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Background: Frequently in orthopedic practice, we come across massive bone defects, which can result from open fractures, gap non- unions and following resection of bone tumours. The problems involved in bridging or regenerating areas of skeletal loss with viable bone while maintaining limb length and alignment, along with satisfactory function remains a substantial challenge. The present study was carried out for evaluation & analysis of the role of non-vascularised fibular grafting in managing such bone defects. Methods: 25 cases with bone gap were treated with non-vascularized fibular strut graft from June 2010 to Sept 2012. There were 13 cases of gap non- union, 9 cases of tumour resection and 3 cases of post traumatic bone loss. Functional outcome was assessed by MSTS Score. Results: A total of 71 graft host junctions were studied, out of which 68 united, in a mean period of 13 weeks. Functional outcome was good with a mean MSTS Score of 76.63%. Average size of bone gap treated was 5.19 cm. Primary cancellous grafting was done in 15 cases. Size of bone gap or use of primary cancellous bone graft had no statistically significant relationship with time taken for union. Conclusion: Non- Vascularized fibular strut grafting is a simple, inexpensive and an effective technique in bridging bone gaps. It takes longer duration to achieve union, but if used in selected patients with good vascular bed and soft tissue coverage, can yield comparable results to vascularized fibular grafts in terms of overall union.

Background: Heart transplant recipients with donor-specific antibodies (DSAs) have an increased risk for antibody-mediated rejection. However, many patients with graft dysfunction and DSA do not have evidence of antibody-mediated rejection by endomyocardial biopsy (EMB)., Methods: Participants from this prospective, multicenter study underwent serial EMB, echocardiogram, DSA, and donor-derived cell-free DNA evaluations. Outcomes were defined as pAMR+ (pAMR≥1) or DSA+/left ventricle (LV) dysfunction (DSA presence+LVEF drop ≥10% to an LVEF≤50%). Cox regression evaluated the association between antibody-mediated rejection categories and death or sustained (for 3 months) reduction of LVEF to <50%., Results: Two hundred sixteen patients (29% women, 39% Black race, median age 55 [interquartile range, 47-62] years) had 1488 EMB, 2792 DSA, 1821 echocardiograms, and 1190 donor-derived cell-free DNA evaluations. DSAs were present in 86 patients (40%). Fourteen patients had isolated pAMR+ episodes and 8 patients had isolated DSA+/LV dysfunction episodes; 2 patients had pAMR+ and then subsequently DSA+/LV dysfunction with pAMR+. Median %dd-cfDNA was significantly higher at diagnosis of pAMR+ (0.63% [interquartile range, 0.23-2.0]; P =0.0002), or DSA+/LV dysfunction (0.40% [interquartile range, 0.36-1.24]; P <0.0001), compared with patients without these outcomes (0.01% [interquartile range, 0.0001-0.10]). Both pAMR+ and DSA+/LV dysfunction were associated with long-term clinical outcome of death (n=18) or prolonged LV dysfunction (n=10): pAMR+ (hazard ratio, 2.8 [95% CI, 1.03-7.4]; P =0.043); DSA+/LV dysfunction (hazard ratio, 26.2 [95% CI, 9.6-71.3]; P <0.001); composite of both definitions (hazard ratio, 6.5 [95% CI, 2.9-14.3]; P <0.001). Patients who developed pAMR+ or DSA+/LV dysfunction within the first 6 months of transplant were more likely to die within 3 years posttransplant (hazard ratio, 3.9 [95% CI, 1.03-14.6]; P =0.031)., Conclusions: Expanding the characterization of antibody-mediated rejection to include patients with DSA and concurrent allograft dysfunction identified DSA+ patients at risk for death and prolonged LV dysfunction.

Background: Diagnosis of hereditary amyloid transthyretin (hATTR) amyloidosis with cardiomyopathy is frequently delayed, in large part because of symptom overlap with other cardiovascular diseases and limited provider knowledge of this disease. The sponsored and provider referred hATTR Compass Genetic Testing Program (Ionis, Carlsbad, CA; Ambry Genetics, Aliso Viejo, CA) provided no-cost genetic testing to adults with a family history or clinical suspicion of hATTR amyloidosis. This study aims to characterize patients with hATTR amyloidosis and increase awareness of genetic testing for hATTR., Methods and Results: Patients were referred to the hATTR genetic testing program, and a cross-sectional post hoc analysis was performed. A pathogenic TTR variant was identified in 1503 (6.6%) of 22 886 patients referred for genetic testing between June 2018 and March 2022. Patients were identified in all US states, 3 US territories, and Canada. Median age at testing was 63 years, and 44% were female. The p.V142I TTR variant was the most common (n=1263, 84.0%). Only 32% of patients with a pathogenic TTR variant reported a known family history; a lower percentage of Black individuals reported a known family history compared with other racial and ethnic groups. Black patients accounted for 23.7% of all patients referred and 81.9% of patients with the p.V142I variant., Conclusions: This sponsored genetic testing program identified a large number of patients with a pathogenic TTR variant, notably, in geographic regions not previously reported, and demographic groups that are historically underrepresented in the literature.

Background: There is significant variability among pathologists in the histopathological interpretation of the endomyocardial biopsy (EMB) for acute cellular rejection (ACR), and assessment of variability in the interpretation of antibody-mediated rejection (AMR) has not been reported. In contemporary practice, the strategy of allograft surveillance with donor-derived cell-free DNA (dd-cfDNA) compared to EMB has not been compared with a focus on long-term clinical outcomes beyond acute rejection (AR)., Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective cohort study that enrolled patients from 2015 to 2020. The center pathologist read was compared to 2 blinded core cardiac pathologists. ACR and AMR were graded based on the International Society for Heart and Lung Transplantation criteria. Weighted Cohen's kappa (κ) was used to evaluate interrater reliability between the center and core reads. To assess long-term outcomes, we evaluated a composite of AR, allograft dysfunction, and mortality within 1 year., Results: The study included 94 patients (median age 55 years [interquartile range (IQR) 45, 62]), 30% female sex, 41% Black race), with 429 paired EMBs and dd-cfDNA measures. The concordance rate between center and core pathologists was 77% for ACR (95% confidence interval [CI]: 66%-89%) and 63% for AMR (95% CI: 53%-74%). Forty-six patients had an elevation in dd-cfDNA without AR by EMB. The median dd-cfDNA was 0.49% (IQR: 0.35, 1.01), and subsequent AR, allograft dysfunction, or mortality occurred in 59% of these patients at 1 year. In patients with AR by EMB and negative dd-cfDNA (n = 5), the composite outcome occurred in 20% of patients at 1 year. At baseline, the positive likelihood ratio (LR+) of dd-cfDNA to detect AR by the center pathologist was 3.74 (95% CI 3.01-4.64) and by core pathologist was 2.59 (95% CI: 1.95-3.45). If the composite outcome was included as a true positive, the LR+ of dd-cfDNA improved to 9.82 (95% CI: 7.04-13.69) and 7.63 (95% CI: 5.61-10.38) at 1 year, respectively., Conclusions: Pathologists' interrater reliability is limited in AMR similar to what has been reported in ACR. The LR+ of dd-cfDNA when compared with traditional histopathology is limited, but when longitudinal clinical outcomes are included to assess diagnostic performance, the LR+ improves significantly. The value of dd-cfDNA extends beyond the diagnosis of AR to include other clinically meaningful outcomes for patients after heart transplant., (Copyright © 2024 International Society for the Heart and Lung Transplantation. All rights reserved.)

Purpose: To conduct a network meta-analysis comparing the safety and efficacy of gabapentin (GBP), pregabalin (PGB), oxcarbazepine (OXC), and duloxetine (DLX) in treating diabetic peripheral neuropathy (DPN)., Materials and Methods: The study's eligibility criteria includee randomized controlled trials (RCTs) with a focus on DPN patients receiving GBP, PGB, DLX, or OXC versus placebo. Noncompliant trials with incomplete information and observational studies were excluded., Results: Twelve (RCTs) of PGB, 2 of GBP, 3 of DLX, and 1 of OXC met the inclusion criteria. When drugs were compared for efficacy (direct comparison), GBP (Odd's ratio [OR] = 3.208, P < 0.001) was most effective followed by OXC (OR = 2.4, P = 0.0248), DLX (OR = 2.346, P < 0.001), and PGB (OR = 2.161, P < 0.001). When drugs were compared for withdrawal due to adverse drug reaction (ADR) (direct comparison), GBP (OR = 1.3818, P = 0.766) was safest followed by PGB (OR = 2.16, P < 0.001), DLX (OR = 2.469, P < 0.001), and OXC (OR = 4.4967, P = 0.001). Indirect comparison was done for efficacy, DLX was statistically significant than PGB and OXC (DLX vs. PGB, P = 0.03; DLX vs. OXC, P = 0.02). When indirect comparison was done for patient withdrawal due to ADR, OXC was worst (GBP vs. OXC, P = 0.0001; PGB vs. OXC, P = 0.007; DLX vs. OXC, P = 0.015). When drugs were compared for individual ADRs (direct comparison), dizziness was most commonly seen with OXC (OR = 9.6535, P = 1.8425), headache with OXC (OR = 3.8686, P = 0.006), somnolence with PGB (OR = 5.189, P < 0.001), and nausea with DLX (OR = 3.264, P < 0.001). GBP was most effective and safest drug followed by OXC > DLX > PGB for efficacy and PGB > DLX > OXC for safety., Conclusion: In evaluating medications for DPN against placebo, GBP and OXC demonstrated the highest effectiveness while maintaining a favorable safety profile., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Perspectives in Clinical Research.)

BACKGROUND. Advanced MRI-based neuroimaging techniques, such as perfusion and spectroscopy, have been increasingly incorporated into routine follow-up protocols in patients treated for high-grade glioma (HGG), to help differentiate tumor progression from treatment effect. However, these techniques' influence on clinical management remains poorly understood. OBJECTIVE. The purpose of this article was to evaluate the impact of MRI-based advanced neuroimaging on clinical decision-making in patients with HGG after treatment. METHODS. This prospective study, performed at a comprehensive cancer center from March 1, 2017, to October 31, 2020, included adult patients treated by chemoradiation for WHO grade 4 diffuse glioma who underwent MRI-based advanced neuroimaging (comprising multiple perfusion imaging sequences and spectroscopy) to further evaluate findings on conventional MRI equivocal for tumor progression versus treatment effect. The ordering neurooncologists completed surveys before and after each advanced neuroimaging session. The percent of episodes of care with a change between the intended and actual management plan on the surveys conducted before and after advanced neuroimaging, respectively, was computed and compared with a published percent using the Wald test for independent samples proportions. RESULTS. The study included 63 patients (mean age, 54.6 ± 12.9 [SD] years; 36 women, 27 men) who underwent 70 advanced neuroimaging sessions. Ordering neurooncologists' intended and actual management plans on the surveys completed before and after advanced neuroimaging, respectively, differed in 44% (31/70; 95% CI: 33-56%) of episodes, which differed from the published frequency of 8.5% (5/59) ( p < .001). These management plan changes included selection of a different plan for six of eight episodes with an intended plan to enroll patients in a clinical trial, 12 of 19 episodes with an intended plan to change chemotherapeutic agents, four of eight episodes with an intended plan of surgical intervention, and one of two episodes with an intended plan of reirradiation. The ordering neurooncologists found advanced neuroimaging to be helpful in 93% (65/70; 95% CI: 87-99%) of episodes. CONCLUSION. Neurooncologists' management plans changed in a substantial fraction of adult patients with HGG who underwent advanced neuroimaging to further evaluate conventional MRI findings equivocal for tumor progression versus treatment effect. CLINICAL IMPACT. The findings support incorporation of advanced neuroimaging into HGG posttreatment monitoring protocols.

Background: Patients with dementia are at increased risk for adverse events following valvular surgery. Outcomes after mitral transcatheter edge-to-edge repair (TEER) for mitral regurgitation in this vulnerable population are not well understood., Methods: We queried the National Inpatient Sample database for all hospitalizations for mitral TEER between 2016 and 2019. Patients with a validated diagnosis code for dementia were identified by ICD-10 codes and compared to a matched cohort of non-dementia patients using multivariable regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes were hospital length of stay, discharge to nursing facility, total hospital charges, and in-hospital adverse events., Results: 24,550 hospitalizations for mitral TEER were identified, including 880 patients (3.6 %) with dementia. Dementia was associated with higher in-hospital mortality (OR 4.31, 95 % CI 2.65 to 6.99, p < 0.001), prolonged length of hospital stay (OR 1.33, 95 % CI 1.12 to 1.57, p 0.001), higher discharge rate to nursing facility (OR 2.71, 95 % CI 2.13-3.44, p < 0.001), and higher rate of in-hospital adverse events including delirium (OR 5.88, 95 % CI 4.06 to 8.52, p < 0.001) and acute stroke (OR 8.87, 95 % CI 5.01 to 15.70, p < 0.001)., Conclusions: Dementia is associated with worse post-procedural outcomes after mitral TEER. Further investigation is needed to elucidate mechanisms of poor clinical outcomes and guide shared decision-making in this vulnerable population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation and the use of cardiovascular magnetic resonance in the diagnosis and management of cardiovascular disease. The 2023 digital collection of cases is presented in this article., Competing Interests: Declaration of competing interests The authors, Jason N. Johnson, Cara Hoke, Anna Lisa Chamis, Michael Jay Campbell, Addison Gearhart, Sarah D de Ferranti, Rebecca Beroukhim, Namrita Mozumdar, Mark Cartoski, Shannon Nees, Jonathan Hudson, Sorayya Kakhi, Yousef Daryani, W. Savindu Pasan Botheju, Keyur B. Shah, Mohammed Makkiya, Michelle Dimza, Diego Moguillansky, Mohammad Al-Ani, Andrew Andreae, Han Kim, Hisham Ahamed, Rajesh Kannan, Chris Ann Joji, Anna Baritussio, Jeffrey M. Dendy, Pranav Bhagirath, Madhusudan Ganigara, Edward Hulten, Robert Tunks, Rebecca Kozor, and Sylvia S.M. Chen, declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author, Sylvia S.M. Chen, is an Editorial Board Member for Journal of Cardiovascular Magnetic Resonance and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Importance: Endometriosis is a prevalent condition within the female reproductive age group, but its presentation and diagnosis still pose a challenge as it mimics other diseases and affects multiple organ systems., Case Presentation: A 24-year-old nulliparous female presented with complaints of menorrhagia, lower abdominal pain, post-coital bleeding, and significant weight loss for 7 months., Clinical Discussion: The case highlights the challenge of diagnosing endometriosis due to its ability to mimic other conditions, such as carcinoma cervix and rectum. The presence of elevated Cancer Antigen-125 (CA-125), typically associated with malignancy, underscores the need for a comprehensive evaluation to differentiate between endometriosis and other pathologies. Furthermore, the involvement of multiple organ systems emphasizes the systemic nature of endometriosis and the importance of considering it in the differential diagnosis of pelvic masses and symptoms in young women., Conclusion: Endometriosis, although a common disease among females of reproductive age its variation in presentation causes significant misdiagnosis and undertreatment. Multi-modal diagnosis and early treatment are necessary for proper outcomes., Competing Interests: The authors declare that they have no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA., Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study. Sequencing was used to quantitate dd-cfDNA and polymerase chain reaction to quantitate cell-free mitochondrial DNA in plasma. AR was defined as ≥2R cellular rejection or ≥1 antibody-mediated rejection. The primary composite outcome was AR, graft dysfunction (left ventricular ejection fraction <50% and decrease by ≥10%), or death., Results: We included 148 patients (65 Black patients and 83 White patients), median age was 56 years and 30% female sex. The incidence of AR was higher in Black patients compared with White patients (43% versus 19%; P =0.002). Antibody-mediated rejection occurred predominantly in Black patients with a prevalence of 20% versus 2% ( P <0.001). After transplant, Black patients had higher levels of dd-cfDNA, 0.09% (interquartile range, 0.001-0.30) compared with White patients, 0.05% (interquartile range, 0.001-0.23; P =0.003). Beyond 6 months, Black patients showed a persistent rise in dd-cfDNA with higher levels compared with White patients. Cell-free mitochondrial DNA was higher in Black patients (185 788 copies/mL; interquartile range, 101 252-422 133) compared with White patients (133 841 copies/mL; interquartile range, 75 346-337 990; P <0.001). The primary composite outcome occurred in 43% and 55% of Black patients at 1 and 2 years, compared with 23% and 27% in White patients, P <0.001. In a multivariable model, Black patient race (hazard ratio, 2.61 [95% CI, 1.35-5.04]; P =0.004) and %dd-cfDNA (hazard ratio, 1.15 [95% CI, 1.03-1.28]; P =0.010) were associated with the primary composite outcome., Conclusions: Elevated dd-cfDNA and cell-free mitochondrial DNA after heart transplant may mechanistically be implicated in the higher incidence of AR and worse clinical outcomes in Black transplant recipients., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070., Competing Interests: Disclosures Dr P. Shah has unrelated grant support paid to the institution from Merck, Bayer, Roche, and Abbott and participated in consulting for Natera, Merck, and Procyrion. Dr K. Shah is a consultant for Eidos and Grant Reviewer for Pfizer. Dr Valantine participated in Board of Directors for CareDx. The other authors report no conflicts.

Background: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo., Methods: In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m 2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level., Results: A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients., Conclusions: In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.)., (Copyright © 2024 Massachusetts Medical Society.)

Peripheral arterial disease (PAD) is common in patients with symptomatic aortic stenosis. PAD exists as a spectrum, and patients with chronic limb-threatening ischemia (CLTI), the most severe form of PAD, are at high risk for limb loss and death. We seek to determine patient characteristics and clinical outcomes among patients who underwent TAVR with or without CLTI. We identified all hospitalizations for TAVR from October 2015 to December 2018 using the National Inpatient Sample database. Patients with any diagnosis of CLTI were identified using the International Classification of Diseases 10th Revision codes. The primary outcome was in-hospital mortality, and secondary outcomes were major complications, open revascularization, and endovascular revascularization after TAVR. During the study period, a total of 31,335 hospitalizations for TAVR procedures were included, including 7,048 (22.5%) in patients with CLTI. CLTI was associated with higher in-hospital mortality (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.13 to 1.74, p = 0.002) and major complications (OR 1.2, 95% CI 1.09 to 1.25, p <0.001). CLTI was also associated with a significantly higher rate of open limb revascularization (OR 5.1, 95% CI 3.94 to 6.48, p <0.001) and endovascular revascularization (OR 4.0, 95% CI 3.54 to 4.59, p <0.001). CLTI among patients who underwent TAVR is associated with higher in-hospital mortality, major complications, and longer lengths of stay compared with patients without CLTI. However, the overall rates of adverse events remain low. Further studies are needed to optimize the multidisciplinary care of these patients before TAVR with a focus on shared decision-making., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Published by Elsevier Inc.)

Objectives: A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries., Design: This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019., Setting: The data involved a single community hospital., Participants: A total of 417 patients were included in the study., Interventions: The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation., Measurements and Main Results: Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663)., Conclusions: The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV-related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients., Methods: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end-organ disease resulting in the initiation/escalation of anti-CMV therapy. The secondary outcome was CMV-related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia., Results: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65-5.88, p < .001) and secondary (adjusted HR 3.19, 95% CI: 1.47-6.94, p = .004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p < .001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p = .698). UP was associated with increased incidence of leukopenia within 6 months post-HT (PET 34.7% vs. UP 43.6%, p = .036)., Conclusion: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV-related hospitalization, and may associate with worse post-HT graft outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

Background: Open appendectomy has been the conventional choice of treatment for acute appendicitis. However, nowadays laparoscopic approach is emerging for the benefits it provides, like lesser postoperative pain and lesser duration of hospital stay, but at the cost of higher expenses and longer operative duration., Methods: A retrospective cohort study was done at Shree Birendra Hospital from January 2018 to December 2021, with a total study population of 450 participants (300 in open appendectomy and 150 in laparoscopic appendectomy). Preoperative. Intraoperative and postoperative parameters were compared and analyzed between two groups using SPSS-25., Results: The mean age was 26.72 ± 9.70 in the open appendectomy (OA) and years 23.89 ± 6.32 in the laparoscopic appendectomy (LA) group. ( p  = 0.010) There was a significant difference between the mean operative time (46.08 ± 13.10 min in OA and 56.86 ±  11.70 min in LA, p  = 0.000), length of hospital stay (1.28 ± 0.80 days in OA and 1.07 ±  0.25 days in LA, p  = 0.000), course of oral analgesics (3.55 ± 0.68 days in OA and 3.00 days in LA p  = 0.000) between OA groups and LA groups, while the total number of complications was less in the LA group however there was no statistically significant difference postoperative complications ( p  = 0.124) between the two groups in the surgical findings., Conclusion: All in all, the laparoscopic approach is a better option for uncomplicated appendicitis due to its less postoperative pain and shorter duration of hospital stay., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Obstructive coronary artery disease (CAD) is common in patients with severe symptomatic aortic stenosis. The management and impact of obstructive CAD in patients undergoing transcatheter aortic valve replacement (TAVR) have not been fully evaluated. We aimed to determine the patient characteristics and clinical outcomes among veterans undergoing TAVR with and without obstructive CAD and to determine temporal trends and association of pre-TAVR percutaneous coronary intervention (PCI) with clinical outcomes., Methods: We identified all patients who underwent TAVR from 2012 to 2021 in the VA Health Care System. The sample population was divided into patients with and without obstructive CAD and further stratified by coronary intervention status 1 year prior to TAVR. The primary outcome was 1-year all-cause mortality, and the secondary outcome was major bleeding., Results: During the study period, 759 patients underwent TAVR, and 282 (37%) had obstructive CAD. Obstructive CAD was associated with higher 1-year mortality (15.6% vs 7.1%; P < .01) after TAVR. The rate of PCI prior to TAVR increased from 2012 until 2016, after which it steadily declined such that 144 patients (51%) underwent PCI pre-TAVR during the entire study period. There was no difference in 1-year mortality (16.0% vs 15.2%; P = .89) or bleeding (16.7% vs 12.3%; P = .33) between patients who underwent or did not undergo pre-TAVR PCI., Conclusions: Among veterans undergoing TAVR, the presence of obstructive CAD is associated with higher mortality though pre-TAVR coronary intervention is not associated with improved outcomes. Further studies could identify a subset of patients who may benefit from coronary revascularization prior to TAVR.

The concept of a 'gut-brain axis' was recently developed when the complex communications between the brain and the gut became evident. The interaction may affect emotions, motivation, mood, and higher cognitive functions as well as gut homeostasis. Human microbe symbiosis's merits are now acknowledged to transcend human mental health. Research has recently indicated that the gut-brain axis plays a vital role in brain health maintenance. The term 'gut-brain axis' can only partially capture the intricacy of these interactions. Dysbiosis of the gut commensals has been seen in patients with psychiatric diseases, such as depression. Major depressive disorder is caused by complicated interactions between the individual gene and the environment. In a forced swimming test, P. Zheng et al. discovered that germ-free mice with no gut microbiota had a shorter immobility duration than healthy mice. More radical effects were expressed on the use of probiotics rather than prebiotics and postbiotics in reducing the symptoms of depression in patients with major depressive disorder. One of prime importance can be given to exploring more microbiota to investigate the better therapeutic effects of probiotics, prebiotics, and postbiotics., Competing Interests: None to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aims to describe the outcomes after heart transplantation using a bridge-to-bridge strategy with a sequence of extracorporeal membrane oxygenation (ECMO) support followed by temporary total artificial heart implantation (TAH-t)., Methods: A retrospective, multicenter analysis of 54 patients who underwent TAH-t implantation following an ECMO for cardiogenic shock was performed (ECMO-TAH-t group). A control group of 163 patients who underwent TAH-t implantation as a direct bridge to transplantation (TAH-t group) was used to assess this strategy's impact on outcomes., Results: Fifty-four patients, averaging 47 ± 13 year old, underwent implantation of a TAH-t after 5.3 ± 3.4 days of ECMO perfusion for cardiogenic shock. In the ECMO-TAH-t group, 20 patients (20/54%; 37%) died after TAH-t implantation and 57 patients (57/163%; 35%) died in the TAH-t group (Gray test; P = .49). The top 3 causes of death of patients on TAH-t support were multisystem organ failure (40%), sepsis (20%), and neurologic events (20%). Overall, 32 patients (32/54%; 59%) underwent heart transplantation in the ECMO-TAH-t group compared with 106 patients (106/163%, 65%) in the TAH-t group (P = .44). No significant difference in survival was observed at 6 months, 1 year, and 3 years after heart transplant (ECMO-TAH-t group: 94%, 87%, and 80% vs 87%, 83%, and 76% in the TAH-t group, respectively). Deterioration of liver function (bilirubin, aspartate transaminase, and alanine aminotransferase levels on TAH-t) was associated with increased mortality before heart transplant in both groups., Conclusions: Sequential bridging from ECMO to TAH-t followed by heart transplantation is a viable option for a group of highly selected patients., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the impact of symptomatic aortic stenosis and subsequent transcatheter aortic valve replacement (TAVR) on stress and health for the caregiver. In this prospective cohort study, we measured caregiver stress before and after TAVR., Methods: We interviewed 34 primary caregivers for patients undergoing outpatient TAVR at an academic institution. Caregiver stress was measured using the Kingston Caregiver Stress Scale (KCSS) and the Caregiver Self-Assessment Questionnaire (CSAQ) before TAVR and at one and six months after. Mean scores were compared pre- and post-TAVR using the Wilcoxon signed-rank test., Results: There was significant improvement in KCSS caregiver stress at one month that was sustained at six months post-TAVR (mean change -1.91 ± 2.50 for six months, p -value 0.01). This was primarily driven by improvement in caregiving issues rather than family or financial issues. There was also significant improvement in CSAQ self-assessed health/illness at one and six months (mean change -2.78 ± 4.01 for six months, p -value 0.016)., Conclusions: Our findings support further investigation of caregiver outcomes in shared decision making before TAVR., Competing Interests: No competing financial interests exist., (© Mohammed Elzeneini et al., 2023; Published by Mary Ann Liebert, Inc.)

Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state is created by increased levels of nerve growth factor (NGF), which causes a cascade of sympathetic sprouting resulting in increased norepinephrine (NE) systemically. Reversal of this cascade by local anesthetic injection into the stellate ganglion thereby reduces NGF and sympathetic sprouting subsequently lowering overall norepinephrine levels. This is the unifying theory by which SGB is able to provide resolution for the varied clinical conditions described in this article.  This review article discusses the physiology of several conditions where stellate ganglion blocks are being investigated as an adjunct treatment modality, including anosmia, PTSD, long-COVID, chronic fatigue syndrome, menopausal hot flashes, and ventricular tachyarrhythmias. Overall, the current literature supporting the use of stellate ganglion blocks for several esoteric conditions is limited; however, case reports to date have shown promising evidence-based results supporting their use as an adjunctive treatment among patients with refractory symptoms to existing treatment algorithms. In conclusion, SGB should be considered among patients with refractory symptoms for medical management in the conditions discussed in this article. Further research is needed to delineate which patients will benefit from the use of SGB, the use of subsequent blocks and timelines in between injections, and unilateral versus bilateral blockade., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kirkpatrick et al.)

Background: Elderly patients presenting with ST-elevation myocardial infarction (STEMI) represent a vulnerable population with comorbid conditions and complex coronary anatomy. We aimed to describe the utilization rate and outcomes of intravascular imaging to guide percutaneous coronary intervention (PCI) in this population., Methods: The Nationwide Readmissions Database was queried for all hospitalizations for STEMI involving PCI from 2018 to 2019. Hospitalizations were stratified by patient age into a younger cohort <75 years (mean age 58.7 ± 9.5 years) and an older cohort ≥75 years. Propensity score-weighed regression analysis was used to identify the association of intravascular imaging with in-hospital mortality, 90-day all-cause readmission, and readmission for myocardial infarction (MI)., Results: A total of 299,619 STEMI PCI hospitalizations were included. Intravascular imaging was utilized less frequently in the older cohort (6.8 % vs 7.8 %, odds ratio [OR] 0.87, 95 % CI 0.82-0.92, p < 0.001). In both cohorts, intravascular imaging was more likely to be used with anterior STEMI, complex PCI, mechanical support, and thrombectomy. Propensity score analysis showed the use of intravascular imaging was associated with lower in-hospital mortality in both cohorts (OR 0.60, 95 % CI 0.52-0.68, p < 0.001 in the younger cohort and OR 0.61, 95 % CI 0.51-0.72, p < 0.001 in the older cohort). There was no difference in 90-day all-cause readmission or readmission for MI with intravascular imaging., Conclusions: Intravascular imaging during STEMI PCI is associated with lower in-hospital mortality regardless of age. Further studies are needed to understand the low utilization rates especially among elderly patients., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cardiac rehabilitation following transcatheter aortic valve replacement (TAVR) is associated with improved outcomes; however, it remains relatively underutilized in this patient population. As part of a quality improvement initiative, we sought to increase the rate of cardiac rehabilitation referral after TAVR at our institution. We designed and implemented a multidisciplinary program that included education of cardiothoracic surgery providers discharging post-TAVR patients on the benefits of cardiac rehabilitation with participation of cardiac rehabilitation personnel during discharge rounds with the surgical team. The study period was defined as 12 months prior to and 6 months following the implementation of the education program. Overall referral rates increased from 5% to 56% ( P < 0.0001), and referrals placed before hospital discharge increased from 0.8% to 53% ( P < 0.0001) over the study period. In conclusion, a combination of education regarding the benefits of cardiac rehabilitation and cardiac rehabilitation personnel participation in discharge rounds significantly increased referral to cardiac rehabilitation after TAVR., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Noninvasive monitoring of heart allograft health is important to improve clinical outcomes. MicroRNAs (miRs) are promising biomarkers of cardiovascular disease and limited studies suggest they can be used to noninvasively diagnose acute heart transplant rejection., Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter prospective cohort study that phenotyped heart transplant patients from 5 mid-Atlantic centers. Patients who had no history of rejection after transplant were compared to patients with acute cellular rejection (ACR) or antibody-mediated rejection (AMR). Small RNA sequencing was performed on plasma samples collected at the time of an endomyocardial biopsy. Differential miR expression was performed with adjustment for clinical covariates. Regression was used to develop miR panels with high diagnostic accuracy for ACR and AMR. These panels were then validated in independent samples from GRAfT and Stanford University. Receiver operating characteristic curves were generated and area under the curve (AUC) statistics calculated. Distinct ACR and AMR clinical scores were developed to translate miR expression data for clinical use., Results: The GRAfT cohort had a median age of 52 years, with 35% females and 45% Black patients. Between GRAfT and Stanford, we included 157 heart transplant patients: 108 controls and 49 with rejection (50 ACR and 38 AMR episodes). After differential miR expression and regression analysis, we identified 12 miRs that accurately discriminate ACR and 17 miRs in AMR. Independent validation of the miR panels within GRAfT led to an ACR AUC 0.92 (95% confidence interval [CI]: 0.86-0.98) and AMR AUC 0.82 (95% CI: 0.74-0.90). The externally validated ACR AUC was 0.72 (95% CI: 0.59-0.82). We developed distinct ACR and AMR miR clinical scores (range 0-100), a score ≥ 65, identified ACR with 86% sensitivity, 76% specificity, and 98% negative predictive value, for AMR score performance was 82%, 84% and 97%, respectively., Conclusions: We identified novel miRs that had excellent performance to noninvasively diagnose acute rejection after heart transplantation. Once rigorously validated, the unique clinical ACR and AMR scores usher in an era whereby genomic biomarkers can be used to screen and diagnose the subtype of rejection. These novel biomarkers may potentially alleviate the need for an endomyocardial biopsy while facilitating the initiation of targeted therapy based on the noninvasive diagnosis of ACR or AMR., (Copyright © 2022 International Society for Heart and Lung Transplantation. All rights reserved.)

Background: Combined heart-liver transplantation (CHLT) is the only curative option for patients with concomitant pathology affecting the heart and liver. In some cases, the native livers of familial amyloidosis (FA) patients may be suitable for domino transplantation into other recipients., Methods: Retrospective analysis (2013 to 2019) of all CHLT at our center was performed. Continuous data were presented as mean with standard deviation and discrete variables as percentages., Results: Familial amyloidosis was the indication for CHLT in 5 out of 6 patients. The mean recipient age was 55 ± 5.62 years. Two patients were bridged with total artificial heart. The mean model for end-stage liver disease score at transplant was 17.17 ± 3.7. Two explanted livers were used for transplantation in a domino fashion. The median intensive care and hospital stays were 5.5 and 19 days, respectively. Complications included renal failure (1), groin abscess (1), pulmonary embolism (1), and cardiac rejection (1). Patient and graft survival for both organs was 100% at a median follow-up of 59 (range 20-76) months., Discussion: Combined heart-liver transplantation for FA achieves excellent outcomes. The possible use of livers explanted from patients with FA for domino liver transplantation can contribute to the liver donor pool.

Pulsed field ablation (PFA) has the potential to evolve into an efficient alternative to traditional RF ablation for atrial fibrillation treatment. However, achieving irreversible tissue electroporation is critical to suppressing arrhythmic pathways, raising the need for accurate lesion characterization. To understand the physics behind the tissue response PFA, we propose a quasi-dynamic model that quantifies tissue conductance at end-electroporation and identifies regions that have undergone fully irreversible electroporation (IRE). The model uses several parameters and numerically solves the electrical field diffusion into the tissue by iteratively updating the tissue conductance until equilibrium at end-electroporation. The model yields a steady-state tissue conductance map used to identify the irreversible lesion. We conducted numerical experiments mimicking a lasso catheter featuring nine 3-mm electrodes spaced circumferentially at 3.75 mm and fired sequentially using a 1500 V and 3000 V pulse amplitude. The IRE lesion region has a surface area and volume of 780 mm 2 and 1411 mm 3 , respectively, at 1500 V, and 1178 mm 2 and 2760 mm 3 , respectively, at 3000 V. Lesion discontinuity was observed at 5.0 mm depth with 1500 V, and 7.2 mm depth with 3000 V. This quasi-dynamic model yields tissue conductance maps, predicts irreversible lesion and lesion penumbra at end-electroporation, and confirms larger lesions with higher pulse amplitudes.

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To assess the outcomes of a single-center experience with percutaneous left ventricular assist device (LVAD) decommissioning., Background: Patients with LVADs may eventually require their removal, either due to recovery of left ventricular function or recurrent complications. Traditionally, withdrawal of LVAD support has been managed with surgical device explantation, which carries significant procedural risks. Transcatheter LVAD decommissioning, with outflow graft occlusion and driveline transection, has recently been described as an alternative to surgical removal., Methods: Here, we report on a retrospective cohort of five consecutive cases treated with transcatheter LVAD decommissioning., Results: The procedure was effective in all cases, and no patient experienced procedure-related complications. At midterm follow-up, the three patients who had myocardial function recovery were alive and had not experienced heart failure-related symptoms or complications., Conclusion: Percutaneous LVAD decommissioning appears to be a safe and effective approach to LVAD treatment discontinuation., (© 2022 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

An in vitro release test based on pulsatile microdialysis (PMD) is presented for the purpose of measuring the release of cyclosporine from ophthalmic emulsions, along with a method to determine the drug distribution within the oil-rich globule, surfactant-rich micelle and aqueous phases of the emulsion formulation. Compositionally equivalent formulations containing 0.05% cyclosporine were prepared with similar physical parameters (globule size, viscosity, surface tension zeta potential, osmolality, pH) but made with different manufacturing conditions. Emulsions were made by ultrasonication, using different ultrasonication times (22-49 min) and temperatures (50-82 °C). Formulations were stored at room temperature (20 °C) and PMD was performed under two conditions, one in which the receiving medium temperature was 20 °C, and another in which the receiving medium temperature was 35 °C to mimic the temperature change expected when a drop of formulation is administered to the eye. The PMD release data were taken at release times of 20, 40, 60, 90, 120, 180, 300 and 600 s. All experiments showed a qualitatively similar release pattern, with a rapid initial rate of drug release (Release-1) for the first few minutes, followed by a much slower release (Release-2). In addition, imposing a sudden temperature change on the formulation was observed to affect the release, with some formulations releasing faster into receiver media at 35 °C than at 20 °C, while others released faster into 20 °C than 35 °C receiver media. The drug distribution was also calculated from PMD release data into 20 °C receiver media using a novel release kinetics model. The drug distribution varied among the formulations, with 54-77% of the cyclosporine in the oil phase of the emulsions. PMD is a promising method to evaluate how manufacturing-induced differences affect the distribution and release kinetics of cyclosporine within the emulsion formulation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Laparoscopic cholecystectomy (LC) has been established as the gold standard treatment for symptomatic gallstones, however surgeons face the risk of injuring bile ducts and vessels due to the inherent limitations of laparoscopy., Methods: This is a cross-sectional study done in the Department of Surgery, Shree Birendra Hospital (SBH) on patients who were posted for LC. The study period was through April 2021 to September 2021. During LC, the anatomy of RS was noted and classified into Group A (RS present) or Group B (RS absent). Data analyses were performed considering a p-value of <0.05 as statistically significant., Results: RS was present in 169 (93.9%) out of 180 cases. The open sulcus type was found in 114 cases (67.5%), followed by closed type in 26 (15.4%), slit sulcus type in 22 (13.0%), and scar type in 7 (4.1%) cases. Injury to cystic artery occurred in one case (0.15%) of Group A while in two cases (18.18%) of Group B (p-value = 0.001). The adjusted operative time in Group A and Group B were 50.61 ± 10.33 min and 69.86 ± 15.28 min respectively (p-value = 0.005). There was significant difference between Group A and Group B in conversion to open surgery - 01 (0.59%) and 04 (36%) respectively (p-value < 0.001). Surgical Site Infection (SSI) was detected in nine (5.33%) cases among Group A and in three (27.2%) cases among Group B (p-value = 0.028)., Conclusion: RS can be considered as an important anatomical landmark for safer LC with fewer injuries to cystic artery, SSI, conversion to open surgery and shorter operative time., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors.)

Purpose: Human milk (HM) is a unique biological fluid that is enriched with a variety of factors, including microRNAs (miRNAs) that potentially provide both short- and long-term benefits to the infants. miRNAs are packaged within exosomes, making them bioavailable to infants. Gestational diabetes mellitus (GDM) may affect the abundance of exosomal miRNAs in HM, providing a mechanism for growth and adiposity variation in infants of mothers with GDM in early life. Therefore, the purposes of this study were to examine the impact of GDM on select miRNAs (miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d) involved in metabolism and to examine the association of these miRNAs with measures of infant body composition in the first 6 months of life., Methods: Milk samples were collected from a cohort of 94 mothers (62 mothers without GDM and 32 mothers with GDM) matched on body mass index strata at 1 month post partum. miRNA abundance was measured by real-time polymerase chain reaction. Linear regression models were used to examine potential differences in miRNA abundance in women with and without GDM, testing associations between miRNA abundance and infant growth and body composition measures from 1 to 6 months., Findings: The abundances of miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d were reduced in milk from mothers with GDM. Independent of GDM status, higher maternal diet quality was associated with increased abundance of each of the measured miRNAs. miRNA-148a was negatively associated with infant weight, percentage of body fat, and fat mass, whereas miRNA-30b was positively associated with infant weight and fat mass at 1 month of age. There was no association of milk miRNA-148a and miRNA-30b with infant weight at 1 month of age or with body composition measures at 3 months of age; however, miRNA-148a was negatively associated with infant weight at 6 months of age., Implications: If supported by randomized dietary supplementation or other intervention trials, HM miRNAs may be a therapeutic target to mitigate risk of metabolic outcomes in offspring of women with GDM., (Copyright © 2022. Published by Elsevier Inc.)