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Background: Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory skin disease. Biologics are now widely used in patients with moderate-to-severe AD. Objective: This work aims to summarize both label and off-label biologics on AD treatment in phase II and phase III stages, and compile evidence on the efficacy of the most-studied biologics. Methods: We conducted a comprehensive literature search through PubMed, EMBASE, and ClinicalTrials.gov to identify all documented biological therapies for AD. The criteria were further refined to focus on those treatments with the highest evidence level for AD with at least one randomized clinical trial supporting their use. Only studies or articles published in English were enrolled in this study. Findings: Primary searches identified 525 relevant articles and 27 trials. Duplicated articles and papers without a full text were excluded. Only completed trials were enrolled. We included 28 randomized controlled trials, 4 unpublished trials, 2 observational studies, and 1 meta-analysis. Eight kinds of biologics, including IL-4/IL-13 inhibitors, JAK inhibitors, anti-IL-13 antibodies, anti-IL-22 antibodies, anti-IL-33 antibodies, thymic stromal lymphopoietin inhibitor (TSLP), OX40 antibodies, and H4R-antagonists were included in this work. Dupliumab, as the most widely used and investigated biologic, was reported in 1 meta-analysis and 4 trials exploring its long-term use and application in both adults and pediatric patients. Besides dupilumab, four other IL-4/IL-13 inhibitors recruited were all randomized, clinical trials at phase 2–3 stage. Six different kinds of JAK inhibitors were summarized with strong evidence revealing their significant therapeutic effects on AD. There were 3 trials for nemolizumab, an anti-IL-13 antibody, all of which were in the phase 2 clinical trial stage. Results showed nemolizumab could be another alternative therapy for moderate-to-severe AD with long-term efficiency and safety. Conclusion: The biological therapies with the most robust evidence on efficacy and long-term safety for AD treatment include dupilumab, barcitinib, abrocitinib, and delgocitinib. Most of the biologics mentioned in this review were still at the exploratory stage. This review will help practitioners advise patients seeking suitable biological therapies and offer experimental study directions for treatment.

In order to study the pleural effusion (PE) in Severe acute pancreatitis (SAP) in patients with the clinical value of diagnosis, in this study, 78 patients with SAP who were included in Shandong Jinan Municipal Hospital of Traditional Chinese Medicine from January 31, 2017 to December 30, 2019 were selected as the experimental group (EG) and 78 patients with mild acute pancreatitis (MAP) as the control group (CG). The PE was diagnosed by computerized tomography (CT) imaging technology, and the patients with PE in the two groups were divided into small group, medium group and large group according to the volume of PE. The concurrent symptoms of SAP were recorded, and the relation between the occurrence of PE and the complications of SAP was analyzed by a multivariate Logistic regression model (LRM). It was concluded that the concurrent rate of PE in the EG was greatly higher than that in the CG, and the number of cases in the medium and multiple groups was also greatly higher than that in the CG (P < 0.05). There were statistically significant differences (SSD) in acute renal failure, hypovolemic shock and pancreatic pseudocyst in the PE small amount group, medium amount group and large amount group (P < 0.05). The complications of SAP in patients with acute renal failure, hypovolemic shock and pancreatic pseudocyst were positively correlated with age and PE (P < 0.05), which showed that CT could present the PE more directly, which was beneficial to the diagnosis of SAP. In addition, the increased amount of PE indicated the aggravation of SAP and the occurrence of concurrent symptoms, which is helpful for early assessment of patients’ condition and prediction of poor prognosis as an independent indicator to evaluate the early stage of SAP.

Background We diagnosed a clinical case of pulmonary infection involving Mycobacterium tuberculosis and Tropheryma whipplei in a patient with acute respiratory distress syndrome. The diagnosis was assisted by metagenomic next-generation sequencing of bronchoalveolar lavage fluid. Case presentation A 44-year-old Han Chinese inmate was transferred to the emergency department because of dry cough, chest tightness, and shortness of breath. The patient’s body temperature rose to 39.3 °C following empirical cephalosporin treatment for 1 week. The blood CD4+/CD8+ ratio was 0.7, suggesting immunodeficiency. Routine microbiological tests were performed, and tuberculosis interferon gamma release assays were positive. Mycobacterium tuberculosis polymerase chain reaction was also positive. Chest computed tomography scan revealed miliary nodules and ground-glass opacifications, which were in accordance with tuberculosis. To fully examine the etiology, we performed routine laboratory tests and metagenomic sequencing, the results of which indicated the presence of Mycobacterium tuberculosis and Tropheryma whipplei. We administered anti-tuberculosis regimen in combination with trimethoprim/sulfamethoxazole. The patient recovered, with chest computed tomography scan showing absorption of lesions. Conclusions Compared with traditional diagnostic methods such as culture and serology, metagenomic next-generation sequencing has the advantage of detecting a wide array of microorganisms in a single test and therefore can be used for clinical diagnosis of rare pathogens and microbial coinfections. It is particularly useful for immunocompromised patients as they are more prone to infection by opportunistic microorganisms.

Summary Background Healthcare-associated infection (HCAI) represents a major problem for patient safety worldwide. Aim To demonstrate the prevalence, causative agents, and risk factors for HCAI in Chinese hospitals. Methods A one-day point-prevalence survey was conducted in 52 Chinese hospitals between October 2014 and March 2015. A web-based software system was developed for data entry and management. Findings Among 53,939 patients surveyed, the prevalence of patients with at least one HCAI was 3.7%. Of 2182 HCAI episodes, the most frequently occurring types were lower respiratory tract infections (47.2%), followed by urinary tract infection (12.3%), upper respiratory tract infection (11.0%), and surgical site infection (6.2%). The prevalence of patients with at least one HCAI in critical care units was highest (17.1%). Device-associated infections, including ventilator-associated pneumonia, catheter-associated urinary tract infection, and central catheter-associated bloodstream infection, accounted for only 7.9% of all HCAIs. The most frequently isolated micro-organisms were Pseudomonas aeruginosa [206 infections (9.4%)], Acinetobacter baumannii [172 infections (7.9%)], Klebsiella pneumoniae [160 infections (7.3%)], and Escherichia coli [145 infections (6.6%)]. Of the survey patients (18,206/53,939), 33.8% were receiving at least one antimicrobial agent at the time of the survey. Risk factors for HCAI included older age (≥80 years), male gender, days of hospital admission, admission into a critical care unit, and device utilization. Conclusion Our study suggests that the overall prevalence of HCAI in surveyed Chinese hospitals was lower than that reported from most European countries and the USA. More attention should be given to the surveillance and prevention of non-device-associated HCAI in China.

Background: Coinfection with influenza virus and bacteria is a major cause of high mortality during flu pandemics. Understanding the mechanisms behind such coinfections is of utmost importance both for the clinical treatment of influenza and the prevention and control of epidemics.Methods: To investigate the cause of high mortality during flu pandemics, we performed coinfection experiments with H1N1 influenza virus and Staphylococcus aureus in which mice were infected with bacteria at time points ranging from 0 to 7 days after infection with influenza virus.Results: The mortality rates of mice infected with bacteria were highest 0–3 days after infection with influenza virus; lung tissues extracted from these co-infected mice showed higher infiltrating cells and thicker lung parenchyma than lung samples from coinfected mice in which influenza virus was introduced at other times and sequences. The levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-6 in the 0–3 day coinfected group were significantly higher than those in the other groups (p < 0.01), as were the mRNA levels of IFN-γ, IL-6, and TNF-α. Coinfection with influenza virus and S. aureus led to high mortality rates that are directly dependent on the sequence and timing of infection by both pathogens. Moreover, coinfection following this particular schedule induced severe pneumonia, leading to increased mortality.Conclusions: Our data suggest that prevention of bacterial co-infection in the early stage of influenza virus infection is critical to reducing the risk of clinical mortality.

ObjectiveKangaroo care (KC), a well-established parent-based intervention in neonatal intensive care units (NICUs), with documented benefits for infants and their parents. However, in China there remains a lack of knowledge and a reluctance to implement KC in hospitals. Therefore, our aim was to investigate the current knowledge, beliefs and practices regarding KC among NICU nurses in China using the ‘Kangaroo Care Questionnaire’.MethodsA quantitative descriptive survey was designed. This questionnaire comprised 90 items classified according to four domains: knowledge, practice, barriers and perception. Data were analysed using SPSS V.20.0, and content analysis was used to summarise data derived from open-ended questions.ResultsThe survey involved 861 neonatal nurses from maternity and general hospitals across China (response rate=95.7%). The findings showed that 47.7% (n=411) of the nurses had participated in the implementation of KC. Neonatal nurses in the ‘experienced in KC’ group showed an overall better understanding of KC and its benefits with a higher ‘correct response’ rate than those in the ‘not experienced in KC’ group. In the ‘experienced in KC’ group, over 90% considered KC beneficial to the parent-baby relationship and attachment, and over 80% believed that KC positively affected outcomes of preterm infants. The ‘not experienced in KC’ group perceived more barriers to KC implementation than did the ‘experienced in KC’ group.ConclusionAlthough most nurses working in NICUs in China were aware of the benefits of KC, there remain substantial barriers to its routine use in practice. Education for both staff and parents is necessary, as is the provision of appropriate facilities and policies to support parents in providing this evidence-based intervention.

Buerger’s disease (BD) etiologies are poorly understood. Beyond smoking cessation, medical-surgical treatments have limited success. We hypothesized that mutations associated with arterial vasospasm (stromelysin-1 5A/6A, eNOS T-786C) and C677T-A1298C methylene tetrahydrofolate reductase (MTHFR) interacted with cigarette-cannabis smoking, reducing vasodilatory nitric oxide (NO), promoting arterial spasm-thrombosis. Of 21 smoking BD patients (14 men [2 siblings], 7 women; 20 white, 1 African-American), compared to 21 age-gender-race matched healthy controls, 5A/6A stromelysin- 1 homozygosity was present in 7 of 21 (33%) BD cases versus 5 of 21 (24%) controls (risk ratio 1.4; 95% confidence interval [CI] 0.5-3.7), and eNOS T-786C homozygosity was present in 3 of 21 (14%) BD cases versus 1 of 21 (5%) controls (risk ratio 3.0; 95% CI 0.3-26.6). C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in 7 of 21 cases (33%) versus 11 of 21 controls (52%) (risk ratio 0.6; 95% CI 0.3-1.3). In 18 patients who stopped and 3 who continued smoking, all stromelysin-1 5A/6A and/or eNOS heterozygotes-homozygotes, superficial phlebitis, lower limb gangrenous ulcers, and intractable ischemic rest pain with arterial occlusion progressed despite conventional medical therapy, threatening amputation. In 15 patients, to increase vasodilatory NO via endothelial NO synthase, l-arginine (15 g/day) was given, along with folic acid (5 mg), vitamin B6 (100 mg), and B12 (2000 mg/day) to optimize homocysteine metabolism and reduce asymmetric dimethylarginine, a NO synthase inhibitor. Unexpectedly quickly and strikingly, within 8 weeks to 8 months receiving l-arginine-folic acid, 11 of 15 treated patients improved with uniform pain reduction, ulcer healing, and in 5, full recovery of previously absent peripheral pulses. In smokers homo/heterozygous for stromelysin-1 5A/6A and eNOS T-786C mutations, we speculate that the development and severity of BD are related to a gene-environment vasospastic interaction with reduced NO-mediated vasodilatation. Increasing NO production by l-arginine while optimizing homocysteine metabolism by folic acid-B6-B12 may have therapeutic benefit. Further blinded, placebo-controlled studies are needed to determine whether our observations can be generalized to larger BD cohorts.

We assessed whether hypofibrinolytic plasminogen activator inhibitor 1 (PAI-1 activity) showed an independent association with first-trimester miscarriage in the 430 women with polycystic ovary syndrome (PCOS) who had previous pregnancies (from a cohort of 967 women with PCOS). Prospectively, we hypothesized that Glucophage (Bristol-Myers Squibb, Princeton, NJ) promotes successful live births in women with PCOS by lowering PAI-1 activity before conception and maintaining further reductions of PAI-1 activity during the first trimester of pregnancy. We also assessed whether PAI-1 activity levels were independently related to PAI-1 genotype and to modifiable risk factors body mass index (BMI), insulin, and triglyceride. By stepwise logistic regression, with the dependent variable being previous pregnancy outcomes at 3 levels (live birth pregnancies only [n = 208]; bothor =1 live birth andor =1 first-trimester miscarriage [n = 111]; or first-trimester miscarriages only [n = 71]) and explanatory variables PAI-1 genotype, PAI-1 activity, insulin, homeostasis model assessment of insulin resistance, BMI, and triglyceride, PAI-1 activity was positively associated with first-trimester miscarriage (P = .004). For each 5 IU/mL increment in PAI-1 activity, the risk being in an adverse first-trimester miscarriage category increased (odds ratio, 1.12; 95% confidence interval, 1.04-1.20). Prospectively, from pretreatment to the last preconception visit on Glucophage, in 30 women who subsequently had live births, PAI-1 activity fell 44%, but rose 19% in 23 women with first-trimester miscarriage (P = .03). In the 30 women with live birth pregnancies, median PAI-1 activity fell continuously from pretreatment through the first trimester (from 16.8 to 6.7 IU/mL), whereas PAI-1 activity was either unchanged or rose in women with first-trimester miscarriage. Of the 921 women with PCOS who had 4G5G data, 718 (78%) had 4G4G-4G5G genotypes vs 87 (69%) of 126 normal female controls (chi(2) = 4.95, P = .026). The 4G allele frequency was 53% in women with PCOS vs 46% in controls (chi(2) = 4.3, P = .04). Of the 866 women with PCOS who had PAI-1 activity data, by stepwise regression, positive independent determinants of PAI-1 activity included BMI (partial R(2) = 10.6%, P.0001), insulin (partial R(2) = 2.8%, P.0001), triglyceride (partial R(2) = 1.1%, P = .0009), and the 4G4G-4G5G genotype (partial R(2) = 1%, P = .0011). The PAI-1 gene 4G polymorphism is more common in women with PCOS than in normal women and, in concert with obesity, hyperinsulinemia, and hypertriglyceridemia, contributes to treatable, hypofibrinolytic, miscarriage-promoting, high PAI-1 activity. Preconception and first-trimester decrements in PAI-1 activity on Glucophage are associated with live births, whereas increments or no change in PAI-1 activity despite Glucophage appears to be associated with first-trimester miscarriage.

We hypothesized that the thrombophilic G1691A factor V Leiden gene mutation was a common significant cause of sporadic first trimester miscarriage. We compared thrombophilia and hypofibrinolysis in 92 women (85 white, 5 black, 2 other) with 1 or more pregnancies and 1 miscarriage (143 live births, 92 miscarriages) (cases) and in 380 female controls (355 white, 21 black, 4 other) with 1 or more pregnancies and 0 miscarriages (964 live births). We used polymerase chain reaction techniques to characterize thrombophilic gene mutations (G1691A V Leiden [FV], G20210A prothrombin, C677T/A1298C MTHFR) and hypofibrinolytic gene mutations (plasminogen activator inhibitor [PAI-1] activity 4G4G). We carried out serologic measures of thrombophilia (homocysteine, anticardiolipin antibodies [ACLA] immunoglobulin G and immunoglobulin M, lupus anticoagulant, factor VIII, factor XI, protein C, total and free protein S, antithrombin III) and hypofibrinolysis (plasminogen activator inhibitor activity [PAI-Fx], lipoprotein[a]). Of the 380 controls, 6 (1.6%) had FV heterozygosity vs 12 heterozygous and 2 homozygous FV cases (15.2% [14/92]; P.0001). Plasminogen activator inhibitor activity was high (or =21.1 U/mL) in 21 (33%) of 63 cases vs 27 (18%) of 152 controls (P = .013). Factor VIII was high (150%) in 15 (31%) of 48 cases vs 19 (18%) of 103 controls (P = .079). By logistic regression, with age and factor VIII (categorical [or =150%,150%]) as explanatory variables and group (cases, controls) as the dependent variable, after adjusting for age, high factor VIII was a significant predictor for miscarriage (odds ratio, 3.28; 95% confidence interval, 1.34-8.04; P = .01). There were no other group differences (P.05) in measures of thrombophilia and hypofibrinolysis. After unexplained sporadic first trimester miscarriage, we suggest that measurements be done of the FV mutation, PAI-Fx, and factor VIII, etiologies for sporadic miscarriage.

Document obesity-extreme obesity in most 20-24, 25-29, and 32-41 years old women with PCOS as a stimulus for physicians to consider the diagnosis of PCOS, an underlying reversible endocrinopathy.In matched age groups 20-24, 25-29, and 32-41 years, we compared BMI in 84, 129, and 188 Caucasian women with PCOS versus 956, 815, and 815 women in NHANES I (general population), and 25, 36, and 45 non-pregnant women (community obstetrics practice).At ages 20-24, 25-29, and 32-41 years, mean+/-S.D. BMIs in women with PCOS (35.3+/-7.7, 36.0+/-9.4, 36.7+/-8.2) were much greater than NHANES I (22.8+/-4.6, 23.3+/-5.0, 24.5+/-5.6; p.0001), and community (26.1+/-6.8, 26.9+/-6.6, 25.2+/-5.2; p.0001). Classifying BMI25 (normal),or =25-30 (overweight),or =30-40 (obese),or =40 (extremely obese), at ages 20-24, 25-29, and 32-41 years: 76, 73, and 78% of PCOS women were obese-extremely obese, versus 7, 11, and 14% of NHANES I, and 20, 28, and 15% of community women. At ages 20-24, 25-29, and 32-41 years, only 10, 12, and 7% PCOS women had BMIs25, versus 78, 74, and 66% NHANES I, and 48, 47, and 58% of community women.Obesity-extreme obesity in women, manifest by ages 20-24 years, continuing through 32-41 years, should alert physicians to the likelihood of PCOS, an underlying, heritable, potentially reversible, insulin resistant endocrinopathy that promotes obesity.

Five inbred strains of mice differing in susceptibility to diet-induced atherosclerosis were compared for neointimal hyperplasia after endothelial denudation with an epoxy resin–modified catheter probe. Results showed that all animals responded similarly to the arterial injury, with increased medial area and thickness after 14 days. In contrast, a significant strain-specific difference in neointimal formation after injury was observed. The atherosclerosis-susceptible C57L/J mice were also susceptible to injury-induced neointimal hyperplasia, and the C3H mice were resistant to both forms of vascular diseases. The 129/Sv mice, which displayed an intermediate level of diet-induced atherosclerosis, also displayed an intermediate level of injury-induced neointimal hyperplasia. Interestingly, the atherosclerosis-susceptible C57BL/6 mice were resistant to neointimal hyperplasia after endothelial denudation, whereas the atherosclerosis-resistant FVB/N mice were susceptible, displaying massive neointimal hyperplasia after arterial injury. All (C57L/J×C57BL/6)F 1 hybrid mice were resistant to injury-induced neointimal hyperplasia. Moreover, N 2 mice generated from backcrossing the F 1 hybrid mice to the susceptible C57L/J mice displayed a range of arterial response to injury, spanning the most severe to the most resistant phenotype. These results indicate that injury-induced neointimal hyperplasia and diet-induced atherosclerosis are controlled by distinct sets of genes; the former appeared to be determined by recessive genes at ≥2 loci.

The potential cytostatic function of apolipoprotein (apo) E in vivo was explored by measuring neointimal hyperplasia in response to vascular injury in apoE-deficient and apoE-overexpressing transgenic mice. Results showed a significant increase in medial thickness, medial area, and neointimal formation after vascular injury in both apoE knockout and wild-type C57BL/6 mice. Immunochemical analysis with smooth muscle α-actin-specific antibodies revealed that the neointima contained proliferating smooth muscle cells. Neointimal area was 3.4-fold greater, and the intima/medial ratio as well as stenotic luminal area was more pronounced in apoE(−/−) mice than those observed in control mice (P < 0.05). The human apoE3 transgenic mice in FVB/N genetic background were then used to verify a direct effect of apoE in protection against neointimal hyperplasia in response to mechanically induced vascular injury. Results showed that neointimal area was reduced threefold to fourfold in mice overexpressing the human apoE3 transgene (P < 0.05). Importantly, suppression of neointimal formation in the apoE transgenic mice also abolished the luminal stenosis observed in their nontransgenic FVB/N counterparts. These results documented a direct role of apoE in modulating vascular response to injury, suggesting that increasing apoE level may be beneficial in protection against restenosis after vascular surgery.

We assessed whether hypofibrinolytic plasminogen activator inhibitor (PAI-Fx) was independently associated with first-trimester miscarriage in 430 women with polycystic ovary syndrome (PCOS) who had previous pregnancies. We hypothesized that Glucophage optimizes live births in women with PCOS by lowering PAI-Fx before conception and further lowering PAI-Fx in the first trimester of pregnancy. We also assessed whether PAI-Fx levels were independently related to PAI-1 genotype and to modifiable risk factors, BMI, insulin, and triglyceride (TG). By stepwise logistic regression with the dependent variable being previous pregnancy outcomes at 3 levels (live birth pregnancies only [n = 208], both one or more 1 live births and $ one or more first-trimester miscarriages [n = 111] or first-trimester miscarriages only [n = 71]), and explanatory variables PAI-1 genotype, PAI-Fx, insulin, HOMA IR, BMI, and TG, PAI-Fx was positively associated with first-trimester miscarriage, p = .004. For each 5 IU/mL increment in PAI-Fx, the risk being in an adverse first-trimester miscarriage category increased, odds ratio 1.12, 95% CI 1.04 to 1.20. Prospectively, from pretreatment to the last preconception visit on Glucophage, in 30 women who subsequently had live births, PAI-Fx fell 44% but rose 19% in 23 women with first-trimester miscarriage, p = .03. In the 30 women with live birth pregnancies, median PAI-Fx fell continuously from pretreatment through the first trimester (from 16.8 to 6.7 IU/mL), while PAI-Fx was either unchanged or rose in women with first-trimester miscarriage. Of the 921 PCOS women who had 4G5G data, 718 (78%) had 4G4G-4G5G genotypes vs 87/126 (69%) normal female controls (x2 = 4.95, p = .026). The 4G-allele frequency was 53% in PCOS women vs 46% in controls (x2 = 4.3, p = .04). By stepwise regression, positive independent determinants of PAI-Fx included BMI (partial R2 = 10.6%, p

Buerger9s disease (BD) etiologies are poorly understood. Beyond smoking cessation, medical-surgical treatments have limited success. We hypothesized that mutations associated with arterial vasospasm (stromelysin-1 5A/6A, eNOS T-786C) and C677T-A1298C methylenetetrahydrofolate reductase (MTHFR) interacted with cigarette-cannabis smoking, reducing vasodilatory nitric oxide (NO), promoting arterial spasm-thrombosis. Of 19 smoking BD patients (13 men [2 siblings], ± women, 18 Caucasian, 1 African American), compared to 200 healthy Caucasian controls, BD patients were more likely to have 6A6A stromelysin-1 homozygosity (7/19 [37%] vs 46/200 [23%]) and to have eNOS T-786C homozygosity (3/19 [16%] vs 22/200 [11%]), but these patient-control differences were not significant, p = .4, 0.5. C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity did not differ in patients vs controls (6/19 [32%] vs 70/200 [35%]), p = .8. In 9 patients who stopped and 1 who continued smoking, all stromelysin-1 5A/6A and/or eNOS heterozygotes-homozygotes, lower limb gangrenous ulcers, and intractable ischemic rest pain with arterial occlusion progressed despite conventional medical therapy, threatening amputation. In these 10 patients, to increase vasodilatory NO via endothelial NO synthase, L-arginine (15 g/day) was given, along with folic acid 5 mg, vitamin B6 (100 mg), and B12 (2,000 μg/day) to optimize homocysteine metabolism and reduce asymmetric dimethylarginine, a NO synthase inhibitor. Unexpectedly quickly and strikingly, within 8 weeks to 8 months on L-arginine-folic acid, all 10 treated patients improved with uniform pain reduction, ulcer healing, and in 5, full recovery of previously absent peripheral pulses. In smokers homo-heterozygous for stromelysin-1 5A/6A, eNOS T-786C, and C677T-A1298C MTHFR mutations, we speculate that the development and severity of BD are related to a gene-environment vasospastic interaction with reduced NO-mediated vasodilatation. Increasing NO production by L-arginine while optimizing homocysteine metabolism by folic acid-B6-B12 may have therapeutic benefit. Further blinded, placebo-controlled studies are needed to determine whether our observations can be generalized to larger BD cohorts.