A comparison between intraosseous and intravenous access in patients with out-of-hospital cardiac arrest: A retrospective cohort study.

INTRODUCTION: The optimal vascular access for patients with out-of-hospital cardiac arrest (OHCA) remains controversial. Increasing evidence supports intraosseous (IO) access due to faster medication administration and higher first-attempt success rates compared to intravenous (IV) access. However, the impact on patient outcomes has been inconclusive. METHODS: This retrospective cohort study in Taoyuan City, Taiwan, from January 1, 2019, to December 31, 2022, included patients aged ≥18 years with non-traumatic OHCA resuscitated by emergency medical technician paramedics (EMT-Ps) with either IVs or IOs for final vascular access. The exclusion criteria were cardiac arrest en route to the hospital and resuscitation during the coronavirus pandemic (from May 1, 2022, to October 31, 2022). The primary and secondary outcomes were sustained ROSC (≥2 h) and cerebral performance category (CPC) 1-2, respectively. Univariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for the primary analysis. Multivariable logistic regression was employed, with variables selected based on a p-value of <0.05 in the univariate analysis. The survival benefits of different insertion sites and subgroups like general ambulance teams (with a composition that includes fewer EMT-Ps and limited experience in using IO access) were also analyzed. RESULTS: A total of 2003 patients were enrolled; 1602 received IV access and 401 IO access. The median patient age was 70 years, and most were male (66.6%). Compared to patients receiving IV access, the adjusted odds ratios (aORs) for primary and secondary outcomes in patients with IOs were 0.83 (95% confidence interval [CI], 0.61-1.11; p = 0.20) and 0.96 (95% CI, 0.39-2.40; p = 0.93), respectively. Different insertion sites showed no outcome differences. In the subgroups of females and patients resuscitated by general ambulance teams, the aORs for sustained ROSC were 0.55 (95% CI, 0.33-0.92; p = 0.02) and 0.62 (95% CI, 0.41-0.94; p = 0.02), respectively. CONCLUSIONS: For patients with OHCA resuscitated by EMT-Ps, IO access was comparable to IV access regarding patient outcomes. However, in females and patients resuscitated by general ambulance teams, IV access might be favorable.

Epinephrine administration in adults with out-of-hospital cardiac arrest: A comparison between intraosseous and intravenous route.

INTRODUCTION: The benefits and risks of the intraosseous (IO) route for vascular access in patients with out-of-hospital cardiac arrest (OHCA) remain controversial. This study compares the success rates of establishing the access route, epinephrine administration rates, and time-to-epinephrine between adult patients with OHCA with IO access and those with intravenous (IV) access established by paramedics in the prehospital setting. METHODS: This was a retrospective study conducted by the San-Min station of Taoyuan Fire Department. Data for IV access were collected between January 1, 2020, and December 31, 2020. Data for IO access were collected between January 1, 2021, and March 10, 2021. Inclusion criteria were adult patients with OHCA who received on-scene resuscitation attempts and in whom either IV or IO route access was established by paramedics. Exclusion criteria were missing data, return of spontaneous circulation before establishing vascular access, cardiac arrest en route to hospital, patients not resuscitated, and OHCA unidentified by the dispatcher. Exposure was defined as IV route vs. IO route (EZ-IO®). The outcome measurements were per-patient based success rates of route establishment (successes/attempts), administration rates of epinephrine (epinephrine administered per case/enrolled OHCAs), and odds ratios of IV versus IO on epinephrine administration. We used nonparametric Mann-Whitney rank sum tests for the analysis in continuous variables and Fisher's exact tests for the analysis of categorical variables and the outcomes. Firth logistic regression method was used for sparse data. Factors associated with epinephrine administration other than vascular access were also analyzed. Time-to-epinephrine (defined as time from paramedic arrival to epinephrine injection) was reviewed and calculated by two independent observers and the Kaplan-Meier method was used to compare the two access routes. RESULTS: A total of 112 adult patients were enrolled in the analysis, including 71 men and 41 women, with an average age of 67 years. There were 90 IV access cases and 22 IO access cases. The groups were compared for median success rates of route establishment (33% vs. 100%, P < 0.001) and administration rates of epinephrine (52% vs. 100%, P < 0.001). The adjusted odds ratio of IO versus IV was 32.445, 95% confidence interval (CI) of 1.844-570.861. Time-to-epinephrine was significantly shorter in the cumulative time-event analysis by the Kaplan-Meier method (P < 0.001). CONCLUSION: The IO route was significantly associated with higher success rates of route establishment, epinephrine administration, and shorter time-to-epinephrine in the prehospital resuscitation of adult patients with OHCA.

Paclitaxel Delivery to the Brain for Glioblastoma Treatment.

The development of paclitaxel-loaded polymeric nanoparticles for the treatment of brain tumors was investigated. Poly(lactide-glycolide) (PLGA) nanoparticles containing 10% w/w paclitaxel with a particle size of 216 nm were administered through intranasal and intravenous routes to male Sprague-Dawley rats at a dose of 5 mg/kg. Both routes of administration showed appreciable accumulation of paclitaxel in brain tissue, liver, and kidney without any sign of toxicity. The anti-proliferative effect of the nanoparticles on glioblastoma tumor cells was comparable to that of free paclitaxel.

Hypertriglyceridaemia Induced Pancreatitis Management: A Case Report.

Acute pancreatitis results in high morbidity and mortality. Gallstones and alcoholism are considered leading causes of acute pancreatitis. However, increasing prevalence of obesity, diabetes and lifestyle choices has resulted in Hypertriglyceridaemia induced pancreatitis (HTAP) becoming more common. HTAP is said to be more severe than other causes. The treatment options available vary including intravenous (IV) insulin, heparin, plasma exchange, fibrates, niacin, omega three fatty acids and dietary restrictions. This is a case report of a patient presenting with HTAP and the dilemma treating physicians faced in trying to balance the need for urgent treatment with invasiveness of procedure and paucity of evidence.

Intravenous Iron Therapy in Heart Failure.

Iron deficiency anemia is both a comorbid condition and an indicator of poor prognosis in heart failure. The mechanisms by which this occurs are multiple and complex. Recent robust randomized clinical trials have shown significant improvements in quality of life and rates of hospitalization with intravenous repletion of iron. In this article, we review the mechanisms by which iron deficiency impacts heart failure and the evidence behind repletion. There remains a good deal to learn about long-term effects of intravenous iron repletion, and clinical trials are ongoing in this regard.

Comparative Analysis of Inpatient Costs for Obstetrics and Gynecology Surgery Patients Treated With IV Acetaminophen and IV Opioids Versus IV Opioid-only Analgesia for Postoperative Pain.

BACKGROUND: Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures. OBJECTIVE: Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption. METHODS: We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients. RESULTS: We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07). CONCLUSION: Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals.

The long-acting azalide antibiotic gamithromycin is marketed for intramuscular treatment of bovine and swine infections. Off-label use in foals leads to severe local lesions likely caused by hyperosmolality of the injected solution. We provide evidence from a pharmacokinetic study in 10 warm-blooded healthy foals for intravenous bolus injection of gamithromycin diluted in distilled water to be a safe and well tolerated alternative. By intravenous dosing, markedly higher plasma exposure and better penetration into bronchoalveolar lavage cells but lower distribution into epithelial lining fluid are achieved as after intramuscular or subcutaneous administration. Intravenously injected gamithromycin was tolerated without any adverse drug reactions. The protocols for treatment of equine pulmonary infections caused by Rhodococcus equi should be revised accordingly.

Molecular epidemiology and clinical features of Hepatitis C Virus (HCV) in epidemic areas of Interior Sindh, Pakistan.

OBJECTIVE: Highly variable genome of HCV and high prevalence in many geographical areas made it necessary to conduct local population studies. This study has been conducted to show HCV parameters along with clinical features in the local population of interior Sindh, province of Pakistan. METHODS: Present study was conducted in from August 2010 to November 2015 in the rural areas of Sindh, Pakistan. All the 31560 screened samples selected for the study were tested by second Generation Enzyme Linked Immunosorbent Assay (ELISA Biokit 480&96). RESULTS: Total 31560 people were screened for HCV and out of these 13.67% (n= 4314) HCV infected patients. When 4314 samples of patients were examined; the anti-HCV was significantly higher in males 2814 (14.98%) than in females 1500 (11.74%) with P value = 0.06. The age of the patients ranged from 18 to 65 years. Out of 4314 HCV samples, 3020 (70%) were of Genotype 3a, 237(5.5%) of Genotype 2a, 108 (2.5%) of Genotype- 1a, 216 (5%) of Genotype 1b, 237 (5.5%) of Genotype 3b and 43 (1%) of Genotype 4. Additionally, 108 (2.5%) had co-infection and 345 (8%) samples showed no result -designated as untypable by the genotyping. CONCLUSION: This study showed that HCV is most frequently reported disease with genotype 3a being the most prevalent genotype.

Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy Drinkers.

BACKGROUND: Preclinical and emerging clinical evidence indicates that varenicline, a nicotinic partial agonist approved for smoking cessation, attenuates alcohol seeking and consumption. Reductions of alcohol craving have been observed under varenicline treatment and suggest effects of the medication on alcohol reward processing, but this hypothesis remains untested. METHODS: In this double-blind, placebo-controlled randomized experimental medicine study, 29 heavy drinkers underwent a functional magnetic resonance imaging scan after 2 weeks of varenicline (2mg/d) or placebo administration. During functional magnetic resonance imaging, participants performed the Alcohol-Food Incentive Delay task, where they could earn points for snacks or alcohol. At baseline and after 3 weeks of medication, participants underwent intravenous alcohol self-administration sessions in the laboratory. RESULTS: During the functional magnetic resonance imaging scan, participants in the varenicline group (N=17) reported lower feelings of happiness and excitement on subjective mood scales when anticipating alcohol reward compared with the placebo group (N=12). Linear mixed effects analysis revealed that anticipation of alcohol reward was associated with significant blood oxygen level dependent activation of the ventral striatum, amygdala, and posterior insula in the placebo group; this activation was attenuated in the varenicline group. The varenicline group showed no difference in intravenous alcohol self-administration relative to the placebo group for either session. Participants with higher insula activation when anticipating alcohol reward showed higher alcohol self-administration behavior across groups. CONCLUSIONS: Our findings suggest that varenicline decreases blood oxygen level dependent activation in striato-cortico-limbic regions associated with motivation and incentive salience of alcohol in heavy drinkers. This mechanism may underlie the clinical effectiveness of varenicline in reducing alcohol intake and indicates its potential utility as a pharmacotherapy for alcohol use disorders.

Factors influencing response to intravenous lacosamide in emergency situations: LACO-IV study.

Status epilepticus (SE) and acute repetitive seizures (ARSs) frequently result in emergency visits. Wide variations in response are seen with standard antiepileptic drugs (AEDs). Oral and intravenous (IV) formulations of lacosamide are approved as adjunctive therapy in the treatment of partial-onset seizures in adults and adolescents. The aim of the retrospective multicenter observational study (LACO-IV) was to analyze data from a large cohort of patients with SE or ARSs of varying severity and etiology, who received IV lacosamide in the emergency setting. Patient clinical data were entered into a database; lacosamide use and efficacy and tolerability variables were analyzed. In SE, IV lacosamide tended to be used mainly in nonconvulsive status epilepticus as second- or third-line treatment. The proportion of patients with no seizures when IV lacosamide was the last drug administered was 76.5% (70.9% SE and 83.7% ARSs). The rate of seizure cessation ≤ 24 h after IV lacosamide administration was 57.1% (49.1% SE and 67.4% ARSs). Of the factors analyzed, a shorter latency from seizure onset to IV lacosamide infusion influenced treatment response significantly. A nonsignificant tendency towards a higher response was seen with lacosamide dose >200mg versus ≤ 200 mg. Analysis of response according to mechanism of action showed no significant differences in response to IV lacosamide in patients receiving prior sodium channel blocker (SCB) or non-SCB AEDs in the overall or SE population; however, in ARSs, a tendency towards a higher response was observed in those receiving non-SCB AEDs. The frequency and nature of adverse events observed were in line with those reported in other studies (somnolence being the most frequent). In the absence of randomized prospective controlled studies of IV lacosamide, our observations suggest that IV lacosamide may be a potential alternative for treatment of SE/ARSs when seizures fail to improve with standard AEDs or when AEDs are contraindicated or not recommended.

Clinical pharmacokinetics of terbutaline in humans: a systematic review.

Terbutaline is used for the management of bronchospasm associated with asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease. A systematic review would be beneficial to assess the impact of routes of administration, stereoisomerism, disease states, smoking, age, exercise, and chronobiology on pharmacokinetics (PK) of terbutaline in humans. PubMed and Google Scholar databases were searched to screen all the relevant articles consisting of at least one of the PK parameters after administration of oral, inhaled, and intravenous (IV) terbutaline in humans. Oral studies of terbutaline depicted a linear relationship between plasma concentration (Cp) and the administered dose. The IV studies demonstrated multi-exponential behavior for disposition and renal clearance. Higher systemic availability was observed with inhaled as compared to oral route, and chrono-pharmacokinetic behavior was notable. Time to reach maximum plasma concentration (Tmax) was prolonged, and maximum plasma concentration (Cmax) was lowered after exercise. The primary route of excretion in chronic kidney disease (CKD) patients is reported to be nonrenal. In pregnant women, the Cp of terbutaline is lowered and clearance is increased. The addition of theophylline to terbutaline did not affect the PK of terbutaline; hence, both can be used without dose adjustment. This review summarizes all the available PK parameters of terbutaline, and it may be helpful for researchers in the development and evaluation of PK models as well as in designing optimal dosage regimens in different clinical conditions.

Effect of other venous access on cardiopulmonary resuscitation quality: A prospective, randomized, controlled trial.

This randomized controlled study aimed to prospectively evaluate the application effects of other venous access in patients undergoing cardiopulmonary resuscitation. A total of 212 patients who underwent respiratory and cardiac arrest were randomly divided into peripheral intravenous (IV) access group (IV group, n = 69), femoral vein catheterization group (FVC group, n = 72), and internal jugular vein catheterization group (IJVC group, n = 71). The puncture time, first administration time, pressure interruption time caused by the establishment of fluid pathway, endotracheal intubation time, complications, ROSC time, and ETCO2 were recorded. The time of establishing venous access was: IVIJVC>IV, P = 0.04). There was no significant difference in EtCO2 between the FVC, IV group, and IJVC group (PVC>IJVC>IV, P = 0.17). Due to catheterization, the time of suspending chest compression in the FVC group was significantly lower than in the IJVC group (5s vs. 12s). The time of establishing an artificial airway in the IV (38s) and FVC (35s) group were significantly longer than that in IJVC (52s) group. Central venous catheterization is more effective than peripheral venous catheterization in cardiopulmonary resuscitation. Moreover, femoral vein access was more effective than internal jugular vein access.

Drug compatibility with various closed intravenous infusion containers.

Objective: The aim was to systematically compare the drug compatibility with various closed intravenous (i.v.) infusion containers, to provide a reference for selecting a relatively superior infusion container and improve the medication safety for patients in clinical practice. Methods: The compatibility of four commonly used clinical injections (ceftazidime, pantoprazole sodium, ambroxol hydrochloride, edaravone) with three representative closed i. v. infusion containers (non-PVC infusion bags, upright polypropylene infusion bags, inner sealed polypropylene infusion bags) prefilled with infusion fluids (0.9% sodium chloride or 5% dextrose) in the Chinese market were investigated in this study. The particle counts of both infusion fluids and diluted chemical injections by infusion fluids in various infusion containers were determined by the light obscuration method. At 0, 2 and 6 h after four injections following dilution with infusion fluids in each container, the pH of the solutions was detected, and the physical properties were examined by visual inspection. Meanwhile, the drug concentrations were assessed by high performance liquid chromatography (HPLC). Results: As for either infusion fluids or diluted injections by infusion fluids, the particle counts in non-PVC infusion bags were significantly greater than those in the other two bags under some circumstances. The particle counts in diluted injections by infusion fluids increased dramatically compared with those in infusion fluids in all infusion containers, especially for the small-size particles. But pH, physical properties and drug concentrations of diluted infusion solutions in all infusion containers remained nearly unchanged over the test period. Conclusion: Closed i. v. infusion containers included in this study are all well-compatible with four injections. Moreover, the closed infusion containers produced by Chinese manufacturers have met the international quality standard. Particularly, the intravenous admixture preparation process needs to be optimized to reduce the overall particulate contaminants.

Study of the hepatitis C virus in the republic of macedonia.

Hepatitis C virus (HCV) is a major public health problem. It is a leading cause of chronic liver disease and the most common indication for liver transplantation. The therapy for eradication of HCV infection is successful in only 50.0-80.0% of patients and is highly dependent on the HCV genotype. Molecular detection and characterization of HCV in the Republic of Macedonia started in 1990. Since then, more than 4000 samples have been analyzed at the Research Centre for Genetic Engineering and Biotechnology (RCGEB) "Georgi D. Efremov," Skopje, Republic of Macedonia. The prevalence of HCV infections in the healthy population of the Republic of Macedonia was found to be 0.4%, while it varies between 23.0 and 43.0% in different at-risk groups of patients. The prevalence of HCV genotypes, according to associated risk factors in HCV infected patients from the Republic of Macedonia, was analyzed. We found genotype 1 to be predominant in a group of hemodialysis patients, while genotype 3 was predominant in intravenous (IV) drug users. Association of six polymorphisms in the Oligoadenylate synthetase (OASL)-like interferon-stimulated gene with a sustained virological response was also analyzed. Our preliminary results suggest that non ancestral alleles in four of the six studies polymorphisms in OASL gene are associated with sustained virological response among HCV infected patients in R. Macedonia.

Biopredictive tools for the development of injectable drug products.

INTRODUCTION: Biopredictive release tests are commonly used in the evaluation of oral medicines. They support decision-making in formulation development and allow predictions of the expected in-vivo performances. So far, there is limited experience in the application of these methodologies to injectable drug products. AREAS COVERED: Parenteral drug products cover a variety of dosage forms and administration sites, including subcutaneous, intramuscular, and intravenous injections. In this area, developing biopredictive and biorelevant methodologies often confronts us with unique challenges and knowledge gaps. Here, we provide a formulation-centric approach and explain the key considerations and workflow when designing biopredictive assays. Also, we outline the key role of computational methods in achieving clinical relevance and put all considerations into context using liposomal nanomedicines as an example. EXPERT OPINION: Biopredictive tools are the need of the hour to exploit the tremendous opportunities of injectable drug products. A growing number of biopharmaceuticals such as peptides, proteins, and nucleic acids require different strategies and a better understanding of the influences on drug absorption. Here, our design strategy must maintain the balance between robustness and complexity required for effective formulation development.

Biodistribution of Intra-Arterial and Intravenous Delivery of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Rat Model to Guide Delivery Strategies for Diabetes Therapies.

Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-MSC-EVs) have become an emerging strategy for treating various autoimmune and metabolic disorders, particularly diabetes. Delivery of UC-MSC-EVs is essential to ensure optimal efficacy of UC-MSC-EVs. To develop safe and superior EVs-based delivery strategies, we explored nuclear techniques including positron emission tomography (PET) to evaluate the delivery of UC-MSC-EVs in vivo. In this study, human UC-MSC-EVs were first successfully tagged with I-124 to permit PET determination. Intravenous (I.V.) and intra-arterial (I.A.) administration routes of [124I]I-UC-MSC-EVs were compared and evaluated by in vivo PET-CT imaging and ex vivo biodistribution in a non-diabetic Lewis (LEW) rat model. For I.A. administration, [124I]I-UC-MSC-EVs were directly infused into the pancreatic parenchyma via the celiac artery. PET imaging revealed that the predominant uptake occurred in the liver for both injection routes, and further imaging characterized clearance patterns of [124I]I-UC-MSC-EVs. For biodistribution, the uptake (%ID/gram) in the spleen was significantly higher for I.V. administration compared to I.A. administration (1.95 ± 0.03 and 0.43 ± 0.07, respectively). Importantly, the pancreas displayed similar uptake levels between the two modalities (0.20 ± 0.06 for I.V. and 0.24 ± 0.03 for I.A.). Therefore, our initial data revealed that both routes had similar delivery efficiency for [124I]I-UC-MSC-EVs except in the spleen and liver, considering that higher spleen uptake could enhance immunomodulatory application of UC-MSC-EVs. These findings could guide the development of safe and efficacious delivery strategies for UC-MSC-EVs in diabetes therapies, in which a minimally invasive I.V. approach would serve as a better delivery strategy. Further confirmation studies are ongoing.

Urgent nephrectomy for rapidly progressive disseminated metastatic Hypermucoid Klebsiella.

Few cases of Hypervirulent Klebsiella Pneumonia (HvKP) have been described. Even fewer cases with renal abscess and metastatic pulmonary spread are reported. Typically, prompt introduction of intravenous antibiotics leads to clinical resolution and more invasive measures of source control are rarely required. To date only one other case of disseminated metastatic HvKP requiring nephrectomy for infective source control is described. Here we present a rare case of metastatic HvKP refractory to intravenous antimicrobial therapy in an immunocompromised newly diagnosed diabetic patient. Specifically, we seek to illustrate the rapid effectiveness of surgical intervention following a poor response to initial treatment.

Effects of Sodium Selenite Injection on Serum Metabolic Profiles in Women Diagnosed with Breast Cancer-Related Lymphedema-Secondary Analysis of a Randomized Placebo-Controlled Trial Using Global Metabolomics.

In our previous study, intravenous (IV) injection of selenium alleviated breast cancer-related lymphedema (BCRL). This secondary analysis aimed to explore the metabolic effects of selenium on patients with BCRL. Serum samples of the selenium-treated (SE, n = 15) or the placebo-controlled (CTRL, n = 14) groups were analyzed by ultra-high-performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). The SE group showed a lower ratio of extracellular water to segmental water (ECW/SW) in the affected arm to ECW/SW in the unaffected arm (arm ECW/SW ratio) than the CTRL group. Metabolomics analysis showed a valid classification at 2-weeks and 107 differential metabolites were identified. Among them, the levels of corticosterone, LTB4-DMA, and PGE3-which are known anti-inflammatory compounds-were elevated in the SE group. Pathway analysis demonstrated that lipid metabolism (glycerophospholipid metabolism, steroid hormone biosynthesis, or arachidonic acid metabolism), nucleotide metabolism (pyrimidine or purine metabolism), and vitamin metabolism (pantothenate and CoA biosynthesis, vitamin B6 metabolism, ascorbate and aldarate metabolism) were altered in the SE group compared to the CTRL group. In addition, xanthurenic acid levels were negatively associated with whole blood selenium level (WBSe) and positively associated with the arm ECW/SW. In conclusion, selenium IV injection improved the arm ECW/SW ratio and altered the serum metabolic profiles in patients with BCRL, and improved the anti-inflammatory process in lipid, nucleotide and vitamin pathways, which might alleviate the symptoms of BCRL.

Time effect of rutaecarpine on caffeine pharmacokinetics in rats.

Rutaecarpine is reported as a potent inducer of CYP1A2 enzyme in rats. There are natural herbal supplements containing rutaecarpine that are designed to enhance the CYP1A2-dependent removal of caffeine from blood so that people can have coffee later in the day without causing sleep interference. This study aimed to determine the minimum amount of time needed from oral rutaecarpine administration until the observed effect of rutaecarpine on caffeine pharmacokinetics (PK) in 15 male Sprague-Dawley rats. PK parameters for caffeine and its metabolites in the control and rutaecarpine groups were calculated using WinNonlin®. Results showed that orally administered rutaecarpine at 100 mg/kg dose as early as 3 h before oral caffeine administration significantly decreased the oral systemic exposure and mean residence time of caffeine and its metabolites due to decreased caffeine bioavailability (by up to 75%) and increased clearance. The systemic exposure of caffeine and its metabolites were also decreased when caffeine was given intravenously, though this effect was less pronounced than when caffeine was given orally. Although plasma level of rutaecarpine was undetectable (less than 10 ng/mL), rutaecarpine still induced hepatic CYP1A2 activity. Results from 7-methoxyresorufin O-demethylation activity, which is specific to CYP1A2, showed that 3 h after one rutaecarpine oral dose, CYP1A2 activity in rat liver tissue was increased by 3- fold. This finding suggested that rutaecarpine effectively induced CYP1A2 activity in the liver.

Serous retinal detachment as a presenting sign of acute lymphoblastic leukemia: A case report and literature review.

PURPOSE: To describe a unique case of unilateral serous retinal detachment as the presenting sign of B-cell acute lymphoblastic leukemia (ALL). OBSERVATIONS: A 74 year old woman presented with right eye blurry vision and was found to have an underlying serous retinal detachment, along with cotton wool spots, inner retinal hemorrhages, and retinal pigment epithelial changes throughout her bilateral fundi. Fluorescein angiography demonstrated bilateral vasculitis and ultrasonography revealed asymmetric thickening and enhancement of the affected eyes' choroid. This prompted a systemic lab workup and results were suspicious for an underlying hematologic malignancy. The patient was admitted to the hospital for bone marrow biopsy confirming B-cell ALL, underwent intensive intravenous and intrathecal chemotherapy, and was discharged one month later. Follow up appointment in the ophthalmology clinic demonstrated functional and anatomic improvement in the serous retinal detachment and choroidal thickening suggestive of infiltration in her right eye. CONCLUSIONS: SRDs are an uncommon ocular manifestation of leukemia, and even less common as a presenting sign of the disease. A comprehensive literature review demonstrated 11 other cases reported worldwide. We present the first such case with additional findings of leukemic retinopathy, optic nerve and choroidal infiltration, and vasculitis, as well as a complete library of ophthalmic imaging from the patient's initial presentation. IMPORTANCE: A new diagnosis of serous retinal detachment(s) without any obvious cause should raise suspicion for leukemia and prompt further workup. Early recognition of this hematologic malignancy is crucial for prompt initiation of life-saving therapy.