COVID-19 infected ST-Elevation myocardial infarction in India (COSTA INDIA).

OBJECTIVE: To find out differences in the presentation, management and outcomes of COVID-19 infected STEMI patients compared to age and sex-matched non-infected STEMI patients treated during the same period. METHODS: This was a retrospective multicentre observational registry in which we collected data of COVID-19 positive STEMI patients from selected tertiary care hospitals across India. For every COVID-19 positive STEMI patient, two age and sex-matched COVID-19 negative STEMI patients were enrolled as control. The primary endpoint was a composite of in-hospital mortality, re-infarction, heart failure, and stroke. RESULTS: 410 COVID-19 positive STEMI cases were compared with 799 COVID-19 negative STEMI cases. The composite of death/reinfarction/stroke/heart failure was significantly higher among the COVID-19 positive STEMI patients compared with COVID-19 negative STEMI cases (27.1% vs 20.7% p value = 0.01); though mortality rate did not differ significantly (8.0% vs 5.8% p value = 0.13). Significantly lower proportion of COVID-19 positive STEMI patients received reperfusion treatment and primary PCI (60.7% vs 71.1% p value=< 0.001 and 15.4% vs 23.4% p value = 0.001 respectively). Rate of systematic early PCI (pharmaco-invasive treatment) was significantly lower in the COVID-19 positive group compared with COVID-19 negative group. There was no difference in the prevalence of high thrombus burden (14.5% and 12.0% p value = 0.55 among COVID-19 positive and negative patients respectively) CONCLUSIONS: In this large registry of STEMI patients, we did not find significant excess in in-hospital mortality among COVID-19 co-infected patients compared with non-infected patients despite lower rate of primary PCI and reperfusion treatment, though composite of in-hospital mortality, re-infarction, stroke and heart failure was higher.

Clinical characteristics and 30-day outcomes in patients with acute decompensated heart failure: Results from Indian College of Cardiology National Heart Failure Registry (ICCNHFR).

BACKGROUND: Acute decompensated heart failure (ADHF) is a challenging medical emergency with high mortality and its prevalence is increasing in India. There is paucity of data on ADHF in the country. METHODS: Indian College of Cardiology National Heart Failure Registry (ICCNHFR) is an on-going observational registry on ADHF contributed by 22 hospitals across India; and we present the in-hospital and 30-day outcomes of ADHF patients enrolled from August 2018 to July 2019. Major objective included capturing demographics, comorbid conditions, aetiology, prescription patterns and assessing clinical outcomes. RESULTS: Of 5269 patients (mean age: 61.90 ± 13.85 years) enrolled in this study, males were predominant (67.09%). Mean duration of hospitalization was 5.74 ± 4.74 days. Ischemic heart disease was the most common (75.44%) aetiology. Abnormal electrocardiogram readings were found in most patients (89.86%). LVEF of ˂40% was found in 68.29% of patients. In-hospital mortality rates were 6.98%. The 30-day cumulative mortality was 12.35% and 30-day rehospitalization rate was 7.98%. At discharge, all guideline-based medical therapy (GDMT) were prescribed only to 24.99% of patients and 23.72% adhered to the prescription until 30 days. Older age, high serum creatinine levels and poor LVEF contributed to high mortality and rehospitalization. CONCLUSION: Patients with ADHF were younger and predominantly males. Usage of GDMT in ADHF patients was low (24.99%) and the in-hospital mortality was high. Older age, high serum creatinine levels, poor LVEF contributed for 30-day mortality and rehospitalization. This data on ADHF, could help in developing strategies to improve outcomes for HF patients in India.

Acute decompensated heart failure (ADHF) during COVID-19 pandemic-insights from South India.

AIM: This retrospective study compares admissions and outcomes due to acute decompensated heart failure (ADHF) during the COVID-19 pandemic from 25 March to 25 July 2020 with the historical patient control who were admitted during the same period in 2019. METHODS AND RESULTS: Data of the participating hospitals was collected and analysed from the ICC NHFR (Indian College of Cardiology National Heart Failure Registry) for 2019 and 2020. Total number of ADHF admissions, demographics, aetiology, co-morbid conditions and in-hospital mortality was compared and analysed. A significant decrease in the number of hospital admissions due to ADHF from 2019 to 2020 (1056 vs. 526 respectively) was noted. Incidence of admissions with <40% ejection fraction (EF) reduced in 2020 (72.4% and 80.2% in2020 and 2019)and >40% (EF) increased (27.6% and 19.8% in 2019 and 2020 respectively, p = 0.0005). Ischemic heart disease (IHD) was the most common aetiology (78.59% in 2019 and 80.98% in 2020, p = 0.268). The in-hospital mortality was numerically higher in 2020 (10%) than in 2019 (8%), but not statistically significant (p = 0.161). CONCLUSION: This study from the registry shows that the incidence of ADHF admissions during COVID-19 lockdown significantly reduced compared to the previous year. Demographic patterns remained similar but patients presenting with de-novo HF increased; IHD was the most common cause. The in-hospital mortality was numerically higher during the lockdown. The impact of lockdown perhaps led to fewer hospitalisations and this is to be factored in future strategies to address health care delivery during such crises.

Multiobjective nonlinear model predictive control of pharmaceutical batch crystallizers.

A rigorous multiobjective nonlinear model predictive control procedure is implemented in solving problems involving batch crystallizations. This technique does not involve the use of weighting functions and additional restrictive constraints. Three cases are considered. The first is the unseeded batch crystallization involving paracetamol, the second is the seeded batch crystallization concerning potassium nitrate while the third problem deals with a temperature controlled batch crystallizer that involves citric acid anyhydrate. The optimization language pyomo with GAMS interface is used to solve the problems.

Mass spectral studies of N-oxides of chemical weapons convention-related aminoethanols by gas chromatography/mass spectrometry after silylation.

N-Alkylaminoethanols, N,N'-dialkylaminoethanols, and triethanolamine are the hydrolyzed products or precursors of V-agents/nitrogen mustards. These compounds are prone to undergo oxidation in environmental matrices. Detection of the oxidized products provides a clue for the presence of parent amine compounds and it is an important task in the verification process of chemical weapons convention. Gas chromatography/mass spectrometry is the technique of choice for the detection of most of the chemical warfare agents; however, it is ideal to develop gas chromatography/mass spectrometry techniques for all the possible degradation products of chemical warfare agents as well. In general, the N-oxides of amines are expected to be thermally unstable; hence, the gas chromatography/mass spectrometry analysis of the N-oxides of triethanolamine, N-alkyldiethanolamines and N,N'-dialkylaminoethanols is not explored. In this study, the N-oxides of chemical weapons convention-related aminoethanols (13 compounds) were successfully silylated and then analyzed by gas chromatography/mass spectrometry under electron ionization and chemical ionization techniques. The electron ionization mass spectra showed abundant molecular ions and structure indicative fragment ions including [M-(O+CH2CH2OH)]+. The alkyl groups attached to nitrogen resulted in structure-specific fragment ions that enable differentiation of isomeric compounds. The methane/chemical ionization spectra showed considerably abundant [M+H]+ (>10%) and the expected adduct ions. The retention indices of all the compounds were calculated using Van den Dool's formula. The gas chromatography/mass spectrometry data together with retention index values could be used for unambiguous identification of the N-oxides of aminoethanols during off-site analysis or proficiency tests.

Differential Cationization of Fatty Acids with Monovalent Cations Studied by ESI-MS/MS and Computational Approach.

RATIONALE: The intercellular and intracellular transport of charged species (Na+ /K+ ) entail interaction of the ions with neutral organic molecules and formation of adduct ions. The rate of transport of the ions across the cell membrane(s) may depend on the stability of the adduct ions, which in turn rely on structural aspects of the organic molecules that interact with the ions. METHODS: Positive ion ESI mass spectra were recorded for the solutions containing fatty acids (FAs) and monovalent cations (X=Li+ , Na+ , K+ , Rb+ and Cs+ ). Product ion spectra of the [FA+X]+ ions were recorded at different collision energies. Theoretical studies were exploited under both gas phase and solvent phase to investigate the structural effects of the fatty acids during cationization. Stability of [FA+X]+ adduct ions were further estimated by means of AIM topological analyses and interaction energy (IE) values. RESULTS: Positive ion ESI-MS analyses of the solution of FAs and X+ ions showed preferential binding of the K+ ions to FAs. The K+ ion binding increased with the increase in number of double bonds of FAs, while decreased with increase in the number of carbons of FAs. Dissociation curves of [FA+X]+ ions indicated the relative stability order of the [FA+X]+ ions and it was in line with the observed trends in ESI-MS. The solvent phase computational studies divulged the mode of binding and the binding efficiencies of different FAs with monovalent cations. CONCLUSIONS: Among the studied monovalent cations, the cationization of FAs follow the order K+ >>Na+ >Li+ >Rb+ >Cs+ . The docosahexaenoic acid showed high efficiency in binding with K+ ion. The K+ ion binding efficiency of FAs depends on the number of double bonds in unsaturated FAs and the carbon chain length in saturated FAs. The cationization trends of FAs obtained from the ESI-MS, ESI-MS/MS analyses were in good agreement with solvent phase computational studies.

The 2017 International Joint Working Group recommendations of the Indian College of Cardiology, the Academic College of Emergency Experts, and INDUSEM on the management of low-risk chest pain in emergency departments across India.

There have been no published recommendations for the management of low-risk chest pain in emergency departments (EDs) across India. This is despite the fact that chest pain continues to be one of the most common presenting complaints in EDs. Risk stratification of patients utilizing an accelerated diagnostic protocol has been shown to decrease hospitalizations by approximately 40% with a low 30-day risk of major adverse cardiac events. The experts group of academic leaders from the Indian College of Cardiology and Academic College of Emergency Experts in India partnered with academic experts in emergency medicine and cardiology from leading institutions in the UK and USA collaborated to study the scientific evidence and make recommendations to guide emergency physicians working in EDs across India.

Rapid screening of N-oxides of chemical warfare agents degradation products by ESI-tandem mass spectrometry.

Rapid detection and identification of chemical warfare agents and related precursors/degradation products in various environmental matrices is of paramount importance for verification of standards set by the chemical weapons convention (CWC). Nitrogen mustards, N,N-dialkylaminoethyl-2-chlorides, N,N-dialkylaminoethanols, N-alkyldiethanolamines, and triethanolamine, which are listed CWC scheduled chemicals, are prone to undergo N-oxidation in environmental matrices or during decontamination process. Thus, screening of the oxidized products of these compounds is also an important task in the verification process because the presence of these products reveals alleged use of nitrogen mustards or precursors of VX compounds. The N-oxides of aminoethanols and aminoethylchlorides easily produce [M + H](+) ions under electrospray ionization conditions, and their collision-induced dissociation spectra include a specific neutral loss of 48 u (OH + CH2OH) and 66 u (OH + CH2Cl), respectively. Based on this specific fragmentation, a rapid screening method was developed for screening of the N-oxides by applying neutral loss scan technique. The method was validated and the applicability of the method was demonstrated by analyzing positive and negative samples. The method was useful in the detection of N-oxides of aminoethanols and aminoethylchlorides in environmental matrices at trace levels (LOD, up to 500 ppb), even in the presence of complex masking agents, without the use of time-consuming sample preparation methods and chromatographic steps. This method is advantageous for the off-site verification program and also for participation in official proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW), the Netherlands. The structure of N-oxides can be confirmed by the MS/MS experiments on the detected peaks. A liquid chromatography-mass spectrometry (LC-MS) method was developed for the separation of isomeric N-oxides of aminoethanols and aminoethylchlorides using a C18 Hilic column. Critical isomeric compounds can be confirmed by LC-MS/MS experiments, after detecting the N-oxides from the neutral loss scanning method.

p-Tolyl isocyanate derivatization for analysis of CWC-related polar degradation products by mass spectrometry.

Most of the precursors and/or degradation products related to the Chemical Weapons Convention (CWC) are polar. Identification of these molecules in environmental samples provides clues regarding the alleged usage and/or synthesis of the parent toxic chemicals. Such polar compounds need to be derivatized in order to analyze them by gas chromatography-mass spectrometry (GC-MS). In this study, we developed a new derivatizing reagent, para-tolyl isocyanate (PTI), for derivatization of polar CWC-related compounds. The PTI reagent selectively derivatizes the -OH and/or-SH functional groups with high efficiency, but does not react with carboxylic acid (-COOH) or phosphonic acid (-(O)P(OH)2) groups. The PTI derivatives of dialkyl aminoethanols, dialkyl aminoethanol-N-oxides, and 3-quinuclidinol were successfully eluted through GC, and their electron ionization (EI) mass spectra were distinct and provided the structure information by which the isomeric compounds can be easily distinguished. We also calculated the GC-retention index values that can be used for further confirmation of the target compounds. All the studied PTI derivatives can be analyzed by EI-MS with direct insertion probe and/or by direct electrospray ionization mass spectrometry (ESI-MS) together with the MS-MS data; both sets of data provide full structure information. The PTI reagent was found to be better in some respects than the conventional bistrimethylsilyl trifluoroacetamide (BSTFA), a trimethyl silylating reagent. The PTI reagent is commercially available, and the PTI derivatives are highly stable for months and are not sensitive to moisture. The applicability of the PTI derivatization for trace-level determination of the target CWC-related polar compounds in environmental matrices and in human plasma samples is also evaluated.

Mass spectral characterization of the CWC-related isomeric dialkyl alkylphosphonothiolates/alkylphosphonothionates under gas chromatography/mass spectrometry conditions.

RATIONALE: The isomeric dialkyl alkylphosphonothiolates and dialkyl alkylphosphonothionates are listed as scheduled chemicals of the Chemical Weapons Convention (CWC) implemented by the OPCW. The P-S and P-R bond connectivity has to be correctly identified for the verification of the CWC. The present study demonstrates successful identification of the target isomers by selective fragmentation under electron ionization (EI) or chemical ionization (CI) conditions. METHODS: All the studied isomeric compounds (27 in total) were synthesized in our laboratory using established methods, then analyzed by EI and CI gas chromatography/mass spectrometry (GC/MS) using an Agilent 6890 gas chromatograph equipped with a HP-5MS capillary column and interfaced to a 5973 N mass-selective detector. The retention index (RI) values of all the compounds were calculated using Van den Dool's formula. GC/MS/MS and GC/HRMS experiments were also performed using a VG-Autospec (magnetic sector) and JEOL-AccuToF (time-of-flight) mass spectrometer, respectively. RESULTS: The EI mass spectra of all the compounds had an abundant molecular ion at m/z 182, except in the case of a few selected butyl-substituted compounds, where this ion was of low abundance. The EI fragmentation pathways include α-cleavage, McLafferty rearrangement, McLafferty + 1 rearrangement, O/S-alkyl radical loss, and an alkene loss with a hydrogen shift. The characteristic fragment ions and their relative abundances are significant in elucidating the alkyl group attached to the P/S/O-atoms as well as the P-S/P = S bond connectivity. The EI and CI mass spectra together with RI values enable unambiguous identification of all the studied isomeric compounds. CONCLUSIONS: The present study highlights the structural characterization of the isomeric phosphonothiolates and phosphonothionates based on their selective EI fragmentation. The assigned fragmentation pathway helps in the assignment of P-S and P-alkyl connectivity in phosphonothiolates and phosphonothionates, consequently the structure of the unknown compounds. The EI mass spectra (27 compounds) of isomeric compounds are immensely useful in the OPCW official proficiency tests and for off-site analysis.

Mass spectral analysis of N-oxides of Chemical Weapons Convention related aminoethanols under electrospray ionization conditions.

N,N'-Dialkylaminoethanols are the hydrolyzed products or precursors of chemical warfare agents such as V-agents and nitrogen mustards, and they are prone to undergo oxidation in environmental matrices or during decontamination processes. Consequently, screening of the oxidized products of aminoethanols in aqueous samples is an important task in the verification of chemical weapons convention-related chemicals. Here we report the successful characterization of the N-oxides of N,N'-dialkylaminoethanols, alkyl diethanolamines, and triethanolamine using positive ion electrospray ionization mass spectrometry. The collision-induced dissociation (CID) spectra of the [M+H](+) and [M+Na](+) ions show diagnostic product ions that enable the unambiguous identification of the studied N-oxides, including those of isomeric compounds. The proposed fragmentation pathways are supported by high-resolution mass spectrometry data and product/precursor ion spectra. The CID spectra of [M+H](+) ions included [MH-CH(4)O(2)](+) as the key product ion, in addition to a distinctive alkene loss that allowed us to recognize the alkyl group attached to the nitrogen. The [M+Na](+) ions show characteristic product ions due to the loss of groups (R) attached to nitrogen either as a radical (R) or as a molecule [R+H or (R-H)] after hydrogen migration.

Balloon mitral valvotomy in patients with mitral stenosis and left atrial thrombus.

OBJECTIVES: To evaluate the safety and efficacy of balloon mitral valvotomy (BMV) in symptomatic rheumatic mitral stenosis (MS) patients with left atrial (LA) thrombus and to address the technical issues. BACKGROUND: LA thrombus in patients with MS has long been regarded as a contraindication for BMV. There are few reports of BMV in presence of LA appendage (LAA) thrombus and reports of BMV in presence of LA body thrombus are still rare. METHODS: 2,763 patients with suitable valve morphology were screened for BMV. 194 patients had LA/LAA thrombus and were put on adequate anticoagulation for 8-12 weeks. A total of 108 patients with persistent LA thrombus who satisfied the inclusion criteria (LA thrombus type Ia, Ib, and IIa) formed the study group and the remaining 2,622 patients who did not have any LA thrombus constituted the control group. All patients in the study group underwent BMV by modified over the wire technique. RESULTS: There was significant and comparable improvement in the mitral valve area, mitral valve gradient, LA mean and pulmonary artery systolic pressure following the procedure in both groups. In the study group, there were no thromboembolic episodes during the procedure. However, there was one case of transient ischemic attack in the study group which occurred 6 hr after a successful BMV. In the study group, one patient had cardiac tamponade needing aspiration and there was no in-hospital death. CONCLUSIONS: In selected patients of mitral stenosis with LA thrombus (type Ia, Ib, and IIa), BMV can be performed safely with the modified over the wire technique. Systemic thromboembolism, technical failures and other complications are very rare when performed by experienced operators.

Riboflavin carrier protein: a serum and tissue marker for breast carcinoma.

We have earlier shown that the estrogen-modulated riboflavin carrier protein (RCP) first isolated from the chicken egg is evolutionarily conserved in mammals and is elaborated by lactating mammary gland as demonstrated with rat mammary epithelial cells in culture and confirmed by isolation of the vitamin carrier from bovine milk. In view of several earlier reports that many milk proteins as well as other estrogen-inducible proteins are up-regulated and secreted into circulation in animal models and in women with neoplastic breast disease, we analyzed serum RCP levels in a double-blind study using a specific radioimmunoassay in pre- and post-menopausal women with clinically diagnosed breast cancer at early and advanced stages of the disease and compared these levels with those in normal age-matched control volunteers. Our data reveal that the serum RCP levels in cycling breast cancer patients are 3- to 4-fold higher (p < 0.01) than those in their normal counterparts. This difference in circulatory RCP levels between cancer patients and their age-matched normal counterparts is further magnified to 9- to 11-fold (p < 0.005) at the post-menopausal stage. In addition, there seems to be a good correlation between rising RCP levels and disease progression, since significantly higher RCP concentrations (p < 0.005) are encountered in patients with advanced metastasizing breast cancer versus those with early disease. Using specific monoclonal antibodies, RCP could be localized immunohistochemically in the cytoplasm of invading neoplastic cells of lobular and ductal carcinomas of the breast, indicating that the malignant cells are probably the source of the elevated serum RCP levels in breast cancer. These findings suggest that measurement of circulatory RCP and the immunohistochemical staining pattern of RCP in biopsy specimens could be exploited as an additional marker in diagnosis/prognosis of breast cancer in women.