Secretion of Sphinganine by Drug-Induced Cancer Cells and Modified Mimetic Sphinganine (MMS) as c-Src Kinase Inhibitor.

BACKGROUND: Cancer cells exhibit selective metabolic reprogramming to promote proliferation, invasiveness, and metastasis. Sphingolipids such as sphingosine and sphinganine have been reported to modulate cell death processes in cancer cells. However, the potential of extracellular sphinganine and its mimetic compounds as inducers of cancer cell death has not been thoroughly investigated. METHODS: We obtained extracellular conditioned medium from HCT-116 cells treated with the previously reported anticancer composition, goat urine DMSO fraction (GUDF). The extracellular metabolites were purified using a novel and in-house developed vertical tube gel electrophoresis (VTGE) technique and identified through LC-HRMS. Extracellular metabolites such as sphinganine, sphingosine, C16 sphinganine, and phytosphingosine were screened for their inhibitory role against intracellular kinases using molecular docking. Molecular dynamics (MD) simulations were performed to study the inhibitory potential of a novel designed modified mimetic sphinganine (MMS) (Pubchem CID: 162625115) upon c-Src kinase. Furthermore, inhibitory potential and ADME profile of MMS was compared with luteolin, a known c-Src kinase inhibitor. RESULTS: Data showed accumulation of sphinganine and other sphingolipids such as C16 sphinganine, phytosphingosine, and ceramide (d18:1/14:0) in the extracellular compartment of GUDF-treated HCT-116 cells. Molecular docking projected c-Src kinase as an inhibitory target of sphinganine. MD simulations projected MMS with strong (-7.1 kcal/mol) and specific (MET341, ASP404) binding to the inhibitory pocket of c-Src kinase. The projected MMS showed comparable inhibitory role and acceptable ADME profile over known inhibitors. CONCLUSION: In summary, our findings highlight the significance of extracellular sphinganine and other sphingolipids, including C16 sphinganine, phytosphingosine, and ceramide (d18:1/14:0), in the context of drug-induced cell death in HCT-116 cancer cells. Furthermore, we demonstrated the importance of extracellular sphinganine and its modified mimetic sphinganine (MMS) as a potential inhibitor of c-Src kinase. These findings suggest that MMS holds promise for future applications in targeted and combinatorial anticancer therapy.

Intracellular Ellagic Acid Derived from Goat Urine DMSO Fraction (GUDF) Predicted as an Inhibitor of c-Raf Kinase.

BACKGROUND: Dietary chemicals and their gut-metabolized products are explored for their anti-proliferative and pro-cell death effects. Dietary and metabolized chemicals are different from ruminants such as goats over humans. METHODS: Loss of cell viability and induction of death due to goat urine DMSO fraction (GUDF) derived chemicals were assessed by routine in vitro assays upon MCF-7 breast cancer cells. Intracellular metabolite profiling of MCF-7 cells treated with goat urine DMSO fraction (GUDF) was performed using an in-house designed vertical tube gel electrophoresis (VTGE) assisted methodology, followed by LC-HRMS. Next, identified intracellular dietary chemicals such as ellagic acid were evaluated for their inhibitory effects against transducers of the c-Raf signaling pathway employing molecular docking and molecular dynamics (MD) simulation. RESULTS: GUDF treatment upon MCF-7 cells displayed significant loss of cell viability and induction of cell death. A set of dietary and metabolized chemicals in the intracellular compartment of MCF-7 cells, such as ellagic acid, 2-hydroxymyristic acid, artelinic acid, 10-amino-decanoic acid, nervonic acid, 2,4-dimethyl-2-eicosenoic acid, 2,3,4'- Trihydroxy,4-Methoxybenzophenone and 9-amino-nonanoic acid were identified. Among intracellular dietary chemicals, ellagic acid displayed a strong inhibitory affinity (-8.7 kcal/mol) against c-Raf kinase. The inhibitory potential of ellagic acid was found to be significantly comparable with a known c-Raf kinase inhibitor sorafenib with overlapping inhibitory site residues (ARG450, GLU425, TRP423, VA403). CONCLUSION: Intracellular dietary-derived chemicals such as ellagic acid are suggested for the induction of cell death in MCF-7 cells. Ellagic acid is predicted as an inhibitor of c-Raf kinase and could be explored as an anti-cancer drug.

Reduced Level of Prolylhydroxyproline in the Nail Clippings of Oral Cancer Patients and its Role as an Activator of Phospholipase C-ß2.

BACKGROUND: The oral cancer microenvironment plays an important role in the development and progression of the disease which depicts the heterogeneous nature of diseases. Several cellular and non-cellular factors, including dipeptides, have been reported to drive tumor progression and metastasis. Among various secreted molecules in the tumor microenvironment, prolylhydroxyproline (Pro-Hyp) is a collagen-degraded product with specific relevance to fibrosis and oral cancer. However, the detection of Pro-Hyp in the nails of oral cancer patients is a potential biomarker, and our understanding of the biological relevance of Pro-Hyp is highly limited. METHODS: Here, the authors have attempted to use a novel and in-house vertical tube gel electrophoresis (VTGE) protocol to evaluate the level of Pro-Hyp in the nails of oral cancer patients and healthy subjects. Furthermore, we employed molecular docking and molecular dynamics (MD) simulations to predict the biological function of Pro-Hyp. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp and a known PLC-ß2 activator, m-3M3FBS, were evaluated by the SWISS-ADME server. RESULTS: We report that among various key metabolites, Pro-Hyp, a dipeptide, is reduced in the nails of oral cancer patients. Molecular docking and MD simulations helped to suggest the potential role of Pro-Hyp as an activator of Phospholipase C-ß2 (PLC-ß2). Pro-Hyp displayed good binding affinity (-7.6 kcal/mol) with specific interactions by a conventional hydrogen bond with key residues, such as HIS311, HIS312, VAL641, and GLU743. MD simulations showed that the activator binding residues and stability of complexes are similar to the well-known activator m-3M3FBS of PLC-ß2. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp were found to be highly comparable and even better than those of m-3M3FBS. CONCLUSION: This study is one of the first reports on Pro-Hyp as a metabolite biomarker in the nails of oral cancer patients. Furthermore, the implications of Pro-Hyp are proposed to activate PLC-ß2 as a pro-tumor signaling cascade. In the future, diagnostic and therapeutic approaches may be explored as biomarkers and mimetic of Pro-Hyp.

Factors Associated With Hypertension and Cardiovascular Parameters in Children With Infrequently Relapsing Nephrotic Syndrome.

OBJECTIVES: To assess the prevalence of hypertension in children with infrequently relapsing nephrotic syndrome (IRNS) and its association with dyslipidemia, and end organ damage including left ventricular hypertrophy (LVH), at relapse and after steroid induced remission. METHODS: Prospective observational study conducted in 83 children aged 1-12 years with IRNS, presenting in relapse. Blood pressure, fundus examination, blood and urine investigations were done at relapse and then at 4 weeks of therapy. Echocardiography at 4 weeks was performed for assessment of LVH and relative wall thickness (RWT) for concentric geo-metry (CG). RESULTS: 27 patients (32.5%) developed hypertension, out of which 21 patients (25.3%) had stage I hypertension. Hypertension in first episode (63.0%, P<0.01) and in previous relapses (87.5%, P<0.001) was significantly associated with hypertension in the current episode. 12 patients had a positive family history of hypertension, of which 8 (66.7%) were classified under the hypertensive group (P=0.016). Concentric geometry (CG) was found in 28% of hypertensive and 5.5% of non-hypertensive children (P=0.011). On regression analysis, a lower Up:Uc at the time of relapse was found to have a protective role for development of hypertension. CONCLUSION: One third children with IRNS had hypertension at relapse and a high proportion of hypertensive patients had CG pattern on echocardiography.

Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs.

OBJECTIVE: The objective of this study was to explore the biological relevance of free fatty acids derived from cow urine DMSO fraction (CUDF) by employing in vitro and in silico approaches. BACKGROUND: Metabolic heterogeneity at the intra- and intercellular levels contributes to the metabolic plasticity of cancer cells during drug-induced response. Free fatty acid (FFA) availability at intra- and intercellular levels is related to tumor heterogeneity at interpatient and xeno-heterogeneity levels. METHODS: We collected fresh urine from healthy cows and subjected it to fractionation in DMSO using drying, vortexing, and centrifugation. Finally, the sterile filtrate of cow urine DMSO fraction (CUDF) was evaluated for antiproliferative and proapoptotic effects in MCF-7 and ZR-75-1 breast cancer cells using routine cell-based assays. Intracellular metabolites were studied with the help of a novel in-house vertical tube gel electrophoresis (VTGE) method to reveal the nature of CUDF components in MCF-7 cells. Identified intracellular FFAs were studied for their molecular interactions with targeted receptor histone deacetylase (HDAC) using molecular docking and molecular dynamics (MD) simulations. RESULTS: CUDF showed a significant reduction in cell viability and cell death in MCF-7 and ZR-75-1 breast cancer cells. Interestingly, FFAs tetracosanedioic acid, 13Z-docosenoic acid (erucic acid), nervonic acid, 3-hydroxy-tetradecanoic acid, and 3-hydroxcapric acid were found inside the treated MCF-7 cancer cells. These FFAs, including tetracosanedioic acid, indicated a specific affinity to HDAC at their inhibitory sites, similar to trichostatin A, a known inhibitor. CONCLUSIONS: This study reports on FFAs derived from CUDF as potential antiproliferative and pro-cell death agents against breast cancer cells. MD simulations hinted at tetracosanedioic acid and other FFAs as inhibitors of HDAC that could explain the observed effects of FFAs in cancer cells.

Ultra-low CONtraSt PCI vs conVEntional PCI in patients of ACS with increased risk of CI-AKI (CONSaVE-AKI).

OBJECTIVES: This prospective, randomized study assessed short-term outcomes and safety of ultra-low contrast percutaneous coronary intervention(ULC-PCI) vs conventional PCI in high risk for contrast induced acute kidney injury(CI-AKI) patients presenting with acute coronary syndrome(ACS). BACKGROUND: Patients at an increased risk of developing CI-AKI can be identified prior to PCI based on their pre-procedural risk scores. ULC-PCI is a novel contrast conservation strategy in such high risk patients for prevention of CI-AKI. METHODS: 82 patients undergoing PCI for ACS were enrolled having estimated glomerular filtration rate(eGFR) < 60 ml/min/1.73 m2 and moderate to very high pre-procedural risk of developing CI-AKI as calculated by Maioli risk calculator. They were randomized into two groups of 41 patients each of ULC-PCI (contrast volume ≤ patient's eGFR) and conventional PCI (contrast volume ≤ 3xpatient's eGFR). Primary end point was development of CI-AKI. RESULTS: Baseline clinical and angiographic characteristics were similar between groups. Primary outcome of CI-AKI occurred more in patients of the conventional PCI group [7 (17.1%)] than in the ULC PCI group [(0 patients), p = 0.012]. Contrast volume (41.02 (±9.8) ml vs 112.54 (±25.18) ml; P < 0.0001) was markedly lower in the ULC-PCI group. No significant difference in secondary safety outcomes between two study arms at 30 days. IVUS was used in 17% patients in ULC PCI. CONCLUSION: ULC-PCI in patients with increased risk of developing CI-AKI is feasible, appears safe, and has the potential to decrease the incidence of CI-AKI specially in resource limited setting such as ours where coronary imaging by IVUS is not possible in every patient.

Outcome of submitral aneurysm.

INTRODUCTION: Submitral aneurysm is a rare cardiac entity with outpouching in relation to the posterior annulus of the mitral valve. Multiple etiology have been described with the role of infection and inflammation with varied clinical presentation in different case reports. However, the literature on clinical outcome and follow-up is lacking. MATERIAL AND METHOD: This retrospective, observational study included all the adult patients (>18 years) who were diagnosed with a submitral aneurysm. Epidemiological, demographic, laboratory, clinical management, and outcome data were extracted and followed for the endpoints of cardiac death, noncardiac death, recurrent hospitalization (due to heart failure, rupture, arrhythmic events, embolic events), surgical repair, and echocardiography parameters for mitral regurgitation or change in the size of the left ventricle for 1-year postdischarge from the index hospitalization. RESULTS: A total of 10 patients were enrolled in the study with a mean age of 31.2 ± 11.1 years. Possible etiology could be established in only five (50%) patients (two patients had tuberculosis and three patients had acute coronary syndrome). At index hospitalization, nine (90%) patients had heart failure, two (20%) patients had rupture of a submitral aneurysm, four patients underwent surgery, and one patient expired. On follow-up of 1 year, one more patient underwent surgical repair while three patients expired. CONCLUSION: A submitral aneurysm is a rare cardiac entity with poor outcomes. Surgical repair with or without mitral valve replacement plays a definitive role in management.

Enigma of Twins: Identical Presentation and Angiographic Lesion in Monozygotic Twins.

We present a case of monozygotic identical twins presenting with coronary artery disease (CAD), there were striking similarities in the symptoms, coronary anatomy, and lesions.

Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme.

Oncometabolites are known to drive metabolic adaptations in oral cancer. Several oncometabolites are known to be shared between cancer cells and non-cancer cells including microbiotas to modulate the tumor microenvironment. Among potential oncometabolites, succinylaminoimidazolecarboxamide ribose5'-phosphate (SAICAR) supports the growth and invasiveness of cancer cells by pyruvate kinase M2 (PKM2) enzyme in a glucose starved tumor microenvironment. There is a significant gap that shows the detection of SAICAR in biological samples including nails of oral cancer patients. Metabolite identification of SAICAR was investigated in the nails of oral cancer patients using novel vertical tube gel electrophoresis (VTGE) and LC-HRMS. Further molecular docking and molecular dynamics simulations (MDS) were employed to determine the nature of molecular interactions of SAICAR (CHEBI ID:18319) with PKM2 (PDB ID: 4G1N). Molecular docking of SAICAR (CHEBI ID:18319) was performed against pyruvate kinase M2 (PDB ID: 4G1N). Data suggest the presence of oncometabolite SAICAR in nails of oral cancer. Molecular docking of SAICAR with PKM2 showed appreciable binding affinity (-8.0 kcal/mol) with residues including ASP407, THR405, GLU410, ARG443, GLY321, ARG436, HIS439, LYS266, and TYR466. Furthermore, MDS confirmed the specific binding of SAICAR within the activator site of PKM2 and the stability of SAICAR and PKM2 molecular interactions. In conclusion, SAICAR is a promising oncometabolite biomarker present in the nails of oral cancer patients. A significant activation potential of SAICAR exists with the PKM2 enzyme.

An Intracellular Tripeptide Arg-His-Trp of Serum Origin Detected in MCF-7 Cells is a Possible Agonist to ß2 Adrenoceptor.

BACKGROUND: The need for agonists and antagonists of ß2 adrenoceptor (ß2AR) is warranted in various human disease conditions, including cancer, cardiovascular and other metabolic disorders. However, the sources of agonists of ß2AR are diverse in nature. Interestingly, there is a complete gap in the exploration of agonists of ß2AR from serum that is a well-known component of culture media that supports growth and proliferation of normal and cancer cells in vitro. METHODS: In this paper, we employed a novel vertical tube gel electrophoresis (VTGE)-assisted purification of intracellular metabolites of MCF-7 cells grown in vitro in complete media with fetal bovine serum (FBS). Intracellular metabolites of MCF-7 cells were then analyzed by LC-HRMS. Identified intracellular tripeptides of FBS origin were evaluated for their molecular interactions with various extracellular and intracellular receptors, including ß2AR (PDB ID: 2RH1) by employing molecular docking and molecular dynamics simulations (MDS). A known agonist of ß2AR, isoproterenol was used as a positive control in molecular docking and MDS analyses. RESULTS: We report here the identification of a few novel intracellular tripeptides, namely Arg-His- Trp, (PubChem CID-145453842), Pro-Ile-Glu, (PubChem CID-145457492), Cys-Gln-Gln, (PubChem CID-71471965), Glu-Glu-Lys, (PubChem CID-11441068) and Gly-Cys-Leu (PubChem CID-145455600) of FBS origin in MCF-7 cells. Molecular docking and MDS analyses revealed that among these molecules, the tripeptide Arg-His-Trp shows a favorable binding affinity with ß2AR (-9.8 Kcal/mol). The agonistic effect of Arg-His-Trp is significant and comparable with that of a known agonist of ß2AR, isoproterenol. CONCLUSION: In conclusion, we identified a unique Arg-His-Trp tripeptide of FBS origin in MCF-7 cells by employing a novel approach. This unique tripeptide Arg-His-Trp is suggested to be a potential agonist of ß2AR and it may have applications in the context of various human diseases like bronchial asthma and chronic obstructive pulmonary disease (COPD).

An Unusual Intracoronary Honeycomb Pattern in a Patient with Coronary Artery Disease with Dextrocardia.

This case highlights the diagnostic dilemma and emphasis the role of Optical Coherence Tomography (OCT) to differentiate between spontaneous coronary artery dissection and recanalized thrombus with multiple channels in a patient with dextrocardia.

Comparing the Modified Frailty Index with conventional scores for prediction of cardiac resynchronization therapy response in patients with heart failure.

OBJECTIVE: The aim of the study was to compare, Modified Frailty Index (mFI), EAARN (LVEF <22%, Atrial Fibrillation, Age ≥70 years, Renal function (eGFR <60 mL/min/1.73m2), NYHA class IV), and ScREEN (female Sex, Renal function (eGFR ≥60 mL/min/1.73m2), LVEF ≥25%, ECG (QRS duration ≥150 ms) and NYHA class ≤III) score for predicting cardiac resynchronization therapy (CRT) response and all-cause mortality. METHODS: In this prospective, non-randomized, single-center, observational study we enrolled 93 patients receiving CRT from August 2016 to August 2019. Pre-implant scores were calculated, and patients were followed for six months. Performance of each score for prediction of CRT response (defined as ≥15% reduction in left ventricular end-systolic volume [LVESV]) and all-cause mortality was compared. RESULTS: Optimal CRT response was seen in seventy patients with nine deaths. All the three scores exhibited modest performance for prediction of CRT response and all-cause mortality with AUC ranging from 0.608 to 0.701. mFI has an additional benefit for prediction of prolonged post-procedure stay and 30-day rehospitalization events. CONCLUSION: mFI, ScREEN and EAARN score can be used reliably for predicting all-cause mortality and response to CRT.

Six months clinical outcome comparison between quadripolar and bipolar left ventricular leads in cardiac resynchronization therapy: A prospective, non-randomized, single-centre observational study.

BACKGROUND AND OBJECTIVES: Quadripolar left ventricular (LV) leads in cardiac resynchronization therapy (CRT) offer multi-vector pacing with different pacing configurations and hence enabling LV pacing at most suitable site with better lead stability. We aim to compare the outcomes between quadripolar and bipolar LV lead in patients receiving CRT. METHODS: In this prospective, non-randomized, single-center observational study, we enrolled 93 patients receiving CRT with bipolar (BiP) (n = 31) and quadripolar (Quad) (n = 62) LV lead between August 2016 to August 2019. Patients were followed for six months, and outcomes were compared with respect to CRT response (defined as ≥5% absolute increase in left ventricle ejection fraction), electrocardiographic, echocardiographic parameters, NYHA functional class improvement, and incidence of LV lead-related complication. RESULTS: At the end of six months follow up, CRT with quadripolar lead was associated with better response rate as compared to bipolar pacing (85.48% vs 64.51%; p = 0.03), lesser heart failure (HF) hospitalization events (1.5 vs 2; p = 0.04) and better improvement in HF symptoms (patients with ≥1 NYHA improvement 87.09% vs 67.74%; p = 0.04). There were fewer deaths per 100 patient-year (6.45 vs 9.37; p = 0.04) and more narrowing of QRS duration (Δ12.56 ± 3.11 ms vs Δ7.29 ± 1.87 ms; p = 0.04) with quadripolar lead use. Lead related complications were significantly more with the use of bipolar lead (74.19% vs 41.94%; p = 0.02). CONCLUSIONS: Our prospective, non-randomized, single-center observational study reveals that patients receiving CRT with quadripolar leads have a better response to therapy, lesser heart failure hospitalizations, lower all-cause mortality, and fewer lead-related complications, proving its superiority over the bipolar lead.

Lead one ratio: A new electrocardiogram marker for cardiac resynchronization therapy response.

BACKGROUND: Wider QRS duration and presence of left bundle branch block (LBBB) predict better cardiac resynchronization therapy (CRT) response. Despite strict patient selection, one-third of patients have a sub-optimal response. We aim to evaluate the impact of lead one ratio (LOR) on CRT response. METHODS: We enrolled 93 patients receiving CRT from August 2016 to August 2019. Pre-implant 12-lead electrocardiogram (ECG) was recorded, and LOR was derived by dividing the maximum positive deflection of QRS complex in ECG lead I by the maximum negative deflection in lead I; cut-off value of 12 was used to divide the cohort into two groups. Patients were followed for 6 months, and outcomes were compared for CRT response, New York Heart Association (NYHA) class improvement, all-cause mortality, and heart failure (HF) hospitalization events. RESULTS: At the end of 6-month follow-up, LOR ≥ 12 was associated with significantly better CRT response (75.76% vs. 51.85% in LOR < 12, P = 0.02), lower mortality per 100 patient-years (9.09 vs. 14.81 in LOR < 12, P = 0.012), and more improvement in HF symptoms (NYHA improvement) (78.79% vs. 55.56% in LOR < 12, P = 0.02). Patients with LOR < 12 had more HF hospitalization events (2.04 vs. 1.81 episodes in LOR ≥ 12, P = 0.029) and less QRS narrowing (∆5.74 ± 2.09 vs. ∆7.10 ± 3.97 ms in LOR ≥ 12, P = 0.01). QRS duration and LBBB morphology were predictors of response in both groups of patients. CONCLUSION: LOR ≥ 12 was associated with better response to CRT, less HF hospitalization, and more relief in HF symptoms. This ratio helps to identify possible sub-optimal response among patients with an indication for CRT.

Acute effect of primary PCI on diastolic dysfunction recovery in anterior wall STEMI - A non-invasive evaluation by echocardiography.

BACKGROUND: It is well established fact that acute coronary occlusion leads to diastolic dysfunction, followed by systolic dysfunction when myonecrosis occur. It is also proven that primary percutaneous coronary intervention (PPCI) is an excellent therapy for ST elevation myocardial infarction (STEMI) to improve outcomes. However there is a paucity of information on efficacy of PPCI in improving diastolic function. Evaluation of the role of PPCI in improving diastolic dysfunction is required. METHODS: 61 patients with first anterior wall STEMI who underwent PPCI to left anterior descending artery were included. Echocardiographic evaluation was performed within 24 h of PPCI and then on day 15, 3 months and 6 months after PPCI. We evaluated the prevalence of diastolic dysfunction after PPCI and its recovery during 6 months along with effect of duration of chest pain on diastolic function. RESULTS: 54.1% of patients had diastolic dysfunction after PPCI whereas it was only 21.3% after 6 months (p value < 0.001). Diastolic function indices like deceleration time, isovolumic relaxation time, E wave, A wave, E/A ratio, left atrial volume and index improved statistically from baseline to 6 months except mitral E/e' ratio. As time required to achieve reperfusion increases (chest pain duration and D to B time) the incidence of residual diastolic dysfunction also increases (p value < 0.001). Patients with TIMI flow < III had more diastolic dysfunction (p value < 0.001). CONCLUSIONS: Primary PCI improves diastolic dysfunction in patients with anterior wall STEMI over a period of 6 months. Time to achieve reperfusion and effectiveness of reperfusion have significant effect on diastolic dysfunction.

Impending Rupture of Internal Carotid Artery Aneurysm Mimicking Peritonsillar Abscess.

Extracranial carotid artery aneurysms are rare but important entity. Impending rupture of such aneurysms can lead to catastrophic hemorrhage, airway compromise and may prove fatal. The authors report a case of true aneurysm of cervical internal carotid artery in a four-year-old girl who presented with fever and swelling of neck and oropharynx. High clinical suspicion is required to differentiate aneurysm from peritonsillar and parapharyngeal abscess as incision and drainage can prove fatal. Securing airway beforehand and timely embolization has led to the favorable outcome in the present case.

Randomized controlled pilot study of the preoperative use of brimonidine 0.33% topical gel for hemostasis in Mohs micrographic surgery.

BACKGROUND: Brimonidine topical gel may be useful in cutaneous surgical procedures because of its vasoconstricting properties. OBJECTIVE: Assess the hemostatic effect of topically applied brimonidine in patients being treated with anticoagulants and undergoing Mohs micrographic surgery (MMS). METHODS: Subjects undergoing MMS were randomly assigned to the control (n = 10) or study arm (n = 14). Controls received standard-of-care MMS, whereas the study arm received the same and preoperative application of brimonidine. Evaluations included rate of blood flow, percentage of wound bed surface area needing electrocautery, and changes in skin colorimeter readings. RESULTS: The treatment arm had 68% less blood loss over 30 seconds versus the control arm (P < .05). No patient in the brimonidine arm had more than 50% of the wound bed cauterized versus 80% in the controls. Erythema in the treatment arm was decreased by 3.89 times (P < .01) versus in the control arm. LIMITATIONS: Limitations were small sample size; sites limited to the face; the fact that measurement of bleeding did not account for anesthetic mixed with blood; visual estimation of percentage of wound surface area requiring cauterization; and no measurement of volume of anesthesia, wound depth, or postoperative complications. CONCLUSION: Preoperative application of brimonidine 0.33% gel may help decrease blood loss and the need for electrocautery during MMS for patients taking anticoagulants.

Veno-venous loop through coronary sinus for LV lead placement during cardiac resynchronization therapy.

Left ventricular lead placement in the appropriate branch of coronary sinus is the key to successful cardiac resynchronization therapy (CRT) and this step is technically challenging. We describe a case of non-ischemic cardiomyopathy with heart failure, taken up for cardiac resynchronization therapy with defibrillator (CRT-D) implantation. The quadripolar left ventricular lead was impossible to advance into the target lateral branch of the coronary sinus. We made a veno-venous loop, advancing the coronary guidewire through the middle cardiac vein to coronary sinus and then to superior vena cava. The guidewire then snared through the same left subclavian vein and exteriorized. Over this loop, the left ventricular lead of the CRT-D device was implanted successfully. This novel approach can be used to successfully implant the LV lead in difficult to implant situations, obviating the need for thoracotomy or other methods of LV lead implantation.

Iatrogenic left main coronary artery dissection due to pin-hole balloon rupture: Not to be panicked .

Iatrogenic left main coronary artery (LMCA) dissection is a rare complication and may have devastating consequences if not immediately intervened. The management includes urgent revascularization mostly with percutaneous coronary intervention (PCI) with bail-out stenting and rarely requires coronary artery bypass graft (CABG) surgery. In clinically and hemodynamically stable patients, a conservative approach may be preferred. Here, we present a rare case of iatrogenic retrograde LMCA dissection due to pin-hole rupture of angioplasty balloon that was managed conservatively.