Encephalitis as a Clinical Manifestation of COVID-19: A Case Series.

COVID-19 is a novel virus which causes a variety of clinical manifestations in the body, some of which are yet to be discovered. The main aim of our study is to highlight the neurological manifestations of COVID-19 as it is still new to the medical world, and to emphasize the fact that the physicians have to be wary of the possibility that patients affected by COVID-19 can present with encephalitis. Only a few studies are available so far regarding the neurological manifestations of this novel virus which highlights the need for this study. We present a case series of 4 patients who were found to have COVID-19 encephalitis. There is still no disease-defining test for diagnosis so the mainstay of diagnosis is exclusion of all the common causes of encephalitis. Brain magnetic resonance imaging and cerebrospinal fluid analysis performs an ancillary in the diagnostic tools. Our study also supports the use of IV tocilizumab (4-8 mg/kg) and IV methylprednisolone (0.5-2 mg/kg) as possible treatment options with good results, as the patients described in our case series responded well to these medications.

Design of thiamine analogues for inhibition of thiamine diphosphate (ThDP)-dependent enzymes: Systematic investigation through Scaffold-Hopping and C2-Functionalisation.

Thiamine diphosphate (ThDP), the bioactive form of vitamin B1, is an essential coenzyme needed for processes of cellular metabolism in all organisms. ThDP-dependent enzymes all require ThDP as a coenzyme for catalytic activity, although individual enzymes vary significantly in substrate preferences and biochemical reactions. A popular way to study the role of these enzymes through chemical inhibition is to use thiamine/ThDP analogues, which typically feature a neutral aromatic ring in place of the positively charged thiazolium ring of ThDP. While ThDP analogues have aided work in understanding the structural and mechanistic aspects of the enzyme family, at least two key questions regarding the ligand design strategy remain unresolved: 1) which is the best aromatic ring? and 2) how can we achieve selectivity towards a given ThDP-dependent enzyme? In this work, we synthesise derivatives of these analogues covering all central aromatic rings used in the past decade and make a head-to-head comparison of all the compounds as inhibitors of several ThDP-dependent enzymes. Thus, we establish the relationship between the nature of the central ring and the inhibitory profile of these ThDP-competitive enzyme inhibitors. We also demonstrate that introducing a C2-substituent onto the central ring to explore the unique substrate-binding pocket can further improve both potency and selectivity.

The risk factors for radial artery and saphenous vein graft occlusion are different.

Objectives. To determine risk factors for radial artery and saphenous vein graft occlusion during long-term follow-up after coronary artery bypass grafting (CABG). Methods: From a cohort of 119 patients who had received a radial artery graft, 76 - of whom 55 also had at least one saphenous vein graft - underwent a preplanned direct angiography and anthropometric, biochemical, and endothelial function assessment 7.6-12.1 (mean 8.9) years after CABG. Comorbidity, medication, and smoking habits were also recorded. The association between these parameters and conduit longevity was analyzed in univariable and multivariable logistic regression models. Results: Radial artery graft occlusions were associated with higher plasma levels of high-sensitive C-reactive protein and patency was best among patients with pharmacologically treated hypertension. The sole independent risk factor identified for saphenous vein graft occlusion was tobacco smoking 8-12 years postoperatively. Conclusion: Our data support the contention that the pathogenesis of radial artery graft failure is distinct from vein graft disease and is related to hypertension status and systemic inflammation. These risk factors are potential targets for preventive measures. Accordingly, the study supports the eventual design of personalized secondary prevention regimens.Clinical registration number: ISRCTN23118170.

Cardiac troponin I and T for ruling out coronary artery disease in suspected chronic coronary syndrome.

To compare the performance of high-sensitivity cardiac troponin I and T (hs-cTnI; hs-cTnT) in diagnosing obstructive coronary artery disease (CAD50) in patients with suspected chronic coronary syndrome (CCS). A total of 706 patients with suspected CCS, referred for Coronary Computed Tomography Angiography, were included. cTn concentrations were measured using the Singulex hs-cTnI (limit of detection [LoD] 0.08 ng/L) and Roche hs-cTnT (LoD 3 ng/L) assays. Obstructive coronary artery disease (CAD50) was defined as ≥ 50% coronary stenosis. Cardiovascular risk was determined by the NORRISK2-score. Median age of the patients was 65 (range 28-87) years, 35% were women. All patients had hs-cTnI concentrations above the LoD (median 1.9 [Q1-3 1.2-3.6] ng/L), 72% had hs-cTnT above the LoD (median 5 [Q1-3 2-11] ng/L). There was a graded relationship between hs-cTn concentrations and coronary artery calcium. Only hs-cTnI remained associated with CAD50 in adjusted analyses (OR 1.20 95% Confidence Interval [1.05-1.38]), p = 0.009). The C-statistics for hs-cTnI and hs-cTnT were 0.65 (95% CI [0.60-0.69]) and 0.60 (0.56-0.64). The highest specificity and negative predictive values for CAD50 were in the lowest NORRISK2-tertile. hs-cTn concentrations provide diagnostic information in patients with suspected CCS, with superior performance of hs-cTnI compared to hs-cTnT in regard to CAD50. The diagnostic performance appeared best in those with low cardiovascular risk.

Direct angiography demonstrates equal 8-12 years patency rates of radial artery and saphenous vein grafts.

Objectives: The benefits of coronary artery bypass surgery depend on lasting graft patency. To aid rational graft selection, the relative long-term merits of radial artery and saphenous vein grafts need to be determined by a gold standard method and with minimal clinically driven selection bias. Methods: The patency rates of various conduits were determined by direct angiography in 76 patients from a cohort of 119 undergoing coronary artery bypass grafting 7.6-12.1 (mean 8.9) years before. Results: 14 out of 76 radial artery and 10 out of 61 saphenous vein grafts were occluded (rates 0.18 and 0.16, respectively). Conclusion: The high long-term patency rate of saphenous vein grafts does not support a preferential use of the radial artery as a coronary artery bypass conduit. Clinical registration number: ISRCTN23118170.

Changes in symptoms of anxiety and depression following diagnostic angiography: a prospective cohort study.

Aims: Coronary angiography is the gold standard diagnostic test for coronary artery disease (CAD), and the diagnostic results can have an immediate effect on symptoms. The aim of this study was to explore the long-term impact of diagnostic angiography on symptoms of anxiety and depression in a group of patients without previous CAD. Methods and results: The prospective cohort study included 459 consecutive patients undergoing invasive angiography and was approved by the regional board of ethics. Data were collected at baseline and after 6 and 12 months using self-reports. Symptoms of anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS). The sample population had a mean age of 62 years and included 197 (43%) women. Fifty-three percent had hypertension, and 17% had diabetes. The diagnostic results indicated that 41% of patients had normal vessels; 21% had wall changes; and 38% had obstructive stenosis. No significant difference was found between the diagnostic groups at baseline regarding the levels of anxiety or depression. After 6 months, participants with obstructive stenosis had significantly lower levels of anxiety than those without obstructive stenosis. Improvements were observed in all groups over time in both HADS subscale scores; the largest improvement occurred in patients with obstructive stenosis. Conclusion: This study demonstrates that patients with normal coronary arteries or minimal coronary disease/non-obstructive coronary disease do not seem to obtain the same benefit from the receipt of information about their coronary status in terms of anxiety and depression as patients with significant obstructive stenosis.

Assessment of myocardial ischemia by strain dobutamine stress echocardiography and cardiac magnetic resonance perfusion imaging before and after coronary artery bypass grafting.

BACKGROUND: Following coronary artery bypass grafting (CABG), testing for myocardial ischemia by noninvasive imaging is often hampered by false-positive results. The aim of this study was to find test parameters with the best potential to identify myocardial ischemia in post-CABG patients. METHODS: Fifty-two consecutive patients scheduled for CABG, underwent both dobutamine stress echocardiography (DSE) and cardiac magnetic resonance first-pass perfusion imaging (CMR-FPPI) with adenosine vasodilation, before and 8-10 months after the surgical revascularization. A pathologic biphasic stress response (PBR) expresses the presence of contractile reserve during low-dose dobutamine that decreases to hypo- or akinesia provoked by high-dose dobutamine. During DSE, potential PBR, segmental wall-motion score (WMS) as well as peak-systolic longitudinal strain (PLS) at peak-dose dobutamine were assessed. RESULTS: Post-CABG, there was still a relatively high prevalence of ischemia-positive segments evaluated by deformation imaging, but the number of such segments was significantly lower by PBR (20% and 22%) compared with peak-dose strain and WMS (62% and 77%, respectively; P<.05). The use of PBR instead of peak-dose WMS and strain could reduce the number of false-positive test results post-CABG. CONCLUSION: Among all imaging modalities tested, PBR by WMS and strain may be useful parameters for identifying patients with the need for new revascularization. We furthermore found that DSE may be interpreted as positive when revealing at least three ischemia-positive segments. The sensitivity of these test modalities for detecting coronary restenosis needs to be determined in further studies on a cohort of symptomatic post-CABG patients.

Antiplatelet Therapy During PCI for Patients with Stable Angina and Atrial Fibrillation.

The pharmacological treatment options for anticoagulation in patients with atrial fibrillation (Afib) have increased with the introduction of novel oral anticoagulants, compared with earlier times, when vitamin K antagonist was the drug of choice. As they age, many Afib patients require percutaneous coronary intervention (PCI), necessitating antiplatelet medication in addition to anticoagulation therapy. Choosing the appropriate combination and duration of anticoagulation and antiplatelet therapies may be challenging in stable coronary artery disease (CAD) and even more complicated during and after coronary intervention with the introduction of additional antithrombotic drugs. In this article, we review the scientific basis for the recent guidelines for anticoagulation and antithrombotic therapy in patients with Afib and stable CAD before, during, and after elective PCI.

Changes in Right Ventricular Shape and Deformation Following Coronary Artery Bypass Surgery-Insights from Echocardiography with Strain Rate and Magnetic Resonance Imaging.

BACKGROUND: This study was designed to assess whether altered RV geometry and deformation parameters persisted well into the recovery period after presumably uncomplicated coronary artery bypass grafting (CABG). It was our hypothesis that the altered geometry of and load in the RV following pericardial opening would change both regional and global deformation indices for an extensive period postoperatively. METHODS AND RESULTS: Fifty-seven patients scheduled for CABG underwent preoperative and 8-10 months postoperative magnetic resonance imaging (MRI) for RV volume measurements, and resting echocardiography with assessment of geometry and RV mechanical function determined by tissue Doppler imaging (TDI) based longitudinal strain. Both MRI and echocardiography revealed postoperative dilatation of the RV apex, shortened longitudinal RV length but unchanged RV ejection fraction. Echocardiography parameters associated with filling of the right atrium showed signs of constraint with a reduced systolic filling fraction and increased right atrial size. Right ventricular segmental strain (-20 ± 13% vs. -29 ± 20% preoperatively; mean ±SD, P < 0.0001) was reduced postoperatively in parallel with TAPSE (1.3 ± 0.3 cm vs. 2.2 ± 0.4 cm; P < 0.0001). CONCLUSION: Post-CABG longitudinal motion of the RV lateral wall is reduced after uneventful CABG despite preserved RV ejection fraction and stroke volume. The discrepancy in various RV systolic performance indicators results from increased sphericity of the RV following opening the pericardium during surgery. Therefore, longitudinal functional parameters may underestimate RV systolic function for at least 8-10 months post-CABG. Changes in deformation parameters should thus always be interpreted in relation to changes in geometry.

Severe regional myocardial dysfunction by stress echocardiography does not predict the presence of transmural scarring in chronic coronary artery disease.

AIMS: Detection and correct localization of transmural lesions can be important for optimal treatment of patients with chronic coronary artery disease (CAD). The aim of the study was to investigate the ability of peak longitudinal ejection strain (PLS) to detect the presence and extent of scar-tissue in CAD patients with normal or near normal ejection fraction, in comparison to cardiac magnetic resonance (CMR). METHODS AND RESULTS: Before coronary artery bypass grafting, 57 patients underwent late gadolinium enhancement (LGE) CMR and echocardiography at rest and dobutamine stress (DS). According to the degree of LGE, segments were allocated to groups of none, subendocardial (1-50%), subtotal (51-75%), and total transmural scars (>75%). Dysfunctional segments were identified by PLS or wall motion scores (WMS). The finding of normal/near normal resting WMS and PLS, excellently identified segments without transmural LGE (AUC 94.0 CI 90.6-97.3 and AUC 85.7 CI 79.0-92.3, respectively). However, the finding of akinesia did not necessarily indicate transmural scarring. The negative predictive value was high (99%, CI 98-100%) while the positive predictive value was low. Detection-rates for subendocardial LGE were low. CONCLUSION: Normo- and slightly hypokinetic myocardium by resting WMS or strain detects the absence of transmural scars. However, the finding of severe hypo- and akinesia does not reliably predict transmural scarring, with no improvement by the addition of DS. Detection of predominant akinesia with less than two normo- or hypokinetic segments in the territory of a high-grade coronary stenosis or occlusion, warrants further examination by LGE-CMR.

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate.

An analogue of thiamine having a furan ring in place of the thiazolium ring has been synthesised by a short and efficient route, involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a very strong inhibitor, with a K i value of 32.5 pM. It was also shown that the furan analogue of thiamine can be functionalised at the C-2 position, which will allow access to mimics of reaction intermediates of various ThDP-dependent enzymes.

Stability of aminooxy glycosides to glycosidase catalysed hydrolysis.

The stability of the amino(methoxy) beta-glycosidic bond to glycosidase catalysed hydrolysis is reported. Beta-O-benzyl glucose and beta-O-benzyl galactose are substrates hydrolysed by beta-glucosidase and beta-galactosidase from almonds and Escherichia coli, respectively. However their beta-N-benzyl-(O-methoxy)-glucoside and beta-N-benzyl-(O-methoxy)-galactoside derivatives are competitive inhibitors.

Persistent dysfunction of viable myocardium after revascularization in chronic ischaemic heart disease: implications for dobutamine stress echocardiography with longitudinal systolic strain and strain rate measurements.

AIMS: Studies of functional recovery after revascularization in chronic coronary artery disease are contradictory and mark a lack of knowledge of persistent dysfunction in the non-scarred myocardium. Based on tissue Doppler-derived regional longitudinal systolic strain and strain rate (SR), both at rest and during dobutamine stress (DS), we assessed to what extent ischaemia-related reduced myocardial function would recover after revascularization in hearts with predominantly viable myocardium. METHODS AND RESULTS: Reference peak systolic strain and SR values were determined from tissue Doppler imaging in 15 healthy volunteers. Fifty-seven patients scheduled for coronary artery bypass grafting (CABG), with an average ejection fraction of 49%, underwent pre-operative magnetic resonance imaging (MRI) with late enhancement, resting echocardiography, and DS echocardiography (DSE), with assessment of systolic strain and SR and post-systolic strain (PSS). Eight to 10 months after CABG, myocardial function was reassessed. Forty per cent of all segments had reduced longitudinal systolic strain pre-operatively despite only 1.4% of segments with transmural infarctions on MRI. After revascularization, 38% of prior dysfunctional segments improved their resting strain, whereas 72% were improved by DS. Positive resting systolic strain indicated the absence of significant scar tissue. Resting systolic strain and DS strain responses were good prognosticators for functional improvement with areas under the receiver operating characteristic curve of 0.753 (0.646-0.860) and 0.790 (0.685-0.895), respectively. CONCLUSION: Persistently reduced longitudinal function was observed in more than half of pre-operatively viable but dysfunctional segments after CABG. We propose that such a functional impairment marks a regional remodelling process not amendable to re-established blood flow.

Radial artery graft patency relates to gender, diabetes mellitus and angiotensin inhibition.

UNLABELLED: The radial artery is resistant to atherosclerotic degeneration and therefore appears more attractive for coronary artery bypass grafting than the saphenous vein. However, the patency of radial artery grafts varies widely among studies. Therefore, before deciding whether to adopt this as the conduit of choice second to internal mammary artery grafts, we have prospectively monitored our first cohort of patients with radial-to-coronary bypasses. DESIGN: Angiographic and clinical outcome parameters were registered for the 119 patients receiving radial artery grafts at our institution during April 4, 2001 to October 7, 2003. RESULTS: Reangiography of 102 patients (86%) showed that after two to three years, 79% of the radial artery and 87% of the saphenous vein grafts remained patent. Radial artery harvesting was well tolerated. Patency of radial artery grafts was correlated to diabetes mellitus (detrimental), gender (women had higher occlusion rates), and use of angiotensin inhibiting medication (beneficial). CONCLUSIONS: The pre-study assumption that radial artery grafts would out-perform those of saphenous vein at mid-term is not borne out. The propensity of radial artery graft failure in diabetics and the higher patency associated with angiotensin inhibition might both relate to endothelial modulation of the muscular tone of the graft.

Tetra-aquabis-(2-sulfamoylbenzoato)manganese(II).

In the title compound, [Mn(C(7)H(6)NO(4)S)(2)(H(2)O)(4)], the Mn atom, lying on an inversion center, exhibits a distorted octa-hedral coordination by six O atoms, two from carboxyl-ate groups and four from water mol-ecules. The SO(2)NH(2) group is involved in a three dimensional polymeric hydrogen bonding network along with the water mol-ecules. π-Stacking inter-actions parallel to the c axis lead to a separation of 4.0050 (12) Šbetween the centroids of the benzene rings.

(2E)-3-(4-Chloro-phen-yl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one.

In the mol-ecule of the title compound, C(13)H(10)ClNO, the benzene and pyrrole rings are oriented at a dihedral angle of 7.37 (12)°. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric R(2) (2)(10) dimers. There are C-H⋯π inter-actions between benzene and pyrrole rings and a benzene C-H group. A weak π-π inter-action between the pyrrole rings [centroid-centroid distance 3.8515 (11) Å] further stabilizes the structure. There is also a π inter-action between the pyrrole ring and the carbonyl group, with a carbon-centroid distance of 3.4825 (18) Å.

Synthesis, characterization and antibacterial activity of azomethine derivatives derived from 2-formylphenoxyacetic acid.

A series of eight new azomethine derivatives were synthesized by reacting 2-formylphenoxyacetic acid with aromatic amines. The chemical structures of these compounds were confirmed by means of 1H-NMR, 13C-NMR, MS and elemental analysis. The compounds were assayed by the disc diffusion method for antibacterial against Staphylococcus aureus and Escherichia coli. Among the compounds tested, 2a, 2b, 2e, 2g and 2h exhibited good antibacterial activity, almost equal to that of Ciprofloxacin used as standard.

Synthesis, spectroscopic and cytotoxic studies of biologically active new schiff bases derived from p-nitrobenzaldehyde.

Thirteen new Schiff bases derived from p-nitrobenzaldehyde were synthesized by condensation with the appropriate amines. An unusual reduction of the p-nitrobenzaldehyde to the corresponding alcohol was also observed in one of the reactions. The structures of the compounds were identified using spectroscopic techniques. Cytotoxicity for the titled compounds was studied against Brine Shrimp, used as the test animal.

Thyroid stimulating hormone and left ventricular function.

CONTEXT: Overt hypo- and hyperthyroidism are associated with cardiac disease, whereas this relation is more uncertain regarding subclinical thyroid dysfunction. OBJECTIVE: The objective was to assess the relation between serum TSH level and cardiac function. DESIGN: We conducted a cross-sectional epidemiological study and a nested case-control study. SETTING: The study was performed at a university hospital. SUBJECTS: A total of 2035 subjects were included in the epidemiological study and 204 subjects in the nested case-control study (serum TSH < 0.50, 0.50-3.49, and 3.50-10.0 mIU/liter in 20, 118, and 66 subjects, respectively, all with normal serum free T(4) and free T(3) levels). MAIN OUTCOME MEASURES: Left ventricular mass by body surface area (LVMI) and indices of left ventricular function, as assessed by conventional and pulsed-wave tissue Doppler (PWTD) echocardiography, were recorded. RESULTS: No significant relation was found between serum TSH level and LVMI. In the nested case-control study, the subjects with serum TSH 3.50-10.0 mIU/liter had no signs of cardiac dysfunction. However, the PWTD data showed higher velocities at all measurement sites in the subjects with serum TSH less than 0.50 mIU/liter as compared with the euthyroid group. CONCLUSIONS: With the possible exception of overt hypo- and hyperthyroidism, there is no significant association between serum TSH level and LVMI. Subjects with subclinical hypothyroidism, in whom the mean serum TSH level is slightly above the reference range, appear to have normal cardiac function, whereas subjects with serum TSH levels less than 0.5 mIU/liter appear to have changes in myocardial velocities detected by PWTD.

Coronary artery disease cannot be reliably evaluated by 16-slice multidetector spiral computed tomography.

OBJECTIVES: Angiography by selective catheterization is the standard method for coronary artery imaging but carries a risk of rare, but serious complications. We investigated whether 16-slice multidetector spiral computed tomography (MDCT) could substitute for selective angiography for evaluation of coronary artery disease in surgically revascularized patients. DESIGN: In a setting closely resembling routine clinical practice, 45 patients who had been operated with coronary artery bypass grafting 508-1135 (mean 811) days before were examined with MDCT and conventional selective angiography on the same day. The interpreters were blinded to the results of the parallel imaging modality. RESULTS: Significant pathology (stenosis >/=50% or occlusion) in the larger coronary artery segments was detected by MDCT with a sensitivity of 70-98% (mean 87%) and a specificity of 0-37% (mean 21%). MDCT failed to identify three of ten left main stem stenoses. CONCLUSION: Sixteen-slice MDCT cannot routinely replace selective angiography for evaluation of coronary artery disease.