Beyond the visible: preliminary evaluation of the first wearable augmented reality assistance system for pancreatic surgery.

PURPOSE: The retroperitoneal nature of the pancreas, marked by minimal intraoperative organ shifts and deformations, makes augmented reality (AR)-based systems highly promising for pancreatic surgery. This study presents preliminary data from a prospective study aiming to develop the first wearable AR assistance system, ARAS, for pancreatic surgery and evaluating its usability, accuracy, and effectiveness in enhancing the perioperative outcomes of patients. METHODS: We developed ARAS as a two-phase system for a wearable AR device to aid surgeons in planning and operation. This system was used to visualize and register patient-specific 3D anatomical models during the surgery. The location and precision of the registered 3D anatomy were evaluated by assessing the arterial pulse and employing Doppler and duplex ultrasonography. The usability, accuracy, and effectiveness of ARAS were assessed using a five-point Likert scale questionnaire. RESULTS: Perioperative outcomes of five patients underwent various pancreatic resections with ARAS are presented. Surgeons rated ARAS as excellent for preoperative planning. All structures were accurately identified without any noteworthy errors. Only tumor identification decreased after the preparation phase, especially in patients who underwent pancreaticoduodenectomy because of the extensive mobilization of peripancreatic structures. No perioperative complications related to ARAS were observed. CONCLUSIONS: ARAS shows promise in enhancing surgical precision during pancreatic procedures. Its efficacy in preoperative planning and intraoperative vascular identification positions it as a valuable tool for pancreatic surgery and a potential educational resource for future surgical residents.

Assessment of effectiveness and safety of thrombolytic therapy to pulmonary emboli by endobronchial ultrasound-guided transbronchial needle injection.

Objective: Endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) may effectively treat acute pulmonary embolisms (PEs). Here, we assessed the effectiveness of clot dissolution and safety of tissue plasminogen activator (t-PA) injection using EBUS-TBNI in a 1-week survival study of a porcine PE model. Methods: Six pigs with bilateral PEs were used: 3 for t-PA injection using EBUS-TBNI (TBNI group) and 3 for systemic administration of t-PA (systemic group). Once bilateral PEs were created, each 25 mg of t-PA injection using EBUS-TBNI for bilateral PEs (a total of 50 mg t-PA) and 100 mg of t-PA systemic administration was performed on day 1. Hemodynamic parameters, blood tests, and contrast-enhanced computed tomography scans were carried out at several time points. On day 7, pigs were humanely killed to evaluate the residual clot volume in the pulmonary arteries. Results: The average of percent change of residual clot volumes was significantly lower in the TBNI group than in the systemic group (%: systemic group 36.6 ± 22.6 vs TBNI group 9.6 ± 6.1, P < .01) on day 3. Considering the elapsed time, the average decrease of clot volume per hour at pre-t-PA to post t-PA was significantly greater in the TBNI group than in the systemic group (mm3/hour: systemic 68.1 ± 68.1 vs TBNI 256.8 ± 148.1, P < .05). No hemorrhage was observed intracranially, intrathoracically, or intraperitoneally on any contrast-enhanced computed tomography images. Conclusions: This study revealed that t-PA injection using EBUS-TBNI is an effective and safe way to dissolve clots.

Associations between overweight, obesity, and mental health: a retrospective study among European adults aged 50.

Background: The comorbidities associated with overweight and obesity have been well researched and scientifically proven while their relationship to mental health is still not verified. Methods: This study is aimed at investigating reciprocal associations between obesity and mental health, and is intended to further analyze possible long-term effects using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). In order to do that, waves 4 and 8, conducted in 2010 and 2019/20 of this survey, were analyzed in a cross-lagged panel approach including 16,184 adult Europeans (50+) using multiple linear regression analysis focusing on the Body Mass Index (BMI), depression status and quality of life (QoL). Results: Findings yield significant cross-lagged effects in one direction regarding BMI predicting QoL and depression state, whereas depression state and QoL do not significantly predict BMI. Findings include people living with obesity, overweight, and underweight showing significantly decreased levels of QoL as well as increased depression scores compared to people of normal weight over a lag time of 10 years, where people living with obesity indicate the strongest effect. Conclusions: However, results do not confirm reciprocal associations in the long term. Hence, there is a strong need to carry out further research on this issue.

Physician utilization in prehospital emergency medical services in Europe: an overview and comparison. / Visión general y comparación de la presencia de médicos en los servicios de emergencias médicas prehospitalarios en Europa.

OBJECTIVES: National and regional systems for emergency medical care provision may differ greatly. We sought to determine whether or not physicians are utilized in prehospital care and to what extent they are present in differentEuropean countries. MATERIAL AND METHODS: We collected information on 32 European countries by reviewing publications and sending questionnaires to authors of relevant articles as well as to officials of ministries of health (or equivalent), representatives of national societies in emergency medicine, or well-known experts in the specialty. RESULTS: Thirty of the 32 of European countries we studied (94%) employ physicians in prehospital emergency medical services. In 17 of the 32 (53%), general practitioners also participate in prehospital emergency care. Emergency system models were described as Franco-German in 27 countries (84%), as hybrid in 17 (53%), and as Anglo-American in 14 (44%). Multiple models were present simultaneously in 17 countries (53%). We were able to differentiate between national prehospital emergency systems with a novel classification based on tiers reflecting the degree of physician utilization in the countries. We also grouped the national systems by average population and area served. CONCLUSION: There are notable differences in system designs and intensity of physician utilization between different geographic areas, countries, and regions in Europe. Several archetypal models (Franco-German, hybrid, and Anglo- American) exist simultaneously across Europe.

OBJETIVO: Los sistemas nacionales y regionales de prestación de atención médica a las emergencias pueden diferir mucho entre sí. Se buscó dilucidar la presencia de médicos en la atención prehospitalaria y su implantación en los diferentes países europeos. METODO: Se analizaron los datos de 32 países europeos recogidos mediante la revisión de artículos publicados y a través de cuestionarios enviados a los autores de artículos científicos pertinentes, funcionarios del ministerio de sanidad (o equivalente), representantes de sociedades nacionales de medicina de urgencias o expertos reconocidos en medicina de urgencias. RESULTADOS: Treinta de los 32 países europeos investigados (94%) disponen de médicos en los servicios de emergencias prehospitalarios. En 17 de 32 (53%), los médicos generalistas también participan en la atención a las emergencias prehospitalarias. Los modelos de los sistemas de emergencias médicas (SEM) se describieron como francoalemanes en 27 países (84%), híbridos en 17 (53%) o angloamericanos en 14 (44%). En 17 países (53%), coexistían diferentes modelos. Utilizando una nueva forma de clasificación por niveles, basada en la población media y el área atendida por el SEM prehospitalario, se pudieron diferenciar claramente los diferentes modelos existentes. CONCLUSIONES: Se observan notables diferencias en los diseños de los SEM y en la presencia de los médicos entre las diferentes áreas geográficas, países y regiones de Europa. Coexisten varios modelos (francoalemán, híbrido y angloamericano), algunos simultáneamente, en los diferentes países.

Chronic in vivo imaging defines age-dependent alterations of neurogenesis in the mouse hippocampus.

Neural stem cells (NSCs) generate new neurons throughout life in the mammalian hippocampus1. Advancing age leads to a decline in neurogenesis, which is associated with impaired cognition2,3. The cellular mechanisms causing reduced neurogenesis with advancing age remain largely unknown. We genetically labeled NSCs through conditional recombination driven by the regulatory elements of the stem-cell-expressed gene GLI family zinc finger 1 (Gli1) and used chronic intravital imaging to follow individual NSCs and their daughter cells over months within their hippocampal niche4,5. We show that aging affects multiple steps, from cell cycle entry of quiescent NSCs to determination of the number of surviving cells, ultimately causing reduced clonal output of individual NSCs. Thus, we here define the developmental stages that may be targeted to enhance neurogenesis with the aim of maintaining hippocampal plasticity with advancing age.

Visión general y comparación de la presencia de médicos en los servicios de emergencias médicas prehospitalarios en Europa / Physician utilization in prehospital emergency medical services in Europe: an overview and comparison

Antecedentes: Los sistemas nacionales y regionales de prestación de atención médica a las emergencias pueden diferir mucho entre sí. Se buscó dilucidar la presencia de médicos en la atención prehospitalaria y su implantación en los diferentes países europeos. Métodos: Se analizaron los datos de 32 países europeos recogidos mediante la revisión de artículos publicados y a través de cuestionarios enviados a los autores de artículos científicos pertinentes, funcionarios del ministerio de sanidad (o equivalente), representantes de sociedades nacionales de medicina de urgencias o expertos reconocidos en medicina de urgencias. Resultados: Treinta de los 32 países europeos investigados (94%) disponen de médicos en los servicios de emergencias prehospitalarios. En 17 de 32 (53%), los médicos generalistas también participan en la atención a las emergencias prehospitalarias. Los modelos de los sistemas de emergencias médicas (SEM) se describieron como francoalemanes en 27 países (84%), híbridos en 17 (53%) o angloamericanos en 14 (44%). En 17 países (53%), coexistían diferentes modelos. Utilizando una nueva forma de clasificación por niveles, basada en la población media y el área atendida por el SEM prehospitalario, se pudieron diferenciar claramente los diferentes modelos existentes. Conclusiones: Se observan notables diferencias en los diseños de los SEM y en la presencia de los médicos entre las diferentes áreas geográficas, países y regiones de Europa. Coexisten varios modelos (francoalemán, híbrido y angloamericano), algunos simultáneamente, en los diferentes países. (AU)

Background: National and regional systems for emergency medical care provision may differ greatly. We sought to determine whether or not physicians are utilized in prehospital care and to what extent they are present in different European countries. Methods: We collected information on 32 European countries by reviewing publications and sending questionnairesto authors of relevant articles as well as to officials of ministries of health (or equivalent), representatives of national societies in emergency medicine, or well-known experts in the specialty. Results: Thirty of the 32 of European countries we studied (94%) employ physicians in prehospital emergency medical services. In 17 of the 32 (53%), general practitioners also participate in prehospital emergency care. Emergency system models were described as Franco-German in 27 countries (84%), as hybrid in 17 (53%), and as Anglo-American in 14(44%). Multiple models were present simultaneously in 17 countries (53%). We were able to differentiate between national prehospital emergency systems with a novel classification based on tiers reflecting the degree of physician utilization in the countries. We also grouped the national systems by average population and area served. Conclusions: There are notable differences in system designs and intensity of physician utilization between different geographic areas, countries, and regions in Europe. Several archetypal models (Franco-German, hybrid, and AngloAmerican) exist simultaneously across Europe. (AU)

Novel insights in the pathomechanism of Brugada syndrome and fever-related type 1 ECG changes in a preclinical study using human-induced pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Brugada syndrome (BrS) is causing sudden cardiac death (SCD) mainly at young age. Studying the underlying mechanisms associated with BrS type I electrocardiogram (ECG) changes in the presence of fever and roles of autophagy for BrS remains lacking. OBJECTIVES: We sought to study the pathogenic role of an SCN5A gene variant for BrS with fever-induced type 1 ECG phenotype. In addition, we studied the role of inflammation and autophagy in the pathomechanism of BrS. METHODS: Human-induced pluripotent stem cell (hiPSC) lines from a BrS patient harboring a pathogenic variant (c.3148G>A/p. Ala1050Thr) in SCN5A and two healthy donors (non-BrS) and a CRISPR/Cas9 site-corrected cell line (BrS-corr) were differentiated into cardiomyocytes (hiPSC-CMs) for the study. RESULTS: Reductions of Nav 1.5 expression, peak sodium channel current (INa ) and upstroke velocity (Vmax ) of action potentials with an increase in arrhythmic events were detected in BrS compared to non-BrS and BrS-corr cells. Increasing the cell culture temperature from 37 to 40°C (fever-like state) exacerbated the phenotypic changes in BrS cells. The fever-effects were enhanced by protein kinase A (PKA) inhibitor but reversed by PKA activator. Lipopolysaccharides (LPS) but not increased temperature up to 40°C enhanced the autophagy level in BrS-hiPSC-CMs by increasing reactive oxidative species and inhibiting PI3K/AKT signalling, and hence exacerbated the phenotypic changes. LPS enhanced high temperature-related effect on peak INa shown in BrS hiPSC-CMs. Effects of LPS and high temperature were not detected in non-BrS cells. CONCLUSIONS: The study demonstrated that the SCN5A variant (c.3148G>A/p.Ala1050Thr) caused loss-of-function of sodium channels and increased the channel sensitivity to high temperature and LPS challenge in hiPSC-CMs from a BrS cell line with this variant but not in two non-BrS hiPSC-CM lines. The results suggest that LPS may exacerbate BrS phenotype via enhancing autophagy, whereas fever may exacerbate BrS phenotype via inhibiting PKA-signalling in BrS cardiomyocytes with but probably not limited to this variant.

Laser interstitial thermal therapy of lung lesions near large vessels: a numerical study.

Objective.Laser interstitial thermal therapy (LITT) is an evolving hyperthermia-based technology that may offer a minimally invasive alternative to inoperable lung cancer. LITT of perivascular targets is challenged by higher risk of disease recurrence due to vascular heat sinks, as well as risk of damage to these vascular structures. The objective of this work is to examine the impact of multiple vessel parameters on the efficacy of the treatment and the integrity of the vessel wall in perivascular LITT.Approach.A finite element model is used to examine the role of vessel proximity, flow rate, and wall thickness on the outcome of the treatment. Main result. The simulated work indicates that vessel proximity is the major factor in driving the magnitude of the heat sink effect. Vessels situated near the target volume may act as a protective measure for reducing healthy tissue damage. Vessels with thicker walls are more at risk of damage during treatment. Interventions to reduce the flow rate may reduce the vessel's heat sink effect but may also result in increased risk of vascular wall damage. Lastly, even at reduced blood flow rates, the volume of blood reaching the threshold of irreversible damage (>43 °C) is negligible compared to the volume of blood flow throughout the treatment duration.Significance.This investigative simulation yields results that may help guide clinicians on treatment planning near large vessels.

Transbronchial real-time lung tumor localization with folate receptor-targeted near-infrared molecular imaging: A proof of concept study in animal models.

OBJECTIVE: The diagnostic yield of bronchoscopy is not satisfactory, even with recent navigation technologies, especially for tumors located outside of the bronchial lumen. Our objective was to perform a preclinical assessment of folate receptor-targeted near-infrared imaging-guided bronchoscopy to detect peribronchial tumors. METHODS: Pafolacianine, a folate receptor-targeted molecular imaging agent, was used as a near-infrared fluorescent imaging agent. An ultra-thin composite optical fiberscope was used for laser irradiation and fluorescence imaging. Subcutaneous xenografts of KB cells in mice were used as folate receptor-positive tumors. Tumor-to-background ratio was calculated by the fluorescence intensity value of muscle tissues acquired by the ultra-thin composite optical fiberscope system and validated using a separate spectral imaging system. Ex vivo swine lungs into which pafolacianine-laden KB tumors were transplanted at various sites were used as a peribronchial tumor model. RESULTS: With the in vivo murine model, tumor-to-background ratio observed by ultra-thin composite optical fiberscope peaked at 24 hours after pafolacianine injection (tumor-to-background ratio: 2.56 at 0.05 mg/kg, 2.03 at 0.025 mg/kg). The fluorescence intensity ratios between KB tumors and normal mouse lung parenchyma postmortem were 6.09 at 0.05 mg/kg and 5.08 at 0.025 mg/kg. In the peribronchial tumor model, the ultra-thin composite optical fiberscope system could successfully detect fluorescence from pafolacianine-laden folate receptor-positive tumors with 0.05 mg/kg at the carina and those with 0.025 mg/kg and 0.05 mg/kg in the peripheral airway. CONCLUSIONS: Transbronchial detection of pafolacianine-laden folate receptor-positive tumors by near-infrared imaging was feasible in ex vivo swine lungs. Further in vivo preclinical assessment is needed to confirm the feasibility of this technology.

Prolonged sedation with sevoflurane in comparison to intravenous sedation in critically ill patients - A randomized controlled trial.

BACKGROUND: Volatile anesthetics are used more commonly for sedation in the intensive-care-unit (ICU). However, evidence for long-term use remains low. We therefore conducted a randomized-controlled trial comparing sevoflurane with intravenous sedation with particular focus on efficacy and safety. METHODS: In this prospective, randomized-controlled phase-IIb monocentric clinical-trial ICU patients requiring at least 48 h of sedation were randomized to receive sevoflurane (S) or propofol/midazolam (P). Sedation quality was monitored using the Richmond-Agitation-Sedation-Scale. Following termination of sedation, the time to spontaneous breathing and extubation, opioid consumption, hemodynamics, ICU and hospital length of stay (LOS) and adverse events were recorded. RESULTS: 79 patients were eligible to randomization. Sedation quality was comparable between sevoflurane (n = 39) and propofol (n = 40). However, the use of sevoflurane lead to a reduction in time to spontaneous breathing (26 min vs. 375 min, P < 0.001). Patients sedated with propofol had lower opioid requirements (remifentanil:400 µg/h vs. 500 µg/h, P = 0.007; sufentanil:40 µg/h vs. 30 µg/h, P = 0.007) while hemodynamics, LOS or the occurrence of adverse events did not differ. CONCLUSION: ICU patients sedated with sevoflurane >48 h may return to spontaneous breathing faster, while the quality of sedation is comparable to a propofol-based sedation regime. Sevoflurane might be considered to be safe for long-term sedation in this patient population, while being non-inferior compared to propofol.

Anatomic evaluation of Pancoast tumors using three-dimensional models for surgical strategy development.

OBJECTIVE: Pancoast tumor resection planning requires precise interpretation of 2-dimensional images. We hypothesized that patient-specific 3-dimensional reconstructions, providing intuitive views of anatomy, would enable superior anatomic assessment. METHODS: Cross-sectional images from 9 patients with representative Pancoast tumors, selected from an institutional database, were randomly assigned to presentation as 2-dimensional images, 3-dimensional virtual reconstruction, or 3-dimensional physical reconstruction. Thoracic surgeons (n = 15) completed questionnaires on the tumor extent and a zone-based algorithmic surgical approach for each patient. Responses were compared with surgical pathology, documented surgical approach, and the optimal "zone-specific" approach. A 5-point Likert scale assessed participants' opinions regarding data presentation and potential benefits of patient-specific 3-dimensional models. RESULTS: Identification of tumor invasion of segmented neurovascular structures was more accurate with 3-dimensional physical reconstruction (2-dimensional 65.56%, 3-dimensional virtual reconstruction 58.52%, 3-dimensional physical reconstruction 87.50%, P < .001); there was no difference for unsegmented structures. Classification of assessed zonal invasion was better with 3-dimensional physical reconstruction (2-dimensional 67.41%, 3-dimensional virtual reconstruction 77.04%, 3-dimensional physical reconstruction 86.67%; P = .001). However, selected surgical approaches were often discordant from documented (2-dimensional 23.81%, 3-dimensional virtual reconstruction 42.86%, 3-dimensional physical reconstruction 45.24%, P = .084) and "zone-specific" approaches (2-dimensional 33.33%, 3-dimensional virtual reconstruction 42.86%, 3-dimensional physical reconstruction 45.24%, P = .501). All surgeons agreed that 3-dimensional virtual reconstruction and 3-dimensional physical reconstruction benefit surgical planning. Most surgeons (14/15) agreed that 3-dimensional virtual reconstruction and 3-dimensional physical reconstruction would facilitate patient and interdisciplinary communication. Finally, most surgeons (14/15) agreed that 3-dimensional virtual reconstruction and 3-dimensional physical reconstruction's benefits outweighed potential delays in care for model construction. CONCLUSIONS: Although a consistent effect on surgical strategy was not identified, patient-specific 3-dimensional Pancoast tumor models provided accurate and user-friendly overviews of critical thoracic structures with perceived benefits for surgeons' clinical practices.

Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.

In combination with immune checkpoint inhibitors, photodynamic therapy can induce robust immune responses capable of preventing local tumor recurrence and delaying the growth of distant, untreated disease (ie. the abscopal effect). Previously, we found that repeated photodynamic therapy (R-PDT) using porphyrin lipoprotein (PLP) as a photosensitizer, without the addition of an immune checkpoint inhibitor, can induce the abscopal effect. To understand why PLP mediated R-PDT alone can induce the abscopal effect, and how the addition of an immune checkpoint inhibitor can further strengthen the abscopal effect, we investigated the broader immune mechanisms facilitated by R-PDT and combination R-PDT + anti-PD-1 monoclonal antibody (αPD-1) in a highly aggressive, subcutaneous AE17-OVA mesothelioma dual tumor-bearing C57BL/6 mice. We found a 46.64-fold and 61.33-fold increase in interleukin-6 (IL-6) after R-PDT and combination R-PDT + αPD-1 relative to PBS respectively, suggesting broad innate immune activation. There was a greater propensity for antigen presentation in the spleen and distal, non-irradiated tumor draining lymph nodes, as dendritic cells and macrophages had increased expression of MHC class II, CD80, and CD86, after R-PDT and combination R-PDT + αPD-1. Concurrently, there was a shift in the proportions of CD4+ T cell subsets in the spleen, and an increase in the frequency of CD8+ T cells in the distal, non-irradiated tumor draining lymph nodes. While R-PDT had an acceptable safety profile, combination R-PDT + αPD-1 induced 1.26-fold higher serum potassium and 1.33-fold phosphorus, suggestive of mild laboratory tumor lysis syndrome. Histology revealed an absence of gross inflammation in critical organs after R-PDT and combination R-PDT + αPD-1 relative to PBS-treated mice. Taken together, our findings shed light on how the abscopal effect can be induced by PDT and strengthened by combination R-PDT + αPD-1, and suggests minimal toxicities after R-PDT.

Optimization of thrombolytic dose for treatment of pulmonary emboli using endobronchial ultrasound-guided transbronchial needle injection.

OBJECTIVE: Severe pulmonary embolism is often managed with thrombolysis. We sought to determine whether endobronchial ultrasound (EBUS)-guided transbronchial thrombolysis remained effective at lower alteplase doses, with the goal of minimizing potential bleeding risk. METHODS: Yorkshire pigs were anesthetized and ventilated. Preformed autologous blood clots were administered into bilateral pulmonary arteries via EBUS-guided transbronchial injection. After documenting baseline clot sizes, alteplase was injected into the clots using a 25-gauge transbronchial needle and clot dissolution was monitored over 30 minutes. The study was performed in 2 phases. First, alteplase doses of 5 and 12.5 mg were evaluated. These results informed dose selection for the second phase. Results were compared with 25-mg dose data using EBUS from a previous study. RESULTS: In the first phase, 3 clots were evaluated. Distilled water, 5 mg, and 12.5 mg alteplase were administered. The dissolved clot volume (Vdis) and percentage clot volume loss (Rdis) were -10.9, 111.6, and 160.3 mm3, and -1.6%, 11.0%, and 59.3%, respectively. In the second phase, alteplase doses of 5, 10, and 15 mg were evaluated in 12 clots across 6 pigs. The Vdis were 247.5 mm3 (Rdis, 20.1%), 910.8 mm3 (Rdis, 80.9%), and 798.3 mm3 (Rdis, 76.0%) for 5, 10, and 15 mg alteplase, respectively. Remakably reduced performance was observed with 5 mg alteplase versus 10 mg (Vdis: P < .001, Rdis: P < .001), and 15 mg (Vdis: P = .004; Rdis: P < .001). No complications were observed. CONCLUSIONS: Alteplase doses ≥10 mg were optimal for EBUS-guided transbronchial thrombolysis. This technique might represent an effective alternative therapy for central pulmonary embolism.

Preclinical feasibility of bronchoscopic fluorescence-guided lung sentinel lymph node mapping.

OBJECTIVE: Lung sentinel lymph node mapping, where peritumorally injected material is tracked through the lymphatics, aims to find the first potential sites of nodal metastasis. We sought to evaluate the preclinical feasibility of bronchoscopic fluorescence-guided sentinel lymph node mapping. METHODS: Healthy Yorkshire pigs were used; sentinel lymph node mapping was performed with indocyanine green. The primary fluorescence imaging method was an ultrathin composite fiberscope placed in the bronchoscope working channel. Secondary methods used a fluorescence thoracoscope placed in the trachea (rigid bronchoscopy) and pretracheal fascial plane (mediastinoscopy) to validate ultrathin composite fiberscope settings for sentinel lymph node detection. A tracheostomy was created, and the pig was placed in a lateral decubitus position. Transbronchial intraparenchymal indocyanine green injection was performed primarily in the right lower lobe. Ultrathin composite fiberscope and rigid bronchoscopy were performed with (n = 6) or without (n = 2) mediastinoscopy, with the former group guiding dose and ultrathin composite fiberscope optimization. Fluorescent targets were interrogated by endobronchial ultrasound before ultrathin composite fiberscope-guided transbronchial needle aspiration. Specimen fluorescence was documented before creating cytological smears. Pigs were killed postprocedure for nodal dissection. RESULTS: A total of 100 µL of 10 mg/mL indocyanine green generated strong transbronchial fluorescence with low risk of indocyanine green contamination. Fluorescence was detectable by 10 minutes postinjection. There was concordance among ultrathin composite fiberscope, rigid bronchoscopy, and mediastinoscopy. Except for 1 pig with airway contamination, ultrathin composite fiberscope-guided endobronchial ultrasound transbronchial needle aspiration obtained fluorescent material in all pigs. Specimen fluorescence was associated with specimen adequacy. CONCLUSIONS: Bronchoscopic fluorescence-guided sentinel lymph node mapping was feasible, with specimen fluorescence providing real-time feedback on sentinel lymph node biopsy success. If translated to clinical practice, attention must be paid to minimizing indocyanine green leakage.

Preclinical evaluation of thin convex probe endobronchial ultrasound-guided transbronchial needle aspiration for intrapulmonary lesions.

Background: Conventional flexible bronchoscopy has not achieved the high diagnostic yield for intrapulmonary lesions as seen with image-guided transthoracic biopsy. A thin convex probe endobronchial ultrasound bronchoscope (TCP-EBUS) with a 5.9-mm tip was designed to improve peripheral access over conventional EBUS bronchoscopes to facilitate real-time sampling of intrapulmonary lesions under ultrasound guidance. Methods: TCP-EBUS was inserted into the distal airways of ex-vivo human lungs to assess bronchial accessibility relative to clinically available bronchoscopes. The short- (≤1 h) and medium-term (≤10 d) safety of TCP-EBUS insertion and EBUS-guided transbronchial needle aspiration (TBNA) using a 25-gauge needle were evaluated physiologically and radiologically in live pigs. TCP-EBUS-guided TBNA feasibility was assessed in-vivo with pig intrapulmonary pseudo-tumors and ex-vivo with resected human lung cancer specimens. Results: For bronchial accessibility, TCP-EBUS demonstrated greater reach than the 6.6-mm convex probe endobronchial ultrasound (CP-EBUS) in all bronchi, as well as surpassed a 5.5-mm conventional bronchoscope in 63% (131/209) and a 4.8-mm conventional bronchoscope in 27% (57/209) of assessed bronchi. The median bronchial generation and the mean diameter of bronchi TCP-EBUS reached was 4 (range, 3-7) and 3.3±0.7 mm, respectively. No major complications related to TCP-EBUS-guided TBNA in distal airways were observed in the live pigs. Scattered mucosal erythema of the bronchial walls was observed immediately after TCP-EBUS insertion; this self-resolved by day 10. TCP-EBUS could successfully reach and visualize intrapulmonary targets via ultrasound, with no difficulty in needle deployment or sampling. Conclusions: TCP-EBUS has the potential to facilitate safe real-time transbronchial sampling of intrapulmonary lesions in the central and middle lung fields.

[Functional and morphological disorders of taste and olfaction in COVID-19 patients]. / Funktionelle und morphologische Geschmacks- und Geruchsstörungen bei COVID-19-Patienten.

OBJECTIVE: This study aimed to test the prevalence and evolution of acute olfactory and gustatory functional impairment and their morphologic correlates in COVID-19 patients who require hospitalization due to COVID-19-related respiratory conditions. METHODS: Included were 53 consecutive hospitalized patients (23 males, 30 females; age 42.54 ± 10.95 years) with an RT-PCR-confirmed COVID-19 diagnosis. Patients were examined twice: just after hospital discharge and 4-6 weeks later. Electrogustometric (EGM) thresholds at the tongue area supplied by the chorda tympani, at the soft palate, and in the region of the vallate papillae were recorded bilaterally. Olfaction was examined by Sniffin' sticks (Burghardt GmbH, Wedel, Germany). The patients' nasal and oral mucosa (fungiform papillae, fpap) were examined by contact endoscopy. Findings were compared to those of 53 healthy individuals matched for sex and age (23 males, 30 females; age 42.90 ± 10.64 years). RESULTS: EGM thresholds in patients were significantly higher than those of healthy subjects at both timepoints. EGM thresholds at the second measurement were significantly lower than those at the first measurement. Accordingly, patient-reported gustatory outcomes were improved at the second measurement. The same pattern was found using Sniffin' sticks. Significant alterations in form and vascularization of fPap were detected in patients, especially at the first instance. Interestingly we did not observe any significant changes in the morphology and vascularization of nasal mucosa. CONCLUSION: COVID-19 affects both gustatory and olfactory functions. In parallel, it also affects the structure and vascularization of both nasal and oral mucosa, albeit the nasal mucosa to a much lesser, non-significant extent. Our findings suggest that COVID-19 may cause a mild to profound neuropathy of multiple cranial nerves.

From Microtiter Plates to Droplets-There and Back Again.

Droplet-based microfluidic screening techniques can benefit from interfacing established microtiter plate-based screening and sample management workflows. Interfacing tools are required both for loading preconfigured microtiter-plate (MTP)-based sample collections into droplets and for dispensing the used droplets samples back into MTPs for subsequent storage or further processing. Here, we present a collection of Digital Microfluidic Pipetting Tips (DMPTs) with integrated facilities for droplet generation and manipulation together with a robotic system for its operation. This combination serves as a bidirectional sampling interface for sample transfer from wells into droplets (w2d) and vice versa droplets into wells (d2w). The DMPT were designed to fit into 96-deep-well MTPs and prepared from glass by means of microsystems technology. The aspirated samples are converted into the channel-confined droplets' sequences separated by an immiscible carrier medium. To comply with the demands of dose-response assays, up to three additional assay compound solutions can be added to the sample droplets. To enable different procedural assay protocols, four different DMPT variants were made. In this way, droplet series with gradually changing composition can be generated for, e.g., 2D screening purposes. The developed DMPT and their common fluidic connector are described here. To handle the opposite transfer d2w, a robotic transfer system was set up and is described briefly.

[Parenchyma sparing or Anatomical Resections for Colorectal Liver Metastases?] / Parenchymsparende Operationen oder anatomische Resektionen bei Lebermetastasen des kolorektalen Karzinoms?

Colorectal cancer is one of the leading causes of death in the Western world. Half of the patients develop colorectal liver metastases (CRLM), while only less than 30% of the patients have surgically resectable metastasis at the time of diagnosis. In case of resectability, classical anatomical (major) hepatectomy offers a high R0 resection rate, but with simultaneously increased perioperative morbidity and mortality. Over the past two decades, the potential benefits of parenchyma-sparing hepatectomy (PSH) for overall oncological outcomes, survival, and re-resection in case of recurrence ("salvageability") have been demonstrated. This article summarizes the current evidence on PSH as a surgical treatment option, and discusses the current "state of the art" in different therapy scenarios.