Shear-Wave Elastography for the Diagnosis of Pediatric Hashimoto's Thyroiditis: A Systematic Review and Meta-Analysis.

Shear-wave elastography (SWE) has emerged as a novel ultrasonographic technique for the diagnosis of pediatric Hashimoto's Thyroiditis (HT). This systematic review and meta-analysis aim to summarize current evidence to determine the diagnostic value of SWE for HT. MEDLINE, a comprehensive search yielded five studies inclusive of 392 subjects. A meta-analysis comparing SWE values (kPa) between children with HT and healthy controls yielded a Cohen's d-value of 1.34 (CI 1.02-1.65), suggesting statistically significant differences in SWE values. Such evidence indicates that SWE may serve as a valuable tool in diagnosing HT in the pediatric population.

Surgical Outcomes Following Robotic Single-Site Versus Multiport Hysterectomy for Treatment of Endometrial Cancer: A Systematic Review and Meta-Analysis.

Robotic single-site hysterectomy (RSSH) has emerged as a novel surgical approach for the treatment of endometrial cancer and atypical endometrial hyperplasia (AEH). Current research regarding the benefits of RSSH compared to robotic multiport hysterectomy (RMPH) for these indications has been inconclusive. Our team sought to compare surgical outcomes between these two approaches of robotic hysterectomy via systematic review and meta-analysis to ensure optimal surgical practices. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Checklist guided our review. MEDLINE, Clinicaltrials.gov, and Cochrane Library were searched, yielding 59 results. Articles were filtered by title and abstract and then reviewed in full for inclusion and exclusion criteria. Inclusion criteria required that (1) studies compared outcomes for RSSH and RMPH, (2) hysterectomy was indicated for endometrial cancer or hyperplasia with atypia, and (3) studies were available in English. Excluded studies (1) compared single-site and multiport laparoscopic approaches, (2) compared robotic approaches to laparoscopic or abdominal (open) techniques, and (3) employed hysterectomy for benign conditions. Publication bias was assessed using the Egger Regression Correlation analysis. Four studies complied with the selection criteria, comprising 138 patients in the RSSH group and 259 in the RMPH group. Similar outcomes were noted across all measures, including conversion rate (relative risk [RR] = 1.84 and confidence interval [CI] = 0.99-3.43), blood loss (Cohen's d = 1.05 and Z = 18.62), operating time (Cohen's d = 0.29 and Z = 4.38), and length of hospital stay (Cohen's d = 1.06 and Z = 3.86). Publication bias was deemed minimal as indicated by Egger regression values of less than 0.05. These findings suggest that either a surgical approach or AEH with the proper standard of care can provide patients with endometrial cancer.

Spider Bite-Induced Facial Nerve Palsy.

Spider bites, while rarely confirmed beyond a doubt, should always be in the differential for any severe symptoms or infection out of proportion to presentation with the suspected presence of appropriate vectors. While most arthropod bites will only result in mild localized irritation, the potential to cause severe cutaneous and systemic effects should not be overlooked. We present one such case, in which a presumed brown recluse (Loxosceles reclusa) bite on the neck resulted in severe illness with systemic manifestations. The patient presented to the emergency room minimally responsive with left-sided facial nerve palsy and septic shock. While the admitting physician initially prioritized stabilizing the patient, he noted the left-sided cervical cellulitis. Thorough history taking revealed that the patient had been worsening since being bitten by a spider three days prior to admission. After a month-long hospital stay and multidisciplinary treatment, the patient was transferred to a larger center with facial paralysis still present.

IL-33-mediated Eosinophilia Protects against Acute Lung Injury.

Pneumonia-induced lung injury and acute respiratory distress syndrome can develop because of an inappropriate inflammatory response to acute infections, leading to a compromised alveolar barrier. Recent work suggests that hospitalized patients with allergies/asthma are less likely to die of pulmonary infections and that there is a correlation between survival from acute respiratory distress syndrome and higher eosinophil counts; thus, we hypothesized that eosinophils associated with a type 2 immune response may protect against pneumonia-induced acute lung injury. To test this hypothesis, mice were treated with the type 2-initiating cytokine IL-33 intratracheally 3 days before induction of pneumonia with airway administration of a lethal dose of Staphylococcus aureus. Interestingly, IL-33 pretreatment promoted survival by inhibiting acute lung injury: amount of BAL fluid proinflammatory cytokines and pulmonary edema were both reduced, with an associated increase in oxygen saturation. Pulmonary neutrophilia was also reduced, whereas eosinophilia was strongly increased. This eosinophilia was key to protection; eosinophil reduction eliminated both IL-33-mediated protection against mortality and inhibition of neutrophilia and pulmonary edema. Together, these data reveal a novel role for eosinophils in protection against lung injury and suggest that modulation of pulmonary type 2 immunity may represent a novel therapeutic strategy.

Protection against Staphylococcus aureus bacteremia-induced mortality depends on ILC2s and eosinophils.

The dysregulated, unbalanced immune response of sepsis results in a mortality exceeding 20%, yet recent findings by our group indicate that patients with allergic, type 2-mediated immune diseases are protected from developing sepsis. We evaluated CD4+ Th cell polarization among patients with Staphylococcus aureus bacteremia and confirmed that survivors had a higher percentage of circulating Th2 cells but lower frequencies of Th17 cells and neutrophils early in the course of infection. To establish the mechanism of this protection, we used a mouse model of lethal S. aureus bacteremia and found that intratracheal pretreatment with the type 2-initiating cytokine IL-33 activated pulmonary type 2 innate lymphoid cells (ILC2s) and promoted eosinophilia. In addition, stimulation of type 2 immunity before lethal infection suppressed the pulmonary neutrophilic response to S. aureus. Mice lacking functional ILC2s did not respond to IL-33 and were not protected from lethal bacteremia, but treatment of these mice with the type 2 cytokines IL-5 and IL-13 rescued them from death. Depletion of eosinophils abrogated IL-33-mediated protection, indicating that eosinophilia is also necessary for the survival benefit. Thus, we have identified a potentially novel mechanism by which type 2 immunity can balance dysregulated septic inflammatory responses, thereby clarifying the protective benefit of type 2 immune diseases on sepsis mortality.

A Microscale Planar Linear Ion Trap Mass Spectrometer.

The planar linear ion trap (PLIT) is a version of the two-dimensional linear quadrupole ion trap constructed using two facing dielectric substrates on which electrodes are lithographically patterned. In this article, we present a PLIT that was successfully miniaturized from a radius of 2.5 mm to a microscale radius of 800 µm (a scaling factor of 3.125). The mathematics concerning scaling an ion trap mass spectrometer are demonstrated-including the tradeoff between RF power and pseudopotential well depth. The time average power for the microscale PLIT is, at best, ~ 1/100 that of the PLIT but at a cost of potential well depth of ~ 1/10 the original. Experimental data using toluene/deuterated toluene and isobutylbenze to verify trap performance demonstrated resolutions around 1.5 Da at a pressure of 5.4 × 10-3 Torr. The microscale PLIT was shown to retain resolutions between 2.3 and 2.7 Da at pressures up to 42 × 10-3 Torr while consuming a factor of 3.38 less time average power than the unscaled PLIT. Graphical Abstract.

Double resonance ejection using novel radiofrequency phase tracking circuitry in a miniaturized planar linear ion trap mass spectrometer.

RATIONALE: Ion trap mass spectrometers are attractive due to their inherent sensitivity and specificity. Miniaturization increases trap portability for in situ mass analysis by relaxing vacuum and voltage requirements but decreases the trapping volume. To overcome signal/resolution loss from miniaturization, double resonance ejection using phase tracking circuitry was investigated. METHODS: Phase tracking circuitry was developed to induce double resonance ejection in a planar linear ion trap using the ß 2/3 hexapole resonance line. RESULTS: Double resonance was observed using phase tracking circuitry. Resolution of 0.5 m/z units and improved signal-to-noise ratio (SNR) compared with AC resonant ejection were achieved. CONCLUSIONS: The phase tracking circuitry proved effective despite deviations from a true phase locked condition. Double resonance ejection is a means to increase signal intensity in a miniaturized planar ion trap.

Experimental Observation of the Effects of Translational and Rotational Electrode Misalignment on a Planar Linear Ion Trap Mass Spectrometer.

The performance of miniaturized ion trap mass analyzers is limited, in part, by the accuracy with which electrodes can be fabricated and positioned relative to each other. Alignment of plates in a two-plate planar LIT is ideal to characterize misalignment effects, as it represents the simplest possible case, having only six degrees of freedom (DOF) (three translational and three rotational). High-precision motorized actuators were used to vary the alignment between the two ion trap plates in five DOFs-x, y, z, pitch, and yaw. A comparison between the experiment and previous simulations shows reasonable agreement. Pitch, or the degree to which the plates are parallel along the axial direction, has the largest and sharpest impact to resolving power, with resolving power dropping noticeably with pitch misalignment of a fraction of a degree. Lateral displacement (x) and yaw (rotation of one plate, but plates remain parallel) both have a strong impact on ion ejection efficiency, but little effect on resolving power. The effects of plate spacing (y-displacement) on both resolving power and ion ejection efficiency are attributable to higher-order terms in the trapping field. Varying the DC (axial) trapping potential can elucidate the effects where more misalignments in more than one DOF affect performance. Implications of these results for miniaturized ion traps are discussed. Graphical Abstract ᅟ.

Improved Miniaturized Linear Ion Trap Mass Spectrometer Using Lithographically Patterned Plates and Tapered Ejection Slit.

We present a new two-plate linear ion trap mass spectrometer that overcomes both performance-based and miniaturization-related issues with prior designs. Borosilicate glass substrates are patterned with aluminum electrodes on one side and wire-bonded to printed circuit boards. Ions are trapped in the space between two such plates. Tapered ejection slits in each glass plate eliminate issues with charge build-up within the ejection slit and with blocking of ions that are ejected at off-nominal angles. The tapered slit allows miniaturization of the trap features (electrode size, slit width) needed for further reduction of trap size while allowing the use of substrates that are still thick enough to provide ruggedness during handling, assembly, and in-field applications. Plate spacing was optimized during operation using a motorized translation stage. A scan rate of 2300 Th/s with a sample mixture of toluene and deuterated toluene (D8) and xylenes (a mixture of o-, m-, p-) showed narrowest peak widths of 0.33 Th (FWHM). Graphical Abstract ᅟ.

Optimal fabrication methods for miniature coplanar ion traps.

RATIONALE: Ion trap mass spectrometers are beneficial due to their intrinsic sensitivity and specificity. Therefore, a portable version for in situ analysis of various compounds is very attractive. Miniaturization of ion traps is paramount for the portability of such mass spectrometers. METHODS: We developed an optimized design for a planar linear ion trap mass spectrometer, consisting of two trapping plates with photolithographically patterned electrodes. Each plate is constructed using a machined glass substrate and standard microfabrication procedures. The plates are attached to a patterned circuit board via wire bonds then positioned approximately 5 mm apart. RESULTS: Trapped ions are detected by ejecting them through tapered slits, which alleviate charge buildup. Mass analysis can be performed through either boundary or resonant ion ejection. Better than unit mass resolution is demonstrated with resonant ejection. CONCLUSIONS: The optimized planar linear ion trap provides good resolution and the potential for further miniaturization. This was accomplished by vigorously testing variables associated with ion trap design including electrical connections, substrate materials, and electrode designs.