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Pharmacokinetic Research in Pediatric Extracorporeal Therapies: Current State and Future Directions.
No full textExtracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions. Children receiving ECMO and/or CRRT routinely receive 20 or more drugs, and data supporting optimal dosing is lacking for most of these medications. The Pediatric Paracorporeal and Extracorporeal Therapies Summit (PPETS) gathered an international group of experts in the fields of ECMO, CRRT, and other ECLS modalities to discuss the current state of these therapies, disseminate innovative support strategies, share clinical experiences, and foster future collaborations. Here, we summarize the conclusions of PPETS and put forward a pathway to optimize pharmacokinetic (PK) research in this population. We must prioritize specific medications for in-depth study to improve drug use in ECLS and patient outcomes. Based on frequency of use, potential for adverse outcomes if dosed inappropriately, and lack of existing PK data, a list of high priority drugs was compiled for future research. Researchers must additionally reconsider study designs, emphasizing pooling of resources through multi-center studies and the use of innovative PK modeling techniques. Finally, the integration of validated PK models into clinical practice must be streamlined to deliver optimal medication use at the bedside. Focusing on the proposed list of highlighted medications and key methodological considerations will maximize the impact of future research
Back to Bedside: Kidney Point-of-Care Ultrasonography (POCUS) by Resident Physicians for Identification of Hydronephrosis in Patients with AKI
No full textBackground: POCUS has emerged as a valuable adjunct to bedside clinical examinations. In context of acute kidney injury (AKI), bedside POCUS may facilitate early identification of hydronephrosis indicative of obstructive uropathy as the underlying etiology, thereby enabling timely diagnosis, expediting therapeutic management and decreasing fragmentation of care. Incorporating renal POCUS training in the internal medicine residency program allows residents to develop new skills for day-to-day clinical practice and enhance bedside assessment of patients with AKI. Methods: We conducted a prospective observational study at Hamad General Hospital, Qatar. Patients were selected from a convenience sample in the Acute Medical Assessment Unit (AMAU) and medical wards for AKI evaluation. Internal Medicine residents underwent mandatory training, including a 30-minute didactic session by a certified physician and performing ten supervised bilateral renal POCUS scans to ensure proper technique. Residents performed bedside renal POCUS to assess hydronephrosis, with findings compared to blinded departmental scans using a common grading system. Results: Fifty patients with provisional AKI diagnoses based on clinical presentation and renal parameters were included, all pending official renal ultrasound scans. Bedside POCUS identified hydronephrosis in nine patients (one bilateral, eight unilateral). Of these, five were confirmed by departmental ultrasound, and one additional patient with hydronephrosis was missed by POCUS but identified on the formal scan. Conclusions: This project demonstrated that using POCUS for diagnosing and managing AKI to identify hydronephrosis had a sensitivity of 83.3%, specificity of 93%, positive predictive value of 55.6%, and negative predictive value of 98%. The strength of our study is utilization of senior clinical physicians for POCUS training to guide junior residents in enhancing their skills and bedside assessment of patients with AKI. POCUS-enhanced bedside exams allow residents to identify hydronephrosis in a sensitive and time-efficient manner, facilitating timely diagnosis of obstructive uropathy and appropriate patient management
History of Infertility and Risk of Endometrial Cancer in the Women\u27s Health Initiative.
No full textBACKGROUND: Several studies have suggested an association between infertility and risk of endometrial cancer. However, most studies have evaluated this relationship in premenopausal people, yet the mean age of endometrial cancer is 60 years, after the average age of menopause.
METHODS: Our study included Women\u27s Health Initiative participants who self-reported whether they had a history of infertility. Cox proportional hazards models were used to examine the association between infertility and incident endometrial cancer. Given that all infertility diagnoses occurred prior to study enrollment, we conducted secondary analyses using logistic regression examining prevalent endometrial cancer cases diagnosed before study baseline.
RESULTS: Approximately 18% of participants reported a history of infertility. No statistically significant association was observed between infertility and risk of incident endometrial cancer overall [incident cases = 1,622; HR = 1.12; 95% confidence interval (CI) = 0.99-1.26]. Although point estimates suggested an increase in risk of endometrial cancer among women with body mass index (BMI) ≥25 (HR = 1.15; 95% CI = 0.99-1.33), none of the associations were statistically significant. There was an association between history of infertility and prevalent endometrial cancer cases (OR = 1.19; 95% CI = 1.06-1.34), with the strongest association for infertility diagnosis due to endometriosis (OR 2.42; 95% CI = 1.83-3.19).
CONCLUSIONS: In a population of postmenopausal participants, we observed a modest, but not statistically significant, association between overall infertility and incident endometrial cancer, with the suggestion of a higher risk among those with a BMI ≥ 25.
IMPACT: Our findings highlight, as observed in previous studies, that risk factors for endometrial cancer may vary by BMI
Rheumatoid Arthritis: A Rare Cause of Pachymeningitis and Optic Neuritis.
No full textINTRODUCTION: Rheumatoid pachymeningitis and optic neuritis are rare complications of rheumatoid arthritis (RA) and are a diagnosis of exclusion.
CASE DESCRIPTION: A 75-year-old male with a history of seronegative RA presented to the emergency department with left eye pain and blurry vision lasting two days. He had been diagnosed with seronegative RA around nine months previously. His blood pressure was elevated at 204/75 mmHg upon arrival. Physical examination revealed left conjunctival injection, mild ptosis, painful extraocular movements and tenderness over the orbit and sinuses. Initial treatments included painkillers and intravenous labetalol, which alleviated his symptoms and decreased his blood pressure. Laboratory tests showed a C-reactive protein of 2.5 mg/dl and an erythrocyte sedimentation rate of 32 mm/h, with other blood work unremarkable. A computed tomography (CT) angiogram of the head and neck showed no high-grade stenosis. Given his RA history, initial concerns included scleritis. A magnetic resonance imaging (MRI) of the brain and orbit revealed inflammation around the left optic nerve, and pachymeningitis at the left cerebral convexity and interhemispheric fissure, suggesting hypertrophic pachymeningitis. An ophthalmologic examination was unremarkable. Treatment was adjusted to include pulse doses of intravenous methylprednisolone for optic neuritis, resulting in significant pain relief. Though inadequate for complete testing, a lumbar puncture indicated an inflammatory disorder with elevated glucose (199 mg/dl), protein (109 mg/dl), and unremarkable WBC/RBC and Gram staining. Cytology and culture were unremarkable. The most likely diagnosis at this point was rheumatological meningitis and rheumatological optic neuritis. The patient improved markedly with high-dose steroids over four days and was discharged on prednisone.
CONCLUSION: In cases of optic neuritis and pachymeningitis, RA should remain on the differential in patients with or without a prior diagnosis.
LEARNING POINTS: Rheumatoid arthritis (RA) is a systemic disease but can rarely cause neurological involvement.Pachymeningitis is an inflammation of the dura mater, rarely caused by RA.Optic neuritis can also rarely be caused by RA and responds to steroids
Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma.
No full textAnaplastic lymphoma kinase ( ALK )-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1 - unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation. Crizotinib can successfully be used to treat unresectable novel ALK fusion sarcomas
Early oral feeding and its impact on postoperative outcomes in head and neck cancer surgery: a meta-analysis.
No full textBACKGROUND: Early oral feeding has been previously postulated to contribute to developing postoperative complications following head and neck reconstructive surgeries using free flaps. This study assessed the association between the timing of oral feeding (early vs. late) and postoperative complications and length of hospital stay among these patients.
METHOD: PubMed, Scopus, Cochrane, and Web of Science were searched using terms such as oral feeding and head or neck cancer. We utilized RevMan software version 5.4 for the analysis. The study defined early oral feeding as feeding within 5-day post-operation, while late oral feeding was defined as feeding after the fifth postoperative day. Five papers that met the inclusion criteria were included in the analysis, with 1097 patients.
RESULTS: The results showed that early feeding was not significantly associated with postoperative fistulas (RR 0.49, 95% CI 0.23 to 1.05, p-value = 0.07), hematoma/seroma (RR 0.71, 95% CI 0.33 to 1.51, p-value = 0.38), or flap failure (RR 0.84, 95% CI = 0.38 to 1.87, p-value = 0.67). However, early oral feeding was significantly associated with shorter hospital stays than late oral feeding (MD -3.18, 95% CI -4.90 to -1.46, p-value = 0.0003).
CONCLUSION: No significant difference exists between early and late oral feeding regarding the risk of postoperative complications in head and neck cancer (HNC) patients who underwent free flap reconstruction surgery. However, early oral feeding is significantly associated with a shorter hospital stay than late oral feeding. Thus, surgeons should consider implementing early oral feeding after free flap reconstruction in HNC patients
