Impact of Baseline Anemia in Patients Undergoing Transcatheter Aortic Valve Replacement: A Prognostic Systematic Review and Meta-Analysis.

Transcatheter aortic valve replacement (TAVR) is currently the treatment of choice for patients aged ≥75 years with severe aortic stenosis. Preoperative anemia is present in a large proportion of patients and may increase the risk of post-procedural complications. The purpose of this prognostic systematic review was to analyze the impact of baseline anemia on short- and mid-term outcomes following TAVR. A computerized search was performed on PubMed and Web of Science databases for studies published between January 2013 and December 2022. Primary outcomes were 30-day need for transfusion, acute renal failure, 30-day and mid-term mortality, and readmission during the first year post-TAVR. Data were analyzed via random effects model using inverse variance method with 95% confidence intervals. Eleven observational studies met our eligibility criteria and included a total of 12,588 patients. The prevalence of baseline anemia ranged between 39% and 72%, with no relevant sex differences. Patients with preprocedural anemia received more blood transfusions [OR: 2.95 (2.13-4.09)]), and exhibited increased rates of acute kidney injury [OR:1.74 (1.45-2.10)], short-term mortality [OR: 1.47 (1.07-2.01], and mid-term [OR: 1.89 (1.58-2.25)] mortality following TAVR compared with those without anemia. Baseline anemia determined an increased risk for blood transfusion, acute kidney injury, and short/mid-term mortality among TAVR recipients.

Clofazimine Inhalation Suspension Demonstrates Promising Toxicokinetics in Canines for Treating Pulmonary Nontuberculous Mycobacteria Infection.

Pulmonary nontuberculous mycobacteria (NTM) infection is recognized as a major global health concern due to its rising prevalence worldwide. As an opportunistic pathogen with increasing antibiotics resistance, prolonged systemic dosing with multiple antibiotics remains the primary treatment paradigm. These prolonged treatments, administered predominantly by oral or parenteral routes, often lead to systemic toxicity. A novel inhaled formulation of clofazimine may finally resolve issues of toxicity, thereby providing for improved NTM therapy. Clofazimine inhalation suspension was evaluated in canines to determine toxicity over 28 days of once-a-day dosing. The good laboratory practice (GLP) repeat dosing study evaluated low, mid, and high dosing (2.72 mg/kg and 2.95 mg/kg; 5.45 mg/kg and 5.91 mg/kg; and 10.87 mg/kg and 10.07 mg/kg, average male versus female dosing) of nebulized clofazimine over 30, 60, and 120 min using a jet nebulizer. Toxicokinetic analyses were performed on study days 29, 56, and 84. All three dose levels showed significant residual drug in lung tissue, demonstrating impressive lung loading and long lung residence. Drug concentrations in the lung remained well above the average NTM MIC at all time points, with measurable clofazimine levels at 28 and 56 days postdosing. In contrast, plasma levels of clofazimine were consistently measurable only through 14 days postdosing, with measurements below the limit of quantitation at 56 days postdosing. Clofazimine inhalation suspension may provide an effective therapy for the treatment of NTM infections through direct delivery of antibiotic to the lungs, overcoming the systemic toxicity seen in oral clofazimine treatment for NTM.

Tumor response and clinical outcome in metastatic gastrointestinal stromal tumors under sunitinib therapy: comparison of RECIST, Choi and volumetric criteria.

PURPOSE: Purpose of the study was to compare radiological treatment response according to RECIST, Choi and volumetry in GIST-patients under 2nd-line-sunitinib-therapy and to correlate the results of treatment response assessment with disease-specific survival (DSS). PATIENTS AND METHODS: 20 patients (mean: 60.7 years; 12 male/8 female) with histologically proven GIST underwent baseline-CT of the abdomen under imatinib and follow-up-CTs 3 months and 1 year after change to sunitinib. 68 target lesions (50 hepatic, 18 extrahepatic) were investigated. Therapy response (partial response (PR), stable disease (SD), progressive disease (PD)) was evaluated according to RECIST, Choi and volumetric criteria. Response according to the different assessment systems was compared and correlated to the DSS of the patients utilizing Kaplan-Meier statistics. RESULTS: The mean DSS (in months) of the response groups 3 months after therapy change was: RECIST: PR (0/20); SD (17/20): 30.4 (months); PD (3/20) 11.6. Choi: PR (10/20) 28.6; SD (8/20) 28.1; PD (2/20) 13.5. Volumetry: PR (4/20) 29.6; SD (11/20) 29.7; PD (5/20) 17.2. Response groups after 1 year of sunitinib showed the following mean DSS: RECIST: PR (3/20) 33.6; SD (9/20) 29.7; PD (8/20) 20.3. Choi: PR (10/20) 21.5; SD (4/20) 42.9; PD (6/20) 23.9. Volumetry: PR (6/20) 27.3; SD (5/20) 38.5; PD (9/20) 19.3. CONCLUSION: One year after modification of therapy, only partial response according to RECIST indicated favorable survival in patients with GIST. The value of alternate response assessment strategies like Choi criteria for prediction of survival in molecular therapy still has to be demonstrated.

The anatomical identification of saccadic omnipause neurons in the rat brainstem.

Omnipause neurons (OPNs) represent a crucial component for the generation of saccadic eye movements. They inhibit saccadic premotor neurons in the paramedian pontine reticular formation (PPRF) as well as in the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF) during the intersaccadic interval. In turn, inhibition of OPNs is a prerequisite in order to generate saccadic eye movements. Although the anatomy of the saccadic system including the OPNs has been extensively studied in primates and cats, no detailed anatomical description of these neurons in rats has been performed so far. The aim of the present study was the identification of putative OPNs in the rat brainstem based on their projection target, localization, and histochemical characteristics. Stereotactic tract-tracer injections into the rostral mesencephalon including the RIMLF in rat resulted in back-labeling of a neuron group adjacent to the midline at the level of traversing fibers of the abducens nerve, which are considered as OPNs lying in the nucleus raphe interpositus. Combined immunohistochemical staining for various markers revealed in these neurons the expression of parvalbumin, chondroitin sulfate proteoglycan, and glycine, but a lack of serotonin. The results of our study demonstrate the striking similarity between individual elements of the premotor saccadic network in rats and primates. The exact knowledge of their location in rats provides a basis for in vitro studies of the OPNs in rat brainstem slices.

Dual energy CT for monitoring targeted therapies in patients with advanced gastrointestinal stromal tumor: initial results.

PURPOSE: Advanced gastrointestinal stromal tumours (GISTs) are treated with tyrosine kinase inhibitors, which also have antiangiogenic properties. Dual-energy CT (DECT) allows to acquire semi-quantitative iodine images which might correlate with blood pool and tumor vascularity. In this feasibility-study, we correlated lesional iodine uptake estimations in correlation to tumor size changes under targeted therapy as first step in the evaluation of dedicated DECT based strategies for monitoring molecular therapies in GIST. PATIENTS AND METHODS: 48 tumor lesions in 18 patients with metastasized histologically proven GIST under tyrosine kinase inhibitor (TKI) therapy were analyzed. Patients were examined with a dual-source CT in dual-energy mode (Voltage tube A: 80 kV, tube B: 140 kV). Using the dual-energy software virtual unenhanced, selective iodine (overlay) and mixed CT numbers (similar to CT numbers at 120 kV) of lesions were calculated. The largest diameter of each lesion on cross-sectional axial images was measured. The mean difference of overlay CT numbers in the baseline and follow-up examinations was calculated and this marker of lesional iodine uptake was compared to lesional size changes under molecular therapy. RESULTS: Utilizing the cut-off value 15 HU of change in overlay, DECT allowed to identify lesions with a stable, increased or decreased lesional iodine uptake with corresponding typical lesion size change patterns after 3 months of targeted therapy: 30 lesions had no significant change of overlay CT numbers (OL) (mean: -2.4 HU) or lesion size (mean: +1.5%). A strong decline of the OL (mean: - 24 HU) in 13 lesions was combined with a pronounced growth (mean: + 26%). 5 lesions showed a strong increase of the absolute OL (mean: + 23 HU) associated with a moderate increase in size (+ 8%). CONCLUSION: Determination of the overlay CT number with DECT enables to stratify metastases with stable, increasing or decreasing iodine uptake over time with -in our collective- typical lesion size change patterns. Investigation of a larger patient cohort, comparison to histology, alternate imaging biomarkers and correlatrion to long-term response will further clarify the significance of these findings for monitoring targeted therapies in GIST.

[Acute intestinal inflammation]. / Akute Entzündung des intestinalen Systems.

Acute intestinal inflammation is common. In most cases the medical history, clinical investigations and laboratory parameters alone are not sufficient for a conclusive diagnosis because of the wide variety of differential diagnoses and the striking similarity of symptoms. Modern imaging methods can help to clarify the diagnosis and multi-slice CT (MSCT) is highly useful in this diagnostic dilemma. It is widely available, employs standardized protocols, is cost-effective and can be performed within an acceptable examination time. MSCT enables the location and extension of the underlying pathology to be assessed and detection of complications which require immediate therapeutic intervention.

[Analysis of incidents, monitoring and safety devices of cardiopulmonary bypass for cardiac surgery for the year 2005 in France]. / Analyse des accidents, des moyens de monitorage et de sécurité de la circulation extracorporelle pour chirurgie cardiaque en France en 2005.

INTRODUCTION: Several surveys demonstrated that cardiopulmonary bypass (CPB) is associated with incidents that negatively affect the outcome of cardiac surgery. OBJECTIVES: In 2004, the French "Haute Autorité de santé" (an independent public scientific authority) and the French "College of Perfusion" issued recommendations concerning safety and monitoring devices for CPB. The aims of the present study were to: 1) investigate the difference between the recommendations and the clinical practice of CPB shortly after publication of the recommendations; 1) investigate the type and rate of perfusion incidents and their outcome. STUDY DESIGN: Retrospective survey. METHODS: A 62 items questionnaire was sent to all 66 centres performing cardiac surgery in France. RESULTS: Fifty-seven centres totalling 34,496 CPB procedures (response rate 86%) returned the questionnaire. There was a wide difference between the recommendations and the reported use of safety and monitoring devices. An incident was reported for every 198 CPB procedures with death occurring 1:4,864 and permanent sequelae 1:11,349 procedures respectively (permanent injury or death 1:3,220 procedures). The most frequent perfusion incidents were adverse effects to protamine (1:1,702), dissection at the arterial canulation site (1:1,792) and coagulation of the circuit (1: 4,864). CONCLUSION: This survey demonstrates that an important effort must be made in order to fill the gap between the recommendations and clinical use of monitoring and safety devices. The analysis of CPB-related incidents suggests that, with the exception of protamine adverse effects, the majority of deaths and severe permanent injuries could probably be avoided by improved use of the monitoring and safety devices.

Luteolysis, onset of estrus, and ovulation in Holstein heifers given prostaglandin F2alpha concurrent with, or 24 hours prior to, removal of an intravaginal, progesterone-releasing device.

The objective was to determine the effects of giving prostaglandin F2alpha (PGF) concurrent with, or 24 h before, removal of an intravaginal, progesterone-releasing (controlled internal drug release [CIDR]) device, on luteolysis, the synchrony of estrus and ovulation. Eighteen postpubertal Holstein heifers were given a CIDR and 100 microg gonadotropin releasing hormone (GnRH) and equally allocated to 3 groups. The PGF was given concurrently with CIDR removal after 7 or 8 d (groups D7/D7 and D8/D8, respectively) or given 1-d before removal of CIDR after 8 d (group D7/D8). There was no difference (P > 0.75) among groups in the intervals (h) from CIDR removal to onset of standing estrus and to ovulation (49.3 h+/-6.2 h and 77.5 h+/-9.0 h, respectively; least squares means+/-standard error of means). We also determined if stage of the estrus cycle influenced the synchrony of estrus or ovulation. In heifers in metestrus at CIDR insertion (versus those at estrus or diestrus), intervals from CIDR removal to estrus and to ovulation were longer by 33.4 h (P < 0.05) and 38.5 h (P = 0.01), respectively. However, the interval from standing estrus to ovulation was not affected. Giving PGF concurrent with CIDR removal did not affect luteal regression, the synchrony of estrus, and ovulation; but heifers in metestrus at the initiation of treatment had longer intervals from CIDR removal to estrus and ovulation.