Enhancing Candida auris Surveillance in High-Risk Settings by Implementing a High-Throughput Molecular Assay on the Hologic Fusion Open Access Platform.

Candida auris, a resilient pathogenic yeast with frequent multidrug resistance, presents a persistent challenge in healthcare settings. The timely identification of C. auris is crucial for infection control and prevention, especially in facilities facing unique hurdles, such as our institution, which serves four major hospitals and approximately 80% of the Texas inmate population. Understaffing, communal living, and financial constraints exacerbate infection control issues. To address common staff shortages, streamline testing services, and enhance testing efficiency, there was a pressing need for rapid and high-throughput detection of C. auris. This study presents the validation and utility of an assay implemented on the Hologic Fusion Open Access platform using samples collected from high-risk patients' axilla and groin areas, as well as environmental swab samples from patient rooms. Our assay complemented efforts to control C. auris outbreaks within our healthcare system, providing valuable insights into its presence within surveillance samples. This assay demonstrated the value of high-throughput molecular detection platforms in challenging healthcare environments by aiding infection preventionists in containing the spread of C. auris and preventing nosocomial infections. Our research contributes essential data on the suitability and performance of the Hologic Fusion Open Access platform for C. auris detection. These findings hold significant implications for enhancing surveillance and control measures in high-risk settings, making a significant impact on the field of infection control and prevention.

Bilateral adrenal hemorrhage and severe anemia in a neonate.

Summary: Neonatal adrenal hemorrhage (NAH) occurs in up to 3% of infants and is the most common adrenal mass in newborns. The most common presentation of NAH is an asymptomatic palpable flank mass which resolves over time without intervention. In rare cases, NAH can present as hemorrhage, shock, or adrenal insufficiency. This case describes a preterm infant born with severe anemia in the setting of bilateral adrenal hemorrhages with resulting adrenal insufficiency. The infant was successfully treated with blood transfusions and steroids. This is a unique presentation of NAH as it was bilateral, presented with severe anemia, and resulted in prolonged adrenal insufficiency. Learning points: Consider adrenal hemorrhage for cases of severe anemia at birth. Adrenal insufficiency is a rare complication of adrenal hemorrhage. Adrenal recovery can take months, if not years.

A cluster investigation of Candida auris among hospitalized incarcerated patients.

Objective: Investigate and mitigate a cluster of Candida auris cases among incarcerated patients in a maximum-security prison hospital utilizing contact tracing, screening, whole genome sequencing, and environmental sampling and decontamination. Design: Outbreak investigation. Setting: Inpatient prison hospital affiliated with an academic tertiary referral center. Patients: Inmates of the Texas Department of Criminal Justice. Methods: Epidemiologic and environmental investigations were conducted including contact tracing, point prevalence surveys, and environmental sampling. Whole genome sequencing was performed on positive patient isolates. Results: Following a clinical case of C. auris fungemia, 344 patients underwent C. auris surveillance screening. Eight (2.3%) patients were identified with C. auris colonization. All patients were male. Our index patient was the only clinical case and death. Whole genome sequencing was performed on the nine patient isolates. All isolates were clade III (Africa) and clustered together with the largest SNP difference being 21. Environmental cultures from 7 of 61 rooms (11.5%) were positive following terminal disinfection with bleach. Sites nearest to the patient were most often positive including the hospital bed rails and bedside table. The transmission cluster was successfully mitigated within 60 days of identification. Conclusions: Implementation of an aggressive surveillance and decontamination program resulted in mitigation of a C. auris transmission cluster among our incarcerated patients. This investigation provides valuable insight into C. auris transmission in the incarcerated population, which is not considered a classic high-risk population as well as the challenges faced to stop transmission in a facility that requires the use of shared patient environments.

Muscle Properties, Gross Motor Performance, and Quality of Life in Children With Sickle Cell Disease.

PURPOSE: To explore muscle properties, gross motor performance, and quality of life (QoL) in children with sickle cell disease (SCD) compared with controls and to assess relationships among these outcomes. METHODS: A cross-sectional study of 24 children assessed muscle properties including: knee extension strength by dynamometry; vastus lateralis (VL) and rectus femoris (RF) muscle thickness by ultrasonography; and VL and RF neuromuscular activation (rate of muscle activation [RoA]) by electromyography (EMG). Gross motor performance and QoL were assessed by standardized tests and questionnaires. RESULTS: Children with SCD had impaired knee extension strength, VL EMG RoA, gross motor performance, and QoL compared with children without SCD. Relationships among muscle properties, gross motor performance, and QoL were identified. CONCLUSIONS: These findings indicate that comprehensive muscle properties, gross motor performance, and QoL assessments should be considered to support and develop individualized physical therapy plans for children with SCD.

Quantifying muscle strength, size, and neuromuscular activation in adolescent and young adult survivors of musculoskeletal sarcoma: Identifying correlates and responses to functional strengthening.

BACKGROUND: Medical and surgical treatment for musculoskeletal sarcoma (MSS) place survivors at risk for impairments in muscle properties including muscle strength, muscle size, and neuromuscular activation. The purpose of this study was to explore muscle properties, gross motor performance, and quality of life (QoL) and the changes in response to a 6-week functional strengthening intervention (PT-STRONG) in MSS survivors of childhood cancer (CCS). METHODS: Eight lower extremity MSS CCS (13-23 years old) performed baseline testing and three completed PT-STRONG. Participants completed measurements of knee extension strength using handheld dynamometry, vastus lateralis (VL) and rectus femoris (RF) muscle thickness using ultrasonography at rest, and neuromuscular activation using electromyography during strength testing and a step-up task. Participants also completed gross motor and QoL assessments. RESULTS: Compared with the non-surgical limb, MSS CCS had lower surgical limb knee extension strength, VL muscle thickness, and RF step-up muscle rate of activation (RoA). Compared with normative values, MSS CCS had decreased bilateral knee extension strength, gross motor performance, and physical QoL. Positive correlations among muscle strength, muscle thickness, and gross motor performance were identified. After PT-STRONG, MSS CCS had improvements in VL muscle thickness, VL and RF RoA duing step-up, gross motor performance, and physical QoL. CONCLUSIONS: Positive association between larger muscle thickness with greater knee extension strength, and higher knee extension strength with better gross motor performance indicate that comprehensive physical therapy assessment and interventions that identify and target impairments in muscle properties to guide clinical decision making should be considered for MSS CCS into survivorship.

The Efficacy of Targeted Exercise on Gross Motor and Neuromuscular Performance in Survivors of Childhood Leukemia: A Pilot Study.

Objectives: This quasi-experimental study examined the efficacy of targeted exercise training on gross motor performance and neuromuscular impairments in survivors of childhood acute lymphoblastic leukemia (ALL CCS). Materials and Methods: Ten ALL CCS (median age: 10 years; range: 6-14 years) performed a 6-week training program three times per week (five in-person sessions), including a warm-up, total body stretching, progressive jump rope training, and a cool down. Gross motor performance (test of gross motor proficiency) and lower extremity rate of muscle activation (electromyography), joint torques (motion capture and force plate), and jump height (motion capture) were measured during a countermovement jump at baseline and post-training. Results: Post-training, ALL CCS demonstrated improvements in body coordination, strength and agilty, bilateral coordination, running speed and agility, and strength gross motor performance (mean change: 1.6-8.1; p < 0.05), the rate of muscle activation of the tibialis anterior and vastus lateralis muscles (mean change: 0.58-0.75; p < 0.05), hip and ankle joint torques (mean change: 0.07; p < 0.05), and jump height (mean change: 0.05; p < 0.05). Conclusion: This study demonstrated that targeted exercise training can improve gross motor performance and neuromuscular impairments in ALL CCS post-medical treatment.

Exploring relationships between inspiratory muscle strength and functional capacity in childhood cancer survivors: a pilot study.

Childhood cancer survivors (CCS) experience short- and long-term side effects from cancer treatment that often impair functional capacity. Inspiratory muscle weakness is a potential mechanism for reduced functional capacity. The objective of this pilot study was to examine the relationship between inspiratory muscle strength and functional capacity in 10 CCS. Inspiratory muscle strength was measured by maximal inspiratory pressure (MIP) while functional capacity was measured by the two-minute walk test (2MWT), the physiological cost index and hemodynamic response to exercise according to changes in heart rate, blood pressure and rate-pressure product (RPP). Overall, MIP and 2MWT distance were below predicted values. Hemodynamic responses to the 2MWT were consistent with little variation, except for elevated diastolic blood pressure (DBP) response. MIP had significant relationships with resting DBP (Spearman's rank correlation coefficient [rs] = -0.70; p = 0.03) and DBP response (rs = 0.72; p = 0.02). Time since completion of cancer treatment had a significant positive relationship with RPP response (rs = 0.67; p = 0.03). Inspiratory muscle weakness in childhood cancer could be an indicator of skeletal muscle dysfunction and should be considered when symptoms of dyspnea or poor functional capacity arise. Inspiratory muscle strength was found to be related to changes in blood pressure in CCS. Future studies should further investigate these relationships and the impact of inspiratory muscle training on hemodynamics and functional capacity in CCS.

Embryonal Rhabdomyosarcoma with Posttherapy Cytodifferentiation and Aggressive Clinical Course.

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents. Embryonal rhabdomyosarcoma (ERMS), its most common subtype, is a malignant soft tissue tumor with morphologic and immunophenotypic features of embryonic skeletal muscle. The histologic findings in ERMS typically include a range of differentiation in rhabdomyoblasts from primitive to terminally differentiated forms, and the latter become more prominent after chemotherapy-induced cytodifferentiation. Several reports have shown therapy-related cytodifferentiation to portend a good prognosis in ERMS. We discuss the case of a pediatric patient who presented with ERMS of the orbit. Although her tumor showed extensive posttreatment cytodifferentiation and several other good prognostic clinicopathologic factors, it pursued an aggressive course, resulting in early metastasis and death. This case represents an unusual course and may be instructive as to the clinicopathologic features impacting prognostication, and ultimately the biology, of this aggressive family of tumors.

Multi-Generational Review of Oncologic Tumors in a Family With TP53 Mutation Presenting With a Pediatric Patient With Osteosarcoma and Lung Acinar Adenocarcinoma.

TP53 mutation, Li-Fraumeni syndrome (LFS), is a syndrome that leads to a hereditary cancer predisposition. Here we describe the case of a 13-year-old male who presented with osteosarcoma, family history of LFS, who developed a second primary tumor of the lung. No other similar cases have been reported. After this osteosarcoma diagnosis, he had pre-operative imaging, which included a positron emission tomography (PET) combined with CT (PET/CT) chest. This revealed a subpleural nodule in the lung of unclear etiology. After completing initial therapy, a repeat chest CT showed that the nodule persisted. Pathology revealed an acinar adenocarcinoma. This tumor is not common in pediatric LFS patients.

Neuromuscular mechanisms that contribute to gross motor performance in survivors of childhood acute lymphoblastic leukemia.

PURPOSE: This study explored neuromuscular mechanisms and clinical measures that contribute to countermovement jump performance in survivors of childhood acute lymphoblastic leukemia (ALL CCS) compared to age- and sex-matched peers. METHODS: This exploratory cross-sectional observational study examined 12 participants, six ALL CCS and six age- and sex-matched peers (7-16 years). During a countermovement jump, rates of muscle activation of lower leg muscles were measured with electromyography, and joint torques and peak jump height with force plates and a motion capture system. Clinical measures included muscle extensibility, balance, and mobility measured by active ankle dorsiflexion, Bruininks-Oseretsky Motor Proficiency (BOT-2), and Timed Up and Go (TUG) tests. RESULTS: Compared to peers, ALL CCS demonstrated reduced gastrocnemius muscle extensibility and tibialis anterior rate of muscle activation, decreased jump height, and poorer performance on the BOT-2 and TUG. Jump height was significantly correlated with clinical measures of the BOT-2 and TUG. CONCLUSION: These ALL CCS demonstrated neuromuscular impairments that may impact jump performance, an essential childhood physical activity. Further research is needed to explore intervention strategies to improve the neuromuscular mechanisms that contribute to high-level gross motor skills in ALL CCS.

Diagnostic limitations and considerations in the imaging evaluation of advanced multicentric infantile myofibromatosis.

Infantile myofibromatosis, the most common fibrous tumor of infancy, is classified in 2 forms; as a solitary nodule or as numerous, widely-distributed multicentric lesions with or without visceral involvement. Although benign, multicentric myofibromas are still associated with a high incidence of morbidity and mortality due to the infiltration of critical structures. Herein, we present a case of an infant with aggressive PDGFRB and NOTCH3 mutation-negative myofibromas distributed throughout the vascular, respiratory, and gastrointestinal systems. The extensive disease resulted in pulmonary hypertension, respiratory failure and gastrointestinal obstruction refractory to chemotherapy and unamenable to surgical resection. Despite the presence of numerous highly invasive myofibromas, multiple imaging modalities largely underestimated, or even missed, tumors found at autopsy. This case demonstrates the limitations of radiographic imaging to assess disease burden in multicentric infantile myofibromatosis. The postmortem findings of extensive disease far exceeding what was demonstrated by multiple imaging modalities suggests that pediatricians should have a high index of suspicion for undetected tumors if clinical deterioration is otherwise unexplained.

Melanotic Neuroectodermal Tumor of Infancy: Case Report and Review of Management.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare pigmented tumor of the head and neck, which most commonly presents during the first year of life. Most cases present in the bones of the craniofacial region, including the maxilla (60.3%), skull (18.1%), and mandible (10.3%). The alveolar crest of the anterior maxilla is the most common site. MNTIs are locally aggressive, but benign, lesions derived from neural crest cells. However, they have a high rate of recurrence, and ≤6.5% of cases will demonstrate metastasis to lymph nodes or distant organs. They present clinically as an expansile pigmented mass. Radiographically, these lesions are often intraosseous expansile lytic lesions that can envelope or displace teeth. Extraosseous components might be better visualized on magnetic resonance imaging, demonstrating an enhancing iso- or hypointense mass on T1- and/or T2-weighted imaging. MNTIs have a distinctive biphasic cell population composed of large pigmented epithelial cells and small blue neuroblastic cells. Many immunohistochemical markers have also been identified. The large cell population often expresses cytokeratins, HMB-45, and vimentin; S100 is much less common. The small cell population typically expresses synaptophysin but will be negative for another neuroendocrine marker, chromogranin A. Rarely, patients will have elevated levels of urine vanillylmandelic acid, similar to findings from other tumors of neuroectodermal origin, such as neuroblastomas. First-line treatment of these lesions should be surgery with the goal of complete local excision. Radiotherapy and chemotherapy have been described but have been largely used as adjuvant or neoadjuvant therapy and for metastatic disease. We present a case of MNTI in an 8-week-old male, who had presented with a nonpigmented mass of the mandible associated with a pathologic fracture. In addition to a review of the data, our case serves to highlight potential prognostic factors, current clinical management, and local complications of this rare tumor.

Diagnosis of biphenotypic acute leukemia: a paradigmatic approach.

Biphenotypic acute leukemia (BAL), or acute leukemia with a single population of blasts coexpressing markers of two different lineages, is a rare clinical entity. To define BAL, a scoring system was proposed by the European Group of Immunological Markers for Leukemias (EGIL) in 1995. However, increasing evidence suggests that this system has limitations, as acknowledged by the 2008 World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues. Although substantially improved in relation to the EGIL, the new WHO Classification is still not optimal for guiding the clinical management of patients with BAL. We propose a new paradigmatic approach to defining BAL based on recent clinical studies of BAL and advances in immunologic marker definition and cytogenetics, and applied our new approach to 8 cases of "BAL" among a cohort of 742 new acute leukemias in our Cancer Center. By our new criteria, 6 cases were reclassified as acute lymphoblastic leukemia (ALL), while only 2 were still classified as BAL. Our approach is also supported by analyses of the BAL cases previously reported by other institutions.

Molecular basis for decreased folylpoly-gamma-glutamate synthetase expression in a methotrexate resistant CCRF-CEM mutant cell line.

A CCRF-CEM mutant, CEM-p, has been shown to exhibit resistance to methotrexate due to decreased methotrexate polyglutamate accumulation. To ascertain the mechanism(s) responsible for this phenotype, we analyzed FPGS and SLC19A1 mRNA expression, examined FPGS promoter activity, and determined nucleotide sequence of the FPGS promoter and full length cDNA from CCRF-CEM and CEM-p cells. We identified in FPGS from CEM-p cells three amino acid substitutions that altered the ATP binding P-loop, glutamate/folate binding, and a conserved domain located at the carboxyl-terminal. Our data demonstrated for the first time the importance of the highly conserved domain (VTGSLHLVGGV) located at the carboxyl-terminal for FPGS activity.