N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) as a Diagnostic Biomarker of Left Ventricular Systolic Dysfunction in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).

INTRODUCTION: Left ventricular systolic dysfunction (LVSD) and cardiac decompensation often accompany AECOPD. Differentiation between the two is difficult and mainly relies on clinical and echocardiographic diagnostic procedures. The value of biomarkers, such as NT-proBNP, as diagnostic tools is still insufficiently investigated. The main goals of this trial were to investigate the value of NT-proBNP as a diagnostic tool for LVSD in AECOPD patients and determine its cut-off value which could reliably diagnose LVSD during AECOPD. PATIENTS AND METHODS: This trial prospectively enrolled 209 patients with AECOPD. The patients were divided into four groups-AECOPD plus chronic pulmonary heart disease (CPHD) with or without left ventricular compromise (LVSD), and AECOPD patients without CPHD with or without LVSD. NT-proBNP was measured within first 48 h of hospitalization. RESULTS: Majority of patients were male (61%) active smokers (41.6%), average age of 68 years. High quality of echocardiography was obtained in 63.3 and 22.5% of the patients had LVSD. Average value of NT-proBNP in patients with LVSD was 3303.2 vs. 1092.5 pg/mL in patients without LVSD. Significant differences in NT-proBNP value (p = 0.0001) were determined between observed patient groups. At the cut-off value of 1505 pg/mL, sensitivity, specificity, and positive and negative predictive values are 76.6, 83.3, 57.1, and 92.47%, respectively. CONCLUSION: At the cut-off value of 1505 pg/mL NT-proBNP could be used as a diagnostic marker for LVSD in acute exacerbation of COPD.

Quaternized α,α'-Amino Acids via Curtius Rearrangement of Substituted Malonate-Imidazolidinones.

An efficient synthesis protocol is presented for accessing quaternized α-amino acids in chiral, nonracemic form via diastereoselective malonate alkylation followed by C- to N-transposition. The key stereodifferentiating step involves a diastereoselective alkylation of an α-monosubstituted malonate-imidazolidinone, which is followed first by a chemoselective malonate PMB ester removal and then a Curtius rearrangement to provide the transposition. The method demonstrates a high product ee (89-99% for eight cases) for quaternizing a range of proteinogenic α-amino acids. The stereogenicity in targets 5a-i supports previous conclusions that the diastereoselective alkylation step proceeds via an α-substituted malonate-imidazolidinone enolate in its Z-configuration, with the auxiliary in an s-transC-N conformation.

Stereoselective formation of quaternary stereogenic centers via alkylation of α-substituted malonate-imidazolidinones.

A new stereoselective alkylation methodology is presented for formation of chiral, nonracemic quaternary centers via a chiral auxiliary protocol involving α-alkylated malonate imidazolidinones. Based on two X-ray structures of quaternized products, the diastereoselectivity observed may be rationalized via a transition-state involving an s-transC-N conformation of the C-N bond of the auxiliary, with the metal cation (K(+)) chelated into the malonate six-membered hole as a Z-enolate. A deprotection protocol involving ethanethiolate exchange of the imide to the corresponding thioester, followed by a standard Fukuyama reduction and a borohydride reduction, furnishes α,α'-quaternized ß-hydroxypropionates in high ee overall.

A Case Report on Serotonin Syndrome in a Patient With Parkinson's Disease: Diagnostic and Management Challenges.

Patients with Parkinson's disease are often at risk of polypharmacy, which can lead to serious medication side effects and interactions. Serotonin syndrome (SS) can develop in this patient population due to a possible drug-drug interaction between antidepressants and antiparkinson drugs with serotoninergic activity. On the other hand, these patients are also at risk of malignant syndrome (MS) secondary to dopaminergic medication withdrawal. In this case report, we present a 71-year-old female with Parkinson's disease who developed symptoms suggestive of SS. The patient was admitted to the medical intensive care unit at the Institute for Pulmonary Diseases of Vojvodina in the Republic of Serbia due to impaired consciousness and a previously witnessed cardiorespiratory arrest. Her chronic antiparkinson medication regimen consisted of levodopa, benserazide, entacapone, ropinirole, and rasagiline. Furthermore, she had been prescribed duloxetine for a remote history of depression, which she had only been taking intermittently. Several days before admission, however, the patient started taking duloxetine again due to low mood. Upon admission, laboratory tests revealed leukocytosis with neutrophilia, elevated C-reactive protein, procalcitonin, lactate, urea, and creatinine. Serum creatine kinase (CK) levels were also elevated at 1250 U/L. Six hours after admission to the ICU, the patient developed hyperthermia, hyperreflexia, spontaneous myoclonus, and tremors. Her CK levels continued to rise, reaching 6900 U/L, and her renal function worsened. Due to the possibility of either SS or MS, external cooling measures with frozen gel packs were administered, resulting in the patient's stabilization over a few hours. Further, serotoninergic medication (rasagiline and duloxetine) was discontinued. On the fifth day of hospitalization, a head CT showed signs of cytotoxic edema. On the 11th day, the patient became hemodynamically unstable and passed away despite all adequate resuscitative measures. The purpose of this case report is to raise awareness of possible SS in patients taking monoamine oxidase-B (MAO-B) inhibitors such as rasagiline. Clinicians should have a high index of suspicion for this complication, especially in patients who are treated for comorbid depression with serotoninergic drugs. Furthermore, we emphasize the importance of correctly differentiating SS from MS, which are both risks for patients with Parkinson's disease. A correct approach to these patients is of utmost importance for adequate management and optimal outcomes.

Characteristics and outcomes of critically ill patients with influenza A (H1N1) in the Western Balkans during the 2019 post-pandemic season.

Background: This study looked at the characteristics and outcomes of critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the Western Balkans in the post-pandemic period. Materials and Methods: This retrospective observational study of medical records and associated data collected during the post-pandemic period included all mechanically ventilated adult patients of two university-affiliated hospitals of the Western Balkans between 1 January and 31 March 2019 who had influenza A (H1N1) pdm09 infection confirmed by real-time reverse transcriptase-polymerase chain reaction from nasopharyngeal swab specimens and respiratory secretions. Results: The study included 89 patients, 49 males (55.1%), aged 56.09 ± 12.64 years. The median time from shift from hospital time to intensive care unit was 1 day (range: 1-2). In the post-pandemic period, cases observed in this study were found to have the following comorbidities: cardiovascular diseases in 44 (49.4%) patients and diabetes in 21 (23.6%) patients. Thirty-one patients (34.8%) in this study were obese. All 89 patients (100%) experienced some degree of acute respiratory distress syndrome, and 39 (44%) had multiorgan failure. Eighty-three patients (93%) were intubated and mechanically ventilated, 6 (7%) received non-invasive mechanical ventilation, 12 (13%) were treated with vvECMO and 36 (40%) received renal replacement therapy. Vasoactive support was needed by 56 (63%) patients. The median duration of mechanical ventilation was 9 (6-15.5) days. The hospital mortality rate was 44%. Conclusion: Critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the post-pandemic season were older, required vasoactive drugs more often, and there was a trend of higher survival compared to H1N1 infection patients in the previous pandemic seasons.

Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and In Vivo Efficacy in the Plasmodium falciparum NSG Mouse Model.

A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure-activity and structure-property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rγnull (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action.

Adjunct corticosteroid treatment in patients with pneumonia: A precision medicine approach.

Pneumonia is the leading infectious cause of death worldwide. While inflammation is critically important in host response to microbial invasion, exaggerated inflammation can damage the lungs, contributing to respiratory failure and mortality. Corticosteroids are effective in reducing inflammation and can also cause immune suppression. Presently, clinicians are unable to reliably distinguish between exaggerated and appropriate immune response and thus cannot rapidly identify patients most likely to benefit from adjunctive corticosteroids. In this review, we propose a biomarker-guided, precision medicine approach to corticosteroid treatment, aimed to give these medications at appropriate dose and time and only to patients who have exaggerated inflammation.