Relationship of Diet and Addiction with Gall Bladder Carcinoma-a Case-Control Study at a Tertiary Health Care Centre, India.

Some dietary elements, tobacco use, have long been suspected as risk factors for gall bladder carcinoma. The objective of the study was to describe the dietary pattern of the patients with gall bladder carcinoma and to compare the dietary ingredients, and addiction between the cases and controls. Fifty-six gall bladder carcinoma cases and 56 matched controls were compared for diet and addiction patterns. Fried food, junk food, vanaspati, frozen fish, dried fish, red meat, kheer, milled mustard oil, puffed rice containing urea, chili powder, less water consumption, extra salt, tobacco exposure, betel leaf, and alcohol consumption were significantly related with gall bladder carcinoma. Green tea, sunflower oil, butter, ghee, fish intake more than twice weekly, sea fish, packaged milk, some fruits, and vegetables were found protective. Some dietary elements and addiction are related to gall bladder carcinoma, whereas some food items have a protective role.

Public-Private Partnership for Treatment of Congenital Heart Diseases: Experiences From an Indian State.

Background: Treatment of congenital heart disease (CHD), being the most common congenital anomaly, puts immense financial burden in low- and middle-income countries (LMICs) and contributes significantly to infant mortality. We report experiences of treatment of CHD in the Indian state of West Bengal by a public-private partnership (PPP) model. Methods: Under the Rashtriya Bal Swasthya Karyakram, the government of the state of West Bengal in India launched a program called the "Sishu Sathi Scheme" to provide free treatment to children who need heart surgeries, irrespective of economic status. Treatment was provided in selected private hospitals and some public hospitals in a reimbursement model where government compensated the hospitals. Data were collected on such procedures from 2013 to 2022 and analyzed. Results: A total of 27,844 patients with CHD received treatment under the Sishu Sathi Scheme from August 2013 to December 2022. The average number of patients per year was 3,093. Detailed data of procedures from January 2016 to December 2022 showed a total of 22,572 procedures (6,249 device interventions, 4,840 cardiac catheterizations, and 11,483 surgical interventions). The in-hospital mortality of surgical procedures and catheterization lab procedures were 5.2% and 0.9%, respectively. Conclusions: A large number of patients with CHD were successfully treated under a PPP in the state of West Bengal in India. In spite of its inherent challenges, this model is of special relevance in LMICs where access and affordability for treatment of CHD always remain a challenge.

A single probe for solvent dependent optical recognition of iron(II/III) and arsenite: discrimination between iron redox states with single crystal X-ray structure evidence.

The detection and discrimination of Fe2+ and Fe3+ ions have been investigated using a simple probe (L), produced by the condensation of ethylenediamine and 3-ethoxysalicyaldehyde. Single crystal X-ray structures demonstrate that L interacts with Fe2+ and Fe3+. In aqueous-DMSO media, the L recognises AsO2- by fluorescence and colorimetry techniques. The AsO2- aided PET inhibition and H-bond assisted chelation enhanced fluorescence (CHEF) boost fluorescence by 91-fold. The L can detect 0.354 ppb Fe2+, 0.22 ppb Fe3+ and 0.235 ppt AsO2-.

Discovery of Novel, Selective Prostaglandin EP4 Receptor Antagonists with Efficacy in Cancer Models.

Prostaglandin E2 (PGE2) receptor 4 (EP4) is one of four EP receptors commonly upregulated in the tumor microenvironment and plays vital roles in stimulating cell proliferation, invasion, and metastasis. Biochemical blockade of the PGE2-EP4 signaling pathway is a promising strategy for controlling inflammatory and immune related disorders. Recently combination therapies of EP4 antagonists with anti-PD-1 or chemotherapy agents have emerged in clinical studies for lung, breast, colon, and pancreatic cancers. Herein, a novel series of indole-2-carboxamide derivatives were identified as selective EP4 antagonists, and SAR studies led to the discovery of the potent compound 36. Due to favorable pharmacokinetics properties and good oral bioavailability (F = 76%), compound 36 was chosen for in vivo efficacy studies. Compound 36 inhibited tumor growth in a CT-26 colon cancer xenograft better than E7046 and a combination of 36 with capecitabine significantly suppressed tumor growth (TGI up to 94.26%) in mouse models.

Glutathione Depleting a Chemoselective Novel Pro-oxidant Nano Metal-Organic Framework Induced G2/M Arrest and ROS-Mediated Apoptotic Cell Death in a Human Triple-Negative Breast Cancer Cell Line.

The progression of a new class of compounds to inhibit the uncontrolled proliferation of carcinoma cells has become one of the most powerful weapons to combat "cancer". To this end, a new Mn(II)-based metal-organic framework, namely, [{Mn(5N3-IPA)(3-pmh)}(H2O)]α (5N3H2-IPA = 5-azidoisophthalic acid and 3-pmh = (3-pyridylmethylene)hydrazone), has been synthesized adopting a mixed ligand approach and exploited as a successful anticancer agent via systematic in vitro and in vivo studies. Single-crystal X-ray diffraction analyses depict that MOF 1 exhibits a 2D pillar-layer structure consisting of water molecules in each 2D void space. Due to the insolubility of the as-synthesized MOF 1, a green hand grinding methodology has been adopted to scale down the particle size to the nanoregime keeping its structural integrity intact. The nanoscale metal-organic framework (NMOF 1) adopts a discrete spherical morphology as affirmed by scanning electron microscopic analysis. The photoluminescence studies revealed that NMOF 1 is highly luminescent, enhancing its biomedical proficiency. Initially, the affinity of the synthesized NMOF 1 for GSH-reduced has been evaluated by various physicochemical techniques. NMOF 1 constrains the proliferation of cancer cells in vitro by inducing G2/M seizure and accordingly leads to apoptotic cell death. More significantly, compared to cancer cells, NMOF 1 exhibits less cytotoxicity against normal cells. It has been demonstrated that NMOF 1 interacts with GSH, causing a drop in cellular GSH levels and the production of intercellular ROS. It is quite intriguing that we discovered that NMOF 1-mediated ROS generation aids in significantly modifying the mitochondrial redox status, which is a crucial factor in apoptosis. According to mechanistic research, NMOF 1 increases the production of proapoptotic proteins and lowers the expression of antiapoptotic proteins, which significantly aids in activating caspase 3 and the subsequent cleavage of PARP1 and cell death via intrinsic apoptotic pathways. Finally, an in vivo investigation using immuno-competent syngeneic mice demonstrates that NMOF 1 can stop tumor growth without causing adverse side effects.

Use of cardiopulmonary bypass machine in intensive care unit as a short term mechanical circulatory support for recovery of cardiac function.

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) is used as a bridge to recovery of cardiac function following completion of congenital cardiac surgeries where there is failure to wean from cardiopulmonary bypass (CPB) or severe low cardiac output states in the post operative periods. Although ECMO is a well-established form of mechanical circulatory support, the associated cost can be a huge financial burden on families. We are an ECMO center and use the same in post operative congenital cardiac surgeries for mechanical cardiovascular support if needed. However, a significant proportion of the children, whom we operate, are funded by government aides. The resources are limited in such circumstances. If needed, we use the same CPB circuit and cannulae used in the Operating Room (OR) and support them at a significantly lower cost compared to ECMO. METHODS: We report our experience of using conventional CPB machine as a short-term bridge to recovery of cardiac function in Intensive Care Unit where there was limitation of funds. Essentially same CPB circuit with roller pump is retained, by omitting cardiotomy suckers. We use D901 Lilliput 1 Oxygenator (Sorin, Italy) for children <5 kg and D902 Lilliput 2 (Sorin, Italy) Oxygenator for children >5 Kg. RESULTS: We supported nine patients on CPB between March 2019 and December 2021. During this time, 1392 congenital cardiac surgeries were performed. We could wean off three patients (33.3%) and discharge two patients (22.2%). Our support time ranged from 21 h to 60 h with a median of 48 h. Beyond 48 h of support, we experienced several CPB induced complications in our cohort. CONCLUSION: In resource-limited settings, conventional CPB machines can be used for short-term cardiac support. Although results may not be comparable to using ECMO, some patients can be definitely salvaged, who would otherwise die in the absence of institution of mechanical circulatory support.

Double left atrial appendage: A diagnostic dilemma.

We report a unique intraoperative finding of an additional double left atrial appendage (LAA) during an arterial switch operation with ventricular septal defect closure in a 4-month-old girl. Immediately after the procedure, a prolapsing mass within the left atrium (LA) on the transesophageal echocardiogram raised concerns of a possible thrombus. The LAA was clearly visible with a pressure monitoring line which was put intraoperatively. To investigate further, cardiopulmonary bypass was resumed, and the heart was arrested and explored. There was an appendage-like structure, separate from the one that had the pressure monitoring line, which was inverted inside. It was pulled out from outside clearly establishing a double LAA. This report illustrates an example of a diagnostic dilemma caused by a double atrial appendage which was invaginated into LA masquerading as a mass or thrombus.

Spectrum and outcome of the use of noninvasive ventilation in a pediatric cardiac intensive care unit: A single-center experience.

Background and Aims: The pediatric cardiac intensive care unit (PCICU) frequently uses noninvasive ventilation (NIV). There are several reasons for its use, including prophylactic use right after the patient has been extubated. It is also used when patients are experiencing acute respiratory failure due to either cardiac or noncardiac reasons but are still able to maintain their airways. The objective of this study was to understand the spectrum of use of NIV following congenital cardiac surgery and analyze the outcome. Methods and Results: A retrospective observational study was conducted in a 14-bed PCICU, reviewing data from August 2019 to August 2022. Among 1750 congenital cardiac surgeries, 523 patients (29.9%) received NIV. The median age of the population was 2.5 months. Factors such as higher Risk-Adjusted Classification for Congenital Heart Surgery-1 category, longer intraoperative cardiopulmonary bypass time, and aortic cross-clamp time were associated with increased NIV use. Preoperative ventilator needs, infections, genetic syndromes, diaphragmatic paralysis, high vasoactive inotrope score (VIS) in the first 24 h, neonatal age, and weight <5 kg were independently associated with increased NIV need. The NIV group had a longer intensive care unit (ICU) stay compared to non-NIV patients. The success rate of NIV was 84%, with 440 successful cases and 83 failures. The mortality rate in the success and failure groups was not significantly different (5.27% vs. 6.0%). Conclusions: NIV is widely used in PCICU, but it is associated with longer ICU stays. It proves beneficial after congenital cardiac surgery, especially for patients with specific risk factors. However, NIV may not directly impact mortality rates, suggesting that other factors contribute to patient survival.

Next-generation Bruton's Tyrosine Kinase (BTK) Inhibitors Potentially Targeting BTK C481S Mutation- Recent Developments and Perspectives.

Bruton's tyrosine kinase (BTK) plays a vital role in B-cell antigen receptor (BCR) signalling transduction pathway. Controlling BCR signalling by BTK inhibitors is a promising therapeutic approach for the treatment of inflammatory and autoimmune diseases. Since the approval of ibrutinib for the treatment of different haematological cancers in 2013, great efforts have been made to explore new BTK inhibitors. Despite the remarkable potency and efficacy of first and second generation irreversible BTK inhibitors against various lymphomas and leukaemia, there are also some clinical limitations, such as off-target toxicity and primary/acquired drug resistance. Acquired drug resistance due to the C481S mutation in BTK is the major challenging problem of irreversible inhibitors. After, the BTK C481S mutation, the irreversible covalent inhibitors cannot form covalent bond with BTK and drop activities. Hence, there is an urgent need to develop novel BTK inhibitors to overcome the mutation problem. In recent years, a few reversible BTK inhibitors have been developed and are under clinical evaluation stages. In addition, a few reversible BTK-PROTACs have been explored and under developments. A number of reversible non-covalent BTK inhibitors, including MK1026/ ARQ531, LOXO305, fenebrutinib are at different stages of clinical trials for autoimmune diseases. In this review, we summarized the discovery and development of nextgeneration BTK inhibitors, especially targeting BTK C481S mutation and their applications for the treatment of lymphomas and autoimmune diseases.

Late presentation of aortopulmonary window: a contemporary series.

Late presentation of aortopulmonary window (APW) beyond infancy is uncommon and many of these cases are inoperable due to development of progressive pulmonary hypertension and Eisenmenger syndrome. Outcome data in this cohort is thus sparse and the aim of this study was to analyze the outcomes in patients with APW operable beyond 1 year of age. Between September 2016 and March 2020, in a single center, 12 consecutive patients older than 1 year, undergoing surgery for APW, were included in the study. The median age and weight at presentation were 7.5 years (interquartile range (IQR) 4-9.5) and 15 kg (IQR 11.7-19.5). Ten (83.3%) patients had type 1 APW (proximal type) and 2 (16.6%) had a type 2 APW (distal type). Eight (66.6%) patients had associated lesions. Transaortic patch closure of APW was done in all cases. Seven (58.3%) patients were extubated within 3.5 h of admission in intensive care. There were no early deaths or during follow-up. The median follow-up duration was 20.5 months (IQR 7.5-24), and all patients were in New York Heart Association (NYHA) class I at last follow-up. Follow-up echocardiography did not reveal any significant residual shunts necessitating any additional procedure and a consistent decrease in pulmonary artery pressures. Surgery in patients with APW beyond 1 year of age is possible in selected patients. The early and intermediate surgical outcomes in patients who remain operable are excellent.

Atrial fibrillation - Can HbA1c levels really predict the risk?

BACKGROUND: Diabetes is associated with higher mortality and worse post-operative outcomes in patients undergoing coronary artery bypass grafting and HbA1c levels have consistently been reported to be associated with adverse post-operative outcomes. However, the role of HbA1c still remains unclear with regards to the occurrence of atrial fibrillation. METHOD: Data for the patients undergoing off-pump coronary artery bypass grafting was analysed in a retrospective fashion. Patients were divided into-those with HbA1c < 6.5% and those with HbA1c ≥ 6.5% and the incidence of atrial fibrillation observed in these two groups. We also compared patient who developed atrial fibrillation in the post-operative period and compared them with those who did not. RESULTS: Of the 5259 patients included in the study HbA1c was <6.5 in 2808 (53.4%) patients and was ≥6.5 in 2451 (46.6%) patients; 623 (11.8%) patients in our study developed atrial fibrillation. Onset of atrial fibrillation in the post-operative period was seen most commonly 235 (38.3%) on between 24 and 48 h after the operation with more than half of them 338 (54.2%) occurring within the first 48 h. On multivariate analysis, HbA1c was not a risk factor for atrial fibrillation (odd's ratio 1.144, 95% confidence interval 0.967-1.354). Only increased age (odd's ratio 1.08; 95% confidence interval 1.069-1.091); EuroSCORE (odd's ratio 1.073; 95% confidence interval 1.048-1.099); history of recent MI (odd's ratio 0.768; 95% confidence interval 0.606-0.971) and peripheral vascular disease (odd's ratio 1.667; 95% confidence interval 1.091-2.517) were found to be independently associated with increased risk of atrial fibrillation in the post-operative period. CONCLUSIONS: After adjusting for confounders HbA1c levels do not independently predict risk of atrial fibrillation after off-pump coronary artery bypass grafting.

On-pump beating heart versus off-pump myocardial revascularization-a propensity-matched comparison.

OBJECTIVE: On-pump beating heart (OP-BH) coronary artery bypass grafting (CABG) is often undertaken as an alternative between off-pump coronary artery bypass (OPCAB) and conventional on-pump coronary artery bypass grafting (On-pump CABG), especially in India. However, outcome data following OP-BH surgery is sparse. The aim of this study was to compare the outcomes of OP-BH CABG with OPCAB. METHODS: From our institutional database, all patients undergoing OP-BH CABG (n = 531) were identified. A propensity-matched cohort undergoing OPCAB (n = 531) was identified from the database. Nearest neighbor matching technique was used and the groups were matched for variables including age, gender, body mass index, EuroSCORE, history of recent myocardial infarction or unstable angina, hypertension, peripheral vascular disease, chronic obstructive airway disease, diabetes, pre-op renal impairment, pre-op neurological events, and left ventricular function. RESULTS: The propensity-matched groups were well matched in terms of baseline characteristics. The mean EuroSCORE was 3.17 and 3.20 in the OP-BH and the OPCAB groups. The unadjusted 30-day mortality in the propensity-matched OPCAB group was 2.07% (11/531) while mortality in the on-pump beating heart group was significantly higher at 6.9% (37/531). Multivariate analysis showed that OP-BH CABG was an independent risk factor for 30-day mortality as well as major adverse post-operative outcomes including renal, neurological, and respiratory outcomes and post-operative atrial fibrillation. CONCLUSIONS: OP-BH CABG is associated with worse clinical outcomes compared to patients undergoing OPCAB.

Impact of COVID-19 pandemic on pediatric cardiac services in India.

BACKGROUND: COVID-19 pandemic has disrupted pediatric cardiac services across the globe. Limited data are available on the impact of COVID.19 on pediatric cardiac care in India. AIMS: The aims are to study the impact of COVID-19 pandemic on the care of children with heart disease in India in terms of number of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries. SETTINGS AND DESIGN: This is a retrospective, multicentric, observational study. METHODS: We collected monthly data on the number and characteristics of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries and major hospital statistics, over a period of 5 months (April to August 2020), which coincided with the first wave of COVID-19 pandemic in India and compared it with data from the corresponding months in 2019. RESULTS: The outpatient visits across the 24 participating pediatric cardiac centers decreased by 74.5% in 2020 (n = 13,878) as compared to the corresponding period in 2019 (n = 54,213). The reduction in the number of hospitalizations, cardiac surgeries, and catheterization procedures was 66.8%, 73.0%, and 74.3%, respectively. The reduction in hospitalization was relatively less pronounced among neonates as compared to infants/children (47.6% vs. 70.1% reduction) and for emergency surgeries as compared to elective indications (27.8% vs. 79.2%). The overall in-hospital mortality was higher in 2020 (8.1%) as compared to 2019 (4.8%), with a higher postoperative mortality (9.1% vs. 4.3%). CONCLUSIONS: The current COVID-19 pandemic significantly impacted the delivery of pediatric cardiac care across India with two-third reduction in hospitalizations and cardiac surgeries. In an already resource-constrained environment, the impact of such a massive reduction in the number of surgeries could be significant over the coming years. These findings may prove useful in formulating strategy to manage subsequent waves of ongoing COVID-19 pandemic.

Outcome of COVID-19-positive children with heart disease and grown-ups with congenital heart disease: A multicentric study from India.

BACKGROUND: Outcome data of children with heart disease who acquired COVID-19 infection are limited. AIMS: We sought to analyze outcome data and identify risk factors associated with mortality in children with heart disease and grown-ups with congenital heart disease (GUCH) who had a laboratory-confirmed COVID-19 infection. SETTINGS AND DESIGN: This is a retrospective, multicentric, observational study. MATERIALS AND METHODS: The study included children with heart disease and GUCH population, who presented with either symptomatic or asymptomatic COVID-19 infection to any of the participating centers. COVID-19-negative patients admitted to these centers constituted the control group. RESULTS: From 24 pediatric cardiac centers across India, we included 94 patients with a median age of 12.5 (interquartile range 3-96) months and 49 (52.1%) patients were males. Majority (83 patients, 88.3%) were children. One-third of the patients (n = 31, 33.0%) had acyanotic congenital heart disease, and 41.5% (n = 39) were cyanotic, with > 80% of the patients being unoperated. Only 30 (31.9%) patients were symptomatic for COVID-19 infection, while the rest were incidentally detected positive on screening. A total of 13 patients died (case fatality rate: 13.8%). The in-hospital mortality rate among hospitalized patients was significantly higher among COVID-19-positive cases (13 of 48; 27.1%) as compared to COVID-negative admissions (9.2%) during the study period (P < 0.001). On multivariate analysis, the independent predictors of mortality among COVID-19-positive cases were severity of illness at admission (odds ratio [OR]: 535.7, 95% confidence interval [CI]: 6.9-41,605, P = 0.005) and lower socioeconomic class (OR: 29.5, 95% CI: 1.1-814.7, P = 0.046). CONCLUSIONS: Children with heart disease are at a higher risk of death when they acquire COVID-19 infection. Systematic preventive measures and management strategies are needed for improving the outcomes.

Mid-term clinical and health-related quality of life outcomes for the Trifecta bioprosthesis.

BACKGROUND: The Trifecta valve has been reported to have excellent hemodynamics. Controversy exists on occurrence of patient-prosthesis mismatch (PPM) and data on mid-term outcome is sparse. Health-related quality of life (HRQoL) assessment for the Trifecta valve has not been reported before. The aim of this study was to report the mid-term clinical and HRQoL outcomes in patients undergoing Trifecta valve implantation at our institution. METHODS: In this prospective, observational study, patients undergoing an aortic valve replacement (AVR) using the Trifecta valve were included. Data collection was retrospective from prospectively collected institutional database. Clinical and echocardiographic data were collected prospectively during follow-up. Quality of life was assessed using the Short Form-36 (SF-36) questionnaire. RESULTS: Forty-seven patients were included in the study of which 9 (19%) were women. Isolated AVR was carried out in 33 (70%) patients. In-hospital mortality and 30-day mortality were 1 (2.1%) and 2 (4.2%), respectively. With a mean indexed effective orifice area (iEOA) 0.96 ± 0.1, none of the patients had severe PPM. Moderate PPM was seen in 19%. The mean follow-up was 3 ± 1.7 years. The 5-year survival estimate was 83.2% in the overall cohort, 81.4% in the isolated and 87.5% in the concomitant procedure group. Freedom from re-operation and structural valve degeneration at 5 years was 95.7% and 97.8%. The mean physical health composite was 69.24 ± 2 and the mean mental health composite was 69.7 ± 25, indicating excellent mental and physical well-being among patients. CONCLUSION: The Trifecta valve provides satisfactory hemodynamics, survival and freedom from re-operation and excellent HRQoL at mid-term follow-up.

Timing of coronary artery bypass grafting after acute myocardial infarction: does it influence outcomes?

INTRODUCTION: The optimal timing of coronary artery bypass grafting (CABG) operations in patients with recent acute myocardial infarction (AMI) remains unclear. AIM: To assess the influence of timing on post-operative outcomes in patients undergoing CABG following AMI. MATERIAL AND METHODS: In this retrospective analysis 12,224 consecutive patients undergoing CABG were included. 2477 (20.5%) patients had a history of AMI. Based on timing, patients were divided into 3 groups: those operated within 7 days of AMI; those operated after 7 days but within 1 month; and a third group operated after 1 month but within 3 months. The 3 groups were compared in terms of baseline, intra-operative, and post-operative morbidity and mortality. Multivariate analysis was carried out to assess the independent influence of timing of CABG on outcomes. RESULTS: There was no difference in terms of previous neurological events (p = 0.554), presence of carotid artery disease (p = 0.555), prevalence of hypertension (p = 0.119), diabetes (p = 0.144), hypothyroidism (p = 0.53), chronic obstructive pulmonary disease (p = 0.079), peripheral vascular disease (p = 0.771), and impaired left ventricular function (p = 0.072). On univariate analysis, mortality risk was highest between 1 week and 1 month (p = 0.003). Multivariate analysis showed that the closer the MI and CABG duration, the higher the mortality (co-efficient -0.517; p = 0.019; odds ratio = 0.596; 95% CI: 0.388-0.917). CONCLUSIONS: The duration between MI and CABG has a direct influence on outcomes after CABG. While it is clear that the longer the duration between MI and CABG, the lower the mortality risk, it is however difficult to decide on an exact cut-off time frame.

Azide-mediated unusual in situ transformation of Mannich base to Schiff-Mannich base and isolation of their Cu(II) complexes: crystal structure, theoretical inspection and anticancer activities.

A new "end-off" compartmental Mannich ligand (HL1) namely 3-((bis(2-methoxyethyl)amino)methyl)-5-bromo-2-hydroxybenzaldehyde containing two methoxyethyl pendant arms and one-CHO functionality has been synthesized through conventional C-C and C-N coupling reactions. On treatment with Cu(ClO4)2, HL1 yields a dinuclear µ-phenolatocopper(II) complex having the molecular formula [Cu2(L1)2](ClO4)2(H2O)1.5 (1). Surprisingly, the ligand HL1 is radically transformed into a new asymmetric Schiff-Mannich base ligand (HLF) in the presence of NaN3 and Cu(ClO4)2 forming a unique dinuclear centro-symmetric Cu(II) complex [Cu(LF)]2 (2) as evident from single-crystal X-ray diffraction (SCXRD) analysis. A probable mechanistic rationalization has been proposed on the basis of theoretical calculations, which suggests systematic fragmentation of HL1 in the presence of azide residue and re-condensation of the fragmented units to yield the final Cu-HLF complex (2). SCXRD analysis portrays a large inter-metallic distance in complex 2 in comparison with complex 1 (5.493 vs. 2.989 Å, respectively) along with other distinct structural features. After physicochemical characterization both the complexes have been exploited to evaluate their possible anticancer proficiency on lung adenocarcinoma cell line (A549). Complex 1 distinctly impeded the proliferation of lung adenocarcinoma cells in a dose-dependent manner more efficiently than complex 2. Due to the behavior of complex 1 as potential therapeutics, cellular transformations of A549 cells have been systematically investigated. As evidenced from various in vitro experiments, the cell death mechanism triggered by complex 1 turned out to be apoptosis, as indicated by the DNA fragmentation, chromatin condensation, membrane blebbing and imbalanced cell cycle distribution as well as retard migration in A549 cells.

Surgical repair of total anomalous pulmonary venous connection: Lateral approach.

We describe the lateral approach to the surgical repair of a total anomalous pulmonary venous connection in this video tutorial. The goal of the operation is to create an unobstructed anastomosis between the pulmonary confluence and the left atrium, ligate the systemic venous connections, and close the atrial septal defect. After a median sternotomy and initial dissection of the structures surrounding the heart, cardiopulmonary bypass is initiated by aortobicaval cannulation. The patient is then cooled to attain mild hypothermia (30°C). The heart is arrested by a dose of antegrade cold cardioplegia. The right pleural cavity is opened widely. The heart is retracted and pushed into the right pleural cavity. The vertical vein is ligated near its connection with the innominate vein. An incision is made along the length of the confluence, stopping short of the individual pulmonary veins. The left atrial appendage is retracted, and the left atrium is opened in alignment with the opening in the confluence. The left atrium and the pulmonary confluence are anastomosed widely with 7-0 polypropylene suture material. The heart is put back into the mediastinum. Rewarming is started. The atrial septal defect is closed through the right atrium using a large untreated autologous pericardium patch. The patient is then weaned off cardiopulmonary bypass.

Next-Generation Kinase Inhibitors Targeting Specific Biomarkers in Non-Small Cell Lung Cancer (NSCLC): A Recent Overview.

Lung cancer causes many deaths globally. Mutations in regulatory genes, irregularities in specific signal transduction events, or alterations of signalling pathways are observed in cases of non-small cell lung cancer (NSCLC). Over the past two decades, a few kinases have been identified, validated, and studied as biomarkers for NSCLC. Among them, EGFR, ALK, ROS1, MET, RET, NTRK, and BRAF are regarded as targetable biomarkers to cure and/or control the disease. In recent years, the US Food and Drug Administration (FDA) approved more than 15 kinase inhibitors targeting these NSCLC biomarkers. The kinase inhibitors significantly improved the progression-free survival (PFS) of NSCLC patients. Challenges still remain for metastatic diseases and advanced NSCLC cases. New discoveries of potent kinase inhibitors and rapid development of modern medical technologies will help to control NSCLC cases. This article provides an overview of the discoveries of various types of kinase inhibitors against NSCLC, along with medicinal chemistry aspects and related developments in next-generation kinase inhibitors that have been reported in recent years.

Utility of late pulmonary artery banding in single-ventricle physiology: A mid-term follow-up.

BACKGROUND: The standard first stage palliation for univentricular heart with unrestricted pulmonary blood flow (PBF) is surgical pulmonary artery (PA) banding for which the ideal age is within the first 8 weeks of life. This study aimed to look for the utility of PA band done beyond 3 months of age for patients presenting beyond the stipulated period. MATERIALS AND METHODS: This is a retrospective analysis of the outcome of twenty patients with single ventricle (SV) physiology with unrestricted PBF who presented late and were selected on the basis of clinical, radiological, and echocardiographic parameters for PA banding. RESULTS: The median age of the patients was 5.5 months (3.5-96 months), and the median body weight was 4.7 kg (3.2-22.0 kg). The patients were divided into three groups as follows: ten patients between 3 and 6 months of age (Group A), seven patients between 6 months to 1 year of age (Group B), and three patients > 1 year of age with additional features of pulmonary venous hypertension (Group C). The mean reduction of PA pressures following PA band was 60.9%, 48.8%, and 58.3% and the mean fall in oxygen saturation was 10.4%, 8.0%, and 6.6% in the three groups, respectively. The postoperative mortality rate was 10%. The mean follow up duration was 13.5 months (7-23 months). There was a statistically significant improvement in weight for age Z scores following PA band (P = 0.0001). On follow up cardiac catheterization, the mean PA pressures were 16.6 (±3.6), 22.7 (±5.7), and 33.3 (±12.4) mmHg, respectively, in the three groups, and the mean pulmonary vascular resistance index was 1.86 (±0.5), 2.45 (±0.7), and 3.5 (±1.6) WU.m2, respectively. Subsequently, seven patients in Group A, three patients in Group B, and one patient from Group C underwent successful bidirectional Glenn (BDG) surgery. CONCLUSIONS: Late PA band in selected patients with SV physiology can have definite benefit in terms of correction of heart failure symptoms and subsequent conversion to BDG and can potentially change the natural history of disease both in terms of survival and quality of life.