Availability Bias Causes Misdiagnoses by Physicians: Direct Evidence from a Randomized Controlled Trial

Objective Empirical evidence on the availability bias associated with diagnostic errors is still insufficient. We investigated whether or not recent experience with clinical problems can lead physicians to make diagnostic errors due to availability bias and whether or not reflection counteracts this bias. Methods Forty-six internal medicine residents were randomly divided into a control group (CG) and experimental group (EG). Among the eight clinical cases used in this study, three experimental cases were similar to the disease of dengue fever (DF) but exhibited different diagnoses, one was actually DF, and the other four filler cases were not associated with DF. First, only the EG received information on DF, while the CG knew nothing about this study. Then, six hours later, all participants were asked to diagnose eight clinical cases via nonanalytic reasoning. Finally, four cases were diagnosed again via reflective reasoning. Results In stage 2, the average score of the CG in the diagnosis of experimental cases was significantly higher than that of the filler cases (0.80 vs. 0.59, p<0.01), but the EG''s average score in the two types of cases was not significantly different (0.66 vs. 0.64, p=0.756). The EG and CG had significantly different scores for each experimental case, while no difference was observed in the filler cases. The proportion of diseases incorrectly diagnosed as DF among experimental cases ranged from 71% to 100% in the EG. There were no significant differences between the mean diagnostic accuracy scores obtained by nonanalytic reasoning and those obtained by the reflective reasoning in any cases. Conclusion Availability bias led to diagnostic errors. Misdiagnoses cannot always be repaired solely by adopting a reflective approach.     

HTR2C polymorphisms,olanzapine-induced weight gain and antipsychotic-induced metabolic syndrome in schizophrenia patients: A meta-analysis

Objective. To conduct meta-analyses of all published association studies on the HTR2C -759C/T (rs3813829) polymorphism and olanzapine-induced weight gain in schizophrenia patients and on the HTR2C -759C/T, -697G/C (rs518147) and rs1414334:C> G polymorphisms and olanzapine/clozapine/risperidone-induced metabolic syndrome in schizophrenia patients. Methods. Eligible studies were identified by searching PubMed and Web of Science databases. Meta-analyses were performed using Cochrane Review Manager (RevMan, version 5.2) to calculate the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI). Results. Our meta-analyses revealed both a significant positive association between the rs1414334 C allele and olanzapine/clozapine/risperidone-induced metabolic syndrome and a marginally significant positive association between the -697C allele and the induced metabolic syndrome in schizophrenia patients, but no significant association between the -759C/T polymorphism and the induced metabolic syndrome in schizophrenia patients. Our analysis further revealed a pronounced trend toward a significant negative association between the -759T allele and high olanzapine-induced weight gain and a trend toward a significant positive association between the -759C allele and high olanzapine-induced weight gain in Caucasian schizophrenia patients. Conclusions. Our results support that HTR2C polymorphisms play a role in antipsychotic-induced metabolic disturbance. More association studies are needed to further elucidate association of different HTR2C polymorphisms and antipsychotic-induced metabolic disturbance.     

Helicobacter pylori and gastric cardia cancer: What do we know about their relationship?

The incidence of gastric cardia cancer is increasing around the world. Since the discovery of Helicobacter pylori (H. pylori), numerous studies have proved that it is a causative factor for many kinds of digestive system tumors. Although the literature on gastric cardia cancer and H. pylori is not scarce, there are still many controversies on the relationship between gastric cardia cancer and H. pylori. Many Western research results showed that there was a negative or no correlation between H. pylori infection and gastric cardia cancer, but in several studies in Asian countries, such as China, H. pylori was demonstrated to be a risk factor for gastric cardia cancer. Therefore, we intended to analyze the related studies to find out the relationship between H. pylori and gastric cardia cancer and find out the causes of the above controversies. We also conducted a meta-analysis of the relationship between cagA positive expression of H. pylori and gastric cardia cancer, to find out whether there is an effect between those two. The primary purpose of this paper was to explore the relationship between gastric cardia cancer and H. pylori. Through analysis, the study showed the reasons for the controversies mentioned above: (1) Geographical factors could affect the relationship between H. pylori and gastric cardia cancer; (2) The definition of gastric cardia cancer in various studies is inconsistent. The result of a meta-analysis about the relationship between H. pylori virulence factor cagA and gastric cardia cancer showed that there was no relationship between these two.     

Paclitaxel‐based supramolecular hydrogel loaded with mifepristone for the inhibition of breast cancer metastasis

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer‐caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel could be an effective strategy for inhibiting breast cancer metastasis. However, their inherent defects, in terms of short blood circulation half‐life and lack of tumor targeting, not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by a nanodelivery system, and explore its mechanism. Herein, a paclitaxel‐conjugated and mifepristone‐loaded hydrogel (PM‐nano) was prepared by self‐assembly. Its characterizations were studied. The antimetastatic effect was evaluated in vitro and in vivo and its mechanism was also explored by western blot assay. The resultant PM‐nano was developed with favorable water solubility and good biocompatibility. Moreover, PM‐nano displayed increased cell uptake properties and stimulated drug release in the tumor micro‐acidic environment. The PM‐nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. The PM‐nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase‐like orphan receptor 1 and MMPs. Taken together, PM‐nano showed superior antimetastatic effects against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for limiting metastasis.     

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2–RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.

This study explored the binding patterns of the wild type and B.1.618 variant using which revealed that the B.1.618 variant possess a stronger binding affinity for the host ACE2 and escape the neutralizing antibodies.     

Comparative Effects between Oral Lactoferrin and Ferrous Sulfate Supplementation on Iron-Deficiency Anemia: A Comprehensive Review and Meta-Analysis of Clinical Trials

Ferrous sulfate is a commonly used iron supplement for the correction of iron-deficiency anemia but with frequent gastrointestinal side effects. Milk-derived iron-binding glycoprotein lactoferrin possesses well gastrointestinal tolerance and fewer side effects caused by the intake of high-dose iron. However, the underlying mechanism of the iron-enhancing effect of lactoferrin remains unclear. In addition, the comparative efficacies between lactoferrin and ferrous sulfate are also remained to be determined. We conducted a systematic review and meta-analysis on published intervention studies to investigate how lactoferrin modulate iron metabolism and evaluate the comparative effects between lactoferrin and ferrous sulfate supplementation on iron absorption, iron storage, erythropoiesis and inflammation. Lactoferrin supplementation had better effects on serum iron (WMD: 41.44 ug/dL; p < 0.00001), ferritin (WMD: 13.60 ng/mL; p = 0.003) and hemoglobin concentration (11.80 g/dL; p < 0.00001), but a reducing effect on fractional iron absorption (WMD: −2.08%; p = 0.02) and IL-6 levels (WMD: −45.59 pg/mL; p < 0.00001) compared with ferrous sulfate. In conclusion, this study supports lactoferrin as a superior supplement to ferrous sulfate regarding the improvement in serum iron parameters and hemoglobin levels. Considering the weak influence of lactoferrin on iron absorption, the anti-inflammation effect of lactoferrin may be the potential mechanism to explain its efficacy on iron status and erythropoiesis.     

Comparison of survival outcomes of neoadjuvant therapy and direct surgery in IB2/IIA2 cervical adenocarcinoma: a retrospective study

Archives of Gynecology and Obstetrics - This retrospective study compared the efficacy and survival of patients with cervical adenocarcinoma (IB2/IIA2; FIGO2009) treated with neoadjuvant...