Strengthening Warfighter Resiliency Using Broad-Spectrum or Host-Directed Therapies within the Rapid Acquisition and Investigation of Drugs for Repurposing Program.

To maintain cadence with looming threats in a prolonged field-care environment, the broader medical countermeasure (MCM) enterprise must adopt new strategies for chemical, biological, radiological, and nuclear (CBRN)-addressing drug development. The Countering Emerging Threats - Rapid Acquisition and Investigation of Drugs for Repurposing (CET RAIDR) program within the Joint Program Manager for CBRN Medical is designed to rapidly tackle known, unknown, and emerging threats by utilizing late-stage or licensed therapeutics. The focus of the CET RAIDR effort is to bridge treatment gaps between threat identification and the implementation of licensed targeted MCMs, thereby strengthening warfighter resiliency. The repurposing approach conserves both time to market and funds by leveraging previous conventional development work as a launch point for repurposing efforts. The CET RAIDR program minimizes development and procurement costs by supplementing the military medical providers' toolbox with post-phase II therapies that demonstrate established safety and manufacturing processes, leading to a cost-sparing model for niche medicines (i.e., CBRN MCMs). SIGNIFICANCE STATEMENT: Countering Emerging Threats - Rapid Acquisition and Investigation of Drugs for Repurposing program candidates are selected based on several pillars: a proven human safety profile, the availability of tools and validated literature on the drug's mechanism of action, well defined assays, and/or animal models to demonstrate efficacy, as well as collaborations with willing and trusted industry partners. This broader repurposing approach to address the growing chemical, biological, radiological, and nuclear threat landscape will better safeguard the warfighter against well documented or unpredictable threats when a direct-acting medical countermeasure is unavailable or not yet conceived.

VIPoma: an unsuspecting culprit of severe secretory diarrhoea in a human immunodeficiency virus-infected patient.

A 35-year-old man with known human immunodeficiency virus experienced chronic diarrhoea for 18 months. He presented to multiple hospitals with profuse secretory diarrhoea and life-threatening electrolyte disturbances. Infectious and non-infectious aetiologies were considered, with focussed history and investigations ultimately leading to a diagnosis of VIPoma. Initiation of somatostatin analogue therapy followed by surgical resection led to complete resolution of symptoms and markedly improved quality of life.

Risk factors, treatment and outcomes of subacute thyroiditis secondary to COVID-19: a systematic review.

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.

Pituitary function following peptide receptor radionuclide therapy for neuroendocrine tumours.

Peptide receptor radionuclide therapy (PRRT) is an increasingly used treatment for unresectable neuroendocrine tumours (NETs) that express somatostatin receptors. Normal pituitary tissue expresses somatostatin receptors so patients receiving PRRT may be at risk of developing hypopituitarism. The aim was to assess the prevalence of clinically significant hypopituitarism a minimum of 2 years following radioisotope therapy for metastatic NET. This was a multicentre study (Australia and New Zealand). Sixty-six patients with unresectable NETs were included-34 had received PRRT and 32 comparison patients. Median follow-up after PRRT was 68 months. Male hypogonadism was the most common hormonal abnormality (16 of 38 men [42%]) from the total cohort. Of these, seven men had primary hypogonadism (five from PRRT group) and nine had secondary hypogonadism (six in PRRT group). There was no difference in either male hypogonadism or other hormonal dysfunction between patients who had received PRRT and those that had not. Patients who have received PRRT out to 68 months following treatment do not show concerning hypopituitarism although there may be the suggestion of growth hormone deficiency developing. However, hypogonadism is common in men with NETs so the gonadal axis should be assessed in men with suggestive symptoms as the treatment of testosterone deficiency may improve the quality of life.

Developing the next generation of healthcare professionals: the impact of an interprofessional education placement model.

Interprofessional education (IPE), as preparation for interprofessional practice, is considered essential for quality, coordinated, outcome-focussed patient care. To develop capacity in our future healthcare practitioners, IPE needs to be developed within curricula, and opportunities provided to practise within the placement setting. The aim of this study was to examine the effect of a structured IPE placement program on students' perceptions of IPE within an authentic healthcare setting. This paper reports on changes in students' attitudes toward IPE, as measured by the SPICE-R2 instrument, in response to program involvement. Thirty-six students from six health professions participated in the study and reported significantly improved perceptions toward IPE, particularly in their understanding of roles and responsibilities, teamwork, and patient outcomes. The outcomes reinforce the importance of offering intentional and structured IPE activities during placement and the value provided to health students, preparing them for future collaborative practice.

Multiple Endocrine Tumors Associated with Germline MAX Mutations: Multiple Endocrine Neoplasia Type 5?

CONTEXT: Pathogenic germline MAX variants are associated with pheochromocytoma and paraganglioma (PPGL), pituitary neuroendocrine tumors and, possibly, other endocrine and nonendocrine tumors. OBJECTIVE: To report 2 families with germline MAX variants, pheochromocytomas (PCs) and multiple other tumors. METHODS: Clinical, genetic, immunohistochemical, and functional studies at University hospitals in Australia on 2 families with germline MAX variants undergoing usual clinical care. The main outcome measures were phenotyping; germline and tumor sequencing; immunohistochemistry of PC and other tumors; functional studies of MAX variants. RESULTS: Family A has multiple individuals with PC (including bilateral and metastatic disease) and 2 children (to date, without PC) with neuroendocrine tumors (paravertebral ganglioneuroma and abdominal neuroblastoma, respectively). One individual has acromegaly; immunohistochemistry of PC tissue showed positive growth hormone-releasing hormone staining. Another individual with previously resected PCs has pituitary enlargement and elevated insulin-like growth factor (IGF-1). A germline MAX variant (c.200C>A, p.Ala67Asp) was identified in all individuals with PC and both children, with loss of heterozygosity in PC tissue. Immunohistochemistry showed loss of MAX staining in PCs and other neural crest tumors. In vitro studies confirmed the variant as loss of function. In Family B, the proband has bilateral and metastatic PC, prolactin-producing pituitary tumor, multigland parathyroid adenomas, chondrosarcoma, and multifocal pulmonary adenocarcinomas. A truncating germline MAX variant (c.22G>T, p.Glu8*) was identified. CONCLUSION: Germline MAX mutations are associated with PCs, ganglioneuromas, neuroblastomas, pituitary neuroendocrine tumors, and, possibly, parathyroid adenomas, as well as nonendocrine tumors of chondrosarcoma and lung adenocarcinoma, suggesting MAX is a novel multiple endocrine neoplasia gene.

PET detectives: Molecular imaging for phaeochromocytomas and paragangliomas in the genomics era.

Phaeochromocytomas and paragangliomas (PPGLs) are rare tumours that arise from the adrenal medulla or extra-adrenal sympathetic or parasympathetic paraganglia. Recent advances in genetics have greatly enhanced understanding of the pathogenesis and molecular physiology of PPGL. Concomitantly, advances in molecular imaging mean four techniques are now available for use in PPGLs: [123 I]-MIBG coupled with SPECT/CT; [18 F]- FDG, [68 Ga]-DOTATATE and [18 F]-FDOPA coupled with PET/CT. Each modality relies on unique cellular uptake mechanisms that are contingent upon the tumour's molecular behaviour-which, in turn, is determined by the tumour's genetic profile. This genotype-phenotype correlation means the appropriate choice of radiotracer may depend on the known (or suspected) underlying genetic mutation, in addition to the clinical indication for the scan-whether confirming diagnosis, staging disease, surveillance or determining eligibility for radionuclide therapy. Given these rapid recent changes in genetic understanding and molecular imaging options, many clinicians find it challenging to choose the most appropriate scan for an individual with PPGL. To this end, recent guidelines published by the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging (EANM/SNMMI) have detailed the preferred radiotracer choices for individuals with PPGL based on their genotype and/or clinical presentation, providing timely clarity in this rapidly moving field. The current review summarizes the implications of the genotype-phenotype relationship of PPGL, specifically relating this to the performance of molecular imaging modalities, to inform and enable practising endocrinologists to provide tailored, personalized care for individuals with PPGL.

Post-acute hospital healthcare services for people with mild stroke: a scoping review.

BACKGROUND: People with mild stroke comprise a significant proportion of the overall stroke population. Previously this population has been viewed as having limited impairments, receiving minimal services following hospital discharge. Recent findings demonstrate that the implications of mild stroke are more significant than originally comprehended, warranting further services. OBJECTIVES: To identify the evidence-base regarding services for people with mild stroke, post-acute hospital discharge, that target secondary prevention and/or changes following stroke. METHODS: Scoping review utilizing the five-stage framework proposed by Arksey and O'Malley, with revisions by Levac, Colquhuon, and O'Brien. Framework stages included: identification of a research question and relevant studies, study selection, charting of data, and collating, summarizing, and reporting. A critical appraisal using the Downs and Black Checklist was added to determine methodological quality of studies. The search strategy used six databases: Pubmed, Embase, PsycINFO, CINAHL, OTseeker, and Scopus, alongside a hand-search. Three researchers were involved in article selection and two in critical appraisal. RESULTS: Twelve articles met inclusion criteria from 589 identified. A number of study methodologies were used to assess services, with varying methodological qualities. Studies were located within two major regions in the world. Five main approaches to service provision were identified: telehealth, exercise and education, Comprehensive Cardiac Rehabilitation, one-off visits and care-plan development, and community group programs. The majority of programs focused on secondary prevention and were aimed at an impairment level, with a mix of findings observed. CONCLUSION: Further development and assessment of services is warranted. Incorporation of the entire transition period, and research that is mild stroke and location-specific is advised. Attention to maximizing participation in daily life, secondary prevention, emotional well-being, and careful reporting is needed.

Oropharyngeal dysphagia in an elderly post-operative hip fracture population: a prospective cohort study.

BACKGROUND: normal ageing processes impact on oropharyngeal swallowing function placing older adults at risk of developing oropharyngeal dysphagia (OD). Anecdotal clinical experience has observed that older patients recovering from hip fracture surgery commonly develop OD post-operatively. OBJECTIVE: to document the presence of OD following hip fracture surgery, and the factors associated with OD. METHODS: one hundred and eighty-one patients with a mean age of 83 years (range: 65-103) admitted to a specialised orthogeriatric unit were assessed for OD post-surgery for hip fracture. Pre-admission, intra-operative and post-operative factors were examined to determine their relationship with the presence of OD. RESULTS: OD was found to be present post-operatively in 34% (n = 61) of the current population. Multivariate logistic regression analyses revealed the presence of pre-existing neurological and respiratory medical co-morbidities, presence of post-operative delirium, age and living in a residential aged care facility prior to hospital admission to be associated with the post-operative OD. CONCLUSION: these results highlight that OD is present in a large number of the older hip fracture population. Early identification of OD has important implications for the provision of timely dysphagia management that may prevent secondary complications and potentially reduce the hospital length of stay.

Acute myeloid leukemia, the 3q21q26 syndrome and diabetes insipidus: a case presentation.

Diabetes insipidus (DI) is a rare presenting complication of acute myeloid leukaemia (AML). Typically, the combination of DI and AML is associated with structural abnormalities of the neurohypophysis. We present a case of AML and DI presenting without any abnormalities of the neurohypophysis on radiological scanning and with normal cerebrospinal fluid examination. The AML karyotype at presentation was characterized by the presence of a t(3; 3)(q21; q26) translocation and monosomy 7. After treatment with induction chemotherapy, the patient achieved a complete remission and his DI resolved. At subsequent AML relapse, characterized by a complex karyotype without the t(3; 3)(q21; q26) translocation or monosomy 7, DI did not recur. Our case provides clinical support to the hypothesis that the t(3; 3)(q21; q26) translocation and/or monosomy 7 in AML may directly result in dysregulation of transcription factors resulting in development of DI in AML patients.

Electroglottographic evaluation of age and gender effects during sustained phonation and connected speech.

The aim of the present study was to evaluate the effects of age and gender on selected vocal fold vibratory behaviors during vowel prolongation and connected speech using electroglottography (EGG). Forty-six young and older individuals (23 males and 23 females) with normal voices participated in this study. EGG parameters including fundamental frequency and contact quotient were measured during sustained vowel prolongation and connected speech tasks. Significant age-by-gender interactions were found for both parameters. Moreover, results from discriminant function analyses revealed that the overall accuracies of the parameters in predicting different age and gender groups were higher for the connected speech tasks than for the sustained vowel prolongation task (89.1% and 73.9% for passage and phrase tasks vs 71.7% for vowel prolongation). These findings suggest that reliability of EGG measures can be affected by the test stimuli. Therefore, one should carefully consider the use of the speech material when assessing vocal fold behaviors using EGG. The findings also support the use of connected speech stimulus, preferably at passage level, in electroglottographic evaluation for a better representation of vocal fold vibrating behaviors.