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.

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.

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.

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.

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.

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.

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.

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.

Water Mediated Direct Thioamidation of Aldehydes at Room Temperature.

A mild, greener approach toward thioamide synthesis has been developed. Its unique features include water-mediated reaction with no input energy, additives, or catalysts as well. The presented protocol is attractive with readily available starting materials and the use of different array amines, along with a scaled-up method. Biologically active molecules such as thionicotinamide and thioisonicotinamide can be synthesized from this procedure.

The thioamidation of gem-dibromoalkenes in an aqueous medium.

The direct integration of sulphur and amine groups with 1,1-dibromoalkenes for thioamide synthesis has been achieved in an aqueous medium. The presented green protocol emphasizes the suitability of aqueous media for the thioamidation reaction and enables greater selectivity with synthetic utility. A wide range of thioamides in moderate to excellent yields has been achieved using readily available starting materials, with the use of no organic solvents, catalysts, or additives.

Direct detection of resistance to fluoroquinolones/SLIDs in sputum specimen by GenoType MTBDRsl v.2.0 assay A study from Eastern Uttar Pradesh, India.

BACKGROUND: According to World Health Organization (WHO), drug-resistant tuberculosis (DR-TB) is a major contributor to antimicrobial resistance globally and continues to be a public health threat. Annually, about half a million people fall ill with DR-TB globally. The gradual increase in resistance to fluoroquinolones (FQs) and second-line injectable drugs (SLIDs), poses a serious threat to effective TB control and adequate patient management. Therefore, WHO suggests the use of GenoType MTBDRsl v.2.0 assay for detection of multiple mutations associated with FQs and SLIDs. Hence, the study was conducted to determine the prevalence of resistance to FQs and SLIDs by comparing direct GenoType MTBDRsl v.2.0 assay with phenotypic drug susceptibility testing (DST). METHODS: The study was conducted on 1320 smear positive sputum samples from a total of 2536 RR-TB, confirmed by GeneXpert MTB/RIF. The smear positive specimens were decontaminated, and DNA extraction was performed. Furthermore, the extracted DNA was used for GenoType MTBDRsl v.2.0 assay. While 20% of the decontaminated specimens were inoculated in Mycobacterium growth indicator tube (MGIT) for drug susceptibility testing (DST). RESULTS: Out of 1320 smear positive sputum samples, 1178 were identified as Mycobacterium tuberculosis complex (MTBC) and remaining were negative by GenoType MTBDRsl v.2.0 assay. Of the 1178 MTBC positive, 26.6% were sensitive to both FQs and SLIDs, whereas 57.3% were only FQs resistant and 15.9% were resistant to both FQs and SLIDs. Further DST of 225 isolates by liquid culture showed that 17% were sensitive to both FQs and SLIDs, 61.3% were only FQs resistant and 21.3% were resistant to both. The specificity for FQs and SLIDs was 92.31% and 100% whereas sensitivity was 100% respectively by GenoType MTBDRsl v.2.0 assay in direct sputum samples. CONCLUSIONS: Our study clearly suggests that GenoType MTBDRsl v.2.0 assay is a reliable test for the rapid detection of resistance to second-line drugs after confirmation by GeneXpert MTB/RIF assay for RR-TB. Though, high rate FQ (ofloxacin) resistance was seen in our setting, moxifloxacin could be used as treatment option owing to very low resistance.

Adapting management strategies for sellar-suprasellar lesions during the COVID-19 pandemic: a pragmatic approach from the frontline.

PURPOSE: During the ongoing COVID-19 pandemic, endonasal surgeries for sellar-suprasellar lesions were discouraged due to the risk of transmission of the disease. We reviewed the changes in our management protocol for these lesions as our disease understanding and preparedness evolved. MATERIALS AND METHODS: This was a retrospective observational study including patients with sellar-suprasellar and clival lesions presenting to us between March and October 2020. Management protocols were divided into three phases based on the prevalence of the disease and the number of mandatory preoperative COVID-19 tests being conducted. The surgical approach used was analyzed in relation to the preferred approach during pre-COVID times, and surgical outcomes and complications were noted. RESULTS: A total of 31 cases were operated during this period. During Phase I (low prevalence; no preoperative COVID testing) endonasal surgeries were largely abandoned in favor of transcranial approaches. In Phase II (medium prevalence; one preoperative COVID test) we gradually resumed endonasal surgeries for 'emergent' and 'essential' cases, and subsequently in Phase III (high prevalence; two preoperative COVID tests), we had no hesitation in performing 'elective' endonasal surgeries with additional barriers for prevention of aerosol transmission. No patient developed COVID-19 infection postoperatively. Eight HCWs in our department acquired the disease during this period, none of whom were directly involved in the surgeries for the above cohort of patients. CONCLUSIONS: With a strict preoperative COVID testing protocol, adherence to proper drilling techniques and using additional barriers to prevent droplet and aerosol spread, endonasal surgeries for sellar-suprasellar lesions are safe during this COVID-19 pandemic.

Severe acute malnutrition and its associated factors among children under-five years: a facility-based cross-sectional study.

BACKGROUND: Despite consistent efforts to enhance child nutrition, poor nutritional status of children continues to be a major public health problem in Nepal. This study identified the predictors of severe acute malnutrition (SAM) among children aged 6 to 59 months in the two districts of Nepal. METHODS: We used data from a cross-sectional study conducted among 6 to 59 months children admitted to the Outpatient Therapeutic Care Centers (OTCC). The nutritional status of children was assessed using mid-upper arm circumference (MUAC) measurement. To determine which variables predict the occurrence of SAM, adjusted odds ratio was computed using multivariate logistic regression and p-value < 0.05 was considered as significant. RESULTS: Out of 398 children, 5.8% were severely malnourished and the higher percentage of female children were malnourished. Multivariate analysis showed that severe acute malnutrition was significantly associated with family size (five or more members) (Adjusted Odds Ratio [AOR]: 3.96; 95% Confidence Interval [CI]: 1.23-12.71). Children from severely food insecure households (AOR: 4.04; 95% CI: 1.88-10.53) were four times more likely to be severely malnourished. Higher odds of SAM were found among younger age-group (AOR: 12.10; 95% CI: 2.06-71.09) children (0-12 vs. 24-59 months). CONCLUSIONS: The findings of this study indicated that household size, household food access, and the child's age were the major predictors of severe acute malnutrition. Engaging poor families in kitchen gardening to ensure household food access and nutritious diet to the children, along with health education and promotion to the mothers of young children are therefore recommended to reduce child undernutrition.

Mutation in MPT64 gene influencing diagnostic accuracy of SD Bioline assay (capilia).

BACKGROUND: Success of India's TB control program relies on rapid case detection, monitoring, care and treatment of drug resistance. Patients on multidrug resistance (MDR) treatment are monitored by follow up cultures. Discordant results (culture and smear positive while capilia negative) are usually declared negative Mycobacterium tuberculosis complex (MTBC). This study was designed to understand the possible causes of discordant results. METHODS: The capilia kit was evaluated to test its utility among 4737 follow up MDR patients enrolled during a period of 1 year. A total of 889 were liquid culture positive, 3375 were negative and 473 were contaminated. Of the 889 cultures positive, 829 were found positive by ZN smear, capilia test and MTBDR plus assay. The cultures which gave a positive result on Mycobacterium Growth Indicator Tube 960 (MGIT 960) and ZN smear but were negative on capilia test with no growth on Brain Heart Infusion agar (BHI) were included in this study. The conflicting results of capilia were compared with other molecular techniques; MTBDR plus assay and DNA sequence analysis of MPT64 gene. RESULTS: Out of 889 culture positive, 60 (6.7%) were found positive on liquid culture and ZN smear but were negative on capilia. Of these 60 cultures, 10 (16.7%) were found positive by both MTBDR plus assay and PCR. The sequencing analysis revealed that all of the capilia negative isolates had mutations within the MPT64 gene. CONCLUSION: Re-evaluation of culture positive but capilia negative isolates should be done before declaring them as Mycobacterium other than tuberculosis (MOTT) because such cases can act as chronic carriers of TB in the population which can lead to the rise of this lethal disease.

Fatty filum terminale (FFT) as a secondary tethering element in children with closed spinal dysraphism.

PURPOSE: The purpose of this study was to assess the prevalence of FFT as an additional tethering element in children operated for closed spinal dysraphism, where FFT was not the primary tethering pathology. METHODS: This is a retrospective study of 195 children (< 18 years of age) who underwent surgery for closed spinal dysraphism and did not have FFT as the primary diagnosis. All patients were operated during the period 2005-2017 by a single surgeon. The commonest diagnosis was a lipomyelomeningocele (LMMC, n = 81, 41.5%), followed by split cord malformations (SCM, types I and II, n = 61, 31.3%), dermal sinus (n = 28, 14.4%), and dermoid cyst (n = 10, 5.1%). Factors such as age and sex, presenting symptoms, intraoperative findings, and radiological presence of a FFT on a magnetic resonance imaging (MRI) were documented, and the relationship between the primary diagnoses and presence of FFT was analyzed. RESULTS: FFT as a secondary finding was seen in 63 patients (32.3%). The mean age of the cohort was 54 months (4.5 years) and the sex distribution was relatively even (51.8% girls). The commonest symptom at presentation was a swelling in the back, followed by lower limb weakness. The mean duration of symptoms was nearly 30 months. FFT was seen on the MRI and confirmed intraoperatively in 55 patients (28.2%). There were 8 patients (4.1%) where a FFT was seen intraoperatively, but was not diagnosed on the preoperative MRI. In 16 patients, FFT was seen > 2 segments away from the primary tethering pathology, 8 of which mandated a second skin incision for sectioning of the FFT. Secondary FFT was most commonly associated with a SCM (types I and II combined) and was seen in 42.6% of those patients. It was least commonly associated with intradural dermoid cysts. CONCLUSION: The presence of a secondary FFT should be considered and actively sought on preoperative thin-slice T1W axial MR images in the sacral region in all patients with spinal dysraphism. Even if a FFT is not seen on preoperative MR images, the filum should be explored and sectioned if it is in the vicinity of the primary surgical field, especially in patients with SCM.

Regulation of a Glycerol-Induced Quinoprotein Alcohol Dehydrogenase by σ54 and a LuxR-Type Regulator in Azospirillum brasilense Sp7.

Azospirillum brasilense Sp7 uses glycerol as a carbon source for growth and nitrogen fixation. When grown in medium containing glycerol as a source of carbon, it upregulates the expression of a protein which was identified as quinoprotein alcohol dehydrogenase (ExaA). Inactivation of exaA adversely affects the growth of A. brasilense on glycerol. A determination of the transcription start site of exaA revealed an RpoN-dependent -12/-24 promoter consensus. The expression of an exaA::lacZ fusion was induced maximally by glycerol and was dependent on σ54 Bioinformatic analysis of the sequence flanking the -12/-24 promoter revealed a 17-bp sequence motif with a dyad symmetry of 6 nucleotides upstream of the promoter, the disruption of which caused a drastic reduction in promoter activity. The electrophoretic mobility of a DNA fragment containing the 17-bp sequence motif was retarded by purified EraR, a LuxR-type transcription regulator that is transcribed divergently from exaA EraR also showed a positive interaction with RpoN in two-hybrid and pulldown assays.IMPORTANCE Quinoprotein alcohol dehydrogenase (ExaA) plays an important role in the catabolism of alcohols in bacteria. Although exaA expression is thought to be regulated by a two-component system consisting of EraS and EraR, the mechanism of regulation was not known. This study shows the details of the regulation of expression of the exaA gene in A. brasilense We have shown here that exaA of A. brasilense is maximally induced by glycerol and harbors a σ54-dependent promoter. The response regulator EraR binds to an inverted repeat located upstream of the exaA promoter. This study shows that a LuxR-type response regulator (EraR) binds upstream of the exaA gene and physically interacts with σ54 The unique feature of this regulation is that EraR is a LuxR-type transcription regulator that lacks the GAFTGA motif, a characteristic feature of the enhancer binding proteins that are known to interact with σ54 in other bacteria.

Functional and radiological outcome in patients undergoing three level corpectomy for multi-level cervical spondylotic myelopathy and ossified posterior longitudinal ligament.

BACKGROUND: To review our experience with patients undergoing 3 level cervical central corpectomy (CC) with un-instrumented fibular autograft fusion. MATERIALS AND METHODS: This is a retrospective study, involving 33 patients with cervical spondylotic myelopathy (CSM) or ossified posterior longitudinal ligament (OPLL) who underwent a 3 level CC between 2002 and 2010. The patients were followed up clinically and radiologically. Their functional status was assessed using Nurick's grading system. Parameters such as intraoperative complications, segmental curvature of the cervical spine, graft subsidence, graft fusion and functional outcome of these patients were assessed. RESULTS: There was transient morbidity in 28.6% of patients, with no permanent morbidity or mortality. We obtained follow up in 29 patients (87.9%) with a mean duration of follow up of 65.1 months (range, 12 to 138 months). The mean difference of segmental cervical curvature on follow up was 3.600 and the average graft subsidence was 5.70 mm. We achieved a fusion rate of 90%. There was no instance of graft extrusion in our series. There was a significant improvement in the functional status of our patients (from Nurick grade 3.55 to 2.42; P = 0.0001), with no clinical deterioration in any patient. CONCLUSIONS: Three level cervical corpectomy with un-instrumented fusion is a relatively safe surgery in experienced hands, and can achieve excellent clinical and radiological outcomes.

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.