Neural correlates of the LSD experience revealed by multimodal neuroimaging

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ego-dissolution” and “altered meaning,” implying the importance of this particular circuit for the maintenance of “self” or “ego” and its processing of “meaning.” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or “psychedelic” that alters consciousness in a profound and characteristic way. First synthesized in 1938, its extraordinary psychological properties were not discovered until 1943 (1). LSD would go on to have a major effect on psychology and psychiatry in the 1950s and 1960s; however, increasing recreational use and its influence on youth culture provoked the drug’s being made illegal in the late 1960s. As a consequence, human research with LSD has been on pause for half a century. However, inspired by a revival of research with other psychedelics, such as psilocybin and ayahuasca, a small number of new reports on the psychological effects of LSD have recently been published (2–6).LSD has a high affinity for a range of different neurotransmitter receptors, but its characteristic psychological effects are thought to be mediated by serotonin 2A receptor (5-HT_2AR) agonism (7). Previous neurophysiological research with LSD is limited to electroencephalography (EEG) studies in the 1950s and 1960s. These reported reductions in oscillatory power, predominantly in the lower-frequency bands, and an increase in the frequency of alpha rhythms (8). Broadband decreases in cortical oscillatory power have been observed in modern EEG and magnetoencephalography (MEG) studies with psilocybin (9, 10), with EEG and the dimethyltryptamine-containing brew “ayahuasca” (11), and with rodent brain local-field potential recordings and a range of different 5-HT_2AR agonists (12–14).The effects of psychedelics (other than LSD) on human brain activity have also previously been investigated with positron emission tomography (PET) (15) and functional magnetic resonance imaging (fMRI) (16). fMRI studies with psilocybin revealed decreased cerebral blood flow (CBF) and blood oxygen level-dependent (BOLD) signal in connector hubs (16), decreased resting state functional connectivity (RSFC) in major resting state networks (RSNs) such as the default-mode network (DMN) (17), and the emergence of novel patterns of communication (18, 19), whereas increased cortical glucose metabolism was found with PET (15). Notably, the spatial locations of the PET-, fMRI-, EEG-, and MEG-measured effects of psychedelics are relatively consistent; for example, high-level cortical regions, such as the posterior cingulate cortex (PCC), and some of the principal effects of psilocybin revealed by fMRI (e.g., decreased DMN RSFC) were recently replicated by a separate team working with ayahuasca (20).Consistent with a prior hypothesis (17), these studies suggest that an “entropic” effect on cortical activity is a key characteristic of the psychedelic state. However, a putative excitation of hippocampal/parahippocampal gyri activity has also been observed with fMRI and psychedelics in humans (19) and animals (14). Moreover, depth EEG studies in the 1950s reported activations in medial temporal lobe regions during psychosis-like states under LSD and other psychedelics (21, 22). Further, patients with epilepsy with resection of the medial temporal lobes showed attenuated LSD effects postsurgery (23), and electrical stimulation of medial temporal lobe circuitry produces visual hallucinations of somewhat similar nature to those produced by psychedelics [e.g., distorted visual perception (24) and dreamlike “visions” (25)].The present study sought to investigate the acute brain effects of LSD in healthy volunteers, using a comprehensive placebo-controlled neuroimaging design incorporating ASL, BOLD signal measures, and MEG resting state scans. It was predicted that major RSNs (e.g., the DMN) and hippocampal/parahippocampal gyri circuitry would be implicated in the drug’s mechanism of action.Twenty healthy participants attended two scanning days (LSD and placebo) at least 2 wk apart in a balanced-order, within-subjects design. Sessions included an fMRI followed by a MEG scan, each lasting 75 min. Data were acquired during eye-closed, task-free, “resting state” conditions. Drug/placebo were administered in solution and injected i.v. over the course of 2 min. Two resting state ASL scans totaling 16 min were completed 100 min after i.v. administration of LSD (75 µg in 10 mL saline) or placebo (10 mL saline), corresponding to the initial phase of the peak subjective effects of LSD (peak effects were reached ∼120–150 min postinfusion). Two resting state BOLD scans totaling 14 min were completed 135 min postinfusion, and two resting state MEG scans totaling 14 min were completed 225 min postinfusion. All analyses applied multiple comparison correction (SI Appendix) and two-tailed hypothesis testing unless particularly strong prior hypotheses were held.     

Psychodynamic day treatment program for borderline personality disorder: factors that predict outcome and dropout: An observational study

The objective of this study was to ascertain changes in symptoms of patients with borderline personality disorder undergoing psychodynamic day treatment with a duration of 9 months and the factors that predict clinical outcome or dropouts from the program.In an observational study, demographic characteristics (age, number of psychiatric hospitalizations, number of suicide attempts, current involvement in work or study activities), day doses of antipsychotic and antidepressant medication, psychiatric symptoms, and social functioning (Health of the Nation Outcome Scales), and symptoms of dissociation (Dissociative Experiences Scale) were assessed in patients at the beginning of treatment (N = 105). Further, psychiatric symptoms and social functioning were assessed at 3 stages: beginning of the program, end of the program, and 1-year follow-up. To study the differences between baseline values and values at the end of the treatment and follow-up values, the Wilcoxon signed-rank test was used. To discover baseline factors related to the effect of the treatment, Spearman correlation coefficients were calculated. To evaluate the differences between patients who completed the program (N = 67) and patients who dropped out (N = 38), differences in baseline factors between both groups were compared, using the Mann–Whitney test for independent samples.Improvement in symptoms (Health of the Nation Outcome Scales – version for external evaluators) at the end of the therapy (N = 67, P < .001) and at the 1-year follow-up (N = 46, P < .001) was found. Experience of an intimate relationship was positively related to clinical improvement at follow-up examinations (P < .001). Predictors of dropout included a higher number of psychiatric hospitalizations (P = .004), suicide attempts (P = .004), more severe pretreatment symptoms (P = .002), and symptoms of dissociation (P = .046).The results indicate that a psychodynamic day treatment is feasible for the treatment of less clinically disturbed patients with a history of intimate relationships. Patients with a higher number of previous psychiatric hospitalizations, more suicide attempts in the past, more severe pretreatment symptoms, and symptoms of dissociation are more likely not to complete the program.     

Pharmacological treatment response according to the severity of symptoms in patients with chronic obstructive pulmonary disease

Background

Pharmacological management of chronic obstructive pulmonary disease (COPD) is recommended according to the individualized assessment of symptoms and exacerbation risks. The aim of this study was to determine the relationship between the baseline Modified British Medical Research Council (mMRC) dyspnea scale and the COPD Assessment Test (CAT) score and pharmacological treatment response in patients with COPD.

Methods

A total of 102 stable COPD patients who were enrolled in prospective cohort studies were analyzed. Pharmacological treatment responses after a 3-month treatment were assessed by changes on the mMRC dyspnea scale, CAT scores, and spirometric pulmonary functions.

Results

Sixty-two patients with a mMRC dyspnea scale ≤1 were classified as having “less dyspnea” and 40 patients with a mMRC dyspnea scale ≥2 as having “more dyspnea”. After a 3-month treatment, the mean mMRC dyspnea scale in the “more dyspnea” group was significantly decreased versus the “less dyspnea” group; however, there were no significant differences in CAT score changes or spirometric pulmonary function changes between the two groups. Baseline mMRC scales (Spearman’s rho =−0.591, P<0.001) and baseline CAT scores (Pearson’s r =−0.337, P=0.001) were significantly correlated with their changes after a 3-month treatment. Multiple logistic regression analysis demonstrated that baseline mMRC scale and CAT score were the only independent predictors of improvement greater than a minimal clinically significant difference after treatment.

Conclusions

The severity of COPD symptoms is associated with their response to pharmacotherapy. COPD patients with a higher baseline mMRC dyspnea scale and CAT score experience greater symptom reduction by pharmacotherapy.     

Mental health of nurses involved with COVID-19 patients in Japan,intention to resign,and influencing factors

The purpose of this study was to investigate the association between mental health (posttraumatic stress disorder, depression, anxiety disorder, and burnout) and intention to resign, and influencing factors regarding nurses involved with COVID-19 patients in A Prefecture as subjects.The design is a cross-sectional questionnaire-based study.Methods are conducted between August 4 and October 26, 2020. Basic attributes (gender, age, years of experience, etc.) were examined. Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7, Impact of Event Scale-Revised, Maslach Burnout Inventory, “intent to resign,” were used to collect data from nurses working at hospitals treating patients with COVID-19 in Japan.As a result, between 20% and 30% of nurses involved with patients with COVID-19 are in a state of high mental distress. Regarding the associations between psychiatric symptoms and intention to resign, “I want to quit being a nurse” was affected by “cynicism” and “professional efficacy”; “I want to change hospitals/wards” was affected by “cynicism”; and “subthreshold depression,” “anxiety disorder,” and “burnout” affected “I want to continue working as a nurse.” The increase in the number of patients with COVID-19 was a factor affecting mental health and intention to resign. When the number of patients increased, anxiety disorders and intention to resign also increased. Damage from harmful rumors increased the severity of every psychiatric symptom. To prepare for a pandemic such as COVID-19, it is necessary in normal times to construct psychological support systems and community systems to prevent damage from harmful rumors.     

Outcome of parapneumonic empyema managed surgically or by fibrinolysis: a multicenter study

BackgroundParapneumonic empyema (PPE) management remains debated. Here we present the outcome of a comparable population with PPE treated over a 4-year period in two Thoracic Surgery University Centers with different approaches: one with an early “surgical” and the other with a “fibrinolytic” approach.MethodsAll operable patients with PPE managed in both centers between January 2014 and January 2018 were reviewed. Patients with persistent pleural effusion/loculations following drainage were managed by a “surgical” approach in one center and by “fibrinolytic” approach in the other. For each patient, we recorded the age, sex, hospital stay, morbidity/mortality and change in pleural opacity on chest X-ray before and at the end of the treatment.ResultsDuring the study period, 66 and 93 patients underwent PPE management in the “surgical” and “fibrinolytic” centers respectively. The population characteristics were comparable. Infection was controlled in all patients. In the “fibrinolytic” group, 20 patients (21.5%) underwent an additional drain placement while 12 patients (12.9%) required surgery to correct PPE. In the “surgical” group, 4 patients (6.1%) developed postoperative arrhythmia while 2 patients (3%) underwent a second surgery to evacuate a hemothorax. Median drainage {3 [2–4] vs. 5 [4–7] days} and hospital {7 [5–10] vs. 11 [7–19] days} durations were significantly lower in the “surgical” compared to the “fibrinolytic” center. Pleural opacity regression with therapy was significantly more important in the “surgical” compared to the “fibrinolytic” group (−22%±18% vs. −16%±17%, P=0.035).ConclusionsSurgical management of PPE was associated with shorter chest tube and hospital duration and better pleural space control. Prospective randomized studies are mandatory.     

Can We Clinically Recognize a Vascular Depression?: The Role of Personality in an Expanded Threshold Model

The vascular depression (VD) hypothesis postulates that cerebrovascular disease may “predispose, precipitate, or perpetuate” a depressive syndrome in elderly patients. Clinical presentation of VD has been shown to differ to major depression in quantitative disability; however, as little research has been made toward qualitative phenomenological differences in the personality aspects of the symptom profile, clinical diagnosis remains a challenge.We attempted to identify differences in clinical presentation between depression patients (n = 50) with (n = 25) and without (n = 25) vascular disease using questionnaires to assess depression, affect regulation, object relations, aggressiveness, alexithymia, personality functioning, personality traits, and counter transference.We were able to show that patients with vascular dysfunction and depression exhibit significantly higher aggressive and auto-aggressive tendencies due to a lower tolerance threshold. These data indicate that VD is a separate clinical entity and secondly that the role of personality itself may be a component of the disease process. We propose an expanded threshold disease model incorporating personality functioning and mood changes. Such findings might also aid the development of a screening program, by serving as differential criteria, ameliorating the diagnostic procedure.     

Personality as a predictor of HbA1c level in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for around 90% of all cases worldwide. One means to strengthen the prevention and treatment of diabetes is via changes in self-management and lifestyle behaviors. However, lifestyle and personal health behaviors are strongly influenced by personality traits, and thus personality may play a significant role in such aspects as medication compliance, exercise habits, blood glucose monitoring, diet control, and maintenance of an ideal body weight.In this study, we examined whether certain personality traits of patients with T2DM are correlated with higher glycohemoglobin (HbA1c) levels.A total of 214 participants with T2DM were recruited from an outpatient setting. χ² test and logistic regression analyses with 5 models were employed.The OR for the “neuroticism” trait was 3.199 (95% CI = 1.228–8.331, P = .017), and those with this trait were 3.199 times more likely to have higher HbA1c levels than those with the “openness-extraversion” personality trait. This strong relationship between neuroticism and a higher HbA1c level was also evident in models 2, 3, 4, and 5. One-way ANOVA also indicated that the group with the neuroticism personality trait had significantly different mean fasting glucose, HbA1c, triglyceride, and high-density lipoprotein cholesterol levels.We found that a personality characterized by neuroticism is an independent predictor of higher HbA1c level in this study. We also found that people in the pre-contemplation and contemplation stages of exercise have higher HbA1c levels.     

Methotrexate can prevent cardiovascular events in patients with rheumatoid arthritis: An updated meta-analysis

Aims:The incidence of cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA) is higher than that in people without RA. This may be because inflammation promotes the progression of atherosclerosis. Anti-inflammatory drugs might reduce the occurrence of CVEs in patients with RA. Methotrexate (MTX) is a conventional synthetic anti-rheumatic drug that is widely used in the treatment of RA. We performed a meta-analysis to determine whether MTX can prevent CVEs in RA patients. Then, we discussed the possibility of using MTX to prevent recurred CVEs in patients with coronary heart disease (CHD).Methods:We searched PubMed, Embase, Web of Science, and the Cochrane Library using the key words “methotrexate,” “cardiovascular,” “acute coronary syndrome,” “coronary heart disease,” “myocardial infarction,” “angina pectoris,” and “rheumatoid arthritis.” The efficacy outcome was defined as a composite of CVEs, including stable angina, acute coronary syndrome, stroke, heart failure, and cardiac death.Results:A total of 10 studies and 195,416 RA patients were included in our meta-analysis, and the effect size of relative risk (RR) was pooled using a fixed effect model. The results showed that MTX prevented CVEs in RA patients (RR: 0.798, 95% CI 0.726–0.876, P = .001, I² = 27. 9%).Conclusion:MTX can prevent CVEs in RA patients, but there is not sufficient evidence for using MTX to treat patients with CHD.     

Surgery vs non-surgery in cutaneous melanoma based on SEER database: A cross-sectional study

This study was to assess the survival outcome of cutaneous melanoma (CM) patients with surgery vs non-surgery through inverse probability of treatment weighting (IPTW) using the propensity score. Patients diagnosed as CM were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. The survival outcome was estimated and compared by IPTW using the propensity score. Totally 2203 CM patients were identified, in which 1921 cases received surgical treatment (surgery group), while 282 cases didn’t (non-surgery group). The median survival time of surgery and non-surgery groups was respectively 150 months and 15 months (unmatched cohort), 70 months and 40 months (matched cohort) and 130 months vs. 75 months (IPTW-weighted cohort). Compared with the non-surgery group, the surgery group had a lower risk of death in unmatched [hazard ratio (HR): 0.647, 95% confidence interval (CI): 0.509–0.821, P < .001] and matched (HR: 0.636, 95%CI: 0.459–0.882, P < .01) cohorts. In multivariate Cox model of IPTW-weighted cohort, the risk of death in the surgery group decreased notably than the non-surgery group (HR: 0.423, 95%CI: 0.383–0.468, P < .001). In conclusion, CM patients receiving surgical treatment are associated with a better survival outcome compared with those without surgical treatment through IPTW using the propensity score.     

A “Bone Marrow Score” for Predicting Hematological Disease in Immunocompetent Patients With Fevers of Unknown Origin

Delayed diagnosis of hematological malignancies in immunocompetent patients with fever of unknown origin (FUO) remains an exhausting challenge for non-hematologist physicians. This retrospective cohort study aimed to establish a scoring system, “bone marrow (BM) score”, to identify FUO patients who require early bone marrow biopsy (BMB) to diagnose hematological disease.Two cohorts, comprising 85 (training) and 20 (validation) eligible immunocompetent patients, with FUOs diagnosed between January 1, 2006 and July 31, 2013, underwent BMBs and were enrolled in the study. Demographic, laboratory, imaging, diagnostic, and outcome data were collected and retrospectively analyzed. Factors associated with hematological etiologies diagnosed using BMBs in the training cohort were identified and scored according to the relative hazards. These were further validated using the validation cohort.For the training cohort, 29 of 85 (34.1%) patients had hematological etiologies diagnosed using BMB. Seven factors significantly predicted the diagnostic yield of hematological diseases in the BM and were scored, with the 6 points for leucoerythroblastic changes in peripheral blood smears, 5.5 for elevated ferritin level (>1000 ng/mL), 4 for splenomegaly, 2 for thrombocytopenia, 1.5 for each of elevated lactate dehydrogenase levels and anemia, and 1 for neutropenia. When the cut-off value of the scoring system was set to 6, its sensitivity and specificity to diagnose hematological diseases in the BM of immunocompetent FUO patients were 93% and 58%, respectively. For the validation cohort, 7 of 20 (35%) patients had hematological disease, and all had BM scores higher than the cut-off, with the sensitivity and specificity at 100% and 77%, respectively.As immunocompetent FUO patients with hematological disease have poor prognoses, the “BM score” is valuable for non-hematologist physicians to identify immunocompetent FUO patients requiring early BMB.     

Prediction of Individual Basal Rate Profiles From Patient Characteristics in Type 1 Diabetes on Insulin Pump Therapy

Background:Basal rate profiles in patients with type 1 diabetes on insulin pump therapy are subject to enormous inter-individual heterogeneity. Tools to predict basal rates based on clinical characteristics may facilitate insulin pump therapy.Methods:Data from 339 consecutive in-patients with adult type 1 diabetes on insulin pump therapy were collected. Basal rate tests were performed over 24 hours. A mathematical algorithm to predict individual basal rate profiles was generated by relating the individual insulin demand to selected clinical characteristics in an exploratory cohort of 170 patients. The predicted insulin pump profiles were validated in a confirmatory cohort of 169 patients.Findings:Basal rates (0.27 ± 0.01 IU.d^−1.kg⁻¹) showed circadian variations with peaks corresponding to the “dawn” and “dusk” phenomena. Age, gender, duration of pump treatment, body-mass-index, HbA_1c, and triacylglycerol concentrations largely predicted the individual basal insulin demand per day (IU/d; exploratory vs prospective cohorts: r² = 0.518, P < .0001). Model-predicted and actual basal insulin rates were not different (exploratory cohort: Δ 0.1 (95% CI −0.9; 1.0 U/d; P = .95; prospective cohort: Δ −0.5 (95% CI −1.5; 0.6 IU/d; P = .46). Similarly, precise predictions were possible for each hour of the day. Actual and predicted “dawn” index correlated significantly in the exploratory but not in the confirmatory cohort.Interpretation:Clinical characteristics predict 52% of the variation in individual basal rate profiles, including their diurnal fluctuations. The multivariate regression model can be used to initiate or optimize insulin pump treatment in patients with type 1 diabetes.     

Effect of 23-Valent Pneumococcal Polysaccharide Vaccine Inoculated During Anti-Cancer Treatment Period in Elderly Lung Cancer Patients on Community-Acquired Pneumonia Hospitalization: A Nationwide Population-Based Cohort Study

To evaluate effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) inoculated during defined “vaccination period,” first 6 months post cancer diagnosis (ie, an anti-cancer treatment period), in elderly lung cancer patients on community-acquired pneumonia (CAP) hospitalization incidence.This was a nationwide population-based cohort study of 157 newly diagnosed elderly lung cancer patients receiving PPSV23 during “vaccination period”, and 628 age and sex one-to-one matched controls enrolled in the National Health Insurance Research Database (NHIRD) of Taiwan between 2007 and 2010. All patients were ≥75 years old and still survival post “vaccination period.” Incidence density (ID) of all-cause inpatient CAP and cumulative survival risk were analyzed by multivariate Poisson regression and Kaplan–Meier method, respectively.After a 4-year follow-up, IDs of all-cause inpatient CAP for vaccination and control cohorts were 297 and 444 per 1000 PYs, respectively. Less vaccinated patients had CAP incidence density >1 time per PY (12.7% vs 21.2%) than non-vaccinated patients. After adjusting for potential confounding variables, like influenza vaccination, comorbidities, cancer treatment modalities, and socioeconomic status, adjusted inpatient CAP incidence rate in PPSV23 vaccination cohort was 0.74 times lower than control cohort (incidence rate ratio [IRR] = 0.740, P = 0.0339). Two-year cumulative CAP hospitalization rates and overall survival rates were 37.1% vs. 55.4%, and 46.6% vs. 26.2%, respectively, for lung cancer patients with and without PPSV23 (both P < 0.001). Subgroup analysis showed that for elderly lung cancer patients not ever receiving influenza vaccine, PPSV23 still had trend to reduce all-cause inpatient CAP.For elderly lung cancer patients aged ≥75 years, PPSV23 inoculated during anti-cancer treatment period could reduce CAP hospitalizations and improve survival.     

Changes in Disability Levels Among Older Adults Experiencing Adverse Events in Postacute Rehabilitation Care: A Prospective Observational Study

This study aimed to assess the relationship between adverse events (AEs) and changes in the levels of disability from admission to discharge during inpatient rehabilitation programs.A prospective cohort study was conducted among a cohort of inpatients (216 older adults) admitted to a rehabilitation unit. The occurrences of any AE were reported. The level of disability regarding mobility activities was estimated using the disability qualifiers from the International Classification of Functioning, Disability, and Health. Changes in the levels of disability between admission and discharge were assessed. Baseline-measured covariates were also selected.Regarding all 4 disability levels (“no limitation,” “mild,” “moderate,” “severe,” and “complete disability”), a total of 159 participants experienced an improvement at discharge (126 participants progressed 1 level, whereas 33 improved 2 disability levels), 56 made no change, and no participants experienced a decline.The occurrence of fall-related events and the diagnostic group (musculoskeletal system) are specific predictive factors of change in the level of disability. The odds of undergoing a change in any disability level between admission and discharge decreases by 68% (1–0.32) when patients experience fall-related events (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.11–0.97, P = 0.041) and increases for individuals with musculoskeletal conditions (OR = 3.91, 95% CI = 1.34–11.38, P = 0.012).Our findings suggest that increased efforts to prevent the occurrence of these AEs, together with early interventions suited to the diagnosis of the affected system, may have a positive influence on the improvement of disability. Further studies should evaluate disability over time after discharge to obtain a better sense of how transient or permanent the associated disability may be.     

Efficacy of ultrasound-accelerated versus traditional catheter-directed thrombolysis in treatment of lower extremity deep venous thrombosis: A protocol for systematic review and meta-analysis

Background:There is no meta-analysis or review in the literature to compare and evaluate the difference and effectiveness of ultrasonic-accelerated thrombolysis (UAT) and catheter directed thrombolysis (CDT) in lower extremity deep vein thrombosis (DVT) patients. Therefore, we conducted this protocol of systematic review and meta-analysis to evaluate the efficacy between UAT and CDT for patients with lower extremity DVT.Methods:We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines to conduct this study. Reviewers will search the PubMed, Cochrane Library, Web of Science, and EMBASE online databases using the key phrases “deep venous thrombosis,” “thrombolysis,” and “ultrasound-accelerated” for all cohort studies published up to July 22, 2021. There is no restriction in the dates of publication or language in the search for the current review. The primary outcome is major bleeding. Secondary outcomes include health-related quality of life and complications such as recurrent venous thromboembolism, pulmonary embolism, in-stent thrombosis, and death. Review Manager software (v 5.4; Cochrane Collaboration) will be used for the meta-analysis. A P value of < .05 is considered to be statistically significant.Results:We hypothesized that these two methods would provide similar therapeutic benefits.OSF registration number:10.17605/OSF.IO/YZB3H.     

A narrative review of progress in airway stents

Background and ObjectiveAirway stents, used to restore airway patency, are mostly utilized by patients with malignant airway strictures, and are occasionally used in a range of other airway related diseases, including conditions which result in benign stenosis, malacia, and fistula. There has been an increasing number of airway stents that are being developed thanks to improvements in interventional therapy. However, the method of promoting airway stents for clinical application remains undetermined. Herein, we describe the recent advances in airway stents by reviewing the published studies, providing the reference for clinical decision-making and further research on airway stents.MethodsRelevant articles between January 1964 and November 2021 were obtained from PubMed, Web of Science, and EMBASE databases. The terms “metallic”, “silicone”, “drug-eluting", “biodegradable”, “radioactive”, “three-dimensional (3D)”, and “stents” were searched in different combinations.Key Content and FindingsIn this review, we focus on the latest evidence in terms of the application of various stents with novel materials and designs including novel metallic, novel silicone, drug-eluting, biodegradable, radioactive, and 3D stents for airway stenosis. Despite reducing the well-known complications of all current commercially available stents, novel stents are still in their infancy without a long track record of utility and safety, and remain some limitations. There are more steps to be taken before such stents enter routine clinical practice.ConclusionsA combination of 3D-printing method and biodegradable material may present a promising avenue of solving the existing problems pertaining to “classic” stents and has potential to become the main trend in the future.     

Incidence of venous thromboembolism in rheumatoid arthritis,results from a “real-life” cohort and an appraisal of available literature

Rheumatoid arthritis (RA) is associated with an increased risk of venous thromboembolism (VTE) occurrence. In this work, we assessed the incidence and predictive factors of VTE in our “real-life” cohort of RA patients. To contextualize our results, we reviewed the available literature about this topic.We performed a retrospective analysis of prospectively followed-up patients with RA attending our Rheumatologic Clinic between January 2010 and December 2020. Each patient was investigated for VTE occurrence. Incident cases were reported as incidence proportion and incidence rate per 1000 person-years at risk. Possible predictive factors were also exploited by regression analyses. Available literature about this topic was also assessed.In this evaluation, 347 consecutive patients without previous evidence of VTE, attending our Rheumatologic Clinic from 2010 to 2020, were studied. In our “real-life” cohort, the incidence proportion of VTE was 3.7% (2.7–4.7%) and considering over 1654 person-years, an incidence rate of 7.8 × 1000 (2.5–11.7). Exploratively assessing predictive factors in our cohort, older age (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01–1.14, p = .015), higher body mass index (HR 1.37, 95% CI 1.04–1.80, P = .026), and longer disease duration (HR 1.11, 95% CI 1.03–1.20, P = .006) resulted to be significant predictors of VTE occurrence during the follow-up.In our “real-life” cohort, VTE burden has been suggested in patients with RA. Comparing our results with previous data derived from randomized controlled trials and administrative data, some different findings were retrieved about incidence of VTE. Assessing predictive factors, older age, higher body mass index, and longer disease duration resulted to be significant predictors of VTE occurrence during the follow-up. Taking together these observations, a further evaluation of this issue on specific designed studies is needed to provide more generalizable results to the daily clinical practice.     

Changes in Echocardiographic Parameters According to the Rate of Residual Renal Function Decline in Incident Peritoneal Dialysis Patients

Residual renal function (RRF) is associated with left ventricular (LV) hypertrophy as well as all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease. However, no studies have yet examined the serial changes in echocardiographic findings according to the rate of RRF decline in incident dialysis patients.A total of 81 patients who started peritoneal dialysis (PD) between 2005 and 2012 at Yonsei University Health System, Seoul, South Korea, and who underwent baseline and follow-up echocardiography within the first year of PD were recruited. Patients were dichotomized into “faster” and “slower” RRF decline groups according to the median values of RRF decline slope (−1.60 mL/min/y/1.73 m²).Baseline RRF and echocardiographic parameters were comparable between the 2 groups. During the first year of PD, there were no significant changes in LV end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), or LV mass index (LVMI) in the “faster” RRT decline group, while these indices decreased in the “slower” RRT decline group. The rate of RRF decline was a significant determinant of 1-year changes in LVEDVI, LAVI, and LVMI. The linear mixed model further confirmed that there were significant differences in the changes in LVEDVI, LAVI, and LVMI between the 2 groups (P = 0.047, 0.048, and 0.001, respectively). During a mean follow-up duration of 31.9 months, 4 (4.9%) patients died. Compared with the “slower” RRF decline group, CV composite (20.29/100 vs 7.18/100 patient-years [PY], P = 0.098), technique failure (18.80/100 vs 4.19/100 PY, P = 0.006), and PD peritonitis (15.73/100 vs 4.95/100 PY, P = 0.064) developed more frequently in patients with “faster” RRF decline rate. On multivariate Cox regression analysis, patients with “faster” RRF decline rate showed 4.82-, 4.44-, and 7.37-fold higher risks, respectively, for each clinical outcome.Preservation of RRF is important for conserving cardiac performance, resulting in an improvement in clinical outcomes of incident PD patients.     

Factorial study of moxibustion in treatment of diarrhea-predominant irritable bowel syndrome

AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome (D-IBS).METHODS: A factorial design was employed to examine the two factors of moxibustion frequency and number of cones. The two tested frequencies were three or six moxibustion sessions per week, and the two tested doses were one or two cones per treatment. A total of 166 D-IBS patients were randomly divided into four treatment groups, which included each combination of the examined frequencies and doses. The bilateral Tianshu acupoints (ST25) and the Qihai acupoint (RN6) were selected for aconite cake-separated moxibustion. Each patient received two courses of treatment, and each course had a duration of 2 wk. For each group, the scores on the Birmingham irritable bowel syndrome (IBS) symptom questionnaire, the IBS Quality of Life scale, the Self-Rating Depression Scale (SDS), the Self-Rating Anxiety Scale (SAS), the Hamilton Depression (HAMD) scale, and the Hamilton Anxiety (HAMA) scale were determined before treatment, after the first course of treatment, and after the second course of treatment.RESULTS: The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all 4 aconite cake-separated moxibustion groups were significantly lower after the first and second courses of treatment than before treatment (P < 0.001 for all). The symptom, quality of life, SDS, SAS, HAMD, and HAMA scores of the patients in all four aconite cake-separated moxibustion groups were significantly lower after the second course of treatment than after the first course of treatment (P < 0.001 for all). Between-group comparisons after the second course of treatment revealed that the symptom scores for group 1 (1 cone, 3 treatments/wk) and group 3 (2 cones, 3 treatments/wk) were significantly lower than that for group 2 (1 cone, 6 treatments/wk) (5.55 ± 5.05 vs 10.45 ± 6.61, P < 0.001; 5.65 ± 4.00 vs 10.45 ± 6.61, P < 0.001). Regarding the two levels of the two examined factors for aconite cake-separated moxibustion, after the first course of treatment, the changes in HAMA scores were significantly different for the two tested moxibustion frequencies (P = 0.011), with greater changes for the “6 treatments/wk” groups than for the “3 treatments/wk” groups; in addition, there were interaction effects between the number of cones and moxibustion frequency (P = 0.028). After the second course of treatment, changes in symptom scores for the 2 tested moxibustion frequencies were significantly different (P = 0.002), with greater changes for the “3 treatments/wk” groups than for the “6 treatments/wk” groups.CONCLUSION: An aconite cake-separated moxibustion treatment regimen of 3 treatments/wk and 1 cone/treatment appears to produce better therapeutic effects for D-IBS compared with the other tested regimens.