Autoimmune hemolytic anemia during pregnancy and puerperium: an international multicenter experience.

Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1-8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.

Interaction between ischemic time and donor age under the new donor heart allocation system: Effect on post-transplant survival.

BACKGROUND: Ischemic time (IT) under the new heart transplant (HTx) allocation system has increased compared to the old system. We investigated the effect of IT and donor age on post-HTx survival. METHODS: The United Network for Organ Sharing (UNOS) database was analyzed to identify adult HTx between October 2015 and August 2020. Recipients were stratified by donor age, transplantation era, and IT. Kaplan-Meier and log-rank tests were used to compare 180-day post-HTx mortality. Cox proportional hazards modeling and propensity score matching were performed to adjust for confounders. RESULTS: Under the new system (N = 3654), IT≥4 h led to decreased survival compared to IT < 4 h (91.4% vs. 93.7%; P = .02), although this decrease was undetectable among those with donors ≥39 years old (90.4% vs. 91.1%; P = .73). IT≥4 h led to decreased survival with donors < 39 years old (91.7% vs. 94.6%; P < .01). Under the old system (N = 5987), IT≥4 h resulted in decreased survival (89.8% vs. 93.9%; P < .01), including with donors ≥39 years old (86.9% vs. 92.4%; P < .01). CONCLUSIONS: IT≥4 h remains a risk for post-HTx mortality under the new system. However, the magnitude of this effect is blunted when donor age is ≥39 years, likely secondary to increased allocation of these organs to lower status, more stable recipients.

Using aortic arch short axis views during transesophageal echocardiographic examination facilitates right ventricular assist device imaging.

Given the increased need for mechanical circulatory support and subsequent development of right ventricular assist devices (RVAD), appropriate imaging needs to be described to facilitate care in patients with cardiogenic shock and heart failure. We present three cases in which the upper esophageal aortic arch short axis (UE AA SAX) view on transesophageal echocardiography (TEE) was utilized to effectively image RVADs: to confirm normal positioning, to detect and guide repositioning, and to visualize malfunction. These cases support the importance of the UE AA SAX TEE view in RVAD outflow imaging and, when obtainable, should be included in routine RVAD assessment.

MicroRNA-21 regulates right ventricular remodeling secondary to pulmonary arterial pressure overload.

Right ventricular (RV) function is a critical determinant of survival in patients with pulmonary arterial hypertension (PAH). While miR-21 is known to associate with vascular remodeling in small animal models of PAH, its role in RV remodeling in large animal models has not been characterized. Herein, we investigated the role of miR-21 in RV dysfunction using a sheep model of PAH secondary to pulmonary arterial constriction (PAC). RV structural and functional remodeling were examined using ultrasound imaging. Our results showed that post PAC, RV strain significantly decreased at the basal region compared with t the control. Moreover, such dysfunction was accompanied by increases in miR-21 levels. To determine the role of miR-21 in RV remodeling secondary to PAC, we investigated the molecular alteration secondary to phenylephrine induced hypertrophy and miR21 overexpression in vitro using neonatal rat ventricular myocytes (NRVMs). We found that overexpression of miR-21 in the setting of hypertrophic stimulation augmented only the expression of proteins critical for mitosis but not cytokinesis. Strikingly, this molecular alteration was associated with an eccentric cellular hypertrophic phenotype similar to what we observed in vivo PAC animal model in sheep. Importantly, this hypertrophic change was diminished upon suppressing miR-21 in NRVMs. Collectively, our in vitro and in vivo data demonstrate that miR-21 is a critical contributor in the development of RV dysfunction and could represent a novel therapeutic target for PAH associated RV dysfunction.

A meta-analysis of transcarotid versus transfemoral transcatheter aortic valve replacement.

BACKGROUND: Carotid access has shown promise as an excellent delivery route for transcatheter aortic valve replacement (TAVR). We aimed to compare outcomes of transcarotid (TC) and transfemoral (TF) TAVR by conducting a search and analysis of the best evidence in the literature to shed light on its safety and effectiveness. METHODS: The PubMed/MEDLINE, Embase, and Cochrane library from inception to July 2020 were searched to identify articles reporting comparative data on TC versus TF approaches for TAVR. Patients' baseline characteristics and clinical outcomes were extracted from the articles and pooled for analysis. RESULTS: Five studies, including a total of 2470 patients, were included in the study with 1859 patients in the TF group and 611 patients in the TC group. The TC group had higher prevalence of peripheral vascular disease, while the patients in the TF group was older. Meta-analysis revealed that there was no significant differences between the two groups with regard to 30-day mortality (p = 0.09), stroke (p = 0.28), new dialysis (p = 0.58), major bleeding (p = 0.69), or pacemaker implantation (p = 0.44). The TF group had a higher incidence of vascular complications (3.9% vs. 2.3%; OR 2.22; 95% CI [1.13, 4.38]; p = 0.02). CONCLUSIONS: Compared with the TF approach, TC-TAVR is associated with comparable procedural and clinical outcomes. Our analysis found a lower rate of vascular complication in TC access compared with TF access. This supports consideration of such an alternative access when there are concerns over the feasibility of TF access.

Untwist the twist: instant hemodynamic improvement in known HeartMate 3 complication.

The HeartMate 3 [HM3 (Abbott, Abbott Park, Illinois)] is a left-ventricular assist device (LVAD) with excellent clinical results. Outflow graft occlusion as a complication secondary to outflow graft twisting was reported to occur in 1.6% within the MOMENTUM 3 trial. The anti-twist metal clip or modified bend relief is made to prevent this complication currently, however, there remain large numbers of early implanted HM3 which may develop this complication. There are limited reports illustrating diagnosis, surgical repair, and post-repair hemodynamic changes of these complications. Thus, we present a case of successful diagnosis and surgical repair of an outflow graft twist. Simple procedure through thoracotomy without cardiopulmonary bypass provides significant immediate hemodynamic improvement.

Left thoracotomy vs full sternotomy for centrifugal durable LVAD implantation: 1-year outcome comparison post-LVAD and post-heart transplantation.

Left ventricular assist device (LVAD) implantations have traditionally been approached through a full median sternotomy (FS). Recently, a minimally invasive left thoracotomy (LT) approach has been popularized. This study sought to compare the outcomes of FS and LT patients post-primary LVAD implantation and post-subsequent heart transplant (HT). This was a single-center retrospective study. 83 patients who underwent primary centrifugal durable LVAD implantation from January 2014 to June 2018 were included (FS, n = 41; LT, n = 42). 41 patients had a subsequent HT (FS, n = 19; LT, n = 22). Pre-operative patient demographics, intraoperative variables, post-operative 1-year survival, length of hospital stay, complications, and outcomes for LVAD implantation and following HT were analyzed. Intraoperative data showed that the LT group had a 23.4% longer mean LVAD implant surgical time (p < 0.01). One-year post-LVAD survival was similar between the two groups (p = 0.05). Complication rates, with the exception of the rate of hemorrhagic stroke (p = 0.04) post-LVAD implant were similar. One-year survival post-HT was similar between groups (p = 0.35). Complication rates and mean length of hospital stay were also similar (p = 1.0) post-HT. Our study demonstrated that LT approach does not negatively affect post-LVAD implantation or post-HT outcomes. Further, larger studies may determine more detailed effects of LT approach.

Successful use of Impella 5.5 to manage cardiogenic shock complicated by COVID-19.

BACKGROUND: Acute decompensated heart failure in patients with coronavirus disease 2019 (COVID-19) is becoming increasingly common. AIMS: In this case report, we describe the successful use of an Impella 5.5 (Abiomed) to treat cardiogenic shock refractory to inotropic therapy. MATERIALS & METHODS: Transthoracic and transesophageal echocardiography confirmed severely diminished left ventricular ejection fraction and a reverse-transcription polymerase chain reaction test revealed that the patient was COVID-19 positive during his hospital admission. RESULTS: Following initiation of inotropic therapy, we placed an Impella 5.5 for further cardiac support. The patient's LVEF and cardiac index improved after 21 days on the Impella 5.5 and was maintained following explant. DISCUSSION & CONCLUSION: The findings reported here demonstrate successful use of an Impella 5.5 to improve native heart function in refractory cardiogenic shock and further indicate its use as an option for those in acute decompensated heart failure who have tested positive for COVID-19 infection.

Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation.

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction, referred for surgical myectomy. Plasma was collected at the surgical preoperative visit, approximately one month prior to surgery and then at the post-surgical visit, approximately 3 months later. Proteomic profiles were generated using the aptamer-based SOMAscan assay. Principal Component Analysis using the highest statistically significant proteins separated all preoperative samples from all postoperative samples. Further analysis revealed a set of 25 proteins that distinguished the preoperative and postoperative states with a paired t-test p-value of <0.01. Ingenuity Pathway analysis facilitated the generation of protein interaction networks and the elucidation of key upstream regulators of differentially expressed proteins, such as interferon-γ, TGF-ß1, and TNF. Biological pathways affected by surgery included organ inflammation, migration, and motility of leukocytes, fibrosis, vasculogenesis, angiogenesis, acute coronary events, endothelial proliferation, eicosanoid metabolism, calcium flux, apoptosis, and morphology of the cardiovascular system. Our results indicate that surgical relief of dynamic outflow tract obstruction in HCM patients is associated with unique alterations in plasma proteomic profiles that likely reflect improvement in organ inflammation and physiological function.

Posttransfusion hyperhemolysis is arrested by targeting macrophage activation with novel use of Tocilizumab.

BACKGROUND: Hyperhemolysis syndrome (HHS) is a posttransfusion complication most frequently seen in sickle cell disease (SCD), characterized by rapid destruction of transfused and autologous red blood cells (RBCs), resulting in reticulocytopenia and a decrease in hemoglobin to below pretransfusion levels. Additional RBC transfusion can be life threatening. Most patients improve with intravenous immune globulin and steroids, but in refractory cases, hyperhemolysis may result in multiorgan failure and death in the absence of salvage therapy. The exact pathophysiology of HHS remains uncertain, yet new insights suggest that RBC destruction is driven by activated macrophages. Therefore, we propose that antimacrophage therapy may represent an effective treatment. CASE REPORT: A case of life-threatening HHS, refractory to intravenous immune globulin and steroids, in a patient with SCD is presented. Marked elevation in ferritin, an indirect marker of macrophage activation, a negative direct antiglobulin test, and the absence of RBC alloantibodies was noted. A hemoglobin nadir of 2.1 g/dL and resultant hypoxemia-induced organ failure prompted the use of tocilizumab, an interleukin-6 receptor monoclonal antibody. Hemoglobin-based oxygen carrier-201, a cell-free polymerized bovine hemoglobin, was used to support the patient during critical anemia. RESULTS: Hemolysis resolved and ferritin dramatically decreased after administration of tocilizumab, which was well tolerated. A full recovery was achieved. CONCLUSION: This case highlights both a novel and successful approach to managing refractory transfusion-induced hyperhemolysis with tocilizumab and provides further evidence supporting the role for macrophage activation in the destruction of RBCs in antibody-negative HHS. We propose that tocilizumab is an effective and rapid salvage therapy for refractory HHS.

A case series: the outcomes, support duration, and graft function recovery after VA-ECMO use in primary graft dysfunction after heart transplantation.

Primary graft dysfunction (PGD) is a rare complication associated with high mortality after heart transplantation, which may require veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) support. A standardized definition for PGD was developed by the International Society of Heart and Lung Transplantation in 2014. Due to limited reports using this definition, the detailed outcomes after VA-ECMO support remain unclear. Therefore, we retrospectively analyzed our single-center outcomes of PGD following VA-ECMO support. Between September 2014 and August 2018, 160 patients underwent heart transplantation in our single center. Nine PGD patients required VA-ECMO support, with an incidence of 5.6%. Pre-operative recipient/donor demographics, intra-operative variables, timing of VA-ECMO initiation and support duration, graft function recovery during 30 days after heart transplant, VA-ECMO complications, and survival were analyzed. The indication for VA-ECMO support was biventricular failure for all nine patients. Six patients had severe PGD requiring intra-operative VA-ECMO, while two patients had moderate PGD and one patient had mild PGD requiring post-operative VA-ECMO. All cohorts were successfully decannulated in a median of 10 days. Survival to discharge rate was 88.9%. One-year survival rate was 85.7%. Left ventricular ejection fraction recovered to normal within 30 days in all PGD patients. Our study showed VA-ECMO support led to high survival and timely graft function recovery in all cohorts. Further larger research can clarify the detailed effects of VA-ECMO support which may lead to standardized indication of VA-ECMO support for PGD patients.

Histopathological evidence for macrophage activation driving post-transfusion hyperhaemolysis syndrome.

Post-transfusion hyperhaemolysis syndrome (PTHS) is a rare life-threatening transfusion complication reported mainly in sickle cell patients. Its pathogenesis is poorly understood. Antibody-mediated haemolysis and bystander effect have been proposed as putative mechanisms, but in half of cases, red cell antibodies are undetectable, and PTHS develops despite transfusion of cross-matched compatible RBC. An alternate hypothesis proposes activated macrophages as the main drivers of red cell destruction through direct phagocytosis. We report the histopathological findings of two patients with PTHS showing extensive macrophage expansion and erythrophagocytosis, supportive of macrophage activation driving PTHS. This supports a possible role for novel therapies that target macrophage activation.

Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide.

Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis, and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase 2 trial of ruxolitinib (JAK1/2 inhibitor) vs best available therapy (BAT) in ET and polycythemia vera patients resistant or intolerant to HC. Here, findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 and 52 patients randomized to receive ruxolitinib or BAT, respectively. There was no evidence of improvement in complete response within 1 year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT (P = .40). At 2 years, rates of thrombosis, hemorrhage, and transformation were not significantly different; however, some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT. Molecular responses were uncommon; there were 2 complete molecular responses (CMR) and 1 partial molecular response in CALR-positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in 1 CMR patient, presumably because of the emergence of a different clone, raising questions about the relevance of CMR in ET patients. Grade 3 and 4 anemia occurred in 19% and 0% of ruxolitinib vs 0% (both grades) in the BAT arm, and grade 3 and 4 thrombocytopenia in 5.2% and 1.7% of ruxolitinib vs 0% (both grades) of BAT-treated patients. Rates of discontinuation or treatment switching did not differ between the 2 trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET. This trial was registered at www.isrctn.com as #ISRCTN61925716.

Changes in Preparation and Practice Patterns Among New Family Physicians.

Family physicians' scope of practice is declining despite being well prepared to provide a range of clinical services. To evaluate whether this is a new phenomenon, we compared the proportions of regional family medicine residency graduates who report practicing and those who report feeling more than adequately prepared to practice various procedures and clinical services from 2 points in time-a survey in 2000 of graduates from 1996-1999 (n = 293) and a survey in 2012 or 2014 of graduates from 2010-2013 (n = 408). The recent graduates felt better prepared, but reported a narrower scope of practice than those who graduated more than a decade earlier. These findings suggest that family medicine residency training has improved over time but the declining scope of practice is a concerning trend.

Voluntary vaccinations and vaccine shortages: A theoretical analysis.

A simple dynamic model of vaccination is presented and analyzed to study how the amount of vaccines available affects people's vaccination decisions. In addition, the model is used to examine how the level of vaccination in equilibrium compares to the efficient or socially optimal level. It is shown that, when the stock of vaccines is large so that a shortage could never arise, an equilibrium is generically unique, and there is too little vaccination compared to the social optimum. When the stock of vaccines is small so that not everyone in a population could get vaccinated, a shortage could occur in equilibrium. Moreover, the occurrence of a shortage could be self-fulfilling: when agents expect a shortage to develop, they have a greater incentive to demand the vaccine right away, which increases the likelihood that a shortage will result; and when agents do not expect a shortage to arise, they are more willing to delay their vaccination decision, which reduces the likelihood of a shortage developing. This leads to the possible co-existence of multiple equilibria that differ in the level of vaccination. Multiple equilibria can arise, however, only if agents are uncertain about the cost of being infected - if agents are sufficiently certain about the cost of infection, then an equilibrium is unique. Furthermore, when the stock of vaccines is small, an equilibrium level of vaccination may be too high relative to the socially optimal level. Increasing the vaccine stock could have ambiguous effects on the level of vaccination in equilibrium but unambiguously increases social welfare.

Long-term outcomes following percutaneous hepatic vein recanalization for Budd-Chiari syndrome.

BACKGROUND & AIMS: A proportion of patients with Budd-Chiari Syndrome (BCS) associated with stenosis or short occlusion of the hepatic vein (HV) or upper inferior vena cava (IVC) can be treated with recanalization by percutaneous venoplasty ± HV stent insertion. We studied the long-term outcomes of this approach. METHODS: Single-centre retrospective analysis of patients referred for radiological assessment ± intervention over a 27-year period. Of 155 BCS patients, 63 patients who underwent venoplasty were studied and compared to a previously reported series treated by TIPSS (n = 59). RESULTS: Patients treated with HV interventions (32 venoplasty alone, 31 endovascular stents): mean age, 34.9 ± 10.9; M:F ratio 27:36; median follow-up, 113.0 months; 62% of patients had ≥1 haematological risk factor. Technical success was 100%, with symptom resolution in 73%. Cumulative secondary patency at 1, 5, 10 years was 92%, 79%, 79% and 69%, 69%, 64% in the stenting and venoplasty groups respectively. Where long-term patency was not achieved, 10 patients required TIPSS, and 8 underwent surgery. Actuarial survival at 1, 5, 10 years was 97%, 89% and 85%. When compared to TIPSS, HV interventions resulted in similar patency and survival rates but significantly lower procedural complications (9.5% vs 27.1%) and hepatic encephalopathy (0% vs 18%). Patient age predicted survival following multivariate analysis. CONCLUSIONS: Our data support the stepwise approach to management of BCS, with very good outcomes from venoplasty combined with stenting when required. TIPSS should only be offered where HV interventions are not feasible or unsuccessful.

Applying lessons from behavioral economics to increase flu vaccination rates.

Seasonal influenza imposes an enormous burden on society every year, yet many people refuse to obtain flu shots due to misconceptions of the flu vaccine. We argue that recent research in psychology and behavioral economics may provide the answers to why people hold mistaken beliefs about flu shots, how we can correct these misconceptions, and what policy-makers can do to increase flu vaccination rates.

Factors Contributing to the Success of Ultrasound-Guided Native Renal Biopsy.

OBJECTIVES: The purpose of this study was to evaluate factors contributing to the success of ultrasound-guided native renal biopsy. METHODS: We retrospectively identified patients who had ultrasound-guided native renal biopsy at our institution over a 10-year period. We reviewed the imaging and electronic medical records to collect demographic information and clinical data, including pathologic results. Biopsy samples were categorized and compared on the basis of the number of glomeruli (optimal [≥20] versus suboptimal [<20]) and the pathologist's reported diagnostic confidence (high confidence versus limited confidence). Procedure details, including the operator and the use of the cortical tangential approach, were also obtained. RESULTS: For 282 patients with biopsies using 18-gauge needles, the number of passes made was significantly higher for optimal (P < .001) and high-confidence (P < .001) specimens than for suboptimal and limited-confidence specimens. The cortical tangential approach was used more frequently for optimal (P< .001) and high-confidence (P = .01) specimens than for suboptimal and limited-confidence specimens. Radiologists routinely doing ultrasound-guided procedures of all types had significantly more optimal (P= .01) and high-confidence (P= .001) specimens than radiologists with limited ultrasound experience. The distance to the kidney, cortical thickness, glomerular filtration rate, and body mass index were not significant factors. CONCLUSIONS: The ultrasound-guided procedural experience of the operator, taking more than 1 specimen, and the use of the cortical tangential approach significantly improved the pathologic material obtained during native renal biopsies.