Background and Objectives: Progressive familial intrahepatic cholestasis (PFIC) is a rare autosomal recessive inherited disease divided into five types (PFIC 1-5). Characteristic for all types is early disease onset, which may result clinically in portal hypertension, fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Liver transplantation (LT) is the only successful treatment approach. Our aim is to present the good long-term outcomes after liver transplantation for PFIC1, focusing on liver function as well as the occurrence of extrahepatic manifestation after liver transplantation. Materials and Methods: A total of seven pediatric patients with PFIC1 underwent liver transplantation between January 1999 and September 2019 at the Department of Surgery, Charité Campus Virchow Klinikum and Charité Campus Mitte of Charité-Universitätsmedizin Berlin. Long-term follow-up data were collected on all patients, specifically considering liver function and extrahepatic manifestations. Results: Seven (3.2%) recipients were found from a cohort of 219 pediatric patients. Two of the seven patients had multilocular HCC in cirrhosis. Disease recurrence or graft loss did not occur in any patient. Two patients  had persistently elevated liver parameters but showed excellent liver function. Patient and graft survival during long-term follow-up was 100%, and no severe extrahepatic manifestations requiring hospitalization or surgery occurred. We noted a low complication rate during long-term follow-up and excellent patient outcome. Conclusions: PFIC1 long-term follow-up after LT shows promising results for this rare disease. In particular, the clinical relevance of extrahepatic manifestations seems acceptable, and graft function seems to be barely affected. Further multicenter studies are needed to analyze the clinically inhomogeneous presentation and to better understand the courses after LT. Persistent neonatal cholestasis can be caused by a manifest liver disease ,2. DiffePFIC is divided into five types PFIC1-5), while PFIC1 is the most common disease. The genetic causes of cholestasis assume an important role in understanding the physiology and pathophysiology of the liver. Type 1 (PFIC1) appears to be associated with defective bile acid secretion and is defined according to genetic criteria based on recessive mutations in the ATP8B1 gene on chromosome 18q21 ,5,6,7,8., while PLiver transplantation (LT) is an important therapeutic tool for the management of PFIC ,20. In tExtrahepatic manifestation post-LT as a potential complication, including pancreatic disease, is more frequently described after LT in PFIC1 ,22,23,24Histologically, steatosis may occur after LT and be associated with increased transminase activity, although graft function might not be compromised. The signal transmission between the hepatic and intestinal tract, which is disturbed in PFIC1 deficiency, seems to change after LT: post-transplant steatosis may be associated with such a change ,26.Follow-up of PFIC1 patients after LT is important for excellent clinical management and for anticipating results in the long term. Here, multicenter data analysis should provide more insight. The balancing act between the consequences of a persistent multisystemic disease with extrahepatic manifestations and graft dysfunction that may affect the LT outcome of recipients as well as graft survival and the need for LT must be addressed.We here report long-term results of seven infants with PFIC1 who received LT as their first line of treatment before the age of two years. The clinical development of infants into adulthood was studied retrospectively, with special emphasis on the influence of PFIC1-typical extrahepatic manifestations and liver biopsies.A total of 219 patients younger than 18 years of age, who underwent LT from 1 January 2000 to 30 September 2019 at the Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum at Charité-Universitätsmedizin Berlin, Germany, were retrospectively analyzed. The analysis and reporting of data received institutional review board approval (EA2/267/20).Primary endpoints were recurrence of PFIC and/or graft-dysfunction. Secondary endpoints included 5-, 10-, 15-, and 18-year patient and graft survival as well as occurrence of extrahepatic manifestations.Living liver donor transplantations were performed after acceptance by our institutional ethics committee and in accordance with standardized protocols. Liver transplants from deceased donors were organized by EUROTRANSPLANT within the framework of an allocation procedure.For this purpose, demographic data, clinical features  and specific laboratory findings were collected at four different points in time , and long-term (from the fourth postoperative month)) during the study period. This was based on annual check-ups and also on unplanned inpatient stays. Particular attention was paid to size–weight developments, the clinical course for different features , trough quantities of immunosuppressive drugs, associated coagulopathies and complications in general, as well as specific histological analysis of available liver biopsies.Tumor follow-up was performed by means of regular ultrasound examination of the abdomen over the course of 6 months and AFP controls.Standard immunosuppression initially was performed with tacrolimus ((tac); 0.1 mg/kg). Tac trough levels were kept at 10–15 ng/mL during the first month and afterwards at 5–7 ng/mL. Prednisolone tapered to 0.1 mg/kg after 10 days and was discontinued three months after LT. In the long-term follow-up, immunosuppression was extended to mycophenolate mofetil (MMF) in one patient and switched to MMF in four recipients. Patients were followed up until September 2019 for patient and graft survival.® SE, Walldorf, Germany) and from archived patient files. Demographic and clinical characteristics of patients included gender, recipient and donor age at time of LT, PELD score prior to transplantation. In addition, previous abdominal and other disease-associated surgeries prior to LT, transplant types , median surgery duration (min), and total hospital duration were also determined.Anonymous donor data were retrieved from the Eurotransplant Network Information System (ENIS), and additionally all available records of recipient data were collected from the hospital information system .A total of seven PFIC children out of 219 pediatric patients analyzed after LT were eligible for this analysis.n = 7) and developed progressive cirrhosis (n = 7). The mean age at the time of LT was 9 months (range 7–23). All patients presented jaundice before liver transplantation, which regressed post-LT. In the long-term course, only one patient presented recurrent episodes of diarrhea, with no pancreatitis. No patient developed portal hypertension post-LT. Two patients had need of endoscopic retrograde cholangiopancreaticography (ERCP) due to biliary complications (biliary anastomosis stenosis and cholangitis). The patient with cholangitis showed no complications in the long-term follow-up after single ERCP and endoscopic papillotomy. The patient with biliary anastomosis stenosis showed a complication-free course after repeated ERCP and a Yamaka dilatation program over the last 12 years.All infants suffered from PFIC1 , left-sided lobe split-grafts (n = 2) and full-size grafts (n = 2) from deceased donors , so that relaparotomy was required. No unplanned hospitalizations were detected during the short-term follow-up.All patients showed a disease-free outcome  during the 17-year follow-up. Especially complications specific for LT, such as bile leakage or need for re-transplantation did not occur in any of the different donor types .During this long observation period, the overall survival rate of all patients and grafts was 100%. None of the seven patients developed a PFIC1 relapse . Both inn = 4) and growth failure (n = 2) were observed over the long-term course.Patients showed varying degrees of extrahepatic manifestations, including intermittent mild diarrhea in one patient. Events of pancreatitis or persistent severe diarrhea were not detected in our patient cohort. In addition, hearing loss  with persistently elevated liver enzymes, resulting in steatohepatitis . HistoloThe consideration of general complications in long-term aftercare presented one patient (no. 2) with stenosis of the bile duct anastomosis and consecutive cholestasis 6.5 years after LT. Endoscopic interventions, such as repetitive dilatations (Yamakawa) were needed for one year. Currently, eleven years after the last endoscopic treatment, the patient is free of complaints and intervention. A second patient (no. 7) developed stenosis of the biliary anastomosis and of the bile duct, with consecutive cholangitis 6 years after LT, which was well-treated with endoscopic dilatation and papillotomy. Nevertheless, this patient received in consequence 10 years post-LT re-operation with biliodigestive anastomosis and is presently in good general condition. Another patient (no. 1) underwent partial lung resection 7 years after LT in recurrent pneumonia due to a middle lobe atelectasis.Progression of PFIC may temporarily present a clinical and laboratory improvement through drug therapies  or through biliary diversion (BD) in the absence of liver cirrhosis ,28,29. EWe herein present long-term outcomes of 6 to 18 years for seven infants with PFIC1 undergoing LT at our surgical department. The seven infants (<2 years of age) in our analysis presented cirrhosis, with two patients exhibiting HCC , and mosAlthough the procedure of LT in infants has entered clinical routine with good results, regarding long-term follow-up, we must take into account late complications for patient- and graft-survival. In this context, for PFIC1, special attention must be given to extrahepatic manifestations occurring and exacerbating post-LT and the process of steatohepatitis .n = 61) and BSEP (n = 84) that PFIC1 patients were more likely to have extrahepatic disease (16), whereas Walkowiak et al. showed that pancreatic secretion was normal in patients with PFIC1 both without and after LT for a prolonged period of time. They observed that steatorrhea was not associated with pancreatic insufficiency [Regarding extrahepatic manifestations, not only their occurrence but also their management play an important role in the routine follow-up. Since the gene for PFIC1 is mainly expressed in the intestine and pancreas, PFIC1 disease also plays a crucial role in extrahepatic tissues . There aficiency .No pancreatitis was observed in our patient cohort. With regard to the often described diarrhea, only one patient in the retrospective study showed intermittent diarrhea, with no serious findings. Five out of seven children showed an age-appropriate development over the long term.Apart from extrahepatic manifestations, liver function is of particular concern in long-term follow-up. Cuttilo et al. showed that LDLT with donor parents with a heterozygous PFIC1 status does not increase the risk of liver dysfunction in both the recipient and the donor . SoubranReports of long-term follow-up data with regard to histological findings of the graft and graft function as well are rare . Only twA further point of our analysis is the first report—so far as we know—of the occurrence of HCC in two infants with PFIC1, and long-term results are provided, which are rather scarce . HoweverRoutine follow-up, in particular the closer and targeted oncological follow-up of HCC patients, includes the monitoring of liver function and the detection of extrahepatic manifestations. The anticipation of possible complications, based on the evaluations of long-term monitoring, is of particular importance. Especially from a socio-economic point of view, patients suffering from this rare multisystemic disease can maximally benefit from targeted aftercare during puberty into adulthood and be better integrated into social working life.Certainly, our study is limited by its retrospective design and a small cohort. Nevertheless, LT for PFIC1 seems to be promising in our analysis in long-term outcome, because poor prognosis after LT in patients with PFIC1 was reported .Biliary diversion can be successful if there is no fully developed cirrhosis of the liver and the disease is diagnosed early after the onset of symptoms in infancy .Shiau et al. showed recently (Hepatology Communications) that an increase in Fibrosis-4 score was associated with 1.36-fold higher odds for LT in PFIC patients. In addition, the aminotransferase-to-platelet ratio index or Fibrosis-4 score appear to associate with risk for future LT in children with PFIC .In our patient cohort, the full picture of advanced liver cirrhosis, associated with severe hypotrophy and developmental delay, was the decisive factor for the need for LT.Our patients were symptomatic since birth and underwent LT at an age of 9 months old (median). Two of the patients transplanted at the ages of 18 and 20 months already had multiple HCC in cirrhosis. Therefore, after confirmation of the diagnosis and in the presence of advanced fibrosis or liver cirrhosis, liver transplantation should be sought as soon as possible.As the urgency of transplantation is not adequately expressed by the labMELD for this group of patients, these patients should be assigned a matchMELD upon request. The disease should be listed under the criteria of the standard exceptions according to the German guideline. The risk of potentially developing HCC should be taken into account. In view of the often postpartum onset of the disease or early manifestation of symptoms, suspected HCC should be taken into account regardless of its size and extent, but after exclusion of distant metastases. As these patients are often infants, histological confirmation should not be mandatory, but should be supplemented by elevated AFP values, high-grade suspected imaging and the determination of biomarkers .Finally, regarding the literature  multicenThe analysis and specific mapping of clinical courses and laboratory chemical characteristics in our PFIC1 patient cohort at four different points in time  may be beneficial in treatment before and after LT as well as for prediction of when transplantation is required.Our aim was to identify characteristics that have been described so far and to analyze the patient and graft survival over time. In addition, a specific checklist, which comprehensively records associated symptoms, clinical expression, histological features and targeted controls in annual controls, could give us information about the prognosis in a multicenter evaluation ,8,13,18.Our results show that extrahepatic disease manifests only slightly, and that liver function is very good in the long-term follow-up. With a median follow-up of more than 14 years, only two patients developed fibrosis. The two patients with hepatocellular carcinoma continued to be free of recurrence during follow-up. Graft and patient survival in our cohort is excellent.


The objective of the present review is to assess the implant survival, marginal bone loss, and biomechanical features of narrow-diameter implants (2.5-3.5 mm) supporting or retaining full-arch fixed or removable restorations.  Three operators screened the literature  and performed a hand search on the main journals that focus on implantology until 24 March 2019. Only articles that considered full-arch restorations supported or retained by narrow-diameter implants (2.5-3.5 mm) were considered if they have a minimum of 10 patients and a mean follow-up of at least 6 months. The outcome variables were survival of implants and marginal bone loss. The review was performed according to the PRISMA statements. Risk of bias assessment was evaluated. Failure rates were analyzed using random effect Poisson regression models to obtain the summary estimate of 5-year survival rate and marginal bone loss.  A total of nine papers were finally selected, reporting a high survival rate of the implants. Eight studies focused only on the mandible while one study reported data from both mandible and maxilla. All studies reported on removable restorations; none focused on fixed rehabilitations. The estimated survival rate for 5 years of follow-up was calculated to be 92.25% for the implants. The estimated marginal bone loss after 5 years was calculated to be 1.40 mm. No study reported implant fractures.  With the limitations of the present study, there is evidence that 2.5-3.5 mm narrow-diameter implants retaining a removable restoration can be a successful treatment in fully edentulous patients. No data on fixed restorations was available. Complete edentulism significantly reduces masticatory function, and it is a significant oral health issue concerning a large part of the adult population .Following tooth extraction, a process of residual ridge resorption (RRR) begins, and it is most intense during the first year, when approximately 60% of the alveolar ridge is resorbed and is directly related to the duration of edentulism –4.Human reentry studies showed horizontal bone loss of 29-63% and vertical bone loss of 11-22% after 6 months following tooth extraction .However, the bone resorption activity continues slowly throughout life, resulting in the loss of a large amount of jawbone structure .Residual ridge resorption (RRR) is a common problem, and it represents a chronic, progressive, irreversible, and disabling disease, probably of multifactorial origin .Most resorption occurs in the alveolar process, whereas the basal portion remains relatively intact but only decreases bone density due to reduced function .The edentulous arch is a vital structure present during the entire life of the patient, regardless of tooth presence or function . All thiConventional dentures represent a noninvasive option for the treatment of complete edentulism and avoid a surgical procedure for the patient. However, in a large number of cases, this rehabilitation does not satisfy the patients' expectations, as many complaints are reported primarily related to functionality and adaptation .On the contrary, the attachment of removable dentures to osseointegrated dental implants brings considerable benefits, including the increase of denture stability, functional efficiency, and comfort. For these reasons, the implant-supported overdenture has become a common clinical practice, and to date, a two-implant overdenture is considered the first choice for the treatment of the fully edentulous mandible , 10.However, in some cases, the inevitable resorption of the alveolar ridges after tooth extraction can make the placement of standard-diameter implants (>3.5 mm) difficult or even impossible without the use of more advanced bone regenerative procedures.The use of standard-diameter implants in narrow alveolar ridges may lead to thin buccal or lingual bone or even large dehiscences, increasing the risk of complication and failure , 12.In addition, elderly patients and, especially, patients with comorbidities are often unwilling to undergo extensive surgical procedures such as bone regeneration in order to receive standard-diameter implants . AdaptinIn many cases, the interforaminal height can be reduced to <10 mm (Class D or E according to Lekholm and Zarb or Class IV according to the classification system for edentulous patients of the American College of Prosthodontics) , 15.This situation represents the most complex to rehabilitate.NDIs (narrow-diameter implants) 10 mm long may be too long for them, while short, wide implants may be too wide for thin residual ridges .Such patients represent the most complex and high-risk treatment situation. MDIs 10 mm long may be too long for them, whereas short and wide implants may be too wide for slim residual ridges , 18.To date, there are few studies in the literature on the use of short implants for the rehabilitation of edentulous arches.In the case of a narrow ridge, two options are available. The first option is to place a standard-diameter implant secondly to bone augmentation procedures [11]; the second option is to use a narrow-diameter implant (NDI < 3.5 mm) [11].Although widely validated in literature, bone augmentation procedures are much more invasive and may have a higher risk of complications than conventional placement of implants.Narrow-diameter implants (NDIs) have been introduced as an alternative treatment option in single-tooth gaps or edentulous ridges with limited width , 20.The reduced-diameter implant classification was updated in 2018  [21].The advantages of NDIs include the following: (1) no bone grafting, (2) reduced bleeding, (3) minimal postoperative discomfort, (4) lower costs for the patients, and (5) faster healing time , 22.However, NDIs also present some disadvantages: (1) reduced bone-to-implant contact (BIC) and osseointegration , (2) incHowever, it is recommended that NDIs are used with caution. The reduction in implant diameter reduces the contact surface between bone and implant, thus increasing the risk of fracture due to reduced mechanical stability .Many publications demonstrate the risk of “fatigue” fracture of small-diameter implants , 24.The neck of the implant represents a potential fracture zone when subjected to high bending force. Due to these mechanical limitations, the NDIs are only recommended to increase retention and stability of mandibular overdenture in cases of limited bone thickness , 26.To reduce this risk, new alloys have been introduced.Preliminary results obtained in one study showed that reduced-diameter implants with a titanium-zirconium alloy can withstand masticatory forces in total rehabilitations .The present review has the primary objective to evaluate the survival rate, the marginal bone loss (MBL), and biomechanical features of NDIs of 2.5 to 3.5 mm of diameter (categories 2 and 3) [21] used in the treatment of completely edentulous patients through full-arch removable or fixed restorations.Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0).This systematic review was written according to the guidelines indicated by the “PRISMA statement” and by the The focused question was “What is the survival rate of narrow-diameter implants (2.5-3.5mm) supporting removable or fixed restorations in fully edentulous patients?” A preliminary PICOS assessment was used to define the search strategy with the following criteria.The participants are edentulous patients (both jaws or either upper or lower jaw) with a full-arch implant-retained fixed or removable prosthesis.The interventions are full-arch fixed or removable overdenture prosthesis supported by narrow-diameter implants (2.5 to 3.5 mm).Implant survival rateProsthesis survival rateMarginal bone lossOther variables were searched and described when present: biomechanical features, prosthesis survival, prosthetic complications, reconstruction material, and implant system used.The types of studies are randomized controlled trials (RCTs) and prospective and retrospective clinical trials . Studies had to report data on a minimum of 10 participants and have a minimum of 6 months of follow-up.(edentulous) AND  OR small-diameter implant) OR narrow implant) OR mini-implant) OR mini implant) OR transitional implant) OR temporary implant) OR provisional implant): 830 hits(Edentulous) AND ”: 178 hits(“edentulous”) AND : 1230 hitsThree investigators conducted an independent electronic search of the English literature , using PubMed, Cochrane Library, and Google Scholar for studies published until March 2019, including the following search strategy (MeSH and free terms) for each database :Full-arch removable or fixed full-arch restorationsFollow-up times greater than six monthsProspective cohort studies, randomized controlled or nonrandomized controlled trial, retrospective case-control or “single cohort” studies, and case seriesStudies reporting data of the same cohort of patients, with different follow-upsCase reports on animal or in vitro modelsAll retrieved articles were screened for duplicates by two reviewers (GP-AC). Titles and abstracts were then independently screened by the same review authors (GP-AC). Articles meeting the inclusion criteria and those whose abstract presented unclear data were collected as full text. The papers were then assessed by three authors (GP-AC-MP) that defined if the articles were to be included or not. Any disagreement was resolved by discussion with the other reviewers (SS-GO).Data were extracted by three reviewers (AC-GP-MP) using data collection forms .Study design, implant manufacturer, and data on restorations were extracted. The survival rates of implant and prosthesis were extracted. Implant survival was considered if the implant was present at the follow-up examination. Moreover, when reported, data on marginal bone loss and patient satisfaction was also extracted. When the reported data were unclear, authors contacted by emails the corresponding authors and asked for more information.The risk of bias assessment for the included studies was performed independently by two reviewers (GP and AC) using The Cochrane Collaboration's tool for assessing the risk of bias including the following domains: allocation concealment, random sequence generation, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias.The assessment was not centered on the outcomes of the paper but the ones of the present review.Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.Each domain was considered at low, unclear, or high risk of bias agreeing to the evaluation criteria as reported in the After judgment was given for each of the domains mentioned above, studies were divided into the following groups: studies with low risk of bias, if all domains were considered at low risk of bias; unclear risk of bias, if one or more domains were considered at unclear risk of bias; and high risk of bias, if one or more domains were reported at high risk of bias. Cases of disagreement were resolved by discussion.p = 0.05. For each study, the estimated MBL at five years was calculated by dividing the MBL reported by years of follow-up and multiplying for five, assuming a constant marginal bone loss over time .In both studies, the overall patient satisfaction with the overdenture was high (score > 60). The results of the questionnaire in Morneburg's study confirm that stabilization of mandibular dentures with reduced-diameter implants leads to considerable improvement of the function of the prosthesis and increased comfort for the patient.Clinical data, from this systematic review, suggest that NDIs of 2.5 mm to 3.3 mm of diameter represent an alternative treatment option in the rehabilitation of a completely edentulous jaw with limited width. This could be considered a possible alternative to bone augmentation, when needed. In a recent study by Papadimitriou et al., the rehabilitation of edentulous patients using NDIs showed to require significantly less bone regeneration. At the moment, there are no studies that compare narrow-diameter implant versus standard diameter with bone augmentation procedures in fully edentulous patients.In conclusion, narrow-diameter dental implants show high survival (>95%) and acceptable, marginal bone level changes (<1.5 mm). Although the selected papers are difficult to compare, the results consider NDI a reliable treatment when used to retain an overdenture in the rehabilitation of edentulous jaw with survival rates and biomechanical features similar to standard-diameter implants.It is possible to consider two-/three-implant overdentures in the mandible as a viable treatment option for edentulous patients with high survival rates.No studies were found concerning rehabilitation fixed restorations in both mandible and maxilla. Only one study reported edentulous maxilla restored with overdentures supported by NDI.Future RCTs should investigate the rehabilitation of edentulous patients with narrow implants vs. standard-diameter implants, as well as fixed restorations for edentulous patients.


Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States . In particular, we validate infection control and biological decontamination of the Smart Pod by testing surfaces and the air-filtration system for the COVID-19 virus and bacterial pathogens. We show the Smart Pod to be efficacious in providing a safe clinical environment for vaccine delivery. Moreover, in the Smart Pod, up-to-date education of community healthcare workers was provided to reduce vaccine hesitancy and improve COVID-19 vaccine uptake. The proposed solution has the potential to augment existing hospital capacity and combat the COVID-19 pandemic locally and globally. Vaccination programs and their overall success result from high effectiveness and high uptake of vaccines ,2,3. TheVaccine hesitancy constitutes a major hindrance to vaccine delivery. Of note, studies have shown vaccine hesitancy to be especially pronounced in underserved communities, in part due to the logistical inconveniences of obtaining vaccines ,10,11,12Portable clinics hold the promise of being able to provide high-quality healthcare services to at-risk populations and bridge existing inequities in health, many of which are exacerbated in pandemic and disaster situations. A growing body of research supports that mobile health clinics are a valuable and cost-effective model to healthcare delivery for a variety of clinical applications ,14,15,16Thus, mobile medical units are economically and logistically viable platforms for healthcare delivery that can augment stationary healthcare facilities ,16 and tWhile environmental contamination control is a part of prevention of nosocomial infection and an established practice for stationary hospitals ,23, therAs nosocomial spread represents an important mode of transmission for pandemic viruses such as SARS-CoV-2, designing and validating a portable clinic from an environmental infection control standpoint are paramount. Furthermore, recent case reports and computer models have supported the possible spread of SARS-CoV-2 viral particles via heating, ventilation, and air conditioning (HVAC) systems, emphasizing the need to validate HVAC systems in mobile clinics for absence of SARS-CoV-2 ,25.To deliver high-quality community-based healthcare services and COVID-19 vaccine administration to underserved populations, the portable COVID-19 Smart Pod isolation clinic with advanced air-purification systems, antimicrobial surface features, and a negative pressure isolation room was deployed in Aldine  during the COVID-19 pandemic in September 2020 . This raIn 2020 and 2021, BCM built and deployed two Smart Pod isolation clinics at the Aldine area in unincorporated central Harris County (Texas) and Pasadena, TX, a city east of Houston and the second-largest city in Harris County, providing infrastructure  and educThe goal of this pilot project is to validate the current clinical/operational protocols for infection control in the Smart Pod isolation clinic by obtaining air-distribution system and surface samples for SARS-CoV-2 and bacterial pathogens before, at the peak, and after a full clinical workday of patient care, which will include all standardized cleaning and disinfection standard operating procedures (SOP) in both positive and negative pressure zones of the Smart Pod .Here, we first describe the features of the Smart Pod so that other mobile clinics can implement similar infection control measures. We then describe our surface sampling protocol and the laboratory procedures utilized to isolate bacteria and viral RNA. We proceed to report the bacterial and viral inoculum on all sampled surfaces over the three sampling points and discuss our results to show that the Smart Pod is a safe clinical environment for vaccine delivery. Altogether, we hope that our work improves vaccine uptake in underserved communities through increased confidence in vaccine delivery for healthcare workers and vulnerable populations.The Smart Pod isolation clinic features an “Americans with Disabilities Act” (ADA)-compliant negative pressure isolation room (Exam Room 1) for severely symptomatic patients and two additional examination rooms (Exam Rooms 2 and 3) with enhanced positive air ventilation that can be used for vaccine administration. In its transport mode, the Smart Pod is the size of a standard 8′ × 20′ shipping container a. The coThe negative pressure isolation room is operated by a Bag-In Bag-Out (BIBO) air purification system with a HEPA filter  that allows elimination of 99.7% of pathogens c–e. In aThe positive pressure air-distribution system is enhanced by an energy-efficient, self-cleaning needlepoint bipolar ionization (NPBI) ozone-free air-purifier  designed to handle up to 2400 cubic feet per minute (CFM) and a short-wavelength ultraviolet (UV-C) light air-purification system that covers approximately 50 CFM . An individual air-duct branch is provided for the cross-contamination area and each of the exam rooms f. Using Antibacterial flooring, aseptic cleanroom walls, a foot pedal-controlled sink, antimicrobial disposable curtains, and bleachable surfaces c,d are sIn this study, infection control was investigated via evaluation of surface and air-filter sampling for the presence of viral and bacterial pathogens as a means of evaluating infection control. Due to unprecedented circumstances during the pandemic and given the volume of patients seen (with known and unknown SARS-CoV-2 infection status), collecting patient metrics has not been feasible. In terms of provider metrics, after 11 months of daily usage, none of the healthcare workers  have tested positive for SARS-CoV-2.In In the COVID-19 Smart Pod isolation clinic, surface and air-filter grille sampling was performed at 7 AM prior to opening, at 5 PM following the final patient encounter, and at 7 PM following the cleaning protocol .We sampled floors, walls, door bars, exam tables, and countertops in high-traffic areas using CDC best practices  Figure . We samp2 area was sampled in a back-and-forth motion, followed by two more passes at 90° to the previous pass. The swab was then placed into the sample tubes and stored at 4 °C until plating or qPCR. This protocol was repeated at each time point.For bacterial sampling, the swab from a sterile sampling kit (Copan eSwab 480C) was wetted in the storage solution (Amies medium). For SARS-CoV-2 sampling, the swab from a sterile sampling kit (Yocon MT0301) was wetted in the storage solution (Hank’s solution). To collect both bacteria and SARS-CoV-2 samples, a 10 cmStaphylococcus aureus (MRSA) detection agar , Vancomycin-Resistant Enterococcus (VRE) detection agar (Thermo Scientific Spectra™ VRE Medium #R01832), and blood agar (Thermo Scientific Remel™ Tryptic Soy Agar #R455006 with 5% defibrinated sheep’s blood #R54008). Plates (4 plates for each sample) were placed in a 37 °C incubator for 16 h. Single colonies were then counted.Bacterial detection samples were plated onto Methicillin-Resistant We chose to measure MRSA and VRE colonies, since MRSA and VRE are common nosocomial pathogens that can cause serious infections. While the incidence of MRSA and VRE exposure in mobile clinics remains unknown, we nevertheless sought to quantify MRSA and VRE colonies in order to suggest that the infection control measures employed in the Smart Pod are robust and comparable to the infection control expectations in a large community hospital.SARS-CoV-2 detection was performed according to the CDC EUA protocol. To extract RNA, 200 µL of each sample was extracted using Purelink Pro 96 Viral RNA/DNA Purification Kit . Detection of SARS-CoV-2 was accomplished by qPCR. Each sample was added to a reaction containing TaqPath 1-Step RT-qPCR Master Mix  and a primer and probe set acquired from IDT (10006770). Assembled reactions were run on an Applied Biosystems Quantstudio DX (4480299). Reverse transcription was accomplished at 25 °C for 2 min, 50 °C for 15 min, and 95 °C for 2 min. The RT-qPCR reaction cycle conditions were 95 °C for 3 s, then 55 °C for 30 s (repeated for 45 cycles).n = 3543) addressed symptoms of upper respiratory illness/COVID-19 management, chronic disease management, annual physical examination, and miscellaneous, uncategorized presentations. Furthermore, more than 3000 vaccines have been administered in the Smart Pod.In conjunction with Harris County Precinct 2, Baylor College of Medicine has provided the mobile clinic infrastructure ,37 and eIn the COVID-19 Smart Pod isolation clinic, all patients that require respiratory or droplet precautions have to be examined inside the negative pressure isolation room. To increase infection control, we implemented a traffic scheme to segregate symptomatic and asymptomatic patients and created an isolation ward that would quarantine infected “mask-off” patients. Once vaccines became available, we pivoted to providing both COVID-19 vaccination in addition to COVID-19 testing.-Visit type: sick visit—5, annual physical—1, other vaccine—1;-COVID-19: vaccine—16; test—14, positive—2, negative—11.On the sampling day, 37 patients (adults (18+)—32, pediatric—5) visited the Smart Pod by the following categories:In 2) was also relatively low. We show the pattern of change in the bacterial load of sampled surfaces across three time points in Additionally, except for the positive control, all surfaces were negative for MRSA and VRE colonies at all time points. Overall bacterial inoculum , a spike in bacterial inoculum was observed across all surfaces, yet following disinfection, the bacterial inoculum decreased. Furthermore, in the morning, prior to the start of operations (7 AM), the bacterial inoculum was similarly low, suggesting the persistence of a sterile environment overnight in the Smart Pod.In Additionally, during peak operation time (5 PM), the air purification system worked to significantly blunt the bacterial load. CFU remained relatively low during the morning, although a slight uptick was observed c. While Thus, we meticulously analyze the infection control features of the COVID-19 Smart Pod isolation clinic that provided enhanced patient and personnel safety in the mobile medical facility. Altogether, the Smart Pod can offer optimal conditions for the administration of vaccines, while also dually serving as a facility to provide acute care for severely symptomatic patients.The Smart Pod isolation clinic employs and builds upon many of the infection control measures utilized by clinical facilities during the COVID-19 pandemic. We designed the facility to ensure 6-feet distancing and unidirectional patient flow. In designing the Smart Pod, we also strived to minimize airborne transmission of SARS-CoV-2 and respiratory pathogens. Morawska et al. recommended the use of germicidal ultraviolet to combat the airborne transmission of SARS-CoV-2 . LikewisThe CDC emphasized triage to mitigate further spread of COVID-19 , and we Equipped with high-standard internet connectivity, the Smart Pod functionality can also include components of telemedicine and telementoring to provide guidance and education to frontline community healthcare workers. Telementoring, by models such as Project ECHO ,49, alloWe hope that our findings will encourage the deployment of other mobile facilities, employing similar infection control measures to minimize the risk to patients and healthcare workers within the mobile facility. We further hope that the Smart Pod will allow for easier access and a novel approach to COVID-19 vaccine delivery, especially in underserved communities with higher rates of vaccine hesitancy .Our study should be interpreted in the context of several important limitations. Due to a lack of standardization and well-defined terminology for mobile clinics , the keyword-based literature search and data comparison might be deficient. To the best of our knowledge, this work is the first comprehensive study of environmental infection control in such clinics. In addition, we recognize an important limitation of our study to be the use of surface disinfection as a proxy measure of infection control. Nonetheless, no providers tested positive during the evaluation period. Given the patient population, collecting statistics on patient infection rate is not feasible, nor is it a valid measure of the efficacy of the Smart Pod in preventing infection, as many incoming patients are positive and may have acquired infection from the outside.In the future, we will focus on development of a Smart Pod educational platform for healthcare workers in community-based clinics, employing augmented reality (AR) and virtual reality (VR) technology and automation of disinfection solutions when it is possible.In summary, we have shown that the Smart Pod is an innovative paradigm for vaccine delivery in disaster and pandemic situations that also adheres to established standards of infection control and prevention. To build confidence in community-based vaccine delivery infrastructure, we have demonstrated that well-designed mobile clinics are capable of providing a safe clinical environment with comprehensive biological decontamination for both patients and healthcare workers. We stress the necessity of regular training of personnel in disinfection protocols and a high standard of services in community-based clinical sites in resource-constrained settings.Patent WO2016077466A1 “Mobile Clinics”. Nos. 62/078,924, filed 12 November 2014, and 62/237,138, filed 5 October 2015.


The recommended stroke prevention for patients with atrial fibrillation (AF) and increased risk of ischemic stroke is oral anticoagulation (OAC). Parts of the patient population are not eligible due to contraindication, and percutaneous left atrial occlusion (LAAO) can then be a preventive treatment option. The aim of this systematic review and meta-analysis is to estimate the long-term clinical effectiveness of LAAO as stroke prevention in patients with AF, increased risk of ischemic stroke, and contraindication to OAC.We performed a systematic review and meta-analysis, using Poisson random effect models, to estimate the incidence rate (events per 100 patient-years) of ischemic stroke, transient ischemic attack, major bleeding, and all-cause death after LAAO treatment. We also calculated the risk reduction of ischemic stroke with LAAO compared with no stroke prevention estimated through a predicted risk in an untreated population (5.5 per 100 patient-years).2DS2-VASc score among the patients in the included studies is 4.32. The pooled incidence rate of ischemic stroke is 1.38 per 100 patient-years . According to a meta-regression model, the estimated incidence rate of ischemic stroke at CHA2DS2-VASc 4 is 1.39 per 100 patient-years. This implies a risk reduction of 74.7% with LAAO compared to predicated risk with no stroke prevention.We included 29 observational studies in our meta-analysis, including 7 951 individuals and 12 211 patient-years. The mean CHAOur results suggest that LAAO is effective as stroke prevention for patients with AF, increased risk of stroke, and contraindication to oral anticoagulation.The online version contains supplementary material available at 10.1007/s10840-021-00953-9. Stroke was globally the second most common cause of death and cause of disability adjusted life years (DALYs) among adults in 2016 .2DS2-VASc scores of ≥2 for men and ≥3 for women. If patients are eligible for non-vitamin K antagonist oral anticoagulant (NOAC), it is preferred over vitamin K antagonist (VKA) [Stroke prevention with oral anticoagulation (OAC)Due to contraindications, parts of the population with AF are not eligible for OAC. According to the ESC guidelines on AF, stroke prevention with percutaneous left atrial appendage occlusion (LAAO)To our knowledge, there are only two completed RCTs evaluating the efficacy of LAAO: the Watchman Left atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) study  and ProsLAAO is associated with a relativity high implementation cost compared to OAC treatment . ResourcWe address this knowledge gap by conducting a systematic review and meta-analysis of the long-term clinical effectiveness of percutaneous endocardial LAAO as stroke prevention in patients with AF, and contraindication to OAC. Specifically, we aim to estimate the incidence rate of ischemic stroke, transient ischemic attack (TIA), major bleeding, and all-cause mortality after the post-procedural period in this population, as well as the risk reduction of ischemic stroke compared to no stroke preventive treatment.atrial appendage AND (occlusion OR closure) sorted by; best match, to generate the greatest number of search results. The search term and process were decided jointly by the lead author of this paper and a medical university librarian. The PubMed search was conducted on October 18, 2019, and the results were screened as follows: as a first step, the lead author screened all titles for potentially relevant studies, followed by reviewing the abstracts belonging to these titles. As a last step, articles were reviewed in full-text, and the final decision of eligibility for inclusion in the systematic review and meta-analysis was made on the full-text article. The search terms used in Google Scholar were left atrial appendage occlusion and left atrial appendage closure. Each term was searched separately, and limited to studies published 2010 or later. This limitation was made since in the initial PubMed search, no studies published before 2012 were included in the systematic review and meta-analysis, and to decrease the number of search results in the Google scholar searches. We screened the 200 first search results in each search, and if any new titles were relevant abstracts were read continuously. We also screened the reference list of the studies included in the systematic review and meta-analysis for additional studies.The main literature search of the systematic review and meta-analysis was conducted in PubMed with complementary searches also conducted using Google Scholar. The applied search term used in PubMed were Inclusion criteria were long-term follow-up of percutaneous endocardial LAAO and inclusion of patients with contraindication for OAC. Reasons for exclusion were, for example, meta-analysis, systematic reviews, epicardial interventions, specific subpopulations such as patients with kidney disease or heart failure, and follow-up less than 11 months, since our aim is to study long-term effects from approximately 1 year and onwards. Furthermore, studies were excluded if we suspected overlapping study populations, and the articles most recently published or largest sample size were included. A full list of exclusion criteria is available in the Supplementary information One person extracted data from the original articles manually. Data were extracted into four main categories: study characteristics, patient characteristics, device, and outcomes. Each main category includes several variables, presented in the Supplementary information 2DS2-VASc score were extracted from the original articles as mean and standard deviations (SD) when reported, and median and interquartile range (IQR) as a secondary choice. For the variables gender, procedural success, ischemic stroke, TIA, major bleeding, and all-cause death, data were extracted in absolute numbers. Data on outcome variables were included if events occurred >7 days after procedure, i.e., excluding peri-procedural and short-term adverse events. Furthermore, when possible data were only included from patients having a successful procedure, e.g., patients received a LAAO device. However, we do not believe that this would have any large impact on the results in our analysis, since the average procedural success rate in our systematic review and meta-analysis was 97.3%.Patient characteristics such as age and CHAThe length of follow-up was extracted as mean follow-up and SD if reported in the original articles and median and IQR as a second choice. A few studies did not present either mean or median follow-up in their articles. In these cases, we assumed that the mean follow-up was 12 months, since these studies were all presented as 1-year follow-up studies. To be able to estimate the incidence rate of health outcomes after LAAO, the total number of patient-years were extracted. The number of patient-years was applied from the original article if it was reported. For the articles that did not report the number of patient-years, we estimated the number of patient-years by multiplying the number of patients with successful procedure with mean follow-up time.Quality assessment of the individual studies was carried out with an adjusted version of the Newcastle-Ottawa scale (NOS) for cohort studies ; detaileDescriptive statistics for the original articles included in the systematic review and meta-analysis is presented as means weighted by sample size.I2 [We conducted a meta-analysis to estimate pooled incidence rates and 95% confidence interval (CI) for each outcome. Our outcome measures reflect numbers of events (counts) per patient-year. In our main analysis, we used random effects Poisson regression to estimate pooled incidence rates to account for potential heterogeneity between studies. The dependent variable was the number of events , while the logarithm of the total number of patient-years was used as explanatory variable. Between-study heterogeneity was measured using I2 .2DS2-VASc scores, based on a cohort of 90,490 patients with AF without VKA treatment in Sweden. The predicted risk for ischemic stroke for a patient with CHA2DS2-VASc score of 4 and no stroke prevention is 5.5 per 100 patient-years [Friberg et al.  present nt-years .2DS2-VASc score in our meta-analysis sample is 4.32. To be able to compare the pooled incidence rate of ischemic stroke from our meta-analysis among patients treated with LAAO with the predicted risk score for patients without stroke prevention (5.5 per 100 patient-years), we adjusted our pooled estimate to reflect patients with CHA2DS2-VASc score 4. This was done using Poisson meta-regression with CHA2DS2-VASc score as a covariate.We calculated the risk reduction with LAAO as stroke prevention compared to the predicted risk of ischemic stroke with no stroke prevention by Friberg et al. . The meaStatistical analyses were carried out using the statistical analysis packages Stata (version 16) and R (version 3.6.3).As a sensitivity analysis, we estimated the pooled incidence rate using the inverse variance method for random effects. In this analysis, we used a continuity correction that added 0.5 events to studies that had no events. To identify and asses potential publication bias, we constructed funnel plots for each outcome. In case of asymmetry in the funnel plots, we used the trim and fill method to minimize that influence of extreme values (trim) and fill in with hypothetical values to create symmetry in the funnel plot , 14.To identify potential causes of heterogeneity between studies, we conducted a Poisson meta-regression for each outcome measure with study-level characteristics as covariates.No ethical approval was sought for this systematic review and meta-analysis, since this study design only includes secondary data, and there is none/minimal risk of causing any harm to the patients in the original studies.Twenty-nine articles were included in the systematic review and meta-analysis. The process of identification, screening, and inclusion is illustrated in a PRISMA flowchart Fig. .Fig. 1PR2DS2-VASc and HAS-BLED scores were 4.32 and 3.19 respectively, which both indicate an increased risk for ischemic stroke and bleedings. In the study population included in the meta-analysis, 37.5% previously had a stroke and 60.3% had a major bleeding on average. The mean age in the included articles ranges from 64.4 years [Pooling the data from the 29 included articles –42 resul.4 years  to 79.6 .4 years  years inLAAO devices used in the included articles include the Amplatzer cardiac plug (ACP), Amplatzer amulet , Watchman (Boston scientific), WaveCrest , and LAmbre (Lifetech scientific).The post-procedural treatment after LAAO differs between and within the included studies. In the majority of the studies, patients were treated with a dual antiplatelet treatment (DAPT) for 1–6 months, followed by life-long single antiplatelet treatment (APT).I2 = 48% and 34%).The number of ischemic strokes was reported in all included articles, and the number of TIAs was reported in 20 out of 29 articles Fig. . The inc2DS2-VASc score of 4, estimated in the meta-regression, is 1.39 . When comparing this predicted incidence rate to the predicted risk score at CHA2DS2-VASc 4 (5.5 per 100 patient-years), this implies a 74.7% decrease in the risk of ischemic stroke with LAAO compared to no stroke prevention. When we calculate the risk reduction between the predicted risk of ischemic stroke [The predicted incidence rate of ischemic stroke after LAAO for patients with a CHAc stroke  and the I2 = 86%).Major bleeding was reported in 27 of the 29 included articles, with incidence rates ranging from zero major bleedings , 24 to 8I2 = 91%).Out of the 29 included studies, 27 reported the number of deaths in their studies. The incidence rates of all-cause death ranged from zero , 28, 32 We used an inverse variance method as a sensitivity analysis; for the outcome measures ischemic stroke, TIA, and major bleeding, there were no considerable differences from the main analysis. Detailed information from the inverse variance analysis is presented in Table Ischemic stroke, major bleeding, and all-cause mortality have noticeable asymmetry in their funnel plots Fig. . FurtherWe conducted a meta-regression to identify potential causes of between-study heterogeneity in incidence rates of major bleeding and all-cause death. Covariates that significantly influenced the between-study heterogeneity in studies reporting major bleeding were mean age and proportion of patients with previous major bleeding, which were associated with increased incidence rates. For all-cause mortality, the sample size and publication year were positively correlated with mortality rates. Detailed results from the meta-regression is available in the Supplementary information 2DS2-VASc 4. Furthermore, we estimated the incidence rates of major bleeding and all-cause mortality after LAAO, which were 2.22 per 100 patient-years and 4.38 per 100 patient-years each.We have conducted a systematic review and meta-analysis of the long-term clinical effectiveness of LAAO as stroke prevention for patients with AF, and contraindication for OAC. Our result indicates that LAAO is effective in preventing ischemic stroke in patients with AF that have a contraindication to OAC, with a 74.7% risk reduction of ischemic stroke after LAAO compared to the predicted ischemic stroke rate in a no stroke prevention population at CHAThe estimated effect size is difficult to compare directly to those from existing clinical trials (PROTECT AF/PREVAIL), as they only included patients without contraindications and compared LAAO to treatment with VKA (instead of no stroke prevention). We can, however, compare the incidence rates in our meta-analysis to the treatment arms in the PROTECT AF/PREVAIL trials that received a LAAO device, to assess if our pooled incidence rates are comparable to the only existing clinical trials. The pooled incidence rate in our meta-analysis is 1.38 ischemic strokes per 100 patient-years after LAAO. This result is consistent with the combined 5-year outcomes of the PROTECT AF and PREVAIL trials , where t2DS2-VASc 4, compared to the predicted risk according to Friberg et al. [Furthermore, our result is also comparable to previous published systematic reviews and meta-analysis , 10, eveg et al. . To our g et al. .clinicaltrials.gov, NCT02928497) that is investigating the effectiveness of LAAO in patients with contraindication, but no results are available yet. In the meantime, our systematic review and meta-analysis contribute with valuable knowledge on the clinical effectiveness of LAAO in patients with contraindications. Thus, the findings in our study can guide policy-makers to make evidence-based decision-making when evaluating and planning treatment strategies for patients with AF, increased risk of ischemic stroke, and contraindication for OAC.There is an ongoing RCT , which implies a high-risk study population. It is unclear if the results are generalizable to populations with lower risk. This is important to keep in mind if the composition of the patient population changes in the future or if other patient populations are recommended LAAO treatment.It is important to consider the generalizability of the results presented. Our analysis included studies from different continents that report long-term outcomes after LAAO for patients with AF, increased risk of ischemic stroke, and contraindication to OAC. This is the patient population that, according to the ESC guidelines is the patient population, is to be considered for LAAO treatment . We noteOur overall aim was to investigate the long-term clinical effectiveness of LAAO as stroke prevention in patients with AF and contraindication to OAC. While beyond the scope of our study, there are several clinically relevant questions that warrant additional attention in future research. For instance, it is important to investigate how the clinical effectiveness differs between different percutaneous endocardial LAAO devices, and to study which post-procedural treatments that are most effective at reducing the risk of device-related thrombosis. To our knowledge there is currently no consensus regarding which post-procedural treatments that are most efficient after LAAO. Another clinically important question is if there are differences in the timing of when patients are at greatest risk of having, for example, an ischemic stroke after LAAO treatment and how it can be prevented.2DS2-VASc 4 is 74.7% lower compared with no stroke prevention. Our results imply that LAAO is equally effective as stroke prevention in patients with contraindications as those patients without contraindications; these findings contribute with valuable input for policy-makers deciding on treatment strategies.Left atrial appendage occlusion is effective in preventing ischemic stroke in patients with AF, increased risk of ischemic stroke, and contraindication to OAC. We estimate that the risk of ischemic stroke for a patient with CHAESM 1(DOCX 12 kb)ESM 2(DOCX 12 kb)ESM 3(DOCX 15 kb)ESM 4(DOCX 16 kb)ESM 5(DOCX 12 kb)ESM 6(DOCX 16 kb)


To evaluate effects of atrial fibrillation (AF) on cardiac biomarkers and outcomes in a trial population of patients with heart failure (HF) with reduced ejection fraction treated with optimal guideline-directed medical therapy.We performed a secondary analysis of 894 patients in the Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure (GUIDE-IT) trial (January 2013–July 2016). Patients were stratified by AF status and compared with regard to guideline-directed medical therapy use, longitudinal levels of N-terminal pro–B type natriuretic peptide (NT-proBNP), and outcomes including HF hospitalization and mortality.P=0.04) and HF hospitalization  but with no difference in mortality during a median 15 months of follow-up. There were no significant differences in medication treatment between those with and those without AF. At 90 days, a higher proportion of patients with AF  had an NT-proBNP level above 1000 pg/mL , and AF patients had higher NT-proBNP levels at all time points through 2 years of follow-up.After adjustment, AF was associated with a significant increase in the risk of HF hospitalization or cardiovascular death (hazard ratio, 1.28; 95% CI, 1.02 to 1.61; Among patients with HF with reduced ejection fraction, prevalent AF was associated with higher NT-proBNP concentrations through 2 years of follow-up and higher risk for HF hospitalization despite no substantial differences in medical therapy. The Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure (GUIDE-IT) trial was a randomized controlled trial (RCT) designed to evaluate the efficacy of an N-terminal pro–B type natriuretic peptide (NT-proBNP)–guided treatment plan in patients with clinical heart failure (HF) and a reduced left ventricular ejection fraction below 40%.The aim of this study was to investigate the effects of AF on cardiovascular (CV) outcomes in a contemporary trial population of patients with HFrEF treated with a goal of optimal GDMT using data from the GUIDE-IT trial. We further compared NT-proBNP concentrations longitudinally for patients with HFrEF with and without AF to better understand how AF affects levels of this important biomarker over time with titration of GDMT.,This study uses the data from the GUIDE-IT trial, the results of which have previously been published.,The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to assess quality of life. The KCCQ is a 23-question instrument that examines the impact of HF on a patient’s life. This study used the overall summary score as the primary measure. It includes subsection measures of physical limitations, total symptoms, quality of life, and social limitations.,t-tests for continuous variables and χ2 tests for categorical variables. Per the annotated forms for the GUIDE-IT trial, ablation was characterized as occurring during hospitalizations after the initial patient recruitment and history for the trial. Of note, baseline anticoagulation was defined as anticoagulation by warfarin, direct Xa inhibitor, or direct thrombin inhibitor at initial patient history. The primary outcomes of this study included all-cause death, CV death, first HF hospitalization, and the primary end point of the original trial—HF hospitalization or CV death. For our main outcomes, all-cause death, CV death, non-CV death, HF hospitalization, any hospitalization, and HF hospitalization or CV death, Cox regression was used. For all analyses, there were 2 regressions. The first regression was unadjusted. The second regression model was adjusted for age, sex, diabetes, chronic kidney disease, prior myocardial infarction, prior stroke, ventricular arrhythmia, baseline NT-proBNP concentration, and baseline ejection fraction consistent with the primary analyses for the GUIDE-IT trial and with additions to control for the increased comorbidity burden of patients with AF.U tests. All statistics were done using SPSS 26 software (IBM Corp). The threshold for significance was a 2-sided P value of less than .05.For this study, participants of the GUIDE-IT trial were stratified into 2 cohorts: those with AF and those without AF. Atrial fibrillation was defined as the presence of AF or atrial flutter in the medical records or on examination during the medical history on enrollment of the patient.A total of 358 patients (40.0%) had a history of AF. However, AF patients had a significantly higher baseline ejection fraction and lower rates of prior drug abuse compared with those who did not have AF. Baseline NT-proBNP level was numerically higher but not significantly different between those with and those without AF. All other demographic and baseline comorbidity, laboratory, and medication data were not significantly different and can be found in P<.001) and 90 days (P=.01), but there were no significant differences in percentage of target dose of beta blockers at subsequent time points, including 6 months, 12 months, and 24 months .In terms of GDMT, AF patients had a significantly higher percentage of target dose of beta blockers at baseline (4 months . There wP=.002). Patients with AF had a higher NT-proBNP concentration across the median 15 months of follow-up of the study . However, the rates of HF hospitalization or CV death, HF hospitalization, and all-cause hospitalization were significantly higher for those with AF compared with those without .There were no significant differences between patients with and patients without AF in terms of unadjusted rates of adverse events during the study, severe adverse events during the study, all-cause death, or CV death (P=.04) and HF hospitalization . When stratified by NT-proBNP level of 1000 pg/mL, AF was associated with increased adjusted odds of HF hospitalization or CV death at baseline and HF hospitalization at both baseline and 90 days in the subgroup with an NT-proBNP level of 1000 pg/mL and higher but not in the subgroup with an NT-proBNP level below 1000 pg/mL at those time points .AF patients had no significant differences in KCCQ overall summary scores compared with those without AF ,The reason for the observed increase in the primary composite end point of HF hospitalization or CV death and in HF hospitalization alone among those with HFrEF and AF in our study is unknown. AF and HF share many common risk factors and have consistently been shown to coexist in 15% to 35% of HF patients.Despite a premature termination of the GUIDE-IT trial because of futility, there was still a median follow-up of 15 months for the patients included.There are multiple limitations to this study. As a secondary analysis of an RCT, we cannot completely eliminate the possibility that residual confounding contributed to the observed differences in outcomes between those with AF and those without AF. This paper is subject to the limitations inherent to a cohort study, and causation cannot be inferred from this study. However, we adjusted our analysis for several sociodemographic and medical characteristics, and our findings were consistent for multiple unadjusted and adjusted analyses. The trial data did not include longitudinal information on the detailed atrial arrhythmia history of patients. More detail about AF or atrial flutter chronicity and treatment including antiarrhythmic drug use, detailed oral anticoagulation data, or prior ablation procedures may augment our understanding of the complex interaction between HFrEF and AF. The lack of data on medical management of AF therefore remains an important limitation to this study. Finally, it is possible that findings from the GUIDE-IT trial may not be generalizable to a systolic HF population outside of a clinical trial setting, although the effect of AF would be expected to be even more profound in patients with less frequent follow-up and poorer HF medical treatment.Our analysis demonstrates the association between AF and worse outcomes in HFrEF among a contemporary population of HF patients being frequently monitored and receiving intensive HF medical management. We showed that AF was associated with an increased risk of HF hospitalization or CV death and an increased risk of HF hospitalization alone. In addition, we found higher NT-proBNP levels among patients with AF through 2 years of study follow-up and actually an increase in this biomarker after 6 months for those with AF despite ongoing efforts at HF medical therapy optimization. Our data demonstrate the pathologic relationship between HFrEF and AF despite optimal HF medical treatment and biomarker evidence corroborating worse HF outcomes for those with AF.


Sarcopenia, defined as a decline in muscle mass and function related to aging, affects both limb and swallowing-related muscles. Sarcopenic dysphagia is characterized by decreased swallowing function; therefore, early detection of subclinical dysphagia and subsequent intervention appear to be crucial in the elderly. Numerous tools have been employed to measure the function, strength, and mass of swallowing-related muscles in sarcopenic elderly. The swallowing function can be evaluated by questionnaires like Eating Assessment Tool, Functional Oral Intake Scale, and Food Intake Level Scale, and tests such as the modified water swallowing test and videofluoroscopic swallowing study. Surface electromyography and high-resolution manometry can be applied for quantifying swallowing-related muscle strength. Modalities such as ultrasonography and magnetic resonance imaging are capable of estimating the swallowing muscle mass. In patients with sarcopenic dysphagia, a thorough assessment should be given followed by an integrated intervention combining swallowing muscle strengthening, nutrition support, food texture modification, physical, and occupational therapies. This article aimed to comprehensively summarize the diagnostic criteria/tools as well as their associations/performance in sarcopenic dysphagia. The intervention strategy will also be narrated in this review. Sarcopenia is described as a decline in muscle mass, strength, and physical function. The pathophysiology of sarcopenia comprises primary and secondary causes. The former is considered as age-related changes without other specific pathologies. Sarcopenia derived from a systemic disease  is termed secondary sarcopenia . Several2 in men and <5.5 kg/m2 in women for low muscle quantity; (2) handgrip strength < 27 kg for men and < 16 kg for women for low muscle strength; (3) 6-m walk < 0.8 m/s, Short Physical Performance Battery score ≤ 8, 5-time chair stand test ≥ 15 s, timed up-and-go test ≥ 20 s, or 400-m walk ≥ 6 min for low physical performance [2 in men and <5.4 kg/m2 in women on dual-energy X-ray absorptiometry; and <7.0 kg/m2 in men and <5.7 kg/m2 in women on bioimpedance analysis; (2) handgrip strength < 28 kg for men and < 18 kg for women for low muscle strength; (3) 6-m walk < 1.0 m/s, Short Physical Performance Battery score ≤ 9, or 5-time chair stand test ≥ 12 s for low physical performance [Sarcopenia is a clinical syndrome that refers to a gradual and generalized loss of skeletal muscle mass and strength . The decformance . Moreoveformance . Of noteformance ,15.Dysphagia is defined as difficulty in eating and swallowing , presentDysphagia caused by sarcopenia is categorized as sarcopenic dysphagia . IndispuDysphagia increases the risk of malnutrition due to reduced oral intake. Patients who can achieve full oral intake without additional nutrition support through parenteral routes are able to obtain higher energy contents from food than those who cannot . DecreasThe consensus on the diagnosis of sarcopenic dysphagia has been established at the 19th Annual Meeting of the Japanese Society of Dysphagia Rehabilitation . The coeA 5-step diagnostic algorithm has been developed by the Working Group on Sarcopenic Dysphagia  Figure . It cateThere are several validated clinical and instrumental methods to evaluate dysphagia in sarcopenic individuals. The tools used in the evaluation of sarcopenia include muscle mass, muscle strength, and physical performance. Dual-energy X-ray absorptiometry (DXA) and bioimpedance analysis (BIA) have been commonly applied for the measurement of muscle mass. The dynamometer is used to evaluate grip strength. The six-minute walk test (6MWT), Short Physical Performance Battery score (SPPB), five-time chair stand test (5TSTS), timed up-and-go test (TUG), and 400 m walk test (400MWT) are employed to assess the physical performance. Similar to the assessment of sarcopenia, the muscle volume and strength—as well as function related to swallowing—should be appraised in participants suspected of sarcopenic dysphagia. Questionnaires, swallowing tests, and videofluoroscopic swallowing study (VFSS) can be utilized to determine the swallowing function. Measurement of tongue pressure, lip force, jaw-opening force, surface electromyography (sEMG), and high-resolution manometry (HRM) can be employed for quantifying swallowing-related muscle strength. Ultrasonography and magnetic resonance imaging (MRI) are modalities useful for estimating the swallowing muscle mass . The cutThe Eating Assessment Tool (EAT-10) is a concise questionnaire that can be applied to screen dysphagia . It consDysphagia severity scale (DSS) and the repetitive saliva swallowing test (RSST) are common means to assess dysphagia. DSS is a 7-point ordinal scale with a lower score indicating a worse condition . DSS hadFunctional Oral Intake Scale (FOIS) is an observer-rated ordinal scale focusing on oral intake, ranging from 1 (worst) to 7 . Patients with an FOIS ≤ 5 are considered to have dysphagia . In 2016Food Intake Level Scale (FILS) is a 10-point scale to determine the severity of swallowing dysfunction. Levels 1–3, 4–6, and 7–10 indicate various degrees of non-oral feeding, oral food intake with alternative nutrition, and oral food intake alone, respectively . The intThe modified water swallowing test (MWST) is a simple measurement to detect aspiration by swallowing water . A totalThe use of videofluoroscopic swallow study (VFSS) provides objective information on bolus transport during swallowing . Two casMaximal isometric tongue pressure (MTP) is measured by a device with a disposable oral balloon probe and a plastic pipe, such as JMS measurement apparatus  or Iowa Oral Performance Instrument (IOPI). The balloon is placed in the mouth and the plastic pipe is bitten at the middle of the central incisors with the lips closed. Patients are then asked to raise their tongue and press the balloon to the hard palate for several seconds with the full effort to obtain the maximal tongue pressure . In 2015Jaw-opening force can be employed to measure the strength of the suprahyoid muscles by using the device like jaw-opening force trainer KT2016 , a spherometer with a head encircling belt, two belts to secure the mandible to the head-encircling belt, a chin cap, and a dynamometer. Participants are asked to open their jaws with their full effort to obtain the value of maximum force. In 2017, Machida et al.  enrolledLip force can be measured by using a device such as Lip de Cum . This instrument records the combinational forces on the vertical axis from sensors implanted into the upper and lower plastic lip holder. The participants are asked to close the lips with the maximal effort to obtain the highest value of lip force. In 2019, Sakai et al.  investigSurface electromyography (sEMG) can be applied to evaluate swallowing muscle activity . The eleHigh-resolution manometry has been employed to assess pharyngeal dysphagia by the measurement of intra-lumen pressure of the gastrointestinal tract . During Ultrasonography has benefits such as noninvasiveness, non-radiation exposure, and the capability of dynamic assessment. Moreover, tongue and geniohyoid muscles can be easily/promptly visualized by ultrasonography ,20,66 F. In 2012Ultrasonography can also be applied for the evaluation of the digastric muscle . In 2020Hyoid movement is related to the opening of the upper esophageal sphincter. Individuals are asked to swallow 3 mL of water during which the hyoid displacement is measured by submental ultrasonography . In 2020Magnetic resonance imaging (MRI) is a useful instrument to assess swallowing-related muscle mass and adjacent structures . In 2015Care for sarcopenic dysphagia requires a multi-disciplinary strategy. The interventions to break the vicious circle between dysphagia and malnutrition include swallowing muscle strengthening, physical therapy, occupational therapy, nutrition support, and texture modification of food . CooperaSwallowing muscle strengthening-including lingual resistance exercises, breathing training, and tongue exercises can be applied in patients with sarcopenic dysphagia . Tongue-In 2015, Robbins et al.  applied Poor nutritional status is a core characteristic of sarcopenic dysphagia whereas intensive nutrition therapy  combinedDysphagia can cause malnutrition due to poor oral intake. Moreover, malnutrition is a risk factor for the development of secondary sarcopenia and sarcopenic dysphagia. In 2019, Tanıgör et al.  evaluateIn addition to swallowing muscle training, intervention for the declined whole-body muscle mass and strength should be given in patients with sarcopenic dysphagia. A combination of exercise and nutritional interventions is essential for the elderly with sarcopenia. Physical therapy emphasizing the strengthening of four limbs brings collateral benefits for swallowing-related muscles ,85. In 2Texture modification of food should be incorporated to improve the safety and efficiency of oral eating in patients with sarcopenic dysphagia. In 2016, Carrion et al.  assessedThrough our literature search, we identified that the diagnostic criteria varied across different studies, which would lead to variations of the prevalence of sarcopenic dysphagia. A systematic review and meta-analysis should be implemented in the future to obtain the summarized estimate of the prevalence in general or disease-specific populations. Furthermore, compared with the diagnostic or observational studies for sarcopenic dysphagia, the number of intervention trials is largely insufficient. The long-term benefit of treatments for sarcopenic dysphagia remains unclear. Therefore, more randomized controlled trials implementing the multidisciplinary therapeutic approach with an extended duration of follow-up are desperately desired henceforth.The coexistence of dysphagia and sarcopenia is the key element for the diagnosis of sarcopenic dysphagia. Several tools are useful for the evaluation of different swallowing components in sarcopenic individuals. These encompass questionnaires and swallowing tests, VFSS, instruments measuring tongue/lip/jaw-opening strength, sEMG, HRM, ultrasonography, and MRI. A multidisciplinary approach combing swallowing muscle strengthening, nutrition support, physical/occupational therapy, and texture modification of food should be given to patients with sarcopenic dysphagia once a diagnosis is confirmed. The goal of these interventions is to recover whole-body and swallowing-related muscle mass and function, breaking the vicious circle between dysphagia and malnutrition.


In context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with certain comorbidities and high age, as well as male sex are considered to represent the risk group for severe course of disease. Corona-virus disease 2019 (COVID-19) typical CT-patterns include bilateral, peripheral ground glass opacity (GGO), septal thickening, bronchiectasis, consolidation as well as associated pleural effusion. We report a 77-year-old heart transplanted patient with confirmed COVID-19 infection and coronary heart disease, diabetes type II and other risk factors. Notably, only slight clinical symptoms were reported and repeated computed tomography (CT) scans showed an atypical course of CT findings during his hospitalization. COVID-19; Heart transplantation; Thorax; Multidetector computed tomography We report a 77-year-old male patient with an allogeneic heart transplantation (HTX) completed in 2003 and resulting long term immunosuppressive therapy with Sirolimus  and Mycophenolat-Mofetil (250mg BID) medication. The patient had risk factors . All images were acquired at full inspiration in one single inspiratory breath-hold without intravenous contrast. A 120 kVp protocol, with 500 ms exposure time and a pitch of 1.5 with head first side patient position and no use of radiation filters.The initial CT scan obtained on the first day of hospitalization showed exclusive left-sided focal ground glass opacity (GGO) B in the On day 5 of hospitalization, a second CT scan was performed. Although this timepoint is described as the point of peak levels of lung involvement in recent literature  the scanSurprisingly, the third and final CT scan performed on day 8 of hospitalization showed only slight residual GGO in the left lower lobe A. Despit3After full recovery, the patient was discharged on hospitalization day 12 without any clinical symptoms and a negative RT-PCR test result for SARS-CoV-2.4In the context of the global pandemic of COVID-19, for high risk patients  with carAgainst our expectations, the patient suffered from mild clinical symptoms throughout the duration of hospitalization. Over the course of three CT scans, we could observe an atypical course of COVID-19. Minimum intensity projections (MinIP) were read additionally, as it has been demonstrated in recent literature that they improve detectability of small GGOs . Our patThere have been descriptions of similarly mild courses, as seen in our patient , 11 withFrom our observations we conclude that not every patient with immunosuppressive therapy and multiple risk factors suffers from a severe course of COVID-19.We therefore hypothesize, that patients with HTX and other risk factors may benefit from the combination of persistent anticoagulative and immunosuppressive therapy in the context of COVID-19.All authors listed have significantly contributed to the investigation, development and writing of this article.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Data included in article/supplementary material/referenced in article.The authors declare no conflict of interest.No additional information is available for this paper.


Left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is a major pathological basis associated with heart failure and increased mortality. Exercise-based cardiac rehabilitation has been verified to significantly improve prognosis and quality of life. As a traditional Chinese Qigong, Baduanjin exercise has effectively alleviated adverse LV remodeling in STEMI patients. Despite this, participation in exercise rehabilitation remains low, and home-based exercise rehabilitation may be an alternative approach. Besides, anterior STEMI is reported to have higher risk of adverse LV remodeling. However, the efficiency regarding home-based Baduanjin exercise on LV remodeling in anterior STEMI patients remains uncertain currently.A single-blind, randomized controlled clinical trial was conducted to explore the efficacy and safety of home-based Baduanjin exercise in anterior STEMI patients compared with moderate intensity aerobic walking. A total of 114 participants were assigned randomly to the Baduanjin group or walking control group at a 1:1 ratio. Eligible participants practiced Baduanjin or walking exercise (5 times a week) for 12 weeks, and then followed up for another 12 weeks. The primary outcome is a relative change in the LV end-diastolic volume. The secondary outcomes include the plasma levels of hypersensitive C-reactive protein and interleukin 6, health-related quality of life measured by EQ-5D-5L, LV ejection fraction, patient health questionnaire-9, generalized anxiety disorder screener-7, short physical performance battery score, and clinical endpoint events. The proportion of circulating regulatory T-cells were also assessed. Adverse events were recorded throughout the trial for safety evaluation. Data were be analyzed by researchers blinded to the treatment allocation.This study provided powerful evidence for the use of home-based Baduanjin exercise in anterior STEMI patients in alleviating LV remodeling and improving clinical outcomes.The Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine has approved this study (ZYYECK[2020]045). Written informed consent of patients were required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2100047298).Our results will be published in peer-reviewed journals and disseminated through academic conferences and the Internet. Acute myocardial infarction (AMI) is a cardiac emergency with substantial morbidity and mortality ; AMI surDespite this, current participation rates in exercise-based rehabilitation are generally extremely low, whether in developed or developing countries. Reported barriers to attendance involve inconvenient transportation, high out of pocket expenses, scheduling conflict, and lack of professional rehabilitation center and facility . NotablyBaduanjin exercise, as a traditional Chinese Qigong exercise designed to enhance health, is a moderate intensity aerobic exercise that can be practiced easily and performed at any place without restrictions . To someT-cells.To date increasing evidences  have shoAgainst this backdrop, we designed a randomized controlled clinical trial to compare the efficacy and safety of 12-week home-based Baduanjin exercise with moderate intensity aerobic walking in patients with anterior STEMI. Patients with a short physical performance battery (SPPB) score more than 9, which are considered to have an exceptional functional capacity, were included to reduce variability among different patients. We assume that home-based Baduanjin exercise is better than moderate intensity aerobic walking in alleviating LV remodeling and improving clinical outcomes such as health-related quality of life (HRQoL) and clinical endpoint events. Flow cytometry was used to detect the changes of T lymphocyte subsets, which can help us to analyze the possible mechanism of home-based Baduanjin exercise in inhibiting LV remodeling after anterior STEMI.This study is a single-center, open, randomized controlled trial that was conducted at The First Affiliated Hospital of Guangzhou University of Chinese Medicine. A total of 114 participants were recruited after providing written informed consent. The participants were randomly assigned in a 1:1 ratio to either the Baduanjin exercise group or the walking control group. This trial consisted of a 12-week intervention period and a 12-week follow-up period. A flowchart of the trial is illustrated in This trial protocol has been approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou University of Chinese Medicine (project number: ZYYECK[2020]045) and registered in China Clinical Trial Registry (ChiCTR2100047298).Participants were recruited from The First Affiliated Hospital of Guangzhou University of Chinese Medicine. The potential patients were informed about the information of this trial, including the objectives, process, intervention methods, potential adverse effects, and advantages. Each eligible participant was asked sign the informed consent.(1) Men or women, between 18 and 75 years old.(2) First anterior STEMI was diagnosed based on typical chest pain, cardiac enzyme elevation, and persistent st-segment elevation of 2 mm in 2 or more contiguous anterior leads or 4 mm total st-segment deviation sum in the anterior leads;(3) Received successful primary percutaneous coronary intervention (PCI) within 12 h after chest pain onset.(4) The SPPB score more than 9 at the inclusion visit before discharge.(5) Volunteer, understand, and provide written informed consent.(1) Plan to have cardiac surgery or elective multivessel PCI during the trial.(2) Patients with prior MI or coronary artery bypass grafting surgery.(3) Patients with myocardial ischemia at rest or on exertion, cardiogenic shock, severe heart failure (LVEF <35%), uncontrollable malignant arrhythmia, severe chronic obstructive pulmonary disease, or severe valvular disease necessitating surgery.(4) Uncontrolled hypertension, systolic blood pressure (SBP) ≥180 mmHg, and/or diastolic blood pressure (DBP) ≥110 mmHg; or SBP <90 mmHg and/or DBP <50 mmHg.(5) Combined with psychiatric manifestations or malignancy.(6) Expectation life <1 year.(7) Participation in other clinical exercise studies within 3 months.(8) Patients who are unable to exercise due to physical disabilities or other reasons.(9) Researcher's estimate that the patient may be unable to complete the study(1) Serious comorbidities, serious complications, or serious adverse events (AEs) during the study, such as repeated hospitalization for MI or heart failure;(2) Receive adjunctive treatments without permission, which will affect the assessment of efficacy and safety.(3) Poor compliance by participants, or the amount of exercise does not meet the regulations (<80% or >120%);(4) Participants request to withdraw from the study halfway;(5) Researchers determine it is not safe to continue participating in the trial.Participants were randomized to the Baduanjin exercise group or the walking control group in a 1:1 ratio using a table of random numbers, which is generated in the R statistical package. The grouping information was retained in an opaque envelope and sealed subsequently. Participants were recruited in a natural, unpredictable order. After screening, the study coordinator opened an envelope sequentially to obtain a random number and grouping information for each included participant.Given the complete difference of the exercise interventions, it is not possible to blind study participants and exercise instructors throughout the entire duration of this trial. However, the staff performing the echocardiography, technicians in clinical laboratory, investigators conducting the outcomes assessments, and statistical analysis were blinded to the assignment.Home-based CR were adopted for both the groups. Eligible participants were allocated randomly to the Baduanjin group or the walking control group, and individualized exercise prescription was formulated.Both groups exercised at least 5 times per week for 12 weeks at home. Exercise intensity was monitored using Borg's rating of perceived exertion (RPE) scale, or regulated based on HRmax determined during the initial 6-min walk test. Exercise sessions in both groups included a warm up, movement, and relaxation period. Moreover, a movement diary was provided to all the participants to record their daily exercise activity for the duration of the trial. At the end of the 12-week mark, patients were encouraged to continue their exercise training at home.The Baduanjin exercise group practiced Baduanjin at home. A professional coach guided the training of participants during hospitalization and supervised them throughout the entire intervention period. A standardized Baduanjin exercise protocol was formulated following the “Healthy Qigong Baduanjin” published by the General Administration of Sports in 2003 . BaduanjThe walking control group practiced moderate intensity walking exercise on a treadmill or outdoors at a frequency of 5 times per week, over a 12-week period. Each routine session contained three components, 5 min of warm up, at least 20-min walking training, and 5 min of relaxation. The exercise intensity and energy expenditure was a constant at Borg's RPE 12–13 scale or 55–75% of the peak HR. All participants were instructed to maintain their usual activities and refrain from new strength training.All participants received standard treatment, such as aspirin, clopidogrel, ticagrelor, anticoagulants, statin, beta-receptor blocker, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). Any medical therapy change was recorded in a combined medication record form.The secondary outcomes are(1) Improvement in HRQoL. This was assessed according to EQ-5D-5L. The EQ-5D is a simple, generic HRQoL instrument that is widely used as a patient-reported outcome measure. EQ-5D-5L consists of utility index (UI) and visual analog score (VAS). The UI is calculated from patient scoring of five dimensions . The EQ-5D-5L UI in Chinese is between −0.391 and 1.00 .(2) Improvement in echocardiographic measurements of LVEF calculated with Simpson's method from 2-dimensional, apical, 2-chamber, and 4-chamber views .(3) Changes in plasma levels of inflammatory cytokine hypersensitive C-reactive protein (hs-CRP) and IL-6.(4) Changes in patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder screener-7 (GAD-7) score.(5) Changes in SPPB score.(6) The incidence rate of clinical endpoint events .Safety outcomes comprise vital signs , electrocardiogram, laboratory examinations , and AEs . AEs may include medication-withdrawal AEs , exercise injury, and fall .T-cells exert a significant role to regulate inflammation and repair after myocardial infarction. In particular, depletion of Tregs exacerbate cardiac inflammation and LV remodeling , including lymphocytes, T-cells (CD3+), and the T-cells subpopulations such as cytotoxic T-cells (CD3+CD8+) and T-helper cells (CD3+CD4+). Additionally, the proportions of Tregs (CD3+CD4+CD25+) was also assessed. Most studies have concluded that adaptive immune response focused on modeling , while tmodeling  or adoptmodeling  contribumodeling , 35.The sample size is calculated based on the expected improvement in LVEDV between the Baduanjin exercise group and the walking control group. Referring to clinical studies , 36, we In this formula, κ is the ratio between the two sample cases, δ is the expected improvement in LVEDV, and σ is the combined SD.t-test was applied for continuous data with a normal distribution. Homogeneity test of variance was conducted among the groups, with a cutoff level of 0.05, and the corrected t-test was used when the variance was uneven. If the data does not follow a normal distribution, the Mann-Whitney U test was performed to analyze intragroup or intergroup differences before and after treatment, respectively. All tests were two-sided, and a P value < 0.05 was considered statistically significant. The method of analysis for specific outcomes is shown in An intention-to-treat analysis was conducted. Moreover, data was also analyzed as per the CONSORT statement. Statistical analysis was conducted by third-party statisticians, who were blinded to the group allocation and intervention process, using statistical software package SPSS 23.0 . Regarding categorical variables, these were described as counts or percentages. Continuous variables with normal distribution were displayed as mean ± SD, whereas data with non-normal distribution was displayed as median and interquartile range. The chi-square test or Fisher's exact probability method was applied for categorical data, whereas the Student's Quality control throughout the entire experimental process was carried out, and a quality control committee was established, which composed of 3–4 experts from the medical technology department, and Statistical Teaching and Research Office. Prior to the trial, all researchers  received unified preclinical trial training to fully understand the trial protocol, standard study procedures, and their corresponding roles, for example, research assistants reminded participants to exercise at home and complete exercise diaries. In addition, all investigators were trained to perform outcome assessments, data management, and fill in the case report forms (CRFs) uniformly. Meanwhile, periodical meetings were organized to discuss problems during the trial and figure out the best solutions. This trial was inspected by the ethics committee, sponsor, and clinical research organization throughout the study.This is an ongoing trial. This study is recruiting participants currently.This study determined the efficacy and safety of home-based Baduanjin exercise in anterior STEMI patients on LV remodeling and clinical outcomes, as well as the changes on T lymphocyte subsets detected by flow cytometry.Acute myocardial infarction is a serious problem in the world and especially brings great physical discomfort and psychological burden to patients, with a high morbidity and mortality . LV remoBaduanjin exercise is a moderate intensity aerobic exercise that can be learned easily and practiced at any place without limitations, which is a popular and safe community exercise in China . A recenCurrently, the potential mechanisms of aerobic exercise training on ameliorating adverse LV remodeling are unclear and partly attributed to immune function. Strong evidences have shown that adaptive immune response focused on T cells after cardiac damage plays an important role to regulate inflammation from the acute to chronic phase, in which T lymphocytes are closely related to the process of AMI damage and repair . FurtherTherefore, this study is designed to explore the effects and safety of home-based Baduanjin exercise on LV remodeling and clinical outcomes in patients with anterior STEMI, and whether it can regulate T lymphocyte subsets, especially the proportion of Tregs. In addition, we included patients with SPPB score more than 9 to reduce variability among different patients, because they are considered to have exceptional functional capacity.Our trial has three main limitations. First, this study is a single-center study, and compared with other multicenter comprehensive studies the sample size is smaller. It is unknown whether similar effects are obtainable in other regions and ethnic groups. Second, this trial has only been followed up for 6 months, and the follow-up time can be appropriately extended to clarify the long-term clinical results and potential effects of home-based Baduanjin exercise. Third, only patients with exceptional physical performance (SBBP>9 score) were evaluated. It is also valuable to explore the efficacy and safety of home-based Baduanjin exercise in those patients with reduced physical performance .The Research Ethics Committee of the First Affiliated Hospital of Guangzhou Chinese Medical University has approved this study (ZYYECK[2020]045). The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.LK, YC, and RL designed the study. YC, KC, YL, XZ, and HL wrote the manuscript. XZ, LK, and RL modified the manuscript. XZ, QC, and RL are responsible for the quality control of the test. YC, XZ, QC, LK, KC, and RL participated in the modification of the study protocol. YC and LK designed the method for statistical analyses. All authors read and approved the final version of the manuscript.This project is supported by the High Levels of Hospital Construction Projects of Guangzhou University of Chinese Medicine (211010010734), the Innovation and Strong Institute Project of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (2019ZWB06), Science and Technology Projects in Guangzhou (202102020927), and Administration of Traditional Chinese Medicine of Guangdong Province of China (20212064).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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