Endoscopic vacuum therapy (eVAC) combined with continuous perianastomotic irrigation for prevention of anastomotic leak after surgical ampullectomy.

PURPOSE: Transduodenal surgical ampullectomy (tAMP) with papillary reimplantation is a valid alternative to pancreaticoduodenectomy for lesions of the periampullary region not amenable to endoscopic resection. As tAMP is burdened by high rates of biliopancreatic-enteric anastomotic leak, we tested preventive endoluminal vacuum therapy (eVAC) combined with post-operative continuous perianastomotic irrigation (CPI) to reduce such anastomotic leak. METHODS: Between 10/2013 and 09/2023, 37 patients undergoing laparotomic tAMP (with or without jejunal transposition) and papillary reimplantation at Hirslanden Klinik Zurich were retrospectively analysed; of these, 16 received prophylactic eVAC combined with CPI, while the remaining represented the historical cohort. RESULTS: The eVAC-CPI-group and the historical-cohort were homogeneous in demographic characteristics. Surgery in the prophylactic eVAC-CPI-group lasted about 30 min longer due to eVAC application (p = 0.008). The biliopancreatico-enteric anastomotic leak rates were 6.2% in the eVAC-CIP-group vs. 19.0% in the historical-cohort (p = 0.266). Along, a strong trend of less severe post-operative complications in general (p = 0.073), and borderline-significantly less cases of acute pancreatitis (p = 0.057) and tAMP-related re-operations or re-interventions (p = 0.057) in particular, were observed in the eVAC-CPI-group. The only anastomotic leak in the eVAC-CPI-group was successfully managed through repeated cycles of eVAC. The device was well tolerated by all patients; no vacuum/irrigation-related complications or malfunctioning occurred. CONCLUSION: Our study is the first to provide some technical insights demonstrating the safety and feasibility of a prophylactic approach with eVAC and perianastomotic irrigation to reduce anastomotic leak after tAMP. Increasing the number of subjects will confirm the benefit of our promising results.

Primary pulmonary meningioma: a case report.

An asymptomatic 68-year-old woman, with a history of breast cancer 19 years ago, was unexpectedly found to have primary pulmonary meningioma during medical evaluation. This discovery is exceedingly rare, with only about 70 cases reported worldwide. Following uncomplicated surgical removal of the mass, the patient was discharged in good health on the third day after the procedure. Notably, initial analysis of a frozen tissue sample indicated hamartoma, but subsequent immune-histochemical pathological examination confirmed the presence of meningioma. Given the uncommon nature of this tumor, it is essential to report such cases to raise awareness about pulmonary meningioma as a potential cause of solitary lung nodules. This awareness can help prevent unnecessary chemotherapy or surgical interventions.

A rare posterior mediastinal mass: chordoma.

A 72-year-old female presented with 2 years of pro-gradient pain in the upper thoracic spine radiating to the left arm and leg. MRI revealed a 2.7 × 2.0 × 12 cm paravertebral mass at T2/T3, extending into the foraminal and epidural nerves with extensive dural sac contact in the left hemithorax. The removed tumour was surprisingly soft for a schwannoma or chordoma. However, after the surgery, histopathology revealed the presence of brachyury protein (T-box transcription factor T), which is characteristic of a chordoma. While chordomas are extremely rare, it is important that they are kept in mind for the differential diagnosis of a posterior mediastinal mass. Successful treatment can only be achieved through a complete en bloc resection. This can often be complex due to their location along the spine. This case report aims to highlight the features and treatment of this rare disease.

The significance of a 'T shaped' incision for resection of giant mediastinal tumors: a case report.

A 37-year-old male, with a 5-year history of liposarcoma of the right thigh, was incidentally diagnosed with two huge thoracic metastases following a fall. One of these masses, measuring 22 cm, was located in the right chest apex, adjacent to a second 20 cm mass situated in the anterior mediastinum, partially invading the left chest. The patient underwent surgical intervention for mass resection that commenced with a hemi-clamshell incision, but was then extended by completing the lower median sternotomy in order to create a T shaped incision. This type of incision provides ample access for large mediastinal tumors that extensively extend into one side of the thoracic cavity, encompass the anterior mediastinum, and partially reach into the opposite cavity. It enhances visualization, facilitates access to vital organs, allows for precise surgical maneuvers, minimizes the risk of inadvertent tissue damage, and enables thorough oncological resection.

Lung transplantation in children.

Lung transplantation is a well-established treatment for children facing advanced lung disease and pulmonary vascular disorders. However, organ shortage remains highest in children. For fitting the small chest of children, transplantation of downsized adult lungs, lobes, or even segments were successfully established. The worldwide median survival after pediatric lung transplantation is currently 5.7 years, while under consideration of age, underlying disease, and peri- and posttransplant center experience, median survival of more than 10 years is reported. Timing of referral for transplantation, ischemia-reperfusion injury, primary graft dysfunction, and acute and chronic rejection after transplantation remain the main challenges.

Maxillary sinus floor augmentation with autogenous bone graft compared with composite grafts: A one-year single-blinded randomized controlled trial.

OBJECTIVE: The objective was to assess the one year implant treatment outcome and patient-related outcome measures (PROMs) following maxillary sinus floor augmentation (MSFA) with autogenous bone graft (ABG) from the zygomatic buttress (control) compared with 1:1 mixture of ABG and anorganic porcine bone mineral (APBM) (Test I) or biphasic bone graft material (BBGM) (Test II). MATERIALS AND METHODS: Sixty healthy patients (34 females, 26 males) were randomly allocated to either control or test groups. Outcome measures included survival of suprastructures and implants, implant stability quotient, health status of peri-implant tissue, peri-implant marginal bone loss, frequency of complications, and PROMs using Oral Health Impact Profile-14 combined with questionnaire assessing patient perception of peri-implant soft tissue, prosthetic solution, implant function, and implant treatment outcome using visual analogue scale. Mean differences were expressed with standard deviation and 95% confidence interval. Level of significance was .05. RESULTS: All suprastructures and implants were well-functioning after one year of functional implant loading. There was no significant difference between control and test groups in any of the applied outcome measures. The implant stability significantly increased from implant placement to abutment connection within all groups (p < .001). High patient satisfaction and significant improvement in oral health-related quality of life was also reported within all groups. CONCLUSION: This study demonstrates that MSFA with composite grafts containing minimal amounts of ABG reveals comparable implant treatment outcomes as compared with ABG alone, after one year of functional implant loading. Extensive ABG harvesting in conjunction with MSFA therefore seems not to be needed.

Structure, biophysics, and circuit function of a "giant" cortical presynaptic terminal.

The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and "flash-and-freeze" electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.

GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles.

GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the "Flash and Freeze-fracture" method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals.

3-D Contrast-Enhanced Fusion Ultrasound for Accurate Volume Assessment of Vessel Lumen and Plaque in Carotid Artery Disease as Compared With Computed Tomography Angiography.

OBJECTIVE: Three-dimensional contrast-enhanced fusion ultrasound (CEFUS) of atherosclerotic carotid arteries provides spatial visualization of the vessel lumen, creating a lumenography. As in 3-D computed tomography angiography (CTA), 3-D CEFUS outlines the contrast-filled lumen. Plaque and vessel contours are distinguished in 3-D CEFUS, allowing plaque volume quantification as a valid estimate of carotid plaque burden. Three-dimensional CEFUS is unproven in intermodality studies, vindicating the assessment of 3-D CEFUS applicability and comparing 3-D CEFUS and 3-D CTA lumenography as a proof-of-concept study. METHODS: Using an ultrasound system with magnetic tracking, a linear array transducer and SonoVue contrast agent, 3-D CEFUS acquisitions were generated by spatial stitching of serial 2-D images. From 3-D CEFUS and 3-D CTA imaging, the atherosclerotic carotid arteries were reconstructed with lumenography in an offline software program for lumen and plaque volume quantification. Bland-Altman analysis was used for inter-image modality agreement. RESULTS: The study included 39 carotid arteries. Mean lumen and plaque volume in 3-D CEFUS were 0.63 cm3 (standard deviation [SD]: 0.26) and 0.62 cm3 (SD: 0.26), respectively. Lumen volume differences between 3-D CEFUS and 3-D CTA were non-significant, with a mean difference of 0.01 cm3 (SD: 0.02, p = 0.26) and limits of agreement (LoA) range of ±0.11 cm3. Mean plaque volume difference was -0.12 cm3 (SD: 0.19, p = 0.006) with a LoA range of ±0.39 cm3. CONCLUSION: There was strong agreement in lumenography between 3-D CEFUS and 3-D CTA. The interimage modality difference in plaque volumes was substantial because of challenging vessel wall definition in 3-D CTA. Three-dimensional CEFUS is viable in quantifying carotid plaque volume burden and can potentially monitor plaque development over time.

Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse.

The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.

Symptoms of arteria spinalis anterior syndrome in a patient with ischaemic stroke and Takayasu arteritis.

In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still being studied, immunotherapy is currently only indicated in the treatment of mismatch-repair deficient (dMMR) metastatic CRC, which accounts for 10-15% of patients. Recent studies indicate high rates of pathologic response in dMMR CRC treated with pre-operative immunotherapy while large-scale studies on novel immunotherapy combinations are ongoing.

Systematic Review and Meta-Analysis of the Incidence of Rupture, Repair, and Death of Small and Large Abdominal Aortic Aneurysms under Surveillance.

BACKGROUND: The ultimate goal of treating patients with abdominal aortic aneurysms (AAAs) is to repair them when the risk of rupture exceeds the risk of repair. Small AAAs demonstrate a low rupture risk, and recently, large AAAs just above the threshold (5.5-6.0 cm) seem to be at low risk of rupture as well. The present review aims to investigate the outcomes of AAAs under surveillance through a comprehensive systematic review and meta-analysis. METHODS: PubMed, Embase, and the Cochrane Central Register were searched (22 March 2022; PROSPERO; #CRD42022316094). The Cochrane and PRISMA statements were respected. Blinded systematic screening of the literature, data extraction, and quality assessment were performed by two authors. Conflicts were resolved by a third author. The meta-analysis of prevalence provided estimated proportions, 95% confidence intervals, and measures of heterogeneity (I2). Based on I2, the heterogeneity might be negligible (0-40%), moderate (30-60%), substantial (50-90%), and considerable (75-100%). The primary outcome was the incidence of AAA rupture. Secondary outcomes included the rate of small AAAs reaching the threshold for repair, aortic-related mortality, and all-cause mortality. RESULTS: Fourteen publications (25,040 patients) were included in the analysis. The outcome rates of the small AAA group (<55 mm) were 0.3% (95% CI 0.0-1.0; I2 = 76.4%) of rupture, 0.6% (95% CI 0.0-1.9; I2 = 87.2%) of aortic-related mortality, and 9.6% (95% CI 2.2-21.1; I2 = 99.0%) of all-cause mortality. During surveillance, 21.4% (95% CI 9.0-37.2; I2 = 99.0%) of the initially small AAAs reached the threshold for repair. The outcome rates of the large AAA group (>55 mm) were 25.7% (95% CI 18.0-34.3; I2 = 72.0%) of rupture, 22.1% (95% CI 16.5-28.3; I2 = 25.0%) of aortic-related mortality, and 61.8% (95% CI 47.0-75.6; I2 = 89.1%) of all-cause mortality. The sensitivity analysis demonstrated a higher rupture rate in studies including <662 subjects, patients with a mean age > 72 years, >17% of female patients, and >44% of current smokers. CONCLUSION: The rarity of rupture and aortic-related mortality in small AAAs supports the current conservative management of small AAAs. Surveillance seems indicated, as one-fifth reached the threshold for repair. Large aneurysms had a high incidence of rupture and aortic-related mortality. However, these data seem biased by the sparse and heterogeneous literature overrepresented by patients unfit for surgery. Specific rupture risk stratified by age, gender, and fit-for-surgery patients with large AAAs needs to be further investigated.

Extracorporeal cytokine adsorption reduces systemic cytokine storm and improves graft function in lung transplantation.

Objectives: Ischemia-reperfusion injury often coincides with a cytokine storm, which can result in primary graft dysfunction following lung transplantation. Our previous research has demonstrated allograft improvement by cytokine adsorption during ex vivo lung perfusion. The aim of this study was to investigate the effect of in vivo extracorporeal cytokine adsorption in a large animal model. Materials and Methods: Pig left lung transplantation was performed following 24 hours of cold ischemic storage. Observation period after transplantation was 24 hours. In the treatment group (n = 6), extracorporeal CytoSorb adsorption was started 30 minutes before reperfusion and continued for 6 hours. A control group (n = 3) did not receive adsorber treatment. Results: During adsorption, we consistently noticed a significant decrease in plasma proinflammatory interleukin (IL)-2, trends of less proinflammatory, tumor necrosis factor- α, IL-1α, and granulocyte-macrophage colony-stimulating factor as well as significantly reduced systemic neutrophils. In addition, a significantly lower peak airway pressure was detected during the 6 hours of adsorption. After 24 hours of observation, when evaluating the left lung allograft independently, we observed significantly improved CO2 removal, partial pressure of oxygen/inspired oxygen fraction ratio, and less acidosis in the treatment group. At autopsy, bronchoalveolar lavage results exhibited significantly lower recruitment of cells and less pro-inflammatory IL-1α, IL-1ß, IL-6, and IL-8 in the treatment group. Histologically, the treatment group had a strong trend, indicating less neutrophil invasion into the alveolar space. Conclusions: Based on our findings, cytokine adsorption during and after reperfusion is a viable approach to reducing posttransplant inflammation following lung transplantation. CytoSorb may increase the acceptance of extended criteria donor lungs, which are more susceptible to ischemia-reperfusion injury.

Imaging brain tissue architecture across millimeter to nanometer scales.

Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.

Dense 4D nanoscale reconstruction of living brain tissue.

Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure-function relationships of the brain's complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue.

[Surgery of old people-Thoracic surgery]. / Chirurgie des alten Menschen ­ Thoraxchirurgie.

Background: The incidence of a large number of diseases relevant to thoracic surgery increases with age; however, old age is still frequently considered a contraindication per se for curative interventions and extensive surgical procedures. Objective: Overview of the current relevant literature, derivation of recommendations for patient selection as well as preoperative, perioperative and postoperative optimization. Material and methods: Analysis of the current study situation. Results: Recent data show that for most thoracic diseases, age alone is not a reason to withhold surgical treatment. Much more important for the selection are comorbidities, frailty, malnutrition and cognitive impairment. A lobectomy or segmentectomy for stage I non-small cell lung cancer (NSCLC) in carefully selected octogenarians can provide acceptable to even comparably good short-term and long-term results as in younger patients. Selected > 75-year-old patients with stages II-IIIA NSCLC even benefit from adjuvant chemotherapy. With appropriate selection high-risk interventions, such as pneumonectomy in > 70-year-old patients and pulmonary endarterectomy in > 80-year-old patients can be performed without an increase in mortality rates. Even lung transplantation can lead to good long-term results in carefully selected > 70-year-old patients. Minimally invasive surgical techniques and nonintubated anesthesia contribute to risk reduction in marginal patients. Discussion: In thoracic surgery the biological age rather than the chronological age is decisive. In view of the increasingly older population, further studies are urgently needed to optimize patient selection, type of intervention, preoperative planning and postoperative treatment as well as the quality of life.

Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.

Integrated mental healthcare and vocational rehabilitation for people on sick leave with stress-related disorders: 24-month follow-up of the randomized IBBIS trial.

OBJECTIVES: Integrating vocational rehabilitation and mental healthcare has shown effects on vocational outcomes during sick leave with common mental disorders. In a previous paper, we showed that a Danish integrated healthcare and vocational rehabilitation intervention (INT) had a surprisingly negative impact on vocational outcomes compared to service as usual (SAU) at 6- and 12-month follow-up. That was also the case with a mental healthcare intervention (MHC) tested in the same study. This article reports the 24-month follow-up results of that same study. METHOD: A randomized, parallel-group, three-arm, multi-centre superiority trial was conducted to test the effectiveness of INT and MHC compared to SAU. RESULTS: In total, 631 persons were randomized. Contrary to our hypothesis, SAU showed faster return to work than both INT [hazard rate (HR) 1.39, P=0.0027] and MHC (HR 1.30, P=0.013) at 24-month follow-up. Overall, no differences were observed regarding mental health and functional level. Compared to SAU, we observed some health benefits of MHC, but not INT, at 6-month follow-up but not thereafter, and lower rates of employment at all follow-ups. Since implementation problems might explain the results of INT, we cannot conclude that INT is no better that SAU. The MHC intervention was implemented with good fidelity and did not improve return to work. CONCLUSION: This trial does not support the hypothesis that INT lead to faster return to work. However, implementation failure may explain the negative results.