Postural orthostatic tachycardia syndrome after COVID-19 vaccination.

BACKGROUND: There is an association between coronavirus disease 2019 (COVID-19) mRNA vaccination and the incidence or exacerbation of postural orthostatic tachycardia syndrome (POTS). OBJECTIVE: The purpose of this study was to characterize patients reporting new or exacerbated POTS after receiving the mRNA COVID-19 vaccine. METHODS: We prospectively collected data from sequential patients in a POTS clinic between July 2021 and June 2022 reporting new or exacerbated POTS symptoms after COVID-19 vaccination. Heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) were compared against those of 24 healthy controls. RESULTS: Ten patients (6 women and 4 men; age 41.5 ± 7.9 years) met inclusion criteria. Four patients had standing norepinephrine levels > 600 pg/mL. All patients had conditions that could raise POTS risk, including previous COVID-19 infection (N = 4), hypermobile Ehlers-Danlos syndrome (N = 6), mast cell activation syndrome (N = 6), and autoimmune (N = 7), cardiac (N = 7), neurological (N = 6), or gastrointestinal conditions (N = 4). HRV analysis indicated a lower ambulatory root mean square of successive differences (46.19 ±24 ms; P = .042) vs control (72.49 ± 40.8 ms). SKNA showed a reduced mean amplitude (0.97 ± 0.052 µV; P = .011) vs control (1.2 ± 0.31 µV) and burst amplitude (1.67 ± 0.16 µV; P = .018) vs control (4. 3 ± 4.3 µV). After 417.2 ± 131.4 days of follow-up, all patients reported improvement with the usual POTS care, although 2 with COVID-19 reinfection and 1 with small fiber neuropathy did have relapses of POTS symptoms. CONCLUSION: All patients with postvaccination POTS had pre-existing conditions. There was no evidence of myocardial injuries or echocardiographic abnormalities. The decreased HRV suggests a sympathetic dominant state. Although all patients improved with guideline-directed care, there is a risk of relapse.

Moving toward point-of-care surgery in Ukraine: testing an ultra-portable operating room in an active war zone.

PURPOSE: In conflict zones, providers may have to decide between delaying time-sensitive surgeries or performing operative interventions in the field, potentially subjecting patients to significant infection risks. We conducted a single-arm crossover study to assess the feasibility of using an ultraportable operating room (U-OR) for surgical procedures on a porcine cadaver abdominal traumatic injury model in an active war zone. METHODS: We enrolled participants from an ASSET-type course designed to train Ukrainian surgeons before deployment to active conflict zones. They performed three standardized consecutive abdominal surgical procedures (liver, kidney, and small bowel injury repair) with and without the U-OR. Primary outcomes included surgical procedure completion rate, procedure time, and airborne particle count at the start of surgery. Secondary survey-based outcomes assessed surgery task load index (SURG-TLX) and perceived operative factors. RESULTS: Fourteen surgeons performed 76 surgical procedures (38 with the U-OR, 38 without the U-OR). The completion rate for each surgical procedure was 100% in both groups. While the procedure time for the liver injury repair did not differ significantly between the two groups, the use of the U-OR was associated with a longer time for kidney (155 vs. 56 s, p = 0.002), and small bowel (220 vs. 103 s, p = 0.004) injury repair. The average airborne particle count within the U-OR was substantially lower compared to outside the U-OR (6,753,852 vs. 232,282 n/m3, p < 0.001). There was no statistically significant difference in SURG-TLX for procedures performed with and without the U-OR. CONCLUSION: The use of the U-OR did not affect the procedure completion rate or SURG-TLX. However, there was a marked difference in airborne particle counts between inside and outside the U-OR during surgery. These preliminary findings indicate the potential feasibility of using a U-OR to perform abdominal damage-control surgical procedures in austere settings.

A Tunable Soft Silicone Bioadhesive for Secure Anchoring of Diverse Medical Devices to Wet Biological Tissue.

Silicone is utilized widely in medical devices for its compatibility with tissues and bodily fluids, making it a versatile material for implants and wearables. To effectively bond silicone devices to biological tissues, a reliable adhesive is required to create a long-lasting interface. BioAdheSil, a silicone-based bioadhesive designed to provide robust adhesion on both sides of the interface is introduced here, facilitating bonding between dissimilar substrates, namely silicone devices and tissues. The adhesive's design focuses on two key aspects: wet tissue adhesion capability and tissue-infiltration-based long-term integration. BioAdheSil is formulated by mixing soft silicone oligomers with siloxane coupling agents and absorbents for bonding the hydrophobic silicone device to hydrophilic tissues. Incorporation of biodegradable absorbents eliminates surface water and controls porosity, while silane crosslinkers provide interfacial strength. Over time, BioAdheSil transitions from nonpermeable to permeable through enzyme degradation, creating a porous structure that facilitates cell migration and tissue integration, potentially enabling long-lasting adhesion. Experimental results demonstrate that BioAdheSil outperforms commercial adhesives and elicits no adverse response in rats. BioAdheSil offers practical utility for adhering silicone devices to wet tissues, including long-term implants and transcutaneous devices. Here, its functionality is demonstrated through applications such as tracheal stents and left ventricular assist device lines.

Apparent Risks of Postural Orthostatic Tachycardia Syndrome Diagnoses After COVID-19 Vaccination and SARS-Cov-2 Infection.

Postural orthostatic tachycardia syndrome (POTS) has been previously described after SARS-CoV-2 infection; however, limited data is available on the relation of POTS with COVID-19 vaccination. Here we show in a cohort of 284,592 COVID-19 vaccinated individuals using a sequence-symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days prior to exposure, and that the odds for POTS are higher than referent conventional primary care diagnoses, but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection. Our results identify a possible association between COVID-19 vaccination and incidence of POTS. Notwithstanding the probable low incidence of POTS after COVID-19 vaccination, particularly when compared to SARS-Cov-2 post-infection odds which were five times higher, our results suggest that further studies, are needed to investigate the incidence and etiology of POTS occurring after COVID-19 vaccination.

Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. TRIAL REGISTRATION: PROSPERO 2020 CRD42020175648.

A Paradigm Shift in Critical Care Infrastructure in Complex Settings: Evaluating an Ultraportable Operating Room to Improve Field Surgical Safety.

INTRODUCTION: Scarcity of operating rooms and personal protective equipment in far-forward field settings make surgical infections a potential concern for combat mortality and morbidity. Surgical and transport personnel also face infectious risks from bodily fluid exposures. Our study aimed to describe the serial, proof-of-concept testing of the SurgiBox technology: an inflatable sterile environment that addresses the aforementioned problems, fits on gurneys and backpacks, and drapes over incisions. MATERIALS AND METHODS: The SurgiBox environmental control unit and inflatable enclosure were optimized over five generations based on iterative feedback from stakeholders experienced in surgery in austere settings. The airflow system was developed by analytic modeling, verified through in silico modeling in SOLIDWORKS, and confirmed with prototype smoke-trail checking. Particulate counts evaluated the enclosure's ability to control and mitigate users' exposures to potentially infectious contaminants from the surgical field in various settings. SurgiBox enclosures were setup over a mannequin's torso, in a configuration and position for either thoracic or abdominal surgery. A particle counter was serially positioned in sternotomy and laparotomy positions, as well as bilateral flank positions. This setup was repeated with open ports exposing the enclosure to the external environment. To simulate stress scenarios, sampling was repeated with enclosure measurements during an increase in external particulate concentration. RESULTS: The airflow technology effectively kept contaminants away from the incision and maintained a pressure differential to reduce particle entry. Benchtop testing demonstrated that even when ports were opened or the external environment had high contaminant burden, the enclosed surgical field consistently registered 0 particle count in all positions. Time from kit opening to incision averaged 54.5 seconds, with the rate-limiting step being connecting the environmental control unit to the enclosure. The portable kit weighted 5.9 lbs. CONCLUSIONS: Analytic, in silico, and mechanical airflow modeling and benchtop testing have helped to quantify the SurgiBox system's reliability in creating and maintaining an operating room-quality surgical field within the enclosure as well as protecting the surgical team outside the enclosure. More recent and ongoing work has focused on specifying optimal use settings in the casualty chain of care, expanding support for circumferential procedures, automating airflow control, and accelerating system setup. SurgiBox's ultimate goal is to take timely, safe surgery to patients in even the most austere of settings.

Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020175648.

Truncations of titin causing dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy and hypertrophic cardiomyopathy arise from mutations in many genes. TTN, the gene encoding the sarcomere protein titin, has been insufficiently analyzed for cardiomyopathy mutations because of its enormous size. METHODS: We analyzed TTN in 312 subjects with dilated cardiomyopathy, 231 subjects with hypertrophic cardiomyopathy, and 249 controls by using next-generation or dideoxy sequencing. We evaluated deleterious variants for cosegregation in families and assessed clinical characteristics. RESULTS: We identified 72 unique mutations (25 nonsense, 23 frameshift, 23 splicing, and 1 large tandem insertion) that altered full-length titin. Among subjects studied by means of next-generation sequencing, the frequency of TTN mutations was significantly higher among subjects with dilated cardiomyopathy (54 of 203 [27%]) than among subjects with hypertrophic cardiomyopathy (3 of 231 [1%], P=3×10(-16)) or controls (7 of 249 [3%], P=9×10(-14)). TTN mutations cosegregated with dilated cardiomyopathy in families (combined lod score, 11.1) with high (>95%) observed penetrance after the age of 40 years. Mutations associated with dilated cardiomyopathy were overrepresented in the titin A-band but were absent from the Z-disk and M-band regions of titin (P≤0.01 for all comparisons). Overall, the rates of cardiac outcomes were similar in subjects with and those without TTN mutations, but adverse events occurred earlier in male mutation carriers than in female carriers (P=4×10(-5)). CONCLUSIONS: TTN truncating mutations are a common cause of dilated cardiomyopathy, occurring in approximately 25% of familial cases of idiopathic dilated cardiomyopathy and in 18% of sporadic cases. Incorporation of sequencing approaches that detect TTN truncations into genetic testing for dilated cardiomyopathy should substantially increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy. Defining the functional effects of TTN truncating mutations should improve our understanding of the pathophysiology of dilated cardiomyopathy. (Funded by the Howard Hughes Medical Institute and others.).