Expanding ACTA2 genotypes with corresponding phenotypes overlapping with smooth muscle dysfunction syndrome.

Pathogenic variants in ACTA2, encoding smooth muscle α-actin, predispose to thoracic aortic aneurysms and dissections. ACTA2 variants altering arginine 179 predispose to a more severe, multisystemic disease termed smooth muscle dysfunction syndrome (SMDS; OMIM 613834). Vascular complications of SMDS include patent ductus arteriosus (PDA) or aortopulmonary window, early-onset thoracic aortic disease (TAD), moyamoya-like cerebrovascular disease, and primary pulmonary hypertension. Patients also have dysfunction of other smooth muscle-dependent systems, including congenital mydriasis, hypotonic bladder, and gut hypoperistalsis. Here, we describe five patients with novel heterozygous ACTA2 missense variants, p.Arg179Gly, p.Met46Arg, p.Thr204Ile, p.Arg39Cys, and p.Ile66Asn, who have clinical complications that align or overlap with SMDS. Patients with the ACTA2 p.Arg179Gly and p.Thr204Ile variants display classic features of SMDS. The patient with the ACTA2 p.Met46Arg variant exhibits exclusively vascular complications of SMDS, including early-onset TAD, PDA, and moyamoya-like cerebrovascular disease. The patient with the ACTA2 p.Ile66Asn variant has an unusual vascular complication, a large fusiform internal carotid artery aneurysm. The patient with the ACTA2 p.Arg39Cys variant has pulmonary, gastrointestinal, and genitourinary complications of SMDS but no vascular manifestations. Identifying pathogenic ACTA2 variants associated with features of SMDS is critical for aggressive surveillance and management of vascular and nonvascular complications and delineating the molecular pathogenesis of SMDS.

Occurrence and outcome of blood-contaminated percutaneous injuries among anesthesia practitioners: a cross-sectional study.

BACKGROUND: Anesthesia practitioners are at risk for percutaneous injuries by blood-contaminated needles and sharp objects that may result in the transmission of human immunodeficiency virus and hepatitis viruses. Reporting these injuries is important for the early prevention and management of blood-borne infections. OBJECTIVE: To investigate the occurrence, reporting, characteristics and outcome of contaminated percutaneous injuries (CPIs) in anesthesia residents, fellows and faculty. METHOD: A cross-sectional anonymous survey electronically distributed to all 214 anesthesia practitioners at a large academic multihospital-based anesthesia practice in Florida, USA. RESULTS: The overall response rate was 51% (110/214) (60% (50/83) for residents, 50% (8/16) for fellows and 45% (52/115) for anesthesia faculty). Fifty-nine percent (65/110) (95% confidence interval (95% CI): 5068) of participants reported having one or more CPIs during their years of anesthesia practice (residents 42% (95% CI: 2955), fellows 50% and faculty 77% (95% CI: 6688)). The number of CPIs per anesthesia practitioner who answered the survey was 0.58 for residents, 0.75 for fellows and 1.5 for faculty. Within the last 5 years, 35% (95% CI: 2644) of participants had one or more CPIs (39% of residents, 50% of fellows and 29% of faculty). CPIs in the last 5 years in faculty older than 45 years of age were 12% (3/25) compared to 44% (12/27) in faculty younger than 45 years of age.Analyzing data from practitioners who had one CPI revealed that 70% (95% CI: 5585) reported the incident at the time of injury (residents 85%, fellows 100% and faculty 58%). Hollow-bore needles constituted 73.5% (95% CI: 5988) of injuries. As per participants' responses, 17% (18/103) of CPIs received postexposure prophylaxis and there were zero seroconversions. CONCLUSION: Based on our study results, most anesthesia practitioners will sustain a CPI during their years of practice. Despite some improvements compared to historic figures, the occurrence of CPIs continues to be high and reporting of percutaneous injuries remains suboptimal among anesthesia residents. A fifth of injuries in the perioperative setting is from an infected source and requires postexposure prophylaxis. Although no infections were reported due to CPI exposure in this study, findings underscore the need for more education and interventions to reduce occupational blood exposures in anesthesia practitioners and improve reporting.

Fibrinolysis Shutdown Is Associated With Thrombotic and Hemorrhagic Complications and Poorer Outcomes After Liver Transplantation.

Detrimental consequences of hypofibrinolysis, also known as fibrinolysis shutdown (FS), have recently arisen, and its significance in liver transplantation (LT) remains unknown. To fill this gap, this retrospective study included 166 adults who received transplants between 2016 and 2018 for whom baseline thromboelastography was available. On the basis of percent of clot lysis 30 minutes after maximal amplitude, patients were stratified into 3 fibrinolysis phenotypes: FS, physiologic fibrinolysis, and hyperfibrinolysis. FS occurred in 71.7% of recipients, followed by physiologic fibrinolysis in 19.9% and hyperfibrinolysis in 8.4%. Intraoperative and postoperative venous thrombosis events occurred exclusively in recipients with the FS phenotype. Intraoperative thrombosis occurred with an overall incidence of 4.8% and was associated with 25.0% in-hospital mortality. Incidence of postoperative venous thrombosis within the first month was deep venous thrombosis/pulmonary embolism (PE; 4.8%) and portal vein thrombosis/hepatic vein thrombosis (1.8%). Massive transfusion of ≥20 units packed red blood cells was required in 11.8% of recipients with FS compared with none in the other 2 phenotype groups (P = 0.01). Multivariate analysis identified 2 pretransplant risk factors for FS: platelet count and nonalcoholic steatohepatitis/cryptogenic cirrhosis. Recursive partitioning identified a critical platelet cutoff value of 50 × 109 /L to be associated with FS phenotype. The hyperfibrinolysis phenotype was associated with the lowest 1-year survival (85.7%), followed by FS (95.0%) and physiologic fibrinolysis (97.0%). Infection/multisystem organ failure was the predominant cause of death; in the FS group, 1 patient died of exsanguination, and 1 patient died of massive intraoperative PE. In conclusion, there is a strong association between FS and thrombohemorrhagic complications and poorer outcomes after LT.

Visceral arterial embolization prior to multivisceral transplantation in recipient with cirrhosis, extensive portomesenteric thrombosis, and hostile abdomen: Performance and outcome analysis.

Multivisceral transplant (MVT) for cirrhosis, and portomesenteric vein thrombosis (PVT), is fraught with life-threatening thrombo-hemorrhagic complications. Embolization of native viscera has been attempted in a handful of cases with mixed results. We carried out a comparative analysis of angiographic, intra-operative, and pathological findings in three recipients of MVT who were deemed exceptionally high hemorrhagic risk and therefore underwent preoperative visceral embolization. All recipients were male with cirrhosis, PVT, and a surgical history indicative of diffuse visceral adhesions; status post-liver transplantation (n = 2) and proctocolectomy (n = 1). The first patient had two Amplatzer II embolization plugs placed 2 cm from the origins of celiac and superior mesenteric (SMA) arteries. Distal migration of the celiac plug into gastroduodenal artery (GDA) and ensuing ischemia reperfusion injury, presumably contributed to severe disseminated intravascular coagulation (DIC) and intra-operative mortality. In the other two recipients, distal Gelfoam embolization of the SMA, GDA, and splenic arteries was performed, and although remarkable hemorrhage and coagulopathy occurred, embolization, undoubtedly, facilitated exenteration and improved outcomes. Pathologic examination in these cases confirmed ischemic necrosis of eviscerated bowel. In conclusion, liver-sparing, preoperative distal embolization of native viscera with Gelfoam is beneficial, but entails several pitfalls. It should currently be reserved for MVT recipients who otherwise are at unacceptably high risk.

Susceptibility-directed anticoagulation after pancreas transplantation: A single-center retrospective study.

Pancreas transplant achieves consistent long-term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous kidney-pancreas or isolated pancreas transplanted between 1/1/2015 and 11/20/2018. Early postoperative anticoagulation regimens included the following: none, subcutaneous heparin/aspirin, with or without dextran, and heparin infusion. The regimens were empirically selected based on each surgeon's assessment of hemostasis of the operative field and personal preference. A sonographic-based global scoring system of AT is presented. The 47-month recipients and graft survival were 95% and 86%, respectively. Recipients with or without AT had similar survival. Five and four grafts were lost due to death and AT, respectively. Outcomes of prophylaxis regimens correlated with intensity of anticoagulation. Compared with no anticoagulation, an increase in hemorrhagic complications occurred exclusively with iv heparin. The higher arterial AT score found in regimens lacking antiplatelet therapy highlights the importance of early antiaggregants therapy. Abnormal fibrinolysis was associated with an increase in AT score. Platelet dysfunction, warm ischemia time, and enteric drainage were predictive of AT and, along with other known risk factors, were incorporated into an algorithm that matches intensity of early postoperative anticoagulation to the thrombotic risk.

Thrombotic and hemorrhagic complications during visceral transplantation: risk factors, and association with intraoperative disseminated intravascular coagulation-like thromboelastographic qualities: a single-center retrospective study.

This study describes the risk of thrombotic and hemorrhagic complications, both intraoperatively, and up to 1 month following visceral transplantation. Data from 48 adult visceral transplants performed between 2010 and 2017 were retrospectively studied [32 multivisceral (MVTx); 10 isolated intestine; six modified-MVTx]. Intraoperatively, intracardiac thrombosis (ICT)/pulmonary embolism (PE) occurred in 25%, 0% and 0% of MVTx, isolated intestine and modified MVTx, respectively, and was associated with 50% (4/8) mortality. Preoperative portal vein thrombosis (PVT) was a significant risk factor for ICT/PE (P = 0.0073). Thromboelastography resembling disseminated intravascular coagulation (DIC) (r time <4 mm combined with fibrinolysis or flat-line) was statistically associated with occurrence of ICT/PE (P < 0.0001). Compared to subgroup without ICT/PE, occurrence of ICT/PE was associated with an increased demand for all blood product components both overall, and each surgical stage. Hyperfibrinolysis (56%) was identified as cause of bleeding in MVTx. Incidence of postoperative thrombotic event at 1 month was 25%, 30% and 17% for MVTx, isolated intestine and modified MVTx, respectively. Incidence of postoperative bleeding complications at 1 month was 11%, 20% and 17% for MVTx, isolated intestine and modified MVTx. In conclusion, MVTx recipients with preoperative PVT are at an increased risk of developing intraoperative life-threatening ICT/PE events associated with DIC-like coagulopathy.

Characteristics, Risk Factors, and Outcome of New-onset Systolic Heart Failure After Liver Transplantation: A Single-center Cohort.

New-onset systolic heart failure (HF) after liver transplantation (LT) is a significant cause of morbidity and mortality; however, its characteristics are still insufficiently delineated. HF may involve the left ventricle (LV), right ventricle (RV), or both ventricles. We explored the incidence, characteristics, etiologies, risks, involved cardiac chambers, and outcomes of HF after LT. Methods: This study included 528 adult patients with preoperative LV ejection fraction ≥ 55% who underwent LT between 2016 and 2020. The primary outcome was new-onset systolic HF, defined by the presence of clinical signs, symptoms, and echocardiographic evidence of reduced LVejection fraction <50% and RV dysfunction within the first year after LT. Results: Thirty-one patients (6%) developed systolic HF within a median of 9 d (1-364). Of those, 23% of patients had ischemic HF, whereas 77% had nonischemic HF. Nonischemic HF was caused by stress (11), sepsis (8), or other factors (5). Nonischemic HF was secondary to isolated LV failure in 58% of patients or RV ± LV failure in 42% of patients. Recursive partitioning identified subgroups with varying risks and uncovered interaction between variables. HF risk increased from 4.2% to 13% when epinephrine and/or norepinephrine drips were used intraoperatively (P < 0.01). When no epinephrine and/or norepinephrine were used, HF risk increased from 3.1% to 38.5% if baseline hemoglobin was <7.2 g/dL (P < 0.01). When baseline hemoglobin was ≥7.2 g/dL, HF risk increased from 0% to 5.2% when ≥3500 mL crystalloid was used intraoperatively (P < 0.01). Posttransplant first-year survival and reversibility of HF depended on the etiology (stress, sepsis, ischemia, etc) and cardiac chamber involvement (isolated LV or RV ± LV). RV dysfunction was associated with inferior recovery of cardiac function and poorer survival than nonischemic isolated LV dysfunction (50% versus 70%, respectively). Conclusions: Posttransplant new-onset HF is mostly nonischemic in nature and is associated with increased morbidity and mortality.

Personal Protective Equipment for Liver Transplant in SARS-CoV-2 Polymerase Chain Reaction-Positive Convalescing Recipients.

Personal protective equipment (PPE) comes in several variations, and is the principal safety gear during the COVID-19 pandemic. Unfortunately, the user is severely impacted by its serious nonergonomic features. What PPE is appropriate for labor-intensive cases, like liver transplant (LT), remains unknown. We describe our experience with 2 types of PPE used during 2 separate LT performed in COVID-19 positive recipients. We conclude that for the safety of both health care workers and patients, hospitals should designate a few PPE kits for labor-intensive surgical procedures. These kits should include powered air-purifying respirators, or a similar loose-fitting powered air hood.

A Less Restrictive Policy for Liver Transplantation in Coronavirus Disease 2019 Positive Patients, Based Upon Cycle Threshold Values.

Coronavirus disease 2019 drastically impacted solid organ transplantation. Lacking scientific evidence, a very stringent but safer policy was imposed on liver transplantation (LT) early in the pandemic. Restrictive transplant guidelines must be reevaluated and adjusted as data become available. Before LT, the prevailing policy requires a negative severe acute respiratory syndrome coronavirus 2 real-time polymerase chain reaction (RT-PCR) of donors and recipients. Unfortunately, prolonged viral RNA shedding frequently hinders transplantation. Recent data reveal that positive test results for viral genome are frequently due to noninfectious and prolonged convalescent shedding of viral genome. Moreover, studies demonstrated that the cycle threshold of quantitative RT-PCR could be leveraged to inform clinical transplant decision-making. We present an evidence-adjusted and significantly less restrictive policy for LT, where risk tolerance is tiered to recipient acuity. In addition, we delineate the pretransplant clinical decision-making, intra- and postoperative management, and early outcome of 2 recipients of a liver graft performed while their RT-PCR of airway swabs remained positive. Convalescent positive RT-PCR results are common in the transplant arena, and the proposed policy permits reasonably safe LT in many circumstances.

Intestinal Autotransplantation and In-Situ Resection of Recurrent Pancreatic Head Intraductal Tubulopapillary Neoplasm with Portal Cavernoma: A Case Report.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) is a new entity of a rare premalignant pancreatic neoplasia, and a radical curative resection is indicated. As with other tumors of the root of the mesentery, the proximity of the lesion to large splanchnic vessels, abdominal aorta, and inferior vena cava poses major risks of a massive hemorrhage and visceral ischemia using conventional surgical techniques. At times, these lesions are amenable for resection using novel techniques developed from organ transplantation. Multivisceral (allo-) transplantation should be considered when radical resection of a benign tumor is likely to compromise portal flow and possibly precipitate acute liver failure, but it may be associated with a long waitlist time and tumor progression. Autotransplantation offers a safe and curative resection of otherwise inoperable tumors in a bloodless field, an excellent exposure, and prevention of warm ischemic injury to the affected viscera, which are then autotransplanted. METHODS: We describe the en bloc resection of a large and recurrent ITPN of the pancreas, distal stomach, proximal duodenum, transverse colon, superior mesenteric vein, and portal cavernoma, followed by intestinal autotransplantation. RESULTS: A complete tumor resection was achieved with negative margins, adequate cold preservation of the reimplanted intestine, and without significant hemorrhage. The patient was discharged from the hospital 10 days later. The histopathologic examination revealed free-margin resection of ITPN with an associated invasive carcinoma. The patient received adjuvant chemotherapy with folinic acid, fluorouracil, and oxaliplatin and remains disease-free 20 months after surgery. CONCLUSIONS: Autotransplantation offers curative resection of otherwise unresectable lesions of the root of the mesentery.

Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation: A retrospective, single center study.

BACKGROUND: There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount. AIM: To identify risk factors associated with delayed graft function (DGF). METHODS: Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF. RESULTS: The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min. CONCLUSION: We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.

Comprehensive Frailty Severity Index for End-Stage Liver Disease Predicts Early Outcomes After Liver Transplantation.

BACKGROUND: Frailty is rampant in candidates of liver transplantation (LT); however, its impact on posttransplant survival is inconclusive. Most studies have used a single measure of frailty; however, a comprehensive frailty severity index (FSI) has not been developed. The objectives of this study were to (1) evaluate frailty utilizing several metrics, (2) develop an FSI for end-stage liver disease (ESLD), and (3) determine its predictive abilities for outcomes after LT. METHODS: Frailty metrics included (1) modified nutrition assessment of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition that includes height-adjusted third lumbar vertebra psoas mass index, (2) physical performance assessment combining Karnofsky Performance Status and pressure injury scale, and (3) Controlling Nutritional Status as a measure of severity of liver disease and inflammation. RESULTS: Moderate to severe frailty was reported in 52%-97% of recipients depending on the metric. A statistically significant threshold FSI value was identified for each adverse outcome studied. FSI ≥ 14 was associated with decreased survival (88% vs 97% for FSI < 14). CONCLUSIONS: The proposed FSI for ESLD is predictive of poorer outcomes after LT.