Patient outcomes and characteristics in a contemporary quaternary Canadian cardiac intensive care unit

BACKGROUND: The modern-day cardiac intensive care unit (CICU) has evolved to care for patients with acute critical cardiac illness. We describe the current population of cardiac patients in a quaternary CICU. METHODS: Consecutive CICU patients admitted to the CICU at the Toronto General Hospital from 2014 to 2020 were studied. Patient demographics, admission diagnosis, critical care resources, complications, in-hospital mortality, and CICU and hospital length of stay were recorded. RESULTS: A total of 8865 consecutive admissions occurred, with a median age of 64.9 years. The most common primary cardiac diagnoses were acute decompensated heart failure (17.8%), non ST-elevation myocardial infarction (16.8%), ST-elevation myocardial infarction (15.5%), and arrhythmias (14.7%). Cardiogenic shock was seen in 13.2%, and out-of-hospital cardiac arrest in 4.1%. A noncardiovascular admission diagnosis accounted for 13.9% of the cases. Over the period studied, rates of admission were higher for cardiogenic shock (P < 0.001 for trend), with a higher use of critical care resources. Additionally, rates of admission were higher in female patients and those who had chronic kidney disease and diabetes. The in-hospital mortality rate of all CICU admissions was 13.2%, and it was highest in those with noncardiac conditions, compared to the rate in those with cardiac diagnoses (29.4% vs 10.6%, P < 0.001). CONCLUSIONS: Given the trends of higher acuity of patients with cardiac critical illness, with higher use of critical care resources, education streams for critical care within cardiology, and alternative pathways of care for patients who have lower-acuity cardiac disease remain imperative to manage this evolving population

Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model

BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma

Virulence genes detection of Salmonella serovars isolated from pork and slaughterhouse environment in Ahmedabad, Gujarat

Aim: The aim was to detect virulence gene associated with the Salmonella serovars isolated from pork and Slaughterhouse environment. Materials and Methods: Salmonella isolates (n=37) used in this study were isolated from 270 pork and slaughter house environmental samples collected from the Ahmedabad Municipal Corporation Slaughter House, Ahmedabad, Gujarat, India. Salmonella serovars were isolated and identified as per BAM USFDA method and serotyped at National Salmonella and Escherichia Centre, Central Research Institute, Kasauli (Himachal Pradesh, India). Polymerase chain reaction technique was used for detection of five genes, namely invA, spvR, spvC, fimA and stn among different serovars of Salmonella. Results: Out of a total of 270 samples, 37 (13.70%) Salmonella were isolated with two serovars, namely Enteritidis and Typhimurium. All Salmonella serovars produced 284 bp invA gene, 84 bp fimA and 260 bp amplicon for enterotoxin (stn) gene whereas 30 isolates possessed 310 bp spvR gene, but no isolate possessed spvC gene. Conclusion: Presence of invA, fimA and stn gene in all isolates shows that they are the specific targets for Salmonella identification and are capable of producing gastroenteric illness to humans, whereas 20 Typhimurium serovars and 10 Enteritidis serovars can able to produce systemic infection

Diagnostic assays for leprosy based on T-cell epitopes.

To date, only a limited number of antigens have been described as specific for Mycobacterium leprae, and in many cases, homologues have subsequently been shown to exist in mycobacteria such as M. avium and M. intracellulare. A Leprosy Synthetic Peptide Skin Test Initiative was established by the Steering Committee on the Immunology of Mycobacteria of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, to investigate the potential of synthetic peptides that encode T-cell epitopes as diagnostic tools, which could be used to develop a skin-test reagent specific for leprosy. Such M. leprae-specific peptides should have unique amino acid sequences, or significant sequence-dissimilarity from those in other mycobacteria. Synthetic peptides, 15 amino acids long, were synthesised from 33 genes or open reading frames within the M. leprae genome. Tuberculoid leprosy patients from four leprosy-endemic countries, Brazil, Ethiopia, Nepal and Pakistan, were tested as subjects known to have been infected with M. leprae, and to make good T-cell responses to antigens of M. leprae; UK blood donors were used as non-exposed or non-infected subjects. Peptides inducing potentially specific responses in leprosy patients and not in UK controls, and those inducing cross-reaction responses, present in both leprosy patients and non-exposed, non-infected controls, were identified. A difference from the equivalent M. tuberculosis sequence of five or more amino acid residues did not, by itself, identify peptides that were M. leprae-specific, suggesting that many of these peptides may have homologues in environmental mycobacteria. To date, this approach has identified a number of peptides with greater than 90% specificity and 19-47% sensitivity, which are undergoing further specificity-testing. Such peptides would have great potential as T-cell reagents with which to monitor exposure to M. leprae within communities, formulated either as skin-test reagents, or as antigens for tests in vitro

FORMULATION AND EVALUATION OF BILAYERED FLOATING TABLET OF DILTIAZEM DRUG

Aim of study was to develop bilayered floating drug delivery for treatment of hypertension by delivering loading and maintenance dose for fast achievement of peak plasma concentration and maintaining the same respectively. The prepared drug loaded bilayered floating tablets were evaluated for pre and post compression parameters. Stability study of the promising formulation was also performed. The tablets were prepared by direct compression method. The loading dose was delivered in the form of immediate release layer prepared by different super-disintegrations and maintenance dose was delivered through sustained release layer prepared by using polymers like HPMC K15M and Carbopol 934P. Both the immediate release layer and sustained release layers were separately optimized and then combined to optimize the bilayered floating tablets. No interactions were found between drug and excipients. Formulation containing crosscarmellose sodium shows immediate drug release. Formulation Containing HPMC K15M shows sustained release action and bilayered formulations FB7 shows releases up to 12 hours with good buoyancy and total floating time. All the Bilayered floating formulations buoyant up to 12 hrs. Bilayered floating tablets with release characteristics offer critical advantages such as, site specificity with improved absorption and efficacy. This technology can be inculcated to various medicaments which have stomach as the major site of absorption. Key words: Diltiazem, Bilayered floating tablet, sustain release table

Excellent outcomes among HIV+ children on ART, but unacceptably high pre-ART mortality and losses to follow-up: a cohort study from Cambodia

BACKGROUND: Although HIV program evaluations focusing on mortality on ART provide important evidence on treatment effectiveness, they do not asses overall HIV program performance because they exclude patients who are eligible but not started on ART for whatever reason. The objective of this study was to measure mortality that occurs both pre-ART and during ART among HIV-positive children enrolled in two HIV-programs in Cambodia. METHODS: Retrospective cohort study on 1168 HIV-positive children <15 years old registered in two HIV-programs over a four-year period. Mortality rates were calculated for both children on treatment and children not started on ART. RESULTS: Over half (53%) of children were 5 years or above and only 69(6%) were <18 months. Overall, 9% (105/1168) of children died since the set-up of the programs. By the end of the observation period, 66(14.5%) patients not on ART had died compared to 39(5.5%) of those under treatment, and 100(22%) who did not start ART were lost-to-follow-up compared to 13(2%) on ART. 66/105 (62.8%) of all in-program deaths occurred before starting ART, of which 56% (37/66) and 79% (52/66) occurred within 3 and 6 months of enrollment respectively. Mortality rate ratio between children not on ART and children on ART was 4.1 (95%CI: 2.7-6.2) (P < 0.001). The most common contributing cause of death in first 3 months of treatment and in first 3 months of program enrollment was tuberculosis. 41/52 (79%) children who died within 6 months of enrollment had met the ART eligibility criteria before death. CONCLUSION: HIV-positive children experienced a high mortality and loss-to-follow-up rates before starting ART. These program outcomes may be improved by a more timely ART initiation. Measuring overall in-program mortality as opposed to only mortality on ART is recommended in order to more accurately evaluate pediatric HIV-programs performance

Rapid Identification of Genetic Modifications in Bacillus anthracis Using Whole Genome Draft Sequences Generated by 454 Pyrosequencing

Background The anthrax letter attacks of 2001 highlighted the need for rapid identification of biothreat agents not only for epidemiological surveillance of the intentional outbreak but also for implementing appropriate countermeasures, such as antibiotic treatment, in a timely manner to prevent further casualties. It is clear from the 2001 cases that survival may be markedly improved by administration of antimicrobial therapy during the early symptomatic phase of the illness; i.e., within 3 days of appearance of symptoms. Microbiological detection methods are feasible only for organisms that can be cultured in vitro and cannot detect all genetic modifications with the exception of antibiotic resistance. Currently available immuno or nucleic acid-based rapid detection assays utilize known, organism-specific proteins or genomic DNA signatures respectively. Hence, these assays lack the ability to detect novel natural variations or intentional genetic modifications that circumvent the targets of the detection assays or in the case of a biological attack using an antibiotic resistant or virulence enhanced Bacillus anthracis, to advise on therapeutic treatments. Methodology/Principal Findings We show here that the Roche 454-based pyrosequencing can generate whole genome draft sequences of deep and broad enough coverage of a bacterial genome in less than 24 hours. Furthermore, using the unfinished draft sequences, we demonstrate that unbiased identification of known as well as heretofore-unreported genetic modifications that include indels and single nucleotide polymorphisms conferring antibiotic and phage resistances is feasible within the next 12 hours. Conclusions/Significance Second generation sequencing technologies have paved the way for sequence-based rapid identification of both known and previously undocumented genetic modifications in cultured, conventional and newly emerging biothreat agents. Our findings have significant implications in the context of whole genome sequencing-based routine clinical diagnostics as well as epidemiological surveillance of natural disease outbreaks caused by bacterial and viral agents

Ethnic Variation in Inflammatory Profile in Tuberculosis

PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A new recurring chromosome 13 abnormality in two older patients with de novo acute myeloid leukemia: An Indian experience

We report here two cases of trisomy 13 in acute myeloid leukemia M1 subtype. short-term unstimulated bone marrow and peripheral blood lymphocyte culture showed 47, XY, +13 in all metaphase plates and trisomy 13 was confirmed with whole chromosome paint probes. Trisomy 13 in AML-M1 is a rare numerical abnormality. This is the first Indian report of sole trisomy 13 in AML-M1. Here, we present two cases of elder male patients, which may constitute a distinct subtype

Heterociklički derivati progesterona s antimikrobnim djelovanjem

The aim of this work was to synthesize steroidal heterocycles and to elucidate the potential role of these compounds as antimicrobial agents. The synthesis of steroidal heterocycles containing the pyrazole, isoxazole, thiazole, pyrane, pyridine, pyridazine, or benzopyrane ring attached to the pregnene nucleus is reported. Progesterone (1) reacts with dimethyl formamide dimethyl acetal to form enamine 2. Heterocyclization of 2 with hydrazines, hydroxylamine, glycine, ethylacetoacetate or cyanomethylene afforded novel steroidal heterocyclic derivatives. The in vitro antimicrobial evaluation showed that all synthesized compounds show activity against the used strains of Gram positive bacteria and fungi.U radu je opisana sinteza steroidnih heterocikličkih spojeva i evaluacija njihovog antimikrobnog djelovanja. Sintetizirani spojevi sadrže pirazol, izoksazol, tiazol, piran, piridin, piridazin ili benzopiran na pregnenskoj jezgri. Progesteron (1) je prvo u reakciji s dimetil formamid dimetil acetalom dao enamin 2. Novi steroidni heterociklički derivati dobiveni su heterociklizacijom spoja 2 s hidrazinima, hidroksilaminom, glicinom, etilacetoaceatom i cijanometilenom. Antimikrobno vrednovanje in vitro pokazalo je da su svi sintetizirani spojevi aktivni protiv testiranih Gram pozitivnih bakterija i gljivica