Objectives To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha ( PIK3CA ) mutations would be found in patients with more common disorders ...including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). Study design We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Children's Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Children's Hospital. Results Most individuals from Boston Children's Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼80% of cases. Seventy-four percent of patients with LM from Seattle Children's Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. Conclusions Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In natural environments, fluid density and viscosity can be affected by spatial and temporal variations of solute concentration, for example, due to saltwater intrusion in coastal aquifers, leachate ...infiltration from waste disposal sites, and upconing of saline water from deep aquifers. Potentially unstable situations may arise in which a dense fluid overlies a less dense fluid. This situation can produce instabilities manifested by dense plume fingers moving vertically downwards counterbalanced by vertical upward flow of the less dense fluid. The resulting free convection increases solute transport rates over large distances and times relative to constant-density flow. Unstable brine flow is further complicated if the porous medium is variably saturated. The results from a laboratory experiment of variably saturated variable-density flow and solute transport from Simmons et al. (2002) are used as the physical basis to define a new mathematical benchmark. This benchmark aims at realistically reproducing the experimental fingering patterns. Random hydraulic conductivity fields were used in the simulations as a numerical perturbation method to realistically mimic the observed dense plume fingering. The HydroGeoSphere code coupled with PEST are used to calibrate the parameter set that defines the benchmark. A grid convergence analysis is performed to obtain the adequate spatial and temporal discretizations. The new mathematical benchmark is useful for model comparison and testing of variably saturated variable-density flow in porous media. Simmons CT, Pierini ML, Hutson JL (2002) Laboratory investigation of variable-density flow and solute transport in unsaturated–saturated porous media. Transp Porous Media. 47(2): 215–244, 10.1023/A:1015568724369.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To evaluate the technical success and clinical outcomes of thoracic duct embolization (TDE) using transabdominal antegrade and transcervical retrograde accesses to treat patients with chyle leak.
...This study was a retrospective, nonblinded, single-institution chart review of all patients aged 18 years or older over a 6-year time frame who underwent lymphangiography with attempted TDE for iatrogenic or spontaneous chyle leaks using transabdominal antegrade and/or transcervical retrograde accesses.
Ninety-nine patients underwent 113 procedures. Eighty-five patients underwent 1 procedure, and 14 patients required 2 procedures. The technical success rate of TDE was 68% (72/106) with transabdominal antegrade access and 44% (15/34) with transcervical retrograde access. The overall technical success rate of TDE, including both the access methods, was 77% (87/113). The most common reasons for transabdominal access failure were small caliber of the cisterna chyli and thoracic duct (TD) occlusion. Five patients were lost to follow-up. Overall clinical success, defined as resolution of the chyle leak, was achieved in 83% (78/94) of the patients. There were 6 Society of Interventional Radiology (SIR) level 1 adverse events (AEs), 5 SIR level 2 AEs, and 2 SIR level 3 AEs. Nontarget embolization occurred in 2 patients.
Although transcervical retrograde TDE is a challenging procedure, with a lower technical success rate than transabdominal antegrade access, retrograde access improved the technical and clinical success rates of the treatment of chyle leaks in cases of thoracic duct occlusion, small cisterna chyli, and leaks located in the abdomen.
, one of the top carcinogens, is associated with most cases of gastric cancer-related deaths worldwide. Over the past two decades, the rising rates of antibiotic resistance in the bacterium have ...reduced the efficacy of conventional antibiotic-based treatments. This underscores the urgency for continued research and novel treatment approaches. Establishing a worldwide accepted physician guideline for antibiotic prescription is crucial to combat antibiotic resistance and improve
infection management. Therefore, it is important to address the challenges that complicate the establishment of a universally accepted treatment protocol to prescribe an antibiotic regimen to eradicate
. The answers to the questions of why conventional standard triple therapy remains a first-line treatment choice despite its low efficacy, and how different factors affect therapy choice, are needed to identify these challenges. Hence, this review addresses concerns related to
treatment choice, role of antibiotic resistance and patient compliance in treatment outcomes, first-line vs. second-line therapy options, and methods for enhancing existing treatment methods. We also present a chart to aid antibiotic treatment prescription, which may support physician guidelines in this aspect. Eradication of
and patient adherence is paramount in overcoming antibiotic resistance in the bacterium, and our chart summarizes key considerations and suggests novel approaches to achieve this goal.
Background
Thoracic duct injury is a rare complication of head and neck surgery. Thoracic duct embolization (TDE) has been proposed to manage postoperative chyle leaks.
Methods
Twelve patients who ...underwent lymphangiography for a chyle leak after head and neck surgery (M:F = 5:7, mean 55 years) were retrospectively reviewed. Lymphangiographic findings, technical success, complications, and clinical outcomes were analyzed.
Results
Chyle leak was identified and TDE attempted in 11 of 12 patients. Three patients required repeat TDE. Technical success of TDE was 86% (12/14). Clinical success for patients with technically successful TDE was 90% (9/10). Median time until drain removal was 2.1 days in nine patients with clinical success. Two major complications were encountered, chylothorax after initial TDE, requiring additional TDE and in one case surgical TD ligation.
Conclusions
TDE is a safe treatment for chyle leaks after head and neck surgery with high technical and clinical success rates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nanobiosensors based on silicon nanowire field effect transistors offer advantages of low cost, label-free detection, and potential for massive parallelization. As a result, these sensors have often ...been suggested as an attractive option for applications in point-of-care (POC) medical diagnostics. Unfortunately, a number of performance issues, such as gate leakage and current instability due to fluid contact, have prevented widespread adoption of the technology for routine use. High-k dielectrics, such as hafnium oxide (HfO2), have the known ability to address these challenges by passivating the exposed surfaces against destabilizing concerns of ion transport. With these fundamental stability issues addressed, a promising target for POC diagnostics and SiNWFETs has been small oligonucleotides, more specifically, microRNA (miRNA). MicroRNAs are small RNA oligonucleotides which bind to mRNAs, causing translational repression of proteins, gene silencing, and expressions are typically altered in several forms of cancer. In this paper, we describe a process for fabricating stable HfO2 dielectric-based silicon nanowires for biosensing applications. Here we demonstrate sensing of single-stranded DNA analogues to their microRNA cousins using miR-10b and miR-21 as templates, both known to be upregulated in breast cancer. We characterize the effect of surface functionalization on device performance using the miR-10b DNA analogue as the target sequence and different molecular weight poly-l-lysine as the functionalization layer. By optimizing the surface functionalization and fabrication protocol, we were able to achieve <100 fM detection levels of the miR-10b DNA analogue, with a theoretical limit of detection of 1 fM. Moreover, the noncomplementary DNA target strand, based on miR-21, showed very little response, indicating a highly sensitive and highly selective biosensing platform.
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IJS, KILJ, NUK, PNG, UL, UM
To describe technical details, success rate, and advantages of direct puncture of the thoracic duct (TD) under direct ultrasound (US) guidance at venous insertion in the left neck.
All patients who ...underwent attempted thoracic duct embolization (TDE) via US-guided retrograde TD access in the left neck were retrospectively reviewed. Indications for lymphangiography were iatrogenic chyle leak, pulmonary lymphangiectasia, and plastic bronchitis. Ten patients with mean age 41.4 years (range, 21 d to 72 y) underwent US-guided TD access via the left neck. Technical details, procedural times, and clinical outcomes were evaluated. TD access time was defined as time from start of procedure to successful access of TD, and total procedural time was defined from start of procedure until TDE.
All attempts at TD access via the neck were successful. Technical and clinical success of TDE was 60%. There were no complications. Mean TD access time was 17 minutes (range, 2-47 min), and mean total procedure time was 49 minutes (range, 25-69 min). Mean follow-up time was 5.4 months (range, 3-10 months).
TDE via US-guided access in the left neck is technically feasible and safe with a potential decrease in procedure time and elimination of oil-based contrast material.
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