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EJC Paediatric Oncology Jun 2024Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an...
Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an alternative to conventional treatment options but require the identification of differentially expressed antigens to direct antitumor activity to sites of disease. B7-H3 (CD276) is an immune regulatory protein that is expressed in a range of malignancies and has limited expression in normal tissues. B7-H3 is highly expressed in pediatric solid tumors including osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma, and many rare tumors. In this article we review B7-H3-targeted chimeric antigen receptor (B7-H3-CAR) T cell therapies for pediatric solid tumors, reporting preclinical development strategies and outlining the landscape of active pediatric clinical trials. We identify challenges to the success of CAR T cell therapy for solid tumors including localizing to and penetrating solid tumor sites, evading the hostile tumor microenvironment, supporting T cell expansion and persistence, and avoiding intrinsic tumor resistance. We highlight strategies to overcome these challenges and enhance the effect of B7-H3-CAR T cells, including advanced CAR T cell design and incorporation of combination therapies.
PubMed: 38957786
DOI: 10.1016/j.ejcped.2024.100160 -
Clinical Nephrology. Case Studies 2024We investigated the pathogenesis of a perihilar variant of focal segmental glomerulosclerosis detected by kidney biopsy in a 16-year-old male. The disease was refractory...
Renal and cardiac biopsy findings in an adolescent patient with the 3243A>G mitochondrial DNA mutation: Favorable renal prognosis post renal transplantation from the mother.
We investigated the pathogenesis of a perihilar variant of focal segmental glomerulosclerosis detected by kidney biopsy in a 16-year-old male. The disease was refractory to steroid therapy, and at the second kidney biopsy, abnormal mitochondrial proliferation was newly observed in the podocytes. The patient also developed late-onset hearing loss and had a family history of diabetes, and genetic testing confirmed the mitochondrial DNA mutation 3243A>G (48%). Eight months after hemodialysis was started, encephalopathy occurred presumably due to rapid dehydration. After changing dialysis into continuous ambulatory peritoneal dialysis, encephalopathy was resolved, but the patient developed myocardial hypertrophy, probably because of the myocardial overreaction to congestion. A myocardial biopsy showed mitochondrial proliferation in the myocardium. After renal transplantation from his mother with a heteroplasmy of 4%, the cardiomyopathy improved, and the renal function has remained stable for 4 years. We speculated that the abnormal mitochondrial morphology in the kidney and heart may be characteristic of mitochondrial genetic disease, and renal transplantation from the mother with a low heteroplasmy was considered desirable for mitochondrial nephropathy with poor prognosis.
PubMed: 38957708
DOI: 10.5414/CNCS111422 -
Open Forum Infectious Diseases Jul 2024We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment...
We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.
PubMed: 38957689
DOI: 10.1093/ofid/ofae335 -
Neurosurgical Focus: Video Jul 2024Hemispherectomy is an effective procedure used in the treatment of drug-resistant hemispheric epilepsy, especially in the pediatric population. A number of resective and...
Hemispherectomy is an effective procedure used in the treatment of drug-resistant hemispheric epilepsy, especially in the pediatric population. A number of resective and disconnective techniques are used, and selection of surgical strategy is paramount to achieving successful results. Notably, disconnective (or functional) hemispherotomy maximizes the benefits of safe, surgical disconnection while minimizing hemispheric tissue resection, thereby avoiding some of the perioperative factors contributing to morbidity in traditional anatomical hemispherectomy procedures. In this video, the authors outline the principal surgical steps of disconnective hemispherotomy and highlight important technical factors leading to optimal outcomes in patients with refractory, oftentimes catastrophic, hemispheric epilepsy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2436.
PubMed: 38957432
DOI: 10.3171/2024.4.FOCVID2436 -
Neurosurgical Focus: Video Jul 2024The responsive neurostimulator system has become increasingly popular in the surgical management of refractory epilepsy, with targeting of various thalamic nuclei...
The responsive neurostimulator system has become increasingly popular in the surgical management of refractory epilepsy, with targeting of various thalamic nuclei showing promising results in select patients. A 42-year-old female presented for evaluation of refractory epilepsy consisting of generalized tonic-clonic and focal seizures with preserved awareness. Phase I and II monitoring suggested multifocal bilateral epilepsy with bilateral frontal onset, and the patient underwent robot-guided bilateral centromedian thalamic placement of the RNS System. In this operative video, the authors share their institutional experience and protocol utilizing the ExcelsiusGPS robot in the placement of the RNS System in the thalamus. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID243.
PubMed: 38957427
DOI: 10.3171/2024.4.FOCVID243 -
Neurosurgical Focus: Video Jul 2024Hypothalamic hamartomas (HHs) are benign masses, often associated with drug-refractory epilepsy (DRE). Open surgery as well as the endoscopic disconnection techniques...
Hypothalamic hamartomas (HHs) are benign masses, often associated with drug-refractory epilepsy (DRE). Open surgery as well as the endoscopic disconnection techniques are fraught with a high risk of morbidity and failure rates. The authors have been performing robotic-guided radiofrequency (RF) ablation for all types of HH presenting with DRE as a standard procedure at their institution. The authors have operated on 25 patients with HH using this technique over the last 8 years. This is a safe, effective, and minimally invasive technique. In this video article, the authors intend to demonstrate their technique of RF ablative disconnection under robotic guidance.
PubMed: 38957419
DOI: 10.3171/2024.4.FOCVID2450 -
Neurosurgical Focus: Video Jul 2024Vagus nerve stimulation (VNS) is a neuromodulatory treatment involving chronic intermittent electrical stimulation of the left vagus nerve, administered through a...
Vagus nerve stimulation (VNS) is a neuromodulatory treatment involving chronic intermittent electrical stimulation of the left vagus nerve, administered through a programmable pulse generator implanted subcutaneously in the chest. This generator connects to a bipolar lead, with electrodes wrapped around the vagus nerve in the neck. Primarily used as an adjunct therapy for patients with refractory epilepsy who cannot undergo or have not benefitted from resective surgery, VNS is generally well tolerated with few severe side effects. Herein is presented an educational surgical video providing a detailed, step-by-step technical description of VNS implantation. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID244.
PubMed: 38957417
DOI: 10.3171/2024.4.FOCVID244 -
Neurosurgical Focus: Video Jul 2024Epilepsy is a common symptom of pediatric cavernous malformations. In medically refractory patients, surgery can achieve high seizure freedom rates with low morbidity....
Epilepsy is a common symptom of pediatric cavernous malformations. In medically refractory patients, surgery can achieve high seizure freedom rates with low morbidity. This video depicts the use of a minipterional craniotomy and transsulcal resection of a frontal opercular cavernous malformation in a 13-year-old female with medically intractable epilepsy. At 1-year follow-up, she was evaluated as Engel class I with a significant improvement in her quality of life. Principles of cavernous malformation resection for the treatment of epilepsy are also reviewed. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2441.
PubMed: 38957416
DOI: 10.3171/2024.4.FOCVID2441 -
Headache Jul 2024Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients.
OBJECTIVES
Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients.
BACKGROUND
SM is defined as a debilitating migraine attack lasting more than 72 h. There is no standard of care for SM, including whether a 72-h duration is required before the attack can be treated as SM.
METHODS
The Refractory Headache Special Interest Group from AHS developed a four-question survey distributed to AHS members enquiring (1) whether they treat severe refractory migraine attacks the same as SM regardless of duration, (2) what their first step in SM management is, (3) what the top three medications they use for SM are, and (4) whether they are United Council for Neurologic Subspecialties (UCNS) certified. The survey was conducted in January 2022. Descriptive statistical analyses were performed.
RESULTS
Responses were received from 196 of 1859 (10.5%) AHS members; 64.3% were UCNS certified in headache management. Respondents treated 69.4% (136/196) of patients with a severe refractory migraine attack as SM before the 72-h period had elapsed. Most (76.0%, 149/196) chose "treat remotely using outpatient medications at home" as the first step, 11.2% (22/196) preferred procedures, 6.1% (12/196) favored an infusion center, 6.1% (12/196) sent patients to the emergency department (ED) or urgent care, and 0.5% (1/196) preferred direct hospital admission. The top five preferred medications were as follows: (1) corticosteroids (71.4%, 140/196), (2) nonsteroidal anti-inflammatory drugs (NSAIDs) (50.1%, 99/196), (3) neuroleptics (46.9%, 92/196), (4) triptans (30.6%, 60/196), and (5) dihydroergotamine (DHE) (21.4%, 42/196).
CONCLUSIONS
Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management.
PubMed: 38957119
DOI: 10.1111/head.14769 -
Colorectal Disease : the Official... Jul 2024Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal... (Review)
Review
AIM
Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal bleeding, tenesmus, mucoid secretion, anal pain and a sense of incomplete evacuation. Diagnosis is based on characteristic clinical symptoms and endoscopic/histological findings. Several treatments have been reported in the literature with variable ulcer healing rates. This study aimed to evaluate the efficacy of different treatments for SRUS.
MATERIALS AND METHODS
A systematic review and network meta-analysis were performed according to the PRISMA guidelines. Studies in English, French and Spanish languages were included. Papers written in other languages were excluded. Other exclusion criteria were reviews, case reports or clinical series enrolling less than five patients, study duplications, no clinical data of interest and no article available. A systematic literature search was conducted from January 2000 to March 2024 using the following databases: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus. The biases of the studies were assessed using the Newcastle-Ottawa scale or the Jadad scale when appropriate. Types of treatment and their efficacy for the cure of SRUS were collected and critically assessed. The study's primary outcome was to estimate the rate of patients with ulcer healing.
RESULTS
A total of 22 studies with 911 patients (men 361, women 550) diagnosed with SRUS were analysed in the final meta-analysis. The pooled effect estimates of treatment efficacy revealed that surgery showed the highest ulcer healing rate (70.5%; 95% CI 0.57-0.83). Surgery was superior in the cure of ulcers with respect to medical therapies and biofeedback (OR 0.09 and OR 0.14).
CONCLUSION
Solitary rectal ulcer syndrome is a challenging clinical entity to manage. Proficient results have been reported with the surgical approach, suggesting its positive role in cases refractory to medical and biofeedback therapy. Further studies in homogeneous populations are required to evaluate the efficacy of surgery in this setting. (PROSPERO registration number CRD42022331422).
PubMed: 38957108
DOI: 10.1111/codi.17080