Regional Anesthesia for High-Risk Patients Undergoing Total Knee Arthroplasty: A Case Report.

Total knee arthroplasty (TKA) is a commonly performed surgery for individuals experiencing advanced knee osteoarthritis. Patients undergoing TKA can present with a variety of comorbidities, ranging from the absence of chronic illnesses to the presence of multiple health conditions. The complexity of these comorbidities can pose challenges in carrying out the desired procedure due to the elevated risk profile; this limits the anesthesia modalities that the physician can utilize. Careful consideration of patients' overall health status and personalized anesthesia approaches are crucial to ensure optimal outcomes in this diverse patient population. This case involves an eighty-year-old male with a history of multiple comorbidities who underwent a left TKA. The patient presented a high-risk profile during evaluation, classified as American Society of Anesthesiology (ASA) class IV, which made general and neuraxial anesthesia unfavorable due to high risks. Regional anesthesia was utilized as the sole modality of anesthesia and was successful. This demonstrates that regional anesthesia is a viable option when attending to patients with high risks associated with other anesthesia modalities.

A systematic review: The relationship of COVID-19 to iron, zinc, and vitamin D.

Background: Primary care physicians are crucial in identifying SARS-CoV-2 infection and transferring suspected cases since they are on the front lines of health care. Micronutrients are used as an adjunctive treatment for viral respiratory infections. Because there is currently no effective antiviral therapy for COVID-19, micronutrients such as iron, zinc, and vitamin D may be important for the survival of critically ill patients. Objective: To establish and emphasize a relationship between iron, zinc, and vitamin D to COVID-19. Materials and Methods: PubMed database was used for articles selection. All relevant articles to our review with the topics regarding the use of iron, zinc and vitamin D in COVID-19 patients. We excluded other articles, which are not related to this field and did not match inclusion criteria. The data extracted according to specific form and double reviewed by the group members. Results: The search of the mentioned database returned a total of 3614 studies that were included for title screening. 2910 of them were included for abstract screening, which lead to the exclusion of 1064 articles. The remaining 1846 publications full texts were reviewed. The full-text revision led to the exclusion of 1812 studies, and 34 were enrolled for final data extraction. Conclusion: This study raised the idea of employing zinc, iron, and vitamin D as ingredients to either protect SARS-CoV-2 patients or to speed up recovery, decrease symptoms severity and decrease mortality rates.

The outcome of high-frequency oscillatory ventilation in pediatric patients with acute respiratory distress syndrome in an intensive care unit.

BACKGROUND: In adults with acute respiratory distress syndrome (ARDS), high-frequency oscillatory ventilation (HFOV) has been associated with higher mortality rates. Therefore, its use in children with ARDS is still controversial. OBJECTIVES: Evaluate the overall mortality of HFOV in children with ARDS and explore mortality-related risk factors; compare the outcome of using HFOV post-endotracheal intubation early (≤24 hours) versus late (≤24 hours). DESIGN: Retrospective (medical record review) SETTING: Pediatric intensive care unit in a tertiary care center in Saudi Arabia. PATIENTS AND METHODS: Data were collected from medical records of all pediatric patients with ARDS aged one week to 14 years, who were admitted to the pediatric intensive care unit (PICU) from January 2016-June 2019 and who required HFOV. MAIN OUTCOME MEASURES: PICU mortality. SAMPLE SIZE AND CHARACTERISTICS: 135 ARDS patients including 74 females (54.8%), and 61 males (45.2%), with a median age (interquar-tile range) of 35 (72) months. RESULTS: The overall mortality rate was 60.0% (81/135), and most died in the first 28 days in the PICU (91.3%, 74/8). Of non-survivors, 75.3% (61/81) were immunocompromised, and 24.7% (20/81) were immuno-competent patients, 52 (64.2%) received inotropic support, 40 (49.4%) had a bone-marrow transplant (BMT) before HFOV initiation. Although the prone position was used in 20.7% (28/135) to improve the survival rate post-HFOV ventilation, only 28.6% (8/28) survived. In addition, altered code status or chemotherapy reported a significant association with mortality (P<.05). Interestingly, early HFOV initiation (≤24 hours) did not seem to have a high impact on survival compared to late initiation (>24 hours); (57.4% vs. 42.6%, P=.721). CONCLUSION: Immunocompromised and oncology patients, including post-BMT, reported poorer outcomes, and neither the prone position nor early use of HFOV improved outcomes. However, it is recommended to replicate the study in a larger cohort to generalize the results. LIMITATIONS: Retrospective single-center study.

Robotic-assisted total knee arthroplasty for extra-articular femur deformity correction.

Femoral shaft fracture is one of the most common injuries encountered. However, improper management can lead to significant long-term complications, of which is malunion. Patients with femoral malunion are at increased risk of developing knee osteoarthritis, and if arthroplasty is indicated, these extra-articular deformities pose a challenge as corrective osteotomy and soft tissue release are also required. In such circumstances, robotic arm-assisted total knee arthroplasty (RATKA) might be an appropriate option. In this case, we present a 66-year-old woman who had previously suffered a femur shaft fracture, which was treated conservatively, and developed a varus malunion and severe knee osteoarthritis, and who was treated with RATKA.

Enhancing Expert Panel Discussions in Pediatric Palliative Care: Innovative Scenario Development and Summarization With ChatGPT-4.

This study presents a novel approach to enhance expert panel discussions in a medical conference through the use of ChatGPT-4 (Generative Pre-trained Transformer version 4), a recently launched powerful artificial intelligence (AI) language model. We report on ChatGPT-4's ability to optimize and summarize the medical conference panel recommendations of the first Pan-Arab Pediatric Palliative Critical Care Hybrid Conference, held in Riyadh, Saudi Arabia. ChatGPT-4 was incorporated into the discussions in two sequential phases: first, scenarios were optimized by the AI model to stimulate in-depth conversations; second, the model identified, summarized, and contrasted key themes from the panel and audience discussions. The results suggest that ChatGPT-4 effectively facilitated complex do-not-resuscitate (DNR) conflict resolution by summarizing key themes such as effective communication, collaboration, patient and family-centered care, trust, and ethical considerations. The inclusion of ChatGPT-4 in pediatric palliative care panel discussions demonstrated potential benefits for enhancing critical thinking among medical professionals. Further research is warranted to validate and broaden these insights across various settings and cultures.

The Early-Enhancing Hepatic Vein: Differentiating Focal Nodular Hyperplasia and Hepatic Adenoma With Pathologic Validation in MRI.

BACKGROUND: Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) are two common benign liver lesions with different management options. In particular, resection is considered for large HA lesions to avoid possible bleeding complications or rarely malignant degeneration. PURPOSE: To determine whether early enhancement of a draining hepatic vein (EDHV) and absence of perilesional enhancement (PLE) on arterial phase MR images are useful for distinguishing FNH from HA. STUDY TYPE: Retrospective. POPULATION: A total of 34 patients: 16 with FNH and 18 with HA lesions. FIELD STRENGTH/SEQUENCE: A1.5 T, axial T1 fat-suppressed arterial postcontrast. ASSESMENT: Four abdominal radiologists blinded to pathologic diagnosis assessed for the presence or absence of EDHV in association with the lesion, definitively characterized by pathology. This was considered present if contrast could be identified in a hepatic vein contiguous with the lesion in question. Secondarily, PLE was evaluated. STATISTICAL TESTS: Fleiss's multirater kappa statistic, Chi-squared statistic, Phi-coefficient. Significance level P < 0.05. RESULTS: Considering all observations obtained from the four readers, an EDHV was identified with FNH 48.5% of the time. EDHV was seen with HA in 8.8% of cases. PLE was seen with significantly greater frequency in HA. The presence of an EDHV was associated with the absence of PLE. DATA CONCLUSION: In a lesion that may be either an FNH or HA, confident identification on arterial phase images of an EDHV should lead the reader to favor FNH, while the presence PLE should dissuade the reader from FNH. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

A Review on Machine Learning Approaches in Identification of Pediatric Epilepsy.

Epilepsy is the second most common neurological disease after Alzheimer. It is a disorder of the brain which results in recurrent seizures. Though the epilepsy in general is considered as a serious disorder, its effects in children are rather dangerous. It is mainly because it reasons a slower rate of development and a failure to improve certain skills among such children. Seizures are the most common symptom of epilepsy. As a regular medical procedure, the specialists record brain activity using an electroencephalogram (EEG) to observe epileptic seizures. The detection of these seizures is performed by specialists, but the results might not be accurate and depend on the specialist's experience; therefore, automated detection of epileptic pediatric seizures might be an optimal solution. In this regard, several techniques have been investigated in the literature. This research aims to review the approaches to pediatric epilepsy seizures' identification especially those based on machine learning, in addition to the techniques applied on the CHB-MIT scalp EEG database of epileptic pediatric signals.

Impact of an electronic alert system for pediatric sepsis screening a tertiary hospital experience.

This study aimed to assess the potential impact of implementing an electronic alert system (EAS) for systemic inflammatory syndrome (SIRS) and sepsis in pediatric patients mortality. This retrospective study had a pre and post design. We enrolled patients aged ≤ 14 years who were diagnosed with sepsis/severe sepsis upon admission to the pediatric intensive care unit (PICU) of our tertiary hospital from January 2014 to December 2018. We implemented an EAS for the patients with SIRS/sepsis. The patients who met the inclusion criteria pre-EAS implementation comprised the control group, and the group post-EAS implementation was the experimental group. Mortality was the primary outcome, while length of stay (LOS) and mechanical ventilation in the first hour were the secondary outcomes. Of the 308 enrolled patients, 147 were in the pre-EAS group and 161 in the post-EAS group. In terms of mortality, 44 patients in the pre-EAS group and 28 in the post-EAS group died (p 0.011). The average LOS in the PICU was 7.9 days for the pre-EAS group and 6.8 days for the post-EAS group (p 0.442). Considering the EAS initiation time as the "zero time", early recognition of SIRS and sepsis via the EAS led to faster treatment interventions in post-EAS group, which included fluid boluses with median (25th, 75th percentile) time of 107 (37, 218) min vs. 30 (11,112) min, p < 0.001) and time to initiate antimicrobial therapy median (25th, 75th percentile) of 170.5 (66,320) min vs. 131 (53,279) min, p 0.042). The difference in mechanical ventilation in the first hour of admission was not significant between the groups (25.17% vs. 24.22%, p 0.895). The implementation of the EAS resulted in a statistically significant reduction in the mortality rate among the patients admitted to the PICU in our study. An EAS can play an important role in saving lives and subsequent reduction in healthcare costs. Further enhancement of systematic screening is therefore highly recommended to improve the prognosis of pediatric SIRS and sepsis. The implementation of the EAS, warrants further validation in multicenter or national studies.

Can First-Dose Therapeutic Drug Monitoring Predict the Steady State Area Under the Blood Concentration-Time Curve of Busulfan in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation?

Busulfan has high intra-individual variability and possible time-dependent changes in clearance, which complicates therapeutic drug monitoring (TDM), as first dose sampling may not predict the steady state concentrations. In this study, we aimed to use Bayesian pharmacokinetic parameters estimated from the first dose to predict the steady state AUC for busulfan. This observational study was conducted among pediatric patients at King Abdullah Specialist Children's Hospital. From each patient, we collected six blood samples (2, 2.25, 2.5, 3, 4, and 6 h after the start of IV infusion of the first dose). A subset of patients were also sampled at the steady state. First, we modeled the data using only the first dose. The model was used to estimate the empirical Bayesian estimates of clearance for each individual patient, then we used the empirical Bayesian estimates of clearance to predict the AUC0-tau at steady state (i.e., predicted AUC0-tau). Steady state AUC0-tau was also calculated for patients sampled at steady state using the trapezoidal method using raw time concentration data; this was considered the reference AUC0-tau.. Then, we compared the AUC0-tau predicted using the Bayesian approach with the reference AUC0-tau values. We calculated bias and precision to assess predictability. In total we had 33 patients sampled after first dose and at steady state. Using the Bayesian approach to predict the AUC0-tau, bias was -2.8% and precision was 33%. This indicates that first dose concentrations cannot accurately predict steady state busulfan concentrations; therefore, follow-up TDM may be required for optimal dosing.

Cardiovascular magnetic resonance characterization of rheumatic mitral stenosis: findings from three worldwide endemic zones.

BACKGROUND: Cardiac remodeling in rheumatic mitral stenosis (MS) is complex and incompletely understood. The objective of this study was to evaluate cardiac structural and functional changes in a cohort of patients with rheumatic MS using cardiovascular magnetic resonance (CMR). METHODS: This retrospective study included 40 patients with rheumatic MS, consisting of 19 patients from India, 15 patients from China, and 6 patients from Mexico (median (interquartile range (IQR)) age: 45 years (34-55); 75% women). Twenty patients were included in the control group. CMR variables pertaining to morphology and function were collected. Late gadolinium enhancement (LGE) sequences were acquired for tissue characterization. Statistical analyses were performed using the Kruskal-Wallis test and the chi-square test. RESULTS: Compared to the control group, patients with MS had lower left ventricular (LV) ejection fraction (51% (42%-55%) vs 60% (57%-65%), p < 0.001), lower right ventricular (RV) ejection fraction (44% (40%-52%) vs 64% (59%-67%), p < 0.001), higher RV end-diastolic volume (72 (58-87) mL/m2 vs 59 (49-69) mL/m2, p = 0.003), larger left atrial volume (87 (67-108) mL/m2 vs 29 (22-34) mL/m2, p < 0.001), and right atrial areas (20 (16-23) cm2 vs 13 (12-16) cm2, p < 0.001). LGE was prevalent in patients with rheumatic MS (82%), and was commonly located at the RV insertion sites. Furthermore, the patient cohorts from India, China, and Mexico were heterogeneous in terms of baseline characteristics and cardiac remodeling. CONCLUSION: Our findings demonstrated that biventricular dysfunction, right and left atrial remodeling, and LGE at the RV insertion sites are underappreciated in contemporary rheumatic MS. Further studies are needed to elucidate the prognostic implications of these findings.

Adductor canal catheter block after total knee arthroplasty in patients with severe osteoarthritis and limited mobility. A single center study in Riyadh, Saudi Arabia.

Purpose: Total knee arthroplasty (TKA) is one of the most performed procedures. Postoperative pain control is an important factor for the improvement of patient's quality of life. The aim of this study is to report pain control results and functional outcome scores associated with adductor canal blockade (ACB) usage post-TKA. Methods: A prospective case series study of patients who underwent TKA for degenerative osteoarthritis with ACB postoperatively from 2018 to 2019 in a single center in Saudi Arabia, Riyadh. Assessment of functional outcome scores and pain level were measured preoperatively and postoperatively respectively using Knee injury and Osteoarthritis Outcome Score (KOOS) and the Visual Analog Scale (VAS). Results: Average KOOS score preoperatively for all 5 domains showed a marked improvement at 3 months compared to preoperative values. Pain score postoperatively was measured at 12, 24, and 48 h with an average of 0.7, 1.2, and 0.6 out of 10 on the VAS scale, respectively. The incidence of associated common side effects with the use of analgesic use was included as an add-on in the postoperative questionnaire. Conclusion: In conclusion, by comparing preoperative and postoperative pain levels and functional outcome scores, our study showed a significant pain control and improved functional outcome scores following TKA using ACB.

A Primary Urothelial Carcinoma Presenting as a Mid-Bulbar Urethral Stricture in a 30-Year-Old Male.

The bulbar urethra is the most common site of anterior urethral strictures. In this case report, we present a 30-year-old male who was referred to us as a case of mid-bulbar urethral stricture. Urethroplasty was booked and a papillary lesion was found on routine diagnostic cystoscopy. An open biopsy was taken which showed invasive high-grade papillary urothelial carcinoma with squamous differentiation. This case is rare in terms of a young age of incidence, a lack of risk factors, an absence of suspicious symptoms, and a short duration of signs and symptoms. Urologists should consider workup for malignancy even in young patients who present with an idiopathic urethral stricture and a short duration of symptoms.

Cultural Adaptation and Validation of an Arabic Version of the Modified Harris Hip Score.

Context Although the Modified Harris Hip Score (MHHS) is used worldwide, it has not been translated into Arabic or validated for use among Arabic populations. Aim This study aimed to translate the MHHS into Arabic and to culturally adapt and validate the Arabic version. Design A cross-sectional study of the MHHS was performed. Methods The MHHS was translated into Arabic using forward-backward translation. A total of 183 adults who could speak and read Arabic completed the questionnaire. Cronbach's alpha was used to assess internal consistency with respect to the total and subscale scores. Pearson's correlation coefficient was used to evaluate associations between the total scores, and the subscales and intersubscales. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC). The Kaiser-Meyer-Olkin value was determined before principal component analysis to evaluate the validity of the construct and the reliability of the data, and correlations among the score items were estimated. Results All the participants understood the questions. The ICCs for the total score, function subscale, and pain subscale were 0.936, 0.936 and 0.893, respectively. Cronbach's alpha was acceptable for the total score (0.792) and good for the function subscale (0.895). The total score and the function (r = 0.976; p < 0.001) and pain (r = 0.971; p < 0.001) subscales correlated significantly. Regarding score validity, all the MHHS items correlated with the total score (p < 0.001). Conclusions The reliability and validity of the Arabic version of the MHHS was demonstrated. The MHHS can be used to assess hip pathology among adults in Saudi Arabia.

Neural Network Analysis of Crystalluria Content to Predict Urinary Stone Type.

PURPOSE: To investigate the relationship between urinary stone type and the type of crystals in the urine. PATIENTS AND METHODS: This retrospective study involved 485 patients with urinary stones treated at King Saud University Medical City from May 2015 to June 2017. Clinical data were obtained from medical records. Different statistical analysis methods were applied, including basic contingency analysis, analysis of variance, logistic regression, discriminant analysis, partition modeling, and neural network evaluations. RESULTS: Of 485 patients, 47 had crystals detected by urinalysis. The most common type of crystal was calcium oxalate (n = 31), which had the highest association with calcium oxalate stones. Uric acid crystals (n = 8) were associated with uric acid stones. The neural network model used for determining the sensitivity and specificity showed an R-square value of 0.88, with an area under the curve of 0.94 for calcium oxalate, 0.94 for carbonate apatite, and 1.0 for uric acid. CONCLUSION: The predictive algorithm developed in the present study may be used with a patient's clinical parameters to predict the stone type. This approach predicts the stone types associated with certain patient characteristics with a high sensitivity and specificity, indicating that the models may be a valuable clinical tool in the diagnosis, management, and monitoring of stone diseases.

Biliary excretion of gadobenate dimeglumine causing degradation of magnetic resonance cholangiopancreatography (MRCP).

PURPOSE: To assess the effect of gadobenate dimeglumine on magnetic resonance cholangiopancreatography (MRCP) and determine an appropriate time frame for performing MRCP sequences. MATERIALS AND METHODS: 2D MRCP sequences obtained after intravenous administration of gadobenate dimeglumine or gadobutrol over 14 months were reviewed retrospectively in randomized order by five abdominal radiologists, using a 3-point scale to rate biliary and pancreatic duct clarity (1 = no-, 2 = limited-, 3 = good visualization). Intraclass correlation coefficients were computed and mean scores were compared for both agents. For gadobenate dimeglumine exams, time delays between arterial phase and MRCP acquisition times were analyzed concerning duct clarity. For gadobutrol, only exams with delays ≥ 15 min were included. RESULTS: 134 exams (107 gadobenate dimeglumine, 27 gadobutrol) were included. Moderate reliability for pancreatic duct visualization and excellent reliability for visualization of intrahepatic bile ducts and upper and lower extrahepatic bile ducts were noted. No difference in mean scores was noted for pancreatic duct visualization (p = 0.66). Bile duct segment scores were lower with gadobenate dimeglumine (mean: 2.1-2.6) compared with gadobutrol (mean: 2.8-2.9) (p ≤ 0.006). For gadobenate dimeglumine, visualization scores varied depending on the delay between the arterial phase and MRCP acquisition (p ≤ 0.047). Good visualization for all bile duct segments was noted with delays of 7.2-9.4 min (95% confidence interval; mean 8.3 min). CONCLUSION: Bile duct clarity degraded on MRCP images with an increasing delay following gadobenate dimeglumine injection. 2D MRCP, thus, should be performed within 7.2 min after obtaining the arterial phase sequence to ensure good visualization of the entire biliary system.

Long-stay patients in pediatric intensive care units. Five-years, 2-points, cross-sectional study.

OBJECTIVES: To explore the changing patterns of long-stay patients (LSP) to improve the utilization of pediatric intensive care units (PICUs) resources. METHODS: This is a 2-points cross-sectional study (5 years apart; 2014-2019) conducted among PICUs and SCICUs in Riyadh, Saudi Arabia. Children who have stayed in PICU for more than 21 days were included. RESULTS: Out of the 11 units approached, 10 (90%) agreed to participate. The prevalence of LSP in all these hospitals decreased from 32% (48/150) in 2014 to 23.4% (35/149) in 2019. The length of stay ranged from 22 days to 13.5 years. The majority of LSP had a neuromuscular or cardiac disease and were admitted with respiratory compromise. Ventilator-associated pneumonia was the most prevalent complication (37.5%). The most commonly used resources were mechanical ventilation (93.8%), antibiotics (60.4%), and blood-products transfusions (35.4%). The most common reason for the extended stay was medical reasons (51.1%), followed by a lack of family resources (26.5%) or lack of referral to long-term care facilities (22.4%). CONCLUSION: A long-stay is associated with significant critical care bed occupancy, complications, and utilization of resources that could be otherwise utilized as surge capacity for critical care services. Decreasing occupancy in this multicenter study deserves further engagement of the healthcare leaders and families to maximize the utilization of resources.

Exposure of Urology Residents to the Management of Urethral Strictures in Saudi Arabia: Should the Program for Postgraduates Be Customized?

PURPOSE: This study aimed to assess the exposure and knowledge of urology residents in the management of urethral stricture (US) and to determine if they would be able to perform urethroplasty after graduation and whether urethroplasty should be included as a competency in the training program. PATIENTS AND METHODS: An online survey was sent to all residents enrolled in any urology training program in Saudi Arabia. Fifty-eight (approximately 50%) of the 114 residents who were sent the survey provided responses. RESULTS: Most of the residents (45 residents, 77.6%) who responded were exposed to fewer than ten cases of US during their last year of training. Fifty-six residents (96.6%) attended five or fewer urethroplasty procedures in their last year of training. Twenty-three (40%) residents did not attend any urethroplasty procedure in the last year. The most common procedures attended by the residents were minimally invasive treatments (89% cystoscopy with dilatation and 79% direct visual internal urethrotomy (DVIU)). Most residents responded that they would manage newly diagnosed 1 cm US with either cystoscopy and dilatation or with DVIU 53 (91%). For the first recurrence of US, 46 (79%) residents responded that they would still prefer dilatation or DVIU. For the second, third, and chronic recurrences of US, 20 (34.5%), 6 (10.3%), and 5 (8.6%) residents, respectively, responded that they would perform dilatation or DVIU. Residents had low expectations for the success rate of urethroplasty; only 32 (55.2%) residents thought it had a high success rate. CONCLUSION: Urethroplasty is a specialized urological procedure, one that residents have variable exposure to. Privilege to perform such a procedure after graduating should be modified to ensure the best outcome for patients.

Severe heterotopic ossification post total knee arthroplasty in a patient with rheumatoid arthritis: a case report.

Stiffness following total knee arthroplasty (TKA) can be a devastating complication to the patient by limiting his function. Various causes have been reported in the literature, including heterotopic ossification (HO). HO is one of the rarely reported complication of TKA characterized by deposition of bone cells in non-skeletal tissue. This is a case of 32-year-old female known to have rheumatoid arthritis with history of TKA 4-years-ago complaining of right knee pain and restricted range of motion. She was later found to have HO and was treated with a revision TKA. In conclusion, the incidence and outcome of HO following total knee replacement in patients with RA remains underexplored topic in the literature.

Population pharmacokinetics of busulfan in Saudi pediatric patients undergoing hematopoietic stem cell transplantation.

Background Busulfan is an antineoplastic drug that is used widely as part of a conditioning regimen in pediatric patients undergoing hematopoietic stem cell transplantation. It has a narrow therapeutic index and highly variable pharmacokinetics; therefore therapeutic drug monitoring is recommended to optimize busulfan dosing. Objective To study the population pharmacokinetics of busulfan in Saudi pediatric patients to optimize its dosing. Settings King Abdullah Specialist Children's Hospital in Riyadh, Saudi Arabia. Methods This pharmacokinetic observational study was conducted between January 2016 and December 2018. All pediatric patients receiving IV busulfan and undergoing routine therapeutic drug monitoring were included. Population pharmacokinetics modeling was conducted using Monolix2019R1. Pharmacokinetic data of busulfan in children. Results The study included 59 patients and 513 samples. The mean ± SD age was 6.10 ± 3.17 years, and the dose administered was 0.994 ± 0.15 mg/kg. The mean ± SD Cmax and area under the curve (AUC) were 900.60 ± 402.8 ng/mL and 1031.14 ± 300.75 µM min, respectively. Based on our simulations, the European Medicines Agency recommended dose were adequate for most patient's groups to achieve the conventional target of an AUC0-tau of 900-1350 µM min. For patients in the lower weight group < 9 kg, higher doses were need at 1.2 mg/kg. With regards to the newly proposed target of AUC 78-101 mg h/mL, all of the doses we tested had low probability of achieving it. Conclusions Most of our patients had less than a proportional increase in busulfan concentration suggesting autoinduction. The high interindividual variability and autoinduction make dose adjustments challenging and AUC at steady state difficult to predict from the first dose. One approach to improve dose predictions is to use Bayesian dosing software. Based on our simulations, the European Medicines Agency recommended doses were adequate for most patient groups, except those in the lower (< 9 kg) and higher weight groups (> 34 kg).

Cementless bipolar hemiarthroplasty in a patient with PMF: a case report.

Myelofibrosis is a myeloproliferative disease that falls under a group of bone marrow malignancies known as myeloproliferative neoplasms. It manifests with splenomegaly, anemia, leukocytosis and, less commonly, bone pain. Ruxolitinib, Janus kinase inhibitor, has been shown to increase survival, to improve symptoms and has the potential to decrease osteosclerotic changes. Herein, we present a case of primary myelofibrosis (PMF) in a 60-year-old female who presented with 8-month history of progressive left hip pain and later was diagnosed with pathological neck of femur fracture that was treated with cementless hemiarthroplasty. In conclusion, the use of cementless implants in hip arthroplasty in the presence of PMF has shown to be an effective and safe choice.