Radiotherapy for head and neck paragangliomas: A 10 year retrospective review 2005-2014 at Groote Schuur Hospital and UCT Private academic hospital

Objective. Over the last two decades there has been increasing evidence that radiosurgery and radiotherapy management of skull-base paragangliomas is as effective as microsurgical resection and carries less morbidity. This 10 year retrospective review of 24 patients in a single institution, treated over 10 years assesses tumour control rates and morbidity associated with radiosurgery and radiotherapy treatment. Method. Patients with a radiological diagnosis of skull-base paragangliomas were treated with different techniques of stereotactic and image-guided radiotherapy delivering hypo fractionated irradiation. Techniques used included conventional radiotherapy or intensity modulated radiotherapy (IMRT), dynamic arc (DA) and volumetric modulated arc therapy (VMAT). Analysis of local tumour control was performed using RECIST criteria and the KaplanMeier method. 69% of patients received 14-16gy in 1-3 fractions while 31% received 48- 50gy in 25 fractions. Radiation-associated toxicity was graded according to the commonly used Radiation therapy Oncology group (RTOG) toxicity criteria. Results. 24 patients with skull-base paragangliomas were treated with a median follow up of 43 months. One patient lost to follow up and was excluded. Tumour control was achieved in 96% of patients. 76% of patients treated reported no radiation associated toxicity. 24% of patients had some radiation associated toxicity: the conventional group 12%, stereotactic radiosurgery 8% and stereotactic radiotherapy 4%. 43% of patients in the conventional group had progression of hearing loss in the affected ear. One patient in the radiosurgery group developed osteonecrosis of the temporal bone at 5 year follow up. Conclusion. Radiosurgery and radiotherapy are efficacious in achieving tumour control with minimal morbidity. Tumour control rates in the study are similar to control rates in literature. Radiation associated toxicities are mainly minor. Study is limited by the retrospective nature and limited duration of follow up

1328. Paenibacillosis: An Emerging Cause of Neonatal Sepsis and Postinfectious Hydrocephalus

Background The etiology of neonatal sepsis is often not identified. Molecular methods can identify pathogens that culture-based methods miss. Most cases of neonatal sepsis globally are treated empirically per WHO guidelines with intravenous ampicillin and gentamicin, which may not be the best regimen for all pathogens. Methods We prospectively enrolled 800 neonates presenting with signs of sepsis to two Ugandan hospitals. Blood and cerebrospinal fluid were subjected to 16S rRNA sequencing, which identified Paenibacillus thiaminolyticus in 33/800 (4%) neonates. We confirmed the presence of P. thiaminolyticus by quantitative polymerase chain reaction (PCR). We describe neonatal and birth characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacillosis. We performed antibiotic susceptibility testing and genomic analyses on three clinical isolates successfully grown in the laboratory. Results Neonates presented at a median age of 3 (1, 7) days. Fever (86%), irritability (78%) and seizures (52%) were common presenting signs (Figure). Most neonates were born vaginally (73%) at a medical facility (79%). Twelve (36%) had an adverse outcome: 5 (15%) neonates died; 4 (14%) survivors developed postinfectious hydrocephalus and three (9%) additional survivors had neurodevelopmental impairment. All three isolates were resistant to vancomycin, two were resistant to penicillin and ampicillin and one was unlikely to be sensitive to ceftriaxone; all were susceptible to gentamicin and meropenem. The genomes of all three strains contained multiple beta-lactamase genes and a cluster of genes that encodes a type IV pilus. Clinical signs at presentation for neonates with good and poor outcomes followng paenibacillosis. Conclusion Molecular methods such as 16S rRNA sequencing and PCR can be used to improve the identification of pathogens causing neonatal sepsis. Paenibacillosis is an important emerging cause of neonatal sepsis in Uganda and is likely an underrecognized cause of postinfectious hydrocephalus in the region and possibly elsewhere. Antibiotics commonly used for neonatal sepsis may be inadequate for the treatment of paenibacillosis. Additional studies to understand the pathophysiology and optimal treatment of this novel infection are urgently needed to prevent neonatal mortality and morbidity including postinfectious hydrocephalus

Neonatal Paenibacilliosis: Paenibacillus infection as a Novel Cause of Sepsis in Term Neonates with High Risk of Sequelae in Uganda

Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at two Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacillosis vs. clinical sepsis. Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%) and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and one (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to two Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis. [Abstract copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].