Impact of Pharmacist Involvement on the Utility of a Gram-Negative Blood Culture Identification Panel on Antimicrobial Usage

Background: A rapid molecular diagnostic test (MDT) is a test used to identify several different species of gram-negative bacteria and their genetic resistance markers. However, the impact of rapid MDT has not been established when combined with pharmacist involvement. Objective: To determine the impact of pharmacy involvement on patient outcomes when using rapid MDT. The primary outcome is the time from gram stain result to the first dose of the targeted antibiotic. Methods: This is a single-center, quasi-experimental, 1-group pretest-posttest design study of patients with gram-negative bacteremia in a community hospital. Hospitalized patients 18 years or older were included if they had a gram-negative blood culture. Patients were excluded if they were discharged or expired prior to culture results. Outcomes were compared between patients prior to and after implementation of the automated MDT. This research was determined to be exempt from institutional review board oversight consistent with West Florida Healthcare and in accordance with institutional policy. Results: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy (pre-intervention group, n = 77, 44.8 ± 17.8 hours versus post-intervention group, n= 80, 4.4 ± 5.8 hours; P ≤.001). There was no significant difference found between secondary outcomes. Limitations included small sample size as well as inconsistent documentation. Conclusions: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy.     

Correlation of aqueous humor electrolytes with serum electrolytes in cataract patients

Purpose:To correlate the aqueous humor electrolytes with serum electrolytes in patients with cataract.Methods:In this study, 348 eyes of patients undergoing cataract surgery, who had presented between 1^st January 2019 and 30^th June 2020, were included. Serum electrolytes were obtained and 0.15 ml of aqueous humor was obtained during surgery using an insulin syringe via the side port incision. Mean and standard deviation was used to analyze all the categorical and continuous data including all the electrolytes levels. Pearson’s correlation of coefficient was used to analyze the comparison between serum and aqueous humor electrolytes. Student T-test was used to compare electrolyte values between the serum and aqueous humor.Results:We observed a significant correlation of the aqueous humor electrolytes with their serum counterparts. The coefficient of correlation is 0.155, 0.44, and 0.405 for Na+, K+, and Cl−, respectively. There is also a significant increase in the aqueous humor electrolytes as compared to the serum levels.Conclusion:A significant increase in electrolytes levels in the aqueous humor of cataract patients possibly could have a role in the etiology of cataract.     

Durable complete response to pembrolizumab in microsatellite stable colorectal cancer

IntroductionImmunotherapy by checkpoint inhibitors, i.e., anti-programmed death-1(PD-1) or anti-programmed death-ligand 1 (PD-L1) antibodies, has gained more attention managing solid tumors. Pembrolizumab (an anti-PD-1 antibody) in metastatic colorectal cancer (CRC) was approved in 2017 by the US FDA.Reason for the reportPembrolizumab is not effective in microsatellite stable, mismatch-repair-proficient (MSS-pMMR) molecular phenotype, which comprises most CRC patients. In this report, we present the first case of metastatic CRC with a dramatic and durable response to pembrolizumab despite being of MSS-pMMR phenotype.Case summaryA 34-year-old woman, presented seven years ago with T3N2bM0 colon cancer and an appendix carcinoid tumor. The last relapse with bilateral pulmonary metastases was refractory to all treatments. Although it seemed unresponsive to immunotherapy because of MSS molecular phenotype, due to the high expression level of PD-L1 (85%), we started treatment with pembrolizumab 200 mg every three weeks and continued for the overall 19 courses. Surprisingly, a rapid and complete response was observed that last until now, i.e., 17 months after discontinuation of pembrolizumab.OutcomeDespite non-promising results in the current clinical trials, MSS-pMMR colorectal cancer patients'' deprivation from immunotherapy seems not to be reasonable. There are ongoing clinical trials on checkpoint inhibitors either alone or in combination with other drugs. However, immunostaining for PD-L1 should be considered as a possible response predictor.Graphical abstractImmunotherapy either by cell-based approaches or by checkpoint inhibitors may revolutionize cancer treatmentPembrolizumab has been approved by the FDA in 2017 for colorectal cancer.However, MSS-pMMR molecular phenotype which comprises the majority of CRC patients, has not shown a good response to checkpoint inhibitors.We present a MSS-pMMR case with complete and durable response to pembrolizumabWe suggest immunostaining for PD-L1 as a possible response predictor to checkpoint inhibitors     

Structural,Electromagnetic and Microwave Properties of Magnetite Extracted from Mill Scale Waste via Conventional Ball Milling and Mechanical Alloying Techniques

This study presents the utilization of mill scale waste, which has attracted much attention due to its high content of magnetite (Fe₃O₄). This work focuses on the extraction of Fe₃O₄ from mill scale waste via magnetic separation, and ball milling was used to fabricate a microwave absorber. The extracted magnetic powder was ground-milled using two different techniques: (i) a conventional milling technique (CM) and (ii) mechanical alloying (MM) process. The Fe₃O₄/CM samples were prepared by a conventional milling process using steel pot ball milling, while the Fe₃O₄/MM samples were prepared using a high-energy ball milling (HEBM) method. The effect of milling time on the structural, phase composition, and electromagnetic properties were examined using X-ray diffraction (XRD) and a vector network analyzer (VNA). XRD confirmed the formation of magnetite after both the magnetic separation and milling processes. The results revealed that Fe₃O₄ exhibited excellent microwave absorption properties because of the synergistic characteristics of its dielectric and magnetic loss. The results showed that the Fe₃O₄/CM particle powder had a greater absorption power (reflection loss: <−10 dB) with 99.9% absorption, a minimum reflection loss of −30.83 dB, and an effective bandwidth of 2.30 GHz for 2 mm thick samples. The results revealed the Fe₃O₄/MM powders had higher absorption properties, including a higher RL of −20.59 dB and a broader bandwidth of 2.43 GHz at a matching thickness of only 1 mm. The higher microwave absorption performance was attributed to the better impedance matching property caused by the porous microstructure. Furthermore, the magnetite, Fe₃O₄ showed superior microwave absorption characteristics because of the lower value of permittivity, which resulted in better impedance matching. This study presents a low-cost approach method by reutilizing mill scale waste to fabricate a high purity crystalline Fe₃O₄ with the best potential for designing magnetic nano-sized based microwave absorbers.     

A new Amplatzer device to maintain patency of Fontan fenestrations and atrial septal defects.

This study evaluated use of Amplatzer fenestrated device to maintain patency of the Fontan fenestration and atrial septal defect. Fenestrations are routinely created in patients with lateral tunnel or extracardiac Fontan. Spontaneous closure of the fenestration can lead to Fontan circulation failure. Other patients without single-ventricle physiology may benefit from a small communication between the left and right atria for decompression if closure of the atrial septal defect leads to failure of a dysfunctional ventricle. Amplatzer septal occluder device was modified to create a fenestration through the disks. Three patients with modified Fontan and one patient with a large atrial septal defect underwent placement of the device by transcatheter technique. The device deployment was guided by transesophageal echocardiography. The procedure was successful in all patients. Contrast injection after placement revealed patent fenestration with free flow. Follow-up ranged from 3 months to 1 year. All devices were patent by transthoracic echocardiography. These preliminary results suggest that the Amplatzer fenestrated device can serve as a valuable tool in failing Fontan circulation and may help to avoid surgical intervention. More studies are needed to assess long-term efficacy of the device.     

Experimentally designed chromatographic method for the simultaneous analysis of dimenhydrinate,cinnarizine and their toxic impurities

Recently, experimental design has beaten the traditional optimization approach (one variable at a time) by providing better quality for chromatographic separation using minimal effort and resources. Benzophenone (BZP) and [1-(diphenylmethyl)piperazine] (DPP) were reported to be the most toxic impurities for dimenhydrinate (DMH) and cinnarizine (CIN), respectively. Additionally, there is no reported HPLC method for the simultaneous determination of DMH, CIN and their toxic impurities. A custom experimental design was adopted to estimate the optimum conditions that achieved the most acceptable resolution with adequate peak symmetry within the shortest run time. Desirability function was used to define the optimum chromatographic conditions and the optimum separation was achieved using XBridge® HPLC RP-C18 (4.6 × 250 mm, 5 μm), acetonitrile: 0.1% sodium lauryl sulphate (SLS) in water (90 : 10, v/v) as a mobile phase at flow rate 2 mL min⁻¹ and UV detection at 215 nm. Method validation was carried out according to ICH guidelines and linearity was achieved in the ranges of 2–25, 1–25, 1–12.5, and 1–12.5 μg mL⁻¹ for DMH, CIN, BZP and DPP, respectively. By application of the proposed method to the market dosage form, no interference from excipients was observed. Moreover, the greenness of the method was evaluated using the National Environmental Method Index (NEMI), Analytical Eco-Scale and Green Analytical Procedure Index (GAPI) metrics and the results revealed the green environmental impact of the developed method.

Experimentally designed HPLC method for simultaneous analysis of dimenhydrinate, cinnarizine and their toxic impurities.