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infusions, intravenous - Top 30 Publications

Clinical Profile, Dosing, and Quality-of-Life Outcomes in Primary Immune Deficiency Patients Treated at Home with Immunoglobulin G: Data from the IDEaL Patient Registry.

Patients with primary immune deficiency (PID) often require immunoglobulin G (IgG, commonly referred to as Ig) replacement therapy to prevent infections and associated comorbidities. Ig therapy can be given either through intravenous or subcutaneous routes, and both can be done in the home setting. There is limited information available on the real-world diagnosis, management, and outcomes of this patient population, given the variable disease presentation and treatment options. The Immunoglobulin Diagnosis, Evaluation, and key Learnings (IDEaL) Patient Registry is designed to capture nursing, pharmacy, and patient-reported data for patients receiving Ig at home.

Development and validation of liquid chromatography tandem mass spectrometry method quantitative determination of polymyxin B1, polymyxin B2, polymyxin B3 and isoleucine-polymyxin B1 in human plasma and its application in clinical studies.

Polymyxin B (PB) is an antibiotic consisting of a cyclic heptapeptide and a tripeptide side chain used in treatment of infections caused by Gram-negative bacteria. Commercial formulations of PB contain multiple structurally related components with major constituents of PB1, PB2, PB3 and ile-PB1. To understand the pharmacokinetics of these major components, we have developed and validated a LC-MS/MS method to quantify PB1, PB2, PB3 and ile-PB1 in human plasma. PB was extracted from plasma by protein precipitation using trichloroacetic acid followed by chromatographic separation on Zorbax Bonus-RP column (100mm×2.1mm, 1.8μm) using stepwise gradient elution of water containing 0.1% of formic acid and 0.1% of trichloroacetic acid (mobile phase A) and 90% acetonitrile with 0.1% formic acid (mobile phase B). Despite of structural similarities, these PBs were completely resolved in the analytical run time of 6.5min. Detection and quantification of PBs were performed by selected reaction monitoring (SRM) under positive ionization mode in the mass spectrometer. Separation of PB1 and ile-PB1, as well as PB2 and PB3, before quantification is crucial because they are structural isomers detected based the same SRM. Excellent linearity was achieved (r(2)>0.99) in the calibration curves of PB. The developed method was accurate (95.3-111.7%) and precise (CV<5.1%). Recovery of PB from the plasma extraction was between 53 and 76% and reproducible (CV<4.5%). Matrix effect was not observed by post-column infusion of PB in the mass spectrometer. This methodology has been successfully applied to clinical study of patients dosed with intravenous infusions of PB.

Standardizing concentrations of adult drug infusions in Indiana.

A multidisciplinary, consensus-driven initiative to promote the use of standardized medication concentrations for adult drug infusions across the state of Indiana is described.

Does remifentanil attenuate renal ischemia-reperfusion injury better than dexmedetomidine in rat kidney?

Ischemia-reperfusion (I/R) injury is a common cause of patient morbidity and mortality in the perioperative period. Patients undergoing long-lasting, abdominal, and urogenital surgeries with risk factors such as advanced age, peripheral artery disease, diabetes mellitus, renovascular disease, and congestive heart failure are candidates for acute kidney injury (AKI) due to impaired renal perfusion and decreased functional renal reserve. Pharmacological agents with multiple functions and anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI. Recently, dexmedetomidine (dex) has been postulated to have renoprotective effects.

Benefits of intralesional injections of sodium thiosulfate in the treatment of calciphylaxis.

Calciphylaxis (CPX) is a rare calcifying thrombotic vasculopathy responsible for painful necrotic ulcers, with a high mortality rate, and its management is often difficult. Recently, intravenous infusions of sodium thiosulfate (STS) have shown efficacy. The aim of this study was to assess the efficacy of intralesional STS (IL STS) in four patients. Our aim was to assess the efficacy of IL STS in a prospective mono-centric open study that included four patients with a biopsy-proven cutaneous CPX. Four women (55-84 years old, mean age: 71·2 years) with a uremic (n = 1) or non-uremic CPX (n = 3) and primary hyperparathyroidism induced by teriparatide or after the initiation of oral anti-vitamin K were treated by IL STS (250 mg/ml). The injections were performed around the ulcers, on the active borders, once or twice a week and then at 1-2 weeks intervals. The injected quantity varied from 1·5 to 15 ml. Pain usually improved after two series of injections. Clinical response was visible after 2 weeks. Three patients (75%) healed completely or almost completely. A failure was observed in the last patient who also had lower limb arteriopathy. The main side effect was the pain during injections. IL STS is an interesting alternative therapeutic option in the management of CPX necrotic ulcers with limited side effects. Larger studies are warranted to precisely define its place, its administration procedure and the patients who could benefit from it.

Long-Term Bone Scintigraphy Results After Intravenous Zoledronate in Paget's Disease of Bone.

Zoledronate produces long-term normalization of biochemical markers in Paget's disease but whether this implies the absence of active disease is unknown. We have determined whether bone scintigraphy, a more sensitive index of disease activity, is also normalized ≥5 years after treatment with zoledronate. A consecutive case series of 11 individuals with Paget's disease treated with zoledronate 5 mg ≥5 years previously is reported. Eight patients received a single zoledronate infusion and were assessed 55-120 months later. Bone scintigraphy showed no evidence of active disease in four of these patients, and there was minimal residual disease activity in the other four. Three other patients required second infusions because of evidence of ongoing disease activity. In two of these, scintigraphy was normal ~90 months after their second infusions. In the third, further follow-up is not available. Procollagen-I N-terminal propeptide and total alkaline phosphatase were normal in all subjects at the time of bone scintigraphy. This case series confirms the high rate of response of Paget's disease to zoledronate, demonstrates the much greater sensitivity of scintigraphy compared with biochemical markers in detecting ongoing disease activity, and indicates that about one-third may be scintigraphically "cured" after one infusion; one-third have scintigraphically trivial disease activity subsequently, and the balance may require a second infusion. Scintigraphic "cure" is achievable after second infusions. Scintigraphy has an important place in the long-term management of Paget's patients following zoledronate, and should guide follow-up decisions in those with normal biochemical markers.

Targets for adapting intravenous iron dose in hemodialysis: a proof of concept study.

Intravenous iron is widely used to control anemia in dialysis patients and limits costs related to erythropoiesis-stimulating agents (ESA). Current guidelines do not clearly set upper limits for serum ferritin (SF) and transferrin saturation (TSAT). International surveys such as the Dialysis Outcomes and Practice Patterns Study (DOPPS) showed that this lack of upper limits potentially led nephrologists to prescribe iron infusions even for patients with a high SF. Recent publications have suggested a risk of short- and long-term adverse effects related to iron overload. We conducted a proof of concept study to assess the impact of reducing intravenous iron administration.

Evaluation of the Safety, Tolerability, and Pharmacokinetics of Gammaplex(®) 10% Versus Gammaplex(®) 5% in Subjects with Primary Immunodeficiency.

This phase 3, multicenter, open-label, randomized, two-period, crossover bioequivalence trial evaluated the safety, tolerability, and pharmacokinetics of intravenous immunoglobulins (IVIGs) Gammaplex 5% and Gammaplex 10% in 33 adults and 15 children with primary immunodeficiency diseases (PIDs).

Further analysis of the inhibition by agmatine on the cardiac sympathetic outflow: Role of the α2-adrenoceptor subtypes.

This study has investigated the role of the α2-adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300μg/kg; α2A), imiloxan (3000μg/kg; α2B), and JP-1302 (300μg/kg; α2C) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine. Also, the effect of the combination BRL 44408 plus JP-1302 plus AGN 192403 (3000μg/kg; I1 antagonist) was evaluated. In this way, i.v. infusions of 1000μg/kg min of agmatine, but not 300, inhibited the tachycardic response induced by electrical stimulation. Furthermore, the antagonists used or their combinations had no effect on the electrically-induced tachycardic response. On the other hand, the inhibitory response of agmatine was: (1) partially antagonized by BRL 44408 or JP-1302 given separately, a similar response was observed when we administered their combination with imiloxan, but not by imiloxan alone, (2) antagonized in greater magnitude by the combination BRL 44408 plus JP-1302 or the combination BRL 44408 plus imiloxan plus JP-1302, and (3) abolished by the combination BRL 44408 plus JP-1302 plus AGN 192403. Taken together, these results demonstrate that the α2A- and α2C-adrenoceptor subtypes and I1-imidazoline receptors are involved in the inhibition of the cardiac sympathetic outflow induced by agmatine.

Safety and tolerability of idelalisib, lenalidomide, and rituximab in relapsed and refractory lymphoma: the Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 trials.

A new generation of biological and targeted agents might potentially replace traditional cytotoxic agents in lymphoma. Lenalidomide plus rituximab was felt to be a safe and promising backbone based on available data. Idelalisib is an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor that has promising activity as a monotherapy in refractory indolent lymphomas. The primary objective of these two trials was to determine the maximum tolerated dose of lenalidomide in combination with rituximab and idelalisib in relapsed follicular and mantle cell lymphoma.

Analyzing the efficacy of frequent sodium checks during hypertonic saline infusion after elective brain tumor surgery.

To assess the utility of frequent sodium checks (every 6h) in patients receiving hypertonic saline (HS) after elective brain tumor surgeries.

Cocaine self-administration in male and female rats perinatally exposed to PCBs: Evaluating drug use in an animal model of environmental contaminant exposure.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants known to adversely impact human health. Ortho-substituted PCBs affect the nervous system, including the brain dopaminergic system. The reinforcing effects of psychostimulants are typically modulated via the dopaminergic system, so this study used a preclinical (i.e., rodent) model to evaluate whether developmental contaminant exposure altered intravenous self-administration (IV SA) for the psychostimulant cocaine. Long-Evans rats were perinatally exposed to 6 or 3 mg/kg/day of PCBs throughout gestation and lactation and compared with nonexposed controls. Rats were trained to lever press for a food reinforcer in an operant chamber under a fixed-ratio 5 (FR5) schedule and later underwent jugular catheterization. Food reinforcers were switched for infusions of 250 μg of cocaine, but the response requirement to earn the reinforcer remained. Active lever presses and infusions were higher in males during response acquisition and maintenance. The same sex effect was observed during later sessions which evaluated responding for cocaine doses ranging from 31.25-500 μg. PCB-exposed males (not females) exhibited an increase in cocaine infusions (with a similar trend in active lever presses) during acquisition, but no PCB-related differences were observed during maintenance, examination of the cocaine dose-response relationship, or progressive ratio (PR) sessions. Overall, these results indicated perinatal PCB exposure enhanced early cocaine drug-seeking in this preclinical model of developmental contaminant exposure (particularly the males), but no differences were seen during later cocaine SA sessions. As such, additional questions regarding substance abuse proclivity may be warranted in epidemiological studies evaluating environmental contaminant exposures. (PsycINFO Database Record

Regional to the Rescue! Axillary Brachial Plexus Nerve Block Facilitates Removal of Entrapped Transradial Catheter Placed for Cardiac Catheterization.

Our objective was to describe the first reported use of an axillary brachial plexus block to treat the entrapment of a transradial artery catheter due to vasospasm.

BioAdvance Patient Support Program Survey: Positive Perception of Intravenous Infusions of Inflixmab.

To understand the perception of intravenous infusions in patients receiving infliximab (Remicade) within the BioAdvance patient support program (PSP).

Oxycodone versus fentanyl for intravenous patient-controlled analgesia after laparoscopic supracervical hysterectomy: A prospective, randomized, double-blind study.

Oxycodone, a semisynthetic thebaine derivative opioid, is widely used for the relief of moderate to severe pain. The aim of this study was to compare the efficacy and side effects of oxycodone and fentanyl in the management of postoperative pain by intravenous patient-controlled analgesia (IV-PCA) in patients who underwent laparoscopic supracervical hysterectomy (LSH).

Piritramide : A critical review.

In many European countries and particularly in Germany, piritramide is the first choice opioid analgesic for the management of postoperative and posttraumatic pain.

Blood Pressure in Healthy Humans Is Regulated by Neuronal NO Synthase.

NO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effects on cardiovascular function, but its composite effects on systemic hemodynamics in humans are unknown. We undertook the first human study to assess the physiological effects of systemic nNOS inhibition on basal hemodynamics. Seventeen healthy normotensive men aged 24±4 years received acute intravenous infusions of an nNOS-selective inhibitor, S-methyl-l-thiocitrulline, and placebo on separate occasions. An initial dose-escalation study showed that S-methyl-l-thiocitrulline (0.1-3.0 µmol/kg) induced dose-dependent changes in systemic hemodynamics. The highest dose of S-methyl-l-thiocitrulline (3.0 µmol/kg over 10 minutes) significantly increased systemic vascular resistance (+42±6%) and diastolic blood pressure (67±1 to 77±3 mm Hg) when compared with placebo (both P<0.01). There were significant decreases in heart rate (60±4 to 51±3 bpm; P<0.01) and left ventricular stroke volume (59±6 to 51±6 mL; P<0.01) but ejection fraction was unaltered. S-methyl-l-thiocitrulline had no effect on radial artery flow-mediated dilatation, an index of endothelial NOS activity. These results suggest that nNOS-derived NO has an important role in the physiological regulation of basal systemic vascular resistance and blood pressure in healthy humans.

The role of genetics on migraine induction triggered by CGRP and PACAP38.

Migraine has a strong genetic component and is characterized by multiphasic events including an initial premonitory phase with premonitory symptoms (PS). Calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide-38 (PACAP38) are endogenous neuropeptides that can trigger migraine attacks and have in recent years gained considerable interest in the migraine field. Yet, the exact pathophysiological mechanisms underlying CGRP- and PACAP38-induced attacks are not fully clarified. Human provocation models have shown that these peptides induce attacks in only two- thirds of migraine patients. Whether this diverse migraine response after CGRP or PACAP38 may be explained by genetic factors is unknown. The present thesis includes four studies that explore different factors that may be associated with the CGRP- and PACAP38-induced migraine response. In study I and II we investigated the role of familial predisposition (family load) and number of risk conferring gene variants on migraine attacks induced by CGRP or PA-CAP38. In study III, we investigated biochemical changes of CGRP, vasoactive intestinal peptide (VIP), S100B and TNF-alpha in the blood after PACAP38. Finally in study IV, we studied whether CGRP or PACAP38 may induce PS. Study I and II demonstrated that PACAP38 and CGRP induce migraine attacks in 63% and 72% of the patients, respectively. Moreover, we showed that patients with high family load or a high number of migraine associated gene variants did not report more migraine attacks after CGRP or PACAP38 than those with no familial predisposition or few gene variants. Study III showed that PACAP38 infusion caused changes in plasma concentrations for VIP and S100B, but not CGRP and TNF-alpha, suggesting activation of parasympathetic nerve endings. Study IV showed absence of PS after CGRP and lack of statistical difference in PS between patients who reported and not reported attacks after PACAP38 suggesting peripheral mechanisms of induction. In conclusion, the present thesis suggests that genetics factors such as family load and genetic variants do not contribute to susceptibility of migraine attacks induced by CGRP or PACAP38. Additionally, our data indicate that CGRP and PACAP38 primarily have a peripheral site of action. We believe that the acquired knowledge from this thesis on how CGRP and PACAP38 might be involved in migraine pathophysiology would contribute to the development of novel and better migraine treatments in the future.

Are abatacept and tocilizumab intravenous users willing to switch for the subcutaneous route of administration? A questionnaire-based study.

Choosing the subcutaneous (SC) route of administration of abatacept and tocilizumab is more cost-effective than the intravenous (IV) route. The objective of this study was to examine patients' reasons for choosing to keep with their IV infusions or to switch to subcutaneous SC injections. This study was based upon a self-administered questionnaire given to consecutive rheumatoid arthritis patients treated with abatacept or tocilizumab. Patients were asked to express their opinions concerning reasons explaining why they chose to keep the IV route or switch to the SC route. A total of 201 questionnaires completed by 127 patients treated by tocilizumab and 74 by abatacept were analysed. Overall, 45.8% of the patients chose to keep the IV route of administration. Another ongoing SC treatment was noted more often in patients choosing the SC route (15.9 versus 4.3%, p < 0.05). Reasons guiding the choice of the SC route were concerns about repeated hospital day-care (72%), greater autonomy with SC injections (38.7%) and economic considerations (21.5%). Reasons associated with choosing to maintain the IV route were worries about a lack of follow-up (72.1%), the absence of medical assistance during the SC injection (61.2%), maintaining social relationships with other patients developed at the hospital (40.5%), lower frequency of injection (32.9%), fear of adverse events (27.7%) and fear of SC injections (17.9%). Patients reject the SC switch from the IV route of tocilizumab and abatacept mainly because of fears about the unknown SC route, while those who accept it find it more convenient.

Pharmacokinetics of conivaptan use in patients with severe hepatic impairment.

Conivaptan is an intravenous dual V1A/V2 vasopressin antagonist approved for the treatment of euvolemic and hypervolemic hyponatremia. Earlier studies showed that patients with moderate liver disease could be safely treated with conivaptan by reducing the dose by 50%, whereas patients with mild hepatic impairment needed no dose adjustment. The objective of this Phase 1, open-label study was to assess the pharmacokinetics, protein binding, and safety of 48 h of conivaptan infusion in individuals with severe hepatic impairment.

The Development of Total Parenteral Nutrition.

The first patient to receive complete nourishment of a patient by intravenous infusion independent of the alimentary tract was an infant girl born with near-total small bowel atresia. Total parenteral nutrition, the intravenous infusion of nutrients, has been attempted since Harvey's description of the circulatory system in the early 17th century. The modern era of parenteral nutrition began in the early 20th century, when infusions of glucose, plasma, and emulsified fat into humans proved feasible. Robert Elman, working in the 1930s and 1940s, demonstrated that carefully prepared protein hydrolysates could be safely infused intravenously and incorporated by the body. Stanley Dudrick and Douglas Wilmore, surgeon researchers at the University of Pennsylvania, worked through the many details of preparation, administration, and clinical monitoring in beagle puppies before testing them on adult patients malnourished from a variety of surgical complications and gastrointestinal conditions. They applied their techniques and formulations on a newborn wasting away from congenital absence of the small bowel, the baby growing and developing for several months while being nourished completely by total parenteral nutrition. Their techniques, inspired by patients with progressive malnutrition from devastating intestinal conditions and malformations, form the basis of the practice of intravenous nutrition practiced today.

Assessment of cetuximab-induced infusion reactions and administration rechallenge at an academic medical center.

Cetuximab is approved for treatment of squamous cell carcinoma of the head and neck (SCCHN). Cetuximab is generally well tolerated, but does carry a black box warning for infusion reactions (IRs). Incidence of IR in clinical trials was 15-20% for all grades and 3-5% for grades III-IV. Retrospective studies reported a higher incidence of all grade IRs and grades III-IV IR in areas of the Southeastern United States. Information regarding rechallenge doses after an IR has not been well described. At our institution, we frequently rechallenge on the same day after an initial IR. The primary objective was to determine the incidence, timing, IR grade, and completion of a rechallenge dose in patients who experienced an initial IR. Secondary objectives included: (1) determining the incidence and grade of IR in patients who received a first dose of cetuximab and (2) identifying specific risk factors for cetuximab IR with the first dose. A single-center retrospective chart review was conducted in SCCHN patients treated with cetuximab between June 2008 and September 2015 at the University of Kansas Hospital Cancer Center and inpatient setting. The majority of patients (87.9%) were able to be quickly and successfully rechallenged after an initial IR. Minimal patients (27.6%) experienced a rechallenge IR, resulting in only 1 patient discontinuation. Rechallenge doses were most frequently (37.9%) administered between 30 and 59 min after initial dose discontinuation. This was a single-center retrospective study based on data collected from electronic medical records. Other limitations include interpretation of infusion reactions on a subjective basis by providers. These findings demonstrate the practice of same-day rechallenges in initial IR patients is feasible and safe.

LONG-TERM OUTCOMES OF RITUXIMAB THERAPY IN PATIENTS WITH NONINFECTIOUS POSTERIOR UVEITIS REFRACTORY TO CONVENTIONAL IMMUNOSUPPRESSIVE THERAPY.

To assess long-term effectiveness of rituximab therapy for refractory noninfectious uveitis affecting the posterior segment.

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections.

We investigated population pharmacokinetics (PK) of doripenem in Korean patients with acute infections, and determined an appropriate dosing regimen using a Monte-Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20∼50 mL/min or >50 mL/min who received a 250-mg or 500-mg dose of doripenem over the course of one hour every eight hours, respectively, were included in this study. Blood samples were taken pre-dose and 0 h, 0.5 h, and 4-6 h after the fourth infusion. A nonlinear mixed effect modeling tool was used for the PK analysis and pharmacodynamics simulation; doripenem PKs were well described by a one-compartment model. Population mean values (relative standard error) were 0.109 L/h/kg (9.197%) and 0.280 L/kg (9.56%) for body weight normalized clearance (CL/WT) and body weight normalized volume of distribution (V/WT), respectively. Doripenem CL was significantly influenced by CLCR The proposed equations to estimate doripenem CL in Korean patients were CL/WT (L/h/kg) = 0.109 × WT × [CLCR/57](0.688) CL in Korean patients was expected to be lower than that of Caucasians was, regardless of renal function. The Monte-Carlo simulation showed 90% attainment of target PK/PD magnitudes could be achieved when the minimum inhibitory concentration (MIC) was ≤ 1 mg/L with the usual dosing regimens. However, prolonged infusions (4 h) should be considered, especially when patients had augmented renal function and for pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and decreased bacterial susceptibility.

Exogenous glucagon-like peptide-1 attenuates glucose absorption and reduces blood glucose concentration after small intestinal glucose delivery in critical illness.

To evaluate the effect of exogenous glucagonlike peptide-1 (GLP-1) on small intestinal glucose absorption and blood glucose concentrations during critical illness.

Role of Antioxidants in Horse Serum-mediated Vasculitis in Swine: Potential Relevance to Early Treatment in Mitigation of Coronary Arteritis in Kawasaki Disease.

Horse serum-induced immune complex coronary vasculitis in swine is the first experimental model to mimic most of the pictures of Kawasaki disease. Immune complex mechanism has been implicated as one of the possible mechanisms in the pathogenesis of vasculitis in Kawasaki disease. Antioxidants have a significant role in the reduction of cardiovascular diseases in both human and animal studies. We tried giving vitamins A, E, and C to treat immune complex vasculitis, in the hope of mitigating coronary vasculitis in Kawasaki disease.

A comparison of cardiopulmonary effects and anaesthetic requirements of two dexmedetomidine continuous rate infusions in alfaxalone-anaesthetized Greyhounds.

To determine the effects of two dexmedetomidine continuous rate infusions on the minimum infusion rate of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent haemodynamic and recovery effects in Greyhounds undergoing laparoscopic ovariohysterectomy.

Is continuous infusion of imipenem always the best choice?

Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT>MIC, 40%fT>MIC and 100%fT>MIC. For the target of 40%fT>MIC, all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT>MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT>MIC and 100%fT>MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary.

Mesenchymal Stromal Cell Therapy for Chronic Lung Allograft Dysfunction: Results of a First-in-Man Study.

Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD. The purpose of this phase 1, single-arm study was to explore the feasibility and safety of intravenous delivery of allogeneic MSCs to patients with advanced CLAD. MSCs from unrelated donors were isolated from bone marrow, expanded and cryopreserved in a GMP-compliant facility. Patients had deteriorating CLAD and were bronchiolitis obliterans (BOS) grade ≥ 2 or grade 1 with risk factors for rapid progression. MSCs (2 x 10(6) cells per kilogram patient weight) were infused via a peripheral vein twice weekly for 2 weeks, with 52 weeks follow-up. Ten Patients (5 male, 8 bilateral, median [interquartile range] age 40 [30-59] years, 3 BOS2, 7 BOS3) participated. MSC treatment was well tolerated with all patients receiving the full dosing schedule without any procedure-related serious adverse events. The rate of decline in forced expiratory volume in one second slowed after the MSC infusions (120 ml/month preinfusion vs. 30 ml/month postinfusion, p = .08). Two patients died at 152 and 270 days post-MSC treatment, both from progressive CLAD. In conclusion, infusion of allogeneic bone marrow-derived MSCs is feasible and safe even in patients with advanced CLAD. © Stem Cells Translational Medicine 2017.

Effects of intermittent intravenous saline infusions in patients with medication-refractory postural tachycardia syndrome.

The postural tachycardia syndrome (POTS) is a heterogeneous group of disorders that results in symptoms of orthostatic intolerance. Excess blood pooling has been observed to cause low effective circulating volume in the central vasculature. Consequently, acute volume loading with IV saline has emerged as a potential strategy for clinical intervention. We evaluated the impact of acute volume loading on both the signs and symptoms of patients suffering from POTS.