The quality of social determinants data in the electronic health record: a systematic review

ObjectiveThe aim of this study was to collect and synthesize evidence regarding data quality problems encountered when working with variables related to social determinants of health (SDoH).Materials and MethodsWe conducted a systematic review of the literature on social determinants research and data quality and then iteratively identified themes in the literature using a content analysis process.ResultsThe most commonly represented quality issue associated with SDoH data is plausibility (n = 31, 41%). Factors related to race and ethnicity have the largest body of literature (n = 40, 53%). The first theme, noted in 62% (n = 47) of articles, is that bias or validity issues often result from data quality problems. The most frequently identified validity issue is misclassification bias (n = 23, 30%). The second theme is that many of the articles suggest methods for mitigating the issues resulting from poor social determinants data quality. We grouped these into 5 suggestions: avoid complete case analysis, impute data, rely on multiple sources, use validated software tools, and select addresses thoughtfully.DiscussionThe type of data quality problem varies depending on the variable, and each problem is associated with particular forms of analytical error. Problems encountered with the quality of SDoH data are rarely distributed randomly. Data from Hispanic patients are more prone to issues with plausibility and misclassification than data from other racial/ethnic groups.ConclusionConsideration of data quality and evidence-based quality improvement methods may help prevent bias and improve the validity of research conducted with SDoH data.     

Effects on physiologic measures of appetite from intragastric balloon and endoscopic sleeve gastroplasty: results of a prospective study

Background:Endoscopic bariatric therapies can help address widening management gaps in obesity. Their ability to facilitate weight loss is largely tied to influences on appetite through perturbations of gastric emptying and accommodation. As these tools gain traction in obesity therapy, their physiologic underpinnings require exploration, which may enhance efficacy, tolerance, and patient-tailored care.Methods:We prospectively assessed consecutive subjects with fluid-filled intragastric balloons (IGBs) (n = 18) placed between October 2016 and June 2017 or underwent endoscopic sleeve gastroplasty (ESG) (n = 23) from March 2018 to June 2018. Patients underwent physiologic appraisal at 3 months with ¹³C-spirulina-based gastric emptying breath test to determine time to half emptying (T50), as well as maximum tolerated volume (MTV) of a standard nutrient drink test. Changes in T50 and MTV at 3 months were compared with percent total body weight loss (%TBWL) at 3 and 6 months using best-fit linear regression.Results:The change in T50 at 3 months correlated with %TBWL at 3 months for IGB (P = 0.01) and ESG (P = 0.01) but with greater impact on %TBWL in IGB compared to ESG (R² = 0.42 vs. 0.26). Change in T50 at 3 months was predictive of weight loss at 6 months for IGB (P = 0.01) but not ESG (P = 0.11). ESG was associated with greater decrease in MTV compared to IGB (340.25 ± 297.97 mL vs. 183.00 ± 217.13 mL, P = 0.08), indicting an enhanced effect on satiation through decreased gastric accommodation. Changes in MTV at 3 months did not correlate with %TBWL for either IGB (P = 0.26) or ESG (P = 0.49) but trended toward significance for predicting %TBWL at 6 months for ESG (P = 0.06) but not IGB (P = 0.19).Conclusion:IGB and ESG both induce weight loss but likely through distinct gastric motor function phenotypes, and gastric emptying may predict future weight loss in patients with IGB.     

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China

Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n = 72) or allo-HSCT (n = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2–143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.     

A study of medial and lateral temporal lobe epilepsy based on stereoelectroencephalography

BackgroundPatients with temporal lobe epilepsy (TLE) originating from different seizure onset zones had distinct electrophysiological characteristics and surgical outcomes. In this study, we aimed to investigate the relationship between the origin and prognosis of TLE, and the stereoelectroencephalography (SEEG) features.MethodsThirty patients with TLE, who underwent surgical treatment in our functional neurosurgery department from January 2016 to December 2017, were enrolled in this study. All patients underwent anterior temporal lobectomy after an invasive pre-operative evaluation with SEEG. Depending on the epileptic focus location, patients were divided into those with medial temporal lobe seizures (MTLS) and those with lateral temporal lobe seizures (LTLS). The Engel classification was used to evaluate operation effectiveness, and the Kaplan-Meier analysis was used to detect seizure-free duration.ResultsThe mean follow-up time was 25.7 ± 4.8 months. Effectiveness was 63.3% for Engel I (n = 19), 13.3% for Engel II, 3.3% for Engel III, and 20.0% for Engel IV. According to the SEEG, 60.0% (n = 18) had MTLS, and 40.0% (n = 12) had LTLS. Compared with the MTLS group, the operation age of those with LTLS was significantly greater (26.9 ± 6.9 vs. 29.9 ± 12.5 years, t = −0.840, P = 0.009) with longer epilepsy duration (11.9 ± 6.0 vs. 17.9 ± 12.1 years, t = −1.801, P = 0.038). Patients with MTLS had a longer time interval between ictal onset to seizure (67.3 ± 59.1 s vs. 29.3 ± 24.4 s, t = 2.017, P = 0.008). The most common SEEG ictal pattern was a sharp/spike-wave rhythm in the MTLS group (55.6%) and low-voltage fast activity in the LTLS group (58.3%). Compared with the LTLS group, patients with MTLS had a more favorable prognosis (41.7% vs. 77.8%, P = 0.049). Post-operative recurrence was more likely to occur within three months after the operation for both groups, and there appeared to be a stable long-term outcome.ConclusionPatients with MTLS, who accounted for three-fifths of patients with TLE, showed a more favorable surgical outcome.     

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients

Background:Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.Methods:One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.Results:HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log₁₀ U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log₁₀ U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score (r = −0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = −0.263, P = 0.014) and HBeAg-negative patients (r = −0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log₁₀ U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).Conclusions:HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.Trial registration:Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1     

Risk factors associated with the progression from keloids to severe keloids

Background:Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients’ quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids.Methods:In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients’ interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids.Results:Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration > 15 years (OR, 2.98; P = 0.046).Conclusion:Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration > 15 years.     

Retrospective analysis of sentinel lymph node biopsy using methylene blue dye for early breast cancer

BackgroundMethylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses.MethodsWe retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves.ResultsBetween January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ² = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ² = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ² = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224−0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006).ConclusionOur single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.     

Can decision support combat incompleteness and bias in routine primary care data?

ObjectiveRoutine primary care data may be used for the derivation of clinical prediction rules and risk scores. We sought to measure the impact of a decision support system (DSS) on data completeness and freedom from bias.Materials and MethodsWe used the clinical documentation of 34 UK general practitioners who took part in a previous study evaluating the DSS. They consulted with 12 standardized patients. In addition to suggesting diagnoses, the DSS facilitates data coding. We compared the documentation from consultations with the electronic health record (EHR) (baseline consultations) vs consultations with the EHR-integrated DSS (supported consultations). We measured the proportion of EHR data items related to the physician’s final diagnosis. We expected that in baseline consultations, physicians would document only or predominantly observations related to their diagnosis, while in supported consultations, they would also document other observations as a result of exploring more diagnoses and/or ease of coding.ResultsSupported documentation contained significantly more codes (incidence rate ratio [IRR] = 5.76 [4.31, 7.70] P < .001) and less free text (IRR = 0.32 [0.27, 0.40] P < .001) than baseline documentation. As expected, the proportion of diagnosis-related data was significantly lower (b = −0.08 [−0.11, −0.05] P < .001) in the supported consultations, and this was the case for both codes and free text.ConclusionsWe provide evidence that data entry in the EHR is incomplete and reflects physicians’ cognitive biases. This has serious implications for epidemiological research that uses routine data. A DSS that facilitates and motivates data entry during the consultation can improve routine documentation.     

Performance and comparison of assessment models to predict 30-day mortality in patients with hospital-acquired pneumonia

BackgroundHospital-acquired pneumonia (HAP) is the most common hospital-acquired infection in China with substantial morbidity and mortality. But no specific risk assessment model has been well validated in patients with HAP. The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.MethodsThis study was a single-center, retrospective study. In total, 223 patients diagnosed with HAP from 2012 to 2017 were included in this study. Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index (PSI); consciousness, urea nitrogen, respiratory rate, blood pressure, and age ≥65 years (CURB-65); Acute Physiology and Chronic Health Evaluation II (APACHE II); Sequential Organ Failure Assessment (SOFA); and Quick Sequential Organ Failure Assessment (qSOFA) scores. The discriminatory power was tested by constructing receiver operating characteristic (ROC) curves, and the areas under the curve (AUCs) were calculated.ResultsThe all-cause 30-day mortality rate was 18.4% (41/223). The PSI, CURB-65, SOFA, APACHE II, and qSOFA scores were significantly higher in non-survivors than in survivors (all P < 0.001). The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores (ROC AUC: APACHE II vs. CURB-65, 0.863 vs. 0.744, Z = 3.055, P = 0.002; APACHE II vs. qSOFA, 0.863 vs. 0.767, Z = 3.017, P = 0.003; SOFA vs. CURB-65, 0.856 vs. 0.744, Z = 2.589, P = 0.010; SOFA vs. qSOFA, 0.856 vs. 0.767, Z = 2.170, P = 0.030). The cut-off values we defined for the SOFA, APACHE II, and qSOFA scores were 4, 14, and 1.ConclusionsThese results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments. The qSOFA score may be a simple tool that can be used to quickly identify severe infections.     

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials

Background:The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19.Methods:Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.Results:Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20–0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75–0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60–2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05–1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18–8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38–0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20–5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02–7.08) vs. SOC with very low quality were associated with an increased risk.Conclusions:COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.     

A double-blind,double-dummy,randomized controlled,multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

Background:Clinical observational studies revealed that ⁹⁹Tc-methylene diphosphonate (⁹⁹Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of ⁹⁹Tc-MDP plus methotrexate (MTX) vs. MTX alone or ⁹⁹Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.Methods:Eligible patients with moderate to severely active RA were randomized to receive ⁹⁹Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or ⁹⁹Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.Results:At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + ⁹⁹Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or ⁹⁹Tc-MDP group (47.5%) (P = 0.03 for MTX + ⁹⁹Tc-MDP vs. MTX, and MTX + ⁹⁹Tc-MDP vs.⁹⁹Tc-MDP, respectively). The participants in the MTX + ⁹⁹Tc-MDP group and the ⁹⁹Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + ⁹⁹Tc-MDP vs. MTX: P = 0.03, ⁹⁹Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.Conclusions:This study demonstrated that the combination of ⁹⁹Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and ⁹⁹Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of ⁹⁹Tc-MDP therapy in patients with RA are warranted.Trial Registration:Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.     

D2 lymphadenectomy with complete mesogastrium excision vs. conventional D2 gastrectomy for advanced gastric cancer

Background:The complete mesogastrium excision (CME) based on D2 radical gastrectomy is believed to significantly reduce the local-regional recurrence compared with D2 radical gastrectomy in advanced gastric cancer, and it is widely used in China. This study aimed to explore whether D2 + CME is superior to D2 on surgical outcomes during gastrectomy from Chinese data.Methods:Feasible studies comparing the D2 + CME (D2 + CME group) and D2 (D2 group) published up to March 2020 are searched from electronic databases. The data showing surgical and complication outcomes are extracted to be pooled and analyzed.Results:Fourteen records including 1352 patients were included. The D2 + CME group had a shorter mean operative time (weighted mean difference [WMD] = —16.72 min, 95% confidence interval [CI]: −26.56 to −6.87 min, P < 0.001), lower mean blood loss (WMD = −39.08 mL, 95% CI: −49.94 to −28.21 mL, P < 0.001), higher mean number of retrieved lymph nodes (WMD = 2.13, 95% CI: 0.58–3.67, P = 0.007), shorter time to first flatus (WMD = −0.31 d, 95% CI: −0.53 to − 0.10 d, P = 0.005), and postoperative hospital days (WMD = −1.09, 95% CI: −1.92 to −0.25, P = 0.010) than the D2 group. Subgroup analysis suggested that the advantages from the D2 + CME group were obvious in traditional open radical gastrectomy, proximal gastrectomy, and distal gastrectomy compared with D2 group. The evaluations of post-operative complications showed that the patients who underwent D2 + CME had a lower incidence of post-operative complications than the patients who underwent D2 surgery alone (relative risk [RR] = 0.65, 95% CI: 0.45–0.87, P = 0.003). The D2 radical gastrectomy plus CME improved 3-year overall survival (OS) (RR = 1.16, 95% CI: 1.02–1.32, P = 0.020) and lowered the local recurrence rate (RR = 0.51, 95% CI: 0.28–0.94, P = 0.030). The patients undergoing laparoscopic surgery or total gastrectomy had more significant advantages compared between D2 + CME and D2 groups in 3-year OS.Conclusion:The data from China show that D2 radical gastrectomy plus CME are reliable procedures and safety compared to D2 radical gastrectomy with faster recovery, lower risk, and better prognosis.     

Curve evolution during bracing in children with scoliosis secondary to early-onset neurofibromatosis type 1: indicators of rapid curve progression

Background:Scoliosis secondary to neurofibromatosis type 1 (NF1) in children aged <10 years is an important etiology of early-onset scoliosis (EOS). This study was performed to investigate the curve evolution of patients with EOS secondary to NF1 undergoing bracing treatment and to analyze high-risk indicators of rapid curve progression.Methods:Children with EOS due to NF1 who underwent bracing treatment from 2010 to 2017 were retrospectively reviewed. The angle velocity (AV) at each visit was calculated, and patients with rapid curve progression (AV of >10°/year) were identified. The age at modulation and the AV before and after modulation were obtained. Patients with (n = 18) and without rapid curve progression (n = 10) were statistically compared.Results:Twenty-eight patients with a mean age of 6.5 ± 1.9 years at the initial visit were reviewed. The mean Cobb angle of the main curve was 41.7° ± 2.4° at the initial visit and increased to 67.1° ± 8.6° during a mean follow-up of 44.1 ± 8.5 months. The overall AV was 6.6° ± 2.4°/year for all patients. At the last follow-up, all patients presented curve progression of >5°, and 20 (71%) patients had progressed by >20°. Rapid curve progression was observed in 18 (64%) patients and was associated with younger age at the initial visit and a higher incidence of modulation change during follow-up (t = 2.868, P = 0.008 and <0.001, respectively). The mean AV was 4.4° ± 1.2°/year before modulation and 11.8° ± 2.7°/year after modulation (t = 11.477, P < 0.010).Conclusions:Curve progression of >10°/year is associated with younger age at the initial visit, and modulation change indicated the occurrence of the rapid curve progression phase.     

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report

Background:Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).Methods:From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People''s Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10⁸ cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.Results:From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).     

Association between follistatin-related protein 1 and the functional status of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Background:Follistatin-like 1 (FSTL1) plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes. We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)-specific indices.Methods:We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV. Clinical and laboratory data and AAV-specific indices were recorded. FSTL1 concentration was determined using the stored sera. The lowest tertile of the short-form 36-item health survey (SF-36) was defined as the current low SF-36. The cutoffs of serum FSTL1 for the current low SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) were extrapolated by the receiver operator characteristic curve.Results:The median age was 62.5 years (55.4% were women). Serum FSTL1 was significantly correlated with SF-36 PCS (r =  − 0.374), SF-36 MCS (r = −0.377), and C-reactive protein (CRP) (r = 0.307), but not with Birmingham vasculitis activity score (BVAS). In the multivariable linear regression analyses, BVAS, CRP, and serum FSTL1 were independently associated with the current SF-36 PCS (β = −0.255, β = −0.430, and β = −0.266, respectively) and the current SF-36 MCS (β = −0.234, β =−0.229, and β = −0.296, respectively). Patients with serum FSTL1 ≥779.8 pg/mL and those with serum FSTL1 ≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without (relative risk 7.583 and 6.200, respectively).Conclusion:Serum FSTL1 could predict the current functional status in AAV patients.     

Small interfering RNA targeting of keratin 17 reduces inflammation in imiquimod-induced psoriasis-like dermatitis

BackgroundPsoriasis is a common chronic inflammatory skin disease with 2% to 3% prevalence worldwide and a heavy social-psychological burden for patients and their families. As the exact pathogenesis of psoriasis is still unknown, the current treatment is far from satisfactory. Thus, there is an urgent need to find a more effective therapy for this disease. Keratin 17 (K17), a type I intermediate filament, is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis. Therefore, we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis. This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA (siRNA) on mice with imiquimod (IMQ)-induced psoriasis-like dermatitis.MethodsEight-week-old female BALB/c mice were administered a 5% IMQ cream on both ears to produce psoriatic dermatitis. On day 3, K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days. The right ears of the mice were treated in parallel with negative control (NC) siRNA. Inflammation was evaluated by gross ear thickness, histopathology, the infiltration of inflammatory cells (CD3⁺ T cells and neutrophils) using immunofluorescence, and the expression of cytokine production using real-time quantitative polymerase chain reaction. The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance.ResultsThe severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears, as evidenced by the alleviated ear inflammation phenotype, including decreased ear thickness, infiltration of inflammatory cells (CD3⁺ T cells and neutrophils), and inflammatory cytokine/chemokine expression levels (interleukin 17 [IL-17], IL-22, IL-23, C-X-C motif chemokine ligand 1, and C-C motif chemokine ligand 20) (P < 0.05 vs. the Blank or NC siRNA groups). Compared to the NC siRNA treatment, the K17 siRNA treatment resulted in increased K1 and K10 expression, which are characteristic of keratinocyte differentiation (vs. NC siRNA, K17 siRNA1 group: K1, t = 4.782, P = 0.0050; K10, t = 3.365, P = 0.0120; K17 siRNA2 group: K1, t = 4.104, P = 0.0093; K10, t = 4.168, P = 0.0042; siRNA Mix group: K1, t = 3.065, P = 0.0221; K10, t = 10.83, P < 0.0001), and decreased K16 expression, which is characteristic of keratinocyte proliferation (vs. NC siRNA, K17 siRNA1 group: t = 4.156, P = 0.0043; K17 siRNA2 group: t = 2.834, P = 0.0253; siRNA Mix group: t = 2.734, P = 0.0250).ConclusionsInhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis. Thus, gene therapy targeting K17 may be a potential treatment approach for psoriasis.     

Impact of a problem-oriented view on clinical data retrieval

ObjectiveThe electronic health record (EHR) data deluge makes data retrieval more difficult, escalating cognitive load and exacerbating clinician burnout. New auto-summarization techniques are needed. The study goal was to determine if problem-oriented view (POV) auto-summaries improve data retrieval workflows. We hypothesized that POV users would perform tasks faster, make fewer errors, be more satisfied with EHR use, and experience less cognitive load as compared with users of the standard view (SV).MethodsSimple data retrieval tasks were performed in an EHR simulation environment. A randomized block design was used. In the control group (SV), subjects retrieved lab results and medications by navigating to corresponding sections of the electronic record. In the intervention group (POV), subjects clicked on the name of the problem and immediately saw lab results and medications relevant to that problem.ResultsWith POV, mean completion time was faster (173 seconds for POV vs 205 seconds for SV; P < .0001), the error rate was lower (3.4% for POV vs 7.7% for SV; P = .0010), user satisfaction was greater (System Usability Scale score 58.5 for POV vs 41.3 for SV; P < .0001), and cognitive task load was less (NASA Task Load Index score 0.72 for POV vs 0.99 for SV; P < .0001).DiscussionThe study demonstrates that using a problem-based auto-summary has a positive impact on 4 aspects of EHR data retrieval, including cognitive load.ConclusionEHRs have brought on a data deluge, with increased cognitive load and physician burnout. To mitigate these increases, further development and implementation of auto-summarization functionality and the requisite knowledge base are needed.     

Effects of bronchial thermoplasty and cryoablation on airway smooth muscle

Background:The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM).Methods:Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups.Results:In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ± 7.75 μm vs. 17.57 ± 15.20 μm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ± 11.02 μm), BT group and CBA group (13.41 ± 4.40 μm and 4.81 ± 4.44 μm, respectively) had significantly decreased ASM thickness after 1 month (P < 0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (P = 0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92 ± 4.42 μm vs. 7.41 ± 7.20 μm, P = 0.540). Compared with the control group (0.161 ± 0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070 ± 0.022, 0.072 ± 0.012, 0.074 ± 0.008, respectively; all P < 0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (P = 0.613).Conclusions:CBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy.     

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism

Background:Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH.Methods:Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0–3 months) and a follow-up phase (3–12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance).Results:Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ± 0.5 cm and 2.0 ± 0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference.Conclusions:The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research.Trial Registration:ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.