Epidemiology and Antifungal Susceptibility Patterns of Invasive Fungal Infections (IFIs) in India: A Prospective Observational Study

The epidemiology of invasive fungal infections (IFI) is ever evolving. The aim of the present study was to analyze the clinical, microbiological, susceptibility, and outcome data of IFI in Indian patients to identify determinants of infection and 30-day mortality. Proven and probable/putative IFI (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group and AspICU criteria) from April 2017 to December 2018 were evaluated in a prospective observational study. All recruited patients were antifungal naïve (n = 3300). There were 253 episodes of IFI (7.6%) with 134 (52.9%) proven and 119 (47%) probable/putative infections. There were four major clusters of infection: invasive candidiasis (IC) (n = 53, 20.9%), cryptococcosis (n = 34, 13.4%), invasive aspergillosis (IA) (n = 103, 40.7%), and mucormycosis (n = 62, 24.5%). The significant risk factors were high particulate efficiency air (HEPA) room admission, ICU admission, prolonged exposure to corticosteroids, diabetes mellitus, chronic liver disease (CLD), acquired immunodeficiency syndrome (AIDS), coronary arterial disease (CAD), trauma, and multiorgan involvement (p < 0.5; odds ratio: >1). The all-cause 30-day mortality was 43.4% (n = 110). It varied by fungal group: 52.8% (28/53) in IC, 58.8% (20/34) in cryptococcosis, 39.8% (41/103) in IA, and 33.9% (21/62) in mucormycosis. HEPA room, ICU admission for IC; HEPA rooms, diabetes mellitus for cryptococcosis; hematological malignancies, chronic kidney disease (CKD), sepsis, galactomannan antigen index value ≥1 for IA and nodules; and ground glass opacities on radiology for mucormycosis were significant predictors of death (odds ratio >1). High minimum inhibitory concentration (MIC) values for azoles were observed in C. albicans, C. parapsilosis, C. glabrata, A. fumigatus, A. flavus, R. arrhizus, R. microsporus, and M. circinelloides. For echinocandin, high MIC values were seen in C. tropicalis, C. guillermondii, C. glabrata, and A. fumigatus. This study highlights the shift in epidemiology and also raises concern of high MICs to azoles among our isolates. It warrants regular surveillance, which can provide the local clinically correlated microbiological data to clinicians and which might aid in guiding patient treatment.

Coronary Microvascular Dysfunction

Coronary microvascular dysfunction (DMK) is a condition of patients who are accompanied by complaints of chest pain where the results of coronary angiography examination are normal and this is almost 49% with 60% of patients diagnosed with DMK. Another study said that about 40% of patients with DMK showed coronary flow reserve (CFR <2) of about 40% and the WISE study (Women's Ischaemia Syndrome Evaluation) showed that about 47% of patients with chest pain had normal coronary arteries. DMK can be divided into 4 groups; DMK with no coronary arterial disease (CAD) obstruction and myocardial disease, DMK with myocardial disease where this occurs due to remodeling of intramural coronary arteries, DMK with CAD (coronary arterial disease) or acute myocardial infarction with or without ST segment, iatrogenic typhoid DMK occurs after coronary recanalization caused by vasoconstriction and distal embolization. The mechanism of action of DMK can be caused by several factors, namely endothelial dysfunction, smooth muscle dysfunction, decreased diastolic perfusion time, damage to blood vessels and damage to the vascular and microvascular remodeling. And to enforce this DMK, there are several tests carried out in diagnosing the disease, some of which are invasive and non-invasive so that by enforcing the diagnosis of this disease, treatment for DMK can be done immediately and optimally.

Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis

Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

Serum Uric Acid and Coronary Arterial Disease in Predialysis Chronic Kidney Disease Patients

Background–Aim: Uric acid is considered a marker of high cardiovascular risk. We investigated the association between serum uric acid and coronary arterial disease (CAD) in pre-dialysis chronic kidney disease (CKD) patients. Methods: We enrolled 110 subjects on mean age 69.02 ± 14.3 years old. The participants were categorized for both estimated glomerular filtration rate (eGFR) and albuminuria according to criteria 2012 of the Kidney Disease Improving Global Outcomes. Estimated pulse wave velocity (ePWV) was calculated using an equation including the age and mean blood pressure. The CAD prevalence rate was recorded. Results: The patients were divided in two groups according to uric acid cutoff point value related to high ePWV. The patients with higher uric acid were older and they had significantly higher systolic blood pressure, pulse pressure, and parathyroid hormone, but significantly lower eGFR and 1,25(OH)2 Vit D3 levels. The association between high uric acid and both high ePWV and CAD occurrence was found to be significant ( x2 = 6.7, P = .008 and x2 = 4.1, P = .03, respectively), although the relationship with albuminuria was found to be nonsignificant. In a built multifactorial model, the low serum uric acid rather than the high was found to be an independent predictor for CAD demonstration entering traditional and specific confounders. Conclusion: The low serum uric acid levels were proved to be a significant predictor for CAD accounting potential covariates, even though the high uric acid per se was found to be connected with cardiovascular disease characteristics including arterial stiffness in predialysis CKD patients.

Association of Abnormal Brachial Index with Diabetic Nephropathy as an Independent Risk Factor for Coronary Arterial Disease in Type 2 Diabetic Patients - A Retrospective Single Centre Real-World Evidence Study in Indian Population

Objective: To study the association between ankle brachial index (ABI) and microvascular complications in Type 2 diabetes (T2DM) patients with the coronary arterial disease (CAD). Methodology: A retrospective study was carried out on 3,458 T2DM patients reportedly with CAD, G1 (n=33), and without CAD, G2 (n=3125), who had given the ABI test. ABI was defined as normal (1.0 - 1.4) and abnormal (<1.0 and >1.4). The logistic regression analysis was used to identify the determinants of CAD positive outcomes in T2DM patients. Results: Overall, patient percentage-wise CAD 10% (333), abnormal ABI 26% (913), neuropathy 37% (1278), nephropathy, 8% (293), and retinopathy <1% (24). The ABI abnormality and CAD positives were higher in patients with nephropathy (32 and 20%) than in neuropathy (28 and 13%). Age-wise, 52 and 62% of neuropathy and nephropathy patients, respectively, were >60 years and had shown increased ABI abnormality from age 50 years onwards. The logistic model had shown nephropathy patients, [OR-1.8 [1.26-2.58], - p-0.001] in association with abnormal ABI, [OR-1.27 [95% CI, 0.99–1.63], p- 0.057] predicted to have CAD positive outcomes. While neuropathy, OR-0.69, [0.54 - 0.90], and hypertension, OR-0.43 [0.33 - 0.57] were not contributing towards CAD in our study population. Conclusion: Type 2 diabetes patients with abnormal ABI were predicted to have a 27% increased odds ratio of CAD outcome and 80% in the presence of nephropathy. Thus, as part of comprehensive diabetes care, albuminuria screening along with ABI measurement is being suggested.

Impact of iron status and inflammatory indices on atherosclerotic burden of patients with helicobacter pylori infection and coronary arterial disease

Objective: Both inflammation and iron deficiency are suggested to be associated with coronary arterial diseases (CAD) and H. Pylori infection. The explanatory interaction depending on serum iron status and inflammatory biomarkers for the extent of atherosclerosis in H. Pylori infection is obscure. Therefore, we aimed to analyze the impact of iron Status and inflammatory indices on atherosclerotic burden of seropositive CAD patients with CagA (cytotoxin-associated gene A) strains of H. Pylori. Materials and Methods: This was an observational study of patients' undergone elective and urgent coronary angiography due to CAD. Serologic H. pylori infection status and iron status was determined in all of 293 subjects. Further seropositive patients were divided into groups to evaluate the extent of coronary atherosclerosis according to Syntax scoring system. Propensity score matching and covariate- adjusted multivariate logistic regression were used to adjust for baseline differences between study groups. Results: The odds ratio of positive serology for the presence of iron deficiency and acute coronary syndromes were 2.5 (95% CI (1.1-5.4); p = 0.02) and 3.0 (95% CI (1.3-7.0); p = 0.007) respectively. After controlling for diabetes mellitus, smoking, MPV, RDW and haemoglobin levels; Tsat ≤ 24.5 remained negatively associated with advanced atherosclerosis (OR:9.9, 95% CI (4.1-24.3); p < 0.0001). In our matched sample, multivariable linear regression analysis showed that association of syntax score with Tsat was independent of hs-CRP (p=0.001). Conclusions: Irrespective of inflammatory status, transferrin saturation can be the decisive mirror indicator of advanced atherosclerosis in seropositive CAD patients with CagA strains of H. Pylori.

Acute coronary syndrome as the first presentation of antiphospholipid antibody syndrome

We describe a case of a 42-year-old man who presented with anginal chest pain. He had objective evidence of ongoing cardiac injury. After initial treatment for coronary arterial disease, cardiac catheterisation revealed diffuse coronary arterial thrombosis with embolisation. Follow-up testing implicated new-onset antiphospholipid antibody syndrome as the aetiology.

Dexmedetomidine as a Heart Rate Control for Off-Pump Coronary Artery Bypass Surgery

Introduction: The traditional surgical approach is performed under cardiac arrest with cardiopulmonary bypass (CPB), which has the potential to result in myocardial injuries. In 1990s, when researchers developed efficient mechanical stabilizer devices, Off-pump coronary artery bypass (OPCAB) gained more widespread interest, as it’s associated with many significant benefits. Avoidance of tachycardia is a goal for anesthetic management during OPCAB surgery. A short-acting Beta-blocker is needed for lowering excessive increases in heart rate. However, in some hospitals these drugs were not available. Case: A 53-yr-old, 73 kg man with a three-vessel coronary arterial disease with left main disease was scheduled for elective OPCAB surgery. Patient has a medical history of heart attack and hypertension. Preoperative echocardiography shows reduced LV systolic function, diastolic dysfunction grade I, with LVEF 47%. Throughout the hour after induction, HR increased in a constant manner to a persistent of 85-90 bpm despite additional fentanyl given. We didn’t have any intravenous beta blocker drug and therefore we started dexmedetomidine. HR decreased to 55-60 bpm and remained at that value throughout the surgical procedure. Patient extubated in OR and transferred to ICU. After 6 days, he was discharged from the hospital without any complications. Conclusion: Perioperative administration of Dexmedetomidine is an effective adjuvant to general anaesthesia, attenuates the stress response to intubation, provides minimal heart rate variations, enabling smooth extubation, also provides adequate sedation in the post-operative period.

Dexmedetomidine as a Heart Rate Control for Off-Pump Coronary Artery Bypass Surgery

Introduction: The traditional surgical approach is performed under cardiac arrest with cardiopulmonary bypass (CPB), which has the potential to result in myocardial injuries. In 1990s, when researchers developed efficient mechanical stabilizer devices, Off-pump coronary artery bypass (OPCAB) gained more widespread interest, as it’s associated with many significant benefits. Avoidance of tachycardia is a goal for anesthetic management during OPCAB surgery. A short-acting Beta-blocker is needed for lowering excessive increases in heart rate. However, in some hospitals these drugs were not available. Case: A 53-yr-old, 73 kg man with a three-vessel coronary arterial disease with left main disease was scheduled for elective OPCAB surgery. Patient has a medical history of heart attack and hypertension. Preoperative echocardiography shows reduced LV systolic function, diastolic dysfunction grade I, with LVEF 47%. Throughout the hour after induction, HR increased in a constant manner to a persistent of 85-90 bpm despite additional fentanyl given. We didn’t have any intravenous beta blocker drug and therefore we started dexmedetomidine. HR decreased to 55-60 bpm and remained at that value throughout the surgical procedure. Patient extubated in OR and transferred to ICU. After 6 days, he was discharged from the hospital without any complications. Conclusion: Perioperative administration of Dexmedetomidine is an effective adjuvant to general anaesthesia, attenuates the stress response to intubation, provides minimal heart rate variations, enabling smooth extubation, also provides adequate sedation in the post-operative period.