Sound speed and attenuation of human pancreas and pancreatic tumors and their influence on focused ultrasound thermal and mechanical therapies.

BACKGROUND: There is increasing interest in using ultrasound for thermal ablation, histotripsy, and thermal or cavitational enhancement of drug delivery for the treatment of pancreatic cancer. Ultrasonic and thermal modelling conducted as part of the treatment planning process requires acoustic property values for all constituent tissues, but the literature contains no data for the human pancreas. PURPOSE: This study presents the first acoustic property measurements of human pancreatic samples and provides examples of how these properties impact a broad range of ultrasound therapies. METHODS: Data were collected on human pancreatic tissue samples at physiological temperature from 23 consented patients in cooperation with a hospital pathology laboratory. Propagation of ultrasound over the 2.1-4.5 MHz frequency range through samples of various thicknesses and pathologies was measured using a set of custom-built ultrasonic calipers, with the data processed to estimate sound speed and attenuation. The results were used in acoustic and thermal simulations to illustrate the impacts on extracorporeal ultrasound therapies for mild hyperthermia, thermal ablation, and histotripsy implemented with a CE-marked clinical system operating at 0.96 MHz. RESULTS: The mean sound speed and attenuation coefficient values for human samples were well below the range of values in the literature for non-human pancreata, while the human attenuation power law exponents were substantially higher. The simulated impacts on ultrasound mediated therapies for the pancreas indicated that when using the human data instead of the literature average, there was a 30% reduction in median temperature elevation in the treatment volume for mild hyperthermia and 43% smaller volume within a 60°C contour for thermal ablation, all driven by attenuation. By comparison, impacts on boiling and intrinsic threshold histotripsy were minor, with peak pressures changing by less than 15% (positive) and 1% (negative) as a consequence of the counteracting effects of attenuation and sound speed. CONCLUSION: This study provides the most complete set of speed of sound and attenuation data available for the human pancreas, and it reiterates the importance of acoustic material properties in the planning and conduct of ultrasound-mediated procedures, particularly thermal therapies.

Management of thyroiditis in the context of Covid-19: cause-effect and beyond.

Background: The COVID-19 pandemic hit the world in late 2019, and by 2020, everyone was affected. Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) belongs to the beta-coronavirus genre and uses the angiotensin-converting enzyme 2 (ACE2) receptor to penetrate cells. Thyroid cells are rich in such receptors. Therefore, this gland is frequently involved alongside other organs in the COVID-19 disease. Aim: To describe COVID-19 inflammation and, eventually, dysregulations of normal thyroid function in a case series of patients diagnosed in a tertiary endocrinology care centre. Patients and Methods: We described subacute thyroiditis cases related to COVID-19 infection or vaccination against SARS-CoV2 infection (clinical manifestations and evolution). We also reviewed the literature data regarding COVID-19 infection or vaccination implications in thyroid pathology. Results: The literature describes two types of thyroid involvement in SARS-CoV2 infection or vaccination: subacute thyroiditis (SAT) and non-thyroidal illness syndrome (NTIS). In our case series, 5 patients (3 males), aged 41-54 years, developed the classical clinical manifestation of SAT related to COVID-19 infection (3 patients, concomitantly to upper respiratory infection or a few weeks apart) or anti-SARS-CoV2 ARNm vaccination (1-2 weeks after the vaccine administration). Clinical, laboratory and imaging findings and the evolution (steroid anti-inflammatory treatment used in 4/5 cases) were unremarkable compared to other SAT etiologies. Conclusion: We found no differences between the "typical" viral and post-COVID-19 SAT regarding clinical presentation, severity, response to treatment, and thyroid function alteration. The only remarkable difference is the association of SAT with anti-SARS-CoV2 ARNm vaccination.

Planar laser induced fluorescence mapping of a carbon laser produced plasma.

We present measurements of ion velocity distribution profiles obtained by laser induced fluorescence (LIF) on an explosive laser produced plasma. The spatiotemporal evolution of the resulting carbon ion velocity distribution was mapped by scanning through the Doppler-shifted absorption wavelengths using a tunable, diode-pumped laser. The acquisition of these data was facilitated by the high repetition rate capability of the ablation laser (1 Hz), which allowed for the accumulation of thousands of laser shots in short experimental times. By varying the intensity of the LIF beam, we were able to explore the effects of fluorescence power against the laser irradiance in the context of evaluating the saturation vs the non-saturation regime. The small size of the LIF beam led to high spatial resolution of the measurement compared to other ion velocity distribution measurement techniques, while the fast-gate operation mode of the camera detector enabled the measurement of the relevant electron transitions.

PAX (Passive-Active Crossing) Method for Sub-Millimeter Coregistration of Passive Acoustic Mapping and B-Mode Images.

Nonlinear ultrasonic emissions produced during a therapeutic ultrasound procedure can be detected, localized, and quantified through a class of methods that can be referred to as passive acoustic mapping (PAM). While a variety of PAM beamforming algorithms may be employed, they share a common limitation that a single sound speed is specified for both phase steering of array elements and for calculation of source power or energy. The specified value may be inadequate whether derived from B-mode-based metrics or literature values for constituent materials. This study employed experiments and simulations with linear and curvilinear array geometries to investigate the impact of in situ sound speed uncertainties on source localization in layered media. The data were also used to evaluate a new method for optimizing coregistration of PAM and B-mode images. Coregistration errors as large as 10 mm were observed with the curvilinear array, which also showed much greater sound speed sensitivity than the linear array. Errors with both array geometries were typically reduced to the order of 0.1 mm using the proposed optimization method regardless of beamformer choice or whether the array was calibrated. In a further step toward reliable implementation of PAM, the current work provides an approach that can help ensure that therapeutic ultrasound procedures are accurately guided by cavitation emissions.

Effectiveness of preoxygenation by conventional face mask versus non-invasive ventilation in morbidly obese patients: measurable by the oxygen-reserve index?

Preoxygenation is a crucial manoeuvre for patients' safety, particularly for morbidly obese patients due to their reduced pulmonary reserve and increased risk for difficult airway situations. The oxygen reserve index (ORI™) was recently introduced as a new parameter of multiple wavelength pulse oximetry and has been advocated to allow assessment of hyperoxia [quantified by the resulting arterial oxygen partial pressure (PaO2)]. This study investigates if ORI can be used to evaluate the impact of two different preoxygenation manoeuvres on the grade of hyperoxia. Two preoxygenation manoeuvres were sequentially evaluated in 41 morbidly obese patients: First, breathing 100% oxygen for 5 min via standard face mask. Second, after achieving a second baseline, 5 min of non-invasive ventilation (NIV) with 100% oxygen. The effect of preoxygenation on ORI compared to PaO2 was evaluated and whether differences in the two preoxygenation manoeuvres can be monitored by ORI. Overall correlation of PaO2 and ORI was significant (Spearman-Rho coefficient of correlation 0.818, p < 0.001). However, ORI could not differentiate between the two preoxygenation manoeuvres although the PaO2 values for NIV preoxygenation were significantly higher compared to standard preoxygenation (median 505 mmHg (M1) vs. 550 mmHg (M3); p < 0.0001). In contrast, ORI values did not differ significantly (median 0.39 (M1) vs. 0.38 (M3); p = 0.758). Absolute values of ORI cannot be used to assess effectiveness of a preoxygenation procedure in bariatric patients, mainly because its range of discrimination is considerably lower than the high ranges of PaO2 attained by adequate preoxygenation. Trial registration German Clinical Trials Register: DRKS00025023 (retrospectively registered on April 16th, 2021).

The impact of Enhanced Recovery after Surgery (ERAS) pathways with regard to perioperative outcome in patients with ovarian cancer.

PURPOSE: Major surgery for ovarian cancer is associated with significant morbidity. Recently, guidelines for perioperative care in gynecologic oncology with a structured "Enhanced Recovery after Surgery (ERAS)" program were presented. Our aim was to evaluate if implementation of ERAS reduces postoperative complications in patients undergoing extensive cytoreductive surgery for ovarian cancer. METHODS: 134 patients with ovarian cancer (FIGO I-IV) were included. 47 patients were prospectively studied after implementation of a mandatory ERAS protocol (ERAS group) and compared to 87 patients that were treated before implementation (pre-ERAS group). Primary endpoints of this study were the effects of the ERAS protocol on postoperative complications and length of stay in hospital. RESULTS: Preoperative and surgical data were comparable in both groups. Only the POSSUM score was higher in the ERAS group (11.8% vs. 9.3%, p < 0.001), indicating a higher surgical risk in the ERAS group. Total number of postoperative complications (ERAS: 29.8% vs. pre-ERAS: 52.8%, p = 0.011), and length of hospital stay (ERAS: 11 (6-23) vs pre-ERAS: 13 (6-50) days; p < 0.001) differed significantly. A lower fraction of patients of the ERAS group (87.2%) needed postoperative admission to the ICU compared to the pre-ERAS group (97.7%), p = 0.022). Mortality within the ERAS group was 0% vs. 3.4% (p = 0.552) in the pre-ERAS group. CONCLUSION: The implementation of a mandatory ERAS protocol was associated with a lower rate of postoperative complications and a reduced length of stay in hospital. If ERAS has influence on long-term outcome needs to be further evaluated.

Raster Thomson scattering in large-scale laser plasmas produced at high repetition rate.

We present optical Thomson scattering measurements of electron density and temperature in a large-scale (∼2 cm) exploding laser plasma produced by irradiating a solid target with a high-energy (5-10 J) laser pulse at a high repetition rate (1 Hz). The Thomson scattering diagnostic matches this high repetition rate. Unlike previous work performed in single shots at much higher energies, the instrument allows for point measurements anywhere inside the plasma by automatically translating the scattering volume using motorized stages as the experiment is repeated at 1 Hz. Measured densities around 4 × 1016 cm-3 and temperatures around 7 eV result in a scattering parameter near unity, depending on the distance from the target. The measured spectra show the transition from collective scattering close to the target to non-collective scattering at larger distances. Densities obtained by fitting the weakly collective spectra agree to within 10% with an irradiance calibration performed via Raman scattering in nitrogen.

Noninvasive assessment of steatosis and viability of cold-stored human liver grafts by MRI.

PURPOSE: A shortage of suitable donor livers is driving increased use of higher risk livers for transplantation. However, current biomarkers are not sensitive and specific enough to predict posttransplant liver function. This is limiting the expansion of the donor pool. Therefore, better noninvasive tests are required to determine which livers will function following implantation and hence can be safely transplanted. This study assesses the temperature sensitivity of proton density fat fraction and relaxometry parameters and examines their potential for assessment of liver function ex vivo. METHODS: Six ex vivo human livers were scanned during static cold storage following normothermic machine perfusion. Proton density fat fraction, T1 , T2 , and T2∗ were measured repeatedly during cooling on ice. Temperature corrections were derived from these measurements for the parameters that showed significant variation with temperature. RESULTS: Strong linear temperature sensitivities were observed for proton density fat fraction (R2 = 0.61, P < .001) and T1 (R2 = 0.78, P < .001). Temperature correction according to a linear model reduced the coefficient of repeatability in these measurements by 41% and 36%, respectively. No temperature dependence was observed in T2 or T2∗ measurements. Comparing livers deemed functional and nonfunctional during normothermic machine perfusion by hemodynamic and biochemical criteria, T1 differed significantly: 516 ± 50 ms for functional versus 679 ± 60 ms for nonfunctional, P = .02. CONCLUSION: Temperature correction is essential for robust measurement of proton density fat fraction and T1 in cold-stored human livers. These parameters may provide a noninvasive measure of viability for transplantation.

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5-15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm3). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices.

Dual-Array Passive Acoustic Mapping for Cavitation Imaging With Enhanced 2-D Resolution.

Passive acoustic mapping (PAM) techniques have been developed for the purposes of detecting, localizing, and quantifying cavitation activity during therapeutic ultrasound procedures. Implementation with conventional diagnostic ultrasound arrays has allowed planar mapping of bubble acoustic emissions to be overlaid with B-mode anatomical images, with a variety of beamforming approaches providing enhanced resolution at the cost of extended computation times. However, no passive signal processing techniques implemented to date have overcome the fundamental physical limitation of the conventional diagnostic array aperture that results in point spread functions with axial/lateral beamwidth ratios of nearly an order of magnitude. To mitigate this problem, the use of a pair of orthogonally oriented diagnostic arrays was recently proposed, with potential benefits arising from the substantially expanded range of observation angles. This article presents experiments and simulations intended to demonstrate the performance and limitations of the dual-array system concept. The key finding of this study is that source pair resolution of better than 1 mm is now possible in both dimensions of the imaging plane using a pair of 7.5-MHz center frequency conventional arrays at a distance of 7.6cm. With an eye toward accelerating computations for real-time applications, channel count reductions of up to a factor of eight induce negligible performance losses. Modest sensitivities to sound speed and relative array position uncertainties were identified, but if these can be kept on the order of 1% and 1 mm, respectively, then the proposed methods offer the potential for a step improvement in cavitation monitoring capability.

Hemodynamics and Metabolic Parameters in Normothermic Kidney Preservation Are Linked With Donor Factors, Perfusate Cells, and Cytokines.

Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of the kidney has been studied extensively during the last two decades and implemented in clinical trials. Biomarker research led to success in identifying molecules with diagnostic, predictive and therapeutic properties in chronic kidney disease. However, perfusate biomarkers and potential predictive mechanisms in NMP have not been identified yet. Twelve discarded human kidneys (n = 7 DBD, n = 5 DCD) underwent NMP for up to 24 h. Eight were perfused applying urine recirculation (URC), four with replacement of urine (UR) using Ringer's lactate. The aim of our study was to investigate biomarkers (NGAL, KIM-1, and L-FABP), cells and cytokines in the perfusate in context with donor characteristics, perfusate hemodynamics and metabolic parameters. Cold ischemia time did not correlate with any of the markers. Perfusates of DBD kidneys had a significantly lower number of leukocytes after 6 h of NMP compared to DCD. Arterial flow, pH, NGAL and L-FABP correlated with donor creatinine and eGFR. Arterial flow was higher in kidneys with lower perfusate lactate. Perfusate TNF-α was higher in kidneys with lower arterial flow. The cytokines IL-1ß and GM-CSF decreased during 6 h of NMP. Kidneys with more urine output had lower perfusate KIM-1 levels. Median and 6-h values of lactate, arterial flow, pH, NGAL, KIM-1, and L-FABP correlated with each other indicating a 6-h period being applicable for kidney viability assessment. The study results demonstrate a comparable cytokine and cell profile in perfusates with URC and UR. In conclusion, clinically available perfusate and hemodynamic parameters correlate well with donor characteristics and measured biomarkers in a discarded human NMP model.

Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis-a proteomics study.

We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n = 8 donors after brain death [DBD], n = 8 donors after circulatory death [DCD]) and three with UR (n = 2 DBD, n = 1 DCD), followed by quantitative analysis by mass spectrometry. Damage-associated molecular patterns (DAMPs) were decreased in kidney tissue after 6 hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilization. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after 12 and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic-oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalizes metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys.

Measurements of ion velocity distributions in a large scale laser-produced plasma.

Laser-produced plasma velocity distributions are an important, but difficult quantity to measure. We present a non-invasive technique for measuring individual charge state velocity distributions of laser-produced plasmas using a high temporal and spectral resolution monochromator. The novel application of this technique is its ability to detect particles up to 7 m from their inception (significantly larger than most laboratory plasma astrophysics experiments, which take place at or below the millimeter scale). The design and assembly of this diagnostic is discussed in terms of maximizing the signal to noise ratio, maximizing the spatial and temporal resolution, and other potential use cases. The analysis and results of this diagnostic are demonstrated by directly measuring the time-of-flight velocity of all ion charge states in a laser produced carbon plasma.

Urine Recirculation Improves Hemodynamics and Enhances Function in Normothermic Kidney Perfusion.

The study compares urine recirculation (URC) to urine replacement (UR) with Ringer's lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device. METHODS: Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5). Cold ischemia time was either 2 or 27 hours for the first or second perfusion (URC or UR) of a kidney pair. An autologous blood-based perfusate, leukocyte-filtered, was used and NMP performed up to 24 hours. Perfusion parameters, biochemistry/metabolic parameters were monitored and samples collected. RESULTS: Physiological mean arterial pressures and flows were achieved in both groups but were sustainable only with URC. Significantly higher arterial flow was observed with URC (326.7 ± 1.8 versus 242.5 ± 14.3 mL/min, P = 0.001). Perfusate sodium levels were lower with URC, 129.6 ± 0.7 versus 170.3±2.7 mmol/L, P < 0.001). Stable physiological pH levels were only observed with URC. Perfusate lactate levels were lower with URC (2.2 ± 0.1 versus 7.2 ± 0.5 mmol/L, P < 0.001). Furthermore, the hourly rate of urine output was lower with URC and closer to physiological levels (150 versus 548 mL/h, P = 0.008). Normothermic kidney perfusion with URC was associated with longer achievable durations of perfusion: the objective in all experiments was a 24-hour perfusion, but this was not achieved in every case. The mean perfusions were 17.3 ± 9.2 hours with URC versus 5.3 ± 1.3 hours NMP with UR; P = 0.02. There appeared to be no differences in baseline tubular condition with and without URC. CONCLUSIONS: URC facilitates long-term kidney NMP in a porcine model. Perfusate homeostasis and stability of renal arterial flow throughout the perfusion period was only achievable with URC, independent of cold ischemia time duration.

Spatiotemporal Assessment of the Cellular Safety of Cavitation-Based Therapies by Passive Acoustic Mapping.

Many useful therapeutic bio-effects can be generated using ultrasound-induced cavitation. However, cavitation is also capable of causing unwanted cellular and vascular damage, which should be monitored to ensure treatment safety. In this work, the unique opportunity provided by passive acoustic mapping (PAM) to quantify cavitation dose across an entire volume of interest during therapy is utilised to provide setup-independent measures of spatially localised cavitation dose. This spatiotemporally quantifiable cavitation dose is then related to the level of cellular damage generated. The cavitation-mediated destruction of equine red blood cells mixed with one of two types of cavitation nuclei at a variety of concentrations is investigated. The blood is placed within a 0.5-MHz ultrasound field and exposed to a range of peak rarefactional pressures up to 2 MPa, with 50 to 50,000 cycle pulses maintaining a 5% duty cycle. Two co-planar linear arrays at 90° to each other are used to generate 400-µm-resolution frequency domain robust capon beamforming PAM maps, which are then used to generate estimates of cavitation dose. A relationship between this cavitation dose and the levels of haemolysis generated was found which was comparable regardless of the applied acoustic pressure, pulse length, cavitation agent type or concentration used. PAM was then used to monitor cellular damage in multiple locations within a tissue phantom simultaneously, with the damage-cavitation dose relationship being similar for the two experimental models tested. These results lay the groundwork for this method to be applied to other measures of safety, allowing for improved ultrasound monitoring of cavitation-based therapies.

New solutions to reduce greenhouse gas emissions through energy efficiency of buildings of special importance - Hospitals.

Saving energy has an important role in the concerted actions to protect the planet from the effects of global warming, particularly the energy consumed by the existing buildings (with various energy consuming functions, inefficient energy), by implementing environmentally friendly solutions. The present paper emphasizes the need to include elements to stimulate the renovation of the existing buildings and of their energy efficiency in the national strategies, these constructions being important energy consumers. The research started with two case studies (2 hospital buildings) dating from 70-80s, with the aim to be energy efficient and modern constructions in Eastern Europe. In the presented best practice model, significant reductions in greenhouse gas emissions, primary energy consumption along with the use of renewable energy have been achieved by transforming some energy-inefficient buildings into intelligent buildings. Thus, the authors propose a new stake: "70-70-70" for similar buildings.

Compensation of array lens effects for improved co-registration of passive acoustic mapping and B-mode images for cavitation monitoring.

Passive acoustic mapping (PAM) techniques offer a simple means of spatio-temporal cavitation monitoring during therapeutic ultrasound procedures. Implementation with a conventional diagnostic ultrasound system allows natural integration of PAM with B-mode imaging. However, the refracting properties of diagnostic array lenses may introduce PAM image registration errors that could lead to inaccuracies in treatment monitoring and guidance. To address these concerns, this paper presents lens characterization of two different array designs, analytical estimation of lens-induced source mapping errors in simple media, and experimental demonstration and correction of lens effects, reducing the depth-averaged image co-registration errors to no more than 0.52 mm.

Transient Cold Storage Prior to Normothermic Liver Perfusion May Facilitate Adoption of a Novel Technology.

Clinical adoption of normothermic machine perfusion (NMP) may be facilitated by simplifying logistics and reducing costs. This can be achieved by cold storage of livers for transportation to recipient centers before commencing NMP. The purpose of this study was to assess the safety and feasibility of post-static cold storage normothermic machine perfusion (pSCS-NMP) in liver transplantation. In this multicenter prospective study, 31 livers were transplanted. The primary endpoint was 30-day graft survival. Secondary endpoints included the following: peak posttransplant aspartate aminotransferase (AST), early allograft dysfunction (EAD), postreperfusion syndrome (PRS), adverse events, critical care and hospital stay, biliary complications, and 12-month graft survival. The 30-day graft survival rate was 94%. Livers were preserved for a total of 14 hours 10 minutes ± 4 hours 46 minutes, which included 6 hours 1 minute ± 1 hour 19 minutes of static cold storage before 8 hours 24 minutes ± 4 hours 4 minutes of NMP. Median peak serum AST in the first 7 days postoperatively was 457 U/L (92-8669 U/L), and 4 (13%) patients developed EAD. PRS was observed in 3 (10%) livers. The median duration of initial critical care stay was 3 days (1-20 days), and median hospital stay was 13 days (7-31 days). There were 7 (23%) patients who developed complications of grade 3b severity or above, and 2 (6%) patients developed biliary complications: 1 bile leak and 1 anastomotic stricture with no cases of ischemic cholangiopathy. The 12-month overall graft survival rate (including death with a functioning graft) was 84%. In conclusion, this study demonstrates that pSCS-NMP was feasible and safe, which may facilitate clinical adoption.

PLASMATIC LEVELS OF NEUROPEPTIDES, INCLUDING OXYTOCIN, IN CHILDREN WITH AUTISM SPECTRUM DISORDER, CORRELATE WITH THE DISORDER SEVERITY.

CONTEXT: Oxytocin has been investigated as a potential medication for psychiatric disorders. OBJECTIVE AND DESIGN: This study prospectively investigates correlations between oxytocin and other neuropeptides plasma levels in patients with autism spectrum disorders (ASD) according to severity and treatment, as compared to controls. SUBJECTS AND METHODS: Thirty-one children (6 neurotypical as control) participated in this study. The patients were classified into mildly and severely-affected, according to Autism Diagnostic Observation Schedule (ADOS) scores. Oxytocin, orexin A and B, α-MSH, ß-endorphins, neurotensin and substance P were investigated using a quantitative multiplex assay or a competitive-ELISA method. RESULTS: Plasma oxytocin levels differed between the groups (F (2, 24) =6.48, p=0.006, η2=0.35, observed power=86%): patients with the mild ASD had higher values of plasma oxytocin than those with the severe form (average difference=74.56±20.74pg/mL, p=0.004). CONCLUSIONS: These results show a negative correlation between plasma levels of oxytocin and the severity of ASD and support the involvement of oxytocinergic mechanisms in ASD.

[Bronchoalveolar lavage in hairy cell leukemia with pulmonary infiltration]. / Bronchoalveoläre Lavage bei Haarzellleukämie mit Lungeninfiltration.

We report a 78-year-old male patient suffering from hairy cell leukemia, presenting clinically mainly with dyspnea. Radiology exhibited bilateral ground-glass shadows. In order to prevent pneumonia as a possible side effect due to conventional chemotherapy, it was decided to first treat the patient with rituximab; however, dyspnea persisted. Therefore, bronchoscopy was performed and specimens were sampled for both histological examination and bronchoalveolar lavage (BAL) analysis. BAL showed lymphocytosis (28.7%), and by means of immunocytochemistry a few CD79a+ B­lymphocytes as well as lymphoid cells positive for the hairy cell marker DBA44 were observed. In addition, molecular study revealed the BRAF V600E mutation. Thus, the findings of BAL were interpreted as lung infiltration by hairy cell leukemia. This result was confirmed by histology. Following a therapy switch to cladribine, a significant improvement was reached. Pulmonary infiltrates by hairy cell leukemia were rarely described. This case represents the first report of hairy cell leukemia diagnosed by means of BAL. It may be difficult to clearly separate between lymphoma infiltration of the lung and medicamentous pneumonitis, but this differential diagnosis can be supported by morphological methods.