Eco-friendly solvent bar microextraction based on a natural deep eutectic solvent and multivariate optimization for simultaneous determination of spironolactone and canrenone in urine and plasma samples.

Simultaneous measurement of spironolactone and canrenone in urine and plasma provides valuable insight into renal function, and therapeutic efficacy and can be utilized to identify potential health risks and ensure patient safety throughout treatment. By adopting greener methods to analyze these compounds, significant reductions in the environmental impact of such studies can be achieved. For this purpose, a sensitive and eco-friendly solvent bar microextraction method using natural deep eutectic solvent (NDE) followed by high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed to determine spironolactone and canrenone in urine and plasma samples. The extraction solvents were synthesized using NDE-based terpenoids containing menthol and camphor in various ratios. The extraction efficiency percentage (EE%) of both drugs was measured using response surface methodology (RSM) based on central composite design (CCD), and 29 extraction tests were conducted to determine the optimum conditions. Although all parameters were found to be significant, the extraction and elution times were critical for isolating the target analytes. Under optimized conditions, the linear dynamic ranges for spironolactone (SPI)/canrenone (CAN) were 11.7-104/13.1-104 µg L-1 and 21.7-104/24.6-104 µg L-1 in urine and plasma samples, respectively with R2 ≥ 0.993. The ranges of intra-/interprecision (relative standard deviation (RSD) %, n = 5) were 1.31-9.17%/ 2.4-11% with extraction recovery ≥ 88.6% for both drugs. The comparison findings with previously published methods confirmed that the developed NDE-solvent bar microextraction (SBME)-HPLC-DAD method for spironolactone and canrenone analysis displayed confident sensitivity, feasible operation, and simple analysis. Furthermore, the method's applicability and effectiveness were proven by successfully analyzing spironolactone and its metabolite canrenone in patients' urine and plasma samples.

Evaluation of the role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) time series as predictors of diagnosis and prognosis of hemotoxic snakebite.

BACKGROUND: This study aimed to assess the predictive value of NLR, PLR, and MPV time series for diagnosis and prognosis of hemotoxic snakebite envenomation. METHODS: This is a prospective study among snakebite patients admitted to the Poison Control Center of Ain Shams University Hospitals and Assiut University Hospitals from the beginning of July 2019 to the end of October 2021. Patients were classified according to their clinical severity into three groups: mild, moderate, and severe. RESULTS: The maximum incidence of snakebite was found in males (95%) from rural areas (80%); at lower limbs (70%); at night (51%); and during the autumn season (43.3%). The admission NLR and PLR can predict hemotoxic snakebite envenomation with an AUC of 0.940 and 0.569. The combination of NLR with PLR can develop a more predominant prediction of snakebite envenomation with an area under the curve (AUC) of 0.979. Furthermore, higher admission NLR and PLR levels are associated with prolonged hospital stays. CONCLUSION: While NLR and PLR levels may be helpful in the diagnosis of snakebite, MPV plays no part in the prognosis of snakebite patients. Serial NLR, PLR initially, at 24 hours, and predischarge can be used to evaluate the early treatment response.

Application of physical vapor deposition technology for practical utilization of nano-size copper oxide for lead uptake from solution: kinetics, equilibrium, and recycling studies.

For the first time, copper oxide-coated glass beads (CuO-GBs) were fabricated using physical vapor deposition (PVD) technology for sequestrating Pb2+ ions from solution is addressed. Compared to other coating procedures, PVD offered high-stability uniform CuO nano-layers attached with 3.0-mm glass beads. Heating of copper oxide-coated glass beads after deposition was rather necessary to achieve the best stability of the nano-adsorbent. Detection of nano-size copper oxide on the beads was made by FTIR (intense peak at 655 cm-1 for CuO bond stretching) and XRF (Cu peak at 8.0 keV). Scanning electron micrographs taken at high magnification power indicated the presence of CuO in nano-range deposited over glass beads. The maximum deposited amount of CuO on the beads was 1.1% and accomplished at the following operational conditions: internal pressure 10-5 mmHg, Ar flow rate 8.0 mL/min, voltage 84 V, pre-sputtering time 20 s, total sputtering time 10.0 min, and post-heating temperature 150 °C for 3 h. A univariate analysis indicated that the optimum Pb2+ uptake by CuO-GBs from solution was achieved at pH 7.0-8.0, 7 beads/50 mL, 120-min contact time, and 15-mg/L initial concentration. Kinetic data for Pb2+ uptake was best presented by a pseudo-second-order model with a relative prediction error of 3.2 and 5.1% for GBs and CuO-GBs, respectively. On the other hand, Pb2+ equilibrium isotherms at 25 °C were fairly presented by the Langmuir model, and the predicted saturation values were 5.48 and 15.69 mg/g for GBs and CuO-GBs, respectively. CuO and CuO-GBs had similar Pb2+ saturation values (~ 16 mg/g), although the latter demonstrated 4 times faster kinetic, thanks to fixation CuO on glass beads. Moreover, the chemical stability of copper oxide-coated glass beads was tested under different conditions. Recycling of copper oxide-coated glass beads was also investigated, and 90% of the surface was recovered using 0.01-M HNO3.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

Simultaneous determination of furosemide and carbamazepine in biological matrices by solvent bar microextraction combined with high-performance liquid chromatography-diode array detector and central composite design.

A sensitive and simple sample pretreatment method based on a two-phase solvent bar microextraction (SBME) technique coupled with HPLC-diode array detector (DAD) was developed for simultaneous extraction and determination of trace amounts of furosemide and carbamazepine in human urine and plasma samples. The significance of operational factors on carbamazepine and furosemide extraction efficiency % (EE%) was screened using full factorial design (FFD) while central composite design (CCD) was used to model the entire process. A quadratic model was found convenient to correlate the extraction EE% of selected drugs with dominant experimental factors. A Pareto chart was also used to examine the importance of factors on drugs' EE%. The analytical performance of the method in urine and plasma samples demonstrated good linearity (R2 ˃ 0.992) with detection limits ranging from 4.2 to 10.9 µg L-1 , and extraction recovery over 89.45% for both drugs in urine and plasma samples. A comparison against published methods was also performed and the results revealed that the developed method exhibits a confident sensitivity, feasible operation, and simple analysis for both drugs. Finally, the practicability of the validated SBME-HPLC-DAD method was demonstrated by successfully applying it to the analysis of furosemide and carbamazepine in real patient urine samples.

The Effect of a Multidisciplinary Spine Clinic on Time to Care in Patients with Chronic Back and/or Leg Pain: A Propensity Score-Matched Analysis.

Chronic back and leg pain are leading causes of disability worldwide. The purpose of this study was to compare the care in a unidisciplinary (USC) versus multidisciplinary (MSC) spine clinic, where patients are evaluated by different specialists during the same office visit. Adult patients presenting with a chief complaint of back and/or leg pain between June 2018 and July 2019 were assessed for eligibility. The main outcome measures included the first treatment recommendations, the time to treatment order, and the time to treatment occurrence. A 1:1 propensity score-matched analysis was performed on 874 patients (437 in each group). For all patients, the most common recommendation was physical therapy (41.4%), followed by injection (14.6%), and surgery (9.7%). Patients seen in the MSC were more likely to be recommended injection (p < 0.001) and less likely to be recommended surgery as first treatment (p = 0.001). They also had significantly shorter times to the injection order (log-rank test, p = 0.004) and the injection occurrence (log-rank test, p < 0.001). In this study, more efficient care for patients with back and/or leg pain was delivered in the MSC setting, which was evidenced by the shorter times to the injection order and occurrence. The impact of the MSC approach on patient satisfaction and health-related quality-of-life outcome measures warrants further investigation.

Use of Temporary Membrane-Covered Self-Expandable Metallic Stent - UVENTATM for Treatment of Recurrent Bulbar Urethral Stricture.

Introduction: Recurrent urethral stricture is a real challenge. Interestingly use of temporary double layered self-expanding nitinol urethral stent with polytetrafluoroethylene (PTFE) membrane coating (UventaTM, Taewoong Medical, South Korea) has been recently reported with promising short-term results in recurrent urethral stricture. However most of the reported studies are published as abstracts of either case reports or case series of miniscule numbers. The aim of our study is to evaluate the outcome of this temporary urethral stent in patients with recurrent urethral stricture after urethroplasty as well as after multiple visual internal urethrotomy. Materials and Methods: In this retrospective study, 22 patients had placement of double-layered self-expanding stent with PTFE membrane coating (Uventa, Taewoong Medical) for recurrent bulbar strictures. The present study included cases between 2017 and 2020. The stricture in each patient were evaluated with Uroflowmetry and ascending urethrography. The data of demographic and clinical characteristics included age, aetiology, location and length of stricture, along with maximum urinary flow rate (Qmax), number of previous interventions, and stent-related complications. Results: The overall clinical success was achieved in 13/22 (59.1%) of patients at a median follow-up of 17 months (range 2-44). The mean maximum urine flow rates were 7.07 ± 3.55mL/sec, 23.50 ± 10.41mL/sec, 21.41± 15.55 mL/sec, 14.88 ± 9.77 and 17.63 ± 12.28 mL/sec before, while stent in place, at 3 months, 6 months and 12 months after the procedure, respectively. Conclusion: In our study, the success rate of temporary urethral stent placement has remained at 59.1% at a median follow-up of 17 months. We conclude that further randomized controlled studies with long-term follow up are required to fully evaluate the outcome.

Survival From Ninety-Five Percent Total Body Surface Area Burn: A Case Report and Literature Review.

Burns can be devastating and result in unwanted consequences with prolonged length of hospital stay. The mortality rate increases as the total body surface area increases, so proper management of patients with extensive degrees of burns is crucial for their survival. We present the hospital course, management, and survival of a patient after he sustained a 95% total body surface area, second-degree burn from a gas flame. Furthermore, we present from the literature different cases of patients with large total body surface area burns and survived after being managed in burns specialty centers. Although large total body surface area burns can result in significant morbidity and mortality, early management and intervention by an expert surgical team can result in positive outcomes.

Solvent Bar Microextraction Combined with HPLC-DAD for Simultaneous Determination of Diuretics in Human Urine and Plasma Samples.

BACKGROUND: A simple and powerful microextraction procedure, the solvent bar microextraction (SBME), was used for the simultaneous determination of two diuretics, furosemide and spironolactone in human urine and plasma samples, using high-performance liquid chromatography coupled with diode array detection (HPLC-DAD). METHODS: The appropriate amount (2 µL) of 1-octanol as an organic solvent confined within 2.5 cm of a porous hollow fiber micro-tube, sealed at both ends was used for this procedure. The conditions for the SBME were optimized in water and the analytical performance was examined in spiked human urine and plasma samples. RESULTS: The optimized method exhibited good linearity (R2> 0.997) over the studied range of higher than 33 to 104µg L-1 for furosemide and spironolactone in urine and plasma samples, illustrating a satisfactory precision level with RSD values between 2.1% and 9.1%. DISCUSSION: The values of the limits of detection were found to be in the range of 6.39 to 9.67µg L-1, and extraction recovery ˃ 58.8% for both diuretics in urine and plasma samples. The applicability and effectiveness of the proposed method for the determination of furosemide and spironolactone in patient urine samples were tested. CONCLUSION: In comparison with reference methods, the attained results demonstrated that SBME combined with HPLC-DAD was proved to be simple, inexpensive, and promising analytical technology for the simultaneous determination of furosemide and spironolactone in urine and plasma samples.

Development of Dioctyl Phthalate@Fe3O4 Nanocomposite Reinforced Hollow Fiber Solid/ Liquid Phase Microextraction Followed by HPLC-DAD for the Determination of Atorvastatin and Gemfibrozil in Human Urine.

BACKGROUND: The desirable levels of lipids, especially in patients with coronary artery disease, might not be achievable with a single lipid-lowering drug; thus, combination therapy using atorvastatin and gemfibrozil seems to be a promising approach. However, the potential for drugdrug interaction needs to be taken into consideration, and the combination (atorvastatin and gemfibrozil) is recommended only when other options for reducing lipids have been exhausted. OBJECTIVES: Many studies are conducted for the determination of atorvastatin or gemfibrozil in biological fluids and tablets; however, the simultaneous determination of the two drugs in complex biological matrices is limited. Consequently, the development of a sensitive method for simultaneous determination of atorvastatin and gemfibrozil in urine samples is urgently needed to make sure that the doses of both medications are given to patients correctly to prevent the risk of side effects outcomes associated with the adverse drug-drug interaction. METHODS: A synthesized nanocomposite sorbent, dioctyl phthalate coated on the surface of magnetite (DOP@Fe3O4), was reinforced and immobilized into the pores of 2.5 cm segment hollow fiber microtube via ultrasonication, and the lumen of the microtube was filled with 1-octanol as an organic solvent with two ends heat-sealed. The prepared (DOP@Fe3O4-HF-SLPME) device was directly immersed into 10 mL of a sample solution containing atorvastatin and gemfibrozil with agitation. Subsequently, the microextraction device was transferred to HPLC-micro-vial containing an appropriate solvent, and the selected analytes were desorbed under ultrasonication prior to HPLCDAD analysis. The main factors influencing the adsorption and desorption process of the selected drugs have been optimized. RESULTS: The DOP@Fe3O4-HF-SLPME combined with the HPLC-DAD method was analytically evaluated for the simultaneous determination of atorvastatin and gemfibrozil in human urine samples using the optimized conditions. In spiked urine samples, the method showed a good linearity R2˃ 0.998, RSD from 1.41- 5.33%, and the limits of detection/ quantification (LOD/ LOQ) were 0.11/ 0.36 and 0.73/ 2.42 µg L-1 for atorvastatin and gemfibrozil, respectively. The enrichment factors of atorvastatin and gemfibrozil were 83.4 and 101.2, with extraction recoveries of 80.9% and 99.0%, respectively. The developed method demonstrated comparable results against referenced methods and a satisfactory result for determining the selected drugs in the patient's urine samples. CONCLUSION: The DOP@Fe3O4-HF-SLPME followed by HPLC-DAD was proved to be an efficient, sensitive, and cost-effective biopharmaceutical analysis method for trace levels of atorvastatin and gemfibrozil in the biological fluid matrix.

QSAR-guided pharmacophoric modeling reveals important structural requirements for Polo kinase 1 (Plk1) inhibitors.

Targeting Polo-like kinase 1 (Plk1) by molecular inhibitors is being a promising approach for tumor therapy. Nevertheless, insufficient methodical analyses have been done to characterize the interactions inside the Plk1 binding pocket. In this study, an extensive combined ligand and structure-based drug design workflow was conducted to data-mine the structural requirements for Plk1 inhibition. Consequently, the binding modes of 368 previously known Plk1 inhibitors were investigated by pharmacophore generation technique. The resulted pharmacophores were engaged in the context of Genetic function algorithm (GFA) and Multiple linear regression (MLR) analyses to search for a prognostic QSAR model. The most successful QSAR model was with statistical criteria of (r2277 = 0.76, r2adj = 0.76, r2pred = 0.75, Q2 = 0.73). Our QSAR-selected pharmacophores were validated by Receiver Operating Characteristic (ROC) curve analysis. Later on, the best QSAR model and its associated pharmacophoric hypotheses (HypoB-T4-5, HypoI-T2-7, HypoD-T4-3, and HypoC-T3-3) were used to identify new Plk1 inhibitory hits retrieved from the National Cancer Institute (NCI) database. The most potent hits exhibited experimental anti-Plk1 IC50 of 1.49, 3.79. 5.26 and 6.35 µM. Noticeably, our hits, were found to interact with the Plk1 kinase domain through some important amino acid residues namely, Cys67, Lys82, Cys133, Phe183, and Asp194.

Clinical and Financial Implications of 2 Treatment Strategies for Donor-derived Hepatitis C Infections.

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays. METHODS: At our institution, 2 strategies for providing DAA therapy to HCV- recipients of HCV+ transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies. RESULTS: One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2-7] vs 10 [IQR, 8-13]; P < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12-29] vs 36 [IQR, 30-47]; P < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients. CONCLUSIONS: Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group.

Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment.

BACKGROUND: There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. METHODS: This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6-9 months) and late follow-up (9-16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. RESULTS: The overall portomesenteric thrombosis burden improved in eight (72%) TIPS patients, three (27%) anticoagulated patients, and two (10%) untreated patients at early follow-up (p = 0.001) and in seven (78%) TIPS patients, two (29%) anticoagulated patients, and three (17%) untreated patients in late follow-up (p = 0.007). No bleeding complications attributable to anticoagulation were observed. CONCLUSION: TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.

Mechanisms of structure formation underlying the creaming reaction in a processed cheese model system as revealed by light and transmission electron microscopy.

The "creaming reaction," a general thickening of the molten cheese mass during the manufacture of processed cheese, which is often seen to occur in a stepwise fashion, affects the viscosity and texture of the finished product. Thus, this phenomenon is of critical importance for the processed cheese industry, yet mechanisms underlying the structure formation in this surprisingly complex and dynamic food system are only poorly understood. Using a model system consisting of micellar casein concentrate, vegetable oil, water, and a mixture of melting salts, we followed the characteristic viscosity profile with its primary and secondary increase over time. A rheometer equipped with a custom-made cup geometry was used, which served as a mini-reaction vessel to simulate the conditions during the manufacture of processed cheese. The mixture was subjected to constant heat (90°C) and stirring (7.93 rpm), comparable to processed cheese cooking, for up to 410 min. At specific time points, samples were taken, and the micro- and ultrastructure was investigated with light and transmission electron microscopy. Results from our extensive study uncovered the following key steps: (1) a decrease in fat globule size with concomitant increase in the number of fat globules, which were also more evenly distributed; (2) a progressive separation of the casein matrix into fibrillogenic and nonfibrillogenic fractions; (3) formation of fibrils and their higher-order structuring followed by their partial degradation; and (4) increasing interactions of the fibrils with the fat globule surface leading to a higher degree of emulsification. Of these different observations, results indicate that after the caseins dissociated under the influence of the melting salts, protein-protein interactions were the primary driver of the structure formation and thus contributed to the initial viscosity increase. Fat globules were involved in the structure formation at later time points. Therefore, fat-protein interactions in addition to continued protein-protein interactions were assumed to contribute to the secondary viscosity increase. An updated processed cheese creaming model is presented. The use of the term "texturization" instead of "creaming" is proposed.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Pancreas transplantation from hepatitis C viremic donors to uninfected recipients.

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.

Hepatic Artery Microvascular Anastomosis in Liver Transplantation: A Systematic Review of the Literature.

BACKGROUND: The operating microscope is used in many centers for microvascular hepatic arterial reconstruction in living as well as deceased donor liver transplantation in adult and pediatric recipients. To date, a systematic review of the literature examining this topic is lacking. METHODS: This systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three different electronic databases (PubMed, Embase OVID, and Cochrane CENTRAL) were queried. RESULTS: A total of 34 studies were included. The rate of hepatic artery thrombosis (HAT) in noncomparative studies (28) ranged from 0% to 10%, with 8 studies reporting patient deaths resulting from HAT. Within comparative studies, the rate of HAT in patients who underwent arterial reconstruction using the operating microscope ranged from 0% to 5.3%, whereas the rate of HAT in patients who underwent arterial reconstruction using loupe magnification ranged from 0% up to 28.6%, and 2 studies reported patient deaths resulting from HAT. Two comparative studies did not find statistically significant differences between the 2 groups. CONCLUSIONS: Our comprehensive systematic review of the literature seems to suggest that overall, rates of HAT may be lower when the operating microscope is used for hepatic arterial reconstruction in liver transplantation. However, matched comparisons are lacking and surgical teams need to be mindful of the learning curve associated with the use of the operating microscope as compared with loupe magnification, as well as the logistical and time constraints associated with setup of the operating microscope.

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS: The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS: Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

Does Salt and Mineral Content of Dead Sea Mud Affect Its Irritation Potential: A Laser Doppler Flowmetry Study.

The aim of the study was to investigate skin microcirculation, flux, and temperature changes induced by the application of Dead Sea mud (DSM) formulas with different mud salts and mineral contents using laser Doppler flowmetry. Instrumental analysis of eight over-the-shelf DSM products and four different samples of nonformulated Dead Sea mud were carried out to determine their contents of various salts and elements, including K, Na, Cl, Mg, Mn, Ca, SO3, SiO2, Al, Br, Fe, Hg, Cr, Co, Ni, Cu, Zn, As, Cd, Pb, and Sr. Three DSM samples with different levels of salts were then used to study the influence of salt content on skin irritation potential using laser Doppler flowmetry. Fifteen healthy nonsmoking females aged 18-45 years participated in the study. Subjects were randomly assigned to either "Salted" mud group (n = 5), "As is" mud group (n = 5), or "Over-the-Shelf" mud group (n = 5). Five circular areas were marked on the ventral aspect of each forearm. One forearm was assigned randomly for mud treatment and the other forearm was untreated. Ten milliliters of mud was applied on the assigned forearm and left for 30 minutes. Two reading protocols were designed and used to study the effects of tested type of mud on skin blood flux and temperature during mud application (protocol 2) as well as before and after mud removal (protocol 1). All types of tested mud were not associated with a significant measurable elevation in skin temperature and skin blood flow. All types of Dead Sea mud did not cause detectable microcirculatory and skin temperature changes regardless of their different mineral and salts contents.

Progressive ultrastructural changes in the casein matrix during the ripening of inadequately acidified feta cheese.

This study investigated the ultrastructural changes underlying the undesired softening of insufficiently acidified feta cheese during cold storage. Experimental feta cheeses with a range of pH values before brining were manufactured by allowing the cheese blocks to ferment overnight at 3 temperatures (35, 20, and 3°C), which resulted in pH values of 4.80, 4.88, and 5.17, respectively. Cheese blocks were stored in pH-adjusted whey brine solutions for up to 120 d, at which point significant decreases in the cheese firmness were confirmed with compression and shear tests. Samples for transmission electron microscopy were taken during the make procedure, after overnight fermentation, and after 7 and 90 d of cold storage. Increasing the initial pH from 4.80 to 5.17 resulted in a fundamentally different ultrastructure at d 90, with the protein matrix as the continuous phase having markedly decreased density compared with the typically open porous and discontinuous protein matrix of high density in the low-pH control feta cheese. Ultrastructural changes were progressive, and the first signs were evident after only 20 h (the overnight fermentation), when fine, proteinaceous material dissociated from the edges of the casein strands into the serum phase. By d 7, the serum phase was completely filled with the loosely aggregated casein closely surrounding the spheroidal fat globules. A further breakdown of the protein matrix was observed after 90 d, with the complete loss of open porous network structure. Image analysis quantitatively confirmed the progressive and significant decrease in density of the protein matrix. In summary, this is the first study to provide a comprehensive and in-depth view of the progressive and most likely irreversible ultrastructural changes that lead to this textural defect.