High-Serum Brain-Derived Neurotrophic Factor Levels Are Associated With Decreased Risk of Poststroke Cognitive Impairment.

BACKGROUND: BDNF (brain-derived neurotrophic factor) is widely implicated in the pathophysiological process of stroke, but the effect of BDNF on poststroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between baseline serum BDNF and the risk of PSCI at 3 months in a multicenter study based on a preplanned ancillary study of the CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke). METHODS: We examined serum BDNF levels at baseline and used the Mini-Mental State Examination and Montreal Cognitive Assessment to evaluate cognitive function at 3-month follow-up after ischemic stroke. PSCI was defined as Mini-Mental State Examination score <27 or Montreal Cognitive Assessment score <25. Logistic regression analyses were performed to evaluate the association between serum BDNF and the risk of 3-month PSCI. RESULTS: In this ancillary study, a total of 660 patients with ischemic stroke with hypertension were included, and 593 patients (mean age, 59.90±10.44 years; 410 males and 183 females) were finally included in this analysis. According to mini-mental state examination score, after adjustment for age, sex, education, baseline National Institutes of Health Stroke Scale score, APOE ɛ4 carriers, and other potential confounders, the odds ratio of PSCI for the highest tertile of BDNF was 0.60 ([95% CI, 0.39-0.94]; P=0.024) compared with the lowest tertile. Multiple-adjusted spline regression model showed a linear association of serum BDNF levels with PSCI at 3 months (P value for linearity=0.010). Adding serum BDNF to conventional prognostic factors slightly improved the risk reclassification of PSCI (net reclassification improvement: 27.46%, P=0.001; integrated discrimination index: 1.02%, P=0.015). Similar significant findings were observed when PSCI was defined by the Montreal Cognitive Assessment score. CONCLUSIONS: Elevated serum BDNF levels were associated with a decreased risk of PSCI at 3 months, suggesting that serum BDNF might be a potential predictive biomarker for PSCI among patients with ischemic stroke with hypertension.

Association between plasma brain-derived neurotrophic factor level and Alzheimer's disease: a Mendelian randomization study.

BACKGROUND: High brain-derived neurotrophic factor (BDNF) concentrations have been found to be associated with a decreased risk of Alzheimer's disease (AD) in observational studies, but the causality for this association remains unclear. Therefore, we aimed to examine the association between genetically determined plasma BDNF levels and AD using a two-sample Mendelian randomization (MR) method. METHODS: Twenty single-nucleotide polymorphisms associated with plasma BDNF concentrations were identified as genetic instruments based on a genome-wide association study with 3301 European individuals. Summary-level data on AD were obtained from the International Genomics of Alzheimer's Project, involving 21,982 AD cases and 41,944 controls of European ancestry. To evaluate the relationship between plasma BDNF concentrations and AD, we employed the inverse-variance weighted method along with a series of sensitivity analyses. RESULTS: The inverse-variance weighted MR analysis showed that genetically determined BDNF concentrations were associated with a decreased risk of AD (odds ratio per SD increase, 0.91; 95% confidence interval, 0.86-0.96; p =0.001). The association between plasma BDNF concentrations and AD was further confirmed through sensitivity analyses using different MR methods, and MR-Egger regression suggested no directional pleiotropy for this association. CONCLUSION: Genetically determined BDNF levels were associated with a decreased risk of AD, suggesting that BDNF was implicated in the development of AD and might be a promising target for the prevention of AD.

Community-associated methicillin-resistant Staphylococcus aureus infection of diabetic foot ulcers in an eastern diabetic foot center in a tertiary hospital in China: a retrospective study.

BACKGROUND: Diabetic foot concerns are a major public health problem. Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in diabetic foot ulcers. Community-associated MRSA has become notorious for skin and skin soft tissue infections over the last two decades. This study investigated MRSA infection in diabetic foot patients at a tertiary hospital, focusing on the epidemiology and characteristics of community-associated MRSA. METHODS: A total of 149 patients with diabetic foot infection whose culture results indicated Staphylococcus aureus as the source were selected. Epidemiological investigations, clinical characteristics, laboratory index records, antibiotic susceptibility analysis, and clinical outcome tracking were performed in all cases. Based on oxacillin resistance using the Vitek Compact 2 system, cases were divided into methicillin-sensitive Staphylococcus aureus and MRSA groups. Subgroup analysis of the MRSA group was performed in accordance with the Centers for Disease Control definition: community-associated MRSA and hospital-associated MRSA. RESULTS: The MRSA group (n = 41, 27.5%) had a longer duration of ulcers and hospital stay and higher hospitalization costs than the methicillin-sensitive Staphylococcus aureus group (n = 108, 72.5%). According to the classification criteria of Infectious Diseases Society of America, the severity of infection in the community-associated MRSA group was higher than that in the hospital-associated MRSA group. The analysis of antimicrobial susceptibility of 41 MRSA isolates showed that the resistance rates to erythromycin, clindamycin, quinolone, gentamicin, tetracycline, and rifampicin were 78.0%, 68.3%, 31.7%, 17.1%, 9.8%, and 2.4%, respectively. All the MRSA strains were sensitive to linezolid, tigecycline, and vancomycin. The resistance rates to quinolones and gentamycin in the community-associated MRSA group (both 0%) were lower than those in the hospital-associated MRSA group. CONCLUSION: Emergence of MRSA in diabetic foot ulcer was associated with a prolonged wound duration and increased consumption of medical resources. Community-associated MRSA strains predominated among MRSA isolates from diabetic foot wounds and caused more severe infections.

A Bibliometric Analysis of the Top-Cited Articles on Diabetic Foot Ulcers.

The aim of this study was to determine the top-cited articles in the field of diabetic foot ulcer (DFU) research. A cross-sectional bibliometric analysis was conducted in January 2021 by using Boolean search terms in the Scopus and the Web of Science databases. The 50 top-cited articles that met the inclusion criteria were ranked and evaluated for several characteristics, including year of publication, country of origin, authorship, publishing journal, topic categories, publishing type, and level of evidence. The median number of citations per article in the list was 442 (interquartile range [IQR], 320-520), with a median of 21.8 citations (IQR, 16.5-34.5) per year since publication. The publication years ranged from 1986 to 2017, with 1998 accounting for the greatest number of studies (n = 7). The citation classics were published in 20 journals and originated from institutions in 9 countries. The majority of the studies were clinical, of which expert opinion/review with Level V evidence and clinical studies with Levels I and II evidence comprised the greater proportion in the list. This study provides useful insights into the history and development of DFU research. The top-cited list may serve as a quick reference for education curriculums and clinical practice, in addition to providing a foundation for further studies on this topic.

Association of continuous glucose monitoring-derived time in range with major amputation risk in diabetic foot osteomyelitis patients undergoing amputation.

Objective: The metrics generated from continuous glucose monitoring (CGM), such as time in range (TIR), are strongly correlated with diabetes complications. This study explored the association of perioperative CGM-derived metrics with major amputation risk in patients with diabetic foot osteomyelitis (DFO). Methods: This study recruited 55 DFO patients with grade 3-4 wounds according to the Wagner Diabetic Foot Ulcer Classification System, all of whom underwent CGM for 5 days during the perioperative period. The CGM-derived metrics were defined in accordance with the most recent international consensus recommendations. Results: Patients with major amputation had significantly less TIR and higher time below range (TBR) (all p < 0.05). In binary logistic regression analyses, a lower TIR was associated with the risk of major amputation (odds ratio: 0.83 (95% confidence interval: 0.71-0.99), p = 0.039). This association remained statistically significant after adjustments for age, sex, body mass index, type of diabetes, smoking, drinking, durations of diabetes and DFU, ankle-brachial index, albumin, estimated-glomerular filtration rate, Society for Vascular Surgery wound, ischemia, and foot infection (WIfi) stage, multidrug-resistant organisms, and hemoglobin A1c. Further adjustment for the mean amplitude of glycemic excursion (MAGE) reduced this association. TBR was also independently associated with the risk of major amputation (odds ratio: 1.60 (95% confidence interval: 1.17-2.18), p = 0.003); this association persisted after adjustment for MAGE. Conclusion: Perioperative TIR (3.9-10.0 mmol/L) and TBR (<3.9 mmol/L) were significantly associated with major amputation in hospitalized patients with DFO.

Combining CRISPR-Cas12a-Based Technology and Metagenomics Next Generation Sequencing: A New Paradigm for Rapid and Full-Scale Detection of Microbes in Infectious Diabetic Foot Samples.

Introduction: Diabetic foot infections (DFIs) pose a huge challenge for clinicians. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is one of the most significant pathogens of DFI. Early pathogen identification will greatly benefit the diagnosis and treatment of the disease. However, existing diagnostic methods are not effective in early detection. Methods: We developed an assay that coupled loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) techniques to enable quick and specific detection of Staphylococcus aureus and differentiate MRSA in samples from patients with DFI. Furthermore, the results were compared using a reference culture, quantitative real-time polymerase chain reaction (qRT-PCR), and metagenomics next generation sequencing (mNGS). Results: The CRISPR-LAMP assay targeting nuc and mecA successfully detected S. aureus strains and differentiated MRSA. The limit of detection (LoD) of the real-time LAMP for nuc and mecA was 20 copies per microliter reaction in comparison to two copies per µL reaction for the qRT-PCR assay. The specificity of the LAMP-CRISPR assay for nuc was 100%, without cross-reactions with non-S. aureus strains. Evaluating assay performance with 18 samples from DFI patients showed that the assay had 94.4% agreement (17/18 samples) with clinical culture results. The results of mNGS for 8/18 samples were consistent with those of the reference culture and LAMP-CRISPR assay. Conclusion: The findings suggest that the LAMP-CRISPR assay could be promising for the point-of-care detection of S. aureus and the differentiation of MRSA in clinical samples. Furthermore, combining the LAMP-CRISPR assay and mNGS provides an advanced platform for molecular pathogen diagnosis of DFI.

[Efficacy analysis of antibiotic bone cement in treating infectious wound of lower extremity].

OBJECTIVE: To discuss the clinical effect of antibiotic bone cement in the treatment of infectious wound of lower extremity. METHODS: From January 2016 to January 2019, 28 patients who had infection wounds of lower extremity were treated by antibiotic bone cement, including 21 males and 7 females with age of 34 to 76 (53.8±16.5) years old. The wound area after the initial debridement was 4 cm×3 cm to 12 cm×8 cm. All patients were treated with the antibiotic bone cement, when infection was controlled and fresh granulation tissue grew on the wound surface, local sutures or skin grafts were performed. The changes of white blood cell (WBC), erythrocyte sedimentation rate(ESR), C reactive protein(CRP) and positive rate of bacterial culture of wound secretions were recorded andcompared before and after 2 weeks of the operation. The healing time, recurrence rate and complications of fresh granulation on wound surface were calculated. RESULTS: All patients were followed up for 3 to 6(4.3±1.2) months. After the recurrence of diabetic foot wound infection, 3 patients presented different degree of rupture, and the remaining patients had good wound healing. No serious complications such as aggravation of infection and amputation occurred. The WBC, ESR and CRP of the patients were decreased significantly after operation compared with that before operation (9.1±1.2)×109/L vs. (11.4±2.2)×109/L, (23.5±7.6) mm/ h vs. (57.1±14.9) mg/L, (44.2±13.1) mg/L vs. (89.2±26.7) mg/L (P<0.05). The formation time of fresh granulation on the wound surface was 12 to 21(15.6±3.2) days. CONCLUSION: The antibiotic bone cement can control infection of lower extremity wound effectively, promote the growth of fresh granulation tissue and wound healing.

Arthroscopy-Assisted Reduction in the Management of Isolated Medial Malleolar Fracture.

PURPOSE: To evaluate the feasibility of arthroscopic reduction percutaneous fixation (ARPF) in the treatment of isolated medial malleolar fracture and compare the results with those of conventional open reduction internal fixation (ORIF). METHODS: This prospective study enrolled 77 patients with isolated medial malleolar fracture between November 2011 and February 2016. The patients were assigned to the ARPF (n = 34) and ORIF (n = 43) groups. The Olerud-Molander ankle score (OMAS), ankle range of motion (ROM), visual analog scale, and radiographic evaluation were determined at the scheduled follow-up. RESULTS: In the ARPF group, 11 of 34 patients (32.4%) had chondral lesions. Tears of the deltoid ligament and anterior inferior tibiofibular ligament were noted in 3 (8.8%) and 15 (44.1%) patients, respectively. The mean follow-up was 5 years. The mean OMAS was higher in the ARPF group than in the ORIF group. The differences were statistically significant at 6 months (mean ± standard deviation, 80.2 ± 4.0 for ARPF vs 77.2 ± 4.1 for ORIF, P = .005) and 1 year (92.9 ± 4.9 vs 88.1 ± 4.6, P < .001), but not at the latest follow-up (P = .081). Ankle ROM was markedly improved in the ARPF group, unlike in the ORIF group at 6 months (dorsiflexion, P = .025; plantarflexion, P < .001) and 1 year (dorsiflexion and plantarflexion, P < .001). The improvement remained at the latest follow-up in plantarflexion (P = .001) but not in dorsiflexion (P = .354). CONCLUSIONS: Arthroscopy-assisted reduction is a feasible alternative modality with superior short-term outcomes for treating isolated medial malleolar fracture, but its superiority may be attenuated in the intermediate term. LEVEL OF EVIDENCE: Level III, comparative study.

Effect of Induced Membrane Formation Followed by Polymethylmethacrylate Implantation on Diabetic Foot Ulcer Healing When Revascularization Is Not Feasible.

No study has investigated the role of induced membrane (IM) formation in treating diabetic foot ulcer (DFU). This retrospective study was aimed (1) at evaluating the potential role of a two-staged surgical approach, comprising polymethylmethacrylate (PMMA) implantation and IM formation, in the treatment of DFU and (2) at comparing the results of those with routine wound debridement in patients with DFUs and nonrevascularized peripheral arterial disease (PAD). Fifty patients with infected DFUs who were not candidates for vascular interventions were enrolled between February 2016 and April 2018 and assigned to the PMMA group (n = 28) and conventional group (n = 22). The healing rate, major amputation rate, duration of healing, frequency of debridement procedures, patient survival rate, and reulceration of DFUs were determined. The Mann-Whitney U test, independent sample t-test, and χ 2 or Fisher exact test were used in statistical analysis. Overall clinical outcomes were statistically different between the groups (Z = -2.495, P = 0.013). In the PMMA group, 16 patients (57.1%) with intact IM formation achieved ulceration healing at 13.1 ± 3.7 weeks with a mean number of debridements of 1.3 ± 0.4, which were significantly different compared to those values in 5 patients of the conventional group (22.7%, P = 0.014; healing duration: 26.4 ± 7.8 weeks, P = 0.016; mean number of debridements: 3.6 ± 0.5, P ≤ 0.001). At a mean 16.8 ± 4.3-month follow-up, patient survival rates were 92.9% and 68.2% in the PMMA and conventional groups, respectively (P = 0.032). The major amputation rate and reulceration of DFUs were similar between the groups. The two-staged surgical approach is an available, effective modality for improving healing of DFUs. This study provides preliminary information of IM formation followed by PMMA implantation in the management of DFUs in PAD when revascularization is not feasible.

[Effectiveness of transverse tibial bone transport in treatment of diabetic foot ulcer].

Objective: To evaluate the effectiveness of transverse tibial bone transport in treatment of diabetic foot ulcer. Methods: Between June 2014 and December 2017, 17 patients with diabetic foot ulcer were treated. There were 11 males and 6 females, with a median age of 57 years (range, 46-72 years). The duration of diabetes was 2.4-32.0 years (mean, 16.0 years). According to the Wagner grading criteria, 7 cases were rated as grade 2, 8 cases as grade 3, and 2 cases as grade 4. The CT angiography (CTA) showed the arterial occlusion or stenosis of varying degrees below knee joint. All cases were treated with transverse tibial bone transport. Bone transport started at 3 to 5 days after placing external fixator and lasted 14 days (1 mm per day), and then reverse transport started. The total transport time was 28-30 days. Results: All 17 patients were followed up 5-12 months (mean, 8.5 months). During transportation, 4 cases had screw orifice infection, and 3 cases had liquefaction and seepage. And other 15 cases ulcers healed and the healing time was 35-72 days (mean, 48 days). There were significant differences in visual analogue scale (VAS) scores, skin temperature, ankle brachial index (ABI) between before and after ulcer healed ( P<0.05). The CTA showed that the collateral circulation was established. The foot ulcer of 2 cases (Wagener grade 3 in 1 case and grade 4 in 1 case) still progressed after treatment, and amputation was performed. Conclusion: Transverse tibial bone transports has good effectiveness for diabetic foot ulcer.