Reforming Medical Physics and Radiopharmaceutical Science Training Through a Programmatic Approach to Assessment.

OBJECTIVES: Programmatic assessment approaches can be extended to the design of allied health professions training, to enhance the learning of trainees. The Australasian College of Physical Scientists and Engineers in Medicine worked with assessment specialists at the Australian Council for Educational Research and Amplexa Consulting, to revise their medical physics and radiopharmaceutical science training programs. One of the central aims of the revisions was to produce a training program that provides standardized training support to their registrars throughout the 3 years, better supporting their registrars to successfully complete the program in the time frame through providing timely and constructive feedback on the registrar's progression. METHODS: We used the principles of programmatic assessment to revise the assessment methods and progression decisions in the three training programs. RESULTS: We revised the 3-year training programs for diagnostic imaging medical physics, radiation oncology medical physics and radiopharmaceutical science in Australia and New Zealand, incorporating clear stages of training and associated progression points. CONCLUSIONS: We discuss the advantages and difficulties that have arisen with this implementation. We found 5 key elements necessary for implementing programmatic assessment in these specialized contexts: embracing blurred boundaries between assessment of and for learning, adapting the approach to each specialized context, change management, engaging subject matter experts, and clear communication to registrars/trainees.

Safety but limited efficacy of donor lymphocyte infusion for post-transplantation cyclophosphamide-treated patients.

The therapeutic efficacy of donor lymphocyte infusions (DLIs) given after allogeneic hematopoietic cell transplantation (HCT) is limited by risk of graft-versus-host disease (GVHD). Post-transplantation cyclophosphamide (PTCy) effectively prevents severe GVHD, but there are limited data on outcomes of DLIs given to PTCy-treated patients. We reviewed 162 consecutive PTCy-treated patients transplanted between 2015-2022 within the Center for Immuno-Oncology at the National Cancer Institute. Of 38 DLIs given to 21 patients after 22 HCTs, few DLIs were associated with toxicities of acute GVHD (7.8%), cytokine release syndrome (CRS, 7.8%), or chronic GVHD (2.6%), and all occurred in those receiving serotherapy-containing pre-HCT conditioning (50% of HCTs). Seven DLIs resulted in complete response (18.4%), with 5 of these given after HCTs using serotherapy-containing conditioning. Excluding infectious indications, complete response to DLIs given after transplants with versus without serotherapy-containing pre-HCT conditioning were 30% and 4.3%, respectively. Two patients received DLI for infection and experienced complete resolution without GVHD or CRS, although the efficacy cannot be definitively attributable to the DLI. DLIs given to PTCy-treated patients had low toxicity but limited efficacy, although pre-HCT serotherapy may modulate both toxicity and response. Novel strategies are needed to enhance the therapeutic efficacy of post-transplant cellular therapies without aggravating GVHD.

Healthcare transition in pediatric neurosurgery: lessons learned from a pilot program for patients with hydrocephalus and spina bifida.

OBJECTIVE: The pediatric neurosurgical community has increasingly recognized the importance of healthcare transition, the process of moving a patient from a pediatric to an adult model of care. However, surveys of pediatric neurosurgeons have revealed that few institutions have formal transition programs. Here, the authors share their preliminary experience with the development of a formal transition pilot program for patients with spina bifida and/or hydrocephalus. METHODS: Patients 18 years of age or older with a diagnosis of spina bifida and/or hydrocephalus who were followed by a pediatric neurosurgeon at Connecticut Children's from January 2017 to December 2023 and were recommended to transition to an adult neurosurgeon were retrospectively reviewed. Patients in the informal transition program (ITP) cohort (i.e., the recommendation to transition was made before the formal transition program [FTP] was developed in early 2020) were compared with those in the FTP cohort. RESULTS: Twenty-two patients met inclusion criteria with 7 (31.8%) in the ITP cohort and 15 (68.2%) in the FTP cohort. The median age at the time of the recommendation to transition was similar in both ITP and FTP cohorts (24 [IQR 20-35] years vs 25 [IQR 24-27] years, respectively). Four (57.1%) patients in the ITP cohort had a confirmed visit with an adult neurosurgeon, compared with 13 (86.7%) patients in the FTP cohort (p = 0.274). One patient in the ITP cohort with a failed transition returned to pediatric neurosurgical care, and 1 patient in the FTP cohort required a shunt revision by an adult neurosurgeon within 1 year of the recommendation to transition. CONCLUSIONS: Healthcare transition is recognized as a priority within pediatric neurosurgery, but structured, formal transition programs remain underdeveloped. The authors' preliminary experience with a pilot transition program demonstrated that patients who underwent a formal transition were more likely to successfully establish care with an adult neurosurgeon and trended toward less resource utilization.

Cemented and Press-fit Femoral Stems for the Management of Oncologic Femoral Tumors.

BACKGROUND: Stem fixation in reconstruction after resection of femoral tumors is debated. Cemented stems offer immediate stability but risk aseptic loosening, while press-fit stems allow bone ingrowth but risk stress shielding and subsidence. Our retrospective review aimed to determine implant failure rates and their associated factors, as well as the rates of infection, debridement, and mortality for both fixation groups (cemented or press-fit stems) used in patients undergoing resection of femoral tumor disease and subsequent arthroplasty. METHODS: We retrospectively studied 252 patients who underwent resection of femoral tumors and subsequent arthroplasty using cemented (n = 173; 69%) or press-fit (noncemented) (n = 79; 31%) stems between 1999 and 2020. Implant failure was the primary outcome, with secondary outcomes including rates of implant infection, debridement, and mortality. Multivariable regression was done to assess risk factors for implant failures. RESULTS: The study found implant failure rates of 11% and 18% for cemented stems and press-fit stems, respectively. Lower stem to diaphyseal ratios ( P = 0.024) and younger patients ( P = 0.008) were associated with a higher risk of implant failure in cemented stems. The infection rates were 14% and 10% for cemented and press-fit stems, respectively. Debridement rates were 16% and 13% for cemented and press-fit stems, respectively, while the 1-year mortality rate was 16% for cemented stems and 1.5% for press-fit stems. CONCLUSIONS: This study is the largest of its kind, providing patient characteristics and outcomes in both cemented and press-fit stems in the setting of reconstruction for femoral tumors. Both methods can be effective, with outcomes dependent on patient-specific factors, such as life expectancy, activity level, and body habitus, as well as proper implant fit. Additional studies of both implants and longer follow-up are required to elucidate the optimal fixation method for each individual patient. LEVEL OF EVIDENCE: Level III, retrospective noncomparative study.

Gardnerella diversity and ecology in pregnancy and preterm birth.

The vaginal microbiome has been linked to negative health outcomes including preterm birth. Specific taxa, including Gardnerella spp., have been identified as risk factors for these conditions. Historically, microbiome analysis methods have treated all Gardnerella spp. as one species, but the broad diversity of Gardnerella has become more apparent. We explore the diversity of Gardnerella clades and genomic species in the vaginal microbiome of pregnant women and their associations with microbiome composition and preterm birth. Relative abundance of Gardnerella clades and genomic species and other taxa was quantified in shotgun metagenomic sequencing data from three distinct cohorts of pregnant women. We also assessed the diversity and abundance of Gardnerella variants in 16S rRNA gene amplicon sequencing data from seven previously conducted studies in differing populations. Individual microbiomes often contained multiple Gardnerella variants, and the number of clades was associated with increased microbial load, or the ratio of non-human reads to human reads. Taxon co-occurrence patterns were largely consistent across Gardnerella clades and among cohorts. Some variants previously described as rare were prevalent in other cohorts, highlighting the importance of surveying a diverse set of populations to fully capture the diversity of Gardnerella. The diversity of Gardnerella both across populations and within individual vaginal microbiomes has long been unappreciated, as has been the intra-species diversity of many other members of the vaginal microbiome. The broad genomic diversity of Gardnerella has led to its reclassification as multiple species; here we demonstrate the diversity of Gardnerella found within and between vaginal microbiomes.IMPORTANCEThe present study shows that single microbiomes can contain all currently known species of Gardnerella and that multiple similar species can exist within the same environment. Furthermore, surveys of demographically distinct populations suggest that some species appear more commonly in certain populations. Further studies in broad and diverse populations will be necessary to fully understand the ecological roles of each Gardnerella sp., how they can co-exist, and their distinct impacts on microbial communities, preterm birth, and other health outcomes.

Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.

People with HIV (PWH) have a higher age-adjusted mortality due to chronic immune activation and age-related comorbidities. PWH also have higher rates of clonal hematopoiesis (CH) than age-matched non-HIV cohorts; however, risk factors influencing the development and expansion of CH in PWH remain incompletely explored. We investigated the relationship between CH, immune biomarkers, and HIV-associated risk factors (CD4+ and CD8+ T cells, nadir CD4+ count, opportunistic infections [OIs], and immune reconstitution inflammatory syndrome [IRIS]) in a diverse cohort of 197 PWH with median age of 42 years, using a 56-gene panel. Seventy-nine percent had a CD4+ nadir below 200 cells/µL, 58.9% had prior OIs, and 34.5% had a history of IRIS. The prevalence of CH was high (27.4%), even in younger individuals, and CD8+ T cells and nadir CD4+ counts strongly associated with CH after controlling for age. A history of IRIS was associated with CH in a subgroup analysis of patients 35 years of age and older. Inflammatory biomarkers were higher in CH carriers compared with noncarriers, supporting a dysregulated immune state. These findings suggest PWH with low nadir CD4+ and/or inflammatory complications may be at high risk of CH regardless of age and represent a high-risk group that could benefit from risk reduction and potentially targeted immunomodulation.

Immune responses to SARS-CoV-2 mRNA vaccination in people with idiopathic CD4 lymphopenia.

BACKGROUND: The immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines is variable in individuals with different inborn errors of immunity or acquired immune deficiencies and is yet unknown in people with idiopathic CD4 lymphopenia (ICL). OBJECTIVE: We sought to determine the immunogenicity of mRNA vaccines in patients with ICL with a broad range of CD4 T-cell counts. METHODS: Samples were collected from 25 patients with ICL and 23 age- and sex-matched healthy volunteers (HVs) after their second or third SARS-CoV-2 mRNA vaccine dose. Anti-spike and anti-receptor binding domain antibodies were measured. T-cell receptor sequencing and stimulation assays were performed to quantify SARS-CoV-2-specific T-cell responses. RESULTS: The median age of ICL participants was 51 years, and their median CD4 count was 150 cells/µL; 11 participants had CD4 counts ≤100 cells/µL. Anti-spike IgG antibody levels were greater in HVs than in patients with ICL after 2 and 3 doses of mRNA vaccine. There was no detectable significant difference, however, in anti-S IgG between HVs and participants with ICL and CD4 counts >100 cells/µL. The depth of spike-specific T-cell responses by T-cell receptor sequencing was lower in individuals with ICL. Activation-induced markers and cytokine production of spike-specific CD4 T cells in participants with ICL did not differ significantly compared with HVs after 2 or 3 vaccine doses. CONCLUSIONS: Patients with ICL and CD4 counts >100 cells/µL can mount vigorous humoral and cellular immune responses to SARS-CoV-2 vaccination; however, patients with more severe CD4 lymphopenia have blunted vaccine-induced immunity and may require additional vaccine doses and other risk mitigation strategies.

Dual Mobility for Oncological Hip Reconstruction: Significantly Reduced Dislocation Rates at 5 years.

BACKGROUND: Although dual mobility total hip arthroplasty has become increasingly common in recent years, limited remains known on dual mobility in surgical oncology. This university-based investigation compared dislocation and revision rates of DMs, conventional total hip arthroplasty (THA), and hemiarthroplasties (HAs) for oncological hip reconstruction. METHODS: An institutional tumor registry was used to identify 221 patients undergoing 45 DMs, 67 conventional THAs, and 109 HAs, performed for 17 primary hip tumors and 204 hip metastases between 2010 and 2020. The median age at surgery was 65 years, and 52% were female. The mean follow-up was 2.5 years. Kaplan-Meier survivorship curves and log-rank tests were done to compare dislocation and revision rates among all 221 patients, after a one-to-one propensity match, based on age, sex, tumor type (metastasis, primary tumor), and tumor localization (femur, acetabulum). RESULTS: The 5-year survivorship free of dislocation was 98% in DMs, 66% in conventional THAs ( P = 0.03; all P values compared with DMs), and 97% among HAs ( P = 0.48). The 5-year survivorship free of revision was 69% in DMs, 62% in conventional THAs ( P = 0.68), and 92% in HAs ( P = 0.06). After propensity matching, the 5-year survivorship free of dislocation was 42% in 45 conventional THAs ( P = 0.027; compared with all 45 DMs) and 89% in 16 matched HAs ( P = 0.19; compared with 16 DMs with femoral involvement only). The 5-year survivorship free of revision was 40% in matched conventional THAs ( P = 0.91) and 100% in matched HAs ( P = 0.19). CONCLUSIONS: DMs showed markedly lower rates of dislocation than conventional THAs, with overall revision rates remaining comparable among different designs. DMs should be considered the option of choice for oncological hip reconstruction if compared with conventional THAs. HAs are a feasible alternative when encountering femoral disease involvement only. LEVEL OF EVIDENCE: III.

Survey of United States neurosurgeons on firearm injury prevention.

OBJECTIVE: Firearm-related injuries and deaths are an endemic problem in the US, posing a burden on the healthcare system with significant social and economic consequences. As front-line care providers for these patients, neurosurgeons are both knowledgeable about these injuries and credible messengers in the public discussion of ways to reduce firearm injuries. The purpose of this study was to explore US-based neurosurgeons' views and behaviors regarding firearms to understand and define a potential role for neurosurgical organizations in advocacy efforts to reduce firearm death and injuries. METHODS: The authors conducted an anonymous survey of US neurosurgeons using the American Association of Neurological Surgeons (AANS) member database from April to June 2023. The 22-question survey included questions related to firearm ownership, personal views on firearms, and support for both general and policy-specific advocacy efforts to reduce firearm deaths and injuries. RESULTS: The survey response rate was 20.7%, with 1568 of the 7587 members invited completing the survey. The survey completion rate was 93.4%, with 1465 of the 1568 surveys completed and included in this analysis. The majority of respondents were male (raw: 81.7%; weighted 81.1%), White (raw: 69.7%; weighted 70.2%), and older than 50 years (raw: 56.2%; weighted: 54%). Most respondents reported treating patients with firearm injuries (raw: 83.3%; weighted: 82%), 85.5% (weighted: 85.1%) had used a firearm, and 42.4% (weighted: 41.5%) reported owning a firearm. Overall, 78.8% (weighted: 78.7%) of respondents felt that organized neurosurgery should participate in advocacy efforts. When examining individual policies, those that restrict the acquisition of firearms garnered the support of at least 65% of respondents, while nonrestrictive policies were supported by more than 75% of respondents. Free-text responses provided insight into both motivations for and objections to organizational advocacy. CONCLUSIONS: The majority of US-based neurosurgeons support involvement in advocacy efforts to reduce firearm deaths and injuries. Themes expressed by members both supporting and objecting to advocacy provide insight into approaches that could ensure broad support. Neurosurgical organizations such as the AANS and Congress of Neurological Surgeons may use the results of this survey to make informed decisions regarding involvement in advocacy efforts on behalf of their membership to lessen the burden of firearm injury in the US.

Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals.

BACKGROUND: Functional T-cell responses are essential for virus clearance and long-term protection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas certain clinical factors, such as older age and immunocompromise, are associated with worse outcome. OBJECTIVE: We sought to study the breadth and magnitude of T-cell responses in patients with coronavirus disease 2019 (COVID-19) and in individuals with inborn errors of immunity (IEIs) who had received COVID-19 mRNA vaccine. METHODS: Using high-throughput sequencing and bioinformatics tools to characterize the T-cell receptor ß repertoire signatures in 540 individuals after SARS-CoV-2 infection, 31 IEI recipients of COVID-19 mRNA vaccine, and healthy controls, we quantified HLA class I- and class II-restricted SARS-CoV-2-specific responses and also identified several HLA allele-clonotype motif associations in patients with COVID-19, including a subcohort of anti-type 1 interferon (IFN-1)-positive patients. RESULTS: Our analysis revealed that elderly patients with COVID-19 with critical disease manifested lower SARS-CoV-2 T-cell clonotype diversity as well as T-cell responses with reduced magnitude, whereas the SARS-CoV-2-specific clonotypes targeted a broad range of HLA class I- and class II-restricted epitopes across the viral proteome. The presence of anti-IFN-I antibodies was associated with certain HLA alleles. Finally, COVID-19 mRNA immunization induced an increase in the breadth of SARS-CoV-2-specific clonotypes in patients with IEIs, including those who had failed to seroconvert. CONCLUSIONS: Elderly individuals have impaired capacity to develop broad and sustained T-cell responses after SARS-CoV-2 infection. Genetic factors may play a role in the production of anti-IFN-1 antibodies. COVID-19 mRNA vaccines are effective in inducing T-cell responses in patients with IEIs.

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

Management of limb length discrepancy after bone sarcoma resection about the knee in the skeletally immature.

Patients with bone sarcomas increasingly choose limb salvage. This can lead to issues with limb length discrepancy (LLD) for the skeletally immature. We synthesize management options into an algorithm and report our results. Patients with bone sarcomas involving any location from the femoral diaphysis to the tibial diaphysis 12 years or younger were reviewed. Our clinical pathway prescribed patients with metadiaphyseal lesions to intercalary allograft reconstruction, epiphyseal lesions and less than 5 cm expected LLD to osteoarticular allograft and patients with more than 5 cm expected LLD to extendable prosthesis. Twenty patients met inclusion criteria: 11 with osteoarticular allografts, 5 with extendable prostheses and 4 with intercalary allografts; median age 11.5 years; median follow-up 8.2 years; and final median LLD 1.6 cm. Five patients had contralateral epiphysiodesis, two patients underwent contralateral femoral shortening and a median of 6 (range 4-8) lengthenings were performed for extendable prostheses. Four patients had residual LLD over 3 cm. There were 13 revisions in 8 patients and 2 amputations. Limb-salvage in paediatric bone sarcoma of the knee can be managed with multiple techniques producing satisfactory results in regards to LLD. Careful pre-operative planning and shared decision making is a requisite given the high rate of secondary procedures for both LLD and reconstructive failures. Level of evidence: Level III Retrospective Comparative Study.

Natural history of mild trigonocephalic deformities.

OBJECTIVE: Ridging along the metopic suture line can be a common cause of concern for parents and has been theorized to represent a mild form of trigonocephaly, a cranial deformity associated with risks of negative cosmetic outcomes, if not surgically corrected. Yet the literature contains sparse reports of long-term cosmetic results or expectations for infants with isolated metopic ridging compared with those with severe trigonocephaly, or even what objective metrics discriminate isolated metopic ridging from severe trigonocephaly. Therefore, the authors' goals for this study were to 1) quantify the degree of frontal deformity among patients with metopic ridge, metopic craniosynostosis, and normocephalic head shapes; and 2) document the natural history of frontal deformities in isolated metopic ridge patients in the 1st year of life. METHODS: This was a retrospective cohort study of patients with normocephalic head shapes, metopic ridges, and metopic craniosynostoses who presented at < 1 year of age to the Connecticut Children's neurosurgery clinic from January 2019 to December 2021. Data were collected regarding demographics and photograph-based craniometrics. RESULTS: A total of 212 normocephalic, 34 metopic ridge, and 29 metopic craniosynostosis patients were included. Both the normocephalic and metopic ridge groups had a significantly higher anterior arc angle (AAA) value compared with the metopic craniosynostosis group (p < 0.0001). The AAA did not differ significantly among normocephalic patients and those with ridging. Over the course of 1 year of follow-up, patients with metopic ridging demonstrated a slight decrease in AAA values, but overall remained within the same range as normocephalic patients. CONCLUSIONS: Photograph-based craniometrics suggest that metopic ridge patients with frontal bone angulations > 2.2 radians have a mild degree of frontal constriction that does not significantly worsen over the 1st year of life.

Long-term Outcomes of Patients With HIV and Pneumocystis jirovecii Pneumonia in the Antiretroviral Therapy Era.

Background: Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in people with HIV (PWH). However, there are limited data on long-term outcomes of PCP in the antiretroviral therapy (ART) era. Methods: We conducted a secondary analysis of 2 prospective studies on 307 PWH, 81 with prior PCP, with a median follow-up of 96 weeks. Laboratory data were measured at protocol-defined intervals. We reviewed clinically indicated chest computerized tomography imaging in 63 patients with prior PCP at a median of 58 weeks after PCP diagnosis and pulmonary function tests (PFTs) of patients with (n = 10) and without (n = 14) prior PCP at a median of 18 weeks after ART initiation. Results: After 96 weeks of ART, PWH with prior PCP showed no significant differences in laboratory measurements, including CD4 count, when compared with those without prior PCP. Survival rates following ART initiation were similar. However, PWH with prior PCP had increased evidence of restrictive lung pathology and diffusion impairment in PFTs. Furthermore, on chest imaging, 13% of patients had bronchiectasis and 11% had subpleural cysts. Treatment with corticosteroids was associated with an increased incidence of cytomegalovirus disease (odds ratio, 2.62; P = .014). Conclusions: PCP remains an important opportunistic infection in the ART era. While it did not negatively affect CD4 reconstitution, it could pose an increased risk for incident cytomegalovirus disease with corticosteroid treatment and may cause residual pulmonary sequelae. These findings suggest that PCP and its treatment may contribute to long-term morbidity in PWH, even in the ART era.

Prevalence and antibiotic resistance of Staphylococcus aureus associated with a college-aged cohort: life-style factors that contribute to nasal carriage.

Staphylococcus aureus is an opportunistic human pathogen that can frequently be found at various body locations, such as the upper respiratory tract, nostrils, skin, and perineum. S. aureus is responsible for causing a variety of conditions, which range from minor skin infections and food poisoning to life-threatening sepsis and endocarditis. Furthermore, S. aureus has developed resistance to numerous antimicrobial agents, which has made treatment of S. aureus infections difficult. In the present study, we examined lifestyle factors that could increase the likelihood of S. aureus carriage, the overall prevalence of S. aureus, as well as assessed the antibiotic resistance profiles of the S. aureus isolates among a population of college students. Five hundred nasal samples were collected and analyzed via selective growth media, coagulase and protein A testing, as well as polymerase chain reaction and DNA sequencing. One hundred four out of the 500 samples collected (21%) were identified as containing S. aureus. The S. aureus isolates were resistant to penicillin (74%), azithromycin (34%), cefoxitin (5%), ciprofloxacin (5%), tetracycline (4%), and trimethoprim (1%), but sensitive to gentamicin and rifampin. Lastly, we identified several lifestyle factors (i.e., pet exposure, time spent at the university recreational facility, musical instrument usage, and tobacco usage) positively correlated with S. aureus nasal colonization.

Anterior hypothalamic parvalbumin neurons are glutamatergic and promote escape behavior.

The anterior hypothalamic area (AHA) is a critical structure for defensive responding. Here, we identified a cluster of parvalbumin-expressing neurons in the AHA (AHAPV) that are glutamatergic with fast-spiking properties and send axonal projections to the dorsal premammillary nucleus (PMD). Using in vivo functional imaging, optogenetics, and behavioral assays, we determined the role of these AHAPV neurons in regulating behaviors essential for survival. We observed that AHAPV neuronal activity significantly increases when mice are exposed to a predator, and in a real-time place preference assay, we found that AHAPV neuron photoactivation is aversive. Moreover, activation of both AHAPV neurons and the AHAPV → PMD pathway triggers escape responding during a predator-looming test. Furthermore, escape responding is impaired after AHAPV neuron ablation, and anxiety-like behavior as measured by the open field and elevated plus maze assays does not seem to be affected by AHAPV neuron ablation. Finally, whole-brain metabolic mapping using positron emission tomography combined with AHAPV neuron photoactivation revealed discrete activation of downstream areas involved in arousal, affective, and defensive behaviors including the amygdala and the substantia nigra. Our results indicate that AHAPV neurons are a functional glutamatergic circuit element mediating defensive behaviors, thus expanding the identity of genetically defined neurons orchestrating fight-or-flight responses. Together, our work will serve as a foundation for understanding neuropsychiatric disorders triggered by escape such as post-traumatic stress disorder (PTSD).

Giant cell-rich osteosarcoma: A match pair analysis of 11 new cases and literature review of 56 patients.

BACKGROUND: Limited remains known on giant cell-rich osteosarcoma (GCRO) with current studies being case reports or smaller series. This investigation compared GCRO and conventional osteoblastic osteosarcoma (OOS) with regard to demographics and survival. METHODS: An institutional tumor registry was used to identify 11 patients (six males) treated for GCRO. Mean age was 43 years. Staging showed American Joint Committee on Cancer (AJCC) stages IIA in four and IIB in seven patients. Mean follow-up was 14 years. Study initiatives were: (1) Comparison of demographics between GCRO and 167 OOS from our institutional registry, (2) Differences in survival between GCRO and 33 OOS case controls (based on sex and AJCC stage), as well as 10 OOS using an age-based propensity match, and (3) Summary of all GCRO cases reported in the literature. RESULTS: (1) Sex (p = 0.53), grading (p = 0.56), AJCC stage (p = 0.42), and chemotherapeutic response rate (p = 0.67) did not differ between groups. Age was significantly increased in GCRO (p = 0.001). (2) Case-control and propensity-matched groups revealed no difference in disease-free survival, local recurrence, and distant disease-free survival at 2 years (p > 0.05). (3) Mean age of 56 patients (50% males) reported in the literature was 26 years. After merging with our 11 cases, the 2-year disease-free survival was 66%. CONCLUSIONS: GCRO remains a rare disease with high short-term mortality. Although affecting older patients more than conventional osteosarcoma, GCRO should not be viewed as a predictor of survival compared to OOS.

A single-institution pediatric and young adult interventional oncology collaborative: Novel therapeutic options for relapsed/refractory solid tumors.

BACKGROUND: Pediatric interventional oncology (PIO) is a growing field intended to provide additional or alternative treatment options for pediatric patients with benign or malignant tumors. Large series of patients treated uniformly and subjected to rigorous endpoints for efficacy are not available. METHODS: We designed a collaborative initiative to capture data from pediatric patients with benign and malignant tumors who underwent a therapeutic interventional radiology procedure. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized as a measure of radiologic response and data were collected regarding improvement in pain and functional endpoints. Cumulative incidence of progressive disease was calculated using both the treated site and the patient as the analytic unit. FINDINGS: Forty patients, 16 with malignant tumors and 24 with benign tumors, underwent a total of 88 procedures. Cryo- and radiofrequency ablation were the most frequently utilized techniques for both cohorts of patients. A complete or partial response, or prolonged disease stability, were achieved in approximately 40% of patients with malignant tumors and 60% of patients with benign tumors. No patients had progressive disease as their best response. Resolution of pain and improved mobility with return-to-baseline activity were demonstrated across patients from both cohorts. Only minor complications were experienced. INTERPRETATION: Interventional radiology-guided interventions can serve as an alternative or complementary approach to the treatment of benign and malignant tumors in pediatric patients. Prospective, multi-institutional trials are required to adequately study utility, treatment endpoints, and durability of response.