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Pharmaceutics May 2024The aim of this study was to develop and validate a fast and sensitive bioanalytical method for the accurate quantification of fosfomycin concentrations in human...
The aim of this study was to develop and validate a fast and sensitive bioanalytical method for the accurate quantification of fosfomycin concentrations in human prostatic tissue. The sample preparation method only required milligrams of tissue sample. Each sample was mixed with two times its weight of water and homogenized. A methanol solution that was three times the volume of the internal standard (fosfomycin-13C3) was added, followed by vortex mixing and centrifugation. After its extraction from the homogenized prostatic tissue, fosfomycin was quantified by means of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) triple quadrupole system operating in negative electrospray ionization and multiple reaction monitoring detection mode. The analytical procedure was successfully validated in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and stability, according to EMA guidelines. The validation results, relative to three QC levels, were 9.9% for both the within-day and inter-day accuracy (BIAS%); 9.8% for within-day precision; and 9.9 for between-day precision. A marked matrix effect was observed in the measurements but was corrected by normalization with the internal standard. The average total recovery was high (approximatively 97% at the three control levels). The dynamic range of the method was 0.1-20 μg/g (R of 0.999). Negligible carry-over was observed after the injection of highly concentrated samples. F in the sample homogenate extracts was stable at 10 °C and 4 °C for at least 24 h. In the tissue sample freeze-thaw experiments, a significant decrease in F concentrations was observed after only two cycles from -80 °C to room temperature. The novel method was successfully applied to measure fosfomycin in prostatic tissue samples collected from 105 patients undergoing prostatectomy.
PubMed: 38794343
DOI: 10.3390/pharmaceutics16050681 -
Clinical Neurology and Neurosurgery Jul 2024Enhanced Recovery after Surgery (ERAS) protocols were developed to counteract the adverse effects of the surgical stress response, aiming for quicker postoperative...
OBJECTIVE
Enhanced Recovery after Surgery (ERAS) protocols were developed to counteract the adverse effects of the surgical stress response, aiming for quicker postoperative recovery. Initially applied in abdominal surgeries, ERAS principles have extended to orthopedic spine surgery, but research in this area is still in its infancy. The current study investigated the impact of ERAS on postoperative pain and opioid consumption in elective spine surgeries.
METHODS
A single-center retrospective study of patients undergoing elective spine surgery from May 2019 to July 2020. Patients were categorized into two groups: those enrolled in the ERAS pathway and those adhering to traditional surgical protocols. Data on demographics, comorbidities, length of stay (LOS), surgical procedures, and postoperative outcomes were collected. Postoperative pain was evaluated using the Numerical Rating Scale (NRS), while opioid utilization was quantified in morphine milligram equivalents (MME). NRS and MME were averaged for each patient across all days under observation. Differences in outcomes between groups (ERAS vs. treatment as usual) were tested using the Wilcoxon rank sum test for continuous variables and Pearson's or Fisher's exact tests for categorical variables.
RESULTS
The median of patient's mean daily NRS scores for postoperative pain were not statistically significantly different between groups (median = 5.55 (ERAS) and 5.28 (non-ERAS), p=.2). Additionally, the median of patients' mean daily levels of MME were similar between groups (median = 17.24 (ERAS) and 16.44 (non-ERAS), p=.3) ERAS patients experienced notably shorter LOS (median=2 days) than their non-ERAS counterparts (median=3 days, p=.001). The effect of ERAS was moderated by whether the patient had ACDF surgery. ERAS (vs. non-ERAS) patients who had ACDF surgery had 1.64 lower average NRS (p=.006). ERAS (vs. non-ERAS) patients who had a different surgery had 0.72 higher average NRS (p=.02) but had almost half the length of stay, on average (p<.001).
CONCLUSIONS
The current study underscores the dynamic nature of ERAS protocols within the realm of spine surgery. While ERAS demonstrates advantages such as reduced LOS and improved patient-reported outcomes, it requires careful implementation and customization to address the specific demands of each surgical discipline. The potential to expedite recovery, optimize resource utilization, and enhance patient satisfaction cannot be overstated. However, the fine balance between achieving these benefits and ensuring comprehensive patient care, especially in the context of postoperative pain management, must be maintained. As ERAS continues to evolve and find its place in diverse surgical domains, it is crucial for healthcare providers to remain attentive to patient needs, adapting ERAS protocols to suit individual patient populations and surgical contexts.
Topics: Humans; Pain, Postoperative; Male; Female; Analgesics, Opioid; Enhanced Recovery After Surgery; Middle Aged; Elective Surgical Procedures; Retrospective Studies; Aged; Adult; Spine; Length of Stay; Pain Measurement
PubMed: 38788543
DOI: 10.1016/j.clineuro.2024.108350 -
The New England Journal of Medicine May 2024Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would...
BACKGROUND
Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown.
METHODS
We randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m of body-surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 ml per minute per 1.73 m and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically.
RESULTS
Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P = 0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%).
CONCLUSIONS
Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW ClinicalTrials.gov number, NCT03819153.).
PubMed: 38785209
DOI: 10.1056/NEJMoa2403347 -
Angewandte Chemie (International Ed. in... May 2024Nucleoside and nucleotide analogues have proven to be transformative in the treatment of viral infections and cancer. One branch of structural modification to deliver...
Nucleoside and nucleotide analogues have proven to be transformative in the treatment of viral infections and cancer. One branch of structural modification to deliver new nucleoside analogue classes explores replacement of canonical ribose oxygen with a sulfur atom. Whilst biological activity of such analogues has been shown in some cases, widespread exploration of this compound class is hitherto hampered by the lack of a straightforward and universal nucleobase diversification strategy. Herein, we present a synergistic platform enabling both biocatalytic nucleobase diversification from 4'-thiouridine in a one-pot process, and chemical functionalization to access new entities. This methodology delivers entry across pyrimidine and purine 4'-thionucleosides, paving a way for wider synthetic and biological exploration. We exemplify our approach by enzymatic synthesis of 5-iodo-4'-thiouridine on multi-milligram scale and from here switch to complete chemical synthesis of a novel nucleoside analogue probe, 5-ethynyl-4'-thiouridine. Finally, we demonstrate the utility of this probe to monitor RNA synthesis in proliferating HeLa cells, validating its capability as a new metabolic RNA labelling tool.
PubMed: 38785103
DOI: 10.1002/anie.202405040 -
The American Surgeon May 2024There is evidence that providers often overprescribe opiates in the postoperative period. Despite an ever-growing geriatric population, there is little research...
There is evidence that providers often overprescribe opiates in the postoperative period. Despite an ever-growing geriatric population, there is little research detailing current opiate usage in older patients after trauma. This population presents a unique set of challenges for pain management and prescription drug dependence due to sensitivity, a narrow therapeutic window, and high rates of pre-existing polypharmacy. Assess the use of narcotics in geriatric trauma patients with various injury patterns to establish a reference point for future intervention for reduction in narcotic dependence. We created a database of trauma patients' age ≥65 years admitted to a single level 1 trauma center in the Southeastern United States during the 2019 calendar year. Information gathered included patient factors, injury patterns, operative intervention, pain medications prescribed during hospitalization and at discharge, total and average daily morphine milligram equivalents (MME) inpatient and outpatient, and requests/prescriptions for narcotics at follow-up. In 2019, there were 475 patients aged ≥65 admitted to our level 1 trauma center for acute traumatic injuries. 219 of those patients required operative intervention. Average total inpatient MME for this cohort was 169.0 with average daily MME of 22.89. The average total prescribed MME upon discharge was 79.27. There were 29 patients documented to request narcotic prescription refill at time of clinic follow-up, 27 of whom were prescribed a narcotic medication at follow-up. This dataset establishes a reference point for opiate use in geriatric trauma patients to facilitate further research for mitigation of risk in this population.
PubMed: 38782463
DOI: 10.1177/00031348241256063 -
Surgical Endoscopy May 2024Robotic donor nephrectomy (RDN) has emerged as a safe alternative to laparoscopic donor nephrectomy (LDN). Having previously demonstrated comparable efficacy, this study...
BACKGROUND
Robotic donor nephrectomy (RDN) has emerged as a safe alternative to laparoscopic donor nephrectomy (LDN). Having previously demonstrated comparable efficacy, this study aims to examine postoperative analgesia use (opioid and non-opioid) in the two groups.
METHODS
We conducted a retrospective review of 300 living donor nephrectomies performed at our center, comparing 150 RDN's with a contemporary cohort of 150 hand-assisted LDN's. In addition to clinical and demographic information, data on postoperative inpatient opioid and non-opioid analgesia (from patient's arrival to the surgical floor after surgery till the time of discharge) was collected. Opioid dosages were standardized by conversion to morphine milligram equivalents (MME). All patients were managed post-operatively under a standardized ERAS pathway for living donor nephrectomy patients.
RESULTS
There were no significant differences in donor age, gender, and BMI between RDN and LDN groups. Total post-operative opioid use (MME's) was significantly lower in RDN patients (RDN 27.1 vs. LDN 46.3; P < 0.0001). Breakdown of opioid use with post-operative (POD) day demonstrated significantly lower use in RDN group on POD1 (RDN 8.6 vs. LDN 17.0; P < 0.05), and POD2 (RDN 3.9 vs LDN 10; P < 0.05). RDN patients had a shorter post-operative length of stay (LOS) (RDN 1.69 days vs. LDN 1.98; P = 0.0003). There were no differences between groups in non-opioid medication use, complications, and readmission rates.
CONCLUSION
RDN has comparable safety to hand-assist LDN and offers additional benefits of lower postoperative opioid requirement and a shorter hospital LOS.
PubMed: 38777895
DOI: 10.1007/s00464-024-10925-5 -
Journal of Pain and Symptom Management May 2024
PubMed: 38777074
DOI: 10.1016/j.jpainsymman.2024.05.018 -
Energy & Fuels : An American Chemical... May 2024Pyrolysis of lignocellulosic biomass and waste plastics has been intensely studied in the last few decades to obtain renewable fuels and chemicals. Various pyrolysis...
Pyrolysis of lignocellulosic biomass and waste plastics has been intensely studied in the last few decades to obtain renewable fuels and chemicals. Various pyrolysis devices have been developed for use in a laboratory setting, operated either in batch or continuously at scales ranging from milligrams per hour to tenths of g per hour. We report here the design and operation of a novel staged free-fall (catalytic) pyrolysis unit and demonstrate that the concept works very well for the (catalytic) pyrolysis of pinewood sawdust, paper sludge, and polypropylene as representative feeds. The unit consists of a vertical tube with a pretreatment section, a pyrolysis section, a solid residue collection section, a gas-liquid separation/collection section, and a catalytic reaction section to optionally perform ex situ catalytic upgrading of the pyrolysis vapor. The sample is placed in a tube, which is transported by gravity through various sections of the unit. It allows for rapid testing with semicontinuous feeding (e.g., 50 g h) and the opportunity to perform reactions under an (inert) gas (e.g., N) at atmospheric as well as elevated pressure (e.g., 50 bar). Liquid yields for noncatalytic sawdust pyrolysis at optimized conditions (475 °C and atmospheric pressure) were 63 wt % on biomass intake. A lower yield of 51 wt % (on a biomass basis) was obtained for the noncatalytic pyrolysis of paper sludge, likely due to the presence of minerals (e.g., CaCO) in the feed. The possibility of using the unit for ex situ catalytic pyrolysis (pyrolysis at 475 °C and catalytic upgrading at 550 °C) was also successfully demonstrated using paper sludge as the feed and H-ZSM-5 as the catalyst (21 wt % catalyst on biomass). This resulted in a biphasic liquid product with 25.6 wt % of an aqueous phase and 11 wt % of an oil phase. The yield of benzene, toluene, and xylenes was 1.9 wt % (on a biomass basis). Finally, the concept was also proven for a representative polyolefin (polypropylene), both noncatalytic as well as in situ catalytic pyrolysis using H-ZSM-5 as the catalyst at 500 °C. The liquid yield of thermal, noncatalytic plastic pyrolysis was as high as 77 wt % on plastic intake, while in situ catalytic pyrolysis gave a combined 7.8 wt % yield of benzene, toluene, and xylenes on plastic intake.
PubMed: 38774064
DOI: 10.1021/acs.energyfuels.3c04733 -
Veterinary Research Communications May 2024Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug for horses. However, because of its gastrointestinal side effects, its administration requires...
Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug for horses. However, because of its gastrointestinal side effects, its administration requires careful attention in veterinary practice. Malondialdehyde (MDA) is a serum biomarker associated with increased damage to the equine gastrointestinal system. This study investigated the hematological effects and alterations in the gastrointestinal tract and assessed serum MDA concentrations following repeated oral PBZ administration at clinical doses. Fourteen horses were randomly divided into control and treatment groups. All horses in the treatment group were administered 4.4 milligrams per kilogram of body weight of PBZ syrup orally twice a day for 7 days, whereas the control group received syrup as a placebo. The development of gastrointestinal side effects was investigated using gastroscopy, abdominal ultrasound, and fecal pH; serum MDA concentrations were assessed using a commercially available enzyme-linked immunosorbent assay kit. Data were compared between PBZ-treated and control horses before and after the treatment period. The treatment group exhibited decreased albumin and total protein concentrations. Moreover, this group exhibited a higher thickness of the right dorsal colon wall (p = 0.03) and had higher scores for squamous gastric ulcers (p = 0.01). Fecal pH was lower in the treatment group than in the control group after PBZ administration (p < 0.01). Although MDA concentrations were higher in the treatment group after PBZ administration, they did not differ significantly from those of the control group. This study highlighted the changes in hematological and gastrointestinal lesions resulting from PBZ administration in horses at clinical doses, even without clinical signs. However, MDA may not be an optimal biomarker for the early detection of gastrointestinal damage due to PBZ treatment in horses.
PubMed: 38771448
DOI: 10.1007/s11259-024-10415-y -
Chemistry (Weinheim An Der Bergstrasse,... May 2024Ecklonialactones, Eiseniachlorides, and Egregiachlorides are synthesized in living organisms via the lipoxygenase-mediated oxidation of polyunsaturated fatty acids....
Ecklonialactones, Eiseniachlorides, and Egregiachlorides are synthesized in living organisms via the lipoxygenase-mediated oxidation of polyunsaturated fatty acids. Originally isolated and identified from brown seaweed (Ecklonia stolonifera, Eisenia bicyclis, and Egregia menziesii), and later replicated on milligram scale through chemical synthesis, the full biological activities of these compounds remain to be elucidated. To bridge this gap in knowledge, we propose a unified methodology to synthesize the 14-membered macrocyclic structures of Ecklonialactones, Eiseniachlorides and analogs using a versatile and convergent approach. This study delineates the synthesis of Ecklonialactone A, B, C, D, and Eiseniachlorides A and B, as well as ent-Ecklonialactone B, 16-epi-Ecklonialactone B and 12,13-diepi-Ecklonialactone B.
PubMed: 38770615
DOI: 10.1002/chem.202401632