Swallowing rehabilitation following spinal injury: A case series.

Context/objective: Swallowing difficulties (dysphagia) are well recognized after spinal injury. There are no published rehabilitation efficacy studies to date. This study explored viability and outcomes of swallowing rehabilitation programs for four patients with persisting dysphagia.Design: Prospective, quantitative experimental longitudinal case series.Setting: Spinal rehabilitation unit or patients' homes.Interventions: Four patients engaged in a 6-week (3×weekly) individualized progressive rehabilitation program.Outcome measures: Objective videofluoroscopic measures of timing and displacement and a validated self-reported questionnaire - the Eating Assessment Tool (EAT-10) were taken pre-therapy, immediately post-therapy and EAT-10 was repeated at 3 months. Feeling and fatigue scale scores were taken before and after each therapy session.Results: Patients (63, 67 yr, 67 yr, 76 yr; 3 male) had varying spinal diagnoses (2 traumatic, all involving the C-spine) and length of dysphagia (6 weeks, 6 weeks, 12 weeks, 10 yr). Common physiological impairments across all patients were: reduced maximum hyoid displacement, reduced pharyngeal constriction and reduced pharyngoesophageal segment maximum opening. Therapy programs were well received with 100% compliance. Participants made quantitative improvements in their videofluoroscopic measures of timing and displacement. Three out of four participants were able to have their percutaneous endoscopic gastrostomies (PEG) removed. EAT-10 scores significantly improved for all patients (P < .001). Poor upper limb function and restricted neck flexion prohibited some exercises.Conclusions: For many patients following spinal injury, dysphagia resolves during the acute phase of post-surgery recovery. For some, significant pharyngeal impairments persist. This case series demonstrates potential to regain functional swallowing following a 6-week tailored rehabilitation program. High-quality research exploring efficacy of rehabilitation programs are warranted.

Microsatellite Instability-High, Malignant Insulinoma With Brain Metastasis.

Insulinomas are the most common type of functional pancreatic neuroendocrine tumor. Although insulinomas usually are noninvasive or benign, 10% are deemed invasive or malignant. The pathologic mechanisms that lead to the malignant phenotype are not well elucidated. In this case report, we present a patient with stage 4 malignant insulinoma with metastasis to the liver, bone, and brain. Genetic analysis of the tumor showed that the tumor was mismatch-repair deficient and had a high rate of microsatellite instability. There was loss of MLH1- and PMS2-encoded protein expression, and MLH1 and MEN1 variants were identified. Notably, the liver metastasis showed considerable tumor heterogeneity (well differentiated) compared with the brain metastasis (poorly differentiated).

Circulating Tumor DNA-Based Testing and Actionable Findings in Patients with Advanced and Metastatic Pancreatic Adenocarcinoma.

PURPOSE: Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing. With this study, we sought to characterize the ctDNA genomic alteration landscape in patients with advanced PDAC with a focus on actionable findings. MATERIALS AND METHODS: From December 2014 through October 2019, 357 samples collected from 282 patients with PDAC at Mayo Clinic underwent ctDNA testing using a clinically available assay. The majority of samples were tested using the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. Clinical data and outcome variables were available for 165 patients; with 104 patients at initial presentation. RESULTS: All patients included in this study had locally advanced or metastatic PDAC. Samples having at least one alteration, when variants of unknown significance (VUS) were excluded, numbered 266 (75%). After excluding VUS, therapeutically relevant alterations were observed in 170 (48%) of the total 357 cohort, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. KRAS, SMAD, CCND2, or TP53 alterations were seen in higher frequency in patients with advanced disease. CONCLUSION: Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC. We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis. IMPLICATIONS FOR PRACTICE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive and samples are often inadequate, requiring repeated invasive procedures and delays in treatment. Noninvasive methods to identify PDAC early in its course may improve prognosis in PDAC. Using ctDNA, targetable genes can be identified and used for treatment.

Aptamers as Modular Components of Therapeutic Nucleic Acid Nanotechnology.

Nucleic acids play a central role in all domains of life, either as genetic blueprints or as regulators of various biochemical pathways. The chemical makeup of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), generally represented by a sequence of four monomers, also provides precise instructions for folding and higher-order assembly of these biopolymers that, in turn, dictate biological functions. The sequence-based specific 3D structures of nucleic acids led to the development of the directed evolution of oligonucleotides, SELEX (systematic evolution of ligands by exponential enrichment), against a chosen target molecule. Among the variety of functions, selected oligonucleotides named aptamers also allow targeting of cell-specific receptors with antibody-like precision and can deliver functional RNAs without a transfection agent. The advancements in the field of customizable nucleic acid nanoparticles (NANPs) opened avenues for the design of nanoassemblies utilizing aptamers for triggering or blocking cell signaling pathways or using aptamer-receptor combinations to activate therapeutic functionalities. A recent selection of fluorescent aptamers enables real-time tracking of NANP formation and interactions. The aptamers are anticipated to contribute to the future development of technologies, enabling an efficient assembly of functional NANPs in mammalian cells or in vivo. These research topics are of top importance for the field of therapeutic nucleic acid nanotechnology with the promises to scale up mass production of NANPs suitable for biomedical applications, to control the intracellular organization of biological materials to enhance the efficiency of biochemical pathways, and to enhance the therapeutic potential of NANP-based therapeutics while minimizing undesired side effects and toxicities.

"A scarlet letter": Stigma and other factors affecting trust in the health care system for women seeking substance abuse treatment in a community setting.

Background: Trust in health care has been shown to influence health care utilization, perceptions of fair treatment, and health outcomes in the general population. The literature on trust in health care in individuals with a history of substance use disorder (SUD) is more limited, primarily examining the patient-provider relationship. Women seeking substance abuse treatment in community-based programs have higher rates of prior trauma and health disparities compared with male counterparts and the general population. With higher rates of prior trauma, this population is theoretically at high risk of decreased interpersonal trust and altered interpersonal relationships. Objective: This study sought to identify factors influencing trust in the health care system for women seeking substance abuse treatment in a community-based residential treatment program. Methods: Six client focus groups (n = 30), 1 provider focus group (n = 7), and 2 individual clinical administrator interviews (n = 2) were conducted between November 2016 and August 2017. Focus groups and interviews were audio recorded and transcribed. Coding and coding reconciliation were conducted by 2 independent coders. Themes were extracted and analyzed from sorted and coded quotes. Results: Six themes emerged. Factors that influence trust in the health care system in this population include (1) prior experiences with diagnosis, treatment, and outcomes; (2) stigma of addiction; (3) payment and reimbursement structure; (4) patient rights and protections; (5) efficiency-driven care; and (6) the health care system's role in causing and/or enabling addiction. Conclusions: These themes demonstrate a general distrust of the health care system by women in this population. Distrust is influenced by a perception of a health care system providing care that is variable in quality, often stigmatizing, unaffordable, efficiency driven, and often influencing individuals' SUD. This aligns with and extends prior literature around trust of health care in individuals with SUD. Future directions in research include formally assessing the impact of trust on health outcomes such as treatment entry and retention.

A Care Process Model to Deliver 177Lu-Dotatate Peptide Receptor Radionuclide Therapy for Patients With Neuroendocrine Tumors.

Purpose: To develop a care process model for the delivery of peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-Dotatate for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: A multidisciplinary, structured PRRT process model was established. Over the last 9 months, meetings were held bi-weekly to discuss the logistics of clinical trials. Meetings are still held regularly at the Mayo Clinic Florida to discuss plans regarding commercially available PRRT treatments. The process model has evolved as we have treated patients on both clinical trials and commercial treatments. Results: An effective process model was formulated. We had 5 patients on our Expanded Access Program (EAP) clinical trial. Our ability to be a part of the EAP allowed us to understand the mechanics of how to treat these patients, and what was involved before it became commercially available. Since commercial availability of the 177Lu-Dotatate, more than 50 treatments (>20 patients) have already been completed, with several new patients getting started on treatment every week. Our nuclear medicine department receives continual requests to schedule new patients for PRRT. This can be attributed to our streamlined approach in delivering PRRT to our patients. Conclusion: A thorough procedural approach was formulated to provide patients with PRRT. Experiences and challenges led to refinement, which has allowed the process to advance. This development could lead to better patient outcomes, treatment efficiency, and a reference standard for other institutions trying to develop this at their location.

Esophageal visualization as an adjunct to the videofluoroscopic study of swallowing.

OBJECTIVE: Complaints of dysphagia for solids lead to speech-language pathology (SLP) referral. Yet many of these patients are later diagnosed with esophageal rather than oropharyngeal dysphagia. Fluoroscopic screening involving the oropharynx alone fails to identify these patients. The aim of this study was to investigate the prevalence of esophageal abnormalities in an SLP-led videofluoroscopic study of swallowing (VFSS) clinic. STUDY DESIGN: Prospective, observational study. SETTING: Radiology suite, public hospital. SUBJECTS AND METHODS: In total, 111 consecutive mixed-etiology patients referred to the clinic by otorhinolaryngology (ORL) (59) or by a speech-language pathologist (52) were recruited. A VFSS was performed according to protocol, and at completion, esophageal visualization (in anterior-posterior plane) was performed by administration of a large liquid barium bolus and a barium capsule. All VFSS recordings were analyzed using objective digital measures of timing and displacement. RESULTS: Sixty-eight percent of patients had an abnormal esophageal transit. One-third of those referred presented exclusively with esophageal abnormalities, while one-third had both oropharyngeal and esophageal abnormalities. Oral abnormalities, reduced pharyngoesophageal segment maximum opening (PESmax), and increasing age were significantly associated with esophageal abnormalities. CONCLUSION: Fluoroscopic evaluation of the pharynx alone, without esophageal review, risks incomplete diagnosis of patients with esophageal disorders. Using esophageal visualization allows timely referral for further investigation by appropriate medical specialties, avoiding incomplete management of patients with dysphagia.

Linking peer victimization to the development of depressive self-schemas in children and adolescents.

Previous theory and research suggest that childhood experiences are more likely to generate depressive self-schemas when they focus attention on negative information about oneself, generate strong negative affect, and are repetitive or chronic. Persistent peer victimization meets these criteria. In the current study, 214 youths (112 females) with empirically-validated histories of high or low peer victimization completed self-report measures of negative and positive self-cognitions as well as incidental recall and recognition tests following a self-referent encoding task. Results supported the hypothesis that depressive self-schemas are associated with peer victimization. Specifically, peer victimization was associated with stronger negative self-cognitions, weaker positive self-cognitions, and an elimination of the normative memorial bias for recall of positive self-referential words. Effects were stronger for relational and verbal victimization compared to physical victimization. Support accrues to a model about the social-developmental origins of cognitive diatheses for depression.

Training mid-level providers on palliative care: bringing advanced directives and symptom assessment and management to community oncology practices.

Palliative care services are not available in most outpatient oncology practices. A program training 11 mid-level providers from oncology practices on advanced directive discussions and supportive symptom assessment and management performed by palliative care specialists was completed. A follow-up session 9 months later identified barriers to implementation. Of the 11 mid-level providers, 8 participated in the follow-up session, and 9 of the 11 providers implemented advanced directive's discussions and symptom assessment and management for patients with metastatic cancer. Main barriers included uncertainties about reimbursement, patients' lack of knowledge about palliative care, and lack of access to supportive services. This program successfully promoted advanced directive discussions and supportive/palliative care symptom assessment and management to community oncology practices, which will hopefully translate into improved quality of life for patients with metastatic cancer.