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Succinylcholine and rocuronium are the most commonly utilized neuromuscular blocker agents (NMBAs) for rapid sequence intubation (RSI) in the emergency department (ED). The duration of action of rocuronium is significantly longer (∼30 min) compared to succinylcholine (∼10 min) and previous studies have shown that patients receiving rocuronium are more likely to have longer time to sedation initiation following RSI. Furthermore, patients receiving rocuronium may be more likely to experience awareness with paralysis than those receiving succinylcholine. The primary goal for this study was to evaluate the association between NMBA use during RSI and post-intubation sedation and analgesia practices in the ED. This was a retrospective, multicenter cohort study including patients 18 years and older that received succinylcholine or rocuronium during RSI in the ED between September 1, 2020 and August 31, 2021. Patients were excluded if they were intubated prior to ED arrival, experienced an out-of-hospital or in ED cardiac arrest, or received sugammadex within 60 min of rocuronium administration. Patients were screened in reverse chronological order until the targeted sample size was achieved and all data was abstracted from the electronic health record. The primary outcome was the time to initiation of analgesia or sedation. Secondary outcomes included dose of sedatives or analgesia administered at 30- and 60 min, and medications administered for post-intubation sedation or analgesia. A total of 200 ED patients were included of which 100 received succinylcholine and 100 received rocuronium. There was no difference in the median time to initiation of analgesia or sedation between the succinylcholine and rocuronium groups (10 vs 8.5 min, p = 0.82) or in Kaplan-Meier cumulative probabilities (p = 0.17). At 60 min post-RSI, those receiving succinylcholine received significantly higher median doses of propofol (20 μg/kg/min vs. 10 μg/kg/min; p = 0.02) and fentanyl [100 μg vs. 84.2 μg; p = 0.02]. While no differences were observed in the time to initiation of post-intubation sedation or analgesia in ED patients receiving succinylcholine compared to rocuronium, differences in the intensity of post-intubation regimens was observed. Further investigation is needed to evaluate the adequacy of sedation following RSI in the ED. [ABSTRACT FROM AUTHOR]

18F-Fluoro-deoxyglucose positron emission computed tomography (18F-FDG PET CT) is an established modality used mainly in oncology. Though it has widespread oncologic indications, it is not tumor specific. Apart from the physiological distribution, uptake of FDG may be seen in many benign conditions, including infection and inflammation in children and adults. Performing and acquiring a technically adequate PET CT study may be more challenging in children. Proper preparation and an acceptable imaging protocol will help to avoid re-acquisition and in minimizing the radiation exposure. Sound knowledge of the physiological variants and benign conditions that are specific to the pediatric population will aid in correct interpretation of the PET CT study. It is important that radiologists and Nuclear Medicine physicians who report these studies are well-acquainted with these pitfalls to avoid false positive studies. [ABSTRACT FROM AUTHOR]

The Indium doped SBA-15 material was prepared by sol-gel method and tested for vapor phase Beckman rearrangement reaction. Among three indium loading, In/Si ratio of 2/100 was found as an optimum composition in terms of caprolactam selectivity (100%) and cyclohexanone oxime conversion (100%). The catalysts were characterized by N 2 adsorption, small-angle X-rays/neutron scattering (SAXS/SANS), XRD, FESEM, HRTEM, EDX, UV, FTIR and NH 3 -TPD techniques. In-situ SANS experiment was performed on the adsorption of CO 2 to detect the micropores in the mesopore wall. All catalysts samples have highly ordered hexagonal structure with well dispersed indium in the silica matrix. The fine tuning of weak and strong acid sites were found in indium doped SBA-15 (In/Si = 2/100) catalyst. The same catalyst showed optimum catalytic performance, high space time yield 114.4 mol/h/g cat and high stability till 6 h of reaction without deactivation. The micro-kinetic analysis showed that there were no external and internal diffusion limitations in the SBA-15 catalyst. The reaction mechanism of Beckmann rearrangement over In-SBA-15 has been elucidated. [ABSTRACT FROM AUTHOR]

Background The incidence and optimal management of postoperative chylous leak of neuroblastoma is inadequately documented. We analyzed the risk factors, management, and the implication of chyle leak following surgery for abdominal neuroblastoma. Methods One hundred sixty patients who underwent surgery for abdominal neuroblastoma between September 2004 and August 2014 were evaluated. To find the oncological implication we evaluated the delay in starting further treatment, local control, event free and overall survival. Results Chyle leak was the most common complication (20%). The median measure of leakage was 100 ml/day and it persisted for a median of 12 days. All patients were managed conservatively except one who needed exploration for wound dehiscence. Number of lymph nodes resected was the only factor associated with the risk of chyle leaks ( p = 0.013). Adjuvant chemotherapy was not delayed in any patient because of chyle leaks per se and the local control, event free and overall survival were not different for patients with and without chyle leak. Conclusion Chylous leakage is a common postoperative complication of abdominal neuroblastoma, predisposed by the number of lymph nodes resected. It responds to conservative management and does not compromise further the oncological treatment and outcome hence; it should not be a deterrent to complete surgery. [ABSTRACT FROM AUTHOR]

Nb doped HMS-X (Nb-HMS-X) was synthesized by sol–gel/emulsion method using non-ionic tri-block copolymer surfactant PEO 140 PPO 39 PEO 140 (P123) as a structure directing agent. The effect of synthesis condition on the pore morphology and nature of pore ordering was investigated. Small-angle X-ray Scattering (SAXS) revealed highly ordered pore structure in Nb-HMS-X. It is demonstrated by Field Emission Scanning Electron Microscopy (FESEM) that the materials possessed various morphologies such as, regular spheres, disordered and tube-spheres depending on synthesis conditions. The solid state 29 Si nuclear magnetic resonance measurements showed that chemical environment of silicon atoms get modified significantly with synthesis condition. Furthermore, the synthesized niobium doped hollow mesoporous silica (Nb-HMS-X) was effective to catalyze ethyl benzene oxidation reaction where activation of C–H bond took place. [ABSTRACT FROM AUTHOR]

A precipitation-deposition method in an organic medium was used to prepare vanadium phosphorus oxide (VPO) catalysts supported on SBA-15 and TUD-1. Oxidation of cyclohexane has been examined over mesoporous silica supported VPO catalyst. The supported VPO catalyst has been characterized by XRD, N 2 physisorption, SEM, HRTEM, H 2 -TPR and NH 3 -TPD techniques. The characteristic X-ray diffraction patterns of bulk VPO catalyst and VPO catalysts supported on mesoporous SBA-15 and TUD-1 showed that each of them are having well-crystallized vanadyl pyrophosphate [(VO) 2 P 2 O 7 ] phase. The vanadium redox centers were easily accessible for supported VPO catalyst. The TUD-1 supported VPO catalyst had higher acidity as found in NH 3 -TPD studies. The conversion of cyclohexane increased in the case of VPO dispersed on TUD-1 mesoporous material. From SEM and HRTEM results it is found that the nature of the support and VPO loading had a profound influence on the crystallinity, morphology and chemical property of the dispersed VPO phase. The changes in all the property had a prominent role on its catalytic activity for the oxidation of the cyclohexane. [ABSTRACT FROM AUTHOR]

Summary In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation. [ABSTRACT FROM AUTHOR]

Objective Readmission after surgery is an unwanted adverse event that is costly to the healthcare system. We sought to evaluate factors associated with increased risk of readmission and to characterize the nature of these readmissions in patients who have esophageal cancer. Methods A retrospective cohort study was performed in 306 patients with esophageal carcinoma who underwent neoadjuvant chemoradiation followed by esophagectomy at Johns Hopkins Hospital between 1993 and 2011. Logistic regression was used to identify factors associated with 30-day readmission. Readmissions were defined as inpatient admissions to our institution within 30 days of discharge. Results The median age at surgery was 61 years; the median postoperative length of stay was 9 days; and 48% of patients had ≥1 postoperative complication (POC). The 30-day readmission rate was 13.7% (42 of 306). In univariate analysis, length of stay and having ≥1 POC were significantly associated with readmission. In multivariate analysis, having ≥1 POC was significantly associated with a >2-fold increase in risk for 30-day readmission (odds ratio 2.35, with 95% confidence interval [1.08-5.09], P = .031) when controlling for age at diagnosis and length of stay. Of the 42 patients who were readmitted, 67% experienced POCs after surgery; 50% of patients who experienced POCs were readmitted for reasons related to their postoperative complication. The most common reasons for readmission were pulmonary issues (29%), anastomotic complications (20%), gastrointestinal concerns (17%), and venous thromboembolism (14%). Conclusions Complications not adequately managed before discharge may lead to readmission. Quality improvement efforts surrounding venous thromboembolism prophylaxis, and discharging patients nothing-by-mouth, may be warranted. [ABSTRACT FROM AUTHOR]

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Abstract: The most important strategy to ensure a safe and an adequate supply of blood and blood products is motivation, recruitment, selection and retention of voluntary non remunerated blood donors. With a view of the increased platelet necessity in our oncology setup, the first platelet donation drive in the city and to the best of our knowledge, in India was conducted by our hospital in November 2009. The aim was to identify target groups and expand our donor database. It was also essential that the donor’s contribution is acknowledged and appropriately felicitated. A campaign called “Save a Life” was initiated and publicized locally. A core team consisting of Transfusion Medicine specialists, clinicians and an NGO (nongovernment organization) was formed. The best suitable date and venue were finalized for the platelet camp. The audience was addressed and willing donors were registered as volunteer platelet donors with our institute. In a span of 40months, 15 platelet camps were organized in colleges, social organizations, and corporate offices. A total of 1035 donors were registered out of which, 382 (37%) donated platelets in our hospital. 125/382 (33.2%) donated Single Donor Platelets (SDP) more than once. The largest number of platelet donations by a single camp donor was 24 times. Due to multiple donations from donors, the SDP number was enhanced considerably and lead to addition of 699 SDP units to our inventory. The annual indoor and camp voluntary platelet donor numbers increased from 142 in 2006 to 631 in 2012 due to platelet drives. All platelet donations were altruistic as no incentives were offered to the donors. Ready availability of platelets and planning SDP inventory as per patient blood group requirements had a positive impact on clinical services. [Copyright &y& Elsevier]

Non-Wilms renal tumors represent a compelling subset of childhood renal tumors. However, their relative rarity renders accurate diagnosis, and therapy challenging which in some instance is inferred from their adult counterparts. To describe the incidence and analyze the diagnostic challenges, therapies and, outcomes of non-Wilms renal tumors at the largest tertiary cancer centre in India. All patients with histologically confirmed non-Wilms renal tumours diagnosed in the paediatric oncology unit of Tata Memorial Hospital between 2006 and 2019 were included. Data regarding clinical and radiological features and treatment outcomes were retrieved from the prospectively maintained institutional database. At the outset, histological types were categorised into a high and low-risk group depending on anticipated survival. Survival analysis was performed utilising the Kaplan–Meier method on SPSS software version 24.0. Of the 569 patients with renal tumors, 109 (19%) patients with primary (n = 97) or recurrent (n = 12) non-Wilms renal tumors were included. Histological high-risk group included clear cell sarcoma (CCSK) (39.4%), renal cell carcinoma (RCC) (19.3%), malignant rhabdoid tumor (MRTK) (12.8%), Ewing's sarcoma (rES) (15.6%), synovial sarcoma (2%), and undifferentiated sarcoma (2%). The low-risk group comprised of congenital mesoblastic nephroma (CMN) (4.6%), cystic partially differentiated nephroblastoma (2%), and other rare tumors (3%). Diagnostic error occurred in 2 patients in the high-risk group. All low-risk tumours were treated with surgery alone and most (97%) high-risk tumors were operated either upfront (61.5%) or after preoperative chemotherapy (38.4%). Adjuvant therapy based on histology was offered to 70%. The recurrent tumors received various salvage treatments including chemotherapy; radiotherapy; surgery and immunotherapy, however, only 2 patients could be salvaged. The 3-year overall survival for the entire cohort with primary tumors was 59%, and the survival rates were 76.7%, 77.9%, 0.0%, and 52% for CCSK, RCC, MRTK, and rES (summary figure). Low-risk tumors had 100% survival while the recurrent tumors had a median survival of 10.5 months. Non-Wilms renal tumors constitute a heterogeneous group of tumors, accounting for less than 20% of all renal tumors. Low-risk tumors are associated with excellent outcomes following surgery alone while the high-risk tumours have a variable outcome. MRTK and recurrent non-Wilms tumour have the worst survival. Favourable outcomes for CCSK and RCC and worst outcomes for MRTK were observed in this study. Renal ES have higher incidence of treatment failure and unsatisfactory outcomes. Recurrent non-Wilms tumours have an extremely poor outcome and more alternative or innovative approaches are needed for their treatment. [ABSTRACT FROM AUTHOR]

Silencing of FMR1 and loss of its gene product, FMRP, results in fragile X syndrome (FXS). FMRP binds brain mRNAs and inhibits polypeptide elongation. Using ribosome profiling of the hippocampus, we find that ribosome footprint levels in Fmr1 -deficient tissue mostly reflect changes in RNA abundance. Profiling over a time course of ribosome runoff in wild-type tissue reveals a wide range of ribosome translocation rates; on many mRNAs, the ribosomes are stalled. Sucrose gradient ultracentrifugation of hippocampal slices after ribosome runoff reveals that FMRP co-sediments with stalled ribosomes, and its loss results in decline of ribosome stalling on specific mRNAs. One such mRNA encodes SETD2, a lysine methyltransferase that catalyzes H3K36me3. Chromatin immunoprecipitation sequencing (ChIP-seq) demonstrates that loss of FMRP alters the deployment of this histone mark. H3K36me3 is associated with alternative pre-RNA processing, which we find occurs in an FMRP-dependent manner on transcripts linked to neural function and autism spectrum disorders. • Loss of FMRP reduces ribosome stalling on specific mRNAs, including Setd2 • Increased SETD2 protein alters H3K36me3 marks in FMRP-deficient hippocampus • Alternative splicing is dysregulated in FMRP-deficient hippocampus • Altered H3K36me3 and splicing occur on genes and transcripts linked to autism Shah et al. show that many neuronal mRNAs are associated with FMRP-stalled ribosomes. FMRP-regulated ribosome stalling influences the chromatin landscape. These events in turn mediate alternative processing of pre-mRNAs linked to autism. [ABSTRACT FROM AUTHOR]

This phase II study evaluated the utility of magnetic resonance imaging (MRI) and positron emission tomography for planning radiation and brachytherapy in patients with postsurgical recurrence of cervical cancer. The study (NCT 01391065) recruited patients with residual or recurrent disease after hysterectomy. Patients underwent baseline T2 weighted (T2W) MRI, 18F-flouro-deoxyglucose (18F-FDG), 18F-flouro thymidine (18F-FLT) and 18F-flouromisonidazole (18F-F Miso) positron emission tomography (PET) and received external radiation (50 Gy/25 fractions for 5 weeks) and weekly cisplatin (40 mg/m2). MRI was performed at brachytherapy and used for delineation of clinical target volume (CTV). Patients with parametrial disease at baseline received interstitial brachytherapy (16-20 Gy/4-5 fractions) and those with vaginal disease received intracavitary brachytherapy (12-14 Gy/2-4 fractions). Kaplan-Meier analysis was performed to evaluate locoregional relapse, disease free survival, and overall survival. Common Toxicity Criteria for adverse event reporting (CTCAE) v4.1 was used for toxicity scoring and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questtionaire Core 30 (QLQC-30) and Cx 24 for quality-of-life reporting. Between January 2011 and February 2016, 60 patients were included, of which 50 received study treatment. The mean gross tumor volume on T2 W MR was 20 (IQR 3.6-90) cc. The metabolic tumor volume was 15 (interquartile range [IQR] 2.1-56.1) cc. The median FLT volume was 10 (IQR 0-48) cc. A total of 8 patients had 18-F F Miso uptake. The median CTV at brachytherapy was 38 (12-85) cc. The median CTVD90 and D 98 was 71 (53-74) and 74 (53-74) Gy. At a median follow-up of 60 (5-93) months, the 5-year local control, disease free survival, and overall survival were 84%, 73%, and 74.5%, respectively. Grade III and IV proctitis and cystitis were observed in 4% and 2% of patients. On multivariate analysis baseline tumor volume, on T2 W MR impacted disease free (91% vs 65%, P =.03) and overall survival (96% vs 77%, P =.06). Image-guided assisted radiation and brachytherapy are associated with good to excellent local control and survival in patients with vaginal recurrences of cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to assess the effect of radiation therapy (RT) dose escalation on outcomes in surgically unresectable Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET).Methods and Materials: Patients with nonmetastatic unresectable ES/PNET (excluding intracranial/chest wall) receiving vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide chemotherapy, planned for definitive RT, were accrued in this single-institution, open-label, phase 3 randomized controlled trial. Randomization was between standard dose RT (SDRT; 55.8 Gy/31 fractions/5 days a week) versus escalated dose RT (EDRT; 70.2 Gy/39 fractions/5 days a week) with a primary objective of improving local control (LC) by 17% (65%-82%). Secondary outcomes included disease-free survival (DFS), overall survival (OS), and functional outcomes by Musculoskeletal Tumor Society score.Results: Between April 2005 and December 2015, 95 patients (SDRT 47 and EDRT 48) with a median age of 17 years (interquartile range, 13-23 years) were accrued. The majority of patients were male (59%). Pelvis was the most common site of primary disease (n = 60; 63%). The median largest tumor dimension (9.7 cm) and the median maximum standardized uptake value (8.2) on pretreatment fluorodeoxyglucose positron emission tomography-computed tomography were similar. At a median follow-up of 67 months, the 5-year LC, DFS, and OS for the entire cohort was 62.4%, 41.3%, and 51.9%, respectively. The 5-year LC was significantly better in EDRT compared with SDRT (76.4% vs 49.4%; P = .02). The differences in DFS and OS at 5 years (for EDRT vs SDRT) did not achieve statistical significance (DFS 46.7% vs 31.8%; P = .22 and OS 58.8% vs 45.4%; P = .08). There was a higher incidence of Radiation Therapy Oncology Group grade >2 skin toxic effects (acute) in the EDRT arm (10.4% vs 2.1%; P = .08) with excellent functional outcomes (median Musculoskeletal Tumor Society score = 29) in both arms.Conclusions: EDRT results in improved LC with good functional outcomes without a significant increase in toxic effects. Radiation dose escalation should be considered for surgically unresectable nonmetastatic ES/PNET. [ABSTRACT FROM AUTHOR]

COVID-19 infection is associated with D-dimer elevations, high rates of thrombus formation, and poor clinical outcomes. We sought to determine if empiric therapeutic anticoagulation (AC) affected survival in COVID-19 patients compared to standard prophylactic AC. Retrospective analysis of 402 COVID-19 patients hospitalized between March 15 and May 31, 2020 was performed. Clinical outcomes were compared between 152 patients treated with therapeutic AC to 250 patients on prophylactic AC. An elastic net logistic regression was designed to first identify the important variables affecting mortality. These variables were then included as covariates to AC in standard multivariate logistic regression models studying the effect of AC on death. Nonparametric survival analysis was conducted, and Kaplan Meier curves were constructed. Increased mortality was associated with therapeutic AC [OR 3.42 (2.06, 5.67)]. The log-rank test was statistically significant at p = 0.001 showing higher mortality for patients treated with therapeutic AC compared to prophylactic AC. Subset analysis of critically ill and intubated patients had similar survival curves regardless of AC dose. The log-rank test was not significant even with Prentice modification. For non-ICU patients, the log rank test favoring prophylactic AC disappeared when the analysis was stratified by D-dimer level less or greater than 3 μg/mL. Approximately 9% of patients receiving therapeutic AC experienced clinically significant bleeding or thrombocytopenia, versus 3% in those receiving prophylactic AC. In our cohort, therapeutic anticoagulation provided no mortality benefit over thromboprophylaxis, independent of co-morbidities or disease severity. More adverse events were observed with therapeutic AC. • Anticoagulation strategies for patients with COVID-19 infections remain unclear. • Outcomes of prophylactic versus therapeutic anticoagulation were compared. • In our cohort, therapeutic anticoagulation provided no mortality benefit over thromboprophylaxis. • Therapeutic anticoagulation was associated with increased adverse events. [ABSTRACT FROM AUTHOR]

Abstract: Curry leaf (Murraya koenegii) is a common flavouring agent in Indian foods. This study characterised the flavonol profile of curry leaf extracted with different solvents and the relative antioxidant capacity of these extracts by quantifying phenolic constituents. Flavonols were extracted using ethanol, methanol, or acetone prior to identification and quantification using liquid chromatography coupled to atmospheric pressure chemical ionisation (APCI) mass spectrometry in tandem mode (LC-MS–MS) with negative ion detection. Major curry leaf flavonols included myricetin-3-galactoside, quercetin-O-pentohexoside, quercetin-3-diglucoside, quercetin-3-O-rutinoside, quercetin-3-glucoside, quercetin-3-acetylhexoside, quercetin-O-xylo-pentoside, kaempferol-O-glucoside, and kaempferol-aglucoside. Lag-time and TBARS tests demonstrated that curry leaf phenolics prevent cupric-ion induced oxidation of LDL. The best extraction yield was obtained with 80% ethanol. Acetone extracts provided better antioxidant activity expressed as increased lag-time formation, than did ethanol or methanol extracts. Curry leaf is a rich source of flavonols that have biological activity in vitro and further studies are warranted in regards to the potential health benefits and identification of the novel flavonols whose identities remain unknown. [Copyright &y& Elsevier]