patients with hyperadrenalism, that is, Cushing syndrome (CS), a reduction in the activated partial thromboplastin time (APTT), an increased level of coagulation factors, and an increased risk of thrombosis have been repeatedly reported.^[1,2]However, no studies reported the hemostatic status of patients with hypoadrenalism which is commonly seen in patients with pituitary diseases.

To the Editor:Alterations of circadian rhythms seem to be the casual contribution to sleep disturbances, depression, and other non-motor symptoms in Parkinson’s disease (PD).^[1,2]By restoring the circadian rhythm, bright light therapy (BLT) might be a potentially new treatment option for PD. However, no studies have conclusively demonstrated the effects of BLT on the non-motor symptoms in PD.

To the Editor:Nephrotic syndrome (NS) is a common clinical syndrome characterized by massive proteinuria and hypoalbuminemia, but it has never been investigated in the Tibetan population. This was a single-center, retrospective study of Tibetan patients who underwent renal biopsy from 2009 to 2016 in West China Hospital of Sichuan University. All patients aged over 14 years were included. Exclusion criteria were insufficient pathological material, transplant kidney biopsies, and pregnancy. Renal pathological characteristics were defined according to the World Health Organization standards and histological glomerular disease classification protocols. Quantitative and qualitative data are expressed as mean ± standard deviation and percentages, respectively. Student’sttests or Mann-Whitney tests were used to compare parametric or nonparametric continuous variables, respectively.χ²and Fisher exact tests were used to compare qualitative variables. All statistics were analyzed by SPSS 23.0 software (SPSS Inc., Chicago, IL, USA);P< 0.05 was considered statistically significant.

To the Editor: Aging can cause changes in human metabolic capacity^[1]and metabolic syndrome is one of the important causes of type 2 diabetes mellitus (T2DM). In recent years, T2DM has become one of the top ten killers of humans.^[2]T2DM has been reported in ≥25% of the population aged over 65 years.^[3]The liver is the most important metabolic center and its metabolic disorders are associated with T2DM.^[4]However, studies on liver metabolic disorders in older adult patients with T2DM are limited. Therefore, it is necessary to analyze liver metabolism in these patients in combination with modern omics methods. In this study, we integrated metabonomics and transcriptomics analyses to analyze the specific metabolites and genes that change in the liver of aging mice with T2DM, and to provide a theoretical basis for the treatment of older adult patients with T2DM.

To the Editor: Multiple myeloma (MM) is currently considered to be an incurable neoplasm and a systemic disease, and the first line of treatment plays a crucial role in MM patients, since the majority of patients do not survive beyond the first-line treatment.^[1]Lenalidomide, a first-line drug in the treatment of MM, is sold as a capsule under the trade name Revlimid^®, which is in great demand for an increasing incidence of MM. Additionally, there is little or no pharmacokinetic (PK) data pertaining to lenalidomide in Chinese MM patients, with most PK trials on lenalidomide being conducted on young healthy volunteers. This study was conducted to compare the PKs and bioequivalence of generic lenalidomide 10 mg capsule (batch No. 1308010) manufactured by Chongqing LUMMY Pharmaceutical Co., Ltd. (Chongqing, China) with Revlimid® 10 mg capsule (batch No. A0263BA), an original lenalidomide drug, manufactured by Celgene International Sarl (Boudry, Switzerland); the comparison was carried out in Chinese patients with MM, to provide an economical alternative to the branded lenalidomide for patients.