Volume 103 · Issue 32 · 2023

Atopic dermatitis (AD) is a chronic, relapsing, pruritic inflammatory disease with a high prevalence, ranking as the leading non-fatal burden of skin diseases. The pathogenesis of AD involves interactions among genetic factors, impaired skin barrier function, dysbiosis, and immune dysregulation. The immune phenotype is highly heterogeneous, with the Th2-dominant immune response. AD exhibits diverse clinical phenotypes, posing challenges for the establishment of clinical diagnostic criteria and personalized management. Targeted biologic therapies focusing on Th2-type inflammatory responses and small-molecule drugs blocking inflammatory signaling pathways have significantly improved the management of the moderate or severe AD. However, the balance between efficacy and safety remains to be evaluated due to limited data. Despite significant advancement in basic and clinical research on AD in recent years, there are still many questions that need to be resolved urgently.

Atopic dermatitis (AD) is a highly heterogeneous skin disease. Many characteristics of AD in the elderly are different from those in other age groups, and AD in the elderly is prone to misdiagnosis or missed diagnosis, which has gradually gained recognition and attention in recent years. The onset of elderly AD is related to changes of aging related barrier and immune function. Elderly AD is more common in Th1 type of skin inflammation, and has certain "reverse" characteristics in clinical manifestations. The diagnosis of elderly AD should be based on exclusion diagnosis. In addition to the stepwise treatment, personalized treatment should also be made based on factors, such as skin characteristics and comorbidities of the elderly.

Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization′s position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category Ⅲ exposure for the first time, as well as in category Ⅱ exposure that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine. Therefore, the anti-rabies virus monoclonal antibody preparation shows great potential for clinical application in PEP.

The population with cirrhosis in China is about 7 million, and portal hypertension is an important factor affecting the prognosis of these patients. The severity of portal hypertension determines the occurrence and development of liver related complications, such as ascites, variceal bleeding, and hepatic encephalopathy. In recent years, ultrasound elastography technology has been rapidly developed and widely applied in the field of liver diseases. Transient elastography, point shear wave elastography, and two-dimensional shear-wave elastography are all of great value for non-invasive evaluation of portal hypertension. However, there is currently no unified operating standard and reference threshold for evaluating cirrhotic portal hypertension using ultrasound elastography. Therefore, Ultrasonic Medicine Branch of the Chinese Medical Association and Chinese Portal Hypertension Alliance (CHESS) initialed and convened domestic experts from multiple disciplines, including ultrasound medicine, hepatology, gastroenterology, to form a consensus based on the latest domestic and international guidelines, medical evidence, and Chinese clinical practice. The aim is to standardize the examination process of different ultrasound elastography techniques, and standardize the application of liver stiffness and spleen stiffness in compensated advanced chronic liver disease, clinically significant portal hypertension, avoidance of endoscopic screening, risk stratification of portal hypertension, and personalized clinical management.

To investigate and analyze the clinical features of elderly atopic dermatitis (AD) in China.

Based on the National Clinical Research and Homogeneous Diagnosis and Treatment Project for Type 2 Inflammation Dermatosis, a total of 2 281 patients aged 65 years or older were enrolled from 172 grade A tertiary hospitals who were diagnosed as atopic dermatitis from June 2021 to February 2023, and their demographics, clinical feature, and disease severity, etc. were collected. Elderly AD patients were divided into groups based on gender, history of allergic diseases (with or without a personal or family history of allergic diseases), and clinical features (site of onset, AD signs) and scales were compared within the groups. Median (Q₁, Q₃) was used for quantitative data.

The age of 2 281 elderly AD patients was 73.02 (68.83, 79.62) years old, among whom there were 1 649 males (72.29%) and 632 females (27.71%). A total of 2 244 cases were recorded with the information of the onset stage, of whom 1 713 cases (76.34%) occurred in the elderly stage. A total of 2 136 cases were recorded with the information of personal or family history of allergic diseases, of which 1 076 cases (50.37%) had a personal or family history of allergic diseases, and 1 060 (49.63%) had no history of allergic diseases. Skin lesions were predominantly involved in the waist, back, buttocks, and AD signs were mainly eczema-like skin lesions on the cheek and/or scalp and/or limb extension. Patients with moderate to severe AD accounted for 60.58% (1 327 cases), moderate to severe itching accounted for 81.32% (1 781 cases). Patients with anxiety and depression accounted for 46.14% (1 011 cases) and 39.27% (860 cases), respectively. Men had a higher EASI score than women [9.67 (4.77, 19.28) vs 8.45 (3.98, 17.11), P=0.040]. EASI, HADS-anxiety and WI-NRS scores were higher in patients with history of allergic diseases than those without allergy history [ (9.79 (4.84, 19.96) vs 8.96 (4.05, 18.31), P=0.015; 7.22 (3.49, 10.00) vs 6.81 (3.12, 9.33), P=0.012; 7.64 (5.62, 9.07) vs 7.38 (5.35, 8.91), P=0.036].

Elderly AD patients have their own exclusive clinical manifestations, and the understanding of these characteristics is beneficial for guiding clinical development of targeted management plans. Elderly AD patients are mostly senile onset, and male patients are more than female patients, skin lesions are mainly distributed on the extended side, and the disease burden is heavy.

To investigate the role of mast cells in atopic dermatitis (AD) phenotype and the immune activation of type 2 inflammatory cytokine release.

Nine AD skin samples were obtained from the Department of Dermatology, the Second Affiliated Hospital of Xi′an Jiaotong University, and nine healthy skin control samples were obtained from the surgical excision of excess normal skin by orthopedic surgery, the Second Affiliated Hospital of Xi′an Jiaotong University, which were subjected to toluidine blue staining and fluorescence staining to clarify the mast cell degranulation activation status of the AD skin lesions. We investigated whether MC903 could directly activate mast cells in vivo through the toe swelling and exudation assay in wild-type mice; we constructed the MC903-AD model using wild-type and Kit^W-sh/W-sh mast cell-deficient mice in order to investigate whether mast cells affected the phenotype, histopathology, and the level of type 2 inflammatory factors in AD mice; we extracted mouse peritoneal mast cells and the ability of MC903 to activate mast cells to release inflammatory mediators in vitro was explored by calcium imaging, tryptase and β-aminohexokinase release assays, and MCP-1 and CXCL-2 release assays.

The number of degranulated mast cells in an activated state was increased in skin lesions of AD patients compared to healthy controls, with (5.40±1.14) and (2.20±0.84), respectively (P<0.001). Kit^W-sh/W-sh mast cell-deficient AD mice had an attenuated phenotype with ADI scores of (5.50±1.05), compared to wild-type AD mice with (10.00±0.89) (P<0.001). The release of type 2 inflammatory factors in wild-type AD mice was higher than those in Kit^W-sh/W-sh mast cell-deficient AD mice, with IL-4 levels of (29.50±1.87) and (15.33±1.86) pg/mg (P<0.001), IL-13 levels were (6.32±0.25) and (3.93±0.22) pg/mg (P<0.001), IL-31 levels were (9.73±0.38) and (6.89±0.27) pg/mg (P<0.001), and TSLP levels were (206.00±4.43) and (99.00±4.86) pg/mg (P<0.001), respectively. MC903 could cause mast cell activation in wild-type mice, leading to increased swelling and exudation in the toes of mice, and MC903 could activate mast cells in vitro, leading to increased degranulation and release of inflammatory factors such as MCP-1 and CXCL-2.

The number of activated mast cells was increased in skin lesions of AD patients than in healthy controls. Kit^W-sh/W-sh mast cell-deficient AD mice showed significantly reduced phenotype, histopathology, and type 2 inflammatory factor levels compared with wild-type AD mice. MC903 activates mast cells in vivo and in vitro. Mast cells play a key role in AD phenotype and immune activation.

To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis.

The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio (OR) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed.

A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients (OR=0.79, 95%CI:0.58-1.07, P=0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients (OR=0.79, 95%CI:0.55-1.14, P=0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients (OR=1.07, 95%CI:0.65-1.77, P=0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related.

The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

To compare the efficacy of off-pump minimally invasive cardiac surgery (MICS) via a single left intercostal space incision with median sternotomy multi-vesselcoronary artery bypass grafting (CABG).

Patients who were diagnosed with multi-artery coronary artery disease (CAD) in the Ward 10 of the Department of Cardiac Surgery, Beijing Anzhen Hospital Affiliated to Capital Medical University and underwent CABG from July 2019 to January 2022 were retrospectively collected. All the patients were divided into MICS group and conventional CABG group according to the surgical methods. The perioperative outcomes were compared between thetwo groups, including intraoperative blood loss, postoperative 24 h thoracic drainage volume, ventilation duration, length of stay (LOS) in intensive care unit (ICU) and total LOS in hospital. Intraoperative blood flow of graft vesselswas measured by transit-time flow measurement (TTFM) after vascular anastomosis, and mean flow (MF) and pulsatile index (PI) were compared between the two groups.

A total of 444 patients were in the final analysis, with 351 males and 93 females, and the mean age of (62.0±8.9) years. There were 179 patients in MICS group and 265 cases in conventional CABG group, respectively. There were no statistically significant differences in the preoperative profiles between the two groups (all P>0.05) except that younger age [(60.7±9.3) years vs (62.8±8.5) years, P=0.017] and lower proportion of female [10.1% (18/179) vs 28.3% (75/265), P<0.001] were detected in MICS group. Likewise, there was no significant difference in the number of graft vessels between MICS group (3.18±0.74) and conventional CABG group (3.28±0.86) (P=0.234). Compared with those in conventional CABG group, patients in MICS group showed longer operation duration [ (5.10±1.09) h vs (4.33±0.86) h], fewer intraoperative blood loss [500 (200, 700) ml vs 700 (600, 900) ml], fewer postoperative 24 h thoracic drainage volume [300 (200, 400) ml vs 400 (250, 500) ml], shorter postoperative ventilation duration [15.0 (12.0, 17.0) h vs 16.5 (12.5, 19.0) h, P<0.001], LOS in ICU [18.0 (15.0, 20.0) h vs 20.0 (16.0, 23.0) h, P<0.001] and total LOS in hospital [(12.6±2.7) d vs (14.5±3.9) d, P<0.001]. MI and PI of graft vessels were similar between the two groups (both P>0.05). Moreover, there were no significant differences in major perioperative complications (i.e., repeat thoracotomy, incision infection, stroke) and mortality between the two groups (all P>0.05).

MICS is an alternative treatment for patients with multi-vessel CAD with better perioperative outcomes compared with conventional CABG.

To explore the correlation between extracellular water/body cell mass (ECW/BCM) ratio and cognitive impairment (CI) in patients on maintenance hemodialysis (MHD).

A multicenter, cross-sectional study was conducted in Guizhou Province. All adult MHD patients in hemodialysis centers of 18 hospitals in Guizhou Province between June and October 2020 were included. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) score. The ECW and BCM was derived from bioelectrical impedance, and the ECW/BCM ratio was calculated. The patients were divided into four groups based on the quartile of ECW/BCM ratio. Multivariate logistic regression analysis and subgroup analysis were conducted.

A total of 3 160 patients were included in the final analysis, of which 761 (24.1%) developed CI. There were 1 868 males (59.1%) and 1 292 females (40.9%), and the mean age was (55±15) years. Multivariate logistic regression analysis showed that the risk of CI in ECW/BCM Q3 group was 1.55 times (95%CI: 1.03-2.34, P=0.035) of that in group Q1, while the risk of CI in Q4 group was 1.62 times of that in group Q1 (95%CI: 1.05-2.51, P=0.029). Subgroup analysis showed that there was an interaction between previous cerebrovascular event and ECW/BCM on CI (P for interaction=0.04). Patients with a previous history of cerebrovascular events had a higher risk of CI than those without. Among those with no previous cerebrovascular events, the risk of CI in group Q4 was 1.62 times of that in group Q1 (95%CI: 1.19-2.20), while the risk of CI in group Q4 was 7.17 times of that in group Q1 (95%CI: 1.59-32.35) in those with previous cerebrovascular events.

Increased ECW/BCM ratio is associated with increased CI risk in patients with MHD, and the risk was more obvious in those with previous history of cerebrovascular events.

In patients with severe trauma, iliac vascular injury is common in penetrating injury, while iliac vascular injury caused by blunt trauma is often combined with pelvic fracture of varying degrees. However, isolated iliac vessel injury without pelvic fracture is rare. It is easy to misdiagnose and miss diagnosis in clinic, and the treatment is relatively difficult, resulting in hemorrhagic shock, deep vein thrombosis of lower limbs and other adverse consequences. A traumatic patient with isolated iliac vein injury was successfully treated by placing inferior vena cava filter and covered stent in our hospital. The diagnosis and treatment process is reported as follows.

Pruritus is the most prominent clinical symptom of atopic dermatitis (AD). Domestic and foreign AD management guidelines put forward that we should pay close attention to the evaluation and treatment of patients' pruritus, sleep and emotional dimensions. Controlling pruritus is the key link of AD management. However, the mechanism of AD pruritus is very complicated, and some traditional drugs lack definite efficacy, so effective itching relief faces great challenges. In recent years, the cognition of the pathophysiology of AD pruritus and the mechanism related to nerve conduction pathway has gradually improved, and new treatment options are constantly emerging. This article reviews the traditional medicines for the clinical management of AD pruritus and the latest treatment options according to the stepwise classification of pruritus severity.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with increasing incidence at any age. At present, there is no definite mechanism to explain the cause of its significant clinical heterogeneity, so the overall clinical management of some AD patients is extremely difficult. Recent research evidence shows that overactivation of helper T cell 2 (Th2) type immune inflammatory response is the most basic feature of many pathological changes of AD, and it has been proved that neurogenic inflammation (NGI), which realizes information communication by skin sensory nerve fibers and skin resident cells with the help of neurotransmitters or inflammatory mediators, is an important link in the formation of inflammatory phenotype of AD. From the perspective of skin NGI formation, the relationship between it and the clinical symptoms of AD will inevitably lead to a deep understanding of the efficacy and safety of targeted skin NGI-related strategies in preventing and treating AD. This paper introduces the structural basis of skin NGI, analyzes the latest research progress of skin NGI in the pathogenesis and treatment strategy update of AD, and looks forward to the future related research based on skin NGI, in order to provide useful reference for the precise clinical management of AD.

Perioperative prophylactic use of glucocorticoids has been done for decades, but it is unclear whether it can improve outcomes in infants following cardiac surgery with cardiopulmonary bypass. The study was a registry-based multicenter, prospective, randomized controlled trial that included 1 263 infants undergoing cardiac surgery with extracorporeal circulation (age<1 year old) were randomized into two groups, one supplemented with methylprednisolone (30 mg/kg) in the extracorporeal circulation prefill and the other supplemented with placebo in the prefill. Differences between the two groups were judged by graded composite outcomes such as surgical death, heart transplantation during hospitalization, any of the 13 major complications, or length of postoperative hospital stay. The findings found that there was no statistically significant difference in the likelihood of a worse outcome between the methylprednisolone and placebo groups among 1 200 infants treated with methylprednisolone (599 infants) or placebo (601 infants) (adjustedOR=0.86，95%CI：0.71~1.05，P=0.140）。 After adjusted analysis, the methylprednisolone group had worse outcomes compared to the placebo group.OR=0.82（95%CIAlthough this result suggests that methylprednisolone may be beneficial in improving postoperative outcomes in infants, children in the methylprednisolone group were more likely to have postoperative hyperglycemia and receive insulin than in the placebo group (19.0% vs. 6.7%,P<0.001）。 Therefore, it is concluded that for infants undergoing cardiac surgery with cardiopulmonary bypass, perioperative prophylactic use of methylprednisolone does not show significant advantages over no use of methylprednisolone in terms of surgical death, heart transplantation during hospitalization, complication occurrence, and length of postoperative hospitalization, and that children with perioperative prophylactic use of methylprednisolone are more likely to develop postoperative hyperglycemia.

In children with severe pulmonary hypertension, the inclusion of Potts shunt in an integrated response strategy may improve the outcome of medical treatment and delay lung transplantation, but there is insufficient evidence to support this decision. The study included and prospectively analyzed 23 children (20 surgical, 3 transcatheter) who underwent Potts shunt and 31 who underwent lung transplantation from 1995 to the present. The results showed that all children who underwent Potts shunt, despite receiving maximum medical therapy, experienced a significantly higher right ventricular pressure than systemic pressure. At mechanical ventilation time (1.3 d vs. 10.2 d,P=0.019), median length of stay (9.8 d vs. 34.0 d,P=0.012) and overall complication rate [35% (7/20) vs 81% (25/31),P=0.003], perioperative outcomes after Potts shunt were better than lung transplantation. Further studies showed that surgical mortality after Potts shunt was higher (20%, 4/20) than lung transplant mortality (6%, 2/31,P=0.195), and risk factors for this outcome included preoperative extracorporeal membrane oxygenation and significant right ventricular dysfunction. At the interim follow-up (median 1.8 years, maximum 6.1 years), the improvement of right ventricular/left ventricular pressure and functional status in patients undergoing Potts shunt was better than that in patients undergoing lung transplantation, and there was no significant difference in survival rate between the two (P=0.258）。 Therefore, it is concluded that Potts shunt is an effective method to relieve hypersystemic pulmonary hypertension in children, and it is one of the strategies to maximize the prolongation of children's life span and improve the functional state of the body.