Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients.

BACKGROUND: Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). METHODS: Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). RESULTS: Of 204 patients, median age at diagnosis was 11.1 years (range, 1-21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3-83.3). At a median follow-up of 10 years (interquartile range, 5-16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4-16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. CONCLUSION: This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.

Clinical Characteristics, Health Care Utilization, and Outcomes Among Patients in a Pilot Surveillance System for Invasive Mold Disease-Georgia, United States, 2017-2019.

Background: Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system. Methods: During 2017-2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases. Results: Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n = 66 [63.5%]), mucormycosis (n = 8 [7.7%]), and fusariosis (n = 4 [3.8%]); the most frequently affected body sites were pulmonary (n = 66 [63.5%]), otorhinolaryngologic (n = 17 [16.3%]), and cutaneous/deep tissue (n = 9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit-level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients. Conclusions: IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases.

Measles immunity gap among reproductive-age women participating in a simulated HIV vaccine efficacy trial in Zambia.

Measles is a vaccine-preventable viral disease whose vaccination coverage remains low in Zambia, where the target group for vaccination is children aged 9 to 18 months. In addition to inadequate measles vaccination coverage among children, few studies address potential resultant immunity gaps among adults. We analyzed data from a simulated HIV vaccine efficacy trial (SiVET) conducted from 2015-2017 among adult Zambian women of childbearing age to determine measles antibody seroprevalence before and after vaccination with the measles, mumps and rubella (MMR) vaccine. We used MMR vaccine as a substitute for an experimental HIV vaccine as part of a simulation exercise to prepare for an HIV vaccine efficacy trial. We found that 75% of women had measles antibodies prior to receiving MMR, which increased to 98% after vaccination. In contrast, mumps and rubella antibody prevalence was high before (93% and 97%, respectively) and after (99% and 100%, respectively) vaccination. The low baseline measles seropositivity suggests an immunity gap among women of childbearing age. We recommend that measles vaccination programs target women of childbearing age, who can pass antibodies on to neonates. Moreover, administering the MMR vaccine to clinical trial candidates could prevent measles, mumps or rubella-related adverse events during actual trials.

Insights into the Geomicrobiology of Biovermiculations from Rock Billet Incubation Experiments.

Biovermiculations are uniquely patterned organic rich sediment formations found on the walls of caves and other subterranean environments. These distinctive worm-like features are the combined result of physical and biological processes. The diverse microbial communities that inhabit biovermiculations may corrode the host rock, form secondary minerals, and produce biofilms that stabilize the sediment matrix, thus altering cave surfaces and contributing to the formation of these wall deposits. In this study, we incubated basalt, limestone, and monzonite rock billets in biovermiculation mixed natural community enrichments for 468-604 days, and used scanning electron microscopy (SEM) to assess surface textures and biofilms that developed over the course of the experiment. We observed alteration of rock billet surfaces associated with biofilms and microbial filaments, particularly etch pits and other corrosion features in olivine and other silicates, calcite dissolution textures, and the formation of secondary minerals including phosphates, clays, and iron oxides. We identified twelve distinct biofilm morphotypes that varied based on rock type and the drying method used in sample preparation. These corrosion features and microbial structures inform potential biological mechanisms for the alteration of cave walls, and provide insight into possible small-scale macroscopically visible biosignatures that could augment the utility of biovermiculations and similarly patterned deposits for astrobiology and life detection applications.

Episodic Visual Distortions and Stroke-Like Symptoms in a 56-Year-Old Man With Intravascular Lymphoma.

A healthy 56-year-old man presented with vision changes and left upper extremity motor and sensory changes. MRI of the brain without contrast was significant for multifocal areas of restricted diffusion in multiple vascular territories. Neuro-Ophthalmic evaluation revealed an inferonasal visual field defect in the left eye, thickened choroid on optical coherence tomography, and bilateral delayed arteriovenous and choroidal filling on fluorescein angiogram. Repeat MRI demonstrated interval enlargement of many of the same foci of abnormal diffusion-weighted imaging signal. Computed tomography of the abdomen and pelvis revealed 3 distinct lobulated retroperitoneal masses that were biopsied and found to be consistent with diffuse large B-cell lymphoma. Brain biopsy specimens showed intravascular lymphocytes, confirming a diagnosis of intravascular lymphoma (IVL). In this diagnostically challenging case, a link was established between the presence of multiple strokes (some of which showed slow evolution over time) and retinochoroidal hypoperfusion, which provided a critical clue to the ultimate diagnosis of IVL.

Development of a new molecular subtyping tool for Salmonella enterica serovar Enteritidis based on single nucleotide polymorphism genotyping using PCR.

The lack of a sufficiently discriminatory molecular subtyping tool for Salmonella enterica serovar Enteritidis has hindered source attribution efforts and impeded regulatory actions required to disrupt its food-borne transmission. The underlying biological reason for the ineffectiveness of current molecular subtyping tools such as pulsed-field gel electrophoresis (PFGE) and phage typing appears to be related to the high degree of clonality of S. Enteritidis. By interrogating the organism's genome, we previously identified single nucleotide polymorphisms (SNP) distributed throughout the chromosome and have designed a highly discriminatory PCR-based SNP typing test based on 60 polymorphic loci. The application of the SNP-PCR method to DNA samples from S. Enteritidis strains (n = 55) obtained from a variety of sources has led to the differentiation and clustering of the S. Enteritidis isolates into 12 clades made up of 2 to 9 isolates per clade. Significantly, the SNP-PCR assay was able to further differentiate predominant PFGE types (e.g., XAI.0003) and phage types (e.g., phage type 8) into smaller subsets. The SNP-PCR subtyping test proved to be an accurate, precise, and quantitative tool for evaluating the relationships among the S. Enteritidis isolates tested in this study and should prove useful for clustering related S. Enteritidis isolates involved in outbreaks.

High resolution assembly and characterization of genomes of Canadian isolates of Salmonella Enteritidis.

BACKGROUND: There is a need to characterize genomes of the foodborne pathogen, Salmonella enterica serovar Enteritidis (SE) and identify genetic information that could be ultimately deployed for differentiating strains of the organism, a need that is yet to be addressed mainly because of the high degree of clonality of the organism. In an effort to achieve the first characterization of the genomes of SE of Canadian origin, we carried out massively parallel sequencing of the nucleotide sequence of 11 SE isolates obtained from poultry production environments (n = 9), a clam and a chicken, assembled finished genomes and investigated diversity of the SE genome. RESULTS: The median genome size was 4,678,683 bp. A total of 4,833 chromosomal genes defined the pan genome of our field SE isolates consisting of 4,600 genes present in all the genomes, i.e., core genome, and 233 genes absent in at least one genome (accessory genome). Genome diversity was demonstrable by the presence of 1,360 loci showing single nucleotide polymorphism (SNP) in the core genome which was used to portray the genetic distances by means of a phylogenetic tree for the SE isolates. The accessory genome consisted mostly of previously identified SE prophage sequences as well as two, apparently full-sized, novel prophages namely a 28 kb sequence provisionally designated as SE-OLF-10058 (3) prophage and a 43 kb sequence provisionally designated as SE-OLF-10012 prophage. CONCLUSIONS: The number of SNPs identified in the relatively large core genome of SE is a reflection of substantial diversity that could be exploited for strain differentiation as shown by the development of an informative phylogenetic tree. Prophage sequences can also be exploited for SE strain differentiation and lineage tracking. This work has laid the ground work for further studies to develop a readily adoptable laboratory test for the subtyping of SE.