Citations

Abstract: The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document. This edition includes new evidence from the literature, focusing on the topics updated during the last 7 years, including indirect pharmacological effects of EVR on the mammalian target of rapamycin complex 2 with the major mechanism of direct inhibition of the mammalian target of rapamycin complex 1. In addition, various concepts and technical options to monitor EVR concentrations, improve analytical performance, and increase the number of options available for immunochemical analytical methods have been included. Only limited new pharmacogenetic information regarding EVR has emerged; however, pharmacometrics and model-informed precision dosing have been constructed using physiological parameters as covariates, including pharmacogenetic information. In clinical settings, EVR is combined with a decreased dose of calcineurin inhibitors, such as tacrolimus and cyclosporine, instead of mycophenolic acid. The literature and recommendations for specific organ transplantations, such as that of the kidneys, liver, heart, and lungs, as well as for oncology and pediatrics have been updated. EVR TDM for pancreatic and islet transplantation has been added to this edition. The pharmacodynamic monitoring of EVR in organ transplantation has also been updated. These updates and additions, along with the previous version of this consensus document, will be helpful to clinicians and researchers treating patients receiving EVR.

Abstract Background and Aims Current guidelines suggest that asymptomatic atrial fibrillation (AF) is independently associated with increased risks of stroke and mortality compared with symptomatic AF. Considering that recent investigations have provided conflicting results, the present study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. Methods Medline, Cochrane Library, and Scopus were searched until 25 March 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses. Results Thirty-six studies (217 850 participants) were included. Based on the frequentist analysis, symptomatic individuals had no significant difference in the risk of all-cause mortality [hazard ratio (HR) .97, 95% confidence interval (CI) .80–1.17], cardiovascular mortality (HR 1.04, 95% CI .72–1.49), thromboembolism (HR 1.06, 95% CI .87–1.28), stroke (HR 1.06, 95% CI .84–1.34), hospitalization (HR 1.34, 95% CI .89–2.02), and myocardial infarction (HR .98, 95% CI .70–1.36), compared to the asymptomatic group. Symptomatic patients had a 33% increased risk of new-onset heart failure (HR 1.33, 95% CI 1.19–1.49) and a 30% lower risk of progression to permanent AF (HR .70, 95% CI .54–.89). The Bayesian analysis yielded comparable results, yet the association between symptom status and new-onset heart failure was not significant (HR 1.27, 95% credible interval .76–1.93; Bayes factor = 1.2). Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR] 1.64, 95% CI 1.33–2.03) and ablation therapy (OR 1.47, 95% CI 1.06–2.05) compared to asymptomatic cases. Conclusions The risk of major clinical outcomes did not differ between individuals with and without AF-related symptoms. Asymptomatic patients had a greater hazard of progression to permanent AF.

AbstractThe current study was inspired by observations from exploratory analyses of an institutional cohort with chronic myelomonocytic leukemia (CMML; N = 398) that revealed no instances of blast transformation in the seven patients with plant homeodomain finger protein 6 (PHF6) mutation (PHF6MUT). A subsequent Mayo Clinic enterprise‐wide database search identified 28 more cases with PHF6MUT. Compared with their wild‐type PHF6 counterparts (PHF6WT; N = 391), PHF6MUT cases (N = 35) were more likely to co‐express TET2 (89% vs. 45%; p < .01), RUNX1 (29% vs. 14%; p = .03), CBL (14% vs. 2%; p < .01), and U2AF1 (17% vs. 6%; p = .04) and less likely SRSF2 (23% vs. 45%; p < .01) mutation. They were also more likely to display loss of Y chromosome (LoY; 21% vs. 2%; p < .01) and platelets <100 × 109/L (83% vs. 51%; p < .01). Multivariable analysis identified PHF6MUT (HR 0.28, 95% CI 0.15–0.50) and DNMT3AMUT (HR 5.8, 95% CI 3.3–10.5) as the strongest molecular predictors of overall survival. The same was true for blast transformation‐free survival with corresponding HR (95% CI) of 0.08 (0.01–0.6) and 9.5 (3.8–23.5). At median 20 months follow‐up, blast transformation was documented in none of the 33 patients with PHF6MUT/DNMT3AWT but in 6 (32%) of 19 with DNMT3AMUT and 74 (20%) of 374 with PHF6WT/DNMT3AWT (p < .01). The specific molecular signatures sustained their significant predictive performance in the context of the CMML‐specific molecular prognostic model (CPSS‐mol). PHF6MUT identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.

Vitamin C is a vital nutrient that functions as an antioxidant and is important as a co-factor and regulator of several immune system pathways. The role of vitamin C in the treatment of COVID-19 is largely debatable. We conducted this meta-analysis to evaluate the efficacy and safety of vitamin C in the treatment of COVID-19. We searched several electronic databases from inception to March 2023 to retrieve randomized controlled trials on the use of Vitamin C for COVID-19. RevMan 5.4 was used to calculate risk ratios (RRs) and Mean Differences (MDs) along with confidence intervals (95% CI) using a random-effects model. We included 9 randomized controlled trials in our meta-analysis. Vitamin C did not reduce the all-cause mortality in patients with COVID-19 compared to the standard treatment [RR 0.86, 95% CI: 0.65-1.14; I 2 =66%]. Vitamin C was found to be associated with an increased incidence of ventilation in COVID-19 patients when compared to standard treatment [RR 1.37, 95% CI: 1.18-1.59; I 2 =58%]. There were no significant differences between both groups regarding the incidence of hospitalization [RR 1.00, 95% CI: 0.98-1.02; I 2 =0%], incidence of recovery [RR 1.57, 95% CI: 0.45-5.50; I 2 =52%], hospital mortality [RR 0.68, 95% CI: 0.44-1.06; I 2 =0%] and length of hospital stay [MD -0.63, 95% CI: -3.04 to 1.78; I 2 =81%]. Vitamin C administration did not reduce all-cause mortality in COVID-19 patients. Additional studies are required to evaluate the role of Vitamin C in the prevention and treatment of COVID-19 especially in ICU patients.

BACKGROUND AND OBJECTIVES: Awake minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) generates minimal surrounding tissue damage and has been shown to be a safe, time-effective, and cost-reductive technique in single-level procedures. The purpose of this study was to advocate for the utilization of multilevel MIS-TLIF even in challenging cases as it has demonstrated positive outcomes. METHODS: Chart review was conducted for consecutive patients undergoing awake multilevel MIS-TLIF from 2020 to 2023. Various demographic, preoperative, and postoperative variables were collected and descriptively analyzed. RESULTS: Sixteen patients underwent multilevel awake MIS-TLIF at our institution during the specified period. Among them, 87.5% underwent a two-level procedure and 12.5% a three-level procedure. The median age ± IQR was 69.5 ± 11 years, with a slight male predominance (56.25%). Common comorbidities included hypertension (56.25%), obesity (37.5%), sleep apnea (25%), and type 2 diabetes (18.75%). The American Society of Anesthesiologists risk was 2 in 43.75% of patients and 3 in 56.25%. All patients presented pain, and 12.5% showed motor deficit. Intraoperative data showed a median of 196 minutes in the operating room where 156 ± 27.75 minutes corresponded to actual procedure time. The median estimated blood loss was 50 ± 70 cc. In the immediate postoperative period, 1 patient had nausea and emesis, and 1 reported fatigue. The median pain score during this period was 4.6 ± 2.03. Pain control medications were required for various patients, with methocarbamol (50%), hydromorphone (37.5%), and oxycodone (25%) being the most commonly prescribed in the postanesthesia care unit. No patient had new neurological deficits after the surgical intervention. The median length of stay was 2 days ±1.25. All patients were discharged with no complications. CONCLUSION: Multilevel awake MIS-TLIF emerges as a safe and effective technique for complex cases, enhancing patient quality of life with minimal blood loss and postoperative pain.

BACKGROUND AND OBJECTIVES: Corpus callosotomy is an effective procedure approach for treating medication-resistant drop seizures, which pose a significant challenge in patients with epilepsy. Laser interstitial thermal therapy offers an alternative to open surgery for performing corpus callosotomy that may limit approach-related comorbidities. Practices vary regarding the number of laser filaments used and staging; outcome data for pediatric patients remain relatively limited. METHODS: We illustrate a set of 4 standardized trajectories for performing MRI-guided stereotactic laser corpus callosotomy (SLCC). For this retrospective cohort study in a pediatric neurosurgery practice, the medical records and imaging were reviewed for 10 consecutive patients who had medication-refractory drop seizures and underwent SLCC. Data collected and analyzed included patient and epilepsy characteristics, procedural details, surgical approaches, and clinical follow-up results. RESULTS: Over 2 years, complete, single-stage SLCC was performed in 8 patients, and posterior completion SLCC was performed in 2 patients who had previously had open anterior corpus callosotomy. Four laser fibers were used in four-eighth complete SLCC, and 3 fibers were used in four-eighth complete SLCC. Seven of 10 patients were discharged from the hospital on postoperative day 1, with only 1 requiring a maximum stay of 6 days. Five of 9 evaluable patients reported no drop seizures at the last clinical follow-up. In the other 4 patients, 1 experienced them only rarely, another experienced less than 25% preoperative frequency, and the remaining 2 had less than a 50% improvement. In addition, improvement in other seizure types exceeded 50% in 8 of 9 patients. Notably, no perioperative or postoperative complications were observed, nor were there any sustained neurological deficits reported. CONCLUSION: Complete SLCC can be safely and effectively performed in pediatric patients. It is comparable in effectiveness with open surgery but has lower complication rates and shorter hospitalization.

Clinical History: A 60-year-old female was found to have a 2 cm Ureteropelvic junction (UPJ) stone in an ectopic right pelvic kidney while undergoing evaluation for gross hematuria. She had no prior stone history and normal renal function. Physical Exam: Physical exam was unremarkable. Computed tomography (CT) Urogram revealed a medial, pelvic kidney with overlying bowel and posterior, tortuous ureter. Renal vein ran longitudinally along the anterior surface of the kidney. Diagnosis: A 2 cm UPJ stone in an ectopic right pelvic kidney. Intervention: Given tortuosity of the ureter and overlying bowel precluded an endoscopic approach, we proceeded with robotic-assisted pyelolithotomy. 1 An open-ended ureteral catheter was advanced to allow for distension of the renal pelvis. After placing robotic trocars, peritoneum and Gerota’s fascia were dissected off the anterior surface of the kidney. Robotic Potts were used to enter the renal pelvis. No stone was visible, thus antegrade ureteroscopy was performed through a robotic port, demonstrating an impacted 2 cm lower pole stone. We performed antegrade ureteroscopy, laser lithotripsy, and basket-extraction. A robotic suction arm was employed to remove remaining dust. A double-J ureteral stent was placed antegrade, and pyelotomy was closed in a running fashion. Follow-Up/Outcomes: The patient had an uneventful postoperative course and CT at 6 weeks demonstrated no residual stone. Laparoscopic or robotic-assisted pyelolithotomy demonstrates higher stone free rates in pelvic kidneys compared with endoscopic treatment (97.2% vs 65.9%–84.9%). 2 However, surgical approach should be decided based on patients’ anatomy, stone density and location, and surgeon experience. Author Disclosure Statement: The authors have no conflicts of interest to disclose. Patient Consent Statement: Authors have received and archived patient consent for video recording/publication in advance of video recording of procedure. Music: Music was obtained from www.pixabay.com and is no copyright music, free for use. Exact Runtime of video: 5 min 00 sec.

Reconstruction of the abductor mechanism remains a primary challenge with contemporary proximal femoral replacement (PFR) surgery. Previously, techniques such as trochanteric preservation or direct repair to the implant have been described; however, these strategies are limited in their ability to tension the repair and reattach other muscles of the hip girdle. The aim of this study was to evaluate the outcomes of patients undergoing oncologic PFR using a novel technique of mesh augmentation for soft tissue repair. Methods: We reviewed 18 (mean age 64 years; 8 female: 10 male) consecutive patients undergoing PFR with Marlex mesh augmentation between 2018 and 2023 at a single institution. The most common indication was metastatic disease (n = 13). The mean follow-up in the 14 surviving patients was 27 months (range 12–34). Results: All patients were ambulatory at final follow-up. There were no post-operative dislocations, infections, or wound issues. At the final follow-up, the mean total MSTS score was 77%. Conclusion: Mesh augmentation of PFRs allowed for adequate soft tissue tensioning and muscular attachment to the body of the implant. In our series, this technique was durable, with no dislocations and no mesh-related complications. In summary, mesh augmentation of PFRs may be considered during reconstruction for oncologic indications.