Hurt, Ryan T.

Purpose of review Once considered to have only local influences on the gut mucosa, short-chain fatty acids (SCFAs) now appear to have a much wider anti-inflammatory, immune-modulating, systemic effect. This article reviews recent evidence to suggest a much wider clinical application of this valued dietary substrate. Recent findings SCFAs act systemically through stimulation of G protein receptors (GPRs) and inhibition of histone deacetylases (HDACs). SCFAs cause appetite suppression, reduce systemic inflammation, improve insulin sensitivity, increase energy expenditure, promote mitochondrial function, stimulate satiety, reduce blood pressure, and improve cognitive function from various neurologic maladies. Summary Dietary strategies should be implemented to provide this beneficial substrate across a wide spectrum of disease conditions. Use of prebiotic fiber or liquid supplements containing high SCFA-producing organisms should be considered as therapeutic targets for multiple metabolic, immunologic, and neurodegenerative diseases.

Objectives: To identify patient characteristics, health concerns, and barriers to care based on overweight or obesity. Methods: A 50-question anonymous survey was administered to patients. Data were compared by body mass index (BMI). Results: Among 3976 distributed surveys, 899 were returned and 682 were analyzed. Most respondents were women (60%), White (94%), and married/partnered (65%) and had some college education (80%). Younger and unmarried persons had higher BMI ( P < .001). Concern for quality of life ( P < .001) and importance of lifestyle changes ( P = .006) increased with BMI, but confidence in making changes decreased as BMI increased ( P < .001). Perceived good health decreased with increasing BMI ( P < .001), whereas depression and other comorbid conditions increased. Self-esteem decreased and stigma increased with higher BMI (both P < .001). Weight discussions with clinicians ( P < .001) and belief that clinicians should be involved in weight management ( P = .002) increased with BMI, yet self-perception of being judged by clinicians also increased ( P < .001). As BMI increased, delays in seeking health care increased ( P < .001). Conclusions: This survey study highlights perceived health concerns and barriers to care among persons with overweight and obesity. With higher BMI, self-esteem decreased, and stigma, self-perception of poor health, perception of being judged by clinicians, and delay in seeking medical care increased.

Objective To describe the immediate clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) in treating long COVID symptoms. Long COVID currently impacts approximately 5.3% of US adults, presenting with persistent fatigue, depression, anxiety, cognitive impairments, and social function decline. Repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex has improved these symptoms in some studies. Methods Five patients (ages 52–63 years, 3 female patients) underwent accelerated rTMS using intermittent theta burst stimulation (600 pulses over 3 minutes 20 seconds, 80%–120% of resting motor threshold) to the left dorsolateral prefrontal cortex. The treatment consisted of twice-daily sessions over 20–30 treatments. Outcomes were measured using the Patient-Reported Outcomes Measurement and Information System (PROMIS) questionnaires, assessing fatigue, depression, anxiety, cognitive function, and social function at baseline and immediately posttreatment. Results One patient discontinued immediately due to intolerable scalp pain. Posttreatment PROMIS scores showed the following: fatigue decreased from 74.5 to 61.8, depression from 60.3 to 51.5, and anxiety from 62.0 to 54.0. Scores increased for cognitive (26.8 to 32.3) and social (31.0 to 32.5) function. These changes, although not statistically significant, indicate a trend toward symptom reduction. Subjectively, 3 of 4 patients who completed the rTMS course reported improvements. Conclusion This case series suggests that rTMS may offer symptomatic relief in long COVID patients. Although the observed improvements in PROMIS were not statistically significant, even minimal improvements are clinically significant for patients enduring prolonged suffering. These preliminary findings are encouraging and underscore the need for further research with larger cohorts to validate the efficacy of rTMS in long COVID symptom relief.

Background: Angiosarcomas are rare tumors that can be difficult to diagnose due to subtle changes in the vascular endothelium. When there is evidence to suggest malignancy, such as a pathologic fracture, further investigation is needed, and a high suspicion for angiosarcoma needs to be present so that appropriate immunohistochemical stains are utilized on biopsied tissue. In situations where such suspicion is high and prior biopsies have been negative, performance of splenectomy, can be both diagnostic and therapeutic when splenomegaly is present. Case Report: This is a case of a 52-year-old woman with splenomegaly, initially attributed to infection, in the setting of upper respiratory symptoms and thrombocytopenia. Three months later, however, she presented with back pain. Imaging showed lytic bone lesions with pathologic vertebral fracture and numerous liver lesions that were too small to characterize further. Initial biopsies of the liver and bone did not reveal a pathologic process. Several months later, still without a unifying diagnosis, she presented to our institution. MRI of the brain was done for neurologic concerns and showed pathologic enhancement in the calvarium. A PET scan showed diffuse avidity of the skeleton and spleen. After discussing the case with a hematologist, splenectomy was performed for both diagnostic and therapeutic purposes. Angiosarcoma was identified in the spleen and in a PET-directed bone biopsy. With a definitive diagnosis, she returned home and subsequently elected to pursue hospice care. Conclusion: When there is a high clinical suspicion for malignant angiosarcoma, a multidisciplinary approach is necessary to direct both tissue acquisition and necessary histochemical staining.

Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.

Within the Department of Medicine (DOM) in a large tertiary academic health care facility in midwestern United States, we have developed an educational offering that incorporates an academic writing program (AWP) blending the approaches of a writing accountability work group, a writing workshop, and didactic writing courses. The purpose of this AWP was to assist healthcare professionals (HCP) with their manuscript writing skills to enhance academic productivity. We report our evolving journey and experiences with this AWP. To date, it has been offered 3 times to 25 HCP over the course of 3 years. Among those responding to a post program follow up survey (N = 11), 8 (73%) indicated that they completed the project that they were working on during the AWP and went on to publish the manuscript (N = 5) or were in the process of submission (N = 2). Some indicated they has also gone on to present posters (N = 2) or were in the process of presenting posters (N = 2) or had received grants (N = 1) or were awaiting grant notice (N = 1). A number of attendees have continued to use and share the tools presented during the AWP. Based on input from attendees and increased requests for this AWP, this educational program has been deemed a success and expansion of this program is currently underway.

Background: In addition to the morbidity and mortality associated with acute infection, COVID-19 has been associated with persistent symptoms (>30 days), often referred to as Long COVID (LC). LC symptoms often cluster into phenotypes, resembling conditions such as fibromyalgia, postural orthostatic tachycardiac syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). LC clinics have been established to best address the needs of LC patients and continuity of care. We developed a cross-sectional survey to assess treatment response through our LC Clinic (LCC). Methods: A 25-question survey (1-10 Likert scale) was expert- and content-validated by LCC clinicians, patients, and patient advocates. The survey assessed LC symptoms and the helpfulness of different interventions, including medications and supplements. A total of 852 LCC patients were asked to complete the survey, with 536 (62.9%) responding. Results: The mean time from associated COVID-19 infection to survey completion was 23.2 ± 6.4 months. The mean age of responders was 52.3 ± 14.1 (63% females). Self-reported symptoms were all significantly improved ( P < .001) from the initial visit to the LCC (baseline) to the time of the follow-up survey. However, only 4.5% (24/536) of patients rated all symptoms low (1-2) at the time of the survey, indicating low levels of full recovery in our cohort. The patients rated numerous interventions as being helpful, including low-dose naltrexone (45/77; 58%), vagal nerve stimulation (18/34; 53%), and fisetin (28/44; 64%). Conclusions: Patients report general improvements in symptoms following the initial LCC visit, but complete recovery rates remain low at 23.2 ± 6.4 months.

Background: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs. Methods: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants. Results: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α ( P < .001) and interleukin 1β ( P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs. Discussion: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.

ABSTRACT Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (“vax-plasma”). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% ( P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization. IMPORTANCE As SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.