Dual-energy CT in acute cholecystitis- features predicting culture-positive bile and outcome.

PURPOSE: Low mono-energetic CT has been shown to improve visualization of acute abdominal inflammatory processes. We aimed to determine its utility in patients with acute cholecystitis and potential added value in clinical decision making. METHODS: Sixty-seven consecutive patients with radiological signs of cholecystitis on contrast-enhanced dual-layer CT imaging were retrospectively identified over a four-year period (2/17-8/21). A ranked Likert scale was created for imaging findings present in acute cholecystitis, including gallbladder mucosal integrity and enhancement and pericholecystic liver parenchymal enhancement. These rankings were correlated with laboratory data, followed by sensitivity, specificity, and odds-ratios calculations. RESULTS: Mucosal integrity and pericholecystic liver enhancement were better seen on low-energetic images by unanimous consensus. Presence of pericholecystic liver enhancement and poorer mucosal wall integrity correlated with positive bile cultures (sensitivity: 93.8 % and 96.9 %, specificity: 37.5 and 50.0 %; odds-ratio: 9.0[1.1-68.1 95 %CI] and 31.0 [2.7-350.7 95 %CI], p = 0.017 and p ≤ 0.001) in patients undergoing cholecystostomy (n = 40/67). Moreover, binary regression modeling showed that the strongest predictor variable for bile culture positivity was the score for pericholecystic liver enhancement (Exp(B) = 0.6, P = 0.022). By contrast, other laboratory markers and other imaging findings (such as GB wall thickness) showed lower sensitivities (76-82 %), specificities (16-21 %) and odds ratios (0.2-4.4) for the prediction of infected bile. CONCLUSIONS: Pericholecystic liver enhancement and gallbladder wall integrity are better visualized on low-DECT images. These findings also potentially predict bile culture positivity in patients with cholecystitis, which may influence clinical management including the need for intervention.

Analyzing the effect of doping concentration in split-well resonant-phonon terahertz quantum cascade lasers.

The effect of doping concentration on the temperature performance of the novel split-well resonant-phonon (SWRP) terahertz quantum-cascade laser (THz QCL) scheme supporting a clean 4-level system design was analyzed using non-equilibrium Green's functions (NEGF) calculations. Experimental research showed that increasing the doping concentration in these designs led to better results compared to the split-well direct-phonon (SWDP) design, which has a larger overlap between its active laser states and the doping profile. However, further improvement in the temperature performance was expected, which led us to assume there was an increased gain and line broadening when increasing the doping concentration despite the reduced overlap between the doped region and the active laser states. Through simulations based on NEGF calculations we were able to study the contribution of the different scattering mechanisms on the performance of these devices. We concluded that the main mechanism affecting the lasers' temperature performance is electron-electron (e-e) scattering, which largely contributes to gain and line broadening. Interestingly, this scattering mechanism is independent of the doping location, making efforts to reduce overlap between the doped region and the active laser states less effective. Optimization of the e-e scattering thus could be reached only by fine tuning of the doping density in the devices. By uncovering the subtle relationship between doping density and e-e scattering strength, our study not only provides a comprehensive understanding of the underlying physics but also offers a strategic pathway for overcoming current limitations. This work is significant not only for its implications on specific devices but also for its potential to drive advancements in the entire THz QCL field, demonstrating the crucial role of e-e scattering in limiting temperature performance and providing essential knowledge for pushing THz QCLs to new temperature heights.

Optimal CT windowing on low-monoenergetic images using a simplex algorithm-based approach for abdominal inflammatory processes.

BACKGROUND: OBJECTIVES: To determine optimal window settings for conspicuity of abdominal inflammatory processes on 50 keV low-monoenergetic images derived from dual-energy spectral CT (DECT). METHODS: A retrospective study of 30 patients with clinically proven pancreatitis (15/30) or pyelonephritis (15/30) with inflammatory lesions visible on DECT scans were selected to serve as reference populations. 50 keV low-monoenergetic images in the portal venous phase were iteratively evaluated by 6 abdominal radiologists in twenty-one different windows (7-350HU center; 120-580HU width), selected using a simplex optimization algorithm. Each reader graded the conspicuity of the parenchymal hypodense lesions and image background quality. Three-dimensional contour maps expressing the relationship between overall reader grade and window center and width were constructed and used to find the ideal window for inflammatory pancreatic and renal processes and the image background quality. Finally, 15 appendicitis cases were reviewed on optimal pancreas and kidney windows and the manufacturer recommended conventional abdominal window settings for conventional imaging. RESULTS: Convergence to optimal windowing was achieved based upon a total of 3,780 reads (21 window settings × 6 readers × 15 cases for pancreas and kidney). Highest conspicuity grade (>4.5 ± 0.0) for pancreas inflammatory lesions was seen at 116HU/430HU, whereas hypodense pyelonephritis had highest conspicuity at 290HU/570HU. This rendered an ideal "compromise" window (>4 ± 0.2) of 150HU/450HU which differed substantially from conventional manufacturer recommended settings of 50HU/380HU (2.1 ± 1.0, p = 0.00001). Appendix mucosal enhancement was best visualized at manufacturer settings. CONCLUSIONS: Optimal visualization of inflammatory processes in abdominal organs on 50 keV low-monoenergetic images may require tailored refinement of window settings.

Negative and positive interpretations of emotionally neutral situations modulate the desire to eat personally craved foods.

Emotions play an important role in modulating food craving. Previous studies demonstrated that exposure to negative or positive stimuli can subsequently influence the desire to eat. However, in many daily situations, individuals self-generate their emotions, for example, by interpreting emotionally-neutral situations as positive or negative. So far, no studies have examined if and how positive and negative interpretations of emotionally-neutral situations modulate food craving. In this study, 65 healthy participants were asked to interpret emotionally-neutral images negatively or positively or observe the images naturally. Subsequently, participants rated their state negative/positive affect and their desire to eat their personally craved foods. The results demonstrate a lower desire to eat craved foods after negative interpretations and a higher desire to eat after positive interpretations, compared to an observe-naturally condition. Additionally, the impact of emotional interpretations on the desire to eat was mediated by participants' state negative/positive affect. These findings suggest that self-generated emotion as a result of negative/positive interpretations plays a significant role in modulating food craving. The results highlight the potential of modifying affective interpretations for the treatment of disorders that are characterized by both dysregulated food craving and emotion.

Split-well resonant-phonon terahertz quantum cascade laser.

We present a highly diagonal "split-well resonant-phonon" (SWRP) active region design for GaAs/Al0.3Ga0.7As terahertz quantum cascade lasers (THz-QCLs). Negative differential resistance is observed at room temperature, which indicates the suppression of thermally activated leakage channels. The overlap between the doped region and the active level states is reduced relative to that of the split-well direct-phonon (SWDP) design. The energy gap between the lower laser level (LLL) and the injector is kept at 36 meV, enabling a fast depopulation of the LLL. Within this work, we investigated the temperature performance and potential of this structure.

SLP76 Mutation Associated with Combined Immunodeficiency and EBV-Related Lymphoma.

Increased susceptibility to develop severe forms of Epstein-Barr virus (EBV) infection in early age is a significant hallmark of an underlying primary immunodeficiency (PID). Here, we present immunologic and genetic evaluations of a 3-year-old child who was born to first-cousins parents and presented with recurrent infections, failure to thrive, and severe EBV-related infection and proliferation. A diagnosis of diffuse large B cell lymphoma was made and the immunological workup was suggestive of T cell immunodeficiency. Unfortunately, the patient succumbed to EBV-related lymphoma. Whole-exome sequencing revealed a novel homozygous mutation, c.991del.C; p. Q331Sfs*6 in the SLP76 gene. The SLP76 protein, a TCR signaling molecule, was recently linked to a human disease of the immune system. In order to examine the effect of this new SLP76 mutation on T cell signaling, a SLP76-deficient Jurkat-derived T cell line was transduced either with wild-type (WT), or with the specific SLP76 mutant, or with a mock vector. Downstream TCR signaling events, including ERK1/2 phosphorylation, CD69 expression, and Ca2 + mobilization, were reduced in cells harboring the reported mutation, linking this novel mutation to the expected immunological outcome. SLP76 deficiency should be added to the growing list of monogenetic diseases that predispose affected individuals to acquire severe and uncontrolled EBV infections and to develop substantial complications. This case further links mutations in the SLP76 gene to a significant human immunodeficiency and extends its clinical phenotype.

Manual Pressure Points Technique for Massive Hemorrhage Control-A Prospective Human Volunteer Study.

BACKGROUND: While commonly thought to be effective for management of limb and junctional hemorrhage, the manual pressure points technique was excluded from leading prehospital guidelines over a decade ago following the publication of a single human-volunteers study presenting unfavorable results. This work aimed to re-assess the efficacy and feasibility of the femoral and supraclavicular pressure points technique for temporary hemorrhage control distal to the pressure point. METHODS: A prospective, non-randomized, human volunteer, controlled environment study. In the study 35 healthy male combat medics (age 21.1 ± 1.3 years) received brief training after which they were requested to apply pressure in the femoral and supraclavicular points in attempts to stop regional blood flow, measured distally by Doppler ultrasound. Success rates in achieving flow cessation in under 2 minutes, time required for achievement of flow cessation, and cumulative flow cessation duration within a 3-minute follow-up after initial success were measured. RESULTS: For the supraclavicular point, success rates were 97.1% with a mean time to success of 12.5 (±20.9) seconds, lasting for 76.2% (±23.7) of the follow-up time. For the femoral point, success rates were 100% with a mean time to success of 5.5 (±4.3) seconds, lasting for 98.7% (±3.8) of the follow-up time. CONCLUSIONS: Manual pressure on the femoral and supraclavicular points is an applicable and efficient method for temporary hemorrhage control distal to the pressure point. As such, with additional study, this method may be considered for re-introduction to prehospital care guidelines and training programs.

Feasibility and Accuracy of a Novel Hands-Free Robotic System for Percutaneous Needle Insertion and Steering.

PURPOSE: To assess the performance and accuracy of CT-guided needle insertion for clinical biopsies using a novel, hands-free robotic system that balances accuracy with the duration of the procedure and radiation dose. MATERIALS AND METHODS: A prospective, multi-center study was conducted on 60 clinically indicated biopsies of abdominal lesions at two centers (Center 1, n=26; Center 2, n=34). CT datasets were obtained for planning and controlled placement of 17g and 18g needles using a patient-mounted, CT-guided robotic system with 5 degrees of freedom. Planning included target selection, skin entry point, and predetermined checkpoints where additional imaging was performed to permit stepwise correction of the needle trajectory. Success rate, needle tip-to-target distance, number of checkpoints used, number of trajectory corrections, procedure duration, and effective radiation dose were recorded and compared between centers. RESULTS: In 55 of 60 procedures (91.7%), the robot positioned the trocar needle successfully on target. In the remaining 5 patients, the procedure was manually performed by the operator due to technical failure (n=3) or patient-related factors (n=2). The average lesion size was 2.8 ± 1.7cm with a lesion depth from the skin of 8.7 ± 2.6cm, and there was no difference between centers. The overall accuracy (needle tip-to-target distance) was 1.71 ± 1.49 (range 0.05-7.20mm), with an accuracy of 2.06 ± 1.45 mm at Center 1 and 1.45 ± 1.52 mm at Center 2 (p=0.1358). Center 1 used significantly more checkpoints (4.96 ± 1.08) and performed target adjustments in 20 of 24 (83%) cases compared to Center 2 (2.77 ± 0.6 checkpoints and target adjustments in 13 of 31 cases, 42%) (p=0.0024). Accordingly, the steering duration from skin entry to the target varied between Centers 1 and 2; 13.1min ± 4.25min vs. 5.7min ± 2.7min, respectively (p <0.001). The average DLP for the entire procedure was 1147 ± 820 mGycm, with a slightly lower average at Center 2 (1031 ± 724 mGycm) compared to Center 1 (1297 ± 925 mGycm) (p=0.236). CONCLUSION: Accurate needle-targeting within an error of 2mm can be achieved in patients using a CT-guided robotic system. The variation in the number of checkpoints did not affect system accuracy but was related to shorter steering times and may contribute to a lower radiation dose. Accurate needle insertion using a hands-free CT-guided robotic system may facilitate difficult needle placement and enhance the performance of less-experienced interventionalists.

Lessons Learned From Five Years of Newborn Screening for Severe Combined Immunodeficiency in Israel.

BACKGROUND: Implementation of newborn screening (NBS) programs for severe combined immunodeficiency (SCID) have advanced the diagnosis and management of affected infants and undoubtedly improved their outcomes. Reporting long-term follow-up of such programs is of great importance. OBJECTIVE: We report a 5-year summary of the NBS program for SCID in Israel. METHODS: Immunologic and genetic assessments, clinical analyses, and outcome data from all infants who screened positive were evaluated and summarized. RESULTS: A total of 937,953 Guthrie cards were screened for SCID. A second Guthrie card was requested on 1,169 occasions (0.12%), which resulted in 142 referrals (0.015%) for further validation tests. Flow cytometry immune-phenotyping, T cell receptor excision circle measurement in peripheral blood, and expression of TCRVß repertoire for the validation of positive cases revealed a specificity and sensitivity of 93.7% and 75.9%, respectively, in detecting true cases of SCID. Altogether, 32 SCID and 110 non-SCID newborns were diagnosed, making the incidence of SCID in Israel as high as 1:29,000 births. The most common genetic defects in this group were associated with mutations in DNA cross-link repair protein 1C and IL-7 receptor α (IL-7Rα) genes. No infant with SCID was missed during the study time. Twenty-two SCID patients underwent hematopoietic stem cell transplantation, which resulted in a 91% survival rate. CONCLUSIONS: Newborn screening for SCID should ultimately be applied globally, specifically to areas with high rates of consanguineous marriages. Accumulating data from follow-up studies on NBS for SCID will improve diagnosis and treatment and enrich our understanding of immune development in health and disease.

Ultrasonographic features can predict outcome of conservative management of acute appendicitis in children.

PURPOSE: To determine whether specific ultrasonographic features can predict failure of conservative treatment of acute appendicitis. METHODS: A 2-year retrospective study was conducted on children admitted with acute appendicitis. Those with uncomplicated appendicitis diagnosed solely by ultrasound, and treated conservatively, were followed 18-24 m to assess treatment outcome. Management was considered successful if recurrent acute appendicitis was not observed during follow-up. Appendix diameter, wall thickness, presence of mucosal ulceration, hyperechogenic fat, free fluid, and lymph nodes were evaluated as potential discriminatory ultrasonographic predictors. T-tests, chi-square, sensitivity, specificity, and odds ratios were calculated. RESULTS: Out of 556 consecutive patients that were admitted with acute appendicitis, 180 (32%) managed conservatively. One hundred eleven (62%) imaged by US only. Ninety-two out of 111 (83%) were followed 18-24 m to assess treatment outcome, and 19/111 (17%) were lost to follow-up. Conservative management was successful in 72/92 (78.2%), with treatment failure in 20/92 (21.8%) (5/92 (5.4%) with recurrent acute appendicitis and 15/92 (16.3%) underwent appendectomy). Of the ultrasonographic features studied, mucosal ulceration demonstrated statistically significant predictive value. Fifteen out of 20 (75%) treatment failures had mucosal ulceration, compared to 21/72 (29.2%) of the patients with successful treatment (p < 0.001). This yielded a positive odds ratio of 7.3 (2.3-22.6, 95% CI), 70.8% (58.9-80.9, 95% CI) specificity, and 75% (50.9-91.3, 95% CI) sensitivity. Positive predictive value was 41.6% (31.5-52.5, 95% CI) while intact mucosa had negative predictive value of 91% (82.4-95.6, 95% CI) for conservative management success. CONCLUSION: The presence or absence of appendiceal mucosal ulceration at ultrasound can predict conservative management outcome in the setting of acute appendicitis, potentially improving pediatric patient selection for conservative management.

Clinical evaluation of a robotic system for precise CT-guided percutaneous procedures.

PURPOSE: To assess accuracy and compare protocols for CT-guided needle insertion for clinical biopsies using a hands-free robotic system, balancing system accuracy with duration of procedure and radiation dose. METHODS: Thirty-two percutaneous abdominal and pelvic biopsies were performed and analyzed at two centers (Center 1 n = 11; Center 2 n = 21) as part of an ongoing prospective, multi-center study. CT datasets were obtained for planning and controlled placement of 17 g needles using a patient-mounted, CT-guided robotic system. Planning included target selection, skin entry point, and predetermined checkpoints. Additional CT imaging was performed at checkpoints to confirm needle location and permit stepwise correction of the trajectory. Center 1 used a more conservative approach with multiple checkpoints, whereas Center 2 used fewer checkpoints. Scanning and needle advancement were performed under respiratory gating. Accuracy, radiation dose, and steering duration were compared. RESULTS: Overall accuracy was 1.6 ± 1.5 mm (1.9 ± 1.2 mm Center 1; 1.5 ± 1.6 mm Center 2; p = 0.55). Mean distance to target was 86.2 ± 27.1 mm (p = 0.18 between centers). Center 1 used 4.6 ± 0.8 checkpoints, whereas Center 2 used 1.8 ± 0.6 checkpoints (p < 0.001). Effective radiation doses were lower for Center 1 than for Center 2 (22.2 ± 12.6 mSv vs. 11.7 ± 4.3 mSv; p = 0.002). Likewise, steering duration (from planning to target) was significantly reduced in relation to the number of checkpoints from 43.8 ± 15.9 min for Center 1 to 30.5 ± 10.2 min for Center 2 (p = 0.008). CONCLUSIONS: Accurate needle targeting with < 2 mm error can be achieved in patients when using a CT-guided robotic system. Judicious selection of the number of checkpoints may substantially reduce procedure time and radiation dose without sacrificing accuracy.

Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects.

The T cell receptor (TCR) signaling pathway is an ensemble of numerous proteins that are crucial for an adequate immune response. Disruption of any protein involved in this pathway leads to severe immunodeficiency and unfavorable clinical outcomes. Here, we describe an infant with severe immunodeficiency who was found to have novel biallelic mutations in SLP76. SLP76 is a key protein involved in TCR signaling and in other hematopoietic pathways. Previous studies of this protein were performed using Jurkat-derived human leukemic T cell lines and SLP76-deficient mice. Our current study links this gene, for the first time, to a human immunodeficiency characterized by early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation. Hereby, we characterized aspects of the patient's immune phenotype, modeled them with an SLP76-deficient Jurkat-derived T cell line, and rescued some consequences using ectopic expression of wild-type SLP76. Understanding human diseases due to SLP76 deficiency is helpful in explaining the mixed T cell and neutrophil defects, providing a guide for exploring human SLP76 biology.

[RISK FACTORS ASSOCIATED WITH THE DEVELOPMENT OF UPPER EXTREMITY DEEP VEIN THROMBOSIS FOLLOWING PERIPHERALLY INSERTED CENTRAL CATHETER INSERTION].

BACKGROUND: The occurrence of upper extremity deep vein thrombosis (UEDVT) is not uncommon following peripherally inserted central catheter (PICC) insertion. However, the risk factors associated with this condition are unknown. Moreover, the role of prophylactic anticoagulation in the prevention of PICC-related UEDVT is not well established. METHODS: A review of the medical records of all patients who underwent PICC insertion during 2016 at the Hadassah Medical Center. RESULTS: Overall, 500 patients underwent PICC insertion during the study period. Of them, 199 (39.8%) received prophylactic anticoagulation following insertion. Patients with active cancer were less likely to receive prophylactic anticoagulation. Twenty-five (5.0%) patients experienced PICC-related UEDVT, which occurred after a median of 8 days following PICC placement. The only factors associated with the development of UEDVT were the presence of active cancer (P=0.04) and higher C-reactive protein level (P=0.02). The rate of UEDVT was comparable between those who received prophylactic anticoagulation and those who did not (P=0.98). CONCLUSIONS: PICC-related UEDVT is a common complication. Active cancer and higher baseline C-reactive protein level were associated with the occurrence of this condition. Future studies are warranted to confirm our findings and further assess the role of prophylactic anticoagulation in this setting.