Onset Of Severe Symptoms Research Articles

Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma

Cytokine release syndrome (CRS) is the most common complication of chimeric antigen receptor redirected T cells (CAR-T) therapy. CAR-T toxicity management has been greatly improved, but CRS remains a prime safety concern. Here we follow serum cytokine levels and circulating immune cell transcriptomes longitudinally in 26 relapsed/refractory multiple myeloma patients receiving the CAR-T product, ciltacabtagene autoleucel, to understand the immunological kinetics of CRS. We find that although T lymphocytes and monocytes/macrophages are the major overall cytokine source in manifest CRS, neutrophil activation peaks earlier, before the onset of severe symptoms. Intracellularly, signaling activation dominated by JAK/STAT pathway occurred prior to cytokine cascade and displayed regular kinetic changes. CRS severity is accurately described and potentially predicted by temporal cytokine secretion signatures. Notably, CAR-T re-expansion is found in three patients, including a fatal case characterized by somatic TET2-mutation, clonal expanded cytotoxic CAR-T, broadened cytokine profiles and irreversible hepatic toxicity. Together, our findings show that a latent phase with distinct immunological changes precedes manifest CRS, providing an optimal window and potential targets for CRS therapeutic intervention and that CAR-T re-expansion warrants close clinical attention and laboratory investigation to mitigate the lethal risk.

Modified Endothelial Activation and Stress Index (mEASIX) Score and Immune Effector Cell Associated Haematotoxicity (ICAHT) Following Varnimcabtagene Autoleucel (IMN-003A), a CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy, in the Phase-2 Study (IMAGINE)

Background: Varnimcabtagene autoleucel (IMN-003A) is an anti-CD19 CAR-T cell immunotherapy for patients (pts) with relapsed refractory B cell malignancies (RR BCM) in first-in-India Industry Phase 2 IMAGINE study, administered in a fractionated (10%/30%/60%) infusion protocol. Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) are commonly associated adverse events with CAR-T cell therapy. The modified Endothelial Activation and Stress Index (mEASIX) score [lactate dehydrogenase (LDH) (U/L) × CRP (mg/dL) / platelets (PLT) (10 9 cells/L)] is a prognostic predictor of outcomes for patients in post-allogeneic transplant setting. Elevated LDH and low PLT levels have been associated with severe ICANS, and high IL-6 level is a recognized marker for CRS. Immune Effector Cell Associated Hemato-Toxicity (ICAHT) represents the most common toxicity after CAR-T cell therapy. CAR-HEMATOTOX score is used to risk stratify patients for cytopenia. This abstract reviews the mEASIX score and ICAHT for pts in the IMAGINE study, prognostic value of mEASIX for CRS, ICANS and responses, and correlation of ICAHT score with outcomes. Methods: mEASIX scores were calculated for each pt at lymphodepletion (LD), D0, D+1 and D+4. CRS and ICANS were graded as per American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Pts were monitored for ICAHT post CAR-T infusion and risk stratified using CAR-HEMATOTOX score. ICAHT was graded using CTCAE v5.0. Appropriate statistical tools were used for analysis. Results: Twenty-four RR BCM pts (12 B-ALL; 12 B-NHL) were treated with var-cel in this study. Overall response rate (ORR) was 91.7% (22/24) at D+28 (B-ALL 91.7%; B-NHL 91.7%) and 80.9% (17/21) at D+90 (B-ALL 80%; B-NHL 81.8%). AESIs reported were CRS (Grade [G] 1 62.5%; G3+ 4.2%; overall 66.7%); ICANS (G1 4.2%; G3+ 0%; overall 4.2%); neutropenia (G3+ 91.7%; overall 100%); anemia (G3+ 29.2%; overall 95.8%); and thrombocytopenia (G3+ 20.8%; overall 91.7%). CRS median onset was D+5 and duration 3 days. No G3+ ICANS was reported. Treatment related mortality was 4.2% (n=1/24, CRS); 3 pts died of disease progression. The mEASIX score at LD, D0, D+1 and D+4 and its correlation with CRS, ICANS and responses is shown in Table 1. At D+1, mEASIX score <1 was predictive for responses (entire cohort, p=0.05; OR 15.0). At D+4, mEASIX score >1 was nearing statistical significance (p=0.07) for CRS (all grades; OR 6.0). However, mEASIX score at other timepoints was not predictive for CRS, ICANS or responses. The incidence of ICAHT was 100% (all grades; n=24), 100% neutropenia (G3+ 91.7%); 95.8% (n=23) anemia (G3+ 29.2%) and 91.7% (n=22) thrombocytopenia (G3+ 20.8%). The median time (range) to resolution of anemia, neutropenia and thrombocytopenia was 90 (11-270), 17.5 (1-181) and 9 (1-181) days respectively. Classical, biphasic and prolonged cytopenia pattern was seen for Neutropenia in 6, 2 and 16 pts respectively; for Anemia in 2, 0 and 21 patients respectively and for Thrombocytopenia in 4, 1 and 17 patients respectively. Overall, all patients, except two, were pancytopenic during their treatment course. Figure 1 shows the temporal course of var-cel mediated haematotoxicity (ICAHT). Two pts (8.3%) each received red cells, platelets, G-CSF and romiplostim; majority did not need supportive treatment. CAR-HEMATOTOX score was low risk in 18 pts and high risk in 6 pts. There was no statistical correlation between low risk (18 pts) and high risk (6 pts) with responses (17 pts, p=0.92) or with relapse / disease progression (9 pts, p=0.21). Conclusions: This is the first-in-India industry study evaluating mEASIX and ICAHT in patients treated with CAR-T cell therapy. mEASIX score <1 was predictive of responses at D+1 and score >1 at D+4 was mildly predictive of CRS. All patients developed ICAHT but only a small number of patients needed supportive treatment. Overall, var-cel was well tolerated with manageable cytopenia. The CAR-HEMATOTOX score was not predictive of relapse / disease progression in the IMAGINE study. mEASIX score may be used as an early predictor of CRS for permissive use of Tocilizumab before onset of severe symptoms. The ICAHT profile was heterogeneous, probably reflective of hematopoietic reserve, lines of treatment and downstream immune responses. The predictive role of mEASIX score and ICAHT profile in a real-world setting needs further study.

Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17.

Spinocerebellar Ataxia Type 17 (SCA17) is the most recently identified member of the polyglutamine (polyQ) family of disorders, resulting from abnormal CAG/CAA expansion in the TATA box-binding protein (TBP), an initiation factor essential for of all eukaryotic transcription. A largely autosomal dominant inherited disease, SCA17, is unique in both its heterogeneous clinical presentation and low incidence of genetic anticipation, the phenomenon in which subsequent generations inherit longer polyQ expansions that yield earlier and more severe symptom onset. Like other polyQ disease family members, SCA17 patients experience progressive ataxia and dementia, and treatments are limited to preventing symptoms and increasing quality of life. Here, we report 2 new Drosophila models that express human TBP with polyQ repeats in either wild-type or SCA17 patient range. We find that TBP expression has age- and tissue-specific effects on neurodegeneration, with polyQ-expanded SCA17 protein expression generally having more severe effects. In addition, SCA17 model flies accumulate more aggregation-prone TBP, with a greater proportion localizing to the nucleus. These new lines provide a new resource for the biochemical characterization of SCA17 pathology and the future identification of therapeutic targets.

The Role of Multimodality Imaging in Pediatric Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies.

Neurological Wilson’s Disease Signs—Hepatic Encephalopathy or Copper Toxicosis?

Wilson's disease (WD) is a rare autosomal recessive (AR) disorder resulting from mutations in the ATP7B gene, which is responsible for the encryption of transmembrane copper transporting ATPase. The symptomatic presentation of the disease is estimated to be about 1 in 30,000. The impairment of ATP7B function results in a copper overload in hepatocytes, which further leads to liver pathology. This copper overload also occurs in other organs, most particularly in the brain. This could then cause the occurrence of neurological and psychiatric disorders. Symptoms differ substantially and most often occur between the ages of 5 and 35 years. Early symptoms are commonly hepatic, neurological, or psychiatric. While disease presentation is most often asymptomatic, it could also range as far as to include fulminant hepatic failure, ataxia, and cognitive disorders. Various treatments are available for Wilson's disease, including chelation therapy and zinc salts, which can reverse copper overload through different mechanisms. In select cases, liver transplantation is recommended. New medications, such as tetrathiomolybdate salts, are currently being investigated in clinical trials. With prompt diagnosis and treatment, prognosis is favorable; however, diagnosing patients before the onset of severe symptoms is a significant concern. Early screening for WD could help in diagnosing patients earlier and improving treatment outcomes.

From Blocking Shots to Blocking GI Transit, This Professional Basketball Player Does It All: A Case Report on Small Bowel Obstruction

Small bowel obstructions (SBO) are a commonly encountered diagnosis within emergency departments. Typically, these patients have evident risk factors including, but not limited to, prior abdominal surgery, personal or family history of gastrointestinal disorders, femoral and inguinal hernias, or neoplasm. In this case, we describe an SBO in a female, professional athlete whose swift, severe symptom onset, rapid resolution with conservative treatment, lack of identifiable risk factors, and prompt return to high level competition without recurrence are certainly unique. A female professional basketball player in her mid-20's with no past medical history presented with a seven-hour history of worsening abdominal pain beginning in the epigastric region and migrating to the right lower quadrant. Physical exam did not reveal abdominal distension, tympany to percussion, or high-pitched bowel sounds. Initial differential diagnosis included appendicitis, ruptured ectopic pregnancy, and other genitourinary pathology. Computed tomography with contrast revealed distended loops of small bowel with wall thickening, enhancement, and decompressed loops of bowel distally, consistent with an SBO. Symptoms resolved after 24 hours with conservative treatment, including decompression with a nasogastric tube. The athlete returned to full participation five days after initial presentation without recurrence of symptoms. Outpatient gastroenterology workup was negative for predisposing conditions. This presentation is rare in the absence of bowel pathology, family history, or prior abdominal surgery. Perhaps, her profession as an athlete, with frequent air travel and extensive exercise, may have contributed to this unique presentation. This case report should serve as a reminder to all providers that SBOs can occur in young, active patients devoid of risk factors. Even in the absence of typical signs on physical examination, providers should use imaging as adjuncts based on their clinical gestalt and utilize conservative management, when appropriate, to maximize chances of recovery with minimal morbidity.

An approach to the understanding of the clinical-etiopathological aspect of COVID-19 (SARS-CoV-2)

Currently, the world is facing a health and socioeconomic crisis caused by the novel coronavirus disease COVID-19. On 11 March 2020, the World Health Organization (WHO) has declared this disease as a pandemic. The condition (COVID-19) is an infectious disorder triggered by a newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2. Most of the COVID-19 infected patients will experience mild to moderate respiratory symptoms and recover without any unique therapy. Assessment of the clinical and epidemiological characteristics of SARS-CoV-2 cases suggests the infected patients will not be contagious until the onset of severe symptoms and affects the other organs. Well-differentiated cells of apical airway epithelia communicating with ACE2 were promptly infected to SARS-CoV-2 virus. But the expression of ACE 2 in poorly differentiated epithelia facilitated SARS spike (S) protein-pseudo typed virus entry and it is replicated in polarized epithelia and especially exited via the apical surface. Limiting the transmission of COVID-19 infection & its prevention can be regarded as a hierarchy of controls. In this article, we briefly discuss the most recent advances in respect to aetiology, pathogenesis and clinical progression of the disease COVID-19.

Easix and Modified-Easix Are Early Predictors of Severe Cytokine Release Syndrome and Neurotoxicity in Patients Treated with Chimeric Antigen Receptor T Cells

Easix and Modified-Easix Are Early Predictors of Severe Cytokine Release Syndrome and Neurotoxicity in Patients Treated with Chimeric Antigen Receptor T Cells

2019 AATS/ACC/ASE/SCAI/STS expert consensus systems of care document: A proposal to optimize care for patients with valvular heart disease: A Joint Report of the American Association for Thoracic Surgery, American College of Cardiology, American Society of Echocardiography, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

This statement was commissioned as a Multisociety Expert Consensus Systems of Care Document by the American Association for Thoracic Surgery (AATS), American College of Cardiology (ACC), American Society of Echocardiography (ASE), Society for Cardiovascular Angiography and Interventions (SCAI), and

Purulent pericarditis and Pasteurella multocida: An extremely rare combination

Abstract Purulent pericarditis is a rare entity, defined as the presence of neutrophilic pericardial effusion which is infected by a bacterial, fungus or parasite agent. The diagnosis can be challenging, especially if patients have taken previous antibiotic therapy; on the other hand the recognition of this pathology is often made late, with the onset of severe symptoms or signs of cardiac tamponade or even only at the autopsy. The authors describe the case of a 82-year-old woman with history of extensive laceration of the right lower limb from a dog bite in July 2016, admitted to the Cardiology Department one month later for Acute Pericarditis. During hospitalization she maintained recurrent fever peaks despite the treatment with non-steroidal anti-inflammatory drugs and colchicine. She collected blood cultures and repeated echocardiogram showed increased pericardial effusion with no signs of hemodynamic compromise. Blood cultures revealed the presence of Pasteurella multocida. Due to clinical suspicion of purulent pericarditis, pericardiocentesis was performed with drainage of liquid compatible with exudate and the patient was presented to the Cardiothoracic Surgery Department for pericardiotomy and adequate drainage of the liquid. Histological examination confirmed the diagnosis of Acute Pericarditis. It should be noted that Pasteurella is a very frequent agent (50-90%) in the gastrointestinal tract and nasopharynx of many domestic animals, namely dogs. The authors emphasize the need to aggressively treat this pathology, since untreated death is inevitable.

P.36 - Limb girdle muscular dystrophy type 2I: Lack of correlation between clinical severity, histopathological alterations and levels of glycosylated α-dystroglycan in patients homozygous for the common FKRP mutation

Limb girdle musclular dystrophy type 2I (LGMD2I) is a progressive disorder caused by mutations in the FuKutin-Related Protein gene (FKRP). LGMD2I displays clinical heterogeneity with onset of severe symptoms in early childhood to mild calf and thigh hypertrophy in the second or third decade. Patients homozygous for the common FKRP mutation c.826C > A (p.Leu276Ile) show phenotypes within the milder end of the clinical spectrum. However, this group also manifests substantial clinical variability. FKRP deficiency causes hypoglycosylation of α-dystroglycan; a component of the dystrophin associated glycoprotein complex. α-Dystroglycan hypoglycosylation is in turn associated with loss of interaction with -, and hence, depletion of laminin α2. Here, we have attempted to clarify if the clinical variability seen in patients homozygous for c.826C > A, is related to alterations in muscle fiber pathology, α-DG glycosylation levels, levels of laminin α2 as well as the capacity of α-DG to bind to laminin. We have assessed vastus lateralis muscle biopsies from 25 LGMD2I patients harboring the c.826C > A/c.826C > A genotype by histological examination, immunohistochemistry and immunoblotting. No clear correlation was found between clinical severity, as determined by self-reported walking function, and the above features, suggesting that more complex molecular processes are contributing to the progression of disease.

Identification of potential biomarkers of hepatotoxicity by plasma proteome analysis of arsenic-exposed carp Labeo rohita

Arsenic (As) is a toxic environmental contaminant and potential human carcinogen. Chronic intake of arsenic-contaminated water and food leads to arsenicosis, a major public health problem in many parts of the world. Early detection of arsenic toxicity would greatly benefit patients; however, the detection of arsenicosis needs to be done early before onset of severe symptoms in which case the tools used for detection have to be both sensitive and reliable. In this context, the present study investigated plasma proteome changes in arsenic-exposed Labeo rohita, with the aim of identifying biomarkers for arsenicosis. Changes in the plasma proteome were investigated using gel-based proteomics technology. Using quantitative image analysis of the 2D proteome profiles, 14 unique spots were identified by MALDI-TOF/TOF MS and/or LC–MS/MS which included Apolipoprotein-A1 (Apo-A1) (6 spots), α-2 macroglobulin-like protein (A2ML) (2 spots), transferrin (TF) (3 spots) and warm-temperature acclimation related 65kDa protein (Wap65). The proteome data are available via ProteomeXchange with identifier PXD003404. Highly abundant protein spots identified in plasma from arsenic-exposed fish i.e. Apo-A1 (>10-fold), A2ML (7-fold) and Wap65 (>2-fold) indicate liver damage. It is proposed that a combination of these proteins could serve as useful biomarkers of hepatotoxicity and chronic liver disease due to arsenic exposure.

Limb girdle muscular dystrophy type 2I: No correlation between clinical severity, histopathology and glycosylated α-dystroglycan levels in patients homozygous for common FKRP mutation

Limb girdle muscular dystrophy type 2I (LGMD2I) is a progressive disorder caused by mutations in the FuKutin-Related Protein gene (FKRP). LGMD2I displays clinical heterogeneity with onset of severe symptoms in early childhood to mild calf and thigh hypertrophy in the second or third decade. Patients homozygous for the common FKRP mutation c.826C>A (p.Leu276Ile) show phenotypes within the milder end of the clinical spectrum. However, this group also manifests substantial clinical variability.FKRP deficiency causes hypoglycosylation of α-dystroglycan; a component of the dystrophin associated glycoprotein complex. α-Dystroglycan hypoglycosylation is associated with loss of interaction with laminin α2, which in turn results in laminin α2 depletion. Here, we have attempted to clarify if the clinical variability seen in patients homozygous for c.826C>A is related to alterations in muscle fibre pathology, α-DG glycosylation levels, levels of laminin α2 as well as the capacity of α-DG to bind to laminin. We have assessed vastus lateralis muscle biopsies from 25 LGMD2I patients harbouring the c.826C>A/c.826C>A genotype by histological examination, immunohistochemistry and immunoblotting. No clear correlation was found between clinical severity, as determined by self-reported walking function, and the above features, suggesting that more complex molecular processes are contributing to the progression of disease.

Pitfalls and problems in the management of the acute abdomen

The acute abdomen is defined as the rapid onset of severe symptoms that may indicate potentially life-threatening intra-abdominal pathology which requires urgent surgical intervention. The article reviewed the pitfalls and problems in the management of the acute abdomen. The importance of simultaneous examination and resuscitation, recognizing the need for physiological support, and maintaining the rapid progress toward a diagnosis and definitive treatment are emphasized.

Late Onset of Severe Symptoms in a Patient with Wolff-Parkinson-White Syndrome with Misleading ECG Pattern of the Accessory Pathway Origin Undergoing Successful Ablation

The case of a female patient with symptomatic Wolff-Parkinson-White syndrome is presented with very late onset of symptoms at the age of 65 years, who had an apparent left-sided posteroseptal accessory pathway, which was ablated via a right-sided approach. A subepicardial location was strongly suspected within the coronary sinus ostium at the origin of the middle cardiac vein by applying both ECG and fluoroscopic criteria.

Asymptomatic Severe Aortic Stenosis in the Elderly

ObjectivesThis study sought to assess the natural history and optimal timing of surgery in elderly patients with severe asymptomatic aortic stenosis (AS). BackgroundAS is increasingly diagnosed in an aging population, and large numbers of elderly patients are undergoing aortic valve procedures. However, the average age of patients represented in most natural history studies on AS is between 60 and 70 years. MethodsA total of 103 consecutive patients >70 years of age (51 female; mean age 77 ± 5 years) with asymptomatic severe AS (peak aortic jet velocity [AV-Vel] 4.7 ± 0.6 m/s) were prospectively followed. ResultsDuring follow-up, 91 events occurred, including an indication for aortic valve replacement in 82 patients and cardiac deaths in 9, respectively. Event-free survival was 73%, 43%, 23%, and 16% at 1, 2, 3, and 4 years, respectively. Physical mobility was impaired in 29% of the patients, and symptom onset was severe (New York Heart Association functional class ≥III) in 43% of those who developed symptoms. Patients with AV-Vel ≥5.0 m/s had event-free survival rates of 21% and 6% at 2 and 4 years, respectively, compared with 57% and 23% for patients with AV-Vel <5.0 m/s (p < 0.001). Seventy-one patients underwent aortic valve replacement, and post-operative survival was 89% and 77% after 1 and 3 years, respectively. ConclusionsIn elderly patients with severe but asymptomatic AS, mild symptoms may be difficult to detect, particularly when mobility is impaired and severe symptom onset is common, warranting close clinical follow-up. Furthermore, a very high event rate can be expected, and cardiac deaths are not infrequent. Thus, elective aortic valve procedures may be considered in selected elderly patients at low procedural risk.

Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention.

Acute respiratory tract infection (ARTI) is the most common reason for antibiotic prescription in adults. Antibiotics are often inappropriately prescribed for patients with ARTI. This article presents best practices for antibiotic use in healthy adults (those without chronic lung disease or immunocompromising conditions) presenting with ARTI. A narrative literature review of evidence about appropriate antibiotic use for ARTI in adults was conducted. The most recent clinical guidelines from professional societies were complemented by meta-analyses, systematic reviews, and randomized clinical trials. To identify evidence-based articles, the Cochrane Library, PubMed, MEDLINE, and EMBASE were searched through September 2015 using the following Medical Subject Headings terms: "acute bronchitis," "respiratory tract infection," "pharyngitis," "rhinosinusitis," and "the common cold." Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected. Clinicians should test patients with symptoms suggestive of group A streptococcal pharyngitis (for example, persistent fevers, anterior cervical adenitis, and tonsillopharyngeal exudates or other appropriate combination of symptoms) by rapid antigen detection test and/or culture for group A Streptococcus. Clinicians should treat patients with antibiotics only if they have confirmed streptococcal pharyngitis. Clinicians should reserve antibiotic treatment for acute rhinosinusitis for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39°C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening). Clinicians should not prescribe antibiotics for patients with the common cold.

Impact of Preoperative Symptoms on Postoperative Survival in Severe Aortic Stenosis: Implications for the Timing of Surgery

The impact of symptoms on the natural history of patients with severe aortic stenosis (SAS) has been well documented. By contrast, the implications of preoperative symptoms on postoperative outcomes remain poorly defined. The long-term survival of 812 patients greater than 65 years old with SAS undergoing bioprosthetic aortic valve replacement (AVR) was analyzed according to their preoperative symptoms. Operative mortality was larger in New York Heart Association (NYHA) III-IV than in NYHA I-II patients (10% vs 6%, p = 0.036). Abrupt symptomatic deterioration from NYHA I to NYHA III-IV within the month preceding surgery was observed in 18% of NYHA III-IV patients and resulted in an increased operative mortality (17% vs 5% in NYHA I, p = 0.035). Long-term survival was also significantly worse in NYHA III-IV than in NYHA I-II patients (56% vs 72%, p = 0.002). Reduced long-term survival of NYHA III/IV patients was observed in subgroups with a left ventricular ejection fraction (LVEF) 0.50 or greater (58 vs. 74%, p = 0.008) and in those with a systolic pulmonary artery pressure (SPAP) less than 40 mm Hg (60% vs 74%, p = 0.014). By contrast, the presence of class III-IV symptoms did not influence outcome in patients with a LVEF less than 0.50 (51 vs. 55%, p = 0.34) or with a SPAP 40 mm Hg or greater (43% vs 48%, p = 0.78). In patients with SAS, preoperative NYHA III-IV symptoms, particularly of recent onset, are independently associated with excess short- and long-term postoperative mortality. This was particularly evident in patients with normal LV function or pulmonary artery pressures. These findings plead in favor of an earlier surgical correction of SAS, before the onset of severe symptoms, especially in low-risk patients.

Abstract WMP24: Thrombolysis within 48 hours after Basilar Artery Occlusion

Introduction: Recanalization therapies and their time window in basilar artery occlusion (BAO) remain empirical and vary among hospitals. Our institutional protocol for BAO does not follow the strict RCT-guided guidelines in hemispheric stroke, and advices thrombolysis up to 12 hours after sudden onset of severe symptoms, and 48 hours after onset of gradually progressing symptoms, provided that extensive infarction changes have not yet occurred. Objective: The aim was to analyse the importance of two fundamental variables, symptom duration and the extent of baseline infarction, on the outcome of thrombolysis-treated BAO. Methods: We prospectively gathered data from 184 consecutive patients with angiography-proven BAO in the Helsinki University Central Hospital, which receives all candidates for stroke thrombolysis in a catchment area of 1.5 million. We took advantage of frequent non-adherence to our management protocol and grouped patients according to "protocol violations" (PVs): exceeded symptom duration (time PV) and large-infarct PV. Patients were divided into 4 categories based on onset-to-treatment time (OTT). Intravenous alteplase (0.9 mg/kg) and concomitant full-dose heparin was administered in the majority of patients. Outcome variables were recanalization of BA, 3-month modified Rankin Scale (mRS) and 1-year mortality. Results: Patients with no PV had the best outcome (when recanalized, 51% had good outcome [mRS 0-2], and 62% were non-dependent [mRS 0-3]), followed by patients with time PV (42% and 58%, respectively). Over 90% of patients with large-infarct PV were dependent, institutionalized, or dead (mRS 4-6), even when recanalized. Compared with 37% in patients with no PV, 1-year mortality was higher in patients with both PVs (68.8%, p&lt;0.05) and large-infarct PV (64.7%, p&lt;0.01); but similar to patients with time PV (45.5%, p=0.61). Importantly, the outcome of recanalized BAO was similar among OTT categories. Conclusions: In the absence of extensive baseline infarct signs, recanalization of BAO up to 48 hours was seldom futile (mRS 4-6) and produced non-dependent outcomes in 60% of patients, which was virtually independent of the exact time window. We recommend a dedicated protocol for BAO in stroke patients screened for thrombolysis.

A now rarely seen anti-reflux device: The Angelchik prosthesis

CASE REPORT A 43­year­old male was presented to our upper gastrointestinal clinic with acute symptoms of reflux and dysphagia to both solids and liquids. He had undergone open anti­reflux surgery 15 years prior with the fitting of a now obsolete device—the Angelchik device. Until this episode, he had enjoyed a normal diet with well controlled gastroesophageal reflux disease (GERD) symptoms. He was listed for surgery due to the sudden onset of severe symptoms and inability to tolerate food. No erosion or injury to the esophagus was noted. However, it was evident that the prosthesis had moved into an abnormal position causing an acquired stenosis of the lumen (Figure 1). It was removed in its entirety and an immediate laparoscopic Nissen's fundoplication was performed. The patient made an uneventful recovery from the procedure and was back to eating a normal diet within two weeks of the procedure. DISCUSSION The Angelchik device was introduced in 1979 [1]. It consisted of a C­shaped ring of silicon fitted around the gastroesophageal junction. The ring was secured in the place by means a fitted Dacron tape. It was well favored at the time compared to other anti­reflux surgeries CLINICAL IMGAE OPEN ACCESS