PIPERACILLIN/TAZOBACTAM IN CONTINUOUS INFUSION VERSUS INTERMITTENT INFUSION IN CHILDREN WITH FEBRILE NEUTROPENIA.

Background: Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective: The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients. Methods: This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results: There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions: There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Serum free ropivacaine concentrations among patients receiving continuous peripheral nerve block catheters: is it safe for long-term infusions?

BACKGROUND: Ropivacaine is a long-acting local anesthetic used for continuous peripheral nerve catheter infusions. Catheters may remain in situ for prolonged time periods. In the present study, patients were enrolled to receive continuous peripheral nerve catheters with measurement of free serum ropivacaine concentrations. METHODS: Peripheral nerve catheters were placed for postoperative pain management in trauma patients and infused with ropivacaine 0.2% or bolused with 0.5%. Blood samples were obtained from each subject on days 0 (preinfusion), 3, 5, 7, 10, and every third day until catheter removal. Serum free ropivacaine concentrations were measured via high-performance liquid chromatography and were compared using the Wilcoxon signed rank test. RESULTS: One hundred thirty-three blood samples were analyzed in 35 patients; all serum free ropivacaine concentrations after infusion initiation (99 samples from 35 subjects) were below 0.34 mg/L (previously determined toxic threshold). The highest concentration achieved in a blood sample was 0.19 mg/L; all other values were <0.09 mg/L. The total amount of drug received during the study ranged from 1146 to 22,320 mg (median of 3722 mg). Catheters remained in situ for a median of 7 days (range: 3-23). From day 0 to 3 (preinfusion), 77% of the study participants had an increase in the serum free-fraction ropivacaine concentrations. The median concentration on day 3 was 0.025 mg/L (95% upper confidence limit for mean: 0.05, range: <0.01-0.19); P < 0.001 compared with preinfusion levels). From day 3 to 5, 68% of the participants had a decrease in the serum free ropivacaine concentrations (median level 0.016 mg/L [95% upper confidence limit for mean: 0.021] P = 0.007 for day 5 compared with day 3). CONCLUSIONS: In this study, free serum ropivacaine concentrations remained well below toxic values despite large amounts of drug administration in combat-wounded patients. The administration of continuous ropivacaine infusions over prolonged time periods, coupled with multiple drug boluses, did not produce toxic or near-toxic serum concentrations.

Energy efficient ventilation and indoor air quality in the context of COVID-19 - A systematic review.

New COVID-19 ventilation guidelines have resulted in higher energy consumption to maintain indoor air quality (IAQ), and energy efficiency has become a secondary concern. Despite the significance of the studies conducted on COVID-19 ventilation requirements, a comprehensive investigation of the associated energy challenges has not been discussed. This study aims to present a critical systematic review of the Coronavirus viral spreading risk mitigation through ventilation systems (VS) and its relation to energy use. COVID-19 heating, ventilation and air conditioning (HVAC)-related countermeasures proposed by industry professionals have been reviewed and their influence on operating VS and energy consumption have also been discussed. A critical review analysis was then conducted on publications from 2020 to 2022. Four research questions (RQs) have been selected for this review concerning i) maturity of the existing literature, ii) building types and occupancy profile, iii) ventilation types and effective control strategies and iv) challenges and related causes. The results reveal that employing HVAC auxiliary equipment is mostly effective and increased fresh air supply is the most significant challenge associated with increased energy consumption due to maintaining IAQ. Future studies should focus on novel approaches toward solving the apparently conflicting objectives of minimizing energy consumption and maximizing IAQ. Also, effective ventilation control strategies should be assessed in various buildings with different occupancy densities. The implications of this study can be useful for future development of this topic not only to enhance the energy efficiency of the VS but also to enable more resiliency and health in buildings.

Pyrene-functionalized nanoparticles: two independent sensors, the excimer and the monomer.

The high surface-to-volume ratio of nanoparticles has been used to obtain a high local concentration of pyrene units on their periphery, making the formation of both pyrene emissive species possible using amazingly small pyrene concentrations. The sensing properties of model pyrene-functionalized nanoparticles was investigated by using different nitroaromatic compounds [m-nitroaniline and p-nitroaniline] and nitrobenzenes [nitrobenzene, p-nitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene]. The hybrid system acts as a dual-fluorescence sensor, in which the decrease of the pyrene emission, induced by the quencher, is hardly reflected in the pyrene excimer emission. The encapsulation capacity of the NPs also plays a key role in their sensitivity to the analyte.

Nitroanilines as quenchers of pyrene fluorescence.

The quenching of pyrene and 1-methylpyrene fluorescence by nitroanilines (NAs), such as 2-, 3-, and 4-nitroaniline (2-NA, 3-NA, and 4-NA, respectively), 4-methyl-3-nitroaniline (4-M-3-NA), 2-methyl-4-nitroaniline (2-M-4-NA), and 4-methyl-3,5-dinitroaniline (4-M-3,5-DNA), are studied in toluene and 1,4-dioxane. Steady-state fluorescence data show the higher efficiency of the 4-NAs as quenchers and fit with a sphere-of-action model. This suggests a 4-NA tendency of being in close proximity to the fluorophore, which could be connected with their high polarity/hyperpolarizability. In addition, emission and excitation spectra evidence the formation of emissive pyrene-NA ground-state complexes in the case of the 4-NAs and, in a minor degree, in the 2-NA. Moreover, time-resolved fluorescence experiments show that increasing amounts of NA decrease the pyrene fluorescence lifetime to a degree that depends on the NA nature and is larger in the less viscous solvent (toluene). Although the NA absorption and the pyrene (Py) emission overlap, we found no evidence of dipole-dipole energy transfer from the pyrene singlet excited state ((1)Py) to the NAs; this could be due to the low NA concentration used in these experiments. Transient absorption spectra show that the formation of the pyrene triplet excited state ((3)Py) is barely affected by the presence of the NAs in spite of their efficiency in (1)Py quenching, suggesting the involvement of (1)Py-NA exciplexes which--after intersystem crossing--decay efficiently into (3)Py.

Further insight into the photostability of the pyrene fluorophore in halogenated solvents.

Pyrene fluorophores of pyrene-functionalized CdSe quantum dots (QD@Py), as well as alkylpyrene and pyrene itself (Py), undergo fast degradation in aerated chloroform under ultraviolet-A (UV-A, 316<λ<400 nm) illumination. Steady-state fluorescence studies of irradiated chloroform solutions of QD@Py show formation of new bands, red-shifted compared to that of the pyrene moiety. Similar behaviour is observed for pyrene and the alkylpyrene system. Column chromatography of the pyrene photolysate in chloroform allowed us to isolate photoproducts arising from pyrene degradation, and to obtain information on the structure of the photoproducts responsible for the emission bands. The most predominant photoproducts were those originating from the reaction of pyrene with dichloromethyl radicals. The phototransformation of QD@Py and the alkylpyrene involves mainly detachment of the alkyl chain from the aromatic ring, induced also by dichloromethyl radicals, and oxidation of the alkyl chain at the benzylic position was detected as well. By contrast, these pyrene systems show a high photostability in aerated dichloromethane. Transient absorption measurements showed formation of both pyrene triplet and pyrene radical cation for all pyrene systems in these halogenated solvents. The yield of pyrene radical cations for Py is higher than for QD@Py and the alkylpyrene. In addition, pyrene radical cations were longer-lived in dichloromethane than in chloroform. The reason for the pyrene photostability in dichloromethane is the different reactivity of chloromethyl and dichloromethyl radicals towards pyrene and oxygen. These studies show that the use of dichloromethane can be a suitable alternative to chloroform when the good solubility properties of these halogenated solvents are needed to dissolve pyrene when this chromophore is used as a fluorescent probe.

Emphysematous Pyelonephritis Complicated With Hyperglycemic Hyperosmolar State and Sepsis: A Case Report and Literature Review.

Emphysematous pyelonephritis (EPN) is an acute life-threatening necrotizing infection of the renal parenchyma and perirenal tissues. There are multiple treatment strategies for EPN depending on the initial classification; over the last three decades, the treatment approach has favored kidney sparing strategies and the use of nephrectomy only as salvage therapy. We report a case involving a patient with unilateral emphysematous pyelonephritis complicated with hyperglycemic hyperosmolar state (HHS), sepsis, and multiple risk factors associated with poor prognosis who was successfully treated with conservative management sparing nephrectomy. This case report aims to create awareness among clinicians that even in the presence of multiple risk factors for poor prognosis, conservative management should be considered before nephrectomy.

A Rare Case of Empagliflozin-Induced Euglycemic Diabetic Ketoacidosis Obscured by Alkalosis.

Empagliflozin-induced euglycemic diabetic ketoacidosis is a life-threatening metabolic complication of diabetes mellitus characterized by metabolic acidosis, ketonemia, and relatively normal serum glucose levels. We present a rare case of empagliflozin-induced diabetic ketoacidosis obscured by alkalosis. This case report aims to create awareness among clinicians about this entity and consider this diagnosis in their differential, especially in patients taking sodium-glucose co-transporter (SGLT-2) inhibitors who present to the hospital with unspecific symptoms that may not suggest DKA.

Secondary Hemophagocytic Lymphohistiocytosis in a Young Hispanic Adult.

Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by a severe immune system reaction that involves an overwhelming inflammatory response with overproduction of cytokines and hemophagocytosis. HLH is classified as primary HLH or familial HLH (PHLH or FHLH) and secondary HLH. PHLH is due to mutations in several genes that regulate immune cells, while secondary HLH is triggered by a severe illness (viral infections or malignancies) that induce an excessive immune response that is difficult to control. We present a case of a young Hispanic adult female with a medical history of diabetes mellitus type 1 and hepatitis E that was diagnosed with HLH secondary to lymphoma caused by Epstein Barr virus infection. The patient was started on broad-spectrum antibiotics and steroid therapy; however, the patient succumbed to the disease. HLH is associated with high mortality, mainly because it is not a very common entity and patients usually present critically ill and deteriorate very fast. Immunosuppression and treatment of the underlying disorder is the target of the treatment of HLH, however, the prognosis remains poor.

Austrian Syndrome in an Immunocompromised Patient-A Case Report.

Austrian syndrome consists of a triad of endocarditis, meningitis, and pneumonia caused by Streptococcus pneumoniae. With the arrival of many antibiotic therapies, the disease remains rare, however, it can be overlooked due to the lack of awareness. We present a case of Austrian syndrome in an immunocompromised patient complicated by multiorgan failure.

Strategies for drug-eluting stent treatment of bifurcation coronary artery disease in the United States: insights from the e-Cypher S.T.L.L.R.trial.

OBJECTIVES: Our goal is to report the first large multicenter data for percutaneous coronary intervention (PCI) of bifurcation disease with drug-eluting stents (DES) in the United States. BACKGROUND: Bifurcation PCI remains a challenge to this date. There are limited data on outcomes of patients treated with bifurcation DES implantation, particularly in the United States. METHODS: There were 161 patients with bifurcation disease [side branch (SB) >or=2-mm] treated with >or=1 sirolimus-eluting stents at 41 centers participating in the Stent deployment Techniques on cLinicaL outcomes of patients treated with the cypheRstent (STLLR) trial. There was no protocol mandated strategy for bifurcation PCI. One-year outcome data were collected. Angiographic and clinical data were adjudicated independently. RESULTS: There were 147 patients (91.3%) treated with single stent strategy. Only 14 (8.7%) patients received sirolimus-eluting stents implantation in both branches. Among patients with single stent strategy, double wire strategy (DW) was selected in 27 (18.4%) patients whereas single wire strategy (SW) was selected in 120 (81.6%) patients. There were 48 (32.7%) Medina 1,1,1 bifurcations treated with SW (n = 34; 70.8%) and DW (n = 14; 29.2%). There were 26 procedures started with SW which had SB dilatation during the procedure, one as a bailout (TIMI-1 grade flow in the SB). Overall 1-year death, myocardial infarction, and target lesion revascularization occurred in 2.4, 4.0, and 5.6%, respectively. There was no significant difference in clinical outcomes between SW and DW. SB dilatation was associated with a high rate of stent thrombosis (8.6%). CONCLUSIONS: Main branch stenting without SB protection is the most common approach utilized in the STLLR study, which may reflect contemporary DES bifurcation strategies in the Unite States. This strategy was associated with an acceptable low incidence of adverse outcomes at 1-year.

Prevalence of refractory hypertension in the United States from 1999 to 2014.

OBJECTIVES: Refractory hypertension has been defined as uncontrolled blood pressure (at or above 140/90 mmHg) when on five or more classes of antihypertensive medication, inclusive of a diuretic. Because unbiased estimates of the prevalence of refractory hypertension in the United States are lacking, we aim to provide such estimates using data from the National Health and Nutrition Examination Surveys (NHANES). METHODS: Refractory hypertension was assessed across multiple NHANES cycles using the aforementioned definition. Eight cycles of NHANES surveys (1999-2014) representing 41 552 patients are the subject of this study. Prevalence of refractory hypertension across these surveys was estimated in the drug-treated hypertensive population after adjusting for the complex survey design and standardizing for age. RESULTS: Across all surveys, refractory hypertension prevalence was 0.6% [95% confidence interval (CI) (0.5, 0.7)] amongst drug-treated hypertensive adults; 6.2% [95% CI (5.1, 7.6)] of individuals with treatment-resistant hypertension actually had refractory hypertension. Although the prevalence of refractory hypertension ranged from 0.3% [95% CI (0.1, 1.0)] to 0.9% [95% CI (0.6, 1.2)] over the eight cycles considered, there was no significant trend in prevalence over time. Refractory hypertension prevalence amongst those prescribed five or more drugs was 34.5% [95% CI (27.9, 41.9)]. Refractory hypertension was associated with advancing age, lower household income, black race, and also chronic kidney disease, albuminuria, diabetes, prior stroke, and coronary heart disease. CONCLUSIONS: We provided the first nationally representative estimate of refractory hypertension prevalence in US adults.

Predicting the risk of apparent treatment-resistant hypertension: a longitudinal, cohort study in an urban hypertension referral clinic.

Apparent treatment-resistant hypertension (aTRH) is associated with higher prevalence of secondary hypertension, greater risk for adverse pressure-related clinical outcomes, and influences diagnostic and therapeutic decision-making. We previously showed that cross-sectional prevalence estimates of aTRH are lower than its true prevalence as patients with uncontrolled hypertension undergoing intensification/optimization of therapy will, over time, increasingly satisfy diagnostic criteria for aTRH. aTRH was assessed in an urban referral hypertension clinic using a 140/90 mm Hg goal blood pressure target in 745 patients with uncontrolled blood pressure, who were predominately African-American (86%) and female (65%). Analyses were stratified according to existing prescription of diuretic at initial visit. Risk for aTRH was estimated using logistic regression with patient characteristics at index visit as predictors. Among those prescribed diuretics, 84/363 developed aTRH; the risk score discriminated well (area under the receiver operating curve = 0.77, bootstrapped 95% CI [0.71, 0.81]). In patients not prescribed a diuretic, 44/382 developed aTRH, and the risk score showed a significantly better discriminative ability (area under the receiver operating curve = 0.82 [0.76, 0.87]; P < .001). In the diuretic and nondiuretic cohorts, 145/363 and 290/382 of patients had estimated risks for development of aTRH <15%. Of these low-risk patients, 139/145 and 278/290 did not develop aTRH (negative predictive value, diuretics - 0.94 [0.91, 0.98], no diuretics - 0.95 [0.93, 0.97]). We created a novel clinical score that discriminates well between those who will and will not develop aTRH, especially among those without existing diuretic prescriptions. Irrespective of baseline diuretic treatment status, a low-risk score had very high negative predictive value.

Revisiting blood transfusion and predictors of outcome in cardiac surgery patients: a concise perspective.

In the United States, cardiac surgery-related blood transfusion rates reached new highs in 2010, with 34% of patients receiving blood products. Patients undergoing both complex (coronary artery bypass grafting [CABG] plus valve repair or replacement) and non-complex (isolated CABG) cardiac surgeries are likely to have comorbidities such as anemia. Furthermore, the majority of patients undergoing isolated CABG have a history of myocardial infarction. These characteristics may increase the risk of complications and blood transfusion requirement. It becomes difficult to demonstrate the association between transfusions and mortality because of the fact that most patients undergoing cardiac surgery are also critically ill. Transfusion rates remain high despite the advances in perioperative blood conservation, such as the intraoperative use of cell saver in cardiac surgery. Some recent prospective studies have suggested that the use of blood products, even in low-risk patients, may adversely affect clinical outcomes. In light of this information, we reviewed the literature to assess the clinical outcomes in terms of 30-day and 1-year morbidity and mortality in transfused patients who underwent uncomplicated CABG surgery.

Impact of Demographic, Socioeconomic, and Psychological Factors on Glycemic Self-Management in Adults with Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is reported as one of the most complex chronic diseases worldwide. In the United States, Type 2 DM (T2DM) is the seventh leading cause of morbidity and mortality. Individuals with diabetes require lifelong personal care to reduce the possibility of developing long-term complications. A good knowledge of diabetes risk factors, including obesity, dyslipidemia, hypertension, family history of DM, and sedentary lifestyle, play an essential role in prevention and treatment. Also, sociodemographic, economic, psychological, and environmental factors are directly and indirectly associated with diabetes control and health outcomes. Our review intends to analyze the interaction between demographics, knowledge, environment, and other diabetes-related factors based on an extended literature search, and to provide insight for improving glycemic control and reducing the incidence of chronic complications.

The MiRNA Journey from Theory to Practice as a CNS Biomarker.

MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders.

The Gap Between Clinical Research and Standard of Care: A Review of Frailty Assessment Scales in Perioperative Surgical Settings.

The elderly population in the United States is increasing exponentially in tandem with risk for frailty. Frailty is described by a clinically significant state where a patient is at risk for developing complications requiring increased assistance in daily activities. Frailty syndrome studied in geriatric patients is responsible for an increased risk for falls, and increased mortality. In efforts to prepare for and to intervene in perioperative complications and general frailty, a universal scale to measure frailty is necessary. Many methods for determining frailty have been developed, yet there remains a need to define clinical frailty and, therefore, the most effective way to measure it. This article reviews six popular scales for measuring frailty and evaluates their clinical effectiveness demonstrated in previous studies. By identifying the most time-efficient, criteria comprehensive, and clinically effective scale, a universal scale can be implemented into standard of care and reduce complications from frailty in both non-surgical and surgical settings, especially applied to the perioperative surgical home model. We suggest further evaluation of the Edmonton Frailty Scale for inclusion in patient care.

Immune Thrombocytopenic Purpura Secondary to Cytomegalovirus Infection: A Case Report.

Immune thrombocytopenic purpura (ITP) is defined as an acquired thrombocytopenia with antibodies detected against platelet surface antigens, and it is the most common form of thrombocytopenia in otherwise asymptomatic adults. ITP secondary to an underlying condition is a diagnosis of exclusion that is essential to establish for treatment efficacy. Secondary thrombocytopenia caused by cytomegalovirus (CMV) is common; however, case reports associated with diagnosis in immunocompetent adults are rare, and to the best of our knowledge only 20 publications have been associated with this diagnosis. Our report is based on a clinical presentation of a 37-year-old female complaining of petechiae, heavy menses, shortness of breath, and a platelet count of 1 × 10(9)/L. Treatment with IVIG and steroids failed to improve platelet count. Subsequently, an infectious laboratory workup was performed, detecting CMV infection, and treatment with antiviral agents was initiated, causing platelet count to increase as viral load decreased.

Piperacillin/tazobactam in continuous infusion versus intermittent infusion in children with febrile neutropenia

Abstract Background Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients. Methods This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Fascitis necrosante: Presentación de caso / Necrotizing Fasciitis: Case Report

La fascitis necrosante es una infección grave de los tejidos blandos, aunque es poco frecuente, presenta una alta tasa de mortalidad, y de no ser diagnosticada rápidamente suele ser fulminante. Su diagnóstico se realiza principalmente por sospecha clínica y confirmación por cirugía; sin embargo, el apoyo imaginológico de la tomografía computarizada (TC) y la resonancia magnética (RM) han sido de gran ayuda. Se trata del caso clínico de un menor de edad, con dolor de alta intensidad y eritema en glúteo y miembro inferior secundario a inyección intramuscular, en quien el diagnóstico se sospecha inicialmente por ecografía y TC. Se destacan los hallazgos imaginológicos y la importancia de estas técnicas para su diagnóstico.

Necrotizing Fasciitis is a severe soft tissue infection, which although infrequent, has a high mortality rate and can be fatal if not diagnosed promptly. Diagnosis is primarily made by clinical suspicion and confirmation by surgery; however imaging support of computed tomography and magnetic resonance imaging are helpful. We present a case of a child with high intensity pain and erythema in buttock and lower limb secondary to intramuscular injection, in which the diagnosis was initially suspected by ultrasonography and computed tomography.