Pharmaceuticals of Emerging Concern in Aquatic Systems: Chemistry, Occurrence, Effects, and Removal Methods.

In the last few decades, pharmaceuticals, credited with saving millions of lives, have emerged as a new class of environmental contaminant. These compounds can have both chronic and acute harmful effects on natural flora and fauna. The presence of pharmaceutical contaminants in ground waters, surface waters (lakes, rivers, and streams), sea water, wastewater treatment plants (influents and effluents), soils, and sludges has been well doccumented. A range of methods including oxidation, photolysis, UV-degradation, nanofiltration, reverse osmosis, and adsorption has been used for their remediation from aqueous systems. Many methods have been commercially limited by toxic sludge generation, incomplete removal, high capital and operating costs, and the need for skilled operating and maintenance personnel. Adsorption technologies are a low-cost alternative, easily used in developing countries where there is a dearth of advanced technologies, skilled personnel, and available capital, and adsorption appears to be the most broadly feasible pharmaceutical removal method. Adsorption remediation methods are easily integrated with wastewater treatment plants (WWTPs). Herein, we have reviewed the literature (1990-2018) illustrating the rising environmental pharmaceutical contamination concerns as well as remediation efforts emphasizing adsorption.

SGLT2-inhibition and Vascular Euphoria a Reconciliation of Vascular Health and Disease Homeostasis.

The concept of SGLT2-inhibition, once regarded as a non-physiological approach to glycemia control, now finds a foundational relevance in risk-modification for cardiovascular, kidney, and metabolic outcomes, spanning beyond type-2 diabetes. Major studies have proven meaningful improvements in various clinical outcomes, with different SGLT2-i agents. Apart from glycosuria, SGLT2-inhibition is associated with several patho-physiological effects, which may contribute to the clinical benefits seen with these agents. This narrative review is an attempt to appraise the different patho-physiological effects mediated by SGLT2-inhibition, based on contemporary evidence. The review classifies these effects in the acronym of EUPHORIA, and grades the possible relevance of each effect, in improving clinical outcomes.

Screening for heart failure in diabetes.

Heart failure (HF) is an important, yet under recognized and under diagnosed complication of diabetes. This communication describes the clinical features of heart failure, and shares a validated tool which helps identify HF. This information will be of help to all health care professionals, especially those who work in primary care settings with minimal access to advanced imaging and biochemical investigations.

Cardiovigilance in COVID 19.

The COVID19 (Corona Virus Disease: pandemic started in 2019) pandemic has created not only a public health problem, but as a clinical challenge as well. To the cardiologist, COVID 19 presents a wide spectrum of possibilities for clinical decision-making intervention and improvement. Cardiac dysfunction has been identified as a risk factor, a prognostic factor, a diagnostic tool, differential diagnosis, a complication of COVID 19, and a side effect of its treatment. Certain cardiotropic drugs have been implicated in the pathogenesis of COVID 19. The risk of transmission of COVID 19 is an occupational hazard which cannot be ignored by cardiologists. This review discusses the need and scope of cardio vigilance in COVID 19 management.

Cardiovigilance.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality across the globe. Prevention and management of the CVD pandemic calls for concerted action on part of all health care professionals, as well as other concerned stakeholders. We call for cardiovigilance in healthcare and define it as "the action or state of keeping careful watch, to prevent, screen, diagnose and manage cardiovascular disease (CVD) in a timely and appropriate manner". We expand upon the concept of cardiovigilance, describe its utility, and suggest various taxonomic rubrics to simplify its practice.

Anginal Equivalents: As simple as ABCDE.

This communication highlights the concept of angina equivalents as an important symptom of cardiovasculardisease in diabetes. The authors share two mnemonics, as simple as ABCDE, which can help identify atypical cardiovascular disease. Use of these learning tools should help improve early detection and management of cardiovascular disease.

Atrial fibrillation: The endocrine connection.

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in cardiology practice. A diagnosis of AF implies a greater need for hospitalization, a higher risk of stroke and heart failure, and earlier mortality. These complications can be avoided if AF is diagnosed and treated in a timely manner. To achieve this, physicians need to maintain a high index of clinical suspicion, practice cardiovigilance, and screen for AF in appropriate clinical settings. This review describes the vast spectrum of endocrine and metabolic disease that are associated with AF. Through this perspective, it encourages physicians and endocrinologists to play an active role in AF detection, referral and long term management.

Atrial fibillation in diabetes: Need for cardiovigilance.

Atrial fibrillation (AF), the commonest arrhythmia in clinical practice, is also the commonest arrhythmia for which hospitalization is required. AF is associated with a 5 fold increase in stroke, a 2 fold increase in all-cause mortality, and a higher risk of heart failure. Hence, it is imperative to focus on the risk factors and clinical features of this condition, so that it can be prevented and managed in a timely manner. AF is linked with multiple metabolic and endocrine morbidities. This implies that the endocrinologist has an important role to play in AF detection and referral. This review, the first of a two part series, encourages preventive cardiovigilance, and especially electro-cardiovigilance, in diabetes practice.

The Lipo- Phenotypic Screening Tool for Familial Hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a common disorder of lipid metabolism. However, it is rarely diagnosed in time, leading to a high burden of preventable cardiovascular (CV) morbidity. The authors describe a lipophenotypic screening tool, which can be used by clinicians to screen for FH. This simple construct is based on history, physical examination, lipid profile and non-invasive cardioimaging. Structured as a bidirectional three column rubric, this tool should be able to improve clinical skills and teaching related to FH.

Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population.

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95 ± 17.16 pg/ml, controls: 70.55 ± 15.87 pg/ml, p < 0.001). G allele of 603A>G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p = 0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p = 0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738-2.651) and 4.41 fold (95% CI 1.404-13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.

Evaluation of role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative DVT patients: a study in India.

Resistance to APC (APCR) is a very important cause of thrombophilia and most frequently caused by the Leiden mutation. APCR is also seen in the absence of FV Leiden and associated with elevated levels of factor V (FV), factor VIII (FVIII) and antiphospholipid antibodies (APLAs). The aim of this prospective case control study was to find out the frequency and role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative deep vein thrombosis (DVT) patients in India. A total 30 APCR positive and FV Leiden negative patients with DVT and similar number of age and sex matched healthy controls were recruited. Significantly higher mean FVIII levels were observed in patients as compared to controls [patients: 132.3 ± 30.7 IU/ml, controls: 117.5 ± 17.7 IU/ml, p = 0.025]. A significant negative correlation was also observed between FVIII and APC ratio (Pearson correlation = 0.368, p = <0.001). Mean FV levels in patients [107.1 ± 13.1 IU/ml] and controls [102 ± 11.9 IU/ml] were not statistically significant (p = 0.119). Anti ß2 glycoprotein I (Anti-ß2-GPI, IgG) showed significant association with APCR phenotype (p = 0.050), unlike other factors such as protein C, protein S, lupus anticoagulant and anticardiolipin antibodies. The strong association of FVIII and anti-ß2 GPI (IgG) antibodies with APCR phenotype is suggestive of incorporation of these factors in APCR positive DVT patients in the absence of FV Leiden mutation in India. However more studies in large sample size are required for setting up the proper investigation protocol in these patients.

3D Xplane Echocardiographic Technique for Validation of Mitral Leaflet Separation to Assess Severity of Mitral Stenosis.

BACKGROUND: Determining the severity of mitral stenosis (MS) is important for both prognostic and therapeutic implications. Mitral valve area (MVA) calculation techniques have more limitations. Mitral leaflet separation (MLS) is a precise and operator friendly alternative to planimetry. In contrast to previous researchers, we have used a novel 3D Xplane technique to validate MLS for assessing the severity of MS. 3D Xplane is superior for validation of MLS due to simultaneous real time acquisition of MLS in parasternal long-axis view and corresponding MVA by planimetry in parsternal short-axis view. METHODS: It was a prospective observational single center study. A total of 174 patients with MS were evaluated for MVA estimation by various echocardiographic modalities. Maximum leaflet separation and corresponding planimetered MVA were measured using novel 3D Xplane technique. RESULTS: With 3D Xplane technique, there was strong positive correlation between planimetered MVA and MLS (R = 0.925, P < 0.001), irrespective of coexisting MR (R = 0.886, P < 0.001) or AF (R = 0.912, P < 0.001). Receiver operating characteristic curves of MLS demonstrated AUC for mild and severe MS to be 0.966 and 0.995, respectively. MLS less than 8.62 mm predicted severe MS with 95.5% sensitivity and 94.7% specificity and MLS more than 12.23 mm predicted mild MS with 93.2% sensitivity and 91.4% specificity. CONCLUSION: In our study, a strong correlation between planimetered MVA and MLS was found using 3D Xplane technique. 3D Xplane thus validates and standardizes MLS by excluding errors due to temporal and spatial variations which are important limitations of 2D echocardiography.

Palmar arch anatomy: Ajmer Working Group classification.

INTRODUCTION: Forearm arteries are frequently used as workhorse site for cardiac catheterization, bypass grafting and haemodialysis access. There is paucity of data on palmar circulation in live human being and only cadaveric data are available till date. We, therefore, made an attempt to look at the various patterns of sufficient or insufficient palmar arch circulation and various anomalies of forearm arteries, to discuss their clinical implications. METHODS AND RESULTS: We obtained the forearm and hand arteriograms of patients (n = 302) through radial (n = 200) and ulnar routes (n = 102). Modified Allen's test was normal in all of our patients. On the basis of predetermined parameters angiograms were analysed and findings were divided into three groups. These three groups were further classified as type A, type B, type C superficial palmar arch. CONCLUSION: We concluded that type A superficial palmar arch is most suitable for providing adequate collateral circulation in case of harvesting of forearm vessel, whereas type C superficial palmar arch appears to be highly susceptible for digital ischemia in case of radial or ulnar artery occlusion. Modified Allen's test alone is not justifiable for documenting good collateral circulation and it should be supplemented by other tests to document good collateral circulation before proceeding to any radical procedure.

The cardiovascular phenotype: impact on choice of glucose- lowering therapy.

One of the major endpoints to be considered while choosing glucose-lowering therapy is their impact on cardiovascular outcomes. As a corollary, the cardiovascular health assessment of a person with diabetes informs the choice of glucose-lowering treatment. The clinical aspects included in this bidirectional relationship are described in this review as the cardiovascular phenotype. Vital signs, cardiac autonomic function, myocardial health and coronary status influence, and are influenced by, choice of glucose-lowering therapy. Such therapy also has an impact on cerebrovascular and peripheral arterial health. These aspects should be considered while planning treatment for type 2 diabetes mellitus.

Factors contributing to APC-resistance in women with recurrent spontaneous miscarriages: Indian perspective.

Phenotypic resistance to APC is a complex mechanism associated with increased risk of venous thrombosis in women with recurrent spontaneous abortions. The primary aim of this prospective case control study was to find out the frequencies of different congenital and acquired thrombophilic factors predisposing to APC resistance and to evaluate the strength of their association with recurrent pregnancy losses. FV Leiden accounted for around 40% of all APCR positive patients and the difference in the group frequencies compared with controls, was found to be statistically significant (p=0.001). 18.33% (11/60) FV Leiden-negative APC-resistant patients had FVIII: c values exceeding 95th percentile of the control population (145IU/dL), as compared to 3% in the control group (p=0.001). Mean FVIII level in control subjects was 118±14.0IUdL(-), compared with 127.7±31.2IUdL(-) in the patient group (p=0.009). Apart from FVIII, only the anti-phospholipid antibodies showed a statistically significant association with APCR phenotype (p=0.028), unlike other thrombophilic factors such as Protein C, Protein S, FV levels, HR2 haplotype or other rarer FV variants. The strong positive association of FVL mutation, anti-phospholipid antibodies and elevated FVIII levels with APCR phenotype calls for incorporating them as first line investigations in patients with recurrent spontaneous miscarriages with APCR positivity.

Feasibility of ulnar artery for cardiac catheterization: AJmer ULnar ARtery (AJULAR) catheterization study.

BACKGROUND: The ulnar artery is rarely selected for cardiac catheterization despite the expanding use of the transradial access (TRA). We tried to compare default transulnar access (TUA) with TRA in terms of feasibility and safety. MATERIALS AND METHODS: This was a prospective, open label, single center, observational study. We analyzed a total of 410 patients with normal Allen's test, who were then scheduled for coronary angiography through TUA with ad hoc PCI if necessary. Procedures were performed by a single operator who had an adequate transradial experience (≥150 transradial coronary procedures per year) but not trained in transulnar procedures. We analyzed observed findings with a retrospective cohort of patients undergoing TRA angiography under a previous study done at our center. We also performed selective ulnar arteriography of 200 patients, through radial route, to predict the bottlenecks of TUA. OBSERVATIONS: There is no statistically significant difference among the number of attempts made till the successful puncture, the total procedure time and the total fluoroscopy time for either radial or ulnar access angiography by an experienced operator (P > 0.05). However, the time taken in arterial access is statistically significant in the initial learning curve for the same (P < 0.05). On the contrary, the arterial access time, the total procedure time, and the total fluoroscopy time, all are statistically significant for the inexperienced operator (P < 0.05). There is a negligible incidence of nonmaneuverable anatomic obstruction in the real-world scenario in TUA, and so fear of the same should not impede the use of this route. Vasospasm in the use of this route is also not different from the radial route, with the experience of the operator. CONCLUSIONS: For an experienced operator, TUA is a safe and also an effective alternative to TRA in terms of feasibility and safety.

Polymorphisms in factor V and antithrombin III gene in recurrent pregnancy loss: a case-control study in Indian population.

Recurrent pregnancy loss (RPL) can be caused due to diverse factors with thrombophilia being one of them. The association of various thrombophilic risk factors with RPL is inconsistent in different studies and the frequency of these risk factors in Indian population is obscure. Five hundred and eighty patients with either recurrent early miscarriage or a history of at least one late miscarriage were screened for deficiency of protein C (PC), protein S (PS), antithrombin III (AT), APC resistance and prothrombin 20210G > A mutation. APC resistance positive patients were typed for the factor V Leiden, factor V Hong Kong/Cambridge mutations, and HR2 haplotype. PstI and rs2227589 AT mutations were detected by direct sequencing. APC resistance (13.4 %) was detected to be most common in Indian RPL patients followed by PS (10.6 %), PC (9.8 %) and AT deficiency (4.31 %.). FV Leiden was shown to be associated with APC resistance while HR2 haplotype was not associated with APC resistance (p values: 0.0001 and 0.327 respectively) and the increased risk of RPL. PstI and rs2227589 polymorphisms were similar in patients and controls and not associated with AT deficiency in RPL. Our study emphasizes the presence of other contributory factors towards APC resistance rather than FV Leiden alone. This is the first Indian study where HR2 haplotype and rs2227589 are observed to be present in RPL population. Although not significant, occurrence of rs2227589 and FV HR2 in homozygous condition necessitates the study of these polymorphisms in a larger sample size.

Platysmal Myocutaneous Flap for Intra Oral Defects:Is It an Underutilized Option? Our Experience of 10 Cases.

Various methods of reconstruction are available for reconstructing oral cancer defects, but all of them have their inherent drawbacks. The superiorly based platysma myocutaneous flap is a common reconstruction option for intra-oral defects following oral cancer resections. We present our results of using platysmal flaps in reconstructing intraoral defects following oral cavity cancer resection in our 7 patients along with resection of three cases of premalignant conditions of oral cavity. All the patients were males of age ranging from 24 to 42 years and diagnosed as squamous cell carcinoma of oral cavity stage I and II were included in this study.Of 10 patients eight had no postoperative complications. One patient developed partial skin loss of neck donor site, which was managed conservatively. Other patient had complete flap loss which healed with secondary intention. We recommend this flap as incision is always away from the face, the scars are hidden beneath collars and the patients are very comfortable with good cosmetics and functional outcomes.\.

Sarcopenic Obesity as a Risk Factor for Cardiovascular Disease: An Underrecognized Clinical Entity.

Sarcopenic obesity (SO) is a chronic condition and an emerging health challenge, in view of the growing elderly population and the obesity epidemic. Due to a lack of awareness among treating doctors and the non-specific nauture of the associated symptoms, SO remains grossly underdiagnosed. There is no consensus yet on a standard definition or diagnostic criteria for SO, which limits the estimation of the global prevalence of this condition. It has been linked to numerous metabolic derangements, cardiovascular disease (CVD) and mortality. The treatment of SO is multimodal and requires expertise across multiple specialties. While dietary modifications and exercise regimens have shown a potential therapeutic benefit, there is currently no proven pharmacological management for SO. However, numerous drugs and the role of bariatric surgery are still under trial, and have great scope for further research. This article covers the available literature regarding the definition, diagnostic criteria, and prevalence of SO, with available evidence linking it to CVD, metabolic disease and mortality, and an overview of current directives on management.

Depolarized Mitochondrial Membrane Potential and Elevated Calcium in Platelets of Sickle Cell Disease.

Hemolysis, a crucial feature of Sickle cell disease (SCD), is a key player for cellular activation leading to various complications including thrombosis. In response to hemolysis, platelets get activated and release components that are necessary for further platelet activation and aggregation. Thus, it is believed that platelets contribute to the development of thrombotic complications. Platelets in SCD are expected to be affected due to common cause of hemolysis. To measure the surface markers of platelets including P-Selectin, Phosphatidyl Serine and integrin αIIbß3 in SCD patients and healthy controls in order to understand the status of the platelets in SCD. To measure the surface markers of activated platelets using flow cytometry. Since mitochondria and calcium play an important role in cellular functions, the mitochondrial membrane potential and calcium content of platelets in SCD were also evaluated using flow cytometry. In the present study, we have observed significant increase of calcium level in SCD platelets. Further, the loss of mitochondrial membrane potential in SCD platelets was found to be significantly higher when compared to platelets of healthy controls. Though the surface markers of activated platelets in SCD remain unchanged, increased level of calcium and mitochondrial membrane potential loss suggest that the platelets in SCD are more prone to become activated. In order to understand the status of the platelets in SCD, apart from the surface markers, it is also important to assess the calcium levels and mitochondrial membrane potential of platelets.