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infusions, intravenous - Top 30 Publications

Successful treatment of pure red cell aplasia because of ABO major mismatched stem cell transplant.

Pure red cell aplasia (PRCA) is a well-documented potential side effect of ABO major mismatched allogeneic hematopoietic stem cell transplants. This side effect may be self-limiting, but is sometimes treated using modalities such as steroids, antithymocyte globulin, donor lymphocyte infusions, rituximab, or plasma exchanges. Another well-documented cause of pure red cell aplasia is a chronic parvovirus B19 infection, which may be seen in immunocompromised hosts. The treatment of this cause of PRCA includes removal of immunosuppression, intravenous immunoglobulin (IVIg), or rituximab; however, this condition may also be self-limiting.

Model-Based Evaluation of Exenatide Effects on the QT Interval in Healthy Subjects Following Continuous IV Infusion.

Investigation of the cardiovascular proarrhythmic potential of a new chemical entity is now an integral part of drug development. Studies suggest that meals and glycemic changes can influence QT intervals, and a semimechanistic model has been developed that incorporates the effects of changes in glucose concentrations on heart rate (HR) and QT intervals. This analysis aimed to adapt the glucose-HR-QT model to incorporate the effects of exenatide, a drug that reduces postprandial increases in glucose concentrations. The final model includes stimulatory drug effects on glucose elimination and HR perturbations. The targeted and constant exenatide plasma concentrations (>200 pg/mL), via intravenous infusions at multiple dose levels, resulted in significant inhibition of glucose concentrations. The exenatide concentration associated with 50% of the stimulation of HR production was 584 pg/mL. After accounting for exenatide effects on glucose and HR, no additional drug effects were required to explain observed changes in the QT interval. Resulting glucose, HR, and QT profiles at all exenatide concentrations were adequately described. For therapeutic agents that alter glycemic conditions, particularly those that alter postprandial glucose, the QT interval cannot be directly compared to that with placebo without first accounting for confounding factors (eg, glucose) either through mathematical modeling or careful consideration of mealtime placement in the study design.

Bridging with Tirofiban during Oral Antiplatelet Interruption: A single-center, case series analysis including patients on hemodialysis.

Surgical patients requiring an interruption in dual-antiplatelet therapy (DAPT) within 6 months of cardiac stenting are at risk for thrombotic events. Bridging with short-acting intravenous antiplatelet agents has been proposed to minimize the risk of thrombotic and hemorrhagic complications.

Analgesic Effects of Intravenous Acetaminophen vs Placebo for Endoscopic Sinus Surgery and Postoperative Pain: A Randomized Clinical Trial.

Intravenous acetaminophen is a commonly prescribed analgesic for the prevention and treatment of postsurgical pain. Its efficacy in the context of endoscopic sinus surgery (ESS) has yielded mixed results.

Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain.

The rapidly-acting antidepressant properties of ketamine are a trend topic in psychiatry. Despite its robust effects, these are ephemeral and can lead to certain adverse events. For this reason, there is still a general concern around the off-label use of ketamine in clinical practice settings. Nonetheless, for refractory depression, it should be an indication to consider. We report the case of a female patient admitted for several months due to a treatment-resistant depressive bipolar episode with chronic suicidal behaviour. After repeated intravenous ketamine infusions without remarkable side effects, the patient experienced a complete clinical recovery during the 4 weeks following hospital discharge. Unfortunately, depressive symptoms reappeared in the 5th week, and the patient was finally readmitted to hospital as a result of a suicide attempt.

Health-Related Quality of Life in Adult Patients with Common Variable Immunodeficiency Disorders and Impact of Treatment.

Common variable immunodeficiency disorder (CVID) is a primary immunodeficiency disease (PIDD) often associated with severe and chronic infections. Patients commonly receive immunoglobulin (Ig) treatment to reduce the cycle of recurrent infection and improve physical functioning. However, how Ig treatment in CVID affects quality of life (QOL) has not been thoroughly evaluated. The purpose of a recent Immune Deficiency Foundation (IDF) mail survey was to assess the factors that are associated with QOL in patients with CVID receiving Ig treatment.

Pre-sleep dietary protein-derived amino acids are incorporated in myofibrillar protein during post-exercise overnight recovery.

The purpose of this study was to determine the impact of ingesting 30 g casein protein with and without 2 g free leucine prior to sleep on myofibrillar protein synthesis rates during post-exercise overnight recovery. 36 healthy young males performed a single bout of resistance-type exercise in the evening (19:45 h) after a full day of dietary standardization. Thirty min prior to sleep (23:30 h), subjects ingested 30 g intrinsically L-[1-(13)C]-phenylalanine-labeled protein with (PRO+leu, n=12) or without (PRO, n=12) 2 g free leucine, or a noncaloric placebo (PLA, n=12). Continuous intravenous L-[ring-(2)H5]-phenylalanine, L-[1-(13)C]-leucine and L-[ring-(2)H2]-tyrosine infusions were applied. Blood and muscle tissue samples were collected to assess whole-body protein net balance, myofibrillar protein synthesis rates and overnight incorporation of dietary protein-derived amino acids into myofibrillar protein. Protein ingestion prior to sleep improved overnight whole-body protein net balance (P<0.001). Myofibrillar protein synthesis rates did not differ significantly between treatments as assessed by L-[ring-(2)H5]-phenylalanine (0.057±0.002, 0.055±0.002, and 0.055±0.004 %∙h(-1) for PLA, PRO, and PRO+leu, respectively; P=0.850) or L-[1-(13)C]-leucine (0.080±0.004, 0.073±0.004, and 0.083±0.006 %∙h-1, respectively; P=0.328). Myofibrillar L-[1-(13)C]-phenylalanine enrichments increased following protein ingestion, but did not differ between the PRO and PRO+leu treatments. In conclusion, protein ingestion prior to sleep improves whole-body protein net balance and provides amino acids that are incorporated into myofibrillar protein during sleep. However, the ingestion of 30 g casein protein with or without additional free leucine prior to sleep does not increase muscle protein synthesis rates during post-exercise overnight recovery.

In vivo endocrine secretion of prostacyclin following expression of a Cox-1/PGIS fusion protein in the salivary glands of rats via non-viral gene therapy.

Pulmonary arterial hypertension is a progressive disease that culminates in right heart failure and death. Prostacyclin(PGI2) and its derivatives are effective treatments for PAH when administered as continuous parenteral infusions. This treatment paradigm requires medical sophistication, and patients are at risk for complications from an indewelling catheter; drug interruptions may result in rebound pulmonary hypertension and death. We hypothesized that the salivary gland can be repurposed into an endogenous production site for circulating PGI2 through the expression of a fusion protein embodying cyclooxygenase-1(Cox1) and prostacyclin synthase(PGIS) domains. We utilized ultrasound-assisted gene transfer (UAGT), a non-viral gene transfer strategy that achieves robust gene transfer to the salivary gland. We initially found that Cox1-PGIS expression in livers of mice using an Adenoviral vector dramatically increased circulating PGI2 relative to untreated rats or rats treated with PGIS alone. We then utilized UAGT to express Cox1-PGIS in the submandibular glands of rats and showed a significant elevation of circulating PGI2 that corresponded to approximately 30% of that seen in humans undergoing intravenous infusion therapy for PAH. These results suggest the feasibility of gene therapy to drive endogenous biosynthesis of PGI2 as a therapeutic strategy for the treatment of PAH.

Measuring osmosis and hemolysis of red blood cells.

Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the cell's interior. The selectively permeable nature of the cell membrane allows the movement of some solutes and prevents the movement of others. This has important consequences for cell volume and the integrity of the cell and, as a result, is of utmost clinical importance, for example in the administration of isotonic intravenous infusions. The concepts of osmolarity and tonicity are often confused by students as impermeant isosmotic solutes such as NaCl are also isotonic; however, isosmotic solutes such as urea are actually hypotonic due to the permeant nature of the membrane. By placing red blood cells in solutions of differing osmolarities and tonicities, this experiment demonstrates the effects of osmosis and the resultant changes in cell volume. Using hemoglobin standard solutions, where known concentrations of hemoglobin are produced, the proportion of hemolysis and the effect of this on resultant hematocrit can be estimated. No change in cell volume occurs in isotonic NaCl, and, by placing blood cells in hypotonic NaCl, incomplete hemolysis occurs. By changing the bathing solution to either distilled water or isosmotic urea, complete hemolysis occurs due to their hypotonic effects. With the use of animal blood in this practical, students gain useful experience in handling tissue fluids and calculating dilutions and can appreciate the science behind clinical scenarios.

Splenic abcesses as infectious complication following&#127; implantation of left ventricular asssist device - case report.

Left ventricular assist device (LVAD) is one of the modern management therapies in patients with advanced heart failure, and it serves as a bridge to heart transplantation or even as destination therapy. However, it is burdened with a high risk of thromboembolic, hemorrhagic, and infectious complications despite prophylactic management. Splenic abscesses, as septic complications following implantation of mechanical ventricular support, have not yet been described in the literature. We report of a patient with severe left ventricular insufficiency (NYHA II/III), pulmonary hypertension, and arrhythmia who underwent implantation of the Heart Ware® pump for left ventricular support with simultaneous tricuspidvalvoplasty, as a bridge therapy to heart transplantation. During two years after LVAD implantation, the patient had three MRSA skin infections, localized at the exit site of the drive-line connecting the artificial ventricle with external unit, that were complicated by sepsis and treated with broad-spectrum antibiotics. A few months later, abdominal CT revealed two abscesses in the spleen, and the patient was qualified for splenectomy. Open splenectomy was performed under full-dose anticoagulant therapy with continuous intravenous infusions of unfractionated heparin (UFH). The intra- and postoperative course was uneventful. UFH therapy was continued for 6 days, and oral anticoagulation was re-administered on day 4 after surgery. The patient was discharged on day 7 after surgery with primary healed wound. Open splenectomy, performed with full-dose anticoagulant therapy, proved to be an effective and definitive method of treatment without any complications.

Renal and Hematologic Side Effects of Long term IVIG Therapy in Patients With Neurologic Disorders.

For patients receiving intravenous immunoglobulin (IVIG), renal and hemolytic side effects are well recognized. However, there is very little data on the effects of chronic IVIG therapy.

Jugular-infused methionine, lysine and branched-chain amino acids does not improve milk production in Holstein cows experiencing heat stress.

Poor utilization of amino acids contributes to losses of milk protein yield in dairy cows exposed to heat stress (HS). Our objective was to test the effect of essential amino acids on milk production in lactating dairy cows exposed to short-term HS conditions. To achieve this objective, 12 multiparous, lactating Holstein cows were assigned to two environments (thermoneutral (THN) or HS) from days 1 to 14 in a split-plot type cross-over design. All cows received 0 g/day of essential amino acids from days 1 to 7 (negative control (NC)) followed by an intravenous infusion of l-methionine (12 g/day), l-lysine (21 g/day), l-leucine (35 g/day), l-isoleucine (15 g/day) and l-valine (15 g/day, methionine, lysine and branched-chain amino acids (ML+BCAA)) from days 8 to 14. The basal diet was composed of ryegrass silage and hay, and a concentrate mix. This diet supplied 44 g of methionine, 125 g of lysine, 167 g of leucine, 98 g of isoleucine and 109 g of valine per day to the small intestine of THN cows. Temperature-humidity index was maintained below 66 for the THN environment, whereas the index was maintained above 68, peaking at 76, for 14 continuous h/day for the HS environment. Heat stress conditioning increased the udder temperature from 37.0°C to 39.6°C. Cows that received the ML+BCAA treatment had greater p.m. rectal and vaginal temperatures (0.50°C and 0.40°C, respectively), and respiration rate (8 breaths/min) compared with those on the NC treatment and exposed to a HS environment. However, neither NC nor ML+BCAA affected rectal or vaginal temperatures and respiration rates in the THN environment. Compared with THN, the HS environment reduced dry matter intake (1.48 kg/day), milk yield (2.82 kg/day) and milk protein yield (0.11 kg/day). However, compared with NC, the ML+BCAA treatment increased milk protein percent by 0.07 points. For the THN environment, the ML+BCAA treatment increased concentrations of milk urea nitrogen. For the HS environment, the ML+BCAA treatment decreased plasma concentrations of arginine, ornithine and citrulline; however, differences were not observed for the THN environment. In summary, HS elicited expected changes in production; however, infusions of ML+BCAA failed to increase milk protein yield. Lower dry matter intake and greater heat load in response to ML+BCAA contributed to the lack of response in milk production in HS cows. The ML+BCAA treatment may have reduced the breakdown of muscle protein in heat-stressed cows.

Severity and outcome of the norovirus infection in children after intestinal transplantation.

In immunocompromised patients, the NoV infection is prolonged and severe. We retrospectively studied the severity of the NoV infection in children after an ITx, the treatment, and the long-term evolution. Norovirus PCR in stools was positive for 19 children in 21 separate episodes. The infection was symptomatic in 18 cases. At diagnosis, the median weight loss was 5% (0-11) and the creatinine clearance was 75 mL/min/1.73 m(2) (19-142). On 14 digestive biopsies, the pathological findings were non-specific with a constant mononuclear infiltration, showing signs of rejection in one case. Fifteen children in 17 cases were hospitalized for a median duration of 41 days (0-119) with IV infusions for 33 days (0-120). The viral shedding lasted 78 days (20-360). Nine children with severe or prolonged diarrhea received intravenous IGs and four of them additional NTZ. On follow-up, five other children developed a rejection 12 months (1-33) after NoV infection. Four uncontrolled rejections led to graft removal. Children mostly needed hospital admission and IV rehydration, but the symptoms upon presentation were moderate. Symptoms and shedding durations are prolonged as expected. The treatment efficacy cannot be assessed. The rejection induction by the NoV cannot be excluded.

Positive clinical outcome in a patient with recalcitrant bullous pemphigoid treated with rituximab and intravenous immunoglobulin.

A 41-year-old white man was treated for bullous pemphigoid (BP) for 4 years, using high-dose prednisone as well as ciclosporin and mycophenolate mofetil. Sustained clinical improvement was not observed. He suffered several serious side effects. Consequently, he was treated with a combination of rituximab (RTX) and intravenous immunoglobulin (IVIg). He received 12 infusions of RTX in 6 months and monthly IVIg until the end of the therapy. Within 5 weeks of this therapy, appearance of new lesions ceased. Within 8 weeks, all previous lesions resolved and previous medications were discontinued. No hospitalizations, relapses, infections or other serious adverse events occurred. The high levels of pathogenic autoantibody decreased and have remained undetectable. After three infusions of RTX, CD19+ B cells were undetectable and returned to normal levels within 18 months. The patient remains in complete clinical remission off all systemic therapy and free of disease for a 20-month follow-up.

The impact of pharmacy monitoring and intervention in patients receiving intravenous heparin.

Background Intravenous unfractionated heparin (IV UFH) has a narrow therapeutic index and poses a high risk of bleeding. Objective To determine the impact of pharmacy monitoring and intervention on adherence to and appropriate implementation of IV UFH protocol. Setting A 438 bed hospital specializing in cardiac services. Methods This is a retrospective chart review study. Pre-pharmacy intervention data were collected from November 2013 to January 2014 and compared to post-pharmacy intervention data obtained between August 2014 and October 2014. Patients were included if they received IV UFH for at least 24 hours. The first three daytime laboratory draws were collected for each patient and analyzed using generalized estimating equations to quantify the association between pharmacy monitoring and adherence to the institution's protocol. Main outcome measures Designation of appropriate protocol, accurate selection of initial infusion rate, timing of anti-Xa levels within 60 min of anticipated due time, change of infusion rate within 120 min of laboratory result, and appropriate adjustment of infusion rates. Results A total of 195 data points were included. The initial selection of infusion rate and subsequent adjustments were more appropriate in the post-intervention period with an odds ratio of 8.36 (95% CI 2.41-29.01, p value = 0.0008), and 4.66 (95% CI 1.41-15.43, p value = 0.0118), respectively. Conclusion The results of this study indicate that pharmacy monitoring of IV UFH therapy has improved adherence to an institution's protocol and is associated with more accurate selection of initial infusion rates and adjustment of infusions based upon laboratory results.

A confirmed case of sugammadex-induced anaphylaxis in a UK hospital.

We report the first published case of confirmed anaphylaxis to sugammadex in a UK hospital. The patient was given a bolus of sugammadex at the end of surgery. Four minutes later, he developed hypotension and a widespread erythematous rash. Multiple epinephrine boluses were administered and a continuous intravenous infusion of epinephrine commenced. The patient later reported auditory awareness, which occurred while the diagnosis of anaphylaxis was being made and initial treatment initiated. Serial serum tryptase levels were consistent with a type I hypersensitivity reaction. Skin prick and intradermal testing were performed 6 months later confirming allergy to sugammadex. This case restates the potential for hypersensitivity reactions to develop following the administration of sugammadex and makes clinicians aware that such reactions may require prolonged treatment with intravenous infusions of epinephrine. Finally, this case highlights the importance of maintaining or re-establishing anaesthesia while managing the emergent situation in order to avoid unintentional awareness.

TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-label, Non-randomized Phase 1 Study.

This phase 1 dose-escalation portion of the study evaluated the safety, pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC).

Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for magnetic resonance imaging.

Case summary This case report describes the clinical signs and treatment of an alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI. The cat was discharged from hospital following a prolonged recovery including obtunded mentation and cardiorespiratory depression for several hours following cessation of anaesthesia. The cat received supportive therapy that included supplemental oxygen via a face mask, intravenous crystalloid fluids and active rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its pharmacokinetics and previously reported lethal doses are discussed. Strategies for reducing the incidence of medication errors are presented. Relevance and novel information An unintentional overdose of alfaxalone by continuous rate infusion has not been reported previously in a cat. Treatment is supportive and directed towards maintenance of the cardiorespiratory systems. Whenever possible, smart pumps that have been designed to reduce human error should be used to help prevent medication errors associated with continuous rate infusions.

Continuous Intravenous Lidocaine Infusion for the Management of Pain Uncontrolled by Opioid Medications.

Limited data exist describing the outcomes of patients receiving continuous lidocaine infusions. The objective of this study was to evaluate the effect of use of continuous lidocaine infusions for pain management at a community teaching hospital. A retrospective chart review was performed that included adult patients receiving continuous systemic lidocaine infusions for the treatment of pain. Twenty-one patients were included in the analysis. Dosing ranged from 0.25 to 2.8 mg/kg/h, with a median infusion time of 64 hours. Eight patients (38%) experienced a response (≥20% reduction in pain score during the infusion compared with prior to the infusion). Among responding patients, there was a decrease in pain scores at rest after starting lidocaine (compared with prior to lidocaine) (6.5 vs. 3.7, P = .001) that was maintained 24 hours after lidocaine discontinuation. There were no differences in pain scores before, during, or after lidocaine in the entire study sample. A difference in oral morphine equivalent intake was present comparing usage during the infusion vs. day +1 (P = .006) and day +2 (P < .001). Similarly, a difference was present comparing morphine equivalent usage on day -2 with day +2 (P = .008) and day -1 with day +1 (P = .006). Continuous infusions of systemic lidocaine appear to be beneficial in some patients experiencing uncontrolled pain and may improve pain scores while decreasing opioid requirements. Overall beneficial effects of systemic lidocaine may last longer than the infusion itself.

Adverse events associated with a large dose of intravenous lipid emulsion for suspected local anesthetic toxicity.

Intravenous lipid emulsion (ILE) has gained favor as a rescue treatment for cardiovascular collapse due to intravenous local anesthetic overdose, however, goals of ILE therapy are still being defined. We describe a case of a girl given 66 mL/kg of 20% lipid emulsion (ILE) in the treatment of presumed mepivacaine toxicity.

Short-Term Outcome of Intravenous Methylprednisolone Pulse Therapy in Patients With Infantile Spasms.

Many studies advocate hormonal treatments including high-dose oral prednisolone as an effective treatment for epileptic spasms. However, little is known about the effects of intravenous methylprednisolone pulse therapy on infantile spasms. We investigated the short-term response to intravenous methylprednisolone pulse therapy for the treatment of infantile spasms.

Continuous thermographic observation may predict extravasation in chemotherapy-treated patients.

Extravasation, or leakage of vesicant drugs into subcutaneous tissues, causes serious complications such as induration and necrosis in chemotherapy-treated patients. As macroscopic observation may overlook symptoms during infusion, we focused on skin temperature changes at puncture sites and studied thermographic patterns related to induration or necrosis caused by extravasation.

Optimising physiology for adolescents with dysautonomia.

I congratulate Armstrong et al (1) on their high quality paper, which will enable us to plan interventions that improve the quality of life of the dysautonomic paediatric population. I support the movement toward programmes that facilitate closely monitored, appropriate exercise regimes, tailored for the dysautonomic adolescent. This may, in the medium to long term be physiologically equivalent to, but more cost-effective than, the intermittent intravenous infusions of saline that have been found to dramatically reduce symptoms and improve the quality of life of patients suffering from postural orthostatic hypotention syndrome (2). This article is protected by copyright. All rights reserved.

Effects of Maternal Magnesium Sulfate Treatment on Neonatal Feeding Tolerance.

To determine whether antenatal exposure to magnesium sulfate has an effect on neonatal enteral feeding tolerance.

Lysosomal Storage Diseases: Challenges in Multiprofessional Patient Care with Enzyme Replacement Therapy.

Background Due to their rarity studies in (ultra-) rare diseases are difficult. Only for a minority of these diseases causal therapies are available. Development and production of enzyme replacement therapies (ERT) for example are challenging and expensive. The number of patients is low, costs per patient are high. We will focus on the challenges of providing long-term ERT to patients with lysosomal storage diseases (LSD) in an out- and inpatient setting based on a literature search in Pubmed and own experience. Many ERTs for LSDs have a positive cost-benefit ratio. Possible side-effects are severe allergic reactions. ERT is covered by the insurance companies when prescribed by a physician, however they are liable to recourse by the insurance company as the expenses for drugs of the prescribing physician will be above average. In most cases the recourse can be averted if diagnoses of individual patients are disclosed. Intravenous infusion of ERT is not well-regulated in Germany/Austria. Infusion on a ward is safe however often not covered by the insurance companies as patients do not stay overnight. Another option is infusion in a day-care setting, however the lump sum paid for infusion does not cover costs for ERT. On an individual basis, reimbursement for medication (ERT) has to be negotiated with the insurance companies before infusion takes place. Home infusions are feasible, however careful evaluations of the infusion-team and the risk for side-effects have to be performed on an individual basis, legal issues have to be considered. In- and outpatient ERT of patients with LSDs is challenging but feasible after individual evaluation of patient and infusion team.

Effect of detomidine or romifidine constant rate infusion on plasma lactate concentration and inhalant requirements during isoflurane anaesthesia in horses.

Influence of detomidine or romifidine constant rate infusion (CRI) on plasma lactate concentration and isoflurane requirements in horses undergoing elective surgery.

Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study.

Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular mortality by 37% through day 180. RELAX-AHF-2 ( NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX-AHF-2 is a multicentre, randomized, double-blind, placebo-controlled, event-driven, phase 3 trial enrolling ∼6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild-to-moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all-cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in-hospital length of stay during index AHF. The results from RELAX-AHF-2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF.

Continuous magnesium infusions in the management of systemic anti-cancer therapy-related hypomagnesaemia.

Background Hypomagnesaemia is a relatively-common side effect of some systemic anti-cancer therapies (SACT). Oral and intravenous magnesium (given as injections or short infusions) have problems arising from their poor tolerability, and need for frequent administrations, respectively. Objective Assessing the effectiveness and safety of weekly continuous magnesium infusions (CMI) in the management of SACT-related hypomagnesaemia. Methods CMIs (initiated at 10 mmol/day and up-titrated subject to response) were prescribed to patients with ≥3 magnesium readings <0.5 mmol/L despite intravenous replacement with bolus-or-short-infusions (BSI). Efficacy (compared to BSI): (a) reduction in the number of moderate/severe hypomagnesaemia episodes, and (b) increase in mean magnesium serum levels.

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty.

Effects of graded removal of lysine from an intravenously infused amino acid mixture on lactation performance and mammary amino acid metabolism in lactating goats.

To investigate responses of milk protein synthesis and mammary AA metabolism to a graded decrease of postruminal Lys supply, 4 lactating goats fitted with jugular vein, mammary vein, and carotid artery catheters and transonic blood flow detectors on the external pudic artery were used in a 4 × 4 Latin square experiment. Goats were fasted for 24 h and then received a 9-h intravenous infusion of an AA mixture plus glucose. Milk yield was recorded and samples were taken in h 2 to 8 of the infusion period; a mammary biopsy was performed in the last hour. Treatments were graded decrease of lysine content in the infusate to 100 (complete), 60, 30, or 0% as in casein. Lysine-removed infusions linearly decreased milk yield, tended to decrease lactose yield, and tended to increase milk fat to protein ratio. Milk protein content and yield were linearly decreased by graded Lys deficiency. Mammary Lys uptake was concomitantly decreased, but linear regression analysis found no significant relationship between mammary Lys uptake and milk protein yield. Treatments had no effects on phosphorylation levels of the downstream proteins measured in the mammalian target or rapamycin pathway except for a tended quadratic effect on that of eukaryotic initiation factor 2, which was increased and then decreased by graded Lys deficiency. Removal of Lys from the infusate linearly increased circulating glucagon and glucose. Removal of Lys from the infusate linearly decreased arterial and venous concentrations of Lys. Treatments also had a significant quadratic effect on venous Lys, suggesting mechanisms to stabilize circulating Lys at a certain range. The 2 infusions partially removing Lys resulted in a similar 20% decrease, whereas the 0% Lys infusion resulted in an abrupt 70% decrease in mammary Lys uptake compared with that of the full-AA mixture infusion. Consistent with the abrupt decrease, mammary Lys uptake-to-output ratio decreased from 2.2 to 0.92, suggesting catabolism of Lys in the mammary gland could be completely prevented when the animal faced severe Lys deficiency. Mammary blood flow was linearly increased, consistent with the linearly increased circulating nitric oxide by graded Lys deficiency, indicating mechanisms to ensure the priority of the mammary gland in acquiring AA for milk protein synthesis. Infusions with Lys removed increased mammary clearance rate of Lys numerically by 2 to 3 fold. In conclusion, the decreased milk protein yield by graded Lys deficiency was mainly a result of the varied physiological status, as indicated by the elevated circulating glucagon and glucose, rather than a result of the decreased mammary Lys uptake or depressed signals in the mTOR pathway. Mechanisms of Lys deficiency to promote glucagon secretion and mammary blood flow and glucagon to depress milk protein synthesis need to be clarified by future studies.