The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Vestibular Schwannoma Stereotactic Radiosurgery in Octogenarians: Case Series.

BACKGROUND AND OBJECTIVES: The management of octogenarians with vestibular schwannomas (VS) has received little attention. However, with the increase in octogenarian population, more effort is needed to clarify the value of stereotactic radiosurgery (SRS) in this population. The aim of this study was to evaluate the safety and efficacy of SRS in this patient age group. METHODS: A retrospective study of 62 patients aged 80 years or older who underwent single-session SRS for symptomatic VS during a 35-year interval was performed. The median patient age was 82 years, and 61.3% were male. SRS was performed as planned adjuvant management or for delayed progression after prior partial resection in 5 patients. RESULTS: SRS resulted in a 5-year tumor control rate of 95.6% with a 4.8% risk of adverse radiation effects (ARE). Tumor control was unrelated to patient age, tumor volume, Koos grade, sex, SRS margin dose, or prior surgical management. Four patients underwent additional management including 1 patient with symptomatic progression requiring surgical resection, 2 patients with symptomatic hydrocephalus requiring cerebrospinal fluid diversion, and 1 patient whose tumor-related cyst required delayed cyst aspiration. Three patients developed ARE, including 1 patient with permanent facial weakness (House-Brackmann grade II), 1 who developed trigeminal neuropathy, and 1 who had worsening gait disorder. Six patients had serviceable hearing preservation before SRS, and 2 maintained serviceable hearing preservation after 4 years. A total of 44 (71%) patients died at an interval ranging from 6 to 244 months after SRS. CONCLUSION: SRS resulted in tumor and symptom control in most octogenarian patients with VS.

Aggressive Stereotactic Radiosurgery Coupled With Immune and Targeted Therapy for Recurrent Melanoma Brain Metastases: A Case Report and Literature Review.

Melanoma is a complex disease with a high propensity for brain metastatic spread. Stereotactic radiosurgery (SRS) is a minimally invasive procedure to treat intracranial metastasis with a high rate of local tumor control. In this report, we describe the ongoing management of a patient with interval development of both new and recurrent brain metastases that required seven SRS procedures for a total of 48 brain metastases during a two-year interval while receiving concurrent immunotherapy with ipilimumab and nivolumab. The most recent imaging of the patient showed three brain areas of likely tumor progression despite maintenance nivolumab, and the treatment was recently changed to encorafenib and binimetinib. Combined management with immunotherapy, initial craniotomy, and repeated SRS for new brain metastases resulted in extended survival while preserving neurological function and reducing adverse treatment effects in a patient with advanced metastatic brain melanoma.

A standardized instrument quantifying risk factors associated with bi-directional transmission of SARS-CoV-2 and other zoonotic pathogens: The COVID-19 human-animal interactions survey (CHAIS).

Similar to many zoonotic pathogens which transmit from animals to humans, SARS-CoV-2 (CoV-2), the virus responsible for the COVID-19 pandemic, most likely originated in Rhinolophus bats before spreading among humans globally. Early into the pandemic, reports of CoV-2 diagnoses in animals from various countries emerged. While most CoV-2 positive animals were confirmed to have been in close contact with CoV-2 positive humans, there has been a paucity of published evidence to-date describing risk factors associated with CoV-2 transmission among humans and animals. The COVID-19 Human-Animal Interactions Survey (CHAIS) was developed to provide a standardized instrument describing human-animal interactions during the pandemic and to evaluate behavioral, spatiotemporal, and biological risk factors associated with bi-directional zoonotic transmission of CoV-2 within shared environments, predominantly households with limited information about human-wildlife or human-livestock interactions. CHAIS measures four broad domains of transmission risk: 1) risk and intensity of infection in human hosts, 2) spatial characteristics of shared environments, 3) behaviors and human-animal interactions, and 4) susceptible animal subpopulations. Following the development of CHAIS, with a One Health approach, a multidisciplinary group of experts (n = 20) was invited to review and provide feedback on the survey for content validity. Expert feedback was incorporated into two final survey formats-an extended version and an abridged version for which specific core questions addressing zoonotic and reverse zoonotic transmission were identified. Both versions are modularized, with each section having the capacity to serve as independent instruments, allowing researchers to customize the survey based on context and research-specific needs. Further adaptations for studies seeking to investigate other zoonotic pathogens with similar routes of transmission (i.e. respiratory, direct contact) are also possible. The CHAIS instrument is a standardized human-animal interaction survey developed to provide important data on risk factors that guide transmission of CoV-2, and other similar pathogens, among humans and animals.

The Importance of Evaluating Positive Welfare Characteristics and Temperament in Working Therapy Dogs.

To date, investigations of the welfare of therapy dogs have focused largely on examining physiological and behavioral measures that could indicate if the animal is experiencing stress or distress. However, this approach does not fully address the definition of welfare which is often described as existing on a continuum from negative (or stressful) to positive. With therapy dogs, it would be worth addressing if they experience positive emotional affect while working since the quality and efficacy of animal-assisted interventions for the human recipient is likely to be influenced by the animal's emotional state during the interaction. The purpose of this review is to articulate how objective measurements of the HPA axis and measurements of behavioral observations and standardized questions can be used to evaluate positive welfare in therapy dogs. A potentially relevant indicator of positive welfare is the peripheral concentration of the neurohormone oxytocin, which has been found to increase in systemic circulation within a variety of species during positive social and affiliative contexts, including during human-dog interaction. Oxytocin is also a negative-feedback regulator of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which culminates with the production of the stress hormone cortisol. Cortisol is widely used as a physiological indicator to assess negative welfare states in animals, including therapy dogs. Observable behavior during interactions with humans that may convey enjoyment could provide indicators of positive welfare in dogs such as engagement in play, or human-directed affiliative behaviors including leaning against, nudging, or licking the patient. However, in assessing positive welfare, it is also critical to consider that all animal behavioral displays and physiological responses are dependent on the dog's individual (and breed) temperament. Temperament directly drives how the animal copes and responds to its current physical and social environment, including during stressful situations such as when therapy dogs interact with unfamiliar humans in novel healthcare settings. Coupled with both positive and negative physiological and behavioral welfare indicators, questionnaire data can provide further context to, and enhance interpretations of, therapy dog welfare assessment results. Overall, to date, no studies have measured all of these factors to assess therapy dog welfare.

Risks associated with animal-assisted intervention programs: A literature review.

The benefits of animal-assisted interventions (AAI), to utilize companion animals as an adjunctive treatment modality, is well-established and a burgeoning research field. However, few studies have evaluated the potential hazards of these programs, such as the potential for therapy animals to transfer hospital-associated pathogens between individuals and the hospital environment. Here we review the current literature on the possible risks of hospital-based AAI programs, including zoonotic pathogen transmission. We identified twenty-nine articles encompassing reviews of infection control guidelines and epidemiological studies on zoonotic pathogen prevalence in AAI. We observed substantial heterogeneity in infection control practices among hospital AAI programs. Few data confirmed pathogen transmission between therapy animals and patients. Given AAI's known benefits, we recommend that future research utilize a One Health framework to evaluate microbial dynamics among therapy animals, patients, and hospital environments. This framework may best promote safe practices to ensure the sustainability of these valuable AAI programs.