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Introduction: The limb-preserving excision is the standard of care in upper limb sarcoma management, but the resulting complex composite defects are exacting the expertise of the reconstructive surgeons. This study was done to evaluate a novel single-stage reconstruction of these defects using an innate chimeric-free fibula flap (a nonfabricated, anatomically available multiple tissue components harvested on independent perforators arising from the same peroneal source vessel)., Patients and Methods: Twenty patients (16 male/4 female) with an average age of 29.5 years with upper extremity sarcoma (Enneking IIA/IIB) were treated by wide local excision and innate chimeric-free fibula flap reconstruction from March 2012 to March 2020. All the patients were followed for an average period of 18.3 months. At the end of the follow-up, the outcome was assessed by musculoskeletal tumor score (MSTS)., Results: The flow-through flap was done in five patients. Muscle-tendon unit defects were reconstructed with a vascularized peroneus longus muscle-tendon unit in 15 patients. Nerve gap reconstruction using vascularized superficial peroneal nerve was done in eight patients. All patients had a segmental defect in the appendicular skeleton that was reconstructed with the vascularized fibular strut component. Soleus chimeric muscle component was used as a void filler and for covering the hardware in seven patients. The average size of the chimeric cutaneous component paddle was 30.7 cm 2 . The average length of fibula used for reconstruction was 16.6 cm. All flaps survived well, facilitating good hand function at the end of the follow-up. The average outcome score as per the MSTS was 22 ( p = 0.035)., Conclusion: The innate chimeric-free fibula flap provides all tissue components facilitating a good functional outcome. The advantage is the restoration of a functional hand in a single-stage reconstruction., (© 2024 Society for Indian Hand Surgery and Micro Surgeons. Published by Elsevier B.V. All rights reserved.)

Surgical aortopulmonary shunting (SAPS) and ductal stenting (DS) are the main palliations in infants with cyanotic congenital heart diseases (CHD). We aimed to study the safety and efficacy of DS and to compare it with SAPS as a palliative procedure in infants with CHD and duct-dependent pulmonary circulation. Retrospective institutional clinical data review of consecutive infants aged < 3 months who underwent DS or SAPS over 5 years. The primary outcome was procedural success which was defined as event-free survival (mortality, need for re-intervention, procedural failure) at 30 days post-procedure. The secondary outcome was defined by a composite of death, major adverse cardiovascular events, or need for re-intervention at 6 months and on long-term follow-up. We included 102 infants (DS, n = 53 and SAPS, n = 49). The median age at DS and SAPS was 4 days (IQR 2.0-8.5) and 8 days (IQR 4.0-39.0), respectively. The median weight at intervention was 3.0 kg (IQR 3.0-3.0) and 3.0 kg (IQR 2.5-3.0) in the two respective arms. Tetralogy of Fallot with pulmonary atresia was the most common indication for DS and SAPS. The 30-day mortality was significantly higher in SAPS group as compared with DS group (p < 0.05). However, 30-day major adverse cardiac events (MACE) rates were similar in both groups (p = 0.29). DS was associated with shorter duration of mechanical ventilation, duration of stay in the intensive care and hospital stay than with SAPS. At 6 months, there was no significant difference in terms of mortality or event-free survival. Long-term MACE-free survival was also comparable (p = 0.13). DS is an effective and safer alternative to SAPS in infants with duct-dependent pulmonary circulation, offering reduced procedure-related mortality and morbidity than SAPS. Careful study of ductal anatomy is crucial to procedural success. However, long-term outcomes are similar in both procedures., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives  Arteriovenous malformations (AVMs) are high-flow, aggressive lesions that cause systemic effects and may pose a risk to life. These lesions are difficult to treat as they have a tendency to recur aggressively after excision or embolization. So, it requires a regulating free flap with robust vascular flow averting the postexcisional ischemia-induced collateralization, parasitization, and recruitment of neovessels from the surrounding mesenchyme-a phenomenon precipitating and perpetuating the recurrence of AVM. Materials and Methods  Sixteen patients (12 males and 4 females) with AVMs Schobinger type 4 involving face were treated from March 2015 to March 2021 with various free flaps: three free rectus abdominis flaps, one free radial forearm flap, and twelve free anterolateral thigh flaps were used for reconstruction following the wide local excision of Schobinger type 4 facial AVM. The records of these patients were analyzed retrospectively. The average follow-up period was 18.5 months. The functional and aesthetic outcomes were analyzed with institutional assessment scores. Results  The average size of the flap harvested was 113.43 cm 2 . Fourteen patients (87.5%) had good-to-excellent score ( p  = 0.035) with institutional aesthetic and functional assessment system. The remaining two patients (12.5%) had only fair results. There was no recurrence (0%) in the free flap group versus 64% recurrence in the pedicled flap and skin grafting groups ( p  = 0.035). Conclusion  Free flaps with their robust and homogenized blood supply provide a good avenue for void filling and an excellent regulating effect in inhibiting any locoregional recurrences of AVMs., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background  Gluteus maximus, by virtue of its continued adjunct contraction with the anal sphincter, has many characteristics and histomorphological features mimicking type I musculature. Hence, anal sphincter replacement therapy with gluteus maximus has all avenues for lasting successful results. This study aimed to evaluate the efficiency of unstimulated gluteus maximus sphincteroplasty for anal incontinence reconstruction and neosphincter reconstruction in perineal colostomy cases. Methods  From March 2015 to March 2020, the records of patients who underwent gluteus maximus sphincteroplasty for fecal incontinence were analyzed in this retrospective cohort study. The mean age was 31.55 years. Eleven patients (females = 4, males = 7) underwent anal incontinence reconstruction. All these cases were followed up for an average period of 28.46 months. Results  Good continence was observed in all patients with an average Cleveland Clinic Florida Faecal Incontinence Score of 3.18 ( p  = 0.0035). At the end of the follow-up period, the average median resting pressure found via manometry was 44.64 mm Hg, and the average median squeeze pressure was 103.55mm Hg. The mean of the average continence contraction time at the end of the follow-up period was found to be 3.64 minutes. None of our patients had complete continence failure. None of our patients used perineal pads or made any lifestyle alterations at the end of the follow-up period. Most of the patients expressed satisfactory continence. Conclusion  Despite being untrained with implantable electrodes, the gluteus maximus muscle produced very good continence results with our way of construct. In addition, with its good lumen occluding effect, it achieves good resting and squeeze anal pressure around the anal canal/bowel with trivial reeducation. Hence, it has become our institution's procedure of choice for anal sphincter reconstruction., Competing Interests: Conflict of Interest None., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The fact that animal models fail to replicate human disease faithfully is now being widely accepted by researchers across the globe. As a result, they are exploring the use of alternatives to animal models. The time has come to refine our experimental practices, reduce the numbers and eventually replace the animals used in research with human-derived and human-relevant 3-D disease models. Oncoseek Bio-Acasta Health, which is an innovative biotechnology start-up company based in Hyderabad and Vishakhapatnam, India, organises an annual International Conference on 3Rs Research and Progress. In 2021, this conference was on 'Advances in Research Animal Models and Cutting-Edge Research in Alternatives'. This annual conference is a platform that brings together eminent scientists and researchers from various parts of the world, to share recent advances from their research in the field of alternatives to animals including new approach methodologies, and to promote practices to help refine animal experiments where alternatives are not available. This report presents the proceedings of the conference, which was held in hybrid mode (i.e. virtual and in-person) in November 2021.

Background: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS)., Materials and Methods: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy., Results: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed., Conclusions: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety., (Copyright © 2021. Published by Elsevier Inc.)

Development of pulmonary AV fistula (PAVF) after bidirectional glenn shunt (BDG) results in significant cyanosis, impaired exercise performance, and increased morbidity and mortality. We attempted to detect and quantify PAVF in post-BDG patients by saline contrast transesophageal echocardiography (TEE) and compare with pulmonary angiography and pulmonary vein oximetry. This was a prospective study done between 2017 and 2018. Twenty-five children who underwent BDG and planned for cardiac catheterization prior to Fontan completion were included in the study. All patients underwent pulmonary angiography, oximetry, and saline contrast TEE at the time of cardiac catheterization. Twenty-two patients had undergone unilateral BDG surgery and three were palliated by bilateral BDG. The mean oxygen saturation was 80 ± 5.2%. Thirteen patients (52%) had preserved antegrade pulmonary blood flow. Eighteen patients (72%) had PAVF by angiography and oximetry, while 19 (76%) had PAVF identified by contrast echocardiography. There was moderate correlation between the degree of pulmonary venous desaturation and grading of PAVF by contrast echocardiography. PAVF was predominantly located in the lower zones of the lungs. Higher grades of PAVF were not seen in patients with preserved antegrade flow after BDG. Angiographically detected PAVF showed a steady increase with increasing delay to cardiac catheterization from BDG. Significant reduction in systemic saturation was limited to advanced grades of PAVF in patients after BDG. Saline contrast TEE, pulmonary venous oximetry, and pulmonary angiography equally identified PAVF in patients after BDG. Prognostic utility of the same needs to be assessed by long-term follow-up of these subjects., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background  "Subfascial void reconstruction" in ischial pressure sores (IPSs) goes a long way in the amelioration of the common complications like persistent drainage, infection, wound dehiscence, and late recurrence. No locoregional flaps suffice this requirement. So we have designed a chimeric pedicled flap based on the inferior gluteal vessel axis (IGVA) perforators with two tissue components: (1) Pacman-style fasciocutaneous flap on a perforator and (2) gluteus maximus muscle (inferior portion) on another independent perforator. Aim and Methods  After confirming the feasibility of novel design of chimeric pedicled IGVA perforator flap with cadaver study, we embarked on the clinical study with this chimeric flap. In this prospective cohort study, the study and the control existed in the same patient so that the biological factors affecting the wound healing would be the same. Results  Twenty-one patients were included whose mean age was 39 years. Late recurrence occurred in one patient (4.8%) of chimeric flap while the control group (who had undergone conventional reconstruction) had recurrence in 11 patients (52.4%). On assessment with overall institutional score, grade A was observed in 18 patients of the chimeric IGVA flap group ( p < 0.045), and in only 3 patients of the control group. Conclusions  This anatomically construed flap, a new addendum in the armamentarium of reconstruction of IPSs, with its potential to congruently fill the ischiogluteal subfascial void may provide a lasting solution for preventing recurrences., Competing Interests: Conflict of InterestFinancial Support and Sponsorship None declared. None., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Microvascular free tissue transfer has revolutionized the management of complex composite head and neck defects., Aim: To evaluate the functional and aesthetic outcomes in the primary reconstruction of post-excisional near total hemifacial defects with the chimeric anterolateral thigh flaps (cALT)., Materials and Methods: The author as a prelude to this clinical study has done a cadaveric study on the quadriceps artery angiosome. In this retrospective cohort study, data are collected from the records of 6 patients who had undergone primary cALT flap reconstruction for their post excisional near total hemifacial defects from January 2013 to December 2017. All 6 patients with various advanced malignancies involving the hemiface underwent wide local excision. Wide local excision resulted in the loss of skin and critical facial muscles that led to near total hemiface composite defects. Reconstructions were done with the cALT flaps that included segment of the vastus lateralis muscle harvested on its independent neurovascular perforator pedicle and the skin paddle on a separate perforator. In all cases, the facial nerve stumps were anastomosed to the nerve to vastus lateralis for reanimation of the face. In addition, 4 patients underwent primary radical neck dissection, but all had postoperative radiotherapy and chemotherapy., Results: All patients attained well-pronounced nasolabial fold, symmetrical smile, and good oral competence in an average period of 10.75 months post operatively. In an average of 22 months follow up, none of them had locoregional recurrences. None required any secondary procedures., Conclusion: In the post excisional near total hemifacial composite defects, primary functional reconstruction with tailored cALT flaps can bring good aesthetic and functional results.

Background: The purpose of this article is to develop a new method for elevating the pedicled terminal pectoral perforator flaps (PTPPFs) and to resolve the difficulties and controversies that shroud the anatomy of terminal pectoral perforators from the pectoral branch of the thoracoacromial axis., Aim: Anatomical study was conducted to assess the feasibility of perforator flaps based on the terminal perforators of the pectoral branch of the thoracoacromial vessel axis. The knowledge that gleaned from this anatomical study was applied in the clinical scenario. A clinical retrospective study was conducted to evaluate the outcome of PTPPFs for the reconstruction of postexcisional head and neck defects., Materials and Methods: Thirty cadaveric specimens were examined for the anatomy of the terminal musculocutaneous pectoral branch perforators. Thirty-two cases (22 males, 10 females) of various head and neck postexcision defects were reconstructed with the PTPPFs in a single-stage manner. Pectoralis major muscle with its innervation was spared in all cases. All the secondary defects were closed primarily., Results: The maximum cutaneous paddle size was 156 cm harvested on a single best terminal pectoral branch perforator. The average size of the cutaneous paddle harvested was 73.47 cm. The flap complications noted (9.3%) were trivial, and all the flaps survived well. The average institutional computed score for esthetic and functional recovery at the donor and reconstructed site done by 2 independent observers were 4.56 and 3.78, respectively., Conclusions: The recruitment of the chest skin on the terminal pectoral branch perforators resulted in a long pedicle flap with adequate qualities like color match, texture match, and pliability. This flap shall serve as a primary option for pedicle and free flap head and neck reconstructions.

Background and Objectives: Various devices have been used to maintain oral hygiene. These include toothbrush and toothpaste, mouthwash, dental floss, miswak, and toothpick. This study attempts to investigate the use of various oral cleaning devices and their perceived benefits among Malaysians., Methods: A quantitative cross-sectional study conducted in two different cities of Malaysia. A convenience sampling approach was adopted. A total of 787 participants agreed to participate in the current research. A validated questionnaire translated into national language was used for data collection., Statistical Analysis Used: Data analysis was performed using Statistical Package for Social Sciences version 20., Results: About 302 respondents were in the age range of 18 - 25 years old (38.4%). There were marginally more females (55.7%) than males (44.3%). Although 99.9% of the participants used a toothbrush, a significant majority ( n = 590, 75%) used more than a single device to maintain their oral hygiene. Only 311 respondents knew that toothpicks were inappropriate to use to remove food between teeth and gums, while a majority ( n = 592, 75.2%) did not realize that some mouthwashes can stain the teeth. Less than half (42.1%) knew that improper use of miswak might harm the teeth., Conclusions: Although their oral hygiene behaviors are relatively at a higher level, their perceived oral health benefits did not compare well.

Competing Interests: There are no conflicts of interest.

Nimbolide is a novel, natural compound with promising potential as a drug candidate for anticancer activity. It is isolated from the Indian traditional medicinal plant Azadirachta indica popularly known as neem. The present study was undertaken to explore the oral bioavailability and pharmacokinetic characteristics of nimbolide in rats using the LC/QTOF/MS method. A simple protein precipitation method using acetonitrile was employed for extracting nimbolide from rat plasma. The chromatographic separation of nimbolide and the internal standard (regorafenib) was attained on an Aquity BEH C18 column (100 × 2.1 mm, 2.7 μm), using ACN and 0.1% of formic acid in water as mobile phase components in a gradient elution mode at a flow rate of 0.45 mL/min over a short run time of 4 min. A mass detection was carried out using target ions of [M + H] + at m/z 467.2074 for nimbolide and m/z 483.0847 for the internal standard. The LC/MS method was validated and all the parameters were found well within the specified limits. The calibration curve was constructed in the range of 1-1000 ng/mL. The method shows good accuracy (91.66-97.12%) and precision (intra 2.21-6.92% CV and inter-day 2.56-4.62% CV). This developed LC/MS method was effectively applied to the pharmacokinetic study of nimbolide upon oral and intravenous administration in rats. In concordance with its physicochemical properties and high lipophilicity, we found that it shows poor oral absorption at different doses (10, 30 and 50 mg/kg). As expected, higher plasma levels were observed upon intravenous (10 mg/kg) administration. This method can be extended for evaluation of drug interaction and drug metabolism in rats as well as in humans. Moreover, our rapid and sensitive method may cater the need to accelerate the preclinical formulation development and lead optimization for future drug development of this potent anticancer agent. Further, our oral bioavailability studies demonstrated that nimbolide possesses poor oral absorption, which could be the probable reason for the delay in therapeutic translation of this promising agent for clinical use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignancy for which the role of radiotherapy is not well-defined. We examine the effect of external beam radiotherapy (EBRT) on cancer-specific survival (CSS) for patients with localized EMC, in a propensity score weighted, population-based analysis., Materials and Methods: The Surveillance, Epidemiology, and End Results database (1973 to 2012) was queried for cases of localized EMC arising from soft connective tissues of the trunk and extremities treated with surgery and/or EBRT. Inverse probability treatment weighting was utilized, with survival analysis by weighted Cox regression and Kaplan-Meier analysis with log-rank testing. The primary endpoint was CSS., Results: One hundred seventy-two patients were identified, diagnosed from 2004 to 2012. Ninety-four percent and 32% of 156 assessable patients underwent surgery and EBRT, respectively. By inverse probability treatment weighting, balancing covariates of age group, sex, race, grade, T stage, N stage, receipt of surgery, and anatomic site, we observed CSS of 97% versus 85% and 94% versus 85% in patients receiving EBRT versus no EBRT, at 3 and 5 years, respectively, at median follow-up of 33 months, P=0.01. A trend toward an overall survival benefit associated with EBRT was noted, P=0.06. Further adjusting for type of resection performed, CSS benefit persisted, 97% versus 85% at 3 years and 94% versus 85% at 5 years, P=0.02, with trend toward an overall survival benefit, P=0.08., Conclusions: The receipt of EBRT is associated with a CSS benefit in localized EMC. Aggressive local therapy, including EBRT, should be considered in these patients.

Introduction: The feeling of incongruence between phenotypic sex and psychological recognition of self-gender is termed gender dysphoria. Transsexualism is the most extreme form of this disorder., Aims and Objectives: The aims and objectives of the study are to evaluate the esthetic and functional outcome of embryonic equivalents-based male-to-female sex reassignment surgery in transwomen using the institutional scoring system., Materials and Methods: Thirty transwomen who had undergone male-to-female embryonic equivalents-based sex reassignment surgery (MFEEbSRS) from October 2012 to March 2016 were retrospectively studied. The outcome was evaluated by two independent plastic surgeons, based on interview with the individuals, visual assessment, and measurements., Surgical Technique: Clitoris was created from reduced glans on dorsal penile pedicle mounted on the crura of the conjoined corpora cavernosa. De-gloved unfurled proximal penile skin formed the introitus, hood for clitoris and labia minora. Neo-external urethral meatus was fashioned from the distal portion of the bulbar urethra. Distal de-gloved inverted penile tube flap was used for the creation of neovagina. Reduced scrotal flaps formed the labia majora., Observation and Results: The maximum length of neovagina in the study was 12 cm, and the average length was 9.8 cm. Based on our institutional scoring system for the assessment of esthetic and functional outcome, we got excellent results in all transwomen., Conclusion: The esthetic and functional outcome in all the patients was good. All patients were relieved of their primordial feminine tension and satisfied with the surgery. Their personality, lifestyle, and self-esteem improved remarkably following surgery., Competing Interests: There are no conflicts of interest.

We describe an unusual case of partial atrioventricular septal defect with malalignment of the septum primum to the left atrium with respect to the ventricular septum, committing the tricuspid valve to both ventricles (double-outlet right atrium). Abnormal attachment of the septum primum to the lateral aspect of mitral annulus resulted in left atrial outflow obstruction. The patient underwent successful surgical correction.

Introduction: Lower third leg soft tissue defects with anatomical and pathological constraints are posing formidable challenges to reconstructive surgeon., Aim: This retrospective study was conducted to assess the effectiveness of ad hoc posterior tibial vessels perforator-propeller flaps for the reconstruction of small and medium sized soft tissue defects in the lower third leg., Patients and Methods: 22 patients (16 were males and 6 were females) were involved in this study between period of January 2012 and December 2016.We followed the protocol of initial non delineating exploratory incision made to find out single best perforator in all patients. All the defects in leg reconstructed with adhoc posterior tibial vessel propeller flaps., Results: All 22 flaps survived well. All in an average of 13 months follow up period, had pain free walking, with minimal scarring and acceptable aesthesis at the reconstruction sites with no need for any secondary procedure., Conclusion: With inability of preoperatively dopplering the perforators in the lower third leg region, the exploratory posterior nondelineating incision was used in all cases to secure the single best perforator for the propeller flaps. Thus adhoc posterior tibial vessel propeller flaps are dependable, easily adoptable for the reconstruction of soft tissue defects of the lower third leg region., Competing Interests: There are no conflicts of interest.

Background: We undertook this study to validate the impact of FFR-guided coronary interventions among Indian patients, which is not readily available as of date. Our patients differ from their western counterparts, both in terms of risk profile (younger, more metabolic syndrome, lipid rich diet) as well as their coronary size., Methods: We retrospectively evaluated 282 patients with intermediate stenosis in their coronary arteries, who underwent FFR to assess the functional severity of the lesion. There were 3 groups: Group 1-FFR>0.8 and kept on medical follow-up; Group 2-FFR≤0.8 and underwent revascularisation; and Group 3-FFR≤0.8 and refused to undergo revascularization. 281(99.6%) patients had regular follow-up in our clinic., Results: Median age-57 years (range=28-78). Males=230, 90 patients were in Group 1, 175 in group 2 (PCI in 144 & CABG in 31) and 17 in group 3. Median follow-up of patients was 17.9 months (2 to 56 months). Three patients(3.4%) in Group 1 had MACE (1 STEMI, 2 UA); 4 patients (2.3%) in Group 2 had Non-STE-ACS; 7 patients (41%) in Group 3 had MACE (3 deaths with acute LVF, 2 NSTEMI, 2 STEMI) CONCLUSION: In our experience, MACE events were not higher in patients with FFR>0.8 and kept under medical therapy and were similarly lower in patients with FFR ≤0.8 and underwent revascularisation (p=0.73). Also MACE events were higher in patients with FFR≤0.8 and did not undergo revascularisation compared to other two appropriately treated groups (p=0.03). FFR based revascularization decision appears to be a safe strategy in Indian patients., (Copyright © 2016. Published by Elsevier B.V.)

A 65-year-old patient underwent pericardiocentesis for cardiac tamponade after radiofrequency ablation for ventricular tachycardia. Subsequent to stabilization, the patient developed pneumopericardium, which was detected in the catheterization laboratory and managed successfully by pericardial aspiration.

Objectives: Balloon atrial septostomy (BAS) is an effective palliative procedure in children with transposition of the great arteries and poor intercirculatory mixing. While the subpulmonary left ventricle (LV) is known to regress with time in these newborns due to the declining afterload, it has not been studied how it behaves following BAS and a consequent decrease in preload. The study was designed to examine the effects of BAS on the LV in infants with simple d-transposition of the great arteries by serial 2D echocardiographic monitoring., Methods: This was a prospective echocardiographic follow-up study of all consecutive children with simple d-transposition of the great arteries who underwent BAS for restrictive interatrial communication and oxygen saturation below 75% between January 2014 and June 2015. Left ventricular mass estimation was done by M-mode transthoracic echocardiography before balloon septostomy and serially on follow-up till surgery., Results: The median age of the 25 children studied was 4 days (1-95 days) when they underwent BAS. Twenty patients underwent arterial switch operation at a mean of 9 days from balloon septostomy. The mean baseline left ventricular mass was 47.9 g/m 2 , which decreased to 38.5, 36.2, 32.1, 32.4, 25.7 and 25.2 g/m 2 on Days 1, 3, 6, 9, 12 and 15, respectively. The left ventricular mass decreased by 1.5 g/m 2 every day during the first 2 weeks following balloon septostomy adjusted for the age of the child in days. Children who underwent BAS beyond 3 weeks of life had faster LV regression than those who underwent the procedure earlier (unstandardized regression coefficient β 0.892, P < 0.001)., Conclusions: BAS is associated with accelerated regression of the LV in infants with simple d-transposition of the great arteries in the first 2 weeks after the procedure. Regression of the LV is faster in children who underwent BAS after 3 weeks of age., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Ventricular interdependence is a salient hemodynamic feature of cardiac tamponade that manifests as discordance between the left and right ventricles in filling and ejection on hemodynamic assessment. Ventricular interdependence can manifest as arterial discordance at the level of the great arteries.

A 50-year-old woman underwent radiofrequency catheter ablation of narrow QRS tachycardia that was terminated with intravenous adenosine. Twelve-lead electrocardiogram was normal during sinus rhythm. The electrophysiological study showed normal atriohisian and hisioventricular intervals during sinus rhythm. Atrial burst pacing reproducibly induced two narrow QRS tachycardias. Figure 1 shows spontaneous switch of tachycardia 1 to tachycardia 2. What are the likely mechanisms of the tachycardia and the transition?, (© 2016 Wiley Periodicals, Inc.)

Over the past decade, first and second generation EGFR inhibitors have significantly improved outcomes for lung cancer patients with activating mutations in EGFR. However, both resistance through a secondary T790M mutation at the gatekeeper residue and dose-limiting toxicities from wild-type (WT) EGFR inhibition ultimately limit the full potential of these therapies to control mutant EGFR-driven tumors and new therapies are urgently needed. Herein, we describe our approach toward the discovery of 47 (EGF816, nazartinib), a novel, covalent mutant-selective EGFR inhibitor with equipotent activity on both oncogenic and T790M-resistant EGFR mutations. Through molecular docking studies we converted a mutant-selective high-throughput screening hit (7) into a number of targeted covalent EGFR inhibitors with equipotent activity across mutants EGFR and good WT-EGFR selectivity. We used an abbreviated in vivo efficacy study for prioritizing compounds with good tolerability and efficacy that ultimately led to the selection of 47 as the clinical candidate.