Parainfluenza virus infection associated with posterior reversible encephalopathy syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Posterior reversible encephalopathy syndrome is a clinical and radiological entity. The most accepted theory of posterior reversible encephalopathy syndrome is a loss of autoregulation in cerebral blood flow with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes, producing vasogenic edema. In infection-associated posterior reversible encephalopathy syndrome, a clinical pattern consistent with systemic inflammatory response syndrome develops. Parainfluenza virus has not been reported in the medical literature to be associated with posterior reversible encephalopathy syndrome.</p> <p>Case presentation</p> <p>We report herein the case of a 54-year-old Caucasian woman with posterior reversible encephalopathy syndrome associated with parainfluenza virus infection who presented with generalized headache, blurring of vision, new-onset seizure and flu-like symptoms.</p> <p>Conclusion</p> <p>Infection-associated posterior reversible encephalopathy syndrome as well as hypertension-associated posterior reversible encephalopathy syndrome favor the contribution of endothelial dysfunction to the pathophysiology of this clinicoradiological syndrome. In view of the reversible nature of this clinical entity, it is important that all physicians are well aware of posterior reversible encephalopathy syndrome in patients presenting with headache and seizure activity. A detailed clinical assessment leading to the recognition of precipitant factors in posterior reversible encephalopathy syndrome is paramount.</p

A Ribosomal Misincorporation of Lys for Arg in Human Triosephosphate Isomerase Expressed in Escherichia coli Gives Rise to Two Protein Populations

We previously observed that human homodimeric triosephosphate isomerase (HsTIM) expressed in Escherichia coli and purified to apparent homogeneity exhibits two significantly different thermal transitions. A detailed exploration of the phenomenon showed that the preparations contain two proteins; one has the expected theoretical mass, while the mass of the other is 28 Da lower. The two proteins were separated by size exclusion chromatography in 3 M urea. Both proteins correspond to HsTIM as shown by Tandem Mass Spectrometry (LC/ESI-MS/MS). The two proteins were present in nearly equimolar amounts under certain growth conditions. They were catalytically active, but differed in molecular mass, thermostability, susceptibility to urea and proteinase K. An analysis of the nucleotides in the human TIM gene revealed the presence of six codons that are not commonly used in E. coli. We examined if they were related to the formation of the two proteins. We found that expression of the enzyme in a strain that contains extra copies of genes that encode for tRNAs that frequently limit translation of heterologous proteins (Arg, Ile, Leu), as well as silent mutations of two consecutive rare Arg codons (positions 98 and 99), led to the exclusive production of the more stable protein. Further analysis by LC/ESI-MS/MS showed that the 28 Da mass difference is due to the substitution of a Lys for an Arg residue at position 99. Overall, our work shows that two proteins with different biochemical and biophysical properties that coexist in the same cell environment are translated from the same nucleotide sequence frame

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Immunosuppressive activity of proteases in cervical carcinoma

Objective. The host immune response is essential for restraining both HPV infections and HPV-related cervical cancer. We previously reported a direct correlation between proteolytic activity and malignant progression from precursor lesions to invasive cervical carcinoma. The present study was undertaken to investigate whether proteinases from cervical carcinoma extracts and representative purified proteinases involved in tumor progression could regulate lymphocyte proliferation to phytohemagglutinin (PHA) mitogen. Methods. Extracts were prepared from tissue samples obtained from patients with invasive cervical squamous carcinoma, squamous intra-epithelial lesions or women with normal cervix. Lymphocytes obtained from a single healthy donor were pre-incubated with one of these extracts in the presence or absence of proteinase inhibitors, and stimulated with PHA during 72 h. The proliferative response was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- tetrazolium bromide (MTT) method (re-validated with thymidine uptake). Results. Lymphocyte proliferation was significantly decreased by cervical carcinoma extracts, while only slightly decreased by squamous intra-epithelial lesions or normal extracts. Inhibitor assays indicated that proteinases from cervical carcinoma were responsible for 53.30% of total suppressive activity. We found that purified enzymes such as trypsin, cathepsin B, uPA and type IV collagenase suppressed the proliferative response in a dose-dependent fashion. Conclusions. Our data suggest that in addition to the classic role in tumor invasion, proteases could represent an immune evasion mechanism in cervical carcinoma. © 2005 Elsevier Inc. All rights reserved

Short and Long-Term Adverse Events in Patients on Temporary Circulatory Support before LVAD: An IMACS Registry Analysis.

Purpose: Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival after LVAD. We aim to characterize complication burden in those requiring preop TCS. Methods: We analyzed 13,511 adults with CF-LVADs in IMACS (2013-2017) according to need for preop TCS (n=5632) vs. no TCS (n=7879, Profiles 1-3). Rates of bleeding, device-related infection and stroke in early (\u3c 3 months) and late (\u3e 3 months) postop periods in those with and without TCS were compared. Results: TCS included ECMO (n=1138), IABP (n=3901), and other-TCS (n=593). Compared with nonTCS Profile 1-3 patients, TCS patients were more likely to have ischemic cardiomyopathy, Profile 1 status (TCS=41% vs 5.3%), with lower albumin preop. Within 3 months postop, patients previously on ECMO or IABP had more major bleeding, hemorrhagic and ischemic strokes, and gastrointestinal bleeding (GIB) than nonTCS patients, while patients on other-TCS had more early device-related infections (Figure, A). After 3 months postop, while clinically of small difference, those on ECMO or other-TCS had statistically lower rates of major bleeding and GIB compared to non-TCS, while IABP group had higher bleeding rates (Figure, B). All groups had low and similar late ischemic stroke rates (Figure, B). Short- and long-term survivals were worst in ECMO compared with other groups (6 mo: 71% ECMO, 84% IABP, 84% other-TCS, 88% non-TCS. 48 mo: 45% ECMO, 51% IABP, 53% other-TCS, 56% non-TCS, p\u3c0.0001). Strokes and multi-organ failure were 2 most common causes of death. Conclusion: Patients requiring TCS prior to durable LVADs had higher rates of early postop adverse events compared to those without TCS. Late event rates were similar. ECMO is associated with very high early ischemic stroke, bleeding burdens and mortality. Multi-organ failure and stroke are the most common causes of death in TCS patients. These results suggest that the extreme CS phenotype needing ECMO warrants a higher-level Profile status, such as “INTERMACS 0”

Longitudinal Impact of Temporary Mechanical Circulatory Support on Durable Left Ventricular Assist Device Outcomes: An IMACS Registry Analysis.

Purpose: To characterize longitudinal outcomes of durable LVAD patients presenting with preoperative cardiogenic shock according to temporary circulatory support (TCS) management strategy. Methods: Patients (n=13813) enrolled into IMACS (2013-2017) supported with continuous flow LVADs were analyzed. Patients were grouped according to use of TCS vs. no TCS by Profile. TCS patients were subgrouped according to support type (ECMO, IABP, other-TCS) and morbidity and mortality were analyzed. Results: TCS was used in 5631 (42%) patients in IMACS. Of these, ECMO was used in 1138 (20%), IABP in 3901 (69%), and other-TCS in 595 (11%). More patients on ECMO had ischemic cardiomyopathy (52% ECMO, 44% IABP, 42% Other-TCS, 40% no-TCS, p \u3c 0.001) and were less like to be bridge-to-transplant with higher preop bilirubin and lower albumin than IABP, other-TCS, and noTCS. Fewer IABP patients were categorized as profile I (78% ECMO, 30% IABP, 45% Other TCS, p \u3c 0.001). Perioperatively, ECMO patients required BiVAD more frequently (22% ECMO, 5% IABP, 7% Other-TCS, 3% no-TCS, p\u3c 0.001) and experienced longer ICU LOS/days (24 d ECMO, 14 d IABP, 18 d Other-TCS, 11d no-TCS, p \u3c0.001). ECMO supported patients had the lowest short- and long-term survivals, while IABP vs other-TCS vs noTCS has similar survivals (table). ECMO conferred inferior survival in BiVAD patients as well (48 mo: 45% ECMO, 51% IABP, 53% Other-TCS, 56% no-TCS, p \u3c 0.001). Conclusion: In cardiogenic shock patients, the use of ECMO prior to LVAD was associated with lower survival, longer ICU stay and more RV failure compared to other TCS. ECMO patients with persistent RV failure have the worst prognosis

Short- and long-term adverse events in patients on temporary circulatory support before durable ventricular assist device: An IMACS registry analysis

BACKGROUND: Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS. METHOD: We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1-3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013-2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (<3 months) and late (≥3 months) post-operative periods. RESULTS: TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p < 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS. CONCLUSIONS: Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS "0."status: publishe