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Satish T Pote,1,2 Mahesh S Sonawane,1 Praveen Rahi,1 Sunil R Shah,3 Yogesh S Shouche,1 Milind S Patole,1 Madhuri R Thakar,2 Rohit Sharma1 1National Centre for Microbial Resource (NCMR), National Centre for Cell Science, NCCS Complex, S.P. Pune University, Pune 411 007, Maharashtra, India; 2National AIDS Research Institute, Pune 411026, Maharashtra, India; 3Bharati Vidyapeeth Deemed University Medical College, Bharati Vidyapeeth, Pune 411043, Maharashtra, IndiaCorrespondence: Rohit SharmaNational Centre for Microbial Resource (NCMR), National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411 007, Maharashtra, IndiaTel +91-20-25329035Fax +91-20-25692259Email rohit@nccs.res.inIntroduction: Species of genus Candida are part of the common microbiota of humans; however, some of the Candida species are known opportunistic pathogens. Formation of biofilms, resistance to antifungal drugs, and increase in asymptomatic infections demands more studies on isolation, identification and characterization of Candida from clinical samples.Methods: The present manuscript deals with assessment of authentic yeast identification by three methods viz., DNA sequencing of 28S rRNA gene, protein profiles using MALDI-TOF MS, and colony coloration on chromogenic media. Antifungal susceptibility and in vitro cell invasion assays were performed to further characterize these isolates.Results: Comparison of three methods showed that DNA sequence analysis correctly identified more than 99.4% of the isolates up to species level as compared to 89% by MALDI-TOF MS. In this study, we isolated a total of 176 yeasts from clinical samples and preliminary morphological characters indicated that these yeast isolates belong to the genus Candida. The species distribution of isolates was as follows: 75 isolates of Candida albicans (42.61%), 50 of C. tropicalis (28.40%), 22 of C. glabrata (12.5%), 14 of C. parapsilosis (7.95%) and 4 of Clavispora lusitaniae (2.27%). Other species like Cyberlindnera fabianii, Issatchenkia orientalis, Kluyveromyces marxianus, Kodamaea ohmeri, Lodderomyces sp., and Trichosporon asahii were less than 2%. Antifungal susceptibility assay performed with 157 isolates showed that most of the isolates were resistant to the four azoles viz., clotrimazole, fluconazole, itraconazole, and ketoconazole, and the frequency of resistance was more in non-albicans Candida isolates. The susceptibility to azole drugs ranged from 7% to 48%, while 75% of the tested yeasts were susceptible to nystatin. Moreover, 88 isolates were also tested for their capacity to invade human cells using HeLa cells. In vitro invasion assay showed that most of the C. albicans isolates showed epithelial cell invasion as compared to isolates belonging to C. glabrata, C. parapsilosis and C. tropicalis.Discussion: The identification of yeasts of clinical origin by sequencing of 28S rRNA gene performed better than MALDI-TOF MS. The present study reiterates the world scenario wherein there is a shift from Candida strains to emerging opportunistic pathogens which were earlier regarded as environmental strains. The present study enlightens the current understanding of identification methods for clinical yeast isolates, increased antifungal drug resistance, epithelial cell invasion as a virulence factor, and diversity of yeasts in Indian clinical samples.Keywords: yeast clinical isolates, chromogenic media, DNA sequencing, MALDI-TOF MS, antifungal drug resistance

James G Shamul,1,2,* Sagar R Shah,1–3,* Jayoung Kim,1,2 Paula Schiapparelli,3 Carla A Vazquez-Ramos,3 Ben J Lee,1,2 Kisha K Patel,1,2 Alyssa Shin,1,2 Alfredo Quinones-Hinojosa,3 Jordan J Green1,2,4–6 1Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA; 2Translational Tissue Engineering Center and Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA; 3Department of Neurosurgery, Mayo Clinic, Jacksonville, FL 32224, USA; 4Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD 21231, USA; 5Department of Oncology, The Sidney Kimmel Comprehensive Cancer, and The Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA; 6Department of Ophthalmology, Department of Materials Science and Engineering, and Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA*These authors contributed equally to this workCorrespondence: Alfredo Quinones-Hinojosa; Jordan J Green Email Quinones-Hinojosa.Alfredo@mayo.edu; green@jhu.eduBackground: Nanomedicine can improve traditional therapies by enhancing the controlled release of drugs at targeted tissues in the body. However, there still exists disease- and therapy-specific barriers that limit the efficacy of such treatments. A major challenge in developing effective therapies for one of the most aggressive brain tumors, glioblastoma (GBM), is affecting brain cancer cells while avoiding damage to the surrounding healthy brain parenchyma. Here, we developed poly(ethylene glycol) (PEG)-poly(beta-amino ester) (PBAE) (PEG-PBAE)-based micelles encapsulating verteporfin (VP) to increase tumor-specific targeting.Methods: Biodegradable, pH-sensitive micelles of different shapes were synthesized via nanoprecipitation using two different triblock PEG-PBAE-PEG copolymers varying in their relative hydrophobicity. The anti-tumor efficacy of verteporfin loaded in these anisotropic and spherical micelles was evaluated in vitro using patient-derived primary GBM cells.Results: For anisotropic micelles, uptake efficiency was ∼100% in GBM cells (GBM1A and JHGBM612) while only 46% in normal human astrocytes (NHA) at 15.6 nM VP (p ≤ 0.0001). Cell killing of GBM1A and JHGBM612 vs NHA was 52% and 77% vs 29%, respectively, at 24 hrs post-treatment of 125 nM VP-encapsulated in anisotropic micelles (p ≤ 0.0001), demonstrating the tumor cell-specific selectivity of VP. Moreover, anisotropic micelles showed an approximately fivefold longer half-life in blood circulation than the analogous spherical micelles in a GBM xenograft model in mice. In this model, micelle accumulation to tumors was significantly greater for anisotropic micelle-treated mice compared to spherical micelle-treated mice at both 8 hrs (∼1.8-fold greater, p ≤ 0.001) and 24 hrs (∼2.1-fold greater, p ≤ 0.0001).Conclusion: Overall, this work highlights the promise of a biodegradable anisotropic micelle system to overcome multiple drug delivery challenges and enhance efficacy and safety for the treatment of brain cancer.Keywords: GBM, verteporfin, micelle, anisotropic, poly(ethylene glycol), PEG, poly(beta-amino ester), PBAE

Purpose: The purpose of this study was to evaluate the incidence of acute renal failure (ARF) in patients with mild to moderate renal dysfunction, receiving renally adjusted zoledronic acid (ZA) and compare it to patients with normal baseline renal function, receiving standard-dose ZA.Methods: This was a retrospective study of patients receiving ZA for the treatment of bone metastasis due to cancer. Patients were divided into two groups: (1) normal group with baseline creatinine clearance (CrCl) of greater than 60 mL/min and standard ZA dose; (2) impaired group with baseline CrCl of 30-60 mL/min and renally adjusted ZA dose. Primary endpoint of ARF was defined as an increase in serum creatinine (SCr) of 0.5 mg/dL or 1.0 mg/dL from a baseline SCr of <1.4 mg/dL or ≥ 1.4 mg/dL, respectively.Results: In total, 1,472 evaluable doses of ZA were given to 220 patients. Of these, 184 patients were in the normal group and 36 patients in the impaired group. There were 38 patients (20.7%) who developed ARF in the normal group versus 7 patients (19.4%) in the impaired group. There was no difference in the mean time to the incidence of ARF at 6.1 months in both groups. Incidence of ARF based on CrCl (≥ 25% decline in CrCl) was similar between groups (39.1% vs. 41.7%; p = 0.78).Conclusion: The incidence of ARF is similar between patients in the normal group and impaired group when the ZA dose is renally adjusted. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive surgery (MIS) has been described for the repair of congenital diaphragmatic hernias (CDH) in neonates, infants, and children. This report evaluates patient selection, operative technique, and clinical outcomes for MIS repair of CDHs from a single center's experience.Methods: All cases of CDH at a tertiary care pediatric hospital with an initial attempt at MIS repair from January 2001 to December 2007 were reviewed.Results: A total of 22 children underwent an initial attempt at MIS repair of their CDH (5 Morgagni and 17 Bochdalek hernias). The children ranged in age from 1 day to 6 years (mean, 13.9 +/- 23 months) and weighed 2.2 to 21 kg (mean, 7.4 +/- 5.50 kg) at the time of the operation. All five Morgagni hernias were managed successfully with laparoscopic primary repair. Six of the Bochdalek hernias were found in infants and children (age range, 6-71 months). All these were managed successfully with primary repair by an MIS approach (2 by laparoscopy and 4 by thoracoscopy). The remaining 11 Bochdalek hernias were found in neonates (age range, 1 day to 8 weeks). Four of the Bochdalek hernias were right-sided. Nine of the Bochdalek hernias in neonates were repaired thoracoscopically. One neonate required conversion to laparotomy, and another underwent conversion to thoracotomy. Four of the neonates with Bochdalek hernias required a prosthetic patch. Two of the neonates also had significant associated congenital cardiac defects. Overall, there were two recurrences involving one 3-day-old who underwent a primary thoracoscopic repair and another 3-day-old who underwent a thoracoscopic patch repair. The follow-up period ranged from 5 months to 5 years.Conclusions: Morgagni hernias can be managed successfully by laparoscopy, whereas thoracoscopy is preferred for neonatal Bochdalek hernias. Either approach can be successful for infants and children with Bochdalek hernias. Additionally, patients with congenital cardiac defects and those requiring prosthetic patches can undergo a MIS CDH repair with a successful outcome. [ABSTRACT FROM AUTHOR]

Background: Seasonal allergic rhinitis (SAR) is an allergen-induced inflammatory reaction that occurs during periods of high pollen count. Current treatments for SAR include allergen avoidance, systemic antihistamines, and steroidal and nonsteroidal intranasal sprays. Olopatadine is a selective antihistamine and an inhibitor of proinflammatory mediators from human mast cells. An intranasal formulation of olopatadine has been developed for the treatment of SAR. Objective: The aim of this study was to compare the efficacy and tolerability of olopatadine hydrochloride nasal spray 0.6% (OLO) relative to azelastine hydrochloride nasal spray 0.1% (AZE) and an inactive vehicle in the treatment of SAR. Methods: This Phase III, multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group study was conducted at 21 centers across the United States. Eligible patients were aged >/=12 years and had a history of SAR and verified allergy to a prevalent local allergen. After a run-in period during which inactive vehicle was administered, patients were randomly assigned to OLO, AZE (active control), or inactive vehicle (identical to OLO; placebo control), 2 sprays in each nostril BID for 16 days. The timing of enrollment was correlated with the start of the allergy season at each site. Symptoms were recorded twice daily in an electronic diary. Efficacy assessments included changes in mean daily reflective total nasal symptom scores (TNSS). Tolerability was evaluated based on adverse events (AEs) and nasal, physical, and cardiovascular parameters. Results: A total of 544 patients were randomized. The mean age was 36 years (range, 12-77 years); men and boys represented 32.2% of the population; and the patients were predominantly white (75.4%). The mean reductions from baseline in reflective TNSS were 26.8%, 29.9%, and 18.4% with OLO, AZE, and inactive vehicle, respectively (P = 0.003 OLO vs inactive vehicle; 95% CI, -2.5% to 8.7% OLO vs AZE [non-inferiority]). The most commonly reported treatment-related AE in the OLO and AZE groups was bitter taste (12.2% [22/180] and 19.7% [37/188], respectively). The prevalence and intensity of bitter taste were significantly lower with OLO than with AZE (P = 0.05 and P = 0.005, respectively). In the group that received inactive vehicle, the prevalence of bitter taste was 1.7% (3/176). The prevalences of other treatment-related AEs, including epistaxis and nasal discomfort, were /=12 years with SAR, the percentage reduction from baseline in TNSS was significantly greater with OLO (2 sprays in each nostril BID) compared with vehicle and not significantly different from that with AZE. OLO and AZE were similarly well tolerated, with the exception of prevalence and intensity of bitter taste, which were significantly lower with OLO. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intranasal corticosteroids are effective for the treatment of allergic rhinitis. Sensory attributes associated with these sprays may affect patient preference and adherence to treatment regimens. OBJECTIVES: These 2 studies compared patients' perceptions of and preferences for specific sensory attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS). METHODS: In 2 multicenter, randomized, single-blind (patient), single-dose, 2-period, 1-day crossover studies, adults with mild to moderate allergic rhinitis received single doses of BANS (one 32-pg spray per nostril in both studies, 64-microg total dose) and FPNS (two 50-microg sprays per nostril in study 1, 200-pg total dose; one 50-microg spray per nostril in study 2, 100-microg total dose). Study 1 compared the once-daily recommended starting doses of BANS and FPNS, and study 2 compared BANS with half the once-daily recommended dose of FPNS to balance the number of actuations for delivery of study drug. Patients completed the 23-item Sensory Perceptions Questionnaire and indicated their product preference (if any). RESULTS: A total of 110 women and 71 men in study 1 and 136 women and 54 men in study 2 were randomized to treatment. None had previously used BANS or FPNS. In both studies, fewer patients perceived scent or taste (both P < 0.001 in both studies), forceful spray (P < 0.001 in both studies), and a wet feel in both the nose and throat (study 1, P < 0.004; study 2, P < 0.002) with BANS than with FPNS. In addition, more patients in both studies liked the spray force (study 1, P < 0.01; study 2, P < 0.001) and moisture content in the throat (study 1, P < 0.001; study 2, P < 0.006) of BANS and indicated a greater overall satisfaction with the sensory features of BANS than those of FPNS (study 1, P < 0.001; study 2, P < 0.015). In analyses that included all responding patients, 54.4% of patients in study 1 preferred BANS and 37.8% preferred FPNS (P < 0.022). In study 2, 47.4% preferred BANS and 41.1% preferred FPNS (not significant). Of the 92.2% of patients in study 1 and 88.4% in study 2 who specified a product preference, 59.0% preferred BANS and 41.0% preferred FPNS in study 1 (P = 0.021), and 53.6% preferred BANS and 46.4% preferred FPNS in study 2 (not significant). CONCLUSIONS: On the basis of perceptions of specific sensory attributes reported after 1 administration in these 2 studies, BANS was rated as more pleasing and preferred over the recommended QD starting dose of FPNS, and was also rated as more pleasing than half the QD recommended starting dose of FPNS. [ABSTRACT FROM AUTHOR]

Purpose: To determine the strength of clinical evidence for individual drugs as a cause of thrombocytopenia.Data Sources: All English-language reports on drug-induced thrombocytopenia.Study Selection: Articles describing thrombocytopenia caused by heparin were excluded from review. Of the 581 articles reviewed, 20 were excluded because they contained no patient case reports. The remaining 561 articles reported on 774 patients.Data Extraction: Two of the authors used a priori criteria to independently review each patient case report. Two hundred fifty-nine patient case reports were excluded from further review because of lack of evaluable data, platelet count of 100000 cells/microL or more, use of cytotoxic or nontherapeutic agents, occurrence of drug-induced systemic disease, or occurrence of disease in children. For the remaining 515 patient case reports, a level of evidence for the drug as the cause of thrombocytopenia was assigned. Data on bleeding complications and clinical course were recorded.Data Synthesis: The evidence supported a definite or probable causal role for the drug in 247 patient case reports (48%). Among the 98 drugs described in these reports, quinidine was mentioned in 38 case reports, gold in 11, and trimethoprim-sulfamethoxazole in 10. Of the 247 patients described in the case reports, 23 (9%) had major bleeding and 2 (0.8%) died of bleeding.Conclusions: Many reports of drug-induced thrombocytopenia do not provide evidence supporting a definite or probable causal relation between the disease and the drug. Future patient case reports should incorporate standard criteria to clearly establish the etiologic role of the drug. [ABSTRACT FROM AUTHOR]

Solid-cystic papillary tumor (SCPT) of the pancreas is a rare neoplasm mainly affecting young women. The clinical presentation is usually nonspecific. A common problem encountered is misdiagnosis of the tumor on imaging. We report two patients with SCPT of the pancreas diagnosed incorrectly on preoperative imaging. Any cystic lesion of the pancreas with solid elements on radiology should raise the suspicion of this diagnosis. Considered to be a tumor of low malignant potential, surgical resection is associated with excellent prognosis. Surgery may be conservative in localized tumors and aggressive if nonlocalized. [ABSTRACT FROM AUTHOR]

Purpose: To reduce the risks associated with splenectomy, there has been a trend toward splenic preservation when performing distal pancreatectomy. Although laparoscopy has gained almost universal acceptance, it is still not utilized often for pancreatic surgery in children. In fact, review of the literature shows only a few case series of splenic-preserving laparoscopic distal pancreatectomy, and even less reported experience in the pediatric population. To our knowledge, there has been only one other report of laparoscopic spleen-preserving distal pancreatectomy in the setting of trauma in a child.Methods: A 13-year-old boy suffered a handlebar injury to the abdomen secondary to a dirt bike accident. He did not report loss of consciousness but complained of abdominal pain. CT scan revealed a grade II splenic laceration with a transected distal pancreas. He was hemodynamically stable with a large contusion in the left upper quadrant. Laboratory evaluation showed that his hematocrit was stable but was significant for elevated amylase and lipase. During his hospitalization, he developed significant abdominal distension and his amylase and lipase continued to rise. He was taken to the operating room for definitive management of his pancreatic injury 72 hours after his initial injury.Results: In the operating room, a central line was placed so that he could receive total parenteral nutrition postoperatively. The video demonstrates the performance of a laparoscopic spleen-preserving distal pancreatectomy. There was a fair amount of old blood seen in the left upper quadrant and behind the pancreas. There was no evidence of active bleeding. The operation was performed without complication and with preservation of the splenic vessels.Conclusions: The postoperative course was very smooth with the child resuming diet by postoperative day (POD) 4. He was sent home on POD 7. This video demonstrates that in the proper trauma patient, a minimally invasive approach to a spleen-preserving distal pancreatectomy can still be performed. [ABSTRACT FROM AUTHOR]

The article discusses the role of family caregivers in coordinating and continuing care of patients with mental illness. It mentions that caregivers are facing unlimited physical, social, psychological, and financial stressors which caused them mild anxiety and depression while caring for mentally ill people. It notes the importance of assisting caregivers to empower and recognize their strengths and limitations to provide them the courage to face challenges relative to their work.

Purpose: Caustic ingestion is a common cause for acquired esophageal strictures in children. Thoracoscopic esophagectomy can be very useful in this setting, particularly for short segments of disease [1-4]. Thus far, the use of endoscopy to guide resection margins has not been described.Methods: A 6-year-old boy developed a tight, short esophageal stricture from a lye ingestion injury at the age of 4 years. He had a gastrostomy tube placed at the time for supplemental feedings and subsequently failed attempts at antegrade and retrograde esophageal dilatation. This video demonstrates an endoscopically guided (endoscopes simultaneously passed retrograde via the gastrostomy and antegrade through the oropharynx) thoracoscopic esophagectomy and primary anastomosis management of the stricture.Methods: In the left lateral decubitus position, four 5-mm ports were placed in the right chest in the fifth intercostal space, anterior-axillary line; sixth intercostal space, midaxillary line; fourth intercostal space, midaxillary line; and seventh intercostal space, posterior axillary line. A 5-mm 30 degrees Storz telescope and 4.9-mm and 9.6-mm Olympus endoscopes were used. The area of esophageal stricture was identified using the endoscopes and thoracoscopically dissected circumferentially. The vagus nerves were identified and circumferentially freed from the strictured esophageal segment. Primary resection and anastomosis was performed using intracorporeal sutures and then tested for leak using the endoscope via the gastrostomy site.Results: Esophagram on postoperative day (POD) 7 revealed no leak and a widely patent anastomosis. He was discharged home on a soft diet on POD 8 and continues to feed orally over 1 year following his operation.Conclusion: As demonstrated by our video, endoscopy is a useful adjunct in the performance of a thoracoscopic esophagectomy for short esophageal stricture. It is particularly helpful because it provides direct visualization of the compromised lumen and allows for a more precise resection. [ABSTRACT FROM AUTHOR]

Despite extensive characterization of mammalian Pol II transcription, the DNA sequence determinants of transcription initiation at a third of human promoters and most enhancers remain poorly understood. Hence, we trained and interpreted a neural network called ProCapNet that accurately models base-resolution initiation profiles from PRO-cap experiments using local DNA sequence. ProCapNet learns sequence motifs with distinct effects on initiation rates and TSS positioning and uncovers context-specific cryptic initiator elements intertwined within other TF motifs. ProCapNet annotates predictive motifs in nearly all actively transcribed regulatory elements across multiple cell-lines, revealing a shared cis-regulatory logic across promoters and enhancers mediated by a highly epistatic sequence syntax of cooperative and competitive motif interactions. ProCapNet models of RAMPAGE profiles measuring steady-state RNA abundance at TSSs distill initiation signals on par with models trained directly on PRO-cap profiles. ProCapNet learns a largely cell-type-agnostic cis-regulatory code of initiation complementing sequence drivers of cell-type-specific chromatin state critical for accurate prediction of cell-type-specific transcription initiation.

Objective: Access to assistive products (APs) is essential to maximising function, participation, and inclusion of persons with disabilities. Challenges to AP access in low- and middle-income countries include stigma, costs, supply, and rehabilitation capacity gaps. This study aimed to examine AT access in the context of a low-resource setting in rural South India. Objectives were to examine rehabilitation professionals' perceptions of AP needs, barriers and facilitators of AP provision, and AT knowledge., Methods: A descriptive study design with a 2-part online survey methodology was utilized. This study was conducted in April-September 2020 at a non-governmental organization (NGO) serving children and adults with disabilities in 3 districts of rural South India. Purposive sampling of NGO's multidisciplinary rehabilitation professionals (N=62) was used. The survey was developed based on WHO's Assistive Products List (APL). Barriers and facilitators were classified according to the principles of AT access. Analyses revealed acceptability, affordability, and availability as the top three barrier themes across disciplines, including poor acceptance by clients/families due to stigma, high AP costs, and a long waitlist for government-provided devices. Acceptability, affordability, and accessibility were the top three facilitator themes, including community awareness, availability of AP funding, client/family education, and AT service provision training., Impact: Our study identified key enabling strategies for AT access, aimed at reducing reported barriers. Enabling AP provision was determined to be multi-factorial, aimed at users/ families, service providers, organizations, communities, and policymakers. Local stakeholder groups are crucial to understanding challenges and opportunities to AP provision within a low-resource context.

Background: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally., Method: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts., Results: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC., Conclusions: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To conduct a systematic review and meta-analysis to compare the efficacy of conservative treatment versus surgical debridement versus debridement followed by vascularized tissue coverage to provide evidence-based guidance on the management of osteoradionecrosis of the anterior and central skull base., Data Sources: PubMed, Embase, and Cochrane Library., Review Methods: Systematic review and data sources including PubMed, Embase, and Cochrane Library were accessed using PRISMA guidelines. Meta-analysis was performed on treatment type and resolution of osteoradionecrosis., Results: A total of 13 articles met the inclusion criteria. Patients were categorized into conservative medical treatment versus surgical treatment. Conservative treatment included patients undergoing hyperbaric oxygen therapy, antibiotics, pentoxifylline-tocopherol-clodronate, or a combination of the three. Eight out of 197 patients treated with conservative therapy had resolution of symptoms (4.1%) while 135 of 188 patients treated with surgical intervention had resolution of symptoms (71.8%). Of these, 104 patients (91.2%) in the vascularized tissue group experienced resolution of symptoms., Conclusion: Surgery was superior to medical treatment alone in the resolution of skull base osteoradionecrosis. Vascularized surgical treatment fared significantly better when compared with both surgical debridement only and/or medical treatment. Our findings suggest that surgical treatment should be considered earlier in patients with skull base osteoradionecrosis to prevent severe or fatal sequelae., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Complications are associated with postoperative mortality and readmission. However, the timing of complications relative to discharge and the extent to which timing is associated with failure to rescue (FTR) and readmission after pediatric surgery is unknown. Our goal was to describe the timing of complications relative to discharge after inpatient pediatric surgery and determine the association between complication timing, FTR, and unplanned readmission., Materials and Methods: National cohort study of patients within the NSQIP-Pediatric database who underwent inpatient surgery (2012-2019). Complications were categorized based on when they occurred relative to discharge: only pre-discharge, only post-discharge, both. The association between perioperative outcomes and the timing of postoperative complications was evaluated with multivariable hierarchical regression., Results: Among 378,551 patients, 30,213 (8.0%) had at least one postoperative complication. Relative to patients with pre-discharge complications, post-discharge complications were associated with significantly decreased odds of FTR (odds ratio 0.21, 95% confidence interval [0.15-0.28]) and significantly increased odds of readmission (odds ratio 19.37 [17.93-20.92]). Odds of FTR and readmission in patients with complications occurring both before and after discharge were similar to that of patients with only post-discharge complications., Conclusions: FTR and readmission are associated with complications occurring at different times relative to discharge (FTR primarily pre-discharge; readmission primarily post-discharge). This suggests a 'one size fits all' approach to surgical quality improvement may not be effective and different approaches are needed to address different quality indicators., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: COVID-19 has led to delays in providing healthcare in both emergency and non-emergency settings, especially in surgical subspecialties which rely heavily on referrals and in-person visits. Without an established telehealth infrastructure, many otorhinolaryngological departments experienced decreases in consultations. Telemedicine has attempted to bridge the gap between pre- and post-pandemic periods by creating a safe avenue of communication between otorhinolaryngologists and patients. This review hopes to address the accuracy of telemedicine in patient diagnosis and management., Methods: Searches were conducted since study conception until June 30, 2022, on multiple databases including PubMed, SCOPUS, and CINAHL for this systematic review and meta-analysis. Diagnostic accuracy, management accuracy, kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were meta-analyzed by comparing virtual visits to in-person visits (gold standard)., Results: Nineteen studies were included in this review. A total of 1518 patients were included across all studies. When comparing virtual visits against in-person visits, accurate diagnosis was made in 86.2% [82.1,89.9, I 2  = 73.5%, P  < 0.0001] of patients and management accuracy was 91.5% [86.1,95.7, I 2  = 81.8%, P  < 0.0001] when treating patients. Kappa value determining interrater reliability was 0.8 [0.7,0.9, I 2  = 81.8%, P  < 0.0001]., Conclusion: Our data suggest that diagnostic and management concordance is above 80% when comparing diagnosis and management strategies in patients who underwent both telehealth and in-person visits with an otorhinolaryngologist. In uncomplicated patients, telehealth might be a reliable source for diagnosis and management however, in-person consultation is likely still required for pathologies in which physical exam, imaging or procedural elements represent a vital component of the work-up., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder resulting from mutations in the NF1 gene. Patients harboring these mutations are predisposed to a spectrum of peripheral nerve sheath tumors (PNSTs) originating from Schwann cells, of which malignant peripheral nerve sheath tumors (MPNSTs) are the deadliest, with limited treatment options. Therefore, an unmet need still exists for more effective therapies directed at these aggressive malignancies. Cold atmospheric plasma (CAP) is a reactive oxygen species (ROS) and reactive nitrogen species (RNS) generating ionized gas that has been proposed to be a potential therapeutic modality for cancer. In this study, we sought to determine the effects of CAP on NF1-associated PNSTs. Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors.

Background: Severe aortic stenosis (AS) can present insidiously, with the end stages resulting in significant valvular-induced cardiomyopathy and can lead to cardiogenic shock (CS). Such cases result in a myriad of complex manifestations and are often associated with a poor prognosis. These patients require emergent cardiac evaluation and valvular intervention. Unfortunately, the immediate nature of the CS provides little time for a detailed valvular evaluation. Possible management involves use of mechanical circulatory support (MCS) prior to urgent transcatheter aortic valve replacement (TAVR)., Case Summary: The patient was a 70-year-old female who developed refractory CS, and acute decompensated heart failure was complicated by AV block secondary to severe AS. Due to progressively worsening haemodynamics, the need for MCS for cardiovascular support and eventual valve replacement resulted in the decision to pursue TandemHeart® (TH; LivaNova Inc, Pittsburgh, PA, USA). We discuss the novel implementation of the TH as a means of bridging to TAVR., Discussion: TandemHeart system provides the benefits of improving haemodynamic support in CS while allowing unencumbered access to the stenotic valve for balloon aortic valvuloplasty (BAV) or TAVR. In our evaluation, we discuss the utilization and benefits associated with TH to TAVR in allowing for cardiac rest, replacement of the valve, and recovery of left ventricular function., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background Amblyopia, often linked to high astigmatism in children, presents challenges in understanding the contributing factors and visual outcomes. Methods A total of 132 samples were included in this prospective pre- and post-interventional study using the purposive sampling technique. Descriptive statistics were applied for age, gender, uncorrected visual acuity, corrected visual acuity, type, and magnitude of astigmatism. A repeated measure ANOVA was used, and a paired t-test was also done for groups with corrected visual acuity in meridional amblyopia at two follow-ups spaced six months apart. Logistic regression was used to identify the association between astigmatism types and patients' recovery from amblyopia after intervention. Results The age of participants was 4-11 years with meridional amblyopia. Initial findings showed a mean uncorrected visual acuity of 0.73 LogMAR in the right eye (RE) and 0.71 LogMAR in the left eye (LE), improving significantly to 0.35 LogMAR post-intervention in both eyes. The calculated mean difference between the first correction and the first follow-up was 0.12 and 0.13 LogMAR, while it was 0.20 and 0.21 LogMAR in the RE and LE, respectively, at the second follow-up. Spherical refractive errors averaged +0.93 DS, with mean cylindrical refraction indicating predominant with-the-rule corneal astigmatism (-3.46 DS). We observed a significant improvement in visual acuity (p-value < 0.001) and an increase in the magnitude of cylindrical prescription (p-value < 0.001). However, astigmatism types are not associated with response to therapy. Conclusion The study concluded that early detection of meridional amblyopia and early intervention with spectacles significantly improve visual acuity., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Hospital Ethical Committee of Avicenna Medical Complex, Islamabad, Pakistan, issued approval AVC-HI-PUB-ERC/March 23/24. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

Background: Patient navigation interventions (PNIs) can provide personalized support and promote appropriate coordination or continuation of health and social care services. Online PNIs have demonstrated excellent potential for improving patient knowledge, transition readiness, self-efficacy, and use of services. However, the characteristics (ie, intervention type, mode of delivery, duration, frequency, outcomes and outcome measures, underlying theories or mechanisms of change of the intervention, and impact) of existing online PNIs to support the health and social needs of individuals with illness remain unclear., Objective: This scoping review of the existing literature aims to identify the characteristics of existing online PNIs reported in the literature., Methods: A scoping review based on the guidelines outlined in the Joanna Briggs Institute framework was conducted. A search for peer-reviewed literature published between 1989 and 2022 on online PNIs was conducted using MEDLINE, CINAHL, Embase, PsycInfo, and Cochrane Library databases. Two independent reviewers conducted 2 levels of screening. Data abstraction was conducted to outline key study characteristics (eg, study design, population, and intervention characteristics). The data were analyzed using descriptive statistics and qualitative content analysis., Results: A total of 100 studies met the inclusion criteria. Our findings indicate that a variety of study designs are used to describe and evaluate online PNIs, with literature being published between 2003 and 2022 in Western countries. Of these studies, 39 (39%) studies were randomized controlled trials. In addition, we noticed an increase in reported online PNIs since 2019. The majority of studies involved White females with a diagnosis of cancer and a lack of participants aged 70 years or older was observed. Most online PNIs provide support through navigation, self-management and lifestyle changes, counseling, coaching, education, or a combination of support. Variation was noted in terms of mode of delivery, duration, and frequency. Only a small number of studies described theoretical frameworks or change mechanisms to guide intervention., Conclusions: To our knowledge, this is the first review to comprehensively synthesize the existing literature on online PNIs, by focusing on the characteristics of interventions and studies in this area. Inconsistency in reporting the country of publication, population characteristics, duration and frequency of interventions, and a lack of the use of underlying theories and working mechanisms to inform intervention development, provide guidance for the reporting of future online PNIs., (©Meghan Marsh, Syeda Rafia Shah, Sarah E P Munce, Laure Perrier, Tin-Suet Joan Lee, Tracey J F Colella, Kristina Marie Kokorelias. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 19.08.2024.)

Aortic stenosis is a common and significant valve condition requiring bioprosthetic heart valves with transcatheter aortic valve replacement (TAVR) being strongly recommended for high-risk patients or patients over 75 years. This meta-analysis aimed to pool existing data on postprocedural clinical as well as echocardiographic outcomes comparing valve-in-valve (ViV)-TAVR to redo-surgical aortic valve replacement to assess the short-term and medium-term outcomes for both treatment methods. A systematic literature search on Cochrane Central, Scopus, and Medline (PubMed interface) electronic databases from inception to August 2023. We used odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Twenty-four studies (25,216 patients) were pooled with a mean follow-up of 16.4 months. The analysis revealed that ViV-TAVR group showed a significant reduction in 30-day mortality (OR 0.50, 95% confidence interval [CI] 0.43 to 0.58, p <0.00001), new-onset atrial fibrillation (OR 0.34, 95% CI 0.17 to 0.67, p = 0.002), major bleeding event (OR 0.28, 95% CI 0.17 to 0.45, p <0.00001) and lower rate of device success (OR 0.25, 95% CI 0.12 to 0.53, p = 0.0003). There were no significant differences between either group when assessing 1-year mortality, stroke, myocardial infarction, postoperative left ventricular ejection fraction, and effective orifice area. ViV-TAVR cohort showed a significantly increased incidence of paravalvular leaks, aortic regurgitation, and increased mean aortic valve gradient. ViV-TAVR is a viable short-term option for older patients with high co-morbidities and operative risks, reducing perioperative complications and improving 30-day mortality with no significant cardiovascular adverse events. However, both treatment methods present similar results on short-term to medium-term complications assessment., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Left atrial appendage occlusion (LAAO) with WATCHMAN currently requires preprocedural imaging, general anesthesia, and inpatient overnight admission. We sought to facilitate simplification of LAAO., Aims: We describe and compare SOLO-CLOSE (single-operator LAA occlusion utilizing conscious sedation TEE, lack of outpatient pre-imaging, and same-day expedited discharge) with the conventional approach (CA)., Methods: A single-center retrospective analysis of 163 patients undergoing LAAO between January 2017 and April 2022 was conducted. The SOLO-CLOSE protocol was enacted on December 1, 2020. Before this date, we utilized the CA. The primary efficacy endpoint was defined as successful LAAO with ≤5 mm peri-device leak at time of closure. The primary safety endpoint was the composite incidence of all-cause deaths, any cerebrovascular accident (CVA), device embolization, pericardial effusion, or major postprocedure bleeding within 7 days of the index procedure. Procedure times, 7-day readmission rates, and cost analytics were collected as well., Results: Baseline characteristics were similar in both cohorts. Congestive heart failure (37.5% vs. 11.1%) and malignancy (28.8% vs. 12.5%) were higher in SOLO-CLOSE. Median CHA 2 D 2 SVASc score was 5 in both cohorts. The primary efficacy endpoint was met 100% in both cohorts. Primary safety endpoint was similar between cohorts (p = 0.078). Mean procedure time was 30 min shorter in SOLO-CLOSE (p < 0.01). Seven-day readmissions for SOLO-CLOSE was zero. After SOLO-CLOSE implementation, there was a 188% increase in positive contribution margin per case., Conclusions: The SOLO-CLOSE methodology offers similar efficacy and safety when compared to the CA, while improving clinical efficiency, reducing procedural times, and increasing economic benefit., (© 2024 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Spinal anesthesia is the most preferred method for cesarean section (C-section). This meta-analysis was performed to determine the effect of low and high intrathecal doses of pethidine on the maternal outcomes after C-section., Methods: A systematic search of PubMed, Scopus, Cochrane Library, and Google Scholar was performed. Random-effects meta-analysis was performed to derive odds ratios (ORs) from dichotomous data., Results: Seventeen randomized controlled trials with 1304 C-section patients were included. Patients who had received intrathecal pethidine experienced decreased shivering and intensity of shivering (OR 0.13; P <0.001) and (OR 0.21; P <0.001), respectively. Moreover, vomiting (OR 2.47; P =0.002) and pruritus (OR 5.92; P <0.001) were significantly higher in the pethidine group. There was no statistically significant difference in the incidence of nausea (OR 2.55; P =0.06) and hypotension (OR 0.91; P =0.67)., Conclusions: Intrathecal pethidine can effectively decrease shivering, although it increases the risk of vomiting and pruritus. No significant difference was found both in the maternal hypotension and nausea., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Traditional Li-ion intercalation chemistry into graphite anodes exclusively utilizes the cointercalation-free or cointercalation mechanism. The latter mechanism is based on ternary graphite intercalation compounds (t-GICs), where glyme solvents were explored and proved to deliver unsatisfactory cyclability in LIBs. Herein, we report a novel intercalation mechanism, that is, in situ synthesis of t-GIC in the tetrahydrofuran (THF) electrolyte via a spontaneous, controllable reaction between binary-GIC (b-GIC) and free THF molecules during initial graphite lithiation. The spontaneous transformation from b-GIC to t-GIC, which is different from conventional cointercalation chemistry, is characterized and quantified via operando synchrotron X-ray and electrochemical analyses. The resulting t-GIC chemistry obviates the necessity for complete Li-ion desolvation, facilitating rapid kinetics and synchronous charge/discharge of graphite particles, even under high current densities. Consequently, the graphite anode demonstrates unprecedented fast charging (1 min), dendrite-free low-temperature performance, and ultralong lifetimes exceeding 10 000 cycles. Full cells coupled with a layered cathode display remarkable cycling stability upon a 15 min charging and excellent rate capability even at -40 °C. Furthermore, our chemical strategies are shown to extend beyond Li-ion batteries to encompass Na-ion and K-ion batteries, underscoring their broad applicability. Our work contributes to the advancement of graphite intercalation chemistry and presents a low-cost, adaptable approach for achieving fast-charging and low-temperature batteries.

Purpose of Review: Neurofibromatosis type 1 (NF-1) is a cancer predisposition syndrome caused by mutations in the NF1 tumor suppressor gene that encodes the neurofibromin protein, which functions as a negative regulator of Ras signaling. We review the past, current, and future state of therapeutic strategies for tumors associated with NF-1., Recent Findings: Therapeutic efforts for NF-1-associated tumors have centered around inhibiting Ras output, leading to the clinical success of downstream MEK inhibition for plexiform neurofibromas and low-grade gliomas. However, MEK inhibition and similar molecular monotherapy approaches that block Ras signaling do not work for all patients and show limited efficacy for more aggressive cancers such as malignant peripheral nerve sheath tumors and high-grade gliomas, motivating novel treatment approaches. We highlight the current therapeutic landscape for NF-1-associated tumors, broadly categorizing treatment into past strategies for serial Ras pathway blockade, current approaches targeting parallel oncogenic and tumor suppressor pathways, and future avenues of investigation leveraging biologic and technical innovations in immunotherapy, pharmacology, and gene delivery., (© 2024. The Author(s).)