Search

Kush S Patel,1 Ronald J Anderson,1,* Carolyn B Becker,1,* William C Taylor,1,* Anne F Liu,1,* Anubodh S Varshney,2,* Nadaa B Ali,1,* Barbara J Nath,3,* Stephen R Pelletier,4 Helen M Shields,1 Nora Y Osman1 1Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 2Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Palo Alto, CA, USA; 3Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; 4Office of Medical Education, Harvard Medical School, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Helen M Shields, Department of Medicine, Brigham and Women’s Hospital, 75 Francis St, Boston, MA, 02115, USA, Tel +1 617 678 6077, Fax +1 617 525 8740, Email hmshields@bwh.harvard.eduPurpose: Coaching is a well-described means of providing real-time, actionable feedback to learners. We aimed to determine whether dual coaching from faculty physicians and real inpatients led to an improvement in history-taking skills of clerkship medical students.Patients and Methods: Expert faculty physicians (on Zoom) directly observed 13 clerkship medical students as they obtained a history from 26 real, hospitalized inpatients (in person), after which students received immediate feedback from both the physician and the patient. De-identified audio-video recordings of all interviews were scored by independent judges using a previously validated clinical rating tool to assess for improvement in history-taking skills between the two interviews. Finally, all participants completed a survey with Likert scale questions and free-text prompts.Results: Students’ history-taking skills – specifically in the domains of communication, medical knowledge and professional conduct – on the validated rating tool, as evaluated by the independent judges, did not significantly improve between their first and second patient interviews. However, students rated the dual coaching as overwhelmingly positive (average score of 1.43, with 1 being Excellent and 5 being Poor), with many appreciating the specificity and timeliness of the feedback. Patients also rated the experience very highly (average score of 1.23, with 1 being Excellent and 5 being Poor), noting that they gained new insights into medical training.Conclusion: Students value receiving immediate and specific feedback and real patients enjoy participating in the feedback process. Dual physician-patient coaching is a unique way to incorporate more direct observation into undergraduate medical education curricula.Keywords: direct observation, immediate feedback, medical student education, real patients, virtual teaching

Background: Endovascular recanalization (ER) has demonstrated efficacy as a treatment modality for patients presenting with acute ischemic stroke (AIS) caused by large-vessel occlusion (LVO) within a 24-hour timeframe. Nevertheless, the safety and effectiveness of ER in patients with a time of onset exceeding 24 h remain uncertain., Objective: To evaluate the safety and efficacy of ER treatment for mild ischemic stroke beyond 24-h from symptom onset., Methods: A retrospectively maintained database of mild AIS due to LVO from March2018 to September 2022 at a comprehensive stroke center was screened.Patients received ER or standard medical therapies (SMT) for anterior circulation AIS due to LVO > 24-h were selected., Results: We included 47 LVO patients with mild AIS beyond 24-h who suffered neurological deterioration (ND). 34 of these patients underwent ER, the other 13 received SMT. The technical success rate of recanalization was 82.4% (28/34). Patients received ER had significantly lower NIHSS score at discharge and 90-day mRS score ( p  = 0.028, p  = 0.037, respectively) compared to SMT. In addition, they had significantly lower 90-day recurrence of ischemic stroke and lower incidence of moderate-severe stroke (with a NIHSS score at least 5) ( p  = 0.037, p  = 0.033). There were 4 patients (11.7%) had perioperative complications, and no symptomatic intracranial hemorrhage occurred., Conclusion: ER treatment for mild AIS due to LVO encountered ND was generally safe and effective, even beyond 24-h, and resulted in a good prognosis and lower 90-day recurrence compared to SMT.

Background and Objective: Futile recanalization (FR) is defined as patients with acute ischemic stroke (AIS) due to large vessel occlusion who still exhibits functional dependence although undergoing successful mechanical thrombectomy (MT). We aimed to develop and validate a simple nomogram for predicting the probability of FR after MT treatment in AIS patients., Methods: Clinical data of AIS patients in the Jrecan clinical trial in China from March 2018 to June 2019 were collected as the derivation set ( n = 162). Meanwhile, clinical data of AIS patients who underwent MT in Baotou Central Hospital and Ningbo No.2 Hospital from 2019 to 2021 were collected as the validation set ( n = 170). Multivariate logistic regression analysis was performed for all variables that had p < 0.2 in the univariate analysis in the derivation set. The independent risk factors of FR were further screened out and a nomogram was constructed. The performance of the nomogram was analyzed in the derivation and validation set using C-index, calibration plots, and decision curves., Results: No significant difference in FR rate was detected between the derivation set and the validation set [88/162 (54.32%) and 82/170 (48.23%), p = 0.267]. Multivariate logistic regression analysis showed that age ≥ 65 years old (OR = 2.096, 95%CI 1.024-4.289, p = 0.043), systolic blood pressure (SBP) ≥ 180 mmHg (OR = 5.624, 95%CI 1.141-27.717, p = 0.034), onset to recanalization time (OTR) ≥ 453 min (OR = 2.759, 95%CI 1.323-5.754, p = 0.007), 24 h intracerebral hemorrhage (ICH; OR = 4.029, 95%CI 1.844 ~ 8.803, p < 0.001) were independent risk factors for FR. The C-index of the nomogram of the derivation set and the verification set were 0.739 (95%CI 0.662~0.816) and 0.703 (95%CI 0.621~0.785), respectively., Conclusion: The nomogram composed of age, SBP, OTR, and 24 h ICH can effectively predict the probability of FR after MT in AIS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lai, Yao, Li, Liu, Li, Liu, Jiang, Zhang, Jin, Lv and Jiang.)

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.

Background: The past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT., Methods: A total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4-6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram., Results: The overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016-1.083]; p  = 0.003), glucose level (OR: 1.163, 95% CI [1.038-1.303]; p  = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995-1.142]; p  = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688-8.245]; p  = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411-8.106]; p  = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693-0.832) in the training set and 0.804 (0.719-0.889) in the validation set., Conclusion: The proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li, Liu, Jiang, Zhang, Liu, Zhang, Li, Jiang and Lv.)

Objective: A meta-analysis of randomized controlled trials was conducted to assess efficacy and safety of bilateral ultrasound-guided erector spinae plane block (ESPB) for postoperative analgesia in patients receiving spine surgery., Methods: PubMed, Embase, and CENTRAL databases were searched by 2 reviewers independently to identify randomized controlled trials evaluating the efficacy of ultrasound-guided ESPB for pain management in patients undergoing spine surgery. For meta-analysis, mean difference (MD) and 95% confidence interval (CI) were selected for continuous data, and risk ratio (RR) and 95% CI were selected for dichotomous variables., Results: A total of 25 randomized controlled trials including 1917 patients (873 in ESPB group and 874 in control group) were eligible for inclusion. At rest, ESPB was associated with significantly lower pain intensity at 0, 2, 4, 6, 8, 12, 24, and 48 hours compared with the control group. During movement, ESPB was associated with significantly lower pain intensity at 0, 4, 6, 8, 12, 24, and 48 hours compared with the control group. Significantly reduced opioid consumption (MD = -6.29, 95% CI [-8.16, 4.41], P < 0.001), prolonged time for first rescue analgesia (MD = 7.51, 95% CI [3.47, 11.54], P < 0.001), fewer patients needing rescue analgesia (RR = 0.34, 95% CI [0.28, 0.43], P < 0.0001), improved patient satisfaction (MD = 1.34, 95% CI [0.88, 1.80], P < 0.001), and shorter length of hospital stay (MD = -0.38, [95% CI -0.50, -0.26], P < 0.001) were demonstrated after use of ESPB. Additionally, ESPB was associated with decreased risks of any adverse event (RR = 0.51, 95% CI [0.43, 0.60], P < 0.001) and postoperative nausea and vomiting events (RR = 0.39, 95% CI [0.31, 0.49], P < 0.001)., Conclusions: Ultrasound-guided ESPB is an effective adjunctive technique with good tolerability for multimodal analgesia in management of pain in patients undergoing spine surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Chronic non-specific low back pain (CNLBP) is one of the most common health problems worldwide. According to the clinical guideline released by the American College of Physicians, exercise has been recommended for the treatment of chronic LBP. In recent years, traditional Chinese medicine (TCM) is becoming increasingly popular for the management of chronic LBP. Baduanjin exercise is one of the exercise therapies in TCM. N-of-1 trial is a randomised cross-over self-controlled trial suitable for patients with this chronic disease. A series of similar N-of-1 trials can be pooled to estimate the overall and individual therapeutic effects synchronously by hierarchical Bayesian analysis. And N-of-1 trials are considered as a good tool for evaluating the therapeutic effect of TCM. Therefore, this study aims to conduct a series of N-of-1 trials with hierarchical Bayesian analysis for assessing whether Baduanjin exercise is effective and safe for CNLBP., Methods and Analysis: This study conducts a series of N-of-1 trials on Baduanjin exercise for the management of CNLBP. Fifty participants will receive 1-3 treatment cycles. They will be randomised into a Baduanjin exercise or waiting list group for a week during the two periods of each treatment cycle. The primary outcome is the 10-point Visual Analogue Scale. The secondary outcomes include the Oswestry Disability Index, the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and the Short Form Health Survey 12. Statistical analysis will be conducted with WinBUGS V.1.4.3 software. Overall and individual therapeutic effects will be estimated synchronously by hierarchical Bayesian analysis., Ethics and Dissemination: This study is approved by the Medical Ethics Committee of Tianjin University of TCM (reference number TJUTCM-EC20220005). Our findings will be published in a peer-reviewed journal or international conference., Trial Registration Number: ChiCTR2200063307., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To critically evaluate the efficacy and safety of early versus delayed anterior cruciate ligament reconstruction (ACLR) for anterior cruciate ligament (ACL) injuries based on the different cut-off values of the timing of operation., Methods: PubMed, Medline, Embase, Cochrane library, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang Digital Periodical database were searched from inception to November 2022 without language restrictions. Randomized controlled trials (RCTs) and cohort studies (CSs) comparing early ACLR with delayed ACLR for ACL injuries were included., Results: Twenty-four studies (10 RCTs and 14 CSs) were included. According to the information from included studies, 3 weeks, 4 weeks, 6 weeks, 6 months, and 12 months after ACL injuries were considered as the cut-off values of early and delayed ACLR. When 4 weeks were considered as the cut-off value, early ACLR could significantly improve Lysholm score, IKDC score and VAS score at 6 and 12 months postoperatively and decrease the incidence of adverse events compared with delayed ACLR (P < 0.05). However, no statistically significant difference in positive rate of Lachman test and incidence of meniscus injuries and chondral lesions between the two groups when 3 weeks, 6 weeks, 6 months or 12 months after ACL injuries were considered as the cut-off values of early and delayed ACLR (P > 0.05)., Conclusion: The present study suggests that early ACLR, especially conducted within 3-4 weeks after ACL injuries, may be more effective for improving knee function and relieving pain compared with delayed ACLR. More high-quality RCTs are warranted., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ai-Feng Liu reports financial support was provided by National Natural Science Foundation of China. Ai-Feng Liu reports financial support was provided by Basic Scientific Research Project of Public Welfare on Central Level of Chinese Academy of Medical Sciences. The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Proximal tibial aspect ratio (PTAR) is closely related to age, disease status and cutting parameters with considerable inter-individual variation independent of gender and race, nevertheless the aspect ratio of tibial components from different manufacturers remains relatively constant from smallest to largest size. As a result, component mismatching is an unavoidable dilemma during tibia preparation in total knee arthroplasty (TKA). Various prosthesis systems all can achieve more than 80% coverage on proximal tibia, whereas their optimal fit rates are generally not more than 50%. It is difficult for symmetrical components to avoid anteroposterior mismatch, internal malrotation tends to occur when maximum coverage is pursued on the resected surface with a medial dominant plateau or lower PTAR. Although it is easier to achieve a balance of rotation and coverage with anatomical components, significant anteromedial overhang tends to appear on the resected surface with a symmetrical or lateral dominant plateau. Further researches should focus on the law of inter-individual variability of proximal tibial morphology, the quantitative definition of "ideal matching" safety zone of key morphological parameters on different areas of proximal tibia and the methodology of realizing"ideal matching"in the majority patients with the least amount of component sizes. In addition, with the rapid development of additive manufacturing and digital orthopedic technology, individual customized implant is expected to become a breakthrough point in the field of TKA component fitting.

Objective: The aim of this study was to identify the influence of a tourniquet on the blood loss, transfusion requirement, swelling, pain, knee function, range of motion (ROM), operation time, bone cement mantle thickness, and complications in patients operated with total knee arthroplasty (TKA)., Methods: Two authors independently retrieved PubMed, Embase, and CENTRAL to identify eligible randomized controlled trials (RCTs) evaluating the effectiveness of a tourniquet in TKA. Fixed- ( I 2  < 50%) or random-effects ( I 2  > 50%) models were selected to perform meta-analysis according to the value of I 2 . Mean difference (MD) and risk ratio were selected as the effect sizes for continuous and dichotomous variables, respectively., Results: A total of 29 RCTs, involving 2,512 operations (1,258 procedures with a tourniquet and 1,254 procedures without a tourniquet), were included, and 18 outcomes were compared. Tourniquet application could significantly decrease intraoperative blood loss (MD = -138.72 ml, p  < 0.001), shorten operation duration (MD = -1.77 min, p  < 0.001), and increase cement mantle thickness (MD = 0.17 mm, p  < 0.001). However, it was significantly associated with increased postoperative pain intensity, decreased full ROM/flexion ROM/extension ROM, poorer knee function, increased knee swelling, and increased length of hospital stay (LOS) at several follow-up points ( p  < 0.050). No significant difference was found for postoperative draining volume, total blood loss, transfusion rate, change of Hb level, and risks of deep venous thrombosis and all complications., Conclusions: Tourniquet application could only decrease the intraoperative blood loss but has no effectiveness on the total blood loss and transfusion requirement. On the contrary, it has a reverse effect on the pain score, knee function, ROM, swelling, and LOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Han, Zhang, Mu, Liu, Cui, Zhang and Liu.)

The basilar artery has the most perioperative complications in stenting compared to the other intracranial arteries. We aim to study whether the procedural safety in stenting for basilar stenosis has improved. This study was a single-arm, non-randomized trial that included historically controlled patients for comparison. Between January 2012 and March 2019, 147 consecutive patients with symptomatic basilar stenoses receiving elective stenting treatment were included in current basilar artery stenting (BAS) group. The prospectively collected and registered 120 patients by the same interventional team from September 2001 to November 2011 were set as historical BAS group for control. A total of 267 individuals were included in this study, with a mean age of 59.5 ± 8.1 years. The proportion of patients with lesion length >15 mm was 26.5% (39/147) in the current BAS group versus 4.2% (5/120) in the historical BAS group. We found significant differences between these 2 groups in Mori A (17.7% vs 42.5%) and Mori C patients (42.9% vs 13.3%). The proportion of patients receiving preoperative high-resolution magnetic resonance (HRMRI) evaluation was 83.0% (122/147) in the current BAS group versus 20.8% (25/120) in the historical group (P < .05). Balloon-expendable stent (BES) (n = 1), Wingspan (n = 34), and Enterprise (n = 112) stents were placed in the current BAS group. In contrast, only balloon-expendable stent (BES) (n = 48) and Wingspan (n = 72) were deployed in the historical BAS group. The incidence of the safety endpoint (SE) was 4.1% (involving 6 patients) in the current BAS group versus 11.7% (involving 14 patients) in the historical BAS group (P < .05). In multivariate analysis, no risk factor was associated with the occurrence of the safety endpoint (SE). When BAS cases operated by the surgical team accumulated to 120 to 150, the incidence of complications decreased significantly. This is the largest sample size study to discuss the safety of BAS. The significantly decreased incidence of complications indicates that the improving technical measures and the accumulation of operation experience are necessary., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In people with hepatitis B virus (HBV) infection, persistence of hepatitis B e antigen (HBeAg) is associated with clinical progression and need for treatment. HBeAg loss represents partial immune control and is a critical event in the natural history of chronic HBV., Methods: We conducted a systematic review and meta-analysis of cohort studies that report HBeAg loss among people with untreated chronic HBV. We evaluated HBeAg loss using a random-effects model and conducted subanalysis on region., Results: We screened 10 560 publications, performed 196 full-text analyses, and included 26 studies for meta-analysis. The pooled rate of HBeAg loss was 6.46/100 person-years (PYs) (95% confidence interval, 5.17-8.08). Meta-regression showed that older age of participants and studies in Europe were associated with higher rate of HBeAg loss. Rates per 100 PYs were 7.43 (95% confidence interval, 6.30-8.75; 1 study) in Africa, 3.24 (2.61--4.02; 1 study) in the Eastern Mediterranean, 13.67 (11.21-16.66; 4 studies) in Europe, 7.34 (4.61--11.70; 5 studies) in North America, and 5.53 (4.05--7.55; 15 studies) in the Western Pacific., Conclusions: Spontaneous HBeAg loss occurs at a rate of 6.46/100 PYs. Variations by region and age group may reflect epidemiological, immunological, or HBV genotype-related differences., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study focused on the prediction factors of catastrophic outcomes of all-cause mortality at 90 days after mechanical thrombectomy and selection of candidates for clinical decision making up by the generating pre-MT and peri-MT prognostic models., Method: A secondary analysis based on the prospective, multicenter, randomized, non-inferiority clinical trial of Jrecan retriever from China were performed in this study. 187 stroke patients with a large-vessel anterior circulation occlusion, NIHSS score ≥ 6, ASPECT ≥ 7, and stroke onset time within 8 h were enrolled from March 1, 2018 to June 30, 2019 and followed up for 90 days. Data with mRS cumulative rates of 6, as well as mortality were analyzed and potential predictors for the mortality risk were identified by univariate and multivariate regression analysis., Results: Among 186 patients, the median age was 66 years (IQR, 58-74) and 106 patients (56.4%) were male. The mortality was 20.8% (39/186) and general favorable outcome was obtained in 78 patients (41.7%, 78/187) at 90 days after MT. Five variables including ASPECT≤ 9 (3.136 [1.239-7.939], P = 0.016), Occlusion location with IC-ICA (3.538 [1.604-7.803], P = 0.002), un-Successful recanalization; PH (7.644 [1.890-30.917], P = 0.004), and END (without PH) with a significance of P < 0.05 were entered into the multivariable logistic regression analysis and were incorporated into pre-procedure model and peri-procedure models respectively., Conclusions: Occlusion with IC-ICA and PH were the strong predictors for mortality risk at 90-day, which could be reduced through good management and evaluation during pre-procedure and peri-procedure of mechanical thrombectomy., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Undernutrition is the leading cause of tuberculosis (TB) in India and is associated with increased TB mortality. Undernutrition also decreases quality of life and economic productivity., Methods: We assessed the cost-effectiveness of providing augmented rations to undernourished Indians through the government's Targeted Public Distribution System (TPDS). We used Markov state transition models to simulate disease progression and mortality among undernourished individuals in 3 groups: general population, household contacts (HHCs) of people living with TB, and persons living with human immunodeficiency virus (HIV). The models calculate costs and outcomes (TB cases, TB deaths, and disability-adjusted life years [DALYs]) associated with a 2600 kcal/day diet for adults with body mass index (BMI) of 16-18.4 kg/m2 until they attain a BMI of 20 kg/m2 compared to a status quo scenario wherein TPDS rations are unchanged. We employed deterministic and probabilistic sensitivity analyses to test result robustness., Results: Over 5 years, augmented rations could avert 81% of TB cases and 88% of TB deaths among currently undernourished Indians. Correspondingly, this intervention could forestall 78% and 48% of TB cases and prevent 88% and 70% of deaths among undernourished HHCs and persons with HIV, respectively. Augmented rations resulted in 10-fold higher resolution of undernutrition and were highly cost-effective with (incremental cost-effectiveness ratio [ICER] of $470/DALY averted). ICER was lower for HHCs ($360/DALY averted) and the HIV population ($250/DALY averted)., Conclusions: A robust nutritional intervention would be highly cost-effective in reducing TB incidence and mortality while reducing chronic undernutrition in India., Competing Interests: Potential conflicts of interest. L. M. L. reports Thrasher Research Fund Early Career award to study anemia in India. C. R. H. reports being a consultant for Otsuka Pharmaceuticals (no fees received to date); being on the DSMB for the BEAT-TUBERCULOSIS Study, the SUDOCU Study, and the Stool4TB study (all unpaid); and is the Vice-President of the International Union Against Tuberculosis and Lung Disease. N.S.H. reports being on American Society of Tropical Medicine and Hygiene, Respiratory Diseases and Tuberculosis Working Group, Scientific Program Committee. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To identify the ABO positive and negative stereotypic inconsistencies in a dizygotic twin with positive stereotypic patterns and mixed agglutination, and explore the application of serological characteristics and gene sequence in congenital blood group chimeras., Methods: ABO blood group identification, Rh and MN typing were performed using the microcolumn gel method and ABO genotyping was performed using the PCR-SSP method., Results: In this patient, both anti-A and anti-B tubes had mixed hemagglutination of red blood cells, and the anti-ABO tube was AB type. The Rh typing of the patient was CcDEe. Mixed agglutination of red blood cells was observed in both anti-M and anti-N tubes in MN typing. The patient's father and mother was normal Type O and AB, respectively. There were three alleles in the ABO gene of the patient, O0101 came from his father, while A102 and B01 came from his mother., Conclusion: The patient has two groups of red blood cells (type A and B). Because the patients is a dizygotic twin, these two groups of red blood cells can be chimeras formed by blood exchange between the twins. Through gene sequencing, it can be determined that the patient is a congenital A/B blood type chimera.

Objective: The aim of this study is to investigate the safety and efficiency of a Jrecan ® flow restoration system, a novel thrombectomy device, in an arterial thromboembolic occlusion model of Beagle dogs., Methods: A total of 12 Beagle dogs with acute thromboembolism were randomized to receive mechanical thrombectomy with either Jrecan ® flow restoration device or Trevo TM PROVUE Device (2:1). The efficacy and safety of the two devices, including recanalization rate, the presence of distal embolism, vasospasm, vessel perforation, and vessel injuries were evaluated through DSA and microscopic examination., Result: A 100% recanalization rate (mTICI 2b/3) was achieved in both groups. Endothelial and subendothelial injuries occurred in all target vessels. Focal disruption of internal elastic lamina was observed in 4 cases. The mean vessel injury score of the Jrecan ® group was 1.16 ± 0.48, significantly lower than that of the Trevo TM group (1.54 ± 0.8) ( P < 0.001)., Conclusion: The Jrecan ® and Trevo TM devices demonstrated an equally high recanalization rate in Beagle dogs with acute thromboembolism. However, histological findings revealed that the Jrecan ® stent seemed to be safer than the Trevo TM device during clot retrieval, which might be related to a more appropriate radial force provided by the Jrecan ® stent that resulted from its wider cell design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhou, Zhang, Lv, Zhang, Qiu, Liu and Jiang.)

Component malrotation is one of the major causes of failure in total knee arthroplasty.Based on previous researches,Insall line has excessive external rotation tendency.Although Akagi line is the most recognized anatomical axis at present,it still has a certain tendency of internal rotation.The tibial posterior condylar axis is not suitable for symmetrical component and yet the Curve-on-Curve technique is not suitable for anatomic component.In addition,reference to any fixed anatomical markers cannot ensure the rotation consistency of tibiofemoral component in extension position.Although range of motion technique is beneficial to tibiofemoral rotation synchronization,its clinical effect seems to be unstable.Nevertheless,Patients can obtain good postoperative results with all major techniques.Before the recognized "gold standard" is defined,orthopedic surgeons can determine the rotation alignment of tibial component according to their most accustomed surgical method.With a deeper understanding of knee anatomy,biomechanics and kinematics,digital assistive technology may be expected to become a breakthrough in the tibial rotational alignment.

Objective: We critically evaluated the efficacy and safety of oblique lumbar interbody fusion (OLIF) versus transforaminal lumbar interbody fusion (TLIF) for degenerative lumbar spondylolisthesis (DLS)., Methods: PubMed, Embase, Cochrane Library, the Web of Science Core Collection, Chinese Biomedical Literature, China National Knowledge Infrastructure, Wanfang Digital Periodicals, and Chinese Science and Technology Periodicals were searched from their inception to February 2021. Randomized controlled trials and retrospective or prospective cohort studies (CSs) comparing OLIF and TLIF for DLS were included. A meta-analysis was conducted, if possible., Results: Ten studies were included in the statistical analysis. The pooled results of the CSs showed no statistically significant differences (P > 0.05) in pain relief at 3 or 6 months of follow-up and functional improvement at 1 or 3 months of follow-up in DLS patients between those who had undergone OLIF versus TLIF. The pooled results of the CSs showed that OLIF could significantly improve the degree of lumbar lordosis, foraminal height, and disc height and decrease the intraoperative blood loss, postoperative drainage volume, operative duration, bed rest time, and hospital length of stay (P < 0.05) compared with TLIF. The incidence of adverse events was not significantly different statistically between OLIF and TLIF., Conclusions: The results from the present study suggest that pain relief and functional improvement were not significantly different between OLIF and TLIF. Nevertheless, the use of OLIF might improve radiological outcomes and reduce intraoperative blood loss, postoperative drainage volume, operative duration, bed rest duration, and hospital length of stay compared with TLIF. Additional high-quality randomized controlled trials are still required to confirm these findings., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: We aimed to investigate the ability of MRI radiomics features-based machine learning (ML) models to classify the time since stroke onset (TSS), which could aid in stroke assessment and treatment options., Methods: This study involved 84 patients with acute ischemic stroke due to anterior circulation artery occlusion (51 in the training cohort and 33 in the independent test cohort). Region of infarct segmentation was manually outlined by 3D-slicer software. Image processing including registration, normalization and radiomics features calculation were done in R (version 3.6.1). A total of 4312 radiomic features from each image sequence were captured and used in six ML models to estimate stroke onset time for binary classification (≤ 4.5 h). Receiver-operating characteristic curve (ROC) and other parameters were calculated to evaluate the performance of the models in both training and test cohorts., Results: Twelve radiomics and six clinic features were selected to construct the ML models for TSS classification. The deep learning model-based DWI/ADC radiomic features performed the best for binary TSS classification in the independent test cohort, with an AUC of 0.754, accuracy of 0.788, sensitivity of 0.952, specificity of 0.500, positive predictive value of 0.769, and negative predictive value of 0.857, respectively. Furthermore, adding clinical information did not improve the performance of the DWI/ADC-based deep learning model. The TSS prediction models can be visited at: http://123.57.65.199:3838/deeptss/ ., Conclusions: A unique deep learning model based on DWI/ADC radiomic features was constructed for TSS classification, which could aid in decision making for thrombolysis in patients with unknown stroke onset., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of the study was to identify the effectiveness of the continuous passive motion application on clinical outcomes after total knee arthroplasty, based on evidence from recently published high-quality randomized controlled trials., Design: Two reviewers retrieved platforms of PubMed, Embase, and CENTRAL independently, for identifying eligible randomized controlled trials evaluating the effect of continuous passive motion applied after total knee arthroplasty for knee osteoarthritis. Subgroup meta-analyses were performed for all syntheses based on the follow-up intervals., Results: A total of 10 randomized controlled trials, involving 841 patients, were finally included. Data were available for 15 different outcomes (including active/passive knee extension/flexion/full range of motion, Western Ontario and McMaster Universities Osteoarthritis Index-pain/physical function/stiffness/total score, visual analogue scale, time up and go, knee girth, Knee Society Scale-function/knee score), at several time points. In general, most of the pools demonstrated similar outcome between continuous passive motion and noncontinuous passive motion groups. Exclusively, the active knee extension at 1 wk (mean difference = 3.00, 95% confidence interval = 0.5-5.5, P = 0.019*), passive knee extension at 1 wk (mean difference = 3.00, 95% confidence interval = 0.28-5.72, P = 0.031*), and 3 mos (mean difference = 3.00, 95% confidence interval = 0.5-5.5, P = 0.019*) were shown to be significantly slightly different between two groups., Conclusions: This study demonstrated a limited role of continuous passive motion in patients operated with total knee arthroplasty. Thus, there is at this stage no indication for continuous passive motion procedures in patients operated with total knee arthroplasty as a standard postoperative care., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We looked at the association between Terry nails and liver cirrhosis in an ambulatory population from hepatology and gastroenterology clinics., Methods: We prospectively investigated the prevalence and determinants of Terry nails in 1,000 consecutive patients from hepatology and gastroenterology clinics at 2 institutions between May 2016 and February 2020., Results: A total of 117 subjects manifested Terry nails, with a 25.6% prevalence in patients with cirrhosis. When adjusted for age, heart failure, diabetes mellitus type 2, and chronic liver disease, cirrhosis was the only significant correlate (odds ratio 5.7 [95% confidence interval 3.3-9.8]), irrespective of liver disease etiology, with a strong association with hepatic fibrosis stage (P < 0.0001)., Discussion: Sensitivity and specificity of Terry nails for cirrhosis (25.8%, 92.7%) was similar to palmar erythema but less than spider angioma., (Copyright © 2021 by The American College of Gastroenterology.)

Objective: To assess whether the effectiveness and safety of recanalization therapy for acute ischemic stroke (AIS) caused by large-artery occlusion (LAO) differ between patients aged 60-79 years and patients aged ≥80 years., Methods: We analyzed prospective data of patients with LAO (≥60 years) who underwent recanalization therapy at the Department of Vascular Neurosurgery, New Era Stroke Care and Research Institute, PLA Rocket Force Characteristic Medical Center, from November 2013 to July 2017. The data were compared between elderly patients (60-79 years) and very elderly patients (≥80 years). The effectiveness of recanalization therapy was evaluated using the 90-day modified Rankin scale (mRS) score, while safety was assessed by the rates of symptomatic intracranial hemorrhage (SICH) and mortality within 30 days., Results: A total of 151 patients with AIS induced by LAO were included in this study. Seventy-three patients (48.3% [73/151]) had an overall favorable outcome (mRS score 0-2) after treatment. A higher proportion of patients in the elderly group showed a favorable outcome compared with the very elderly group (58.6% [34/58] vs. 41.6% [39/93], respectively; P = 0.046). The incidence of SICH (12.7% vs. 16.13%, respectively; P = 0.561) and mortality (10.3% vs. 7.5%, respectively; P = 0.548) within 30 days was not significantly different between the two groups., Conclusion: Recanalization treatment of LAO is more effective in elderly patients compared with very elderly patients, while the safety of recanalization treatment is comparable between these two groups., Competing Interests: All of the authors have no disclosure-conflict of interest., (Copyright © 2021 Qi Wang et al.)

Background: Treatment of perforator involving aneurysm (piAN) remains a challenge to open and endovascular neurosurgeons. Our aim is to demonstrate a primary outcome of endovascular therapy for piANs with the use of perforator preservation technologies (PPT) based on a new neuro-interventional classification., Methods: The piANs were classified into type I: aneurysm really arises from perforating artery, type II: saccular aneurysm involves perforating arteries arising from its neck (IIa) or dome (IIb), and type III: fusiform aneurysm involves perforating artery. Stent protection technology of PPT was applied in type I and III aneurysms, and coil-basket protection technology in type II aneurysms. An immediate outcome of aneurysmal obliteration after treatment was evaluated (satisfactory obliteration: the saccular aneurysm body is densely embolized (I), leaving a gap in the neck (IIa) or dome (IIb) where the perforating artery arising; fusiform aneurysm is repaired and has a smooth inner wall), and successful perforating artery preservation was defined as keeping the good antegrade flow of those perforators on postoperative angiography. The periprocedural complication was closely monitored, and clinical and angiographic follow-ups were performed., Results: Six consecutive piANs (2 ruptured and 4 unruptured; 1 type I, 2 type IIa, 2 type IIb, and 1 type III) in 6 patients (aged from 43 to 66 years; 3 males) underwent endovascular therapy between November 2017 and July 2019. The immediate angiography after treatment showed 6 aneurysms obtained satisfactory obliteration, and all of their perforating arteries were successfully preserved. During clinical follow-up of 13-50 months, no ischemic or hemorrhagic event of the brain occurred in the 6 patients, but has one who developed ischemic event in the territory of involving perforators 4 h after operation and completely resolved within 24 h. Follow-up angiography at 3 to 10M showed patency of the parent artery and perforating arteries of treated aneurysms, with no aneurysmal recurrence., Conclusions: Our perforator preservation technologies on the basis of the new neuro-interventional classification seem feasible, safe, and effective in protecting involved perforators while occluding aneurysm.

Objective: To investigate the relationship between asymmetric prominent hypointense vessels (prominent vessel sign, PVS) on susceptibility-weighted imaging (SWI) and leptomeningeal collateralization in patients with acute ischemic stroke due to large vessel occlusion., Methods: We retrospectively enrolled patients with M1 segment occlusion of the middle cerebral artery who underwent emergency magnetic resonance imaging and digital subtraction angiography within 24 hours from stroke onset. The extent of PVS on SWI was assessed using the Alberta Stroke Program Early CT Score (ASPECTS). Leptomeningeal collateralization on digital subtraction angiography images was assessed using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale. Spearman's rank correlation test was performed to explore the correlation of ASITN/SIR scores with SWI-ASPECTS and SWI-diffusion-weighted imaging (DWI) mismatch scores., Results: Thirty-five patients were enrolled. There was no significant correlation between SWI-ASPECTS and ASITN/SIR scores. However, SWI-DWI mismatch scores were positively correlated with ASITN/SIR scores., Conclusion: The range of PVS on SWI did not closely reflect the collateral status, while the range of SWI-DWI mismatch was significantly correlated with the leptomeningeal collateralization. In patients with acute anterior circulation stroke due to large vessel occlusion, larger SWI-DWI mismatch was associated with better leptomeningeal collaterals.

In sub-Saharan Africa, there exist distinct HCV genotype (GT) subtypes harbouring resistance-associated substitutions to commonly used non-structural protein 5A (NS5A) inhibitor-based direct-acting antiviral (DAA) regimens. In particular, GT4r subtype has demonstrated high rates of treatment failure. In the absence of routine viral sequencing in sub-Saharan Africa, it is important to identify sociodemographic, epidemiologic, and clinical characteristics that may be associated with GT4r infection. Methods: A secondary analysis was performed on data from 300 adults with HCV GT4 enrolled in a prospective trial assessing the safety and efficacy of sofosbuvir-ledipasvir in Rwanda in 2017. The association between characteristics at enrolment and GT subtype was assessed by chi-square analysis and logistic regression. In multivariate analysis, there were a higher proportion of participants with GT4r subtype with age <40 years (OR: 3.6, 95% CI: 1.3-10.5, p = 0.02), previous hospitalization (OR: 2.5, 95% CI: 1.3-5.0, p = 0.006), previous surgery (OR: 2.2, 95% CI: 1.1-4.2, p = 0.03), cirrhosis (OR: 3.2, 95% CI: 1.3-7.5, p = 0.008) and baseline HCV RNA >1 million IU/ml (OR: 3.4, 95% CI: 1.6-6.9, p = 0.001). Rwandan adults with GT4r are more likely to be younger, have a history of hospital admissions and surgeries and have more active or advanced liver disease compared to those with other GT4 subtypes. In the absence of advanced diagnostics to assess GT subtype, patients with these characteristics may warrant closer monitoring for treatment failure or alternative DAA regimens. More treatment experience with diverse DAA regimens is urgently needed for GT subtypes particular to this region., (© 2021 John Wiley & Sons Ltd.)

The prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) is not displayed in all cases of acute ischemia. We aimed to investigate the factors associated with the presence of PVS in stroke patients. Consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission. Associated factors for the presence of PVS were analyzed using univariate analyses and multivariable logistic regression analyses. A total of 218 patients were enrolled. The occurrence rate of PVS was 55.5%. Univariate analyses showed significant differences between PVS-positive group and PVS-negative group in age, history of coronary heart disease, baseline NIHSS scores, total cholesterol, hemoglobin, anterior circulation infarct, large vessel occlusion, and cardioembolism. Multivariable logistic regression analyses revealed that the independent factors associated with PVS were anterior circulation infarct (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.5-53.3), large vessel occlusion (OR 123.3; 95% CI 33.7-451.5), and cardioembolism (OR 5.6; 95% CI 2.1-15.3). Anterior circulation infarct, large vessel occlusion, and cardioembolism are independently associated with the presence of PVS on SWI.

Background: The aim of this study was to use umbilical cord mesenchymal stem cells (UCMSCs) loaded with graphene oxide (GO) granular lubricant to treat knee osteoarthritis (KOA) animal models and to analyze their effect on cytokine levels in the articular cavity., Methods: Twenty-four New Zealand rabbit models of KOA were established by the modified Hulth and cartilage injury method, and they were assigned to the blank group, the GO group, the UCMSC group, and the GO + UCMSC group, each group containing six animal models. The GO and UCMSC groups were treated by a single intra-articular injection. The treatment was started one month after surgical modeling, and the observation period was eight weeks. The expression levels of nitric oxide (NO), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), glycosaminoglycan (GAG), and collagen-II (COL-II) in serum and articular fluid after treatment were compared to analyze the efficacy., Results: The GO granular lubricant caused no significant improvement in the intra-articular environment of the knee joint, and UCMSCs caused a certain degree of improvement in the inflammatory environment. The improvement results of NO, IL-6, TNF-α, GAG, and COL-II were the best in the GO + UCMSC group, but the improvement results of inflammatory cytokine levels in serum and articular fluid were not consistent, especially the differences in NO, IL-6, and TNF-α were greater., Conclusion: UCMSCs loaded with the GO granular lubricant can reduce the inflammatory level and improve the level of biochemical environment in the articular cavity, and thus promote cartilage repair.

Background: Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited., Methods: We used real-time polymerase chain reaction (qPCR), Western blotting, and RNA pull down to investigate the relationship between miR-186 and MOB Kinase Activator 1A (Mob1). Also, we investigated the effect of exosome in osteogenesis using alkaline phosphatase (ALP) staining. And hematoxylin eosin (HE) staining was used to verify the osteogenesis in PMO model., Results: Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO + Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis., Conclusions: We concluded that exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.

Objective: To determine the expression level of linc-223 and miR-125a in the patients with adult acute leukemia (AL) and explore the relationship between the expression level and the occurrence, development, prognosis of leukemia., Methods: Bone marrow samples of 93 patients with AL treated in our hospital from January 2017 to September 2017 were enrolled, including 21 cases of acute lymphoblastic leukemia (ALL) and 72 cases of acute non-lymphocytic leukemia (ANLL). At the same time, bone marrow samples from 20 cases of non-malignant hematopathy patients in the same period were enrolled as control group. Real-time quantitative PCR (qRT-PCR) was used to test the expression level of linc-223 and miR-125a in bone marrow of 93 AL patients and the relationship between the level and the occurrence, development, prognosis of leukemia was analyzed., Results: There was no significant difference in the expression of linc-223 between AL patients (ANLL and ALL) and control group (P>0.05). Moreover, there was no significant correlation between linc-223 and PML-RARα gene or the remission rate of patients after treatment. The expression of miR-125a in ANLL patients was significantly lower than those in the control group (P<0.01), but there was no significant difference between the initial treatment, recurrence and remission group (P>0.05), and also for ALL and control group (P>0.05). In the newly treatment ANLL patients, the expression level of miR-125a showed negatively correlated with LDH level and the ratio of immature cells (r=-0.454, r=-0.400), but not with sex, degree of risk, peripheral blood leukocyte count, platelet count, hemoglobin content, WT1, CRP, etc. (P>0.05). There was a positive correlation between linc-223 and miR-125a in ANLL patients (r=0.296)., Conclusion: No abnormal expression of linc-223 was found in the bone marrow of AL patients, but miR-125a expression shows a low level and positively correlate with the expression level of linc-223 in ANLL, which is helpful for the diagnosis.

Background: The efficacy of acupuncture for acute ankle sprain (AAS) is controversial. This study aimed to critically assess the efficacy and safety of acupuncture for AAS., Methods: Parallel-group randomized controlled trials (RCTs) were included regardless of language or publication date. Participants with AAS were included regardless of age, sex, race, nationality, or diagnostic criteria for AAS. Experimental interventions included acupuncture alone or in combination with traditional therapies. Control interventions included no treatment, placebo, or traditional therapies. The primary outcome was the Kofoed ankle score. The secondary outcomes included visual analogue scale, duration of pain, use of painkiller, ankle circumference, effective rate, cure rate, and adverse events. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Digital Periodicals, and Chinese Science and Technology Periodicals database were searched to identify potentially eligible studies from inception to September 10, 2020. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, Chinese Clinical Trial Registry (ChiCTR), and the reference list of eligible RCTs were checked to identify ongoing or unpublished studies. Risk of bias was assessed by the Cochrane Collaboration's tool. Statistical analyses were performed by RevMan 5.3 software. P < 0.05 indicated statistical significance., Results: Seventeen eligible studies were included for the statistical analysis. There was no statistically significant difference of Kofoed ankle score between acupuncture and Rest, Ice, Compression, and Elevation (RICE) group ( P =0.75). However, acupuncture could significantly relieve pain ( P =0.02) and increase cure rate ( P =0.004) compared with RICE. Moreover, acupuncture plus RICE could also significantly relieve pain ( P < 0.00001) and increase cure rate ( P =0.01) compared with RICE alone. Acupuncture combined with massage could significantly relieve pain ( P =0.04) compared with massage alone. Acupuncture plus Chinese medicine might be more effective for relieving pain ( P < 0.00001), reducing the duration of pain ( P < 0.00001), and increasing cure rate ( P =0.0002) compared with Chinese medicine alone. Two studies reported no adverse reactions. One study reported that a participant suffered from mild drug-related allergic reaction and was healed without treatment., Conclusions: The findings of the present study suggest that acupuncture may be beneficial for AAS. However, more large-scale and well-designed RCTs are warranted., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Ai-Feng Liu et al.)

Setting: India's National Tuberculosis Elimination Programme (NTEP) covers diagnostic and therapeutic costs of TB treatment. However, persons living with TB (PLWTB) continue to experience financial distress due to direct costs (payment for testing, treatment, travel, hospitalization, and nutritional supplements) and indirect costs (lost wages, loan interest, and cost of domestic helpers)., Objective: To analyze the magnitude and pattern of TB-related costs from the perspective of Indian PLWTB., Design: We identified relevant articles using key search terms ('tuberculosis,' 'India,' 'cost,' 'expenditures,' 'financing,' 'catastrophic' and 'out of pocket') and calculated variance-weighted mean costs., Results: Indian patients incur substantial direct costs (mean: US$46.8). Mean indirect costs (US$666.6) constitute 93.4% of the net costs. Mean direct costs before diagnosis can be up to four-fold that of costs during treatment. Treatment in the private sector can result in costs up to six-fold higher than in government facilities. As many as one in three PLWTB in India experience catastrophic costs., Conclusion: PLWTB in India face high direct and indirect costs. Priority interventions to realize India's goal of eliminating catastrophic costs from TB include decreasing diagnostic delays through active case finding, reducing the need for travel, improving awareness and perception of NTEP services, and ensuring sufficient reimbursement for inpatient TB care., Competing Interests: Conflicts of interest: none declared., (© 2020 The Union.)

Objective: To investigate the interactive effect of susceptibility-diffusion mismatch and recanalization status on clinical outcome in patients with acute ischemic stroke due to large vessel occlusion., Methods: In this prospective study, consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission, including diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and time-of-flight magnetic resonance angiography (TOF-MRA). Patients with large vessel occlusion within the anterior circulation were recruited. Follow-up MRI was performed within 24 h after recanalization therapy (intravenous thrombolysis, endovascular therapy, or both). Multivariable logistic regression analysis was performed to estimate the interaction between SWI-DWI mismatch score and recanalization status on clinical outcome., Results: A total of 90 patients were enrolled. A multiplicative interaction between SWI-DWI mismatch score and recanalization status on clinical outcome was observed (P=0.037). The interaction term "SWI-DWI mismatch score × successful recanalization" was significantly associated with favorable outcome (modified Rankin Scale score of 0-2 at 90 days; adjusted odds ratio [aOR], 2.162; 95% confidence interval [CI], 1.046-4.468). Stratified analysis showed that the likelihood of favorable outcome increased with the increase of SWI-DWI mismatch score in the successful recanalization group (OR, 2.140; 95% CI, 1.376-3.326), while there was no significant relationship between SWI-DWI mismatch score and clinical outcome in the unsuccessful recanalization group (OR, 1.212; 95% CI, 0.933-1.574)., Conclusions: The effects of SWI-DWI mismatch and recanalization status on clinical outcome were realized through their interaction. In anterior circulation stroke due to large vessel occlusion, patients with both high SWI-DWI mismatch scores and successful recanalization were more likely to achieve a favorable outcome, while patients with unsuccessful recanalization, or with successful recanalization but low SWI-DWI mismatch scores, were less likely to have a good prognosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Ischemia-reperfusion injuries (IRIs) can aggravate the condition of some patients with acute occlusion of major intracranial artery (AOMIA) who received endovascular thrombectomy. Here, we provided data confirming the association of Repressor Element-1 Silencing Transcription factor (REST) with the long-term neuroprotective effect of the middle cerebral artery occlusion (MCAO) rats underwent Gradual Flow Restoration (GFR)., Methods: Long term neuroprotective effects of GFR intervention were evaluated on MCAO rats model after 3d and 7d reperfusion. The neurological deficit score and TTC staining were performed to evaluate the degree of brain damage in GFR and other interventions at different time. Differentially expressed genes related to cerebral ischemia reperfusion injury (CIRI) were initially screened and identified using GSE32529 microarray analysis. REST protein expression in rat brain cortex infarction was detected by Western blot analysis., Results: MCAO rats intervened with GFR exhibited reduced neurological deficit (P < 0.05) and alleviated brain infarction volume (P < 0.01). The REST gene with up-regulated expression and its downstream genes with down-regulated expression were screened by Microarray analysis. The brain cortex infarction in MCAO rats produced high levels of REST expression. The GFR intervention inhibited REST expression, and alleviated brain injury on MCAO rats., Conclusion: Our results demonstrated that GFR intervention plays a long-term neuroprotective role and reduces brain edema and damage at reperfusion, possibly by inhibiting REST expression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Covered stenting is an optional strategy for traumatic carotid pseudoaneurysm, especially in malignant conditions of potential rupture, but the long-term outcomes are not clear. Our aim was to determine if covered stenting is an effective option for traumatic carotid pseudoaneurysm with promising long-term outcomes., Methods: Self-expanding Viabahn and balloon-expandable Willis covered stents were separately implanted for extra- and intracranial traumatic carotid pseudoaneurysm. The covered stent was placed across the distal and proximal pseudoaneurysm leakage under roadmap guidance. Procedural success was defined as technical success (complete exclusion of the pseudoaneurysm and patency of the parent artery) without a primary end point (any stroke or death within 30 days after the procedure). Long-term outcomes were evaluated as ischemic stroke in the territory of the qualifying artery by clinical follow-up through outpatient or telephone consultation and as the exclusion of the pseudoaneurysm and patency of the parent artery by imaging follow-up through angiography., Results: Five patients with traumatic carotid pseudoaneurysm who underwent covered stenting were enrolled. The procedural success rate was 100%. No ischemic stroke in the territory of the qualifying artery was recorded in any of the five patients during a mean clinical follow-up of 44±16 months. Complete exclusion of the pseudoaneurysm and patency of the parent artery were maintained in all five patients during a mean imaging follow-up of 39±16 months., Conclusion: Satisfactory procedural and long-term outcomes were obtained, suggesting that covered stenting is an effective option for traumatic carotid pseudoaneurysm.

Background: The development of carotid-cavernous fistulas (CCFs) during surgical recanalization of chronic internal carotid artery occlusion (ICAO) may be secondary to severe ICA dissection rather than a focal tear of the cavernous ICA seen in typical traumatic CCFs. The purpose of this study is to investigate the causal relationship between the CCFs and severe ICA dissections and to characterize technical outcomes after treatment with stenting., Methods: Five patients underwent treatment with self-expanding stents due to intraprocedural CCF and ICA dissection following surgical removal of ICAO plaque. The stents were telescopically placed via true channel of the dissection. Safety of the procedure was evaluated with 30-day stroke and death rate. Procedural success was determined by the efficacy of CCF obliteration and ICAO recanalization with angiography., Results: All CCFs were associated with spiral and long segmental dissection from the cervical to cavernous ICA. After stenting, successful dissection reconstruction with TICI 3 was achieved in all patients, with complete ( n = 4) or partial CCF ( n = 1) obliteration. No patient had CCF syndrome, stroke, or death during follow-up of 6 to 37 months; but one patient had pulsatile tinnitus, which resolved 1 year later. Angiography at 6 to 24 months demonstrated CCF obliteration in all 5 patients and durable ICA patency in 4 patients., Conclusions: Intraprocedural CCFs with spiral and cervical-to-cavernous ICA dissection during ICAO surgery are dissection-related because of successful obliteration after stenting for dissection reconstruction. Self-expanding stenting through true channel of the dissection, serving as implanting stent-autograft, may be an optimal therapy for the atypical CCF complication from ICAO surgery., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Objectives: The optimal treatment of symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) beyond 24 h from onset remains uncertain. We investigate the outcomes of late endovascular recanalization for symptomatic non-acute atherosclerotic ILAO., Patients and Methods: From September 2013 to July 2018, with safety as the first principle, late endovascular recanalization for symptomatic non-acute atherosclerotic ILAO beyond 24 h from onset was attempted in 32 consecutive patients. Primary safety outcome was any stroke or death within 30 days. Primary efficacy outcome were functional independence at 90 days., Results: The median time from imaging-documented occlusion to treatment was 25.5 days (interquartile range: 10.5-36.5) for all patients. Technical success in recanalization was achieved in 17 patients (53.1%, 17/32). The 30-day rate of any stroke or death was 5.9% (1/17) in the recanalized group versus 6.7% (1/15) in the failure group (P = 0.927). The rate of functional independence at 90 days (70.5%, 12/17) was increased significantly as compared with that before operation (23.5%, 4/17) in the recanalized group (P = 0.015). The rate of functional independence at 90 days (66.7%, 10/15) was not different from that before operation (66.7%,10/15) in the failure group (P = 1.00). The median score reduction in mRS from baseline at 90 days was 1.0 (interquartile range: 1.0-2.0) in the recanalized group versus 0 (interquartile range: 0.0-0.0) in the failure group (P＜0.001)., Conclusion: For carefully selected patients with symptomatic non-acute atherosclerotic ILAO beyond 24 h from onset, late endovascular recanalization is technically feasible. The periprocedural safety of late endovascular recanalization is acceptable. Successful recanalization may effectively improve the degree of disability in such patients. However, it should be emphasized that revascularization of non-acute ILAO is a high risk procedure, which should only be performed by experienced operators with safety as the first principle., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: An in situ recanalization procedure of endovascular therapy (ET) or carotid endarterectomy (CEA) has been attempted in patients with symptomatic chronic internal carotid artery occlusions (ICAOs), though the recanalization rates of both are low., Objective: To investigate the outcomes of Multimodality In situ Recanalization for ICAOs in a Hybrid Operating Room (MIRHOR) at the same session., Methods: Symptomatic chronic ICAOs were classified into type A or B (short occlusion with or without a tapered residual root [TRR]), and C or D (long occlusion with or without TRR), and managed in a hybrid operating room with ET, CEA, or both, as needed. Primary efficacy outcome was technical success of recanalization with Thrombolysis in Myocardial Infarction 3. Secondary efficacy outcome was any stroke or death within 30 days (primary safety outcome) plus an ipsilateral ischemic stroke after 30 days., Results: Technical success was finally achieved in 35 (83.3%) of 42 consecutively enrolled patients with ICAO, which was significantly higher than 35.7% (15/42, p<0.001) from the initial ET or CEA alone. Furthermore, the success rate was in descending order: 100% (18/18) for type A and B occlusions, 75% (6/8) for type C occlusions, and 69% (11/16) for type D occlusions (p=0.017). Two secondary efficacy outcome events (5.1%) without mortality, including one (2.4%) primary safety outcome, were observed during a mean follow-up of 10.5 months., Conclusion: The MIRHOR for symptomatic chronic ICAOs at the same session significantly improves technical success, with low periprocedural complications and favorable clinical outcomes. The ICAO classification appears valuable in predicting technical success., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Cerebral ischemia‑reperfusion injury (CIRI) usually causes detrimental complications following reperfusion therapy in stroke patients. The present study systematically investigated the regulatory mechanism involved in the pathogenesis of CIRI using gene set enrichment analysis of the transient middle cerebral artery occlusion mouse stroke model. The results revealed a total of 13 CIRI‑related transcription factors (TFs), including CCAAT enhancer binding protein b (Cebpb), Cebpa, early growth response‑1, Fos, Rela, Jund, signal transduction and activator of transcription 5a/b, transformation related protein 53, GLI family zinc finger 2 (Gli2), Sp3, TF AP‑2 α (Tfap2a) and spleen focus forming virus proviral integration oncogene (Spi1). To the best of our knowledge, five TFs (Cebpa, Gli2, Sp3, Tfap2a and Spi1) were the first to be reported associated with CIRI in the present study. The five novel CIRI‑related TFs were mainly associated with pathways of inflammation and responses to reperfusion, including the tumor necrosis factor signaling pathway (Gli2, Spi1 and Tfap2a, P=0.0035, 0.0035 and 0.048, respectively), interleuking‑17 signaling pathway (Cebpa, Gli2, Sp3, Spi1 and Tfap2a, P=0.019, 0.047, 0.019, 0.035 and 0.005, respectively) and fluid shear stress and atherosclerosis (Gli2, Sp3, Spi1 and Tfap2a, P=0.047, 0.046, 0.013 and 0.003, respectively). These results may improve understanding of the potential molecular mechanism underlying the pathogenesis of CIRI at the genome‑wide level.

Objective: To investigate the safety of triple antiplatelet therapy (TAT) with cilostazol in patients undergoing stenting for extracranial and/or intracranial artery stenosis., Methods: A prospectively collected database was reviewed to identify patients who underwent stenting for extracranial and/or intracranial artery stenosis and showed resistance to aspirin and/or clopidogrel as assessed by pre-stenting thromboelastography (TEG) testing. Patients were assigned to a TAT group and a dual antiplatelet therapy (DAT) group. Major complications were defined as thromboembolic events (transient ischemic attack (TIA), ischemic stroke, and stent thrombosis) or major bleeding events within 30 days, and minor complications were defined as extracranial bleeding that did not require vascular surgery or transfusion within 30 days., Results: A total of 183 patients were identified. The incidence of major complications was significantly lower in the TAT group than in the DAT group (TAT group vs. DAT group, 1/110 vs. 6/73; P=0.017). TIAs occurred in four patients, with one in the TAT group and three in the DAT group (1/110 vs. 3/73; P=0.303). Ischemic strokes occurred in three patients in the DAT group (TAT group vs. DAT group, P=0.062). No major bleeding events or stent thrombosis was recorded in either group. Two patients (one in each group) experienced minor complications that resolved without additional treatment (1/110 vs. 1/73; P>0.999)., Conclusions: TAT under TEG guidance appears to be a safe antiplatelet strategy in patients undergoing stenting for extracranial and/or intracranial artery stenosis. By employing TAT under TEG guidance, favorable outcomes can be achieved in these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Subacute combined degeneration (SCD) is a relatively rare myelopathy mainly caused by vitamin B 12 (VitB12) deficiency. There are many causes contributing to VitB12 deficiency. Autoimmune gastritis might lead to severe VitB12 malabsorption and in its advanced stage pernicious anemia (PA) may occur. Besides, long-term hypergastrinemia arising from achlorhydria in autoimmune gastritis is associated with neuroendocrine tumors (NETs). Patients diagnosed with SCD coexistent with PA and NET are seldomly reported. We describe a 34-year-old woman with an initial complaint of progressive fatigue, weakness and numbness in her limbs and disturbed gait. Physical examination revealed appearance of anemia, ataxia, decrease of superficial and deep sense, and positive Babinski's sign. Laboratory tests disclosed macrocytic anemia, elevated intrinsic factor antibody and spinal MRI showed extensive T2-weighted hyperintensity in the dorsal columns. A gastric polyp was revealed by gastroscopy and histology showed an NET in the background of severe atrophic gastritis. Symptoms of the patient were relieved by a multidisciplinary therapy. In patients with SCD, PA should be suspected and prompt further investigations to elucidate causes and direct treatment.

Objective: To assess the feasibility and safety of interventional treatment of symptomatic intracranial in-stent restenosis (SISR). Methods: Clinical data of 21 patients with SISR who underwent interventional treatment in the General Hospital of the PLA Rocket Force from January 2012 to May 2018 were retrospectively analyzed. Perioperative complications, angiographic and clinical follow-up results were recorded. Results: The success rate of treatment was 100%, including 21 lesions of SISR (7 at the V4 segment of the vertebral artery, 7 at the basilar artery, 5 at the M1 segment of middle cerebral artery, 2 at the internal carotid artery). The residual stenosis rate was preoperative 84±7, postoperative 30±14 respectively. Balloon angioplasty and stent implantation were performed in 10 patients (48.6%) and 11 patients (52.4%), respectively. After treatment, 1 patient experienced perforating event without neurological sequelae. Of the 11 patients (52.4%) completed angiography follow-up, 3 (3/11, 27.3%) ocurred restenosis and 1 was retreated. During clinical follow-up, 1 patients received intravenous thrombolysis for the symptom of acute cerebral infarction in territory of stenting artery, in-stent restenosis or occlusion was not demonstrated by emergency cerebral angiography. Conclusion: Interventional treatment of SISR is feasible and safe, however, further studies need to warrant the long-term effects.

Objective: To compare the clinical effects of stent-assisted embolization and surgical clipping in the treatment of middle cerebral artery bifurcation wide-necked aneurysms. Methods: From July 2014 to March 2017, the clinical and imaging data of 45 patients with Hunt-Hess 0-Ⅲ grade middle cerebral artery bifurcation wide-necked aneurysms were divided into stent-assisted embolization group (20 patients from PLA Rocktet Army Hospital) and surgical clipping group (25 patients from Peking University International Hospital). The total occlusion rates of aneurysm, operation-related adverse events, clinical outcomes, and results of follow-up imaging from the two groups were compared. Results: The total occlusion rates in the stent-assisted embolization group and surgical clipping group were 90.0% (18/20) and 92.0% (23/25), respectively, and the difference was not statistically significant ( P =0.815). The favorable six-month postoperative outcomes defined as the modified Rankin Scale ≤2 were 94.7% (18/19) in the stent-assisted embolization group and 91.3% (21/23) in the surgical clipping group ( P =0.667). Fewer patients experienced the operation-related adverse events in the stent-assisted embolization group (15.0%, 3/20), as compared to that of the surgical clipping group (24.0%, 6/25), but the difference were not significant ( P =0.453). After 2-24 months (median 7 months) of the operation, the follow-up imaging indicated that in the stent-assisted embolization group, 2 out of the 19 patients had residual or recurrent aneurysms.While in the surgical clipping group, residual or recurrent aneurysms were identified in 2 out of the 23 patients 2-14 months (median 3 months) after the surgery; the frequency was not statistically different between the two groups ( P =0.841). Conclusion: Stent assisted embolization is a safe and effective treatment for the low grade middle cerebral artery bifurcation wide-necked aneurysms.

The leaching effect of the rainfall process for removing heavy metals from farmland soils is a critical physical process. To study the leaching effect of the rainfall process on heavy metals in soil, the pollution characteristics of seven heavy metals in farmland soil have been investigated in the suburban Tianjin region by combining the current data with previously reported runoff data in the same region. There is a large difference for these tested heavy metals in soils, with Zn having the highest concentration at 106.61±56.24 mg·kg -1 and Cd having the lowest concentration at 0.31±0.31 mg·kg -1 . Compared with the background value in Tianjin, only the content of Cd is at higher levels (a four-fold increase). The results from a single factor pollution index and comprehensive pollution index analysis indicate that the comprehensive pollution index ranking is Cd > Cu > Ni > Zn > As ≈ Cr > Pb. Cd, Cu, Ni, and Zn are in the moderate pollution, mild pollution, and alert level categories, respectively. Except for As, the results from a correlation analysis, the principal component analysis (PCA), and the cluster analysis indicate the possible similar origins of Cr, Ni, Cu, Zn, Cd, and Pb. The multivariate statistical analysis indicates that Cd is mainly derived from human activities, Zn, Cu, Cr, Ni, and Pb are affected by anthropogenic and natural sources, and As is mainly influenced by natural conditions. By comparing the ratios of individual heavy metals to Cr in soils and runoffs, the leaching behaviors have been studied, with the leaching capacity ranked as Cd > As > Cu ≈ Pb > Ni > Cr ≈ Zn. In summary, Cd pollution in soil is more prominent than pollution from other metals and should receive attention.

Ischemia-reperfusion injury (IRI) is an important cause of adverse prognosis after recanalization in patients with acute occlusion of major intracranial artery (AOMIA). Here, we provided data indicating that gradual flow restoration (GFR) would be superior to rapid flow restoration (RFR) in alleviating cerebral IRIs in middle cerebral artery occlusion (MCAO) rats. A total of 94 MCAO rats with 15, 30 and 60-minute occlusion were randomly assigned to receive either GFR or RFR intervention. There were significant differences between GFR and RFR group in mean neurological severity score (1.02 versus 1.28; p < 0.05), median infarct ratio (0.016 versus 0.12; p < 0.001), median neuronal apoptosis ratio (1.81 versus 14.46; p < 0.001), and mean histopathological abnormality score (0.92 versus 1.66; p < 0.001). In addition, these differences were mainly distributed in 30-minute and 60-minute occlusion rats, not in 15-minute occlusion rats. These results indicated that GFR rather than RFR could effectively alleviate cerebral IRIs in MCAO rats, especially in rats with longer occlusion duration, suggesting that GFR may be particularly applicable to AOMIA patients who are presented to neurointerventionalists in the later-time of recanalization therapy window.