Effects of a 6-month multi-strain probiotics supplementation in endotoxemic, inflammatory and cardiometabolic status of T2DM patients: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of this trial was to characterize the beneficial effects of probiotics on decreasing endotoxin levels and other cardiometabolic parameters in Arab patients with type 2 diabetes mellitus (T2DM). METHODS: Saudi adults with naïve T2DM (n = 30; 12 males and 18 females) were randomly allocated to receive twice daily placebo or 2.5 × 109 cfu/g of Ecologic®Barrier (multi-strain probiotics; n = 31; 14 males and 17 females) in a double-blind manner over a 6 month period, respectively. Anthropometrics were measured and fasting blood samples were collected to analyze endotoxin, glycemic parameters [glucose, insulin, c-peptide and homeostasis model assessment for insulin resistance (HOMA-IR)], lipids [triglycerides, total cholesterol, low and high-density lipoprotein (LDL and HDL, respectively) cholesterol and total/HDL-cholesterol ratio], inflammatory markers [tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP)] and adipocytokines [leptin, adiponectin and resistin] at baseline and after 3 and 6 months of intervention. RESULTS: Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-α (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (-3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers. CONCLUSION: Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01765517.

Does current cefazolin dosing achieve adequate tissue and blood concentrations in obese women undergoing cesarean section?

BACKGROUND: Prophylactic administration of antibiotics preceding cesarean delivery is the most effective measure taken for preventing postpartum infection. While obese women are at greater risk for infection than non-obese women, evidence-based recommendations for modifying dosing in these women are limited. OBJECTIVES: The purpose of this study was to determine whether obese women undergoing cesarean delivery similarly reach adequate cefazolin concentrations within tissue and blood when weighing <120kg and dosed 2g versus weighing ≥120kg and dosed 3g. STUDY DESIGN: We prospectively studied women ≥18 years old with body mass index ≥30kg/m2 who underwent scheduled cesarean delivery with singleton pregnancy from August 2014 through March 2016. Women were dosed with 2g and 3g of cefazolin for body weights <120kg and ≥120kg, respectively. Samples of subcutaneous adipose tissue (following skin incision and before skin closure), myometrial tissue, fetal cord blood, and maternal blood were collected to assess whether cefazolin concentrations were adequate, i.e., at/above the minimum inhibitory concentration (MIC). Concentrations, based on inhibition zones for Streptococcus sanguinis, were calculated per gram of solid tissue and milliliter of blood. For all sample types, log-transformed concentrations were compared between dosage groups. Using a range of published MICs (1-8µg/mL or µg/g), odds ratios, describing differential odds of falling below the MIC between dosage groups, were also computed. RESULTS: Women who received 2g (n=65) versus 3g (n=19) of cefazolin did not significantly differ by maternal or gestational age, race/ethnicity, pre-operative hemoglobin, estimated blood loss, fluid administration, duration of surgery, or timing of sample collections relative to cefazolin administration (Ps>0.05). Dosage groups also did not differ in cefazolin concentration (median [interquartile range]) within adipose tissue following skin incision (5.30µg/g [3.00-9.60] vs. 6.35µg/g [3.90-8.40]; P=0.551), adipose tissue before skin closure (4.45µg/g [2.78-7.25] vs. 6.90µg/g [2.60-10.6]; P=0.342), myometrial tissue (13.1µg/g [8.60-19.6] vs. 15.7µg/g [10.8-21.7]; P=0.116), or maternal blood (41.6µg/mL [26.3-57.0] vs. 45.3µg/mL [36.7-68.3]; P=0.143). However, cord blood concentrations differed significantly (19.5µg/mL [13.7-28.5] vs. 27.9µg/mL [15.8-39.4]; P=0.032), and, in 3 of 5 sample types, group concentrations differed at the dosing cut-point of 120kg (Ps<0.02). Within the range of MICs considered, differences in the odds of concentration inadequacy were not detected between dosage groups for any sample type. Across all patients, inadequate concentrations in one or more solid tissue types were observed in 1.19%, 17.9%, 59.5%, and 86.9% of patients, given the MICs of 1µg/g, 2µg/g, 4µg/g and 8µg/g, respectively. In adipose tissues, specifically, and both dosage groups, mean concentrations were significantly lower than the MIC of 8µg/g (Ps<0.03). Concentrations in one or both blood sample types were inadequate for only 8.33% of patients, given the 8-µg/mL MIC. CONCLUSIONS: Adequate cefazolin concentrations were achieved in blood for the majority of our patients. However, concentration adequacy was not achieved in solid tissue for a nearly equally large proportion of patients. Larger scale studies for determining modified protocols for dosing and applying MICs are warranted.

Foley catheter placement for induction of labor with or without stylette: a randomized clinical trial.

BACKGROUND: Foley catheters are used for cervical ripening during induction of labor. Previous studies suggest that use of a stylette (a thin, rigid wire) to guide catheter insertion decreases insertion failure. However, stylette effects on insertion outcomes have been sparsely studied. OBJECTIVE: The purpose of this study was to compare catheter insertion times, patient-assessed pain levels, and insertion failure rates between women who received a digitally placed Foley catheter for cervical ripening with the aid of a stylette and women who received the catheter without a stylette. STUDY DESIGN: We conducted a randomized clinical trial of women aged ≥ 18 years who presented for induction of labor. Inclusion criteria were singletons with intact membranes and cephalic presentation. Women received a computer-generated random assignment of a Foley catheter insertion with a stylette (treatment group, n = 62) or without a stylette (control group, n = 61). For all women, a standard insertion technique protocol was used. Three primary outcomes were of interest, including the following: (1) insertion time (total minutes to successful catheter placement), (2) patient-assessed pain level (0-10), and (3) failure rate of the randomly assigned insertion method. Treatment control differences were first examined using the Pearson's test of independence and the Student t test. Per outcome, we also constructed 4 regression models, each including the random effect of physician and fixed effects of stylette use with patient nulliparity, a history of vaginal delivery, cervical dilation at presentation, or postgraduate year of the performing resident physician. RESULTS: Women who received the Foley catheter with the stylette vs without the stylette did not differ by age, race/ethnicity, body mass index, or any of several other characteristics. Regression models revealed that insertion time, patient pain, and insertion failure were unrelated to stylette use, nulliparity, and history of vaginal delivery. However, overall insertion time and failure were significantly influenced by cervical dilation, with insertion time decreasing by 21% (95% confidence interval [CI], 5-34%) and odds of failure decreasing by 71% (odds ratio, 0.29; 95% CI, 0.10-0.86) per 1 cm dilation. Resident postgraduate year also significantly influenced insertion time, with greater time required of physicians with less experience. Mean insertion time was 51% (95% CI, 23-69%) shorter for fourth-year than second-year residents. Statistically nonsignificant but prominent patterns in outcomes were also observed, suggesting stylette use may lengthen the overall insertion procedure but minimize variability in pain levels and decrease insertion failure. CONCLUSIONS: The randomized trial suggests that, even after accounting for nulliparity, history of vaginal delivery, cervical dilation, and physician experience, Foley catheter insertions with and without a stylette are equivalent in insertion times, patient pain levels, and failure of catheter placement.

Early MRI Characteristics after MRI-Guided Laser-Assisted Cingulotomy for Intractable Pain Control.

BACKGROUND AND PURPOSE: Cingulotomy is a well-accepted stereotactic procedure in the treatment of debilitating pain syndromes. At our institution, we used a 980-nm diode laser to perform MR imaging-guided laser-assisted cingulotomy. We report the early MR imaging changes associated with this technique. MATERIALS AND METHODS: In this retrospective analysis, MR imaging-guided laser-assisted cingulotomy was performed in 4 patients with intractable pain secondary to metastatic disease. Patients were imaged at various time points postprocedure, with visual analysis of MR imaging changes in the cingulate gyri during that timeframe. RESULTS: Twenty-four hours postablation, 4 distinct zones of concentric rings reminiscent of an "owl eye" shape were noted in the cingulate gyri. Extrapolating from the imaging characteristics of the rings, we defined each zone as follows: The central zone (zone 1) represents a laser probe void with fluid, zones 2 and 3 have signal characteristics that represent hemorrhage and leaked protein, and zone 4 has a peripheral ring of acute infarction, enhancement, and surrounding edema. One patient with 1-year follow-up showed persistent concentric rings with resolution of enhancement and edema. CONCLUSIONS: Post-MR imaging-guided laser-assisted cingulotomy rings appear to represent a continuum of injury created by the laser probe and thermal injury. The imaging changes are similar to those described for laser ablation of tumor-infiltrated brain with a 1064-nm laser. This is the first study to characterize early MR imaging changes after MR imaging-guided laser-assisted cingulotomy by using a 980-nm laser. It is important for neuroradiologists and neurosurgeons to understand expected imaging findings as laser ablation cingulotomy re-emerges to treat intractable pain.

Serum 25-hydroxyvitamin D, calcium, and calcium-regulating hormones in preeclamptics and controls during first day postpartum.

The evidence for a link between vitamin D and preeclampsia is conflicting. There is a paucity of studies reporting simultaneous 25-hydroxyvitamin D (inactive form) and 1,25-dihydroxyvitamin D (biologically active form). We investigated if levels of serum 25-hydroxyvitamin D, calcium-regulating hormones (1,25-dihydroxyvitamin D, parathyroid hormone), and calcium differ significantly between preeclamptics and controls. On postpartum day one, 98 subjects (44 with preeclampsia, 54 controls) were recruited among women admitted to the postdelivery unit, and their serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, serum calcium, and serum albumin levels were prospectively measured. The majority of participants (70%) had serum 25-hydroxyvitamin D level<20 ng/mL; 53% had <15 ng/mL. Mean serum 25-hydroxyvitamin D level was similar between cases and controls (p=0.50). Mean total serum calcium adjusted for albumin and magnesium was similar between cases and controls (p=0.78). Mean serum 1,25-dihydroxyvitamin D and parathyroid hormone levels were normal, and there were no differences between cases and controls. The only significant differences found between preeclamptic cases and controls were mean body mass index, parity, and season of blood draw. Vitamin D levels did not differ among preeclamptic cases and controls.

Umbilical cord plasma and salivary insulin and leptin concentrations in AGA neonates: a preliminary report.

UNLABELLED: Background and objective: Insulin and leptin hormones are important regulators of food intake and energy balance. There is limited information about insulin and leptin hormones in neonates. This preliminary study aimed to investigate the concentrations of insulin and leptin in umbilical cord plasma and neonate's saliva and their relationships. METHODS: Umbilical cord plasma and salivary samples were obtained from 13 healthy, appropriate for gestational age (AGA) neonates. Insulin and leptin concentrations in umbilical cord plasma and saliva were measured using the MILLIPLEX MAP® Human Metabolic Hormone Magnetic Bead Panel. RESULTS: Insulin concentrations in umbilical cord plasma correlates positively and significantly with leptin concentrations in umbilical cord plasma (r = 0.55, p = 0.04). CONCLUSIONS: More research is needed to explore the relationships between insulin and leptin hormones in neonate's saliva.

American college of obstetricians and gynecologists practice bulletins: ascertaining their citation, influence, and utilization.

OBJECTIVE: To ascertain the influence and utilization of the American College Obstetricians and Gynecologists practice bulletins (PBs) by measuring their citations in three different search tools. STUDY DESIGN: PBs in obstetrics (OB-PBs) and gynecology (GYN-PBs) published from September 1998 to December 2009 were identified. PubMed, Ovid MEDLINE, and Web of Science were utilized to determine how often PBs were cited. The citations were quantified by three parameters, most citations, highest citation rate, and highest impact factor. RESULTS: The OB-PB with the most citations (125) was PB no. 33 (Diagnosis and Management of Preeclampsia and Eclampsia), highest citation rate (44) was PB no. 101 (Ultrasonography in Pregnancy), highest OBGYN impact factor (4.39) was PB no. 71 (Episiotomy), and highest non-OBGYN impact factor (53.49) was PB no. 38 (Perinatal Care at Threshold of Viability). The GYN-PB with the highest citation rate (103) was PB no. 109 (Cervical Cytology Screening), highest OBGYN impact factor (3.85) was PB no. 103 (Hereditary Breast and Ovarian Cancer Syndrome), and highest non-OBGYN impact factor (20.89) was PB no. 35 (Cervical Carcinoma). CONCLUSIONS: No one PB had the most citations, highest citation rate, and highest impact factor.

Diagnostic accuracy of optical coherence tomography parameters in predicting in-stent hemodynamic severe coronary lesions: validation against fractional flow reserve.

BACKGROUND: By means of optical coherence tomography (OCT), coronary dimensions can be assessed accurately. However, whether OCT can identify hemodynamic significant coronary lesions as determined by fractional flow reserve (FFR) in patients with an in-stent lesion is not known. Therefore, we tried to assess the predictive value of OCT parameters in this setting as compared to FFR. METHODS AND RESULTS: In patients who underwent a percutaneous coronary intervention for an in-stent restenotic lesion, pre-, post-procedural and 6-month follow-up OCT and FFR acquisitions were performed. In case of an FFR ≤ 0.80, a lesion was classified as hemodynamically severe. Diagnostic efficiency of several OCT parameters were assessed with receiver operating characteristic curves. In 27 patients, 66 coupled OCT and FFR segments were analyzed and compared. The diagnostic efficiencies of OCT-based minimal luminal diameter (MLD) and minimal luminal area (MLA) are good, with an area under the curve (AUC) of 0.83 (95% confidence interval: 0.74-0.93) and 0.83 (0.73-0.93), and a best cutoff value of 1.77 mm (sensitivity 74% and specificity 78%) and 2.54 mm(2) (sensitivity 71% and specificity 84%), respectively. The diagnostic efficiency of OCT-based maximum neointimal area is moderate [AUC 0.73 (0.61-0.85)], and regarding maximum neointimal area stenosis, it is poor [0.39 (0.25-0.53)]. The corresponding best cutoff values are 5.01 mm(2) (sensitivity 66% and specificity 72%) and 49% (sensitivity 40% and specificity 66%), respectively. CONCLUSIONS: With OCT, a good diagnostic efficiency can be achieved in identifying coronary severity in in-stent lesions in a per-group analysis. This hallmark provides an extra dimension, next to morphological information, when acquiring OCT images in scientific studies. However, OCT seems limited in a per-patient clinical decision making process due to reasonable but limited sensitivity and specificity in predicting coronary severity.

Racial and ethnic disparities in infant mortality in the United States: the role of gestational age.

OBJECTIVE: We assessed the association among gestational age (GA) at birth, timing of death, and risk status of the pregnancy and racial/ethnic disparities in infant mortality rate in the United States. STUDY DESIGN: We utilized U.S. 2000 to 2004 birth cohort-linked birth and infant death data restricted to nonanomalous singleton live births. Multivariable log-binomial regression models were fit to evaluate racial/ethnic disparities in infant mortality while adjusting for potential confounders. RESULTS: Compared with whites, blacks had a higher adjusted infant mortality rate (IMR) (risk ratio [RR] 1.96, 95% confidence interval [CI] 1.91, 2.01), and Hispanics had a lower adjusted IMR (RR 0.79, 95% CI 0.76, 0.82). When categorized by GA, at 24 to 31 weeks, the adjusted early neonatal mortality (ENM) is significantly lower for black than whites, similar at 32 to 36 weeks, and at 37 weeks or more, blacks have significantly higher ENM. CONCLUSIONS: The racial/ethnic disparities in infant mortality in the United States persist and vary across GA. These disparities may largely be driven by the excess post-neonatal deaths among blacks.

Skin closure of pfannenstiel incision with dermabond, staples, or suture during cesarean delivery: experience of a single attending.

OBJECTIVE: We aimed to compare the rates of wound separation (WS) and surgical site infection (SSI) after cesarean delivery (CD) by a single surgeon. Pfannenstiel skin incision (PSI) was closed with Dermabond, staples, or suture. STUDY DESIGN: Retrospectively all women having CD via PSI were identified. WS and SSI rates with Dermabond were compared with other two techniques. RESULTS: Of 239 CDs performed, 88% (n = 211) were available for postpartum evaluation. The PSI was closed with Dermabond in 85 (40%), staples in 76 (36%), and suture in 50 (24%). Overall WS rate was 7%; with Dermabond, it was 5% versus 13% with staple (p = 0.090) and 2% with suture (p = 0.651). Post hoc calculation suggests a randomization of 4325 women is needed to determine if Dermabond has one-third less wound complication than suture. CONCLUSION: For the PSI closure, Dermabond may be a useful alternative skin closure device, though a randomized trial is warranted.

Functional localization and visualization of the subthalamic nucleus from microelectrode recordings acquired during DBS surgery with unsupervised machine learning.

Microelectrode recordings are a useful adjunctive method for subthalamic nucleus localization during deep brain stimulation surgery for Parkinson's disease. Attempts to quantitate and standardize this process, using single computational measures of neural activity, have been limited by variability in patient neurophysiology and recording conditions. Investigators have suggested that a multi-feature approach may be necessary for automated approaches to perform within acceptable clinical standards. We present a novel data visualization algorithm and several unique features that address these shortcomings. The algorithm extracts multiple computational features from the microelectrode neurophysiology and integrates them with tools from unsupervised machine learning. The resulting colour-coded map of neural activity reveals activity transitions that correspond to the anatomic boundaries of subcortical structures. Using these maps, a non-neurophysiologist is able to achieve sensitivities of 90% and 95% for STN entry and exit, respectively, to within 0.5 mm accuracy of the current gold standard. The accuracy of this technique is attributed to the multi-feature approach. This activity map can simplify and standardize the process of localizing the subthalamic nucleus (STN) for neurostimulation. Because this method does not require a stationary electrode for careful recording of unit activity for spike sorting, the length of the operation may be shortened.

High-frequency oscillations (>200 Hz) in the human non-parkinsonian subthalamic nucleus.

The human basal ganglia, and in particular the subthalamic nucleus (STN), can oscillate at surprisingly high frequencies, around 300 Hz [G. Foffani, A. Priori, M. Egidi, P. Rampini, F. Tamma, E. Caputo, K.A. Moxon, S. Cerutti, S. Barbieri, 300-Hz subthalamic oscillations in Parkinson's disease, Brain 126 (2003) 2153-2163]. It has been proposed that these oscillations could contribute to the mechanisms of action of deep brain stimulation (DBS) [G. Foffani, A. Priori, Deep brain stimulation in Parkinson's disease can mimic the 300 Hz subthalamic rhythm, Brain 129 (2006) E59]. However, the physiological role of high-frequency STN oscillations is questionable, because they have been observed only in patients with advanced Parkinson's disease and could therefore be secondary to the dopamine-depleted parkinsonian state. Here, we report high-frequency STN oscillations in the range of the 300-Hz rhythm during intraoperative microrecordings for DBS in an awake patient with focal dystonia as well as in a patient with essential tremor (ET). High-frequency STN oscillations are therefore not exclusively related to parkinsonian pathophysiology, but may represent a broader feature of human STN function.

Successful utilization of a novel aspiration thrombectomy catheter (Pronto) for the treatment of patients with stent thrombosis.

Stent thrombosis is a rare but catastrophic complication of percutaneous coronary intervention (PCI). Thrombolytic therapy is ineffective for the treatment of patients with stent thrombosis, while primary PCI in such patients is limited by a high thrombus burden in the culprit vessel often leading to distal embolization and extensive tissue infarction. We present three patients with stent thrombosis successfully treated with the adjunctive use of a novel and new aspiration thrombectomy device (Pronto).

Clinical utility of aortic pulses and pressures calculated from applanated radial-artery pulses.

Brachial artery cuff blood pressures are but approximations of central aortic pressures. The actual pressures against which the left ventricle must pump would be useful clinical information if obtained noninvasively. Our aim was to determine the clinical utility of aortic pulses and pressures calculated from noninvasively obtained radial-artery pulses. Radial-arterial pulses were recorded by applanation and calibrated with arm/cuff oscillometric pressures. Aortic pulses and pressures were calculated from the radial pulses by Fourier analysis and transfer functions. These calculated aortic pulses were compared with directly recorded aortic pulses by a transducer-tip catheter in a series of 50 patients undergoing cardiac catheterization. The correlation coefficient (r) of the measured versus the calculated aortic systolic blood pressure was +0.89, but the scatter was large (standard deviation of the differences=+/-11.3 mm Hg). The pulse pressure correlations were less good (r=+0.79) and also had a large scatter (+/-13.6 mm Hg). The average calculated pulse pressure was 11.5 mm Hg lower than the measured value because the cuff diastolic blood pressures, used to calibrate the radial pulses, were systematically higher than those in the aorta (8.9 mm Hg). Multivariable analysis incorporating height, age, heart rate, and ejection fraction as additional, independent variables eliminated mean differences between the new "predicted" and measured pressures, significantly improved correlation coefficients, and reduced the scatter. However, the improvements were small. The inaccuracy of the oscillometric cuff method for measuring arm blood pressure appears to be the limiting factor in the prediction of clinically useful, noninvasive aortic pressures.

Intramedullary low-grade astrocytomas: long-term outcome following radical surgery.

The management of low-grade intramedullary astrocytomas is controversial. Unlike ependymomas, which have a distinct cleavage plane, astrocytomas are diffuse infiltrative tumors. The intramedullary tumor database at NYU Medical Center was searched to identify all patients with intramedullary astrocytoma from 1988 to 1994. Seventeen patients presented with a low-grade diffuse astrocytoma. The medical, surgical and office records were reviewed retrospectively and statistically analyzed. All patients underwent a radical resection of the intramedullary tumor; of these, 12 patients had gross-total removal and 5 had subtotal removal. Nine patients received adjuvant radiotherapy. The median follow-up period was 7.4 years. Fourteen patients are alive and have stable disease. Eleven patients (79%) are functionally independent at last follow-up. The remaining patients are at functional Grade III. The 5-year overall survival was 82% for this group. These results indicate that aggressive surgery is associated with a prolonged survival for patients with intramedullary astrocytomas. Radiation therapy should only be reserved for patients who have radiographic progression or inoperable disease.

Cancer prevention in rural youth: teaching goals for health: the pilot.

BACKGROUND: The Goals for Health project is designed to change the cancer-related behaviors of tobacco use and dietary fat and fiber consumption. The intervention teaches health and life skills to rural, minority sixth and seventh graders in rural Virginia and New York. This article presents the results of the pilot. METHODS: Participants were 129 sixth graders at one rural middle school who were surveyed prior to and following delivery of the pilot sixth-grade intervention. RESULTS: Results include significant changes from pre- to post-intervention in several diet and smoking attitude and self-efficacy variables, dietary fat and fiber knowledge, high-fat snack consumption, and dietary fat scores. Multivariate analyses reveal important contributions of personal control over food choices and family and friend influence on change in dietary fat score from pre- to post-intervention. CONCLUSIONS: These pilot program results suggest avenues for dietary and cancer prevention interventions in high-risk, rural adolescents.