Microbiome of limb-threatening diabetic foot ulcers indicates the association of fastidious Stenotrophomonas and major amputation.

BACKGROUND: Proper identification of the polymicrobial microorganisms in patients with limb-threatening diabetic foot ulcers (LTDFUs) using conventional culture is insufficient. This prospective study evaluates the potential value of adjuvant molecular testing assisting in identify fastidious micro-organisms in LTDFUs compared to standard treatment alone. METHODS: Ninety patients with LTDFUs received interdisciplinary and standard antibiotic treatment in a referral diabetic foot center. A simultaneous 16S amplicon sequencing (16S AS) specimen along with conventional culture collected at admission was used to retrospectively evaluate the microbiological findings and its association with amputation outcomes. RESULTS: The microorganism count revealed by 16S AS overwhelmed that of conventional culturing (17 vs. 3 bacteria/ulcer respectively). The Stenotrophomonas spp. revealed in 29 patients were highly correlated with major (above ankle) amputation (OR: 4.76, 95% CI 1.01-22.56), while only one had been concomitantly identified by conventional culturing. Thus, there were 27 cases without proper antibiotics coverage during treatment. CONCLUSIONS: Adjuvant molecular testing assisted identification of fastidious pathogens such as Stenotrophomonas infection and might be associated with major amputation in patients with LTDFUs.

Are current wound classifications valid for predicting prognosis in people treated for limb-threatening diabetic foot ulcers?

This study aims to investigate whether the current wound classifications were valid for the treatment prognosis of subjects treated for limb-threatening diabetic foot ulcers (LTDFU). A total of 1548 patients with LTDFU and infection were studied, with wounds recorded using the Wagner, Texas, PEDIS and WIfI classifications while major lower extremity amputations (LEAs) or in-hospital mortality incidences were defined as poor outcomes. Among them, 153 (9.9%) patients received major LEAs and 38 (2.5%) patients died. After adjustments, the Wagner classification and Texas stage as well as clinical factors such as comorbidity with major adverse cardiac events (MACE), being under dialysis and having serum levels of C-reactive protein (CRP) and albumin were independent factors for prognosis. For patients without dialysis, Wagner and Texas stage stood out independently for prognosis. For patients on dialysis, only levels of CRP (odds ratio [OR] = 2.2 in Wagner, OR = 2.0 in WIfI, OR = 2.2 in Texas, OR = 2.3 in PEDIS) and albumin (OR = 0.4 in four classifications) were valid predictors. The Wagner system and Texas stage were valid for predicting prognosis in treatment for LTDFUs, suggesting a role of vascular perfusion. MACE history, levels of CRP and albumin level should assist in prediction; more significantly, only levels of CRP and albumin appeared valid for those subjects undergoing dialysis.

Performance of Sequentially Bilateral Cochlear Implanted Children Who Speak Mandarin.

INTRODUCTION: Cochlear implantation is an effective treatment for children with deafness. Although the binaural effect of bilateral cochlear implantation on sound localization and speech perception in noisy environments has been demonstrated, the outcome and performance predictors of the second cochlear implant (CI2) remain uncertain for patients receiving sequential implantation. This study evaluated the hearing performance between the first cochlear implant (CI1), CI2, and bilateral cochlear implants (CI1+2) among children with sequential bilateral cochlear implantation. METHODS: This single-center retrospective study enrolled 14 children and adolescents aged 8-18 years who underwent sequential bilateral cochlear implantation with a mean interimplant interval of 8.2 years. The Mandarin Lexical Neighborhood Test (M-LNT), the Mandarin Hearing in Noise Test (M-HINT), and the Comprehensive Cochlear Implant Questionnaire (CCIQ) scores of participants were evaluated. Mann-Whitney U tests and Spearman correlation analysis were performed to analyze factors associated with CI2 performance. RESULTS: In the 1-year follow-up period after CI2 implantation, although the M-LNT mean score for CI2 was significantly lower than that for CI1, the M-LNT scores for CI2 and CI1+2 improved significantly over time. In a noisy environment, CI1+2 significantly outperformed CI1 in the M-HINT. The M-LNT score for CI2 was significantly associated with preoperative bimodal fitting, residual hearing of the second implanted ear, and CI2 daily-usage time. Specific to CI2, the CCIQ showed improvement 1 year after CI2 implantation. CONCLUSION: CI2 improved the hearing performance and quality of life of recipients with longer interimplant intervals, especially in noisy environments, and its efficacy was associated with preoperative bimodal fitting and regular daily use.

ENERGI-F703 gel, as a new topical treatment for diabetic foot and leg ulcers: A multicenter, randomized, double-blind, phase II trial.

Background: Diabetic foot and leg ulcers are a major cause of disability among patients with diabetes mellitus. A topical gel called ENERGI-F703, applied twice daily and with adenine as its active pharmaceutical ingredient, accelerated wound healing in diabetic mice. The current study evaluated the safety and efficacy of ENERGI-F703 for patients with diabetic foot and leg ulcers. Methods: This randomized, double-blind, multicenter, phase II trial recruited patients from eight medical centers in Taiwan. Patients with intractable diabetic foot and leg ulcers (Wagner Grade 1-3 without active osteomyelitis) were randomly assigned (2:1) to receive topical ENERGI-F703 gel or vehicle gel twice daily for 12 weeks or until complete ulcer closure. The investigator, enrolled patients and site personnel were masked to treatment allocation. Intention to treat (ITT) population and safety population were patient to primary analyses and safety analyses, respectively. Primary outcome was complete ulcer closure rate at the end of treatment. This trial is registered with ClinicalTrials.gov, number NCT02672436. Findings: Starting from March 15th, 2017 to December 26th, 2019, 141 patients were enrolled as safety population and randomized into ENERGI-F703 gel (n = 95) group or vehicle gel (n = 46) group. In ITT population, ENERGI-F703 (n = 90) and vehicle group showed ulcer closure rates of 36.7% (95% CI = 26.75% - 47.49%) and 26.2% (95% CI = 13.86% - 42.04%) with difference of 9.74 % (95 % CI = -6.74% - 26.23%) and 25% quartiles of the time to complete ulcer closure of 69 days and 84 days, respectively. There were 25 (26.3%) patients in ENERGI-F703 group and 11 (23.9%) patients in vehicle group experiencing serious adverse events and five deaths occurred during the study period, none of them related to the treatment. Interpretation: Our study suggests that ENERGI-F703 gel is a safe and well-tolerated treatment for chronic diabetic foot and leg ulcers. Further studies are needed to corroborate our findings in light of limitations. Funding: Energenesis Biomedical Co., Ltd.

Impact of wound microbiology on limb preservation in patients with diabetic foot infection.

AIMS/INTRODUCTION: To investigate the association between specific bacterial pathogens and treatment outcome in patients with limb-threatening diabetic foot infection (LT-DFI). MATERIALS AND METHODS: Consecutive patients treated for LT-DFI in a major diabetic foot center in Taiwan were analyzed between the years 2014 and 2017. Patients with positive wound culture results at first aid were enrolled. Clinical factors, laboratory data, and wound culture results were compared. Lower-extremity amputations and in-hospital mortality were defined as a poor outcome. RESULTS: Among the 558 patients, 272 (48.7%) patients had lower extremity amputation and 22 (3.9%) patients had in-hospital mortality. Gram-negative bacterial (GNB) infection was the independent factor following factors adjustment. When all the 31 microorganisms were analyzed, only E. coli (adjusted odds ratio [aOR], 3.01; 95% CI, 1.60-5.65), Proteus spp. (aOR, 2.99; 95% CI, 1.69-5.29), and Pseudomonas aeruginosa (aOR, 2.00; 95% CI 1.20-3.32) were associated with poor outcome. The analysis of specific GNB species in association with major- or minor- amputation have been reported. No specific pathogen was associated with cause of death in patients with mortality within 30 days. The antimicrobial-resistant strains were not associated with a poor treatment outcome. CONCLUSIONS: The presence of GNB was associated with limb amputations. This study provides insight into more timely and appropriate management of the diabetic foot infection.

Factors related to hospital-to-home transitional self-monitoring blood glucose behaviour among patients with diabetes-related foot ulcer.

AIMS: To explore the factors related to hospital-to-home transitional self-monitoring blood glucose behaviour among patients with diabetes-related foot ulcer. BACKGROUND: The 30-day readmission rate of patients with diabetes-related foot ulcer can be reduced when good glycaemic control is achieved. The practice of self-monitoring blood glucose promotes optimal glycaemic control. DESIGN: A comparative descriptive study. METHODS: In this study, 200 participants, who had been hospitalized due to diabetes-related foot ulcer, were recruited from August 2017 to July 2018. Before participants were discharged from the hospital, psychosocial factors (family support, threat belief, self-efficacy and knowledge) and pre-hospitalization self-monitoring blood glucose behaviour were collected using a structured questionnaire. Then, after discharge, self-monitoring blood glucose behaviour delivery was collected again. RESULTS: Five variables explained 47% of the variance in the delivery of self-monitoring of blood glucose at home. The delivery of hospital-to-home transitional self-monitoring blood glucose behaviour was more likely for individuals with higher pre-discharge self-efficacy, higher post-discharge self-efficacy, more attention to pre-hospitalization glycaemic status and post-discharge insulin usage and those without an insensitive foot. CONCLUSION: Self-monitoring blood-glucose behaviour should be promoted among post-discharge patients with diabetes-related foot ulcer. The modifiable factors identified in this study can be integrated into the discharge plan.

The analysis for time of referral to a medical center among patients with diabetic foot infection.

BACKGROUND: Diabetic foot infection (DFI) is a limb- and life-threatening complication for diabetic patients needing immediate and comprehensive treatment. Early referral of DFI patients to a diabetic foot center is recommended but there appears limited validated evidence, with the association between referral time and clinical outcomes of limb- preservation or in-hospital mortality still lacking. METHODS: This retrospective research studied consecutive type 2 diabetic patients with DFI treated at the major diabetic foot center in Taiwan from 2014 to 2017. Six hundred and sixty-eight patients presented with limb-threatening DFI. After stratifying their referral days into quartiles, the demographic information and clinical outcomes were analyzed. RESULTS: One hundred and seventy-two patients were placed in the first quartile (Q1) with less than 9 days of referral time; 164 in the second quartile (Q2) with 9-21 days; 167 in the third quartile (Q3) with 21-59 days; and 165 in the fourth quartile (Q4) with >59 days. End-stage renal disease (ESRD), major adverse cardiac events (MACE) and peripheral arterial disease (PAD) were noted as being higher in the Q4 group compared with the Q1 group (25.45% vs 20.35% in ESRD, 47.27% vs 26.16% in MACE and 78.79% vs 52.33% in PAD respectively). The Q1 group had more patients presenting with systemic inflammatory responsive syndrome (SIRS) (29.07% in Q1 vs 25.45% in Q4 respectively, P=0.019). Regarding poor outcome (major lower-extremity amputation (LEA) or in-hospital mortality), the Q4 group had 21.21% of patients in this category and the Q1 group had 10.47%. The odds ratio of each increased referral day on poor prognosis was 1.006 with 95% confidence interval 1.003-1.010 (P=<0.001). In subgroups, the impact on poor prognosis by day was most obvious in patients with SIRS (OR 1.011, 95% CI 1.004-1.018, P=0.003) and those with PAD (OR 1.004, 95% CI 1.001-1.008, P=0.028). CONCLUSIONS: The deferred referral of DFI patients to the diabetic foot center might be associated with poor treatment outcome either in major LEA or mortality, particularly in patients with SIRS or PAD. Both physician and patient awareness of disease severity and overcoming the referral barrier is suggested. TRIAL REGISTRATION: Not applicable.

Amino acids and wound healing in people with limb-threatening diabetic foot ulcers.

BACKGROUND: Amino acids are associated with wound healing in traumatic wounds and burns, although their effects on healing in patients with diabetic foot ulcers (DFUs) are limited. This study aimed to evaluate and identify specific amino acids associated with healing outcomes of patients with DFUs. METHODS: Sixty-two out of 85 patients who completed the in-hospital treatment for limb-threatening DFUs were enrolled. All ulcers had epithelialization without clinical evidence of infection at discharge. The patients and their families were instructed on foot-care techniques and committed to regular follow-up for 1 year. Baseline characteristics, PEDIS wound classification, laboratory data and serum amino acid levels were used to analyze their predictive power. RESULTS: Fifty-seven patients completed the study in which 38 had healed and 19 had unhealed ulcers. The unhealed group had higher incidence of coronary artery disease and larger wound size. Most patients received endovascular therapy (81.6% healed group; 78.9% unhealed group) before enrollment. Following adjustments for clinical factors, the serum levels of arginine (326.4 µmol/L vs. 245.0 µmol/L, P = 0.045), isoleucine (166.7 µmol/L vs. 130.1 µmol/L, P = 0.019), leucine (325.8 µmol/L vs. 248.9 µmol/L, P = 0.039), and threonine (186.7 µmol/L vs. 152.0 µmol/L, P = 0.019) were significantly higher in the healed group. CONCLUSIONS: The amino acids associated with wound healing in DFUs differ from those reported for traditional traumatic wounds. These findings affirm the necessity for future large-scaled studies for the application of these amino acids in DFU healing, either as prognostic predictors or supplemented regimens.

Survival and associated risk factors in patients with diabetes and amputations caused by infectious foot gangrene.

BACKGROUND: Infectious gangrene of the foot is a serious complication of diabetes that usually leads to a certain level of lower-extremity amputation (LEA). Nevertheless, the long-term survival and factors associated with mortality in such patients have yet to be elucidated. METHODS: A total of 157 patients with type 2 diabetes who received treatment for infectious foot gangrene at a major diabetic foot center in Taiwan from 2002 to 2009 were enrolled, of whom 90 had major LEAs (above the ankle) and 67 had minor LEAs (below the ankle). Clinical data during treatment were used for the analysis of survival and LEA, and survival was tracked after treatment until December 2012. RESULTS: Of the 157 patients, 109 died, with a median survival time of 3.12 years and 5-year survival rate of 40%. Age [hazard ratio 1.04 (95% confidence interval 1.01-1.06)], and major LEA [1.80 (1.05-3.09)] were independent factors associated with mortality. Patients with minor LEAs had a better median survival than those with major LEAs (5.5 and 1.9 years, respectively, P < 0.01). An abnormal ankle-brachial index was an independent risk factor [odds ratio 3.12 (95% CI 1.18-8.24)] for a poor outcome (major LEA) after adjusting for age, smoking status, hypertension, major adverse cardiac events, and renal function. CONCLUSIONS: Efforts to limit amputations below the ankle resulted in better survival of patients with infectious foot gangrene. An abnormal ankle-brachial index may guide physicians to make appropriate decisions with regards to the amputation level.

Tone production and perception and intelligibility of produced speech in Mandarin-speaking cochlear implanted children.

OBJECTIVE: This study explored tone production, tone perception and intelligibility of produced speech in Mandarin-speaking prelingually deaf children with at least 5 years of cochlear implant (CI) experience. Another focus was on the predictive value of tone perception and tone production as they relate to speech intelligibility. DESIGN: Cross-sectional research. STUDY SAMPLE: Thirty-three prelingually deafened children aged over eight years with over five years of experience with CI underwent tests for tone perception, tone production, and the Speech Intelligibility Rating (SIR). A Pearson correlation and a stepwise regression analysis were used to estimate the correlations among tone perception, tone production, and SIR scores. RESULTS: The mean scores for tone perception, tone production, and SIR were 76.88%, 90.08%, and 4.08, respectively. Moderately positive Pearson correlations were found between tone perception and production, tone production and SIR, and tone perception and SIR (p < 0.01, p < 0.01 and p < 0.01, respectively). In the stepwise regression analysis, tone production, as the major predictor, accounted for 29% of the variations in the SIR (p < 0.01). CONCLUSIONS: Mandarin-speaking cochlear-implanted children with sufficient duration of CI use produce intelligent speech. Speech intelligibility can be predicted by tone production performance.

Effect of limb preservation status and body mass index on the survival of patients with limb-threatening diabetic foot ulcers.

AIMS: To evaluate the effect of limb preservation status and body mass index (BMI) on the survival of patients with diabetic foot ulcers (DFUs). METHODS: A total of 1346 patients treated for limb-threatening DFUs at a major diabetic foot center in Taiwan from 2002 to 2009 were tracked until December 2012. The patients were classified into three groups: limb-preserved (n=858), minor lower-extremity amputation (LEA) (n=249), and major LEA (n=239). Clinical data during treatment were used for survival analysis. RESULTS: With 729 deaths, the median survival time (MST) was 6.14 (95% CI 5.63-6.65) years. Major LEA and BMI were two independent factors associated with mortality after adjusting for age, diabetic duration, HbA1c level, comorbidities and peripheral artery diseases. The mortality hazard ratios for the minor and major LEA groups were 0.92 (95% CI 0.74-1.16) and 1.34 (95% CI 1.07-1.68), respectively, to the reference group (limb-preserved). After stratifying BMI into four categories (underweight, normal weight, overweight and obesity, according to the Taiwanese definition), the MSTs for each category were 2.57, 5.24, 7.47 and 7.85years, respectively (P for trend <0.01). This "obesity paradox" was not observed in the major LEA group (P for trend 0.25). For patients with LEA, the obesity patients had lower MST than those in overweight category (7.97 and 8.84 in minor and 3.25 and 5.42 in major LEA, respectively). CONCLUSIONS: For the patients treated for DFUs, major - but not minor - LEA was associated with poor survival compared with the limb-preserved group. The MST had positive correlation with BMI levels for patients with limb-preserved and minor LEA, but not for those with major LEA.

The impact of nutritional status on treatment outcomes of patients with limb-threatening diabetic foot ulcers.

AIM: This study aimed to investigate the nutritional status of patients with limb-threatening diabetic foot ulcers (DFUs) and its impact on treatment outcomes. METHODS: A total of 478 consecutive patients (mean age, 65.4years) treated for limb-threatening DFUs were enrolled. Nutritional status assessment using the Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) was performed by three qualified dieticians within 48hours of admission. Limb-preservation outcomes were stratified into major lower extremity amputation (LEA) (above the ankle, n=33), minor LEA (distal to ankle, n=117) and no amputation (non-LEA, n=328). RESULTS: Most patients were identified as being at risk of malnutrition (70.5%) or malnourished (14.6%) (mean MNA score, 20.6±3.4). MNA scores decreased with increasing severity of LEA (mean, 21.1, 20.0, and 17.9, respectively; P for linear trend <0.001), associated inversely with the tendency to require LEA (P for linear trend was 0.001), and associated independently with both major and minor LEA outcomes (adjusted odds ratio [aOR]=0.80, 95% confidence interval [CI], 0.65-0.99, P=0.042 and aOR=0.89, 95% CI, 0.80-0.99, P=0.032, respectively). The predictive value was sustained in patients younger than age 65years. Though GNRI results had similar associations with outcomes, its predictive value was limited in minor LEA and younger population. CONCLUSIONS: Patients' nutritional status was shown to have significant influence on limb-preservation outcomes for limb-threatening DFUs. Nutritional assessment of this patient population using the MNA is recommended.

Clinical Characteristics and Risk Factor Analysis for Lower-Extremity Amputations in Diabetic Patients With Foot Ulcer Complicated by Necrotizing Fasciitis.

Patients with diabetes are at a higher risk of having diabetic foot ulcers (DFUs) or necrotizing fasciitis (NF). The present study aims to examine the clinical characteristics and associated risk factors for lower-extremity amputation (LEA) in patients with DFU complicated by NF.We retrospectively reviewed patients treated at a major diabetic foot center in Taiwan between 2009 and 2014. Of the 2265 cases 110 had lower-extremity NF. Limb preservation outcomes were classified as major LEA, minor LEA, or limb-preserved. Clinical characteristics, laboratory data, and bacterial culture results were collected for analysis.Of the 110 patients with NF, 100 had concomitant DFUs (NF with DFU) and the remaining 10 had no DFU (NF without DFU). None of the NF patients without DFU died nor had their leg amputated. Two NF patients with DFU died of complications. The amputation rate in the surviving 98 NF patients with DFU was 72.4% (46.9% minor LEA and 25.5% major LEA). Seventy percent of the NF patients without DFU had monomicrobial infections (60% with Streptococcus species), and 81.4% NF patients with DFU had polymicrobial infections. Anaerobic organisms were identified in 66% of the NF patients with DFU. Multinomial logistic regression analysis revealed an association between high-grade Wagner wound classification (Wagner 4 and Wagner 5) and LEA (adjusted odds ratio [aOR] = 21.856, 95% confidence interval [95% CI] = 1.625-203.947, P = 0.02 and aOR = 20.094, 95% CI = 1.968-205.216, P = 0.01 for major and minor LEA, respectively) for NF patients with DFU. In addition, a lower serum albumin level was associated with major LEA (OR = 0.066, P = 0.002).In summary, once DFUs were complicated by NF, the risk of amputation increased. Empirical treatment for NF patients with DFU should cover polymicrobial infections, including anaerobic organisms. The high-grade wound classification and low serum albumin level were associated with LEA.

Treatment for diabetic foot ulcers complicated by major cardiac events.

OBJECTIVE: Diabetic foot ulcer (DFU) is a major complication in patients with diabetes mellitus and the leading cause of non-traumatic amputation in adults. Patients with DFU are usually fragile due to chronic diabetic comorbidities; therefore, tedious debridement and intervention procedures may not be well tolerated in patients with DFU. This study aimed to identify a casual relationship between in-hospital complications and treatment for limb-threatening DFUs. METHODS: From 2009 to 2011, 1130 consecutive patients who were admitted to the Diabetic Foot Care Center in Chang Gung Medical Center were surveyed. Rates of in-hospital mortality or events that lead to transfer to the intensive care unit (ICU) for various severe complications were retrospectively analyzed. RESULTS: Forty-seven patients (4.2%) experienced in-hospital complications (28 patients died). Major adverse cardiac events (MACE) (n=21, 44.7%) were the most common complications, followed by nosocomial infection (n=18, 38.3%). Previous myocardial infarction was a risk factor for MACE. The presentation of MACE was fulminant (eg, acute pulmonary edema, cardiogenic shock,cardiac arrest), and occurred within 10 days of admission or within 10 days following a major procedure in most cases. ST-T segment abnormality at rest was the most common presentation of electrocardiography for MACE. CONCLUSION: MACE should be prevented during treatment for limb-threatening DFU in high-risk patients. Acute stress might have caused MACE during the first 10 days after admission or a major procedure.

Speech Recognition Performance under Noisy Conditions of Children with Hearing Loss.

OBJECTIVES: In order to understand the communicative abilities of hearing impaired children in noisy situations and their communication problems, this study was undertaken to examine speech recognition at different background noise levels, and to compare how context cues in noisy situations affect speech recognition. METHODS: Thirty-four children with severe/profound hearing impairment were enrolled. Fifteen children had cochlear implants (CIs) and 19 used hearing aids (HAs). The Mandarin Speech Perception in Noise (SPIN) test was performed under two levels of background noise, signal-to-noise ratio (SNR) 10 dB and SNR 0 dB (high and low levels, respectively). High predictive (HP) and low predictive (LP) sentences SPIN test scores were recorded to test the effect of context cues on speech recognition. RESULTS: Performance was significantly better in children with CIs (SNR 10: mean, 49.44, standard deviation [SD], 13.90; SNR 0: mean, 31.95, SD, 15.72) than in children with HAs (SNR 10: mean, 33.33, SD, 9.72; SNR 0: mean, 19.52, SD, 6.67; P<0.05) in both noise backgrounds, but no significant interaction was found between devices and background noise level. Hearing-impaired children performed better at SNR 10 dB (mean, 40.44; SD, 14.12) than at SNR 0 dB (mean, 25.0; SD, 12.98), significantly (P<0.001). Performance for HP sentences (mean, 38.6; SD, 12.66) was significantly (P<0.001) better than that for LP sentences (mean, 25.25; SD, 12.93). An interaction was found to between background noise level and contextual cues in sentences (F=8.47, P<0.01). CONCLUSION: The study shows that SNR conditions significantly influence speech recognition performance in children with severe/profound hearing impairment. Under better SNR listening situations, children have better speech recognition when listening to sentences with contextual cues. Children with CIs perform better than children with HAs at both noise levels.

Risk factors for lower extremity amputation in diabetic foot disease categorized by Wagner classification.

AIMS: To elucidate the risk factors for lower extremity amputation (LEA) in patients of diabetic foot disease with different Wagner gradings. METHODS: This study was conducted in a multidisciplinary diabetic foot care center. Demographic characteristics, laboratory data, disease history, ankle brachial pressure index (ABI) and Wagner classification were considered as independent variables to predict the therapeutic outcome (major LEA, minor LEA, and non-amputation). Risk factors for LEA in different Wagner grades were further analyzed. Multivariate stepwise ordinal logistic regression was performed. RESULTS: Of 789 study subjects, 19.9% received major LEA and 22.9% received minor LEA. Higher Wagner grade, lower ABI, serum albumin and hemoglobin, and elevated white blood cell (WBC) count were significantly associated with an increased risk of LEA. When stratified by Wagner classification, most of the above predictors and estimated glomerular filtration (eGFR) were detected only in grade 3. While in grades 2 and 4, WBC count was identified as primary predictor positively associated with an increased risk of LEA. CONCLUSIONS: Wagner classification remarkably influenced the potential risk factors for LEA, showing different predictors in different grades. The traditionally recognized predictors for diabetic foot amputation such as lower ABI, albumin or eGFR were almost exclusively found in patients with Wagner grade 3.

The agreement of caregivers' initial identification of children's developmental problems with the professional assessment in Taiwan.

Children's developmental problems vary, with some easier to identify than others. The accuracy of caregivers' initial identification of children's developmental problems is important in the timely treatment of those problems by medical professionals. In this study, we investigated the degree to which caregivers' initial identification of children's developmental problems matched the clinical assessment by a team of qualified professionals in a developmental assessment unit of a medical center in Taiwan. The practitioners included a pediatric neurologist, a psychiatrist, a psychologist, an occupational therapist, a physical therapist, and two speech therapists. Caregivers of 943 children (age range: 2-80 months; mean: 37.7 months) who visited the unit for a suspected developmental problem were interviewed about the chief problem that led to the caregivers bringing their children to the unit. The results showed high agreement in the global and the motor domains between the caregivers and the professionals, and low agreement in the cognitive and the speech/language domains. The agreement was significantly related to the caregivers' native origin and socioeconomic status index (SSI). Caregivers with a foreign origin (immigrant mothers) and low SSI were more likely to misidentify their children's problems. It is recommended that pediatric practitioners offer continuing education to caregivers, especially in the domains of cognitive and speech/language development.

Garlic accelerates red blood cell turnover and splenic erythropoietic gene expression in mice: evidence for erythropoietin-independent erythropoiesis.

Garlic (Allium sativum) has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic's other physiological effects.

Tone discrimination and speech perception benefit in Mandarin-speaking children fit with HiRes fidelity 120 sound processing.

OBJECTIVE: To compare tone discrimination, speech perception, and general listening benefit in Mandarin-speaking children using standard HiRes and after 1, 3, and 6 months of HiRes 120 use. The HiResolution Bionic Ear is an implantable prosthesis designed to provide access to sound and to improve perception of speech via electrical stimulation of the auditory nerve. The newest sound-processing strategy is HiRes with Fidelity 120 (HiRes 120). In HiRes 120, the input signal is analyzed in greater spectral detail than with original HiRes to achieve a maximum of 120 spectral bands. HiRes 120 is expected to provide more benefit than the original HiRes because of the increased spectral resolution. SETTING: Cochlear implant/tertiary referral center. SUBJECTS: Seven children, aged 5 to 12 years, who had been implanted with a CII or 90K implant with a fully inserted electrode array and at least 10 contiguous programmable electrodes. DESIGN: Tone discrimination, consonant identification, the Mandarin lexical neighborhood test (M-LNT), and the speech perception in noise (SPIN) tests were administered in 4 sessions: at a baseline visit with standard HiRes before being fit with HiRes 120 and at 1, 3, and 6 months after using HiRes 120. Each subject and his or her parents also completed a strategy preference questionnaire after using HiRes 120 for 6 months. RESULTS: Statistically significant improvements from baseline with HiRes to 6 months with HiRes 120 were found for tone discrimination (61.4 to 73.2%, p = 0.006) and for SPIN low predictability (65.7 to 74.7%, p = 0.039). Mean score changes of 47.4 to 50.4% (p = 0.499) for consonant perception, 82.9 to 86.4% for M-LNT (easy words; p = 0.322), 77.1 to 81.0% for M-LNT (hard words; p = 0.423), and 72.3 to 78.5% for SPIN high predictability (p = 0.427) showed trends for improvement but were not statistically significant. Questionnaire results indicated that all children and parents preferred HiRes 120 to HiRes. Strength of preference was 8.9 for children and 8.1 for parents on a scale of 1 to 10 (1 = weak preference, 10 = strong preference). CONCLUSION: Taken together, the improved tone discrimination and speech perception results, along with subjective improvements in speech fluency, discrimination, and music appreciation, indicate a trend toward superior listening benefit with HiRes 120 compared with standard HiRes in Mandarin-speaking children.