Coronary intravascular lithotripsy in contemporary practice: challenges and opportunities in coronary intervention.

Percutaneous coronary intervention (PCI) of calcified coronary arteries is associated with poor outcomes. Poorly modified calcified lesion hinders the stent delivery, disrupts drug-carrying polymer, impairs drug elution kinetics and results in under-expanded stent (UES). UES is the most common cause of acute stent thrombosis and in-stent restenosis after PCI of calcified lesions. Angiography has poor sensitivity for recognition and quantification of coronary calcium, thereby mandating the use of intravascular imaging. Intravascular imaging, like intravascular ultrasound and optical coherence tomography, has the potential to accurately identify and quantify the coronary calcium and to guide appropriate modification device before stent placement. Available options for the modification of calcified plaque include modified balloons (cutting balloon, scoring balloon and high-pressure balloon), atherectomy devices (rotational atherectomy and orbital atherectomy) and laser atherectomy. Coronary intravascular lithotripsy (IVL) is the newest addition to the tool box for calcified plaque modification. It produces the acoustic shockwaves, which interact with the coronary calcium to cause multiplanar fractures. These calcium fractures increase the vessel compliance and result in desirable minimum stent areas. Coronary IVL has established its safety and efficacy for calcified lesion in series of Disrupt CAD trials. Its advantages over atherectomy devices include ease of use on workhorse wire, ability to modify deep calcium, no debris embolization causing slow flow or no-flow and minimal thermal injury. It is showing promising results in modification of difficult calcified lesion subsets such as calcified nodule, calcified left main bifurcation lesions and chronic total occlusion. In this review, authors will summarize the mechanism of action for IVL, its role in contemporary practice, evidence available for its use, its advantages over atherectomy devices and its imaging insight in different calcified lesion scenarios.

Shock the rock with coronary intravascular lithotripsyPresence of coronary calcium during stenting is associated with the risk of stent under expansion. It's imperative to adequately modify this coronary calcium before placing the stent. Till recent past, the most effective method for calcium modification is debulking it with rotational artherectomy, which is associated with the risk of coronary perforation, slow flow or abrupt vessel closure. Recently, a balloon-based lithotripsy device has established its safety and efficacy for treating such lesions. Coronary intravascular lithotripsy (IVL) is an easy to use calcium modification device and is associated with almost negligible complications, when compared with artherectomy devices. In this review, we will discuss the mechanism of IVL action and its use in different scenarios of calcified coronary artery disease.

Distinct patterns of postoperative fever in paediatric neurosurgery patients.

PURPOSE: Postoperative fever is a common problem following neurosurgery but data on the causes among paediatric patients is sparse. In this report, we determined the incidence, causes, and outcomes of postoperative fever in paediatric neurosurgical patients (< 18 years), and contrasted the findings with an adult cohort published recently from our unit. METHODS: We recruited 61 patients who underwent 73 surgeries for non-traumatic neurosurgical indications over 12 months. A standard protocol was followed for the evaluation and management of postoperative fever. We prospectively collected data pertaining to operative details, daily maximal temperature, clinical features, and use of surgical drains, urinary catheters, and other adjuncts. Elevated body temperature of > 99.9 °F or 37.7 °C for > 48 h or associated with clinical deterioration or localising features was considered as "fever"; elevated temperature not meeting these criteria was classified as transient elevation in temperature (TET). RESULTS: Twenty-six patients (35.6%) had postoperative fever, more frequent than in adult patients. TET occurred in 12 patients (16.4%). The most common causes of fever were aseptic meningitis (34.6%), followed by urinary tract infections (15.4%), pyogenic meningitis, COVID-19, and wound infections. Postoperative fever was associated with significantly longer duration of hospital admission and was the commonest cause of readmission. CONCLUSION: In contrast to adults, early temperature elevations in paediatric patients may portend infectious and serious non-infectious causes of fever, including delayed presentation with aseptic meningitis, a novel association among paediatric patients. Investigation guided by clinical assessment and conservative antibiotic policy in keeping with the institutional microbiological profile provides the most appropriate strategy in managing paediatric postoperative fever.

Regioselective Addition of Sulfur and Amine Nucleophiles To Assemble S═C-S, S-N, and Umpolung C-N Bonds: Exploration of the -CBr3 Group as a Synthetic Equivalent of S═C-S.

The regioselective addition of sulfur and amine nucleophiles to a -CBr3 unit and nitromethyl moiety in a molecule with the installation of a five-diverse bond structure to novel isothiazole-5(2H)-thione is demonstrated. Umpolung of the nitromethyl group leads to a novel scaffold with selective C-N bond formation. Consequently, differentiating reactive centers by sulfur and amine nucleophiles has been proposed to create unique S-N bonds in conjunction with the dithioate (S═C-S-) moiety. This protocol allows for exploration of the -CBr3 moiety as a synthetic equivalent of the dithioate (S═C-S-) unit during the reaction.

Optical Coherence Tomography Predictors of SIde Branch REstenosis after unprotected Left Main bifurcation angioplasty using double kissing crush technique (OP-SIBRE LM Study).

BACKGROUND: Among the two stent strategies, contemporary evidence favors double kissing crush technique (DKC) for complex unprotected distal left main bifurcation (UdLMB) lesions. However one of the major challenges to these lesions is side branch (SB) restenosis. AIMS: Our aim was to identify optical coherence tomographic (OCT) characteristics that may predict SB restenosis (SBR) after UdLMB angioplasty using DKC technique. METHODS: This was a single-center, retrospective study that included 60 patients with complex UdLMB disease, who underwent OCT-guided angioplasty using DKC technique. Angiographic follow-up was performed in all patients at 1 year to identify patients with SBR. Patients with SBR group were compared with patients without SBR (NSBR group) for OCT parameters during index procedure. RESULTS: Twelve (20%) patients developed SBR at 1-year follow-up. The SBR group had longer SB lesion (18.8 ± 3.2 vs. 15.3 ± 3.7 mm, p = 0.004) and neo-metallic carinal length (2.1 vs. 0.1 mm, p < 0.001) when compared to the NSBR group. Longer neo-metallic carinal length was associated with the absence of the dumbbell sign, presence of hanging stent struts across the SB ostium on OCT of final MB pullback. On multivariate regression analysis, SB distal reference diameter (DRD) and SB stent expansion were identified as independent predictors of SBR with SB-DRD of ≤2.8 mm (area under curve-0.73, sensitivity-83.3%, and specificity-62.5%) and SB stent expansion of ≤89% (area under curve-0.88, sensitivity-83.3%, and specificity- 81.2%) as the best cut off values to predict SBR. CONCLUSIONS: SB DRD and SB stent expansion are the OCT predictors of future SBR after UdLMB angioplasty using DKC technique.

aVR: The forgotten lead in acute coronary syndrome: A case series.

Lead aVR is often considered as a neglected lead or forgotten lead owing to its reciprocal location to the lateral leads. However, it has diagnostic and prognostic importance in cases of acute coronary syndromes. We present a series of four cases of acute coronary syndrome with ST elevation (STE) in aVR and critical stenosis in coronary vessels. Patients with STE in aVR have a poor prognosis with increased morbidity not limited to increased chances of heart failure at presentation, greater hemodynamic instability, and in-hospital acute kidney injury, as well as increased mortality due to large infarction areas. Thus, early revascularization is warranted in such cases.

Quantum dots: a tool for the detection of explosives/nitro derivatives.

Nitro derivatives are considered as major environmental pollutants and issues of health concern. In current times, a variety of methods and techniques have been utilized for the sensing of these nitro derivatives. In view of this, the remarkable fluorescence properties of quantum dots (QDs) provide a great opportunity to detect these nitro derivatives. This review highlighted the recent reports of QDs as the sensing material for these nitro derivative explosives. Different modifications in QDs using physical and chemical approaches can be used to improve their sensing output. Various interaction mechanisms have been discussed between QDs and nitro derivatives to change their fluorescence properties. Finally, the current challenges and the perspective for the forthcoming future are provided in the concluding section. We hope this review will be beneficial in guiding the utilization of QDs in sensing applications.

Atmospheric Oxygen Facilitated Oxidative Amidation to α-Ketoamides and Unusual One Carbon Degradative Amidation to N-Alkyl Amides.

A mild, transition-metal-free novel synthetic approach for the construction of C═O and C-N bonds has been demonstrated. Easily accessible gem-dibromoalkenes under similar conditions form oxidative amidation product α-ketoamides and unusual degradative amidation product N-alkyl amides by simply changing the amine substitute. Atmospheric air containing molecular oxygen proved to be an ideal oxidant for an amidation reaction. Under similar conditions, the electron-deficient gem-dibromoalkenes play a dual role with different formamides forming novel oxidative amidation products and by the state of art neighboring group participation of amine to unusual one-carbon degradative amidation products.

Isolation and characterization of a novel mycobacteriophage Kashi-VT1 infecting Mycobacterium species.

Mycobacteriophages are viruses that infect members of genus Mycobacterium. Because of the rise in antibiotic resistance in mycobacterial diseases such as tuberculosis, mycobacteriophages have received renewed attention as alternative therapeutic agents. Mycobacteriophages are highly diverse, and, on the basis of their genome sequences, they are grouped into 30 clusters and 10 singletons. In this article, we have described the isolation and characterization of a novel mycobacteriophage Kashi-VT1 (KVT1) infecting Mycobacterium >smegmatis mc2 155 (M. smegmatis) and Mycobacterium fortuitum isolated from Varanasi, India. KVT1 is a cluster K1 temperate phage that belongs to Siphoviridae family as visualized in transmission electron microscopy. The phage genome is 61,010 base pairs with 66.5% Guanine/Cytosine (GC) content, encoding 101 putative open reading frames. The KVT1 genome encodes an immunity repressor, a tyrosine integrase, and an excise protein, which are the characteristics of temperate phages. It also contains genes encoding holin, lysin A, and lysin B involved in host cell lysis. The one-step growth curve demonstrated that KVT1 has a latency time of 90 min and an average burst size of 101 phage particles per infected cell. It can withstand a temperature of up to 45°C and has a maximum viability between pH 8 and 9. Some mycobacteriophages from cluster K are known to infect the pathogenic Mycobacterium tuberculosis (M. tuberculosis); hence, KVT1 holds potential for the phage therapy against tuberculosis, and it can also be engineered to convert into an exclusively lytic phage.

The Role of Adjunctive Chemical Solutions in the Treatment of Odontogenic Keratocysts: A Scoping Review.

Odontogenic keratocysts (OKC) are aggressive cysts with a high recurrence potential. Treating them with surgical enucleation procedures alone is associated with high recurrence rates; therefore, additional or supportive treatment approaches, such as peripheral osteotomy, cryotherapy, and chemical solutions, are warranted. The objective of the present review was to evaluate the existing literature on the efficacy of chemical approaches, such as Carnoy's solution (CS), in preventing recurrence after the enucleation of OKC. An electronic search was conducted on PubMed, Scopus, and Google Scholar databases to find articles published from January 2010 to December 2022 by using the Medical Subject Headings (MeSH) terms "Odontogenic Keratocyst" "Carnoy's Solution," "Treatment," and "Enucleation." Articles published in the English language were selected for the study. The PICOS criteria (population: patients with non-syndromic OKC with histopathological diagnosis and a minimum follow-up of six months; intervention and comparison: enucleation followed by adjunctive chemical therapy and standard procedure; outcome: recurrence rates; study design: retrospective and prospective studies, randomized controlled trials, and case series involving at least 10 cases of OKC) were employed. Studies involving syndromic (nevoid basal cell carcinoma) cases were excluded from the search. Seventeen studies fulfilled the inclusion criteria and the majority of them were retrospective studies, with a few case series. OKC was found more frequently in the mandible, with a recurrence rate of 11%, when treated with CS following enucleation after four years of follow-up. Modified Carnoy's solution (MC) was used in two studies. The mean follow-up period was 44 months. Based on our findings, adjuvant therapy using a chemical approach following enucleation is a more effective and beneficial modality for the treatment of OKC.

Management of a broken guiding catheter tip: Cut and fix technique.

A 49-year-old male presented with class III exertional angina, 1 year after angioplasty of the left anterior descending artery (LAD) and right coronary artery. Coronary angiogram revealed 90% in-stent restenosis (ISR) in mid-LAD with angiographic impression of stent fracture. Optical coherence tomographic evaluation of mid-LAD ISR showed a distinct 3 mm long "eclipse sign" indicating embolized, broken guiding catheter tip as a cause of ISR, which was confirmed on reviewing 1-year-old angiographic images. This was managed with "cut and fix technique" using cutting balloon and another drug-eluting stent. Optical coherence tomographic at 9 months showed well endothelialized stent with a thin layer of neo-intimal hyperplasia over the sandwiched broken guiding tip.

A Negative-Pressure Face-Mounted System Reduces Aerosol Spread during Endonasal Endoscopic Surgery.

Purpose Due to the potential risk of COVID-19 transmission during endonasal surgery, we studied methods to reduce droplet and aerosol generation during these procedures. Methods Droplet spread was assessed using ultraviolet light and a camera that detected fluorescence in the operative field and surgeon's personal protective equipment. Density of aerosols sized <10 µm was measured using a photometric particle counter. We designed a face-mounted negative-pressure mask placed on the patients' face during endoscopic endonasal surgery. Sixteen patients were recruited between October 2020 and March 2021 and randomly assigned to the mask and no-mask groups. We compared droplet spread and aerosols generated in both groups, with copious irrigation and continuous suction during drilling forming the mainstay of surgical technique in all cases. Results Droplet contamination due to direct spillage of fluorescein from the syringe was noted in two patients. Aerosol density rose during sphenoid drilling in both groups, with no significant difference when continuous suction and irrigation were employed (1.27 times vs. 1.07 times the baseline, p = 0 .248 ). Aerosol density rose significantly when suction and irrigation were interrupted in the no-mask group (44.9 times vs. 1.2 times, p = 0 .028) , which was not seen when the mask was used. Conclusion Aerosol generation increases during drilling in endonasal procedures and is a concern during this pandemic. The use of a rigid suction close to the drill along with copious irrigation is effective in reducing aerosol spread. The use of a negative pressure mask provides additional safety when inadvertent blockage of suction and inadequate irrigation occur.

Percutaneous coronary intervention of anomalous right coronary arteries arising from the left sinus of Valsalva: a single-centre experience from Northern India.

Background: An anomalous right coronary artery (ARCA) arising from the left sinus of Valsalva is an uncommon congenital anomaly. The unusual location, take-off and intramural courses of ARCA pose a considerable technical challenge during percutaneous coronary intervention (PCI). Aims: We sought to report our experience of PCI of ARCA in 35 cases of atherosclerotic occlusion. Methods: The PCI database of 35 cases of ARCA was retrospectively analysed. The details about demography, clinical presentation, PCI procedure and clinical follow-up were noted. Results: The mean age was 56.7±13.5 years. The clinical presentation included stable angina in 45.7%, unstable angina in 20% and acute myocardial infarction in 34.3% of patients. Vascular access was transradial in 37.1% of cases, transfemoral in 60% of cases, and transbrachial in 1 case (2.9%). Judkins left and Amplatz left were commonly used guide catheters. Two patients with balloon-uncrossable, calcified lesions required rotablation-assisted PCI. Intravascular imaging was performed in 12 patients (34.3%). Optical coherence tomography demonstrated a proximal intramural course in 3 patients, and a slit-like orifice in 4 patients. The mean radiation dose and fluoroscopy time were 877±687.3 mGy and 18.8±11.6 minutes, respectively. Twenty-eight (80%) patients had an asymptomatic median follow-up of 49 (interquartile range: 29.0-97.5) months. Conclusions: We performed successful PCI in a cohort of 35 patients with ARCA, with favourable long-term clinical outcomes. The selection of an appropriate guide catheter and technical skills were important factors in achieving favourable results.

Microcosm-omics centric investigation reveals elevated bacterial degradation of imidacloprid.

Imidacloprid, a broad-spectrum insecticide, is widely used against aphids and other sucking insects. As a result, its toxic effect is becoming apparent in non-targeted organisms. In-situ bioremediation of residual insecticide from the environment utilizing efficient microbes would be helpful in reducing its load. In the present work, in-depth genomics, proteomics, bioinformatics, and metabolomics analyses were employed to reveal the potential of Sphingobacterium sp. InxBP1 for in-situ degradation of imidacloprid. The microcosm study revealed ∼79% degradation with first-order kinetics (k = 0.0726 day-1). Genes capable of mediating oxidative degradation of imidacloprid and subsequent decarboxylation of intermediates were identified in the bacterial genome. Proteome analysis demonstrated significant overexpression of the enzymes coded by these genes. Bioinformatic analysis revealed significant affinity and binding of the identified enzymes for their respective substrates (the degradation pathway intermediates). The nitronate monooxygenase (K7A41 01745), amidohydrolase (K7A41 03835 and K7A41 07535), FAD-dependent monooxygenase (K7A41 12,275), and ABC transporter enzymes (K7A41 05325, and K7A41 05605) were found to be effective in facilitating the transport and intracellular degradation of imidacloprid. The metabolomic study identified the pathway intermediates and validated the proposed mechanism and functional role of the identified enzymes in degradation. Thus, the present investigation provides an efficient imidacloprid degrading bacterial species as evidenced by its genetic attributes which can be utilized or further improved to develop technologies for in-situ remediation.

Trigeminal hybrid nerve sheath tumor - a case report and literature review.

BACKGROUND: Hybrid nerve sheath tumors (HNST) contain elements of more than one established sub-type of nerve sheath tumor and have been recently recognized in the 2016 WHO classification of central nervous system tumors. While common in the peripheral nerves and extracranial branches of cranial nerves, only one case has been previously documented of an intracranial HNST arising from a cranial nerve. CASE DESCRIPTION: We describe a large, multi-compartmental intracranial hybrid nerve sheath tumor arising from the trigeminal nerve in a 22-year-old lady who presented with clinical and radiological features suggestive of a right cerebellopontine angle mass. Histopathological examination following retrosigmoid excision of the tumor revealed histological and immunohistochemical features of a schwannoma and a perineurioma. CONCLUSIONS: HNSTs are likely to be underreported in the intracranial region. The clinical course of these tumors and the reason for their occurrence in this location are not known.

Validity and correlation of quantitative flow ratio with fractional flow reserve for assessment of intermediate coronary lesions.

BACKGROUND: The angiographic percent diameter stenosis (%DS) do not assess the physiological significance of epicardial coronary stenosis. The currently practised physiological indices require pressure wires with or without adenosine-induced hyperaemia. Quantitative flow ratio (QFR) is an angiography-based method to determine the functional significance of coronary stenosis. The present study aimed to analyse the diagnostic performance of QFR in comparison to fractional flow reserve (FFR) in intermediate coronary lesions. MATERIALS AND METHODS: It was a single centre retrospective study to analyse the diagnostic performance of offline QFR with the previously performed FFR in the last six years. A total of 56 interrogated vessels were included for the analysis. Offline QFR analysis was performed and correlated with FFR values in the intermediate coronary stenoses. RESULTS: The mean age of the study population was 62.4 ± 9.1 years, including 81% men. The left anterior descending artery (50%) was the most common analysed vessel followed by left circumflex (27%) and right coronary (21%) arteries. The mean % DS and % area stenosis were 45.25 ± 11.22% and 57.45% ± 16.25%, respectively. The mean FFR and QFR values were 0.83 ± 0.06 and 0.82 ± 0.10, respectively. A strong positive correlation was found between FFR and QFR with a Spearman correlation coefficient of 0.56. Receiver operating curve analysis for QFR and %DS with a FFR cut off value <0.80 showed an area under the curve of 0.97 and 0.77, respectively. The sensitivity, specificity and diagnostic accuracy of QFR were 87.5%, 95% and 92.8%, respectively. There was a discordance in four vessels (7.1%) between QFR and FFR. CONCLUSION: QFR has a good diagnostic performance in comparison to the gold standard FFR for physiological assessment of intermediate lesions. Its performance is significantly better than the anatomical % DS (p < 0.001).

An in vitro and computational validation of a novel loss-of-functional mutation in PAX9 associated with non-syndromic tooth agenesis.

Congenital tooth agenesis (CTA) is one of the most common craniofacial anomalies. Its frequency varies among different population depending upon the genetic heterogeneity. CTA could be of familial or sporadic and syndromic or non-syndromic. Five major genes are found to be associated with non-syndromic CTA, namely PAX9, MSX1, EDA1, AXIN2, and WNT10A. Very few studies have been carried out so far on CTA on this Indian population making this study unique and important. This study was initiated to identify potential pathogenic variant associated with congenital tooth agenesis in an India family with molar tooth agenesis. CTA was investigated and a novel c.336C > G variation was identified in the exon 3 of PAX9, leading to substitution of evolutionary conserved Cys with Trp at 112th amino acid position located at the functionally significant DNA-binding paired domain region. Functional analysis revealed that p.Cys112Trp mutation did not prevent the nuclear localization although mutant protein had higher cytoplasmic retention. EMSA using e5 probe revealed that mutant protein was unable to bind with the paired-domain-binding site. Subsequently, GST pull-down assay revealed lower binding activity of the mutant protein with its known interactor MSX1. These in vitro results were consistent with the computational results. The in vitro and computational observations altogether suggest that c.336C > G (p.Cys112Trp) variation leads to loss of function of PAX9 leading to CTA in this family.

Mutation detection and minimum inhibitory concentration determination against linezolid and clofazimine in confirmed XDR-TB clinical isolates.

BACKGROUND: The emergence of multidrug-resistant tuberculosis (MDR-TB) has complicated the situation due to the decline in potency of second-line anti-tubercular drugs. This limits the treatment option for extensively drug-resistant tuberculosis (XDR-TB). The aim of this study was to determine and compare the minimum inhibitory concentration (MIC) by agar dilution and resazurin microtiter assay (REMA) along with the detection of mutations against linezolid and clofazimine in confirmed XDR-TB clinical isolates. RESULTS: A total of 169 isolates were found positive for Mycobacterium tuberculosis complex (MTBC). The MIC was determined by agar dilution and REMA methods. The isolates which showed non-susceptibility were further subjected to mutation detection by targeting rplC gene (linezolid) and Rv0678 gene (clofazimine). The MIC for linezolid ranged from 0.125 µg/ml to > 2 µg/ml and for clofazimine from 0.25 µg/ml to > 4 µg/ml. The MIC50 and MIC90 for linezolid were 0.5 µg/ml and 1 µg/ml respectively while for clofazimine both were 1 µg/ml. The essential and categorical agreement for linezolid was 97.63% and 95.26% and for clofazimine, both were 100%. The sequencing result of the rplC gene revealed a point mutation at position 460 bp, where thymine (T) was substituted for cytosine (C) while seven mutations were noted between 46 to 220 bp in Rv0678 gene. CONCLUSION: REMA method has been found to be more suitable in comparison to the agar dilution method due to lesser turnaround time. Mutations in rplC and Rv0678 genes were reasons for drug resistance against linezolid and clofazimine respectively.