2022年 · 第135卷第14期

Chimeric antigen receptor T-cell (CAR-T) therapy has greatly improved the disease remission rate and long-term survival rate of patients with relapsed/refractory hematological malignancies.^[1,2,3]Currently, several commercial CAR-T products are available in the market and numerous CAR-T clinical trials have been conducted. Attention should be paid to the safety of CAR-T therapy. The main adverse effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).^[4]Moreover, CAR-T therapy-associated coagulopathy (CARAC) is also prominent [Supplementary Table 1, http://links.lww.com/CM9/B173]. Among the patients with hematological malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma, and multiple myeloma (MM), more than half of them experienced thrombocytopenia or showed at least one abnormal coagulation parameter after CAR-T therapy. Approximately 19.6% of coagulopathy patients experienced clinically significant bleeding and 14% to 50% of coagulopathy patients further developed disseminated intravascular coagulation (DIC); 6.7% to 42.9% of DIC patients died. The current international grading criteria and treatment guidelines for CAR-T therapy-related adverse events only focus on CRS and ICANS, while CARAC has not been systematically summarized. To standardize the management of CARAC and to promote the safe application of CAR-T therapy, experts from Thrombosis and Hemostasis Group and Biotherapeutics Committee formulated this consensus based on worldwide clinical experience and research progress (detailed information was in the Supplementary File, http://links.lww.com/CM9/B173).

The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD.

A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.

Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09–30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55–31.43). NAFLD has become more prevalent during the year 2011–2021 (31.63%, 95% CI 30.23–33.04) compared with year 2000–2010 (27.94%, 95% CI 26.23–29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13–21.01), 46.49% (95% CI 35.93–57.20), and 46.72% (95% CI 37.57–55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21–49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90–2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55–37.18) death per 1000 person-years.

The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.

PROSPERO, No. CRD42020171104.

Gut microbiota-derived metabolites influence host physiology and pathology, where short-chain fatty acids (SCFAs) are the main class of gut microbiota-derived metabolites.^[1]SCFAs are fatty acids containing 1 to 6 carbon atoms, including acetate, propionate, butyrate, and pentanoate, which provide 6% to 10% of the body’s total daily energy and 60% to 70% of the colonic epithelial energy needed.^[2]Anaerobic bacteria principally generate the SCFAs^[1]in the intestine. Once produced, SCFAs are mainly absorbed in the colon (90%–95%), reach circulation, and play roles for distal organs and tissues.^[2]

Vitiligo is an autoimmune skin disorder characterized by white patches of the skin losing functional epidermal melanocytes. Progressive depigmentation of the skin impairs patients’ quality of life badly. More than 80% of patients with vitiligo have bilateral symmetric patterns of depigmentation, which is classified as nonsegmental vitiligo. However, few research revealed the cellular and molecular mechanisms that orchestrate the patterned activities of cutaneous immune cells in vitiligo patients. Understanding what orchestrates the activities of cutaneous immune cells is essential for determining the therapeutic targets of the disease.

Gallbladder and biliary tract cancer (GBTC) has greatly damaged the health of patients and is accompanied by a dismal prognosis. The worldwide distribution of GBTC shows extensive variance and the updated data in China is lacking. This study was to determine the current status, trends, and predictions in the burden of GBTC over the past 30 years in China.

This was a descriptive, epidemiological, secondary analysis of the Global Burden of Disease, Injuries, and Risk Factor Study 2019 data. Data including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of GBTC in China by year, age, and sex were assessed. Joinpoint regression analysis was conducted to evaluate trends of disease burden due to GBTC from 1990 to 2019. Nordpred age-period-cohort analysis was applied for the projection of mortality and incidence due to GBTC from 2019 to 2044.

Nationally, there were 38,634 (95% uncertainty interval [UI]: 27,350–46,512) new cases and 47,278 (95% UI: 32,889–57,229) patients due to GBTC, causing 34,462 (95% UI: 25,220–41,231) deaths, and 763,584 (95% UI: 566,755–920,493) DALYs in 2019. Both cases and rates of burden owing to GBTC were heavier among males and at old age. From 1990 to 2019, the age-standardized rates of incidence, prevalence, mortality, and DALYs of GBTC generally increased from 1990 to 2019, with average annual percentage change at 0.8% (95% confidential interval [CI]: 0.6–1.0%), 1.3% (95% CI: 1.1–1.5%), 0.4% (95% CI: 0.2–0.6%), and 0.2% (95% CI: 0.1–0.4%), respectively. Even though the age-standardized incidence rate and age-standardized mortality rate in both sexes were predicted to decline gradually from 2019 to 2044, the number of new cases and deaths were expected to grow steadily.

GBTC is becoming a major health burden in China, particularly among males and older individuals. Given the aging population and increasing burden, effective strategies and measurements are urged to prevent or reduce the number of new cases and deaths of GBTC.

High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.

This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.

A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (–9.19% in the ITT analysis, –9.21% in the MITT analysis, and –9.73% in the PP analysis) was greater than the predefined non-inferiority margin of –10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.

Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.

Clinicaltrials.gov, NCT04678492.

As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin.

Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses.

Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera (Enterobacter and Enterococcus) are unaffected by rifaximin therapy.

IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.

Chinese Clinical Trial Registry, ChiCTR1800017911.

The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-encoding gene, however, is frequently mutated or deleted as the cancer progresses to the late stage and, under such circumstance, the p53 homolog TAp63 can harness HCC growth by transactivating several important p53-target genes.

To determine whether HBx regulates TAp63, we performed co-immunoprecipitation assay, real-time quantitative polymerase chain reaction, immunoblotting, and flow cytometry analysis in p53-null cancer cell lines, Hep3B and H1299.

HBx interacts with the transactivation domain of TAp63, as HBx was co-immunoprecipitated with TAp63 but not with ΔNp63. The interaction between HBx and TAp63 abolished transcriptional activity of TAp63, as evidenced by the reduction of the levels of its target genes p21 and PUMA, consequently leading to restricted apoptosis and augmented proliferation of HCC cells.

HBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63.

This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive (ER+) metastatic breast cancer in routine clinical practice.

The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially for various combination regimens. The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed.

A total of 186 patients from 89 cities in 18 provinces in China were enrolled. The median progression-free survival (PFS) was similar among different palbociclib-combined groups (P = 0.566): 10.0 months (95% confidence interval [CI] 3.8–16.1) in the +exemestane group, 9.7 months (95% CI 6.3–13.1) in the +letrozole group, 7.8 months (95% CI 5.5–10.2) in the +fulvestrant group, 7.2 months (95% CI 3.2–11.3) in the +toremifene group, and 6.1 months (95% CI 1.2–11.0) in the +anastrozole group. Thirty-four patients (18.3%) had received everolimus for their metastatic disease before the prescription of palbociclib. The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group (50.0% vs. 82.2%, P < 0.001). Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group (3.4 months vs. 8.8 months, P = 0.001). After propensity score matching, patients pre-treated with everolimus had similar PFS (4.4 months, 95% CI 0.5–8.2) compared with everolimus-naïve patients (6.1 months, 95% CI 4.7–7.5, P = 0.439).

Various palbociclib-based regimens have promising efficacy in ER+ metastatic breast cancer in real-world settings, even in patients who had been pre-treated with everolimus.

Joint dislocations significantly impact public health. However, a comprehensive study on the incidence, distribution, and risk factors for joint dislocations in China is lacking. We conducted the China National Joint Dislocation Study, which is a part of the China National Fracture Study conducted to obtain the national incidence and risk factors for traumatic fractures, and to investigate the incidence and risk factors for joint dislocations.

For this national retrospective epidemiological study, 512,187 participants were recruited using stratified random sampling and probability-proportional-to-size method from January 19 to May 16, 2015. Participants who sustained joint dislocations of the trunk, arms, or legs (skull, sternum, and ribs being excluded) in 2014 were personally interviewed to obtain data on age, educational background, ethnic origin, occupation, geographic region, and urbanization degree. The joint-dislocation incidence was calculated based on age, sex, body site, and demographic factors. The risk factors for different groups were examined using multiple logistic regression.

One hundred and nineteen participants sustained 121 joint dislocations in 2014. The population-weighted incidence rate of joint dislocations of the trunk, arms, or legs was 0.22 (95% confidence interval [CI]: 0.16, 0.27) per 1000 population in 2014 (men, 0.27 [0.20, 0.34]; women, 0.16 [0.10, 0.23]). For all ages, previous dislocation history (male: OR 42.33, 95% confidence interval [CI]: 12.03–148.90; female: OR 54.43, 95% CI: 17.37–170.50) and alcohol consumption (male: OR 3.50, 95% CI: 1.49–8.22; female: OR 2.65, 95% CI: 1.08–6.50) were risk factors for joint dislocation. Sleeping less than 7 h/day was a risk factor for men. Compared with children, women aged ≥15 years (female 15–64 years: OR 0.16, 95% CI: 0.04–0.61; female ≥65 years: OR 0.06, 95% CI: 0.01–0.41) were less likely to sustain joint dislocations. Women with more than three children were at higher dislocation risk than women without children (OR 6.92, 95% CI: 1.18–40.78).

The up-to-date data on joint dislocation incidence, distribution, and risk factors can be used as a reference for national healthcare, prevention, and management in China. Specific strategies for decreasing alcohol consumption and encouraging adequate sleeping hours should be developed to prevent or reduce dislocation incidents.

Chinese Clinical Trial Registry, ChiCTR-EPR-15005878.

Gastroesophageal reflux disease (GERD) is caused by esophageal dysfunction resulting in reflux of gastric and duodenal contents into the esophagus, which leads to a series of symptoms.^[1]The incidence of GERD in East Asia ranges from 2.5% to 7.8%.^[2]Hiatal hernia (HH) refers to the upper part of the stomach protruding into the chest through the esophageal hiatus. HH is closely related to GERD and can play a role in the development and increased incidence of GERD.^[3]The surgical treatment of patients with GERD and HH includes HH repair and Nissen, Toupet, or Dor fundoplication (DF). However, post-operative complications have been associated with fundoplication, including dysphagia and abdominal distension, which reduce the benefit of fundoplication.

In 2020, the first generic isosulfan blue product for injection (notification number: 2020 LP00901, batch number: 118210301, 5 mL: 50 mg, Guangdong Hebo Pharmaceutical Co., Ltd.) was approved by the National Medical Products Administration of China. This multi-center, single-arm, phase III, open clinical validation trial was organized by the Chinese Society of Breast Surgery to evaluate the efficacy and safety of this domestically produced generic isosulfan blue injection for sentinel lymph node biopsy (SLNB) in patients with early breast cancer (BC) in China.

To the Editor: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious public health crisis threatening human health and survival worldwide.^[1]Reportedly, laboratory characteristics such as C-reactive protein, lactate dehydrogenase, D-dimer, plasma cytokines, blood platelets, and leukocytes are abnormal in patients with SARS-CoV-2 infections.^[2,3]To enhance the protective immune response against SARS-CoV-2, vaccines have been rapidly developed and administered to healthy individuals or patients with various diseases in several countries.^[4,5]However, some healthy individuals have still become infected with SARS-CoV-2 despite vaccination. Changes in the clinical and laboratory indices of vaccinated patients with COVID-19 remain unknown. In the present study, we report the effects of vaccination in patients with COVID-19.

To the Editor: Psoriasis is a chronic immune-related inflammatory skin disease. The clinical severity of psoriasis varies greatly, and recurrence occurs frequently.^[1]Many attempts have been made to identify biomarkers for psoriasis; however, there are currently no specific markers that can accurately monitor disease severity and treatment efficacy. Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that are highly stable and resistant to RNase R since they can form covalently closed loops without 5^′caps and 3^′tails.^[2]It has been reported that circRNAs could exist in body fluids, such as serum and plasma, and could serve as molecular biomarkers in the diagnosis and prognosis of several diseases.^[3]In this study, we detected the alteration of circRNAs and investigated the potential value of hsa_circ_0056856 as a biomarker for disease severity in serum samples from psoriasis patients and healthy controls (HCs).

To the Editor: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and sleep disturbance is a major disabling non-motor symptom.^[1]Excessive daytime sleepiness (EDS) is defined as inappropriate and undesirable sleepiness during waking hours, which may occur during activities such as talking or driving. In PD patients, EDS increased the risk of accidents and resulted in a poor quality of life.^[2]