A simple high-volume culture technique-Good substitute for polymerase chain reaction for the detection of Aspergillus species in bronchoalveolar lavage samples.

BACKGROUND: Aspergillus species is the most common agent of invasive pulmonary fungal disease. Culture-based diagnosis considered as gold standard is limited by the fungal load in samples. Detection of Aspergillus by polymerase chain reaction (PCR) has been included as a diagnostic criterion by European Organisation for Research and Treatment of Cancer (EORTC). Most routine laboratories lack facilities for molecular diagnosis. Better yield using high-volume culture (HVC) technique has been reported. Studies have not compared HVC and PCR for detection of Aspergillus species in respiratory samples from patients with suspected invasive pulmonary Aspergillosis (IPA) not on antifungal therapy. OBJECTIVE: This pilot study compared HVC and PCR for the detection of Aspergillus species in respiratory samples from treatment naïve patients. METHODS: Bronchoalveolar lavage (BAL) samples from 30 patients with clinical suspicion of IPA were evaluated. Direct microscopy, culture both conventional (CC) and HVC and qualitative Pan Aspergillus PCR were performed. Latent class model was used for statistical analysis. RESULTS: Sensitivity of HVC (100%) was better compared with CC (60%) and comparable to that of PCR (100%). Specificities of CC, HVC and PCR were 100%, 100% and 25%, respectively. CONCLUSION: High-volume culture is a simple cost-effective technique with a high sensitivity and specificity. It can be easily introduced in routine microbiology laboratories. In centres with the availability of infrastructure for molecular analysis, Aspergillus PCR with other mycological techniques can be used for better diagnosis and management of patients with IPA.

A 3D printing personalized percutaneous puncture guide access plate for percutaneous nephrolithotomy: a pilot study.

OBJECTIVE: CT-Urography combined with 3D printing technology, digital design, construction of individualized PCNL puncture guides, and preliminary analyze their efficacy, safety puncture positioning for PCNL. METHODS: Twenty-two patients with renal calculi were randomly selected at the affiliated Hospital of Xuzhou Medical University during 2017-2018. We randomly divided the patients into two groups: in 10 experimental groups, we used our 3D printing personalized percutaneous puncture guide access plate for PCNL, and in the control group, 12 patients with standard USG guide PCNL. The accuracy of puncture position, puncture time, and intraoperative blood loss was compared. RESULTS: In the experimental group, 10 patients with 3D printing personalized percutaneous puncture guide access plate. The puncture needle was accessed through the guide plate and verified by the color Doppler. The single puncture, needle position, and depth success rate were 100.00% (10/10). The angles were consistent with the preoperative design. In the control group, 12 patients via USG guided PCNL success rate was 75.00% (9/12). The puncture time and amount of hemorrhage was (7.78 ± 0.94) min and (49.31 ± 6.43) mL, and (9.04 ± 1.09) min and (60.08 ± 12.18) mL, respectively. The above data of the two groups were statistically significant (P < 0.05). CONCLUSION: 3D printing personalized percutaneous nephrolithotomy guide plate for PCNL can improve PCNL renal puncture channel positioning accuracy, shorten puncture time, reduce intraoperative blood loss, bleeding-related complications and provide a new method for PCNL renal puncture positioning, which is worthy of further clinical exploration.

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.

Romiplostim treatment for children with immune thrombocytopenia: Results of an integrated database of five clinical trials.

BACKGROUND: Treatment for chronic immune thrombocytopenia (cITP) in children is largely limited to immunosuppressive agents. Thrombopoietin receptor agonists (TRAs) have been used to treat cITP in adults for over a decade. The objective of this integrated analysis was to examine the safety and efficacy of the TRA romiplostim in children with ITP. METHODS: We examined efficacy and safety in children with ITP across five romiplostim trials: final data from two double-blind placebo-controlled trials and two open-label extensions, and interim data from an ongoing single-arm trial. RESULTS: Patients (n = 24 initially placebo; n = 262 initially romiplostim) had a median age of 10.0 years (Q1: 6.0, Q3: 13.0), ITP duration of 1.9 years (Q1: 1.0, Q3: 4.0), and baseline platelet count of 14.3 × 109 /L (Q1: 7.5, Q3: 23.0). Among 282 patients receiving romiplostim, median treatment duration was 65 weeks (range 8-471 weeks) and median weekly dose was 6.6 µg/kg (range 0.1-9.7 µg/kg). Overall, 89% of romiplostim-treated patients had platelet responses. Nineteen patients (7%) maintained treatment-free responses for ≥6 months while withholding all ITP therapy. Grade 3 and 4 adverse events of bleeding occurred in 10% and <1% of romiplostim-treated patients, respectively. Twenty-five percent of patients had a serious adverse event, most commonly epistaxis (6%). Seven patients (2%) had neutralizing antibodies against romiplostim postbaseline and none had neutralizing antibodies against endogenous thrombopoietin. Efficacy and safety results appeared similar between children with ITP for ≤12 months and >12 months at baseline. CONCLUSIONS: Across five pediatric clinical trials, romiplostim was well tolerated. Most patients had a platelet response; some maintained responses for at least 6 months while withholding all ITP therapy.

Long-term treatment with romiplostim and treatment-free platelet responses in children with chronic immune thrombocytopenia.

Children with immune thrombocytopenia for ≥6 months completing a romiplostim study received weekly subcutaneous romiplostim (1-10 µg/kg targeting platelet counts of 50-200×109/L) in this extension to examine romiplostim's long-term safety and efficacy. Sixty-five children received romiplostim for a median of 2.6 years (range: 0.1-7.0 years). Median baseline age was 11 years (range: 3-18 years) and platelet count was 28×109/L (range: 2-458×109/L). No patient discontinued treatment for an adverse event. Median average weekly dose was 4.8 mg/kg (range: 0.1-10 mg/kg); median platelet counts remained >50×109/L, starting at week 2. Nearly all patients (94%) had ≥1 platelet response (≥50×109/L, no rescue medication in the previous 4 weeks), 72% had responded at ≥75% of visits, and 58% had responded at ≥90% of visits. Treatment-free response (platelets ≥50×109/L ≥24 weeks without immune thrombocytopenia treatment) was seen in 15 of 65 patients while withholding romiplostim doses. At onset of treatment-free response, the nine girls and six boys had a median immune thrombocytopenia duration of four years (range: 1-12 years) and had received romiplostim for two years (range: 1-6 years). At last observation, treatment-free responses lasted for a median of one year (range: 0.4-2.1 years), with 14 of 15 patients still in treatment-free response. Younger age at first dose and platelet count >200×109/L in the first four weeks were associated with treatment-free responses. In this 7-year open-label extension, three-quarters of the patients responded ≥75% of the time, and romiplostim was well tolerated, with no substantial treatment-related adverse events. Importantly, 23% of children maintained treatment-free platelet responses while withholding romiplostim and all other immune thrombocytopenia medications for ≥6 months. (Registered at clinicaltrials.gov identifier: 01071954).

Chronotropic incompetence and myocardial injury after noncardiac surgery: planned secondary analysis of a prospective observational international cohort study.

BACKGROUND: Physiological measures of heart failure are common in surgical patients, despite the absence of a diagnosis. Heart rate (HR) increases during exercise are frequently blunted in heart failure (termed chronotropic incompetence), which primarily reflects beta-adrenoreceptor dysfunction. We examined whether chronotropic incompetence was associated with myocardial injury after noncardiac surgery. METHODS: This was a predefined analysis of an international cohort study where participants aged ≥40 yr underwent symptom-limited cardiopulmonary exercise testing before noncardiac surgery. Chronotropic incompetence was defined as the ratio of increase in HR during exercise to age-predicted maximal increase in HR <0.6. The primary outcome was myocardial injury within 3 days after surgery, defined by high-sensitivity troponin assays >99th centile. Explanatory variables were biomarkers for heart failure (ventilatory efficiency slope [minute ventilation/carbon dioxide production] ≥34; peak oxygen consumption ≤14 ml kg-1 min-1; HR recovery ≤6 beats min-1 decrease 1 min post-exercise; preoperative N-terminal pro-B-type natriuretic peptide [NT pro-BNP] >300 pg ml-1). Myocardial injury was compared in the presence or absence of sympathetic (i.e. chronotropic incompetence) or parasympathetic (i.e. impaired HR recovery after exercise) thresholds indicative of dysfunction. Data are presented as odds ratios (ORs) (95% confidence intervals). RESULTS: Chronotropic incompetence occurred in 396/1325 (29.9%) participants; only 16/1325 (1.2%) had a heart failure diagnosis. Myocardial injury was sustained by 162/1325 (12.2%) patients. Raised preoperative NT pro-BNP was more common when chronotropic incompetence was <0.6 (OR: 1.57 [1.11-2.23]; P=0.011). Chronotropic incompetence was not significantly associated with myocardial injury (OR: 1.05 [0.74-1.50]; P=0.78), independent of rate-limiting therapy. HR recovery <12 beats min-1 decrease after exercise was associated with myocardial injury in the presence (OR: 1.62 [1.05-2.51]; P=0.03) or absence (OR: 1.60 [1.06-2.39]; P=0.02) of chronotropic incompetence. CONCLUSIONS: Chronotropic incompetence is common in surgical patients. In contrast to parasympathetic dysfunction which was associated with myocardial injury, preoperative chronotropic incompetence (suggestive of sympathetic dysfunction) was not associated with postoperative myocardial injury.

An unusual case of anemia in a cardiac transplant recipient.

Anemia is a well-described comorbidity in patients with heart failure and has been associated with decreased survival rates after heart transplant. The causes of anemia are broad, and identification of the underlying etiology is critical for management. Herein, we report an unusual case of severe anemia complicating cardiac transplantation.

Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study.

BACKGROUND: The thrombopoietin receptor agonist romiplostim could be an effective treatment in symptomatic children with persistent or chronic immune thrombocytopenia. We aimed to assess whether romiplostim is safe and effective in children with immune thrombocytopenia of more than 6 months' duration. METHODS: In this phase 3 double-blind study, eligible participants were children with immune thrombocytopenia aged 1 year to 17 years and mean platelet counts 30 × 10(9)/L or less (mean of two measurements during the screening period) with no single count greater than 35 × 10(9)/L, and were recruited from 27 sites in the USA, Canada, and Australia. Participants were randomly assigned (2:1) through the interactive voice response system to receive weekly romiplostim or placebo for 24 weeks stratified by age (1 year to <6 years, 6 years to <12 years, 12 years to <18 years), adjusting the dose weekly from 1 µg/kg to 10 µg/kg to target platelet counts of 50-200 × 10(9)/L. Patients and investigators were blinded to the treatment assignment. The primary analysis included all randomised patients and the safety analysis included all randomised patients who received at least one dose of investigational product. The primary endpoint, durable platelet response, was defined as achievement of weekly platelet responses (platelet counts ≥50 × 10(9)/L without rescue drug use in the preceding 4 weeks) in 6 or more of the final 8 weeks (weeks 18-25). This study is registered with ClinicalTrials.gov, NCT 01444417. FINDINGS: Between Jan 24, 2012, and Sept 3, 2014, 62 patients were randomly assigned; 42 to romiplostim and 20 to placebo. Durable platelet response was seen in 22 (52%) patients in the romiplostim group and two (10%) in the placebo group (p=0·002, odds ratio 9·1 [95% CI 1·9-43·2]). Durable platelet response rates with romiplostim by age were 38% (3/8) for 1 year to younger than 6 years, 56% (10/18) for 6 years to younger than 12 years, and 56% (9/16) for 12 years to younger than 18 years. One (5%) of 19 patients in the placebo group had serious adverse events compared with 10 (24%) of 42 patients in the romiplostim group. Of these serious adverse events, headache and thrombocytosis, in one (2%) of 42 patients in the romiplostim group, were considered treatment related. No patients withdrew due to adverse events. INTERPRETATION: In children with chronic immune thrombocytopenia, romiplostim induced a high rate of platelet response with no new safety signals. Ongoing romiplostim studies will provide further information as to long-term efficacy, safety, and remission in children with immune thrombocytopenia. FUNDING: Amgen Inc.

Losartan for the nephropathy of sickle cell anemia: A phase-2, multicenter trial.

Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase-2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA = 14, MicroA = 12, MacroA = 6). The primary endpoint was met in 83% of the MacroA group (P < 0.0001) and 58% of the MicroA group (P < 0.0001). Median fold-change in UACR was -0.74 for MacroA and -0.46 for MicroA. In MacroA and MicroA, UACR classification improved in 50% but worsened in 11%. Urine osmolality and estimated glomerular filtration rate (eGFR) did not change significantly. Losartan was discontinued in three participants [leg cramps, N = 1; decline in eGFR >25% (142➝104 mL/minute/1.73 m2 ), N = 1; rise in serum creatinine >50% (0.2➝0.3 mg/dL), N = 1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase-3, randomized, placebo-controlled trial of losartan for the nephropathy of SCA.

A novel immunomodulatory treatment involving mycophenolate mofetil and corticosteroids for pediatric autoimmune cytopenias.

BACKGROUND: Successful treatment of both pediatric autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), specifically those that are refractory to first-line therapies, remains unsatisfactory in terms of long-term remission and medication side effects. Here, we propose a novel combination therapy of mycophenolate mofetil (MMF), an adjunct immunosuppressive, and short-term corticosteroids for the treatment of persistent or chronic autoimmune cytopenias in children. This combination may allow for rapid decrease of steroid usage as well as prolonged count stabilization with minimal toxicity to the patient. PROCEDURE: Prospective case series of nine patients, six with persistent or chronic ITP and three with persistent or chronic AIHA, between the ages of 5 and 19 years who are being treated with combination therapy consisting of corticosteroids and MMF. RESULTS: All patients with ITP (Patients 4-9) and AIHA (Patients 1-3) met complete response (CR) criteria, as they all initially achieved platelet counts 100 × 109 l-1 or more or hemoglobin level greater than or equal to 10 g/dl, respectively, while on combination therapy and then maintained this level or higher while on MMF alone after steroids were discontinued. CONCLUSIONS: Our results are very promising, as MMF appears to be an effective and well-tolerated adjunct immunosuppressant that allows for rapid weaning of steroid usage, minimal adverse side effects to the patients, and long-term stabilization of counts, a goal that has not been achieved successfully with other secondary treatment modalities. Therefore, this novel combination therapy may be an excellent alternative for the treatment of persistent or chronic autoimmune cytopenias in the pediatric population.

Long-term Erythrocytapheresis Is Associated With Reduced Liver Iron Concentration in Sickle Cell Disease.

BACKGROUND: Erythrocytapheresis procedures are increasingly used in sickle cell disease. Serum ferritin and noninvasive magnetic resonance imaging measurements of liver iron concentration (LIC) are frequently used to monitor iron overload secondary to hypertransfusion. There is a paucity of data describing the impact of long-term erythrocytapheresis (LTE) on LIC. MATERIALS AND METHODS: We measured magnetic resonance imaging liver and cardiac iron on LTE subjects and stratified them into 2 groups: higher LIC (>3 mg/g) and lower LIC (<3 mg/g). χ(2) and t test were used to test for differences between the 2 groups. Logistic regression and generalized linear mixed-effects models were used to test what impacted LIC. RESULTS: None of 29 sickle cell disease subjects maintained on LTE had high cardiac iron concentration. LIC was associated with serum ferritin (r=0.697, P<0.001) but was not associated with the total number of LTE procedures (r=-0.088, P=0.656) or total number of simple transfusions (r=0.316, P=0.108). The total number of LTE procedures was not associated with serum ferritin (r=0.040, P=0.838), the total number of simple transfusions (r=-0.258, P=0.184), or LIC group (r=-0.111, P=0.566). CONCLUSION: There was no significant correlation between duration of LTE maintenance and LIC.

Esophageal perforation, inflammatory mediastinitis and pseudoaneurysm of the thoracic aorta as potential complications of botulinum toxin injection for achalasia.

Primary achalasia is a motility disorder of the esophagus involving impaired relaxation of the esophageal sphincter and, in later stages, dilatation and aperistalsis of the tubular esophagus. Endoscopic botulinum toxin injection to the lower esophageal sphincter is an effective and safe option in the treatment algorithm of achalasia, particularly in high-surgical-risk patients. In the present case report, we describe a rare complication of esophageal perforation following botulinum injection, resulting in associated inflammatory mediastinitis and formation of a pseudoaneurysm in the descending aorta. To the authors' knowledge, this is the first report in the literature of this rare complication of endoscopic botulinum injection. A contributing factor might have been the use of an injecting device with a significantly longer adjustable needle. Endoscopists should remain clinically vigilant to the potential complications associated with this common procedure.

Impact of long-term erythrocytapheresis on growth and peak height velocity of children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) lag in weight and height and have a delayed growth spurt compared to normal children. We studied the effect of long-term erythrocytapheresis (LTE) on the growth of children with SCD and the age at which they attained peak height velocity. PROCEDURE: A retrospective chart review was performed recording weight, height, and body mass index (BMI) measurements of 36 patients with SCD who received LTE every 3-5 weeks for an average duration of 5 years. The z-scores for weight, height, and BMI of these patients were compared with that of patients with SCD from the Cooperative Study of Sickle Cell Disease (CSSCD) and a sub-set of 64 controls matched for age, sex, and initial growth parameter z-scores at the start of LTE. RESULTS: The z-scores for all parameters improved significantly for our patients on LTE compared to match controls from CSSCD and the entire pediatric CSSCD cohort (P-value: <0.01). Peak height velocity was achieved 2 months earlier for females (P-value: 0.94) and 11 months earlier for males (P-value: 0.02), who started LTE before 14 years of age, compared to matched CSSCD controls. The study subjects who had not been on regular simple transfusions prior to starting LTE had a mean serum ferritin of 681 ng/ml after LTE for an average duration of 63 months. CONCLUSION: LTE improves the growth of children with SCD without the risk of iron overload.

A clinical study on roxadustat for anemia in diabetic nephropathy: a 8-week study.

PURPOSE: The development of roxadustat is a standard treatment for renal anemia, and multiple clinical trials have proved its safety and efficacy. However, less information is available from trials of the population with diabetic nephropathy (DN). This study aimed to determine whether roxadustat is effective for treating DN. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study. The patients with DN were chosen and given roxadustat or erythropoietin (EPO) for 8 weeks. The mean hemoglobin (Hb) level after 8 weeks of treatment served as the primary outcome. Alterations in the iron index and lipid levels were considered secondary objectives. Sub-group analysis was performed to observe the impact of inflammation and glycemic status on Hb. RESULTS: A total of 80 patients were enrolled, 40 in each group. After 8 weeks of treatment, the Hb levels in the roxadustat group were higher than those in the control group. The number of patients who achieved Hb response was higher in the roxadustat group than in the control group (77.5% versus 27.5%; P < 0.001). In addition to lowering total cholesterol and low-density lipoprotein cholesterol, roxadustat decreased ferritin and elevated total iron-binding capacity. Compared to the control group, roxadustat was more beneficial for patients with an inflammatory condition and poor glycemic control. CONCLUSIONS: Roxadustat treatment remarkably corrected anemia in patients with DN, and its effectiveness was unaffected by inflammation or glycemic control levels. In addition, roxadustat can also reduce a patient's blood lipid level and enhance the body's use of iron. CLINICAL TRIAL REGISTRATION: ChiCTR2200057232.

Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study.

BACKGROUND: Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs). METHODS: This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60-100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency. RESULTS: Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, - 20.09 ng/mL; 95% CI, - 30.26 to - 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, - 7.87 nmol/L; 95% CI, - 12.11 to - 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study. CONCLUSIONS: Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients. TRIAL REGISTRATION: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231).

Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells.

BACKGROUND: Angiogenesis and energy metabolism mediated by adipose mesenchymal stem cell-derived exosomes (AMSC-exos) are promising therapeutics for vascular diseases. OBJECTIVES: The current study aimed to explore whether AMSC-exos have therapeutic effects on oxygen and glucose deprivation (OGD) human umbilical vein endothelial cells (HUVECs) injury by modulating the SIX1/HBO1 signaling pathway to upregulate endothelial cells (E.C.s) glycolysis and angiogenesis. METHODS: AMSC-exos were isolated and characterized following standard protocols. AMSC-exos cytoprotective effects were evaluated in the HUVECs-OGD model. The proliferation, migration, and tube formation abilities of HUVECs were assessed. The glycolysis level was evaluated by detecting lactate production and ATP synthesis. The expressions of HK2, PKM2, VEGF, HIF-1α, SIX1, and HBO1 were determined by western blotting, and finally, the SIX1 overexpression vector or small interfering RNA (siRNA) was transfected into HUVECs to assess the change in HBO1 expression. RESULTS: Our study revealed that AMSC-exos promotes E.C.s survival after OGD, reducing E.C.s apoptosis while strengthening E.C.'s angiogenic ability. AMSC-exos enhanced glycolysis and reduced OGD-induced ECs injury by modulation of the SIX1/HBO1 signaling pathway, which is a novel anti-endothelial cell injury role of AMSC-exos that regulates glycolysis via activating the SIX1/HBO1 signaling pathway. CONCLUSION: The current study findings demonstrate a useful angiogenic therapeutic strategy for AMSC-exos treatment in vascular injury, thus providing new therapeutic ideas for treating ischaemic diseases.

Utility of impedance cardiography for the detection of hemodynamic changes in stable patients with sickle cell disease.

OBJECTIVES: The study sought to assess the potential utility of impedance cardiography (ICG) to detect hemodynamic changes after erythrocytapheresis in stable children with sickle cell disease (SCD). METHODS: We prospectively monitored cardiac index, systemic vascular resistance index, heart rate, and blood pressure using ICG before and after erythrocytapheresis in 26 stable children with SCD. Echocardiography was carried out in all patients to evaluate left ventricular systolic function. Hemoglobin (Hb), sickle cell hemoglobin (HbS), and ferritin levels were also measured. RESULTS: Of a total of 78 erythrocytapheresis procedures in 26 children with SCD, 22 (28.2%) had hypotensive episodes defined as a decrease in systolic, diastolic, or mean blood pressure by 10 mmHg. Risk factors for developing hypotension during erythrocytapheresis were identified with logistic regression analysis: lower-body surface area and decrease in cardiac index. In contrast, age, prepheresis Hb and HbS, serum ferritin levels, and left ventricular function at baseline were not associated with hypotension. CONCLUSIONS: This study demonstrates the feasibility of the ICG technique to detect the hemodynamic changes in children with SCD after an erythrocytapheresis procedure.

Comparing new templates and atlas-based segmentations in the volumetric analysis of brain magnetic resonance images for diagnosing Alzheimer's disease.

BACKGROUND: The segmentation of brain structures on magnetic resonance imaging scans for calculating regional brain volumes, using automated anatomic labeling, requires the use of both brain atlases and templates (template sets). This study aims to improve the accuracy of volumetric analysis of hippocampus (HP) and amygdala (AMG) in the assessment of early Alzheimer's disease (AD) by developing template sets that correspond more closely to the brains of elderly individuals. METHODS: Total intracranial volume and HP and AMG volumes were calculated for elderly subjects with no cognitive impairment (n = 103), with amnestic mild cognitive impairment (n = 68), or with probable AD (n = 46) using the following: (1) a template set consisting of a standard atlas (atlas S), drawn on a young adult male brain, and the widely used Montreal Neurological Institute template (MNI template set); (2) a template set (template S set) in which the template is based on smoothing the image from which atlas S is derived; and (3) a new template set (template E set) in which the template is based on an atlas (atlas E) created from the brain of an elderly individual. RESULTS: Correspondence to HP and AMG volumes derived from manual segmentation was highest with automated segmentation by template E set, intermediate with template S set, and lowest with the MNI template set. The areas under the receiver operating curve for distinguishing elderly subjects with no cognitive impairment from elderly subjects with amnestic mild cognitive impairment or probable AD and the correlations between HP and AMG volumes and cognitive and functional scores were highest for template E set, intermediate for template S set, and lowest for the MNI template set. CONCLUSIONS: The accuracy of automated anatomic labeling and the diagnostic value of the derived volumes are improved with template sets based on brain atlases closely resembling the anatomy of the to-be-segmented brain magnetic resonance imaging scans.

An investigation of PreMCI: subtypes and longitudinal outcomes.

BACKGROUND/AIMS: To investigate the clinical features and rates of progression of conditions that are not considered to be normal, but do not fulfill criteria for mild cognitive impairment (MCI). METHODS: We longitudinally evaluated 269 elderly subjects who did not meet formal criteria for MCI at baseline but had: (1) a clinical history suggesting MCI without neuropsychological deficits (PreMCI-Clinical); or (2) neuropsychological deficits on one or more memory measures in conjunction with a negative clinical examination (amnestic PreMCI-NP) or were normal on both neuropsychological and clinical examination. RESULTS: The rate of progression to MCI or dementia over an average of 2- to 3 years was 3.7% for no cognitive impairment subjects, whereas it was significantly greater for all PreMCI subtypes (22.0% for PreMCI-Clinical, 38.9% for amnestic PreMCI-NP subjects with two or more memory impairments). Among PreMCI subjects as a whole, lower baseline scores on object memory and category fluency tests were the best predictors of progression to MCI or dementia. Cardiovascular risk factors, Parkinsonian symptoms, and hippocampal atrophy were not associated with progression. CONCLUSION: Distinct PreMCI subtypes defined on the basis of clinical and neuropsychological evaluations were found to have distinct characteristics, but both subtypes demonstrated elevated risk for progression to MCI or dementia. Despite the lack of evidence of clinical impairment, subjects with neuropsychological deficits in two memory domains were particularly at increased risk for progression of their deficits.