Proteomic and phosphoproteomic characterization of cardiovascular tissues after long term exposure to simulated space radiation.

Introduction: It may take decades to develop cardiovascular dysfunction following exposure to high doses of ionizing radiation from medical therapy or from nuclear accidents. Since astronauts may be exposed continually to a complex space radiation environment unlike that experienced on Earth, it is unresolved whether there is a risk to cardiovascular health during long-term space exploration missions. Previously, we have described that mice exposed to a single dose of simplified Galactic Cosmic Ray (GCR5-ion) develop cardiovascular dysfunction by 12 months post-radiation. Methods: To investigate the biological basis of this dysfunction, here we performed a quantitative mass spectrometry-based proteomics analysis of heart tissue (proteome and phosphoproteome) and plasma (proteome only) from these mice at 8 months post-radiation. Results: Differentially expressed proteins (DEPs) for irradiated versus sham irradiated samples (fold-change ≥1.2 and an adjusted p-value of ≤0.05) were identified for each proteomics data set. For the heart proteome, there were 87 significant DEPs (11 upregulated and 76 downregulated); for the heart phosphoproteome, there were 60 significant differentially phosphorylated peptides (17 upregulated and 43 downregulated); and for the plasma proteome, there was only one upregulated protein. A Gene Set Enrichment Analysis (GSEA) technique that assesses canonical pathways from BIOCARTA, KEGG, PID, REACTOME, and WikiPathways revealed significant perturbation in pathways in each data set. For the heart proteome, 166 pathways were significantly altered (36 upregulated and 130 downregulated); for the plasma proteome, there were 73 pathways significantly altered (25 upregulated and 48 downregulated); and for the phosphoproteome, there were 223 pathways significantly affected at 0.1 adjusted p-value cutoff. Pathways related to inflammation were the most highly perturbed in the heart and plasma. In line with sustained inflammation, neutrophil extracellular traps (NETs) were demonstrated to be increased in GCR5-ion irradiated hearts at 12-month post irradiation. NETs play a fundamental role in combating bacterial pathogens, modulating inflammatory responses, inflicting damage on healthy tissues, and escalating vascular thrombosis. Discussion: These findings suggest that a single exposure to GCR5-ion results in long-lasting changes in the proteome and that these proteomic changes can potentiate acute and chronic health issues for astronauts, such as what we have previously described with late cardiac dysfunction in these mice.

Telehealth outpatient palliative care in the COVID-19 pandemic: patient experience qualitative study.

OBJECTIVES: Outpatient in-person early palliative care improves quality of life for patients with advanced cancer. The COVID-19 pandemic forced a rapid shift to telehealth visits; however, little is known about how telehealth in outpatient palliative care settings should be optimised beyond the pandemic. We aimed to explore, from the perspective of patients attending an outpatient palliative care clinic, the most appropriate model of care for in-person versus telehealth visits. METHODS: A qualitative study using the grounded theory method. One-on-one, semistructured qualitative interviews were conducted with 26 patients attending an outpatient palliative care clinic at a tertiary cancer centre recruited from two groups: (1) those with >1 in-person appointment prior to 1 March 2020 and >1 telehealth appointment after this date (n=17); and (2) patients who had exclusively telehealth appointments (n=9). Purposive sampling was used to incorporate diverse perspectives. RESULTS: Overall, participants endorsed a flexible hybrid approach incorporating both in-person and telehealth visits. Specific categories were: (1) in-person outpatient palliative care supported building interpersonal connections and trust; (2) telehealth palliative care facilitated greater efficiency, comfort and independence and (3) patient-preferred circumstances for in-person visits (preferred for initial consultations, visits where a physical examination may be required and advance care planning discussions), versus telehealth visits (preferred during periods of relative heath stability). CONCLUSIONS: The elements of in-person and telehealth outpatient palliative care clinic visits described by patients as integral to their care may be used to develop models of hybrid outpatient palliative care delivery beyond the pandemic alongside reimbursement and regulatory guidelines.

Indications and Recommendations for Tracheostomy in Trauma Population With COVID-19 Infection: A Review of the Literature.

This review explores the current body of evidence pertaining to tracheostomy placement in COVID-19 seropositive patients and summarizes the research by tracheostomy indications, timing, and procedure. Literature review was performed in accordance with the 2020 PRISMA guidelines and includes 12 papers discussing protocols for adult patients seropositive for COVID-19. The studies demonstrated high mortality rates after tracheostomy, especially in geriatric patients, and suggested a multifactorial determination of whether to perform a tracheostomy. There was inconclusive data regarding wait time between testing seropositive, tracheostomy, and weaning off of ventilation. COVID-19 generally reaches highest infectivity between days 9 and 10; furthermore, high early mortality rates seen in COVID-19 may confound mortality implicated by tracheostomy placement. Due to the aerosol-generating nature of tracheostomy placement, management and maintenance, techniques, equipment, and personnel should be carefully considered and altered for COVID-19 patients. With surgical tracheostomy, literature suggested decreased usage of electrocautery; with percutaneous tracheostomy, single-use bronchoscope should be used. The nonemergent exchange of tracheostomy should be done only after the patient tested negative for COVID-19. Placement of tracheostomy should only be considered in COVID-19 patients who are no longer transmissible, with rigorous attention to safety precautions. Understanding procedures for airway maintenance in a respiratory disease like COVID-19 is imperative, especially due to current shortages in ventilators and PPE. However, because of a lack of available data and its likelihood of change as more data emerges, we lack complete guidelines for tracheostomy placement in COVID-19 seropositive patients, and those existing will likely evolve with the disease.

Role Modeling in Medical Education: A Twenty-First Century Learner's Perspective.

Traditional role modeling is a complex process of observation and emulation delivered by experienced senior physicians with an unknown outcome. Role modeling through organized modalities has been utilized as an educational tool in medical school for years. However, effects of parenting, near peers, gender, race, and social media on role modeling in medical education have not been well characterized yet play a significant role in the development of modern clinicians. The aim of this paper is to encourage students as future medical and clinical educators through an in-depth analysis of role modeling, with the goal of improving their "role modeling consciousness."

Prosthetic Mitral Valve Thrombosis: A Complication Following Mitral Valve Surgery and Coronary Artery Bypass Graft Surgery.

Mitral valve regurgitation is a common valvular defect that can lead to severe complications, requiring surgical intervention, often in the form of either mitral valve repair or replacement. This case report follows a 63-year-old male with multivessel coronary artery disease, who initially presented to the emergency department (ED) with a non-ST elevation myocardial infarction (NSTEMI) secondary to multivessel coronary artery disease with severe mitral regurgitation, and subsequently underwent coronary artery bypass grafting (CABG) with repair of the mitral valve. He was readmitted a month later with endocarditis of the mitral valve and underwent a reoperation with a bioprosthetic mitral valve replacement and massive reconstruction of the right ventricle, after which he failed to recover postoperatively. A repeat transesophageal echocardiogram (TEE) during his final chest washout procedure revealed echodensities suspicious for thrombi and, despite the team's best efforts, the patient expired. This report demonstrates that even with appropriate medical decision-making, poor outcomes still result, especially in patients with comorbidities including multivessel disease, respiratory illness, and endocarditis. This study suggests that continuing to characterize repairs or replacements of the mitral valve is essential. Additionally, aggressive and newly emerging procedures, such as percutaneous approaches to mitral valve repair or replacement, may be considered for use to mitigate negative outcomes, especially with an aging population.

Recurrent Peritonsillar Abscess in Post-tonsillectomy Patient.

Peritonsillar abscess (PTA) is a common deep tissue infection of the head and neck. In the literature, most cases demonstrate PTA following acute tonsillitis; however, less documented are cases arising in post-tonsillectomy patients. Here, we report a 45-year-old woman with a history of tonsillectomy 16 years prior, who presented to the emergency department with signs and symptoms consistent with PTA, including sore throat and the presence of a right-sided abscess in the posterolateral oropharynx with apparent pus. The patient reported three previous episodes of right-sided PTA, all of which were addressed via drainage and antibiotic treatment. This episode was treated similarly; cultures from the abscess revealed no growth of organisms. The patient was started on a short course of clindamycin and discharged to follow-up with her primary care physician. Several theories for the etiology of PTA development in post-tonsillectomy patients exist. One theory suggests that PTA may develop in this group of patients due to imperfect margins during the initial surgery, with residual tonsil tissue serving as a nidus for abscess development. Other theories suggest that a congenital fistula may exist in these patients, which, when occluded by scar tissue following a tonsillectomy, may lead to PTA development. Similarly, occlusion of minor salivary ducts has also been suggested to play a role in this unique pathophysiology. Overall, documenting rare cases of PTA development in post-tonsillectomy patients serves as a means of better understanding the complicated etiology behind PTA development and may be able to guide treatment in the future.

Percutaneous Endoscopic Gastrostomy Misplacement in the Transverse Colon of a Neurocognitively Compromised Patient.

Percutaneous endoscopic gastrostomy (PEG) tube placement is a widespread method of delivering sustained nutrition to individuals requiring long-term support. Multiple techniques exist to achieve this, and adverse events can arise if not done properly including but not limited to pneumoperitoneum and bowel perforation. Safeguard tactics exist to prevent these complications but they are not always successful. Herein, we explore a case of PEG tube misplacement through the transverse colon.  A 69-year-old male with a history of advanced dementia, cerebrovascular accident (CVA), and seizure disorder presented for a replacement of his malfunctioning PEG tube at a different site. On postoperative day one, the patient developed abdominal pain and shortness of breath. His subsequent imaging workup revealed pneumoperitoneum, and the patient ultimately underwent an exploratory laparotomy to repair the damage, washout his abdomen, and reinsert the PEG tube. Postoperatively, the patient had a lengthy hospital stay, which was complicated and prolonged by sepsis and mechanical ventilation.  The PEG tube placement procedure is not without its difficulties in all stages, pre- intra- and post-operatively, especially in patients with neurocognitive compromise, therefore, it is important to continue exploring methods to optimize the operation.

Progression of aortic valve insufficiency during centrifugal versus axial flow left ventricular assist device support.

OBJECTIVES: Long-term left ventricular assist device (LVAD) support can cause accelerated progression of aortic insufficiency (AI). The MOMENTUM trial has led to increased use of the HeartMate 3 (HM3) LVAD, due to greater hemocompatibility. However, the differential effect on the rate of progression of AI during HM3 support versus HeartMate 2 (HM2) has not been extensively studied. This analysis compares the rates of progression to moderate or severe AI (MSAI) comparing a cohort of patients supported with the HM2 versus HM3. METHODS: A retrospective review was performed on all consecutive patients implanted with HM2 or HM3 between May 2005 and June 2020. Follow-up time was limited to the first 6 years after LVAD implantation. Demographics and 4005 echocardiograms were assessed for 536 HM2 and 300 HM3 patients. The primary end point was progression to MSAI. Univariable and multivariable Cox proportional hazard regression and landmark analyses were performed. RESULTS: Progression to MSAI was greater in the HM2 (17%) versus HM3 (9.9%) cohort. On the univariable analysis, the hazard ratio for HM3 was 0.581 (95% confidence interval 0.370-0.909, P = 0.02) whereas on multivariable analysis hazard ratio was 0.624 (95% confidence interval 0.386-1.008, P = 0.0537). Preoperative AI, female sex and body surface area <2 were significantly associated with progression to MSAI. Landmark analysis suggests that LVAD type has the most significant effect on progression to MSAI between 1 and 2 years post-implantation. CONCLUSIONS: Current practice strategies achieved low rates of progression to MSAI. Preoperative AI, female sex and body surface area <2 were the most important predictors of progression to MSAI. Pump type appears to be of secondary importance.

Palliative medicine outpatient clinic 'no-shows': retrospective review.

OBJECTIVES: Patients who do not attend outpatient palliative care clinic appointments ('no-shows') may have unmet needs and can impact wait times. We aimed to describe the characteristics and outcomes associated with no-shows. METHODS: We retrospectively reviewed new no-show referrals to the Princess Margaret Cancer Centre Oncology Palliative Care Clinic (OPCC) in Toronto, Canada, between January 2017 and December 2018, compared with a random selection of patients who attended their first appointment, in a 1:2 ratio. We collected patient information, symptoms, performance status (Eastern Cooperative Oncology Group (ECOG) and outcomes. Univariable and multivariable logistic regression analyses were used to identify significant factors. RESULTS: Compared with those who attended (n=214), no-shows (n=103), on multivariable analysis, were at higher odds than those who attended of being younger (OR 0.98, 95% CI 0.96 to 1.00, p=0.019), living outside Toronto (OR 2.67, 95% CI 1.54 to 4.62, p<0.001) and having ECOG ≥2 (OR 2.98, 95% CI 1.41 to 6.29, p=0.004). No-shows had a shorter median survival compared with those who attended their first appointment (2.3 vs 8.7 months, p<0.001). CONCLUSION: Compared with patients who attended, no-shows lived further from the OPCC, were younger, and had a poorer ECOG. Strategies such as virtual visits should be explored to reduce no-shows and enable attendance at OPCCs.

Symptom Assessment and Early Access to Supportive and Palliative Care for Patients With Advanced Solid Tumors in Mexico.

BACKGROUND: Early specialized palliative care improves quality of life of patients with advanced cancer, and guidelines encourage its integration into standard oncology care. However, many patients fail to obtain timely palliative/supportive care evaluations, particularly in limited-resource settings. We aimed to determine the proportion of patients with advanced cancer who received an assessment of symptoms and were referred to supportive and palliative care services during the first year after diagnosis in a Mexican hospital. METHODS: Individuals with newly diagnosed advanced solid tumors and 1 year of follow-up at the oncology clinics in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City from October 2015 to April 2016 were included in this retrospective study. RESULTS: Seventy-seven patients were included. Forty-two (54.5%) were referred to the various supportive care services during the first year after diagnosis, and 23 (29.8%) were referred to the palliative care clinic. The most commonly assessed symptoms by oncologists were pain (77.9%), anorexia (74.0%), fatigue (68.8%), and nausea (55.8%), while depression/anxiety were evaluated in 10 (12.9%) patients. The oncologist offered to clarify treatment goals in 39 (50.6%) cases and evaluated the understanding of diagnosis/illness and prognosis in 22 (28.5%). CONCLUSION: Palliative and supportive care services were widely underutilized, which may be related to a lack of standardized symptom assessments and poor end-of-life communication. Novel strategies are needed to improve the implementation of tools for systematic symptom assessment and to optimize the integration of supportive care interventions into oncology care in developing countries.