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Marie Haase Juhl,1,2 Anne Estrup Olesen,1,2 Ellen Tveter Deilkås,3 Niels Henrik Bruun,4 Kirsten Høgh Obling,5 Nikoline Rytter,6 Maya Damgaard Larsen,6 Solvejg Kristensen7 1Department of Clinical Pharmacology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 3Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway; 4Research Data and Biostatistics, Aalborg University Hospital, Aalborg, Denmark; 5Care and Rehabilitation, Department of Health and Care Services (Danish: “pleje Og Rehabilitering, Staben Sundhed Og Omsorg”), the Municipality of Aarhus, Aarhus, Denmark; 6Digitalization and Quality, Department of Health and Care Services (Danish: “digitalisering og Kvalitet, Sundhed og Omsorg”), The Municipality of Aarhus, Aarhus, Denmark; 7Aalborg University Hospital, Psychiatry, Aalborg, DenmarkCorrespondence: Anne Estrup Olesen, Department of Clinical Pharmacology, Aalborg University Hospital, Gartnerboligen, Ground Floor, Mølleparkvej 8a, Aalborg, 9000, Denmark, Tel +45 97664376, Email aneso@rn.dkBackground: A lack of instruments to assess patient safety climate within primary care exists. The objectives of this study were as follows: 1) To adapt the Danish hospital version of the Safety Attitudes Questionnaire (SAQ-DK) for use in primary care; 2) Test the internal consistency and the construct validity of this version; 3) Present benchmark data; and 4) Analyze variance.Methods: The SAQ-DK was adapted for use in Danish primary care settings (SAQ-DK-PRIM) and distributed to healthcare staff members from nursing homes (N = 11), homecare units (N = 4) and healthcare units (N = 2), within the municipality of Aarhus, Central Denmark Region, Denmark. Face- and content validity were assessed. The construct validity was evaluated by a set of goodness-of-fit indices. The internal reliability was evaluated using the item-rest correlations, the inter-item correlations, and Cronbach’s alpha (α).Results: The adaptation process resulted in a questionnaire of 10 items. Eight hundred and thirty healthcare staffs participated (78% of the eligible respondents). In total 586 (70.6%) responses were complete and were included in the analysis. Goodness-of-fit indices from the confirmatory factor analysis showed: Chi2=46.90CFI=0.97, RMSEA = 0.063 (90% CI: 0.044– 0.084), Probability RMSEA (p close)=0.12. Internal reliability was high (Cronbach’s α=0.76). Proportions of participants with a positive attitude was 41.1% and did not differ between the healthcare services. Scale mean score was 70.19 (SD: 18.05) and differed between healthcare services. The safety climate scale scores did not vary according to healthcare service type. ICC was 0.68% indicating no clustering of scores by healthcare service type.Conclusion: Considering the questionnaire’s applicability, short length, strengthened focus on one area of interest and validity, the SAQ-DK-PRIM can serve as a valuable tool for measuring patient safety climate within primary care settings in Denmark.Keywords: primary care, patient safety culture, patient safety climate, questionnaire, validity, reliability, Denmark

Bente Mertz Nørgård, 1–4 Michael Due Larsen, 1, 2 Sonia Friedman, 1–4 Jens Fedder 5, 6 1Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark; 2Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Crohn’s and Colitis Center, Brigham and Women’s Hospital, Boston, MA, USA; 4Harvard Medical School, Boston, MA, USA; 5Centre of Andrology and Fertility Clinic, Department D, Odense University Hospital, Odense, Denmark; 6Research Unit of Human Reproduction, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkCorrespondence: Bente Mertz NørgårdCenter for Clinical Epidemiology, Odense University Hospital, Sdr. Boulevard 29, Entrance 216, Odense C DK-5000, DenmarkTel +45 2133 3258Email bente.noergaard@rsyd.dkPurpose: Former studies have suggested that women with Crohn’s disease (CD) and ulcerative colitis (UC) have a decreased chance of a live born child after assisted reproductive technology (ART) treatment. It is debated whether corticosteroids before ART may improve outcomes, either by decreasing inflammatory bowel disease-related inflammation or increasing endometrial receptivity. We examined the efficacy of corticosteroids before embryo transfer in women with CD and UC.Patients and Methods: Our cohort study is based on nationwide Danish health registries, comprising women with CD and UC receiving an embryo transfer (1 January 2006 through 2017). Exposed cohorts constituted women with CD and UC who had received corticosteroids within three months before embryo transfer, and the unexposed cohorts women with CD and UC who did not receive corticosteroids. Our primary outcome was live birth. We controlled for multiple covariates in the analyses.Results: We examined 2408 embryo transfers. In patients with CD, 114 embryo transfers were preceded by a corticosteroid prescription, and 964 were not. The corresponding numbers in UC were 122 and 1208, respectively. The adjusted odds ratio (aOR) for live birth in women with CD receiving corticosteroids before embryo transfer, relative to women with CD not receiving corticosteroids, was 0.89 (95% CI 0.49– 1.63). The corresponding aOR in UC was 0.98 (95% CI 0.55– 1.74).Conclusion: Corticosteroids prior to ART in women with CD and UC did not increase the chance of a live born child. The exact impact of corticosteroids prior to embryo transfer in patients with CD and UC still remains to be determined.Keywords: corticosteroids, Crohn’s disease, ulcerative colitis, inflammatory bowel disease, assisted reproductive technology, ART, assisted reproduction

Line Riis Jølving,1,2 Michael Due Larsen,1,2 Jens Fedder,3,4 Sonia Friedman,1,2,5,6 Bente Mertz Nørgård1,2,5,61Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark; 2Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Centre of Andrology and Fertility Clinic, Department D, Odense University Hospital, Odense, Denmark; 4Research Unit of Human Reproduction, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 5Crohn’s and Colitis Center, Brigham and Women’s Hospital, Boston, MA, USA; 6Division of Gastroenterology, Hepatology and Endoscopy Research, Harvard Medical School, Boston, MA, USAPurpose: Women with thyroid disorders may have increased infertility and poor reproductive outcomes, but it is unclear if assisted reproductive technology (ART) is effective in this population. The aim of this study was to examine the chance of a pregnancy (biochemical and clinical), and a live birth after ART, in women with thyroid disorders undergoing ART treatment, compared to women without thyroid disorders. Among live-born children, we assessed the risk of congenital malformations.Patients and methods: In a nationwide cohort study of all women undergoing ART treatments in Denmark from 1 January 1994 throughout June 2017, we calculated the chance of a pregnancy and a live birth after embryo transfer. Women with thyroid disorders were stratified into two groups: those diagnosed with hypothyroid or hyperthyroid disorders. The adjusted OR (aOR) of a biochemical and a clinical pregnancy, a live born child and a congenital malformation was computed using multilevel logistic regression models.Results: In total, 199,674 embryo transfers were included in 2,101 women with thyroid disorders and in 65,526 women without thyroid disorders. The chance of a biochemical pregnancy was significantly reduced in women with hyperthyroidism (aOR=0.80, 95% CI 0.69–0.93), and the aOR of a live birth was 0.86, 95% CI 0.76–0.98. The aOR for a live birth in women with hypothyroidism was 1.03 (95% CI 0.94–1.12). Children of women with hypothyroidism, who were conceived after ART treatment, had a significantly increased risk of any congenital malformation (aOR=1.46 [95% CI 1.07–2.00]).Conclusion: Women with hyperthyroidism receiving ART treatment had a decreased chance of a live birth per embryo transfer compared to women without thyroid disorders. Women with hypothyroidism did not have a decreased chance of a live birth but their offspring had an increased risk of congenital malformation.Keywords: assisted reproductive technology, in vitro fertilization, hyperthyroidism, hypothyroidism, clinical epidemiology

Lone Larsen,1 Michael Dam Jensen,2 Michael Due Larsen,3 Rasmus Gaardskær Nielsen,4 Niels Thorsgaard,5 Ida Vind,6 Signe Wildt,7 Jens Kjeldsen8 1Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg,2Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Vejle, 3Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 4Department of Paediatrics, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense C, 5Department of Internal Medicine, Section of Gastroenterology, Hospital Unit West, Herning, 6Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, 7Department of Medicine, Section of Gastroenterology, Køge Hospital, Køge, 8Department of Medical Gastroenterology, Odense University Hospital, Odense C, Denmark Aim: The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD) receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research. Study population: The study population comprises all Danish patients with IBD (both children and adults) with ulcerative colitis, Crohn's disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated. Main variables: The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician's global assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology. Descriptive data: Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator, a standard has been defined based on the available evidence. National results will be published in an annual report and local results on a quarterly basis. The indicators will be reported as department-specific proportions with 95% confidence intervals, and the national average will be provided for comparison. An estimated 1,200–1,300 new biological therapies are initiated each year in Danish patients with IBD. Conclusion: The database will be available for research during 2016. Data will be made available by The Danish Clinical Registries (www.rkkp.dk). Keywords: inflammatory bowel disease, biological therapy, anti-TNF-α agents, quality indicators, database

Ulla Darling Hansen,1 Kim Oren Gradel,2 Michael Due Larsen2 1Department of Gynaecology and Obstetrics, Odense University Hospital, 2Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark Abstract: The Danish Urogynaecological Database is established in order to ensure high quality of treatment for patients undergoing urogynecological surgery. The database contains details of all women in Denmark undergoing incontinence surgery or pelvic organ prolapse surgery amounting to ~5,200 procedures per year. The variables are collected along the course of treatment of the patient from the referral to a postoperative control. Main variables are prior obstetrical and gynecological history, symptoms, symptom-related quality of life, objective urogynecological findings, type of operation, complications if relevant, implants used if relevant, 3–6-month postoperative recording of symptoms, if any. A set of clinical quality indicators is being maintained by the steering committee for the database and is published in an annual report which also contains extensive descriptive statistics. The database has a completeness of over 90% of all urogynecological surgeries performed in Denmark. Some of the main variables have been validated using medical records as gold standard. The positive predictive value was above 90%. The data are used as a quality monitoring tool by the hospitals and in a number of scientific studies of specific urogynecological topics, broader epidemiological topics, and the use of patient reported outcome measures. Keywords: urogynecology, pelvic organ prolapse surgery, incontinence surgery, surgical quality monitoring

Summary: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field.

Objective:. The objective of this study was to evaluate the long-term oncological outcomes of patients with colorectal liver metastasis (CRLM) randomized for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Introduction:. For advanced CRLM, TSH or ALPPS may be needed for tumor freedom. The randomized, controlled, multicenter trial LIGRO showed an increased resection rate in patients who underwent ALPPS but no difference in morbidity or mortality. The 2-year survival analysis revealed better overall survival in the ALPPS group. Here, the long-term survival analysis from the LIGRO trial is reported. Methods:. In the LIGRO trial, 100 patients were randomized to TSH or ALPPS, with the option of rescue ALPPS if insufficient growth was found after the initial step of TSH. Patients were enrolled between June 2014 and August 2016. Follow-up data for this study were collected between November 2022 and February 2023. Results:. In total, 16 patients were alive at the end of the follow-up period. The estimated median follow-up time was 93 months. Estimated median overall survival times were 45 months in the ALPPS group and 27 months in the TSH group (P = 0.057), with 5-year survival rates of 31% and 20%, respectively. Positive prognostic factors were liver tumor-free status at the first follow-up and rectal primary tumor. Negative prognostic factors were extrahepatic disease and increasing CLRM size. Conclusion:. Liver tumor-free status is a predictor of long-term survival, along with extrahepatic disease, large CRLM size, and rectal primary tumor. Survival did not significantly differ between patients treated with ALPPS or TSH.

ABSTRACT: Background: The aging spine often presents multifaceted surgical challenges for the surgeon because it can directly and indirectly impact a patient’s spinal alignment and quality of life. Elderly and osteoporotic patients are predisposed to progressive spinal deformities and potential neurologic compromise and surgical management can be difficult because these patients often present with greater frailty. Methods: This was a literature review of spinal alignment changes, preoperative considerations, and spinal alignment considerations for surgical strategies. Results: Many factors impact spinal alignment as we age including lumbar lordosis flexibility, hip flexion, deformity, and osteoporosis. Preoperative considerations are required to assess the patient’s overall health, bone mineral density, and osteoporosis medications. Careful radiographic assessment of the spinopelvic parameters using various classification/scoring systems provide the surgeon with goals for surgical treatment. An individualized surgical strategy can be planned for the patient including extent of surgery, surgical approach, extent of the constructs, fixation techniques, vertebral augmentation, ligamentous augmentation, and staging surgery. Conclusions: Surgical treatment should only be considered after a thorough assessment of the patient's health, deformity, bone quality and corresponding age matched alignment goals. An individualized treatment approach is often required to tackle the deformity and minimize the risk of hardware related complications and pseudarthrosis. Anabolic agents offer a promising benefit in this patient population by directly addressing and improving their bone quality and mineral density preoperatively and postoperatively.

Purpose: Lipopolysaccharide (LPS)-type endotoxins are naturally found in the gut microbiota and there is emerging evidence linking gut microbiota and neuroinflammation leading to retinal neurodegeneration. Thinning of the retinal nerve fiber layer (RNFL) is a biomarker of retinal neurodegeneration, and a hallmark of glaucoma, the second leading cause of blindness worldwide. We assessed the association of a blood biomarker of LPS with peripapillary RNFL thickness (RNFLT) and its longitudinal evolution up to 11 years. Design: The Alienor study is a single center prospective population-based cohort study. Subjects: The studied sample of this study includes 1062 eyes of 548 participants receiving ≥1 gradable RNFL measurement. Methods: Plasma esterified 3-hydroxy fatty acids (3-OH FAs) were measured as a proxy of LPS burden. Retinal nerve fiber layer thickness was acquired using spectral-domain OCT imaging every 2 years from 2009 to 2020 (up to 5 visits). Main Outcome Measures: Associations of plasma esterified 3-OH FAs with RNFLT were assessed using linear mixed models. Results: Mean age of the included 548 participants was 82.4 ± 4.3 years and 62.6% were women. Higher plasma esterified 3-OH FAs was significantly associated with thinner RNFLT at baseline (coefficient beta = −1.42 microns for 1 standard deviation-increase in 3-OH FAs, 95% confidence interval [−2.56; −0.28], P = 0.02). This association remained stable after multivariate adjustment for potential confounders. No statistically significant association was found between 3-OH FAs and longitudinal RNFLT change. Conclusions: Higher plasma esterified 3-OH FAs were associated with thinner RNFLT at baseline, indicating an involvement of LPS in the early processes of optic nerve neurodegeneration and highlighting the potential importance of the human microbiota in preserving retinal health. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background. Belatacept, a selective T-cell costimulation blocker, was associated with improved survival and renal function but also with a risk of posttransplant lymphoproliferative disorder (PTLD) in adult kidney transplant recipients in phase 3 trials. This registry examined long-term safety in Epstein–Barr virus (EBV)–seropositive kidney transplant recipients treated with belatacept. Methods. This US-based, prospective, voluntary, multicenter registry (Evaluating Nulojix Long-Term Safety in Transplant [ENLiST]) included adult EBV-seropositive kidney-only transplant recipients treated de novo (within 14 d of transplantation) with belatacept. Primary objectives were to estimate incidence rates of confirmed PTLD, central nervous system (CNS) PTLD, and progressive multifocal encephalopathy (PML). The minimum follow-up was 2 y. Results. Of 985 enrolled transplant recipients, 933 EBV-seropositive patients received belatacept, with 523 (56.1%) receiving concomitant tacrolimus at transplant (for up to 12 mo). By study end, 3 cases of non-CNS PTLD (incidence rate, 0.08/100 person-years), 1 case of CNS PTLD (0.03/100 person-years), and no cases of PML had been reported. Two patients with non-CNS PTLD received concomitant belatacept and tacrolimus and 1 received belatacept and lymphocyte-depleting therapy. Incidence rates were comparable between patients who received concomitant belatacept and tacrolimus and those who did not receive tacrolimus (0.09/100 person-years and 0.07/100 person-years, respectively; P = 0.96). Two of 4 patients with PTLD died, and 2 were alive at the end of the study. Cumulatively, 131 graft losses or deaths were reported by study end. Conclusions. Our results from the ENLiST registry, a large, prospective real-world study, showed that the incidence rates of PTLD and CNS PTLD in belatacept-treated EBV-seropositive transplant recipients were consistent with findings from previous phase 3 trials.

Objective:. This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant

Background:. Informed consent is a fundamental pillar of patient rights and is an essential part of good clinical practice. In 2019, the International Confederation of Plastic Surgery Societies launched a survey to collect feedback on informed consent practices, with an aim to develop an international guideline for cosmetic surgery Methods:. A 15-question survey was sent to delegates of the International Confederation of Plastic Surgery Societies for dissemination to their national society members. The survey comprised a range of quantitative and qualitative questions. Descriptive and thematic analysis was performed. Results:. There were 364 respondents. Over half of the respondents reported no local informed consent policy, whereas others noted national society, specialist college, or government policies. The majority of respondents believed that the performing surgeon should be responsible for obtaining informed consent with at least two face-to-face consultations. Most respondents agreed with a cooling-off period (duration based on procedure type and use of high-risk devices). Regarding cosmetic breast augmentation, the majority of respondents felt that the performing surgeon should be responsible for postoperative management, including cases that occur as part of surgical tourism. Some respondents incorporate financial consent as part of their informed consent practice. Most supported the development of an international informed consent guideline. Conclusions:. Informed consent should result from face-to-face consultations with the performing surgeon. There should be a minimum cooling-off period. Postoperative surveillance should be available in all settings. The findings of this survey will help inform an international standardized informed consent guideline for cosmetic surgery.

Left ventricular aneurysm is a potentially serious but rare condition in children. This case describes delayed but fatal rupture of an occult posttraumatic left ventricular aneurysm in an 11-year-old boy with a history of blunt chest trauma from a high-impact automobile collision 7 months earlier. (Level of Difficulty: Intermediate.)

Although anti-thyroid drugs (ATDs) are the most common cause of drug-associated anti-neutrophil cytoplasmic antibody (ANCA) vasculitis (AAV), many other classes of drugs can lead to drug-associated AAV. We present a unique case of rivaroxaban-associated AAV. A 76-year-old female with a past medical history of atrial fibrillation on rivaroxaban presented with fatigue, bilateral lower extremity purpura, and hemoptysis to an outside hospital. Investigations revealed a positive cytoplasmic-ANCA (c-ANCA) titer of 1:320 and a positive anti-myeloperoxidase (anti-MPO), and negative perinuclear-ANCA (p-ANCA) and anti-proteinase 3 (anti-PR3). In addition, chest imaging demonstrated bilateral ground-glass opacities which raised suspicion for diffuse alveolar hemorrhage (DAH). A lung biopsy revealed acute and ongoing DAH with focally active capillaritis and characteristic pathological findings, which strongly suggested that was likely secondary to rivaroxaban. Rivaroxaban was discontinued, and the patient received pulses of intravenous glucocorticosteroids and rituximab. Her symptoms improved. She continued immunosuppressive therapy with rituximab for 2 years. She presented to our hospital for a second opinion regarding the discontinuation of rituximab, and we decided to discontinue rituximab. After discontinuation, the patient remained stable after 1.5 years of follow-up and did not have any relapses. This is a unique case of rivaroxaban-associated AAV. Clinicians should consider drug-associated AAV in all patients who present with an atypical clinical presentation and/or pathological findings of AAV. Given the broad and rapidly increasing use of novel anticoagulants, it is important to raise awareness of this potential complication. Prompt discontinuation of the drug and initiation of immunosuppressant treatment in severe cases may be lifesaving.

Background Vitamin D deficiency has recently been suggested as an independent risk factor for thrombosis. Notably, vitamin D deficiency is common in pregnant populations, whom already have an increased thrombotic risk. However, pregnant women are commonly excluded from studies investigating the hemostatic system, and knowledge on the impact of vitamin D on hemostasis in pregnancy is therefore limited. Methods A cross-sectional study comparing the hemostatic profile of pregnant women (gestational week 12.9 ± 0.7) with vitamin D deficiency (≤50 nmol/L) (n = 70) and high adequate vitamin D status (≥100 nmol/L) (n = 59). Results Vitamin D deficient women displayed increased plasminogen activator inhibitor 1 levels and an increased plasminogen activator inhibitor 1/plasminogen activator inhibitor 2 ratio, even after adjusting for factors with potential influence on hemostasis (body mass index, smoking and use of fish oil supplements). Conclusions Vitamin D deficiency is associated with increased plasminogen activator inhibitor 1/plasminogen activator inhibitor 2 ratio in pregnant women. As an increased plasminogen activator inhibitor 1/plasminogen activator inhibitor 2 ratio with high plasminogen activator inhibitor 1 levels may increase thrombotic risk and is associated with the development of pregnancy complications, further research is needed to determine the optimal vitamin D supplementation in pregnancy.

Despite extensive treatment with surgery and chemotherapy many patients with peritoneal metastases from colorectal cancer experience intraperitoneal disease relapse. The α-emitting 224 radium-labelled microparticle radionuclide therapeutic Radspherin® is being explored as a novel treatment option for these patients. Radspherin® is specially designed to give local radiation to the surface of the peritoneal cavity and potentially kill remaining attached micrometastases as well as free-floating cancer cells, thus preventing future relapse. The effect of Radspherin® on the immune system is not known. Systemic and local inflammatory responses were analyzed in plasma, intraperitoneal fluid and urine collected prospectively as part of a phase 1 dose-escalation study of intraperitoneal instillation of the α-emitting therapeutic radiopharmaceutical Radspherin®, at baseline and the first 7 postoperative days from nine patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. All patients additionally received intraperitoneal instillation of Radspherin® on postoperative day 2. Complement activation products C3bc and the terminal complement complex were analyzed using enzyme-linked immunosorbent assay. Cytokines ( n = 27), including interleukins, chemokines, interferons and growth factors, were analyzed using multiplex technique. The time course and magnitude of the postoperative cytokine response after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy displayed a modest systemic response in plasma, in contrast to a substantial local intraperitoneal response. After administration of Radspherin®, a significant increase ( P

Association between alcohol intake and atrioventricular block is rare. This case describes a previously healthy 27-year-old man experiencing syncopes preceded by moderate alcohol intake. An implantable loop recorder demonstrated episodes of total atrioventricular block coinciding with an additional syncope after alcohol intake, resulting in pacemaker implantation. (Level of Difficulty: Intermediate.)

Background. Maintenance immunosuppression with belatacept following kidney transplantation results in improved long-term graft function as compared with calcineurin inhibitors. However, broad application of belatacept has been limited, in part related to logistical barriers surrounding a monthly (q1m) infusion requirement. Methods. To determine whether every 2-mo (q2m) belatacept is noninferior to standard q1m maintenance, we conducted a prospective, single-center randomized trial in low-immunologic-risk, stable renal transplant recipients. Here, post hoc analysis of 3-y outcomes, including renal function and adverse events, are reported. Results. One hundred sixty-three patients received treatment in the q1m control group (n = 82) or q2m study group (n = 81). Renal allograft function as measured by baseline-adjusted estimated glomerular filtration rate was not significantly different between groups (time-averaged mean difference of 0.2 mL/min/1.73 m2; 95% confidence interval: −2.5, 2.9). There were no statistically significant differences in time to death or graft loss, freedom from rejection, or freedom from donor-specific antibodies (DSAs). During the extended 12- to 36-mo follow-up, 3 deaths, 1 graft loss occurred in the q1m group, compared with 2 deaths, and 2 graft losses in the q2m group. In the q1m group, 1 patient developed DSAs and acute rejection. In the q2m group, 3 patients developed DSAs and 2 associated with acute rejection. Conclusions. Based on the similar renal function and survival at 36 mo compared with q1m, q2m belatacept is a potentially viable maintenance immunosuppressive strategy in low immunologic risk kidney transplant recipients that may facilitate increased clinical utilization of costimulation blockade-based immunosuppression.

Rhinocerebral mucormycosis (RCM) is a rare and rapidly progressive, destructive, angioinvasive fungal infection, which primarily affects immunocompromised patients. A high suspicion is required to diagnose RCM as initial clinical manifestations are often nonspecific. A cornerstone of the management is early diagnosis and radical surgery, which often requires complex reconstructive procedures.The optimal timing of reconstructive surgery is controversial.This case series presents the reconstructive perspective on four RCM cases treated with aggressive debridement, targeted antifungal treatment, and hyperbaric oxygen therapy followed by an early local flap or microsurgical reconstruction – to enable adequate local blood perfusion, antifungal treatment, and to decrease the risk of secondary infection. In all four patients, the early reconstructive surgery was successful without relapse of RCM or flap failure.We suggest aggressive surgical debridement till clear resection margins are obtained based on histopathology and/or microbiology, at a point which reconstructive surgery can be performed safely.

Background: Excessive supraventricular ectopic activity (ESVEA), defined as ≥720 premature atrial contractions (PAC) per day or any runs of ≥20 PACs, has been proposed as a surrogate marker for paroxysmal atrial fibrillation (PAF). Objective: We aimed to estimate the prognostic impact of ESVEA on the future development of PAF in consecutive patients referred to ambulatory cardiac monitoring. Methods: The cohort consists of a population with comorbidities referred to 48-hour ambulatory electrocardiogram aged 30–98 (n = 1316) between 2009 and 2011. After exclusion of known or current atrial fibrillation (AF) (n = 527) and patients with pacemakers (n = 7), 782 patients were included, with a median follow-up of 8.1 years. Events of incident AF and death were retrieved from patient records. Results: Mean age was 58.6 ± 15.5 years and 56.5% were women. A total of 101 patients had ESVEA at baseline (12.9%). During follow-up, 69 (8.9%) developed incidental AF. Twenty-three patients with ESVEA developed AF (23%). Incidence rate of AF in patients with and without ESVEA was 37.1/1000 person-years and 9.1 per 1000 person-years, respectively (P < .001). ESVEA was associated with incident AF after adjustment for potential confounders in Cox regression analysis (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.40–4.09) and in competing risk analysis with death as competing risk (subdistribution HR: 2.35; 95% CI: 1.30–4.17). Conclusion: ESVEA increases the risk of incident AF substantially in a population referred to ambulatory cardiac monitoring.

Background. Cytopenias, a common complication for immunosuppressed patients, are known to be associated with adverse transplant outcomes. However, there is little information on cytopenias in recipients treated with the costimulation blockade agent, belatacept. Methods. We compared cytopenia incidence and manifestations in patients undergoing kidney transplant at Emory University Hospital on tacrolimus and belatacept. To reduce selection bias, the tacrolimus group was narrowed to include only patients eligible for belatacept. Results. Of 1651 patients transplanted between 2009 and 2019, 187 (11%) experienced severe anemia, 309 (19%) experienced leukopenia, and 62 (4%) thrombocytopenia. On multivariable regressions, deceased-donor transplant, cytomegalovirus viremia, and thymoglobulin treatment were associated with risk of developing leukopenia, anemia, and thrombocytopenia. High-risk cytomegalovirus status was also associated with development of leukopenia and anemia. Additionally, azathioprine was associated with development of anemia, and both tacrolimus therapy and Caucasian race were associated with thrombocytopenia. Longitudinal quantifications of hematologic cell lines over the first-year posttransplant were extracted from generalized linear models fit using splines. Only hemoglobin range was significantly different between groups (greater in belatacept patients). Plots of mean cell count for each group suggest an earlier recovery from posttransplant anemia in belatacept patients. Conclusions. Belatacept patients are not at increased risk of cytopenia but may have improved recovery from posttransplant anemia.

Greater trochanteric pain syndrome may be caused by atypical femoral fractures, and this should be taken into consideration in the diagnostic workout. A 63-year-old woman was referred to our orthopedic outpatient hip clinic with a history of greater trochanteric pain syndrome without known trauma for 1 year. Initially X-ray of the hip and magnetic resonance imaging were found without pathology, and she was given a diagnosis of gluteus medius tendinopathy. As physiotherapy and steroid injections did not resolve her pain, a second look on the magnetic resonance imaging and X-ray revealed a discrete atypical femoral fracture in the lateral cortex with the presence of an isolated Looser zone, which were attributed to her pain syndrome. Two years after onset of symptoms, and with no pain relief on medical treatment, she was treated with an intramedullary nail. One-year postoperative the patient was pain free. This case emphasizes the important utility of magnetic resonance imaging in refractory greater trochanteric pain syndrome.

Background. Costimulatory blockade with belatacept has demonstrated long-term benefits in renal transplantation, but de novo use in liver transplant recipients has resulted in increased rejection, graft loss, and death. However, belatacept conversion as a calcineurin inhibitor (CNI) avoidance strategy has not been studied and may be of benefit in liver transplantation where CNI-induced renal dysfunction and toxicity are barriers to improved outcomes. Methods. Using clinical data extracted from our institutional medical record, we report on 8 patients who underwent kidney after liver transplantation and were treated with belatacept-based immunosuppression and transient CNI therapy. Results. All patients tolerated belatacept therapy without any patient deaths or graft losses. No episodes of rejection, de novo donor-specific antibody formation, or major systemic infections were observed, and all patients demonstrated preserved liver and excellent renal allograft function. Patients received belatacept for a median duration of 13.2 mo, and at a median follow-up of 15.9 mo post–kidney transplant, 6 of 8 patients continued on belatacept with 3 completely off and 3 poised to transition off CNI. Conclusions. These findings are the first evidence that in liver transplant recipients requiring subsequent kidney transplantation, belatacept-based therapy can potentially facilitate CNI-free maintenance immunosuppression. This supports the possibility of belatacept conversion in stand-alone liver transplant recipients as a viable method of CNI avoidance.

Malignant melanoma demonstrates the highest rate of cardiac metastases. The incidence of melanoma is rising. The prognosis of people with advanced melanoma is generally poor. This case report emphasizes the potential need for early detection of cardiac involvement in advanced melanoma in view of promising advances in treatment with immune checkpoint inhibitors. (Level of Difficulty: Advanced.)

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14–0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10–9.06). The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response. • Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. • CRT was associated with a degradation of diastolic dysfunction in non-responders. Grade I diastolic dysfunction was associated with a better outcome. • Non-responders with grade II or grade III diastiloc dysfunction had the worse prognosis (HR 4.36, 95%CI: 2.10–9.06). • So, the evaluation of diastolic dysfunction in CRT candidates is crucial for best stratification of patients according to their own risk of cardio-vascular event, independently from CRT-response. [ABSTRACT FROM AUTHOR]

Background. The current surge of coronavirus 2019 (COVID-19) cases in certain parts of the country has burdened the healthcare system, limiting access to tertiary centers for many. As a result, COVID-19-positive Solid Organ Transplant (SOT) recipients are increasingly being managed by local healthcare providers. It is crucial for community providers to understand disease severity and know if COVID-19-impacted SOT recipients have a different clinical course compared with COVID-19-negative SOT recipients with a similar presentation. Methods. We conducted a retrospective analysis on SOT recipients suspected to have COVID-19 infection tested during March 14, 2020–April 30, 2020. Patients were followed from time of testing to May 31, 2020. Results. One hundred sixty SOT recipients underwent testing: 22 COVID-19 positive and 138 COVID-19 negative. COVID-19-positive patients were more likely to have rapid progression of symptoms (median 3 vs 6 d, P = 0.002), greater hospitalizations (78% vs 64%, P < 0.017), and need for intensive care unit care (45% vs 17%, P < 0.001) Severe COVID-19 infection was not observed in patients on Belatacept for immunosuppression (30% vs 87%,P = 0.001). COVID- 19 positive patients in the intensive care unit were more likely to have multifocal opacities on radiological imaging in comparison to those admitted to the medical floor (90% vs 11%). Survival probability was similar in both cohorts. Conclusion. COVID-19-infected SOT recipients have a propensity for rapid clinical decompensation. Local providers need to be work closely with transplant centers to appropriately triage and manage COVID-19 SOT recipients in the community.