Acyclovir dosing in herpes encephalitis: A scoping review.

BACKGROUND: Herpes encephalitis, a rare yet potentially fatal viral infection, is treated exclusively with acyclovir, the sole antiviral medication used for this condition. Acyclovir recommended dose is 10 mg/kg/dose intravenous every 8 hours; however, it is unclear what body weight should be utilized in obese patients. Using the ideal body weight may result in subtherapeutic ineffective concentrations, while utilizing the actual body weight might result in acyclovir induced adverse effects, either nephrotoxicity or neurotoxicity or both. OBJECTIVE: The objective of this scoping review is to explore existing evidence regarding acyclovir dosing for obese patients afflicted with herpes encephalitis. METHODS: MEDLINE, EMBASE, Scopus, Web of Science, and CINAHL databases were searched on 26 May 2023, with no language restrictions. Two independent reviewers utilized the Covidence software to carry out the screening and selection of the articles. A total of 22 articles were included in the current review. RESULTS: The prevalence of acyclovir-associated nephrotoxicity ranged from 13% to 21%, while the prevalence of neurotoxicity was not clearly defined. However, there is lack of evidence regarding what may arise from subtherapeutic concentrations. An approach has been suggested to help clinicians to give the most appropriate acyclovir dose to herpes encephalitis patients. Patients with normal kidney function could receive the normal doses based on actual weight if normal weight and based on adjusted body weight if obese. On the other hand, if the patients are experiencing augmented renal clearance, they could receive up to the maximum recommended doses. CONCLUSION: Overall, there is a lack of consistency on which body weight to use to calculate acyclovir dose in obese patients. So it is recommended that further studies compare the concentration of intravenous acyclovir between obese and nonobese patients and relating the resultant concentration with patient outcomes.

Drug-disease interaction: Clinical consequences of inflammation on drugs action and disposition.

Inflammation is a culprit in many conditions affecting millions of people worldwide. A plethora of studies has revealed that inflammation and inflammatory mediators such as cytokines and chemokines are associated with altered expression and activity of various proteins such as those involved in drug metabolism, specifically cytochrome P450 enzymes (CYPs). Emphasis of most available reports is on the inflammation-induced downregulation of CYPs, subsequently an increase in their substrate concentrations, and the link between the condition and the inflammatory mediators such as interleukin-6 and tumor necrosis factor alpha. However, reports also suggest that inflammation influences expression and/or activity of other proteins such as those involved in the drug-receptor interaction. These multifaced involvements render the clinical consequence of the inflammation unexpected. Such changes are shown in many inflammatory conditions including rheumatoid arthritis, Crohn's disease, acute respiratory illnesses as well as natural processes such as aging, among others. For example, some commonly used cardiovascular drugs lose their efficacy when patients get afflicted with inflammatory conditions such as rheumatoid arthritis and Crohn's disease. Interestingly, this is despite increased concentration subsequent to reduced clearance. The observation is attributed to a simultaneous reduction in the expression of target receptor proteins such as the calcium and potassium channel and ß-adrenergic receptor as well as the metabolic enzymes. This narrative review summarizes the current understanding and clinical implications of the inflammatory effects on both CYPs and drug-receptor target proteins.

Needlescopic Primary Paediatric Inguinal Hernia Repair By Hernia Sac Disconnection And Peritoneal Closure.

Objectives: To evaluate the short-term outcome of the needlescopic hernia sac disconnection and peritoneal closure in the treatment of primary paediatric inguinal hernia. Method: The prospective study was conducted from April 2019 to April 2021 at the Paediatric Surgery Unit of the General Surgery Department at Kafrelsheikh University Hospital, Egypt, and comprised patients aged 6-144 months having uncomplicated paediatric inguinal hernia. The patients were subjected to needlescopic hernia sac disconnection and peritoneal closure. The follow-up protocol included outpatient visits at 1 week and at 1, 3 and 6 months postoperatively to check for recurrence and other complications. Data was analysed using SPSS 24. RESULTS: Of the 50 patients with 65 hernias, 37(74%) were males and 13(26%) were females. The overall mean age was 50.78± 31.74 months (range: 9-120 months) and mean internal ring diameter was 11.90±3.518mm (range: 8-20mm). The mean operative time was 20.66±2.94 minutesfor unilateral cases and 30.60±5.15 minutesfor bilateral cases. There was no conversion to conventional laparoscopy or to open herniotomy. All cases were followed up for a mean of 11.56± 3.99 months. No recurrence was encountered in any case and the scars were invisible in 40(80%) cases 6 months postoperatively. CONCLUSIONS: Needlescopic hernia sac disconnection and peritoneal closure wasfound to be feasible,safe and effective in the treatment of primary paediatric inguinal hernia.

A Survey of Canadian Pharmacists' Knowledge and Comfort in the Management of Epilepsy and Antiepileptic Drugs.

Background: As antiepileptic drugs (AED) remain the mainstay of epilepsy management, pharmacists have the potential to play an integral role in the management. Objective: The goal of our study was to characterize Canadian pharmacists' knowledge and comfort in managing epilepsy and AED and identify areas of need for the development of support tools. Methods: An electronic survey was designed and distributed to Canadian pharmacists through professional organizations. The survey consisted of 4 sections, including demographics, knowledge, comfort, and needs assessment around epilepsy management. Results: A total of 605 complete responses were included. Nearly two-thirds of the participants were females (61.6%) and most reported more than 10 years of practice experience (61.6%). For comfort, a majority of the participants responded agree or strongly agree to the statement inquiring about the comfort in checking prescriptions, answering questions about drug interactions, and counseling on AED. Conversely, more than 50% of the participants selected disagree or strongly disagree when asked about their comfort regarding interpreting therapeutic drug monitoring and assisting patients withdraw from AED. For the knowledge section, the overall average score was 57.6% ± 19.1%. Hospital practice, recent graduation, and neurology experience were independent predictors of high scores. Many participants indicated a need for tools addressing newer AED and monitoring of therapy. Conclusion: Although Canadian pharmacists displayed knowledge and comfort in certain aspects of epilepsy management, some clear knowledge and comfort gaps are prevalent. These findings indicate a need for the development of epilepsy educational support tools.

Enantioselective assay of nimodipine in human plasma using liquid chromatography-tandem mass spectrometry.

Nimodipine is a dihydropyridine calcium channel blocker that exhibits higher selectivity toward cerebral blood vessels compared with other members of the same class. It has been shown to improve outcomes and prevent delayed cerebral ischemia in the setting of aneurysmal subarachnoid hemorrhage, a life-threatening brain bleed. Nimodipine is a chiral compound and it is marketed as a racemic mixture of (+)-R and (-)-S enantiomers. (-)-S-Nimodipine is approximately twice as potent a vasorelaxant as the racemic mixture and is more rapidly eliminated than the (+)-R counterpart following oral dosing. Few analytical procedures have been reported to determine nimodipine enantiomers in biological samples; however, the reported methods were time-consuming, involved multistep extraction procedures and required large sample volumes. Herein, we present an LC-MS/MS method for quantifying nimodipine enantiomers in human plasma using a small sample volume (0.3 ml) and a single liquid-liquid extraction step. The peak area ratios were linear over the tested concentration ranges (1.5-75 ng/ml) with r2 > 0.99. The intraday CV and percentage error were within ±14% while the interday values were within ±13%, making this analytical method feasible for research purposes and pharmacokinetic studies.

Drug Dosing in Patients Undergoing Therapeutic Plasma Exchange.

Therapeutic plasma exchange (TPE) is an extracorporeal process in which a large volume of whole blood is taken from the patient's vein. Plasma is then separated from the other cellular components of the blood and discarded while the remaining blood components may then be returned to the patient. Replacement fluids such as albumin or fresh-frozen plasma may or may not be used. TPE has been used clinically for the removal of pathologic targets in the plasma in a variety of conditions, such as pathogenic antibodies in autoimmune disorders. TPE is becoming more common in the neurointensive care space as autoimmunity has been shown to play an etiological role in many acute neurological disorders. It is important to note that not only does TPE removes pathologic elements from the plasma, but may also remove drugs, which may be an intended or unintended consequence. The objective of the current review is to provide an up-to-date summary of the available evidence pertaining to drug removal via TPE and provide relevant clinical suggestions where applicable. This review also aims to provide an easy-to-follow clinical tool in order to determine the possibility of a drug removal via TPE given the procedure-specific and pharmacokinetic drug properties.

Stress-Related Gastrointestinal Bleeding in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Observational Study.

BACKGROUND/OBJECTIVE: Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB. METHODS: This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) < 48 h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU), and hospital LOS were collected for the first 21 days of admission or until hospital discharge, whichever came first. Descriptive statistics were used to analyze the data. A multivariate logistic regression modeling was utilized to examine the relationship between specific risk factors and the incidence of clinically important GI bleeding in patients with aSAH. RESULTS: A total of 627 patients were included. The overall incidence of clinically important GI bleeding was 4.9%. Of the patients with clinically important GI bleeding, 19 (61%) received pharmacologic prophylaxis prior to evidence of GI bleeding, while 12 (39%) were not on pharmacologic prophylaxis at the onset of GI bleeding. Patients who received an acid suppressant agent were less likely to experience GI bleeding than patients who did not receive pharmacologic prophylaxis prior to evidence of bleeding (OR 0.39, 95% CI 0.18-0.83). The multivariate regression analysis identified any instance of elevated intracranial pressure, creatinine clearance < 60 ml/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79). CONCLUSIONS: Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation (> 48 h), creatinine clearance < 60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

Inflammatory Pathways Following Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is an acute cerebrovascular emergency resulting from the rupture of a brain aneurysm. Despite only accounting for 5% of all strokes, SAH imposes a significant health burden on society due to its relatively young age at onset. Those who survive the initial bleed are often afflicted with severe disabilities thought to result from delayed cerebral ischemia (DCI). Consequently, elucidating the underlying mechanistic pathways implicated in DCI development following SAH remains a priority. Neuroinflammation has recently been implicated as a promising new theory for the development of SAH complications. However, despite this interest, clinical trials have failed to provide consistent evidence for the use of anti-inflammatory agents in SAH patients. This may be explained by the complexity of SAH as a plethora of inflammatory pathways have been shown to be activated in the disease. By determining how these pathways may overlap and interact, we hope to better understand the developmental processes of SAH complications and how to prevent them. The goal of this review is to provide insight into the available evidence regarding the molecular pathways involved in the development of inflammation following SAH and how SAH complications may arise as a result of these inflammatory pathways.

The Impact of Nimodipine Administration through Feeding Tube on Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: Delayed cerebral ischemia (DCI) and vasospasm are the main challenges contributing to unfavorable outcomes following aneurysmal subarachnoid hemorrhage. Nimodipine has been shown to decrease the incidence of delayed cerebral ischemia and improve outcomes. In patients who are unable to swallow, nimodipine tablets are crushed and administered through enteral feeding tubes. However, it is not clear whether this may result in reduced clinical effectiveness. The aims of the study were to investigate the impact of nimodipine administration through enteral feeding tubes, in the first 7 days and over the 21-days period on patient outcomes. METHODS: A retrospective chart review of subarachnoid hemorrhage patients admitted at the University of Alberta Hospital, Edmonton, Alberta, Canada was carried out. Logistic regression modelling was utilized to identify predictors of vasospasm and delayed cerebral ischemia. Main outcome measures were angiographic evidence of moderate to severe vasospasm, development of delayed cerebral ischemia and hospital mortality. RESULTS: 85 patients were included. Following adjustment for disease severity, nimodipine administration technique was associated with vasospasm in the first 7 days of patient admission where patients receiving nimodipine via enteral feeding tubes had increased odds of vasospasm compared to those administered it as whole tablets (OR 8.9, 95% CI 1.1-73.1, p value 0.042). When analyzed over the 21-day period, nimodipine administration by feeding tube was associated with increased odds of DCI compared to whole tablets (OR 38.1, 95% CI 1.4-1067.9, p value 0.032). CONCLUSIONS: Our findings suggest that nimodipine administration via enteral feeding tubes may be associated with vasospasm and DCI in subarachnoid hemorrhage patients secondary to reduced exposure. Prospective studies are needed to confirm such association and alternate methods of administration should be explored to ensure patients are getting the benefits of nimodipine.

Critical Care Management of Status Epilepticus at a Tertiary Care University Hospital.

BACKGROUND: Status epilepticus (SE) is a neurological emergency associated with significant morbidity and mortality. The objective of this study was to review the critical care management of patients with SE focusing on antiepileptic drugs (AEDs) as well as to determine the optimal dosing strategies of phenytoin (PHT) and predictors of its effectiveness. METHODS: A retrospective chart review of adult patients with SE admitted to the University of Alberta Hospital, Canada, was conducted. RESULTS: Fifty-six admissions were included. Benzodiazepines (BDZs) were initially given in 89% of our patients. Following BDZs, PHT and levetiracetam were the most commonly initiated AEDs as first- and second-line agents and were deemed effective in 30/44 and 5/11 patients, respectively. Patients who received a PHT loading dose (LD) of 1000 mg were less likely to reach target levels compared with a weight-based LD ≥15 mg/kg (29% vs. 60%). Likewise, patients who received a maintenance dose (MD) of 300 mg/day were less likely to reach target compared with 400 mg/day or >5 mg/kg per day; however, this did not reach statistical significance. Three variables were found to be associated with PHT effectiveness: tonic-clonic SE (OR 5.01, 95% CI 1.02-24.7, p = 0.048), history of seizures and BMI <30 kg/m2 (OR 0.16, 95% CI 0.03-1.07, p = 0.059). CONCLUSIONS: Further studies of the predictors of PHT effectiveness, specifically obesity, are necessary to help individualize care. Finally, we suggest that PHT should be loaded according to the guidelines as 20 mg/kg followed by an MD of at least 400 mg/day or >5 mg/kg per day.

Gérer les soins intensifs prodigués à des patients atteints de l'état de mal épileptique qui ont été admis dans un hôpital universitaire de niveau tertiaire Contexte: L'état de mal épileptique (status epilepticus) constitue une urgence neurologique associée à des taux notablement élevés de morbidité et de mortalité. L'objectif de cette étude a été d'examiner la gestion des soins intensifs prodigués à des patients atteints de cette complication en mettant l'accent sur des médicaments antiépileptiques. Nous avons aussi cherché à déterminer des stratégies optimales de posologie pour la phénytoïne et des indicateurs de son efficacité. Méthodes: Nous avons effectué un examen rétrospectif des dossiers de patients adultes atteints de l'état de mal épileptique qui ont été admis au University of Alberta Hospital (Canada). Résultats: Au total, cinquante-six patients admis ont été inclus dans cette étude. Soulignons que des benzodiazépines (BZD) ont été donnés à 89 % de ces patients dès leur admission. Une fois ces médicaments administrés, la phénytoïne et le lévétiracétam se sont avérés les antiépileptiques les plus couramment utilisés comme traitements de première intention et de seconde intention. À cet égard, la phénytoïne a été jugée efficace chez 30 patients sur 44 tandis que le lévétiracétam l'a été chez 5 patients sur 11. Les patients à qui l'on avait administré une dose d'attaque (loading dose) de 1000 mg de phénytoïne étaient moins susceptibles d'atteindre des cibles de traitement en comparaison avec une dose d'attaque fondée sur le poids (≥ 15 mg/kg ; 29 % contre 60 %). De même, les patients ayant reçu une dose de maintien de 300 mg par jour étaient moins susceptibles d'atteindre des cibles de traitement en comparaison avec une dose de 400 mg par jour ou > 5 mg/kg par jour. Cela dit, ces résultats n'ont pas revêtu de signification statistique valable. Il a été constaté par ailleurs que trois variables pouvaient être associées à l'efficacité de la phénytoïne: une manifestation tonico-clonique de l'état de mal épileptique (rapport des cotes 5,01; IC 95 % 1,02­24,7; p = 0,048), des antécédents de crises convulsives et un IMC < 30 kg/m2 (rapport de cotes 0,16; IC 95 % 0,03­1,07; p = 0,059). Conclusions: Des études plus poussées portant sur les prédicteurs de l'efficacité de la phénytoïne, l'obésité en particulier, demeurent nécessaires pour contribuer à individualiser les soins prodigués. Enfin, nous suggérons aussi que les doses d'attaque de phénytoïne devraient respecter une ligne directrice de 20 mg/kg et être suivies par des doses de maintien d'au moins 400 mg par jour ou >5 mg/kg par jour.

Therapeutic Drug Monitoring of Levetiracetam in Select Populations.

PURPOSE: Levetiracetam (LEV) is a broad spectrum antiepileptic drug (AED) that has a more favorable side effect profile compared to older AEDs. Therapeutic drug monitoring (TDM) of LEV is generally unnecessary given its linear and predictable dose-serum concentration relationship, lack of drug-drug interactions, and broad therapeutic window. However, there is growing evidence showing that alteration of LEV pharmacokinetics (PK) may occur in special populations calling for the need for TDM. The purpose of this review was to summarize current literature surrounding altered LEV PK in special patient populations and determine if there is a need for levetiracetam TDM. METHODS: A literature search of MEDLINE (1946 - November 2017) database of available evidence pertaining to altered LEV PK in humans was conducted. RESULTS: A total of 51 articles were found.  There has not been a positive correlation shown between LEV levels and efficacy or toxicity. Variable LEV levels are reported in the literature with respect to adverse effects, seizures and efficacy occurring below, within and above the supposed reference ranges. Age is a major contributor to altered pharmacokinetics of LEV as shown in elderly patients and pediatric patients. Compared to adults, clearance of LEV has been shown to be decreased by almost half in patients over 65 and increased by 30-40% in pediatric patients. LEV pharmacokinetics varied further when data from its use in neonates was explored. LEV clearance declined in a linear fashion with declining estimates of creatinine clearance but was variable in patients with end-stage renal failure or those requiring renal replacement therapy. In patients who were critically ill, LEV clearance may be augmented and these patients may require higher doses of medications to maintain drug levels. In patients who are pregnant, LEV levels are likely to decline as pregnancy progresses due to changes in glomerular filtration rate and remain variable in the post-partum period. CONCLUSION: Routine TDM of levetiracetam is not recommended for all populations, however, it may be beneficial to maintain an individual therapeutic range in patients where the PK of LEV may be altered, such as in patients who are critically ill patients, pregnant, pediatrics or elderly.

Seizures and Choice of Antiepileptic Drugs Following Subarachnoid Hemorrhage: A Review.

Seizures are important complications following a subarachnoid hemorrhage (SAH). The evidence for the use of antiepileptic drugs (AEDs) in treatment and prevention of those seizures is conflicting. The purpose of this review is to provide an up-to-date evidence summary of the incidence and outcomes of seizures following an SAH as well as the use of different AEDs post-SAH in order to evaluate the need for seizure prophylaxis, the choice of AEDs, and their dosing considerations in SAH patients. A literature search of PubMed, Medline, Embase, and the Cochrane Library was performed. A total of 37 studies were reviewed, mostly observational. Definitions of seizures in temporal relation to initial hemorrhage were variable. Similarly, the rates of seizures varied in the literature, ranging from 0 to 31%. Given the reported adverse outcomes associated with AED usage, seizure prophylaxis is not warranted. Levetiracetam appears to be better tolerated than phenytoin in SAH patients, though further research is needed. Higher initial dosing of levetiracetam might be required due to its enhanced clearance in SAH patients. In conclusion, there is a lack of quality evidence to definitively recommend the use of one AED over another. Further prospective research comparing the use of different AEDs in patients with an SAH is needed.

Risk of Hyponatremia in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Exogenous Vasopressin Infusion.

BACKGROUND: Vasopressin is one of the vasopressors used to augment blood pressure in subarachnoid hemorrhage (SAH) patients with clinically significant vasospasm. The purpose of the present study was to determine whether the administration of vasopressin to a population of SAH patients was an independent predictor of developing hyponatremia. METHODS: A retrospective review on the health records of 106 patients admitted to the University of Alberta Hospital Neurosciences ICU, Edmonton AB, Canada, with SAH from June 2013 to December 2015 was conducted. Serum sodium changes in patients receiving vasoactive drugs were compared. In addition, independent predictors for hyponatremia (Na < 135 mmol/L) were determined using a multivariate logistic regression model. RESULTS: Patients treated with vasopressin in addition to other vasoactive drugs had significantly higher sodium changes compared to those treated with other vasoactive drugs (-4.7 ± 6 vs -0.1 ± 2.4 mmol/L, respectively, p value 0.001). Hyponatremia occurred in 14 patients (70 %) treated with vasopressin, 10 patients (44 %) treated with vasoactive drugs other than vasopressin (p value 0.081), and 24 patients (38 %) who did not receive any vasoactive drug (p value 0.013). In multivariate logistic regression analysis, when adjusting for disease severity, age, sex, aneurysm location, and treatment, vasopressin was associated with hyponatremia (OR 3.58, 95 % CI, 1.02-12.5, p value 0.046). CONCLUSIONS: The results of the present study suggest that hyponatremia may be more common in SAH patients treated with exogenous vasopressin compared to those who did not receive it. Serum sodium should be monitored closely when vasopressin is being used in the SAH population. Further studies are needed to confirm the effect of exogenous vasopressin on serum sodium levels in SAH populations.

Microwave ablation versus transarterial chemoembolization in large hepatocellular carcinoma: prospective analysis.

OBJECTIVE: Limited therapies are offered for large hepatocellular carcinoma (HCC). It carries dismal prognosis and efforts tried changing its management from a palliative to a curative mode. Transarterial chemoembolization (TACE) is a palliative procedure that may have survival benefit if compared to non-management of large lesions. Microwave ablation (MWA) has emerged as a relatively new technique with promise of larger and faster ablation. We aim to evaluate the efficacy and safety of percutaneous MWA versus TACE for large tumors (5-7 cm) and to assess their effects on local tumor progression and survival. PATIENTS AND METHODS: Sixty-four patients with large lesions are managed in our multidisciplinary HCC clinic and were divided into two groups treated either by MWA or TACE. Complete response rate, local recurrence, de novo lesions, and overall survival analysis are compared between both procedures. RESULTS: Both groups were comparable as regards the demographic and ultrasonographic features. MWA showed higher rates of complete ablation (75%) with fewer sessions, lower incidence of tumor recurrence (p = 0.02), development of de novo lesions (p = 0.03), occurrence of post-treatment ascites (p = 0.003), and higher survival rates (p = 0.04). The mean survival of the microwave group was 21.7 months with actuarial probability of survival at 12 and 18 months 78.2% and 68.4%, respectively. The mean survival of the TACE group was 13.7 months with actuarial probability of survival at 12 and 18 months being 52.4% and 28.6%, respectively. CONCLUSION: MWA showed better results than TACE in the management of large HCC lesions.

Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-L-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha-fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value<0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5% and specificity to 62.1%. There were positive significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP.

Efficacy and survival analysis of percutaneous radiofrequency versus microwave ablation for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary tumor of the liver with poor prognosis. For early stage HCC, treatment options include surgical resection, liver transplantation, and percutaneous ablation. Percutaneous ablative techniques (radiofrequency and microwave techniques) emerged as best therapeutic options for nonsurgical patients. AIMS: We aimed to determine the safety and efficacy of radiofrequency and microwave procedures for ablation of early stage HCC lesions and prospectively follow up our patients for survival analysis. PATIENTS AND METHODS: One Hundred and 11 patients with early HCC are managed in our multidisciplinary clinic using either radiofrequency or microwave ablation. Patients are assessed for efficacy and safety. Complete ablation rate, local recurrence, and overall survival analysis are compared between both procedures. RESULTS: Radiofrequency ablation group (n = 45) and microwave ablation group (n = 66) were nearly comparable as regards the tumor and patients characteristics. Complete ablation was achieved in 94.2 and 96.1% of patients managed by radiofrequency and microwave ablation techniques, respectively (p value 0.6) with a low rate of minor complications (11.1 and 3.2, respectively) including subcapsular hematoma, thigh burn, abdominal wall skin burn, and pleural effusion. Ablation rates did not differ between ablated lesions ≤ 3 and 3-5 cm. A lower incidence of local recurrence was observed in microwave group (3.9 vs. 13.5% in radiofrequency group, p value 0.04). No difference between both groups as regards de novo lesions, portal vein thrombosis, and abdominal lymphadenopathy. The overall actuarial probability of survival was 91.6% at 1 year and 86.1% at 2 years with a higher survival rates noticed in microwave group but still without significant difference (p value 0.49). CONCLUSION: Radiofrequency and microwave ablations led to safe and equivalent ablation and survival rates (with superiority for microwave ablation as regards the incidence of local recurrence).

The Impact of Augmented Renal Clearance on Vancomycin Pharmacokinetics and Pharmacodynamics in Critically Ill Patients.

Augmented renal clearance (ARC), defined as a creatinine clearance (CrCl) > 130 mL/min/1.73 m2, is observed in 30-65% of critically ill patients. When following standard dosage guidelines, patients with ARC often experience subtherapeutic vancomycin levels, resulting in treatment failure due to accelerated drug elimination. This review aims to explore ARC's impact on vancomycin pharmacokinetics and pharmacodynamics (PK/PD) indices in ARC patients, seeking to identify an accurate dose adjustment method for this patient population. In September 2023, a comprehensive literature search was conducted on the MEDLINE and EMBASE databases to include all available studies providing information on the impact of ARC on vancomycin therapy in critically ill adults. Articles that studied the pediatric population and those with insufficient PK data were excluded. A total of 21 articles met the inclusion criteria. The findings revealed a positive correlation between CrCl and vancomycin clearance, indicating low serum concentrations. Therefore, upward dosing adjustments are necessary to improve treatment success. Younger age consistently emerged as a major contributor to ARC and vancomycin PK/PD alterations. This study summarizes the PK/PD alterations, current dosage recommendations and proposes preliminary recommendations on possible dosing approaches to decrease the risk of subtherapeutic exposure in this patient population.

The impact of photoreceptor layer loss on different ocular tissues: Insights from FTIR spectroscopy.

Photoreceptor loss has significant consequences for visual function, and its management is a critical component for treating not only retinal diseases such as age-related macular degeneration and retinitis pigmentosa but also its ocular consequences. On the other hand, Fourier transform infrared spectroscopy is an excellent tool to investigate molecular structure and dynamics of biological samples, and as a non-destructive and label free measurement, it does not perturb the samples. In this study, detailed analyses of the recorded FTIR spectra from cornea, lens and sclera were performed to monitor the distribution of ocular abnormalities due to photoreceptor layer loss after 1, 3 and 6 days. FTIR data were statistically evaluated by multivariate analysis and Bonferroni means comparison. The obtained results revealed that ocular abnormalities associated with photoreceptor layer loss are varied among the investigated tissues, and comprise changes in both hydrogen bond network around proteins and lipid disorder. Structural modifications of protein secondary structure were reported in all investigated tissues. Clinically, the concluded information from FTIR data and its statistical evaluation can contribute to the development of therapeutic strategies for these heterogeneous changes.

Analyzing Tear Fluid Composition by Synchronous Fluorescence for Diagnosing Dry Eye Disease and the Role of Phytotherapy Intervention.

PURPOSE: Tear fluid gained attention as a representative biological fluid. Its simple and non-invasive collection methods as well as richness of candidate biomarkers made it a potential diagnostic tool for different diseases such as dry eye. Synchronous fluorescence spectroscopy is a highly sensitive analytical tool that results in narrowing and enhanced peak resolution, and has a potential role in disease diagnosis, biomarker identification, and therapeutic monitoring. We applied synchronous fluorescence spectroscopy to monitor variations of tear fluid composition during the development of dry eye disease and to evaluate the potential effects of phytotherapy. METHODS: Dry eye model was induced in Chinchilla rabbits by instillation of 1% atropine sulfate ophthalmic solution. Then, the tear fluid was collected at 3, 7, and 14 days and subjected to synchronous fluorescence spectroscopy. Phytotherapy was achieved by topical instillation of 20 µl of water extracts of pomegranate peel or green tea powders. RESULTS: The fluorescence results revealed changes in the structure of tear fluid over time and the eye is subjected to toxification due to oxidative stress. In addition, dry eye disease was found to affect the metabolic/energetic state of the eye. On the other hand, phytotherapy led to enhancement of the metabolic/biosynthesis state due to activation of flavin adenine dinucleotide-associated proteins. CONCLUSION: There was change in the electrical conductivity of tear fluid proteins. In the case of dry eyes, they became electrical insulators, while in the case of treatment with extracts, their electrical conductivity properties improved. The effects of phytotherapy can be related to the high content of ellagic acid and anthocyanin of pomegranate extract, while in green tea, they are related to catechins and phenolic compounds.

Bioavailability of Orally Administered Drugs in Critically Ill Patients.

Critically ill patients managed in the Intensive Care Unit (ICU) suffer from several pathophysiological alterations due to critical illness resulting in potential changes in the pharmacokinetics of drugs including systemic absorption. Nevertheless, these patients are still given some medications in unadjusted doses thereby putting the patients at a risk for therapy failure. The objective for this study was to summarize the available evidence regarding oral drug absorption in the ICU. A literature search of the databases MEDLINE, EMBASE, and PubMed was conducted on (February 24, 2020). Articles discussing the rate and/or extent of orally administered drugs in critically ill patients were included. A total of 58 studies were found: 17 interventional studies, 33 observational studies (30 prospective, 3 retrospective) and 8 case reports. A total of 43 articles reported altered drug absorption in critically ill patients suggesting the need for alternative measures to facilitate treatment success. The absorption of orally administered drugs may be altered in critically ill patients. Measures for altered drug absorption in critically ill patients were suggested such as holding tube feeding before and after medication administration, increasing doses of orally administrated drugs and using alternate routes of administration.