Sutureless Valves, a "Wireless" Option for Patients With Aortic Valve Disease: JACC State-of-the-Art Review.

Transcatheter technologies triggered the recent revision of the guidelines that progressively widened the indications for the treatment of aortic stenosis. On the surgical realm, a technology avoiding the need for sutures to anchor the prosthesis to the aortic annulus has been developed with the aim to reduce the duration of cardiopulmonary bypass and simplify the process of valve implantation. In addition to a transcatheter aortic valve replacement (TAVR)-like stent that exerts a radial force, these so-called "rapid deployment valves" or "sutureless valves" for aortic valve replacement also have cuffs to improve sealing and reduce the risk of paravalvular leak. Despite promising, the actual advantage of sutureless valves over traditional surgical procedures (surgical aortic valve replacement) or TAVR is still debated. This review summarizes the current comparative evidence reporting outcomes of "sutureless valves" for aortic valve replacement to TAVR and surgical aortic valve replacement in the treatment of aortic valve stenosis.

Intestinal Microbiota and Derived Metabolites in Myocardial Fibrosis and Postoperative Atrial Fibrillation.

The high incidence of atrial fibrillation (AFib) following cardiac surgery (postoperative atrial fibrillation, POAF) relies on specific surgical features. However, in the setting of POAF, the role of the microbiome in the modulation of cardiac fibrosis is still not clear. This study aimed to analyze the effect of the microbiome and its main metabolic product (trimethylamine-N-oxide, TMAO) in the fibrosis of myocardial tissue, to investigate its role in POAF. Patients undergoing elective cardiac surgery with cardiopulmonary bypass, central atrio-caval cannulation and no history of AFib, were included. A fragment of the right atrium was analyzed for qualitative and mRNA-quantitative evaluation. A preoperative blood sample was analyzed with enzyme-linked immunosorbent assay (ELISA). A total of 100 patients have been included, with POAF occurring in 38%. Histologically, a higher degree of fibrosis, angiogenesis and inflammation has been observed in POAF. Quantitative evaluation showed increased mRNA expression of collagen-1, collagen-3, fibronectin, and transforming growth factor beta (TGFb) in the POAF group. ELISA analysis showed higher levels of TMAO, lipopolysaccharide and TGFb in POAF, with similar levels of sP-selectin and zonulin. TMAO ≥ 61.8 ng/mL (odds ratio, OR 2.88 [1.35-6.16], p = 0.006), preoperative hemoglobin < 13.1 g/dL (OR 2.37 [1.07-5.24], p = 0.033) and impaired right ventricular function (OR 2.38 [1.17-4.83], p = 0.017) were independent predictors of POAF. Also, TMAO was significantly associated with POAF by means of increased fibrosis. Gut microbiome product TMAO is crucial for myocardial fibrosis, which is a key factor for POAF. Patients in preoperative sinus rhythm who will develop POAF have increased genetic expression of pro-fibrotic genes and enhanced fibrosis in histological staining. Elevated TMAO level (≥61.8 ng/mL) is an independent risk factor for POAF.

In vitro functional analysis and in silico structural modelling of pathogen-secreted polyglycine hydrolases.

Polyglycine hydrolases are fungal effectors composed of an N-domain with unique sequence and structure and a C-domain that resembles ß-lactamases, with serine protease activity. These secreted fungal proteins cleave Gly-Gly bonds within a polyglycine sequence in corn ChitA chitinase. The polyglycine hydrolase N-domain (PND) function is unknown. In this manuscript we provide evidence that the PND does not directly participate in ChitA cleavage. In vitro analysis of site-directed mutants in conserved residues of the PND of polyglycine hydrolase Es-cmp did not specifically impair protease activity. Furthermore, in silico structural models of three ChitA-bound polyglycine hydrolases created by High Ambiguity Driven protein-protein DOCKing (HADDOCK) did not predict significant interactions between the PND and ChitA. Together these results suggest that the PND has another function. To determine what types of PND-containing proteins exist in nature we performed a computational analysis of Foldseek-identified PND-containing proteins. The analysis showed that proteins with PNDs are present throughout biology as either single domain proteins or fused to accessory domains that are diverse but are usually proteases or kinases.

Late device-related thrombus associated with occult malignancy years after left atrial appendage closure.

INTRODUCTION: The use of Left Atrial Appendage (LAA) occluder devices has been on the rise in patients with atrial fibrillation. Studies regarding the long-term risks of occluder devices remain sparse. MATERIALS & METHODS: In this brief report, we discuss the unusual case of an 85-year-old female with long-term complication from Left Atrial Appendage (LAA) closure: Device-Related Thrombus (DRT) about two years after insertion. RESULTS: Compared to the expected stroke rate without anticoagulation, patients with DRT on their LAAO device still had a 28 % relative reduction in ischemic stroke. This suggests that these strokes may have emanated from alternate etiologies other than the DRT. CONCLUSIONS: Patients with active or known history of cancer appears to have a higher risk of DRT. More data is needed on this topic to augment awareness and understanding of LAAO complications and DRT management strategies.

The negative pressure wound therapy for prevention of sternal wound infection: Can we reduce infection rate after the use of bilateral internal thoracic arteries? A systematic literature review and meta-analysis.

BACKGROUND: Negative pressure wound therapy (NPWT) is traditionally used to treat postoperative wound infections. However, its use in closed wound sternotomy post cardiac surgery in high-risk patients has become increasingly popular. The potential preventive benefit of reducing sternal wound infections has been recently acknowledged. Bilateral internal mammary artery (BIMA) grafts are used in coronary artery bypass grafting but have been associated with an increased risk of sternal wound infections (SWIs). OBJECTIVES: This systematic analysis examines whether NPWT can reduce the incidence of SWI following BIMA grafts, leading to more patients benefiting from the better survival outcome associated with BIMA grafting. METHOD: A comprehensive systematic search and meta-analysis were performed to identify studies on the use of NPWT in closed wound sternotomy. Ovid MEDLINE (in-process and other nonindexed citations and Ovid MEDLINE 1990 to present), Ovid EMBASE (1990 to present), and The Cochrane Library (Wiley), PubMed, and Google Scholar databases were searched from their inception to May 2022 using keywords and MeSH terms. Thirty-four articles from 1991 to May 2022 were selected. RESULT: Three studies reported on the outcome of NPWT following BIMA grafting. The pooled analysis did not show any significant difference in the incidence of sternal wound infection between NPWT and standard dressing (RR 0.48 95% CI 0.17-1.37; P = 0.17) with substantial heterogeneity (I2 65%). Another seven studies were found comparing the outcome of SWI incidence of negative pressure closed wound therapy with conventional wound therapy in patients undergoing adult cardiac surgery. The pooled analysis showed that NPWT was associated with a low risk of SWIs compared to conventional dressing (RR 0.47 95% CI 0.36-0.59; P < 0.00001), with low heterogeneity (I2 1%). CONCLUSION: The literature identified that NPWT significantly decreased the incidence of sternal wound complications when applied to sutured sternotomy incisions in high-risk patients, and in some cases, it eliminated the risk. However, the inadequate number of randomized controlled trials assessing the effectiveness of NPWT in BIMA grafting emphasizes the need for further, robust studies.

Enhanced recovery protocols after surgery: A systematic review and meta-analysis of randomized trials in cardiac surgery.

BACKGROUND: Previous meta-analyses combining randomized and observational evidence in cardiac surgery have shown positive impact of enhanced recovery protocols after surgery (ERAS) on postoperative outcomes. However, definitive data based on randomized studies are missing, and the entirety of the ERAS measures and pathway, as recently systematized in guidelines and consensus statements, have not been captured in the published studies. The available literature actually focuses on "ERAS-like" protocols or only limited number of ERAS measures. This study aims at analyzing all randomized studies applying ERAS-like protocols in cardiac surgery for perioperative outcomes. METHODS: A meta-analysis of randomized controlled trials (RCTs) comparing ERAS-like with standard protocols of perioperative care was performed (PROSPERO registration CRD42021283765). PRISMA guidelines were used for abstracting and assessing data. RESULTS: Thirteen single center RCTs (N = 1704, 850 in ERAS-like protocol and 854 in the standard care group) were selected. The most common procedures were surgical revascularization (66.3%) and valvular surgery (24.9%). No difference was found in the incidence of inhospital mortality between the ERAS and standard treatment group (risk ratio [RR] 0.61 [0.31; 1.20], p = 0.15). ERAS was associated with reduced intensive care unit (standardized mean difference [SMD] -0.57, p < 0.01) and hospital stay (SMD -0.23, p < 0.01) and reduced rates of overall complications when compared to the standard protocol (RR 0.60, p < 0.01) driven by the reduction in stroke (RR 0.29 [0.13; 0.62], p < 0.01). A significant heterogeneity in terms of the elements of the ERAS protocol included in the studies was observed. CONCLUSIONS: ERAS-like protocols have no impact on short-term survival after cardiac surgery but allows for a faster hospital discharge while potentially reducing surgical complications. However, this study highlights a significant nonadherence and heterogeneity to the entirety of ERAS protocols warranting further RCTs in this field including a greater number of elements of the framework.

Minimally invasive epicardial surgical left atrial appendage exclusion for atrial fibrillation patients at high risk for stroke and for bleeding.

BACKGROUND: Atrial fibrillation (AF) patients at high risk for stroke and for bleeding may be unsuitable for either oral anticoagulation or endocardial left atrial appendage (LAA) occlusion. However, minimally invasive, epicardial left atrial appendage exclusion (LAAE) may be an option. OBJECTIVE: The purpose of this study was to evaluate outcomes of LAAE in high-risk AF patients not receiving oral anticoagulation. METHODS: A retrospective analysis of Medicare claims data was conducted to evaluate thromboembolic events in AF patients who underwent LAAE compared to a 1:4 propensity score-matched group of patients who did not receive LAAE (control). Neither group was receiving any oral anticoagulation at baseline or follow-up. Fine-Gray models estimated hazard ratios and evaluated between-group differences. Bootstrapping was applied to generate 95% confidence intervals (CIs). RESULTS: The LAAE group (n = 243) was 61% male (mean age 75 years). AF was nonparoxysmal in 70% (mean CHA2DS2-VASc score 5.4; mean HAS-BLED score 4.2). The matched control group (n = 972) had statistically similar characteristics. One-year adjusted estimates of thromboembolic events were 7.3% (95% CI 4.3%-11.1%) in the LAAE group and 12.1% (95% CI 9.5%-14.8%) in the control group. Absolute risk reduction was 4.8% (95% CI 0.6%-8.9%; P = .028). Adjusted hazard ratio for thromboembolic events for LAAE vs non-LAAE was 0.672 (95% CI 0.394-1.146). CONCLUSION: In AF patients not taking oral anticoagulation who are at high risk for stroke and for bleeding, minimally invasive, thoracoscopic, epicardial LAAE was associated with a lower rate of thromboembolic events.

Direct Oral Anticoagulant Failures in Atrial Fibrillation With Stroke: Retrospective Admission Analysis and Novel Classification System.

Introduction: Breakthrough acute ischemic stroke (AIS) in patients with known, nonvalvular Atrial Fibrillation (AF), on Direct Oral Anticoagulants (DOAC), is an ongoing clinical conundrum. Switching anticoagulants was shown to be ineffective in preventing recurrent AIS. Systematic, patient-level chart review of so-called "DOAC failures" may offer insight into this phenomenon. Methods: We conducted an IRB-approved, 6-year, retrospective study of AIS admissions, already prescribed DOAC for known AF. We sought plausible, alternative reasons for the AIS using a novel classification schema, CLAMP: C for Compliance concerns, L for Lacunes (small-vessel disease), A for Arteriopathy (atherosclerosis, web, or vasculitis), M for Malignancy, and P for Patent Foramen Ovale (PFO). These categories were labeled as DOAC "Pseudo-failures." Conversely, absence of CLAMP variables were labeled as DOAC "Crypto-failures" conceivably from AF itself ("atriopathy") or pharmacokinetic/pharmacogenomic dysfunction (ie, altered DOAC absorption, clearance, metabolism, or genetic polymorphisms). Forward logistic regression analysis was performed on prespecified DOAC subgroups. Results: Of 4890 AIS admissions, 606 had AF, and 87 were previously prescribed DOAC (14.4% overall DOAC failure rate, 2.4% annualized over 6 years). Pseudo-failures comprised 77%: Compliance concerns (48.9%), Lacunes (5.7%), Arteriopathy (17.0%), Malignancy (26.1%), and PFO (2.3%). Crypto-failures comprised 23%, had lower CHADSVASc scores (AOR = .65, P = .013), and occurred more with rivaroxaban (41%) than apixaban (16%) or dabigatran (5.6%). Conclusion: In AIS patients with known AF, DOAC Pseudo-failures, with identified alternate etiologies, are 3 times more likely than DOAC Crypto-failures. The CLAMP schema represents a novel approach to diagnostic classification and therapeutic adjustments in patients already prescribed DOAC for AF.

Early Re-Exploration versus Conservative Management for Postoperative Bleeding in Stable Patients after Coronary Artery Bypass Grafting: A Propensity Matched Study.

BACKGROUND: Postoperative bleeding requiring re-exploration in cardiac surgery has been associated with complications impacting short-term outcomes and perioperative survival. Many aspects of decision-making for re-exploration still remain controversial, especially in hemodynamically stable patients with significant but not acutely cumulating chest drain output. We investigated the impact of re-exploratory surgery on short-term outcomes in a "borderline population" of CABG patients who experienced significant non-acute bleeding, but that were not in critically hemodynamic unstable conditions. METHODS: A prospectively collected database of 8287 patients undergoing primary isolated elective CABG was retrospectively interrogated. A population of hemodynamically stable patients experiencing significant non-acute or rapidly cumulating bleeding (>1000 mL of blood loss in 12 h, <200 mL per hour in the first 5 h) with normal platelet and coagulation tests was identified (N = 1642). Patients belonging to this group were re-explored (N = 252) or treated conservatively (N = 1390) based on the decision of the consultant surgeon. Clinical outcomes according to the decision-making strategy were compared using a propensity score matching (PSM) approach. RESULTS: After PSM, reoperated patients exhibited significantly higher overall blood product consumption (88.4% vs. 52.6% for red packed cells, p = 0.001). The reoperated group experienced higher rates of respiratory complications (odds ratio 5.8 [4.29-7.86] with p = 0.001 for prolonged ventilation), prolonged stay in intensive care unit (coefficient 1.66 [0.64-2.67] with p = 0.001) and overall length of stay in hospital (coefficient 2.16 [0.42-3.91] with p = 0.015) when compared to conservative management. Reoperated patients had significantly increased risk of multiorgan failure (odds ratio 4.59 [1.37-15.42] with p = 0.014) and a trend towards increased perioperative mortality (odds ratio 3.12 [1.08-8.99] with p = 0.035). CONCLUSIONS: Conservative management in hemodynamically stable patients experiencing significant but non-critical or emergency bleeding might be a safe and viable option and might be advantageous in terms of reduction of postoperative morbidities and hospital stay.

Crystal structure of a polyglycine hydrolase determined using a RoseTTAFold model.

Polyglycine hydrolases (PGHs) are secreted fungal proteases that cleave the polyglycine linker of Zea mays ChitA, a defensive chitinase, thus overcoming one mechanism of plant resistance to infection. Despite their importance in agriculture, there has been no previous structural characterization of this family of proteases. The objective of this research was to investigate the proteolytic mechanism and other characteristics by structural and biochemical means. Here, the first atomic structure of a polyglycine hydrolase was identified. It was solved by X-ray crystallography using a RoseTTAFold model, taking advantage of recent technical advances in structure prediction. PGHs are composed of two domains: the N- and C-domains. The N-domain is a novel tertiary fold with an as-yet unknown function that is found across all kingdoms of life. The C-domain shares structural similarities with class C ß-lactamases, including a common catalytic nucleophilic serine. In addition to insights into the PGH family and its relationship to ß-lactamases, the results demonstrate the power of complementing experimental structure determination with new computational techniques.

Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis.

This study aims to compare treatments and outcomes of mechanical complications of acute myocardial infarction (MI) during the Covid-19 and in the pre-Covid-19 era. Electronic databases have been searched for MI mechanical complications during the Covid-19 era and in the previous period from January 1998 to January 2020 (pre-Covid-19 era), until October 2021. To perform a quantitative analysis of non-comparative series, a meta-analysis of proportion has been conducted. Early mortality after surgical treatment was 15.0% while it was significantly higher after conservative treatment (62.4%) (P = 0.026). Early mortality after surgical treatment was seemingly higher in the pre-Covid-19 era but the difference did not reach statistical significance (15.0% vs 38.9%; P = 0.13). Mortality in patients treated conservatively, or turned down for surgery, was lower during the Covid-19 pandemic (62.4% vs 97.7%; P = 0.001). The crude mean prevalence of the use rate of conservative or surgical treatment across the studies during Covid-19 and in the pre-Covid-19 era was comparable. The current increased incidence of MI mechanical complications might be a consequence of delayed presentation or restricted access to hospital facilities. Despite the general negative impact of Covid-19 on cardiac surgery volumes and outcomes and the apparent increase of the incidence of MI complications, the outcomes of their surgical and clinical treatment seem not to have been affected during the pandemic.

Effect of Hospital-associated SARS-CoV-2 Infections in Cardiac Surgery. A Multicenter Study.

BACKGROUND: The effect of hospital-associated SARS-CoV-2 infections in cardiac surgery patients remains poorly investigated, and current data are limited to small case series with conflicting results. METHODS: A multicenter European collaboration was organized to analyze the outcomes of patients who tested positive with hospital-associated SARS-CoV-2 infection after cardiac surgery. The study investigators hypothesized that early infection could be associated with worse postoperative outcomes; hence 2 groups were considered: (1) an early hospital-associated SARS-CoV-2 infection group comprising patients who had a positive molecular test result ≤7 days after surgery, with or without symptoms; and (2) a late hospital-associated SARS-CoV-2 infection group comprising patients whose test positivity occurred >7 days after surgery, with or without symptoms. The primary outcome was 30-day mortality. Secondary outcomes included all-cause mortality or morbidity at early follow-up and SARS-CoV-2-related hospital readmission. RESULTS: A total of 87 patients were included in the study. Of those, 30 were in the early group and 57 in the late group. Overall, 30-day mortality was 8%, and in-hospital mortality was 11.5%. The reintubation rate was 11.4%. Early infection was significantly associated with higher mortality (adjusted OR, 26.6; 95% CI, 2, 352.6; P < .01) when compared with the late group. At 6-month follow-up, survival probability was also significantly higher in the late infection group: 91% (95% CI, 83%, 98%) vs 75% (95% CI, 61%, 93%) in the early infection group (P = .036). Two patients experienced COVID-19-related rehospitalization. CONCLUSIONS: In this multicenter analysis, hospital-associated SARS-CoV-2 infection resulted in higher than expected postoperative mortality after cardiac surgery, especially in the early infection group.

Total arterial coronary artery bypass grafting in patients with preoperative anemia.

OBJECTIVES: Blood transfusions after coronary artery bypass grafting (CABG) has been associated to adverse outcomes, especially in anemic patients. However, little is known about the influence of the modality of revascularization. Total arterial revascularization (TAR) was shown to reduce postoperative transfusion when compared to saphenous vein-based (SV)-CABG (LIMA plus one/more SV grafts). We, therefore, aimed to investigate the impact of TAR-CABG versus SV-CABG on blood products use and perioperative outcomes in patients with preoperative anemia, normally at higher risk for postoperative transfusions. METHODS: From a cohort of 936 patients with mild preoperative anemia undergoing primary elective on-pump CABG, 166 matched pairs of patients undergoing either TAR- or SV-CABG were obtained. Anemia was defined as hemoglobin level <13 g/dl for men and <12 g/dl for women. The primary endpoint was the evaluation of red packed cells (RPC) use over the entire hospital stay. RESULTS: TAR patients showed significantly reduced RPC usage compared with SV (mean difference 0.45 units). TAR patients had a reduced intubation time (mean difference 7.6 h) and were discharged 1.24 days earlier than SV patients. Pneumonia and acute kidney injury were doubled among SV patients. Adjusted regression showed that TAR technique is a predictor of reduced RPC unit use regardless of age and EuroSCORE II (odds ratio: 0.63, p < .01). CONCLUSION: Patients with preoperative anemia might benefit from TAR regardless of age or calculated operative risk. TAR-CABG was associated to reduced postoperative use of blood products and postoperative length of stay in comparison with SV-CABG in this subset of patients.

Management of Patients With Aortocoronary Saphenous Vein Graft Aneurysms: JACC State-of-the-Art Review.

Saphenous vein graft aneurysms (SVGAs) following coronary artery bypass grafting (CABG) surgery were first described in 1975. Although rare, in the absence of a prompt diagnosis, SVGAs can be responsible for serious complications and adverse outcomes. The clinical presentation of SVGAs described in the literature can vary from an asymptomatic patient with an incidental radiological finding to a profoundly shocked patient with life-threatening hemorrhage secondary to SVGA rupture. Improvements in diagnostic tools within the last decade, such as multislice computed tomographic scanning, has enabled early detection of SVGAs, and therefore, an expansion of the current management options. In this review, the current data and knowledge about clinical presentation, diagnosis, natural history, and treatment of SVGAs are updated, with a specific emphasis on the evolution of management strategies of this rare complication over the last 45 years. Finally, a clinical algorithm to guide decision-making and management is proposed.

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer.

BACKGROUND: Single-agent pembrolizumab treatment of hormone receptor-positive metastatic breast cancer (MBC) has demonstrated modest clinical responses. Little is known about potential biomarkers or mechanisms of response to immune checkpoint inhibitors (ICIs) in patients with HR+ MBC. The present study presents novel immune correlates of clinical responses to combined treatment with CDK4/6i and ICI. METHODS: A combined analysis of two independent phase I clinical trials treating patients with HR+ MBC was performed. Patients treated with the combination of the CDK4/6i palbociclib+the ICI pembrolizumab+the aromatase inhibitor (AI) letrozole (palbo+pembro+AI) were compared with patients treated with pembrolizumab+AI (pembro+AI). Peripheral blood mononuclear cells collected at pretreatment, 3 weeks (cycle 2 day 1) and 9 weeks (cycle 4 day 1) were characterized by high-parameter flow cytometry to assess baseline immune subset composition and longitudinal changes in response to therapy. RESULTS: In the peripheral blood, higher pretreatment frequencies of effector memory CD45RA+ CD8+ T cells and effector memory CD4+ T cells were observed in responders to palbo+pembro+AI. In contrast, this was not observed in pembro+AI-treated patients. We further characterized T-cell subsets of effector-like killer cell lectin-like receptor subfamily G member 1 (KLRG1+) ICOS+ CD4+ T cells and KLRG1+ CD45RA+ CD8+ T cells as baseline biomarkers of response. In comparison, pretreatment levels of tumor-infiltrating lymphocyte, tumor mutation burden, tumor programmed death-ligand 1 expression, and overall immune composition did not associate with clinical responses. Over the course of treatment, significant shifts in myeloid cell composition and phenotype were observed in palbo+pembro+AI-treated patients, but not in those treated with pembro+AI. We identified increased fractions of type 1 conventional dendritic cells (cDC1s) within circulating dendritic cells and decreased classical monocytes (cMO) within circulating monocytes only in patients treated with palbociclib. We also demonstrated that in palbociclib-treated patients, cDC1 and cMO displayed increased CD83 and human leukocyte antigen-DR isotype (HLA-DR) expression, respectively, suggesting increased maturation and antigen presentation capacity. CONCLUSIONS: Pre-existing circulating effector CD8+ and CD4+ T cells and dynamic modulation of circulating myeloid cell composition denote response to combined pembrolizumab and palbociclib therapy for patients with HR+ MBC. TRIAL REGISTRATION NUMBER: NCT02778685 and NCI02648477.

Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels.

OBJECTIVES: Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH. METHODS: At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be "cryptogenic" (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data. RESULTS: All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups. CONCLUSIONS: In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient's pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.

Incidental gastric diverticulum in a young female with chronic gastritis: A case report.

INTRODUCTION: Gastrointestinal upset is a common presentation to surgical departments, often requiring investigation with endoscopy. Pathologies such as gastritis or ulcers are common culprits. Occasionally, rare or unusual pathologies, such as gastric diverticula as was seen in the case presented, are found. CASE PRESENTATION: A 26 year old female, with no known co-morbid conditions presented with a two week history of abdominal pain associated with nausea and vomiting. On further inquiry, she had one episode of blood stained vomiting, prompting investigation with an oesophagogastroduodenoscopy (OGD). Findings included diffuse haemorrhagic gastritis with a single outpouching measuring 1-2 cm in the gastric fundus. A gastric diverticulum was confirmed on barium swallow. Investigation with sonar and a Computed Tomography (CT) scan reported the stomach as normal. CONCLUSION: The patient was successfully treated non-operatively with proton pump inhibitor therapy for her concomitant gastritis. Gastric Diverticula are often associated with other gastric findings and their individual contribution varies from case to case. DISCUSSION: Gastric Diverticula are the manifestation of a common condition in an unusual location. Their clinical implications vary from being insignificant to life threatening when complicated by haemorrhage, perforation or malignant transformation. The associated symptoms are non-specific and diagnosis may be challenging. The case highlights the importance of selecting appropriate imaging modalities for luminal structures, being only diagnosed in 2 (OGD, Swallow) of the four modalities (incl. ultrasound and CT scan) used. Treatment may be conservative or surgical and is patient dependent. Written consent and ethical approval was obtained. The work is reported in line with the SCARE criteria.

Immediate Transfer for Clot Extraction in a Young Woman With Leukemia and Asparaginase-Associated Acute Cerebral Vein Thrombosis.

We present the case of an 18-year-old woman with B-cell acute lymphoblastic leukemia (ALL) who developed hemorrhagic stroke and epilepsia partialis continua due to acute cerebral vein thrombosis (CVT). The patient had 10 risk factors for CVT (including use of asparaginase chemotherapy for the ALL) and also unfortunately had 4 biomarkers for poor prognosis for outcome post-CVT diagnosis. Immediate transfer to a Comprehensive Stroke Center allowed for hyperacute neurointerventional clot extraction with rapid restoration of the patency of the superior sagittal sinus. This resulted in an unexpectedly favorable neurological outcome and simultaneously allowed for early resumption of chemotherapy for ALL after only a 5-day hiatus. Our case highlights the importance of immediate transfer of highest risk patients with multiple biomarkers for poor prognosis to a Comprehensive Stroke Center with endovascular and neurosurgical capabilities and the possibility of overcoming the odds of a poor outcome with venous clot extraction if medical management fails. Neurological deterioration due to escalating intracranial pressure with impending herniation may occur rapidly, and treatment at such facilities can be life-saving.