Outcomes of Vacuum-Assisted Closure in Patients with Empyema Thoracis: A 10-Year Experience.

BACKGROUND: Video-assisted thoracic surgery is currently the recommended treatment for patients with empyema thoracis. However, open-window thoracostomy (OWT) is not uncommon and is performed as a last resort in patients who are in poor general condition or with complicated empyema. Although several professional associations have recommended vacuum-assisted closure (VAC) as an adjunct to standard treatment, exact data regarding the clinical role of intrathoracic VAC are not available. The primary objective of this study was to determine the safety and efficacy of intrathoracic VAC in debilitated patients and to compare the results with those of previous OWT studies. METHODS: We investigated 127 patients with a poor performance status who initially received inpatient intrathoracic VAC for stage II/III empyema thoracis between January 2010 and December 2020. RESULTS: The median duration of VAC was 15 days, and the median length of stay was 18 days. Two patients had complications, and the in-hospital mortality rate was 11.8% (15 of 127). Among the 112 surviving patients, 25 (22.3%) were discharged with OWT and 87 (77.7%) were discharged with a closed chest. Empyema recurred in 5 patients. Ultimately, we recorded an absolute success rate of 64.6% (82 of 127). CONCLUSIONS: Intrathoracic VAC appears to be safer and associated with less morbidity and mortality than OWT in debilitated patients with empyema. Our results revealed a reduced hospital length of stay and an improved success rate. The results of this work should contribute to improving treatment success in pleural empyema patients.

Performance of Intraoperative Contrast-Enhanced Ultrasound (Io-CEUS) in the Diagnosis of Primary Lung Cancer.

BACKGROUND: Suspicious tumors of the lung require specific staging, intraoperative detection, and histological confirmation. We performed an intrathoracic, intraoperative contrast-enhanced ultrasound (Io-CEUS) for characterization of lung cancer. METHODS: Retrospective analysis of prospectively collected data on the application of Io-CEUS in thoracic surgery for patients with operable lung cancer. Analysis of the preoperative chest CT scan and FDG-PET/CT findings regarding criteria of malignancy. Immediately before lung resection, the intrathoracic Io-CEUS was performed with a contrast-enabled T-probe (6-9 MHz-L3-9i-D) on a high-performance ultrasound machine (Loqic E9, GE). In addition to intraoperative B-mode, color-coded Doppler sonography (CCDS), or power Doppler (macrovascularization) of the lung tumor, contrast enhancement (Io-CEUS) was used after venous application of 2.4-5 mL sulfur hexafluoride (SonoVue, Bracco, Italy) for dynamic recording of microvascularization. The primary endpoint was the characterization of operable lung cancer with Io-CEUS. Secondly, the results of Io-CEUS were compared with the preoperative staging. RESULTS: The study included 18 patients with operable lung cancer, who received Io-CEUS during minimally invasive thoracic surgery immediately prior to lung resection. In the chest CT scan, the mean size of the lung tumors was 2.54 cm (extension of 0.7-4.5 cm). The mean SUV in the FDG-PET/CT was 7.6 (1.2-16.9). All lung cancers were detected using B-mode and power Doppler confirmed macrovascularization (100%) of the tumors. In addition, Io-CEUS showed an early wash-in with marginal and mostly simultaneous central contrast enhancement. CONCLUSIONS: The intrathoracic application of Io-CEUS demonstrated a peripheral and simultaneous central contrast enhancement in the early phase, which seems to be characteristic of lung cancer. In comparison to preoperative imaging, Io-CEUS was on par with the detection of malignancy and offers an additional tool for the intraoperative assessment of lung cancer before resection.

Priorities and strategy for the implementation of enhanced recovery after surgery (ERAS) in thoracic surgery.

Background: Enhanced recovery after surgery (ERAS) is a perioperative care protocol, which was introduced several years ago and has gained increasing importance in thoracic surgery. The aim of this study was to provide guidance through clinical implementation and to identify factors for better compliance. Methods: This prospective cohort study collected data between July 2021 and June 2022 at the Department of Thoracic Surgery (University Hospital Regensburg, Germany). A modified enhanced recovery after thoracic surgery (ERATS) protocol with recommendations covering the pre-, intra- and postoperative phases was established and followed. The primary objective was to evaluate the implementation of the ERATS protocol. Secondary, specific and clinically relevant recommendations were analyzed regarding their compliance. Results: The study included 139 patients undergoing elective lung resections. Many ERATS recommendations were already part of standard perioperative care, including perioperative antibiotics, venous thromboembolism prophylaxis and intraoperative warming. Other measures such as anemia management, carbohydrate loading or chest drain management were updated or newly established and standardized according to our ERATS protocol. The recommendations emphasizing early postoperative mobilization were found to be crucial. We identified three groups with significantly different compliance rates: (I) patient-dependent measures which require active participation (49.3%); (II) treatment measures requiring interdisciplinary consensus (85.8%); and (III) surgical measures (88%). Conclusions: The implementation and continuous evaluation of our perioperative ERATS protocol led to a new categorization of targeted measures into three groups with actors of different competencies. The new grouping enables gradual implementation and a step-by-step targeted approach in order to achieve a higher compliance of ERATS in the future as well as long-term sustainability.

Mate choice in the brain: species differ in how male traits 'turn on' gene expression in female brains.

Mate choice plays a fundamental role in speciation, yet we know little about the molecular mechanisms that underpin this crucial decision-making process. Stickleback fish differentially adapted to limnetic and benthic habitats are reproductively isolated and females of each species use different male traits to evaluate prospective partners and reject heterospecific males. Here, we integrate behavioural data from a mate choice experiment with gene expression profiles from the brains of females actively deciding whether to mate. We find substantial gene expression variation between limnetic and benthic females, regardless of behavioural context, suggesting general divergence in constitutive gene expression patterns, corresponding to their genetic differentiation. Intriguingly, female gene co-expression modules covary with male display traits but in opposing directions for sympatric populations of the two species, suggesting male displays elicit a dynamic neurogenomic response that reflects known differences in female preferences. Furthermore, we confirm the role of numerous candidate genes previously implicated in female mate choice in other species, suggesting evolutionary tinkering with these conserved molecular processes to generate divergent mate preferences. Taken together, our study adds important new insights to our understanding of the molecular processes underlying female decision-making critical for generating sexual isolation and speciation.

Extinction training suppresses activity of fear memory ensembles across the hippocampus and alters transcriptomes of fear-encoding cells.

Contextual fear conditioning has been shown to activate a set of "fear ensemble" cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells-the "extinction ensemble." Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.

The evolution of exceptional diversity in parental care and fertilization modes in ray-finned fishes.

Among vertebrates, ray-finned fishes (Actinopterygii) display the highest diversity in parental care, and their diversification has been hypothesized to be related to phylogenetic changes in fertilization modes. Using the most comprehensive, sex-specific data from 7,600 species of 62 extant orders of ray-finned fishes, we inferred ancestral states and transitions among care types and caring episodes (i.e., the stage of offspring development). Our work has uncovered 3 novel findings. First, transitions among different care types (i.e., male-only care, female-only care, biparental care, and no care) are common, and the frequencies of these transitions show unusually diverse patterns concerning fertilization modes (external, or internal via oviduct, mouth, or brood pouch). Second, both oviduct and mouth fertilization are selected for female-biased care, whereas fertilization in a brood pouch is selected for male-biased care. Importantly, internal fertilization without parental care is extremely unstable phylogenetically. Third, we show that egg care in both sexes is associated with nest building (which is male-biased) and fry care (which is female-biased). Taken together, the aquatic environment, which supports considerable flexibility in care, facilitated the diversification of parenting behavior, creating the evolutionary bases for more comprehensive parenting to protect offspring in semiterrestrial or terrestrial environments.

[Management of Malignant Pleural Effusion]. / Management des malignen Pleuraergusses.

Malignant pleural effusion is a common diagnosis in metastasized cancers. It is always of palliative character. Main symptoms are dyspnoea and reduced quality of life. Diagnosis is made by ultrasound-guided puncture of the pleural effusion (cytology) and often video-assisted thoracic surgery with biopsy of the pleural surface (histology). The goal of treatment is a fast, sustainable, minimally invasive, patient-centred therapy that increases quality of life. Besides systemic therapy and best supportive care the patient can be treated with local therapy including either pleurodesis (via drainage or VATS) or an indwelling-pleural catheter (IPC). Decision for one of these procedures is made upon performance index (ECOG), expandability of the lung, prognosis and the patient's wish. For the first technique, the lung must be expandable. The latter one (IPC) can be implanted both with expandable and trapped lung. Both are similarly effective in symptom control.

Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy.

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

[Scientific Activity in German Thoracic Surgery, as Measured in Publication Output]. / Wissenschaftliche Aktivität in der deutschen Thoraxchirurgie gemessen an der Publikationsleistung.

Thoracic surgery in Germany is primarily provided in non-university centres with a clinical focus and less at university hospitals. The extent to which scientific activity can be achieved within these different structures is investigated on the basis of publication output.A PubMed analysis was carried out for selected authors (leader in thoracic surgery in Germany) between Jan 2012 to Dec 2021. University hospitals, DKG-certified lung cancer centres (DKG: German Cancer Society) and DGT-certified thoracic centres (DGT: German Society for Thoracic Surgery) were included.An analysis of n = 54 non-university centres (DKG certificate n = 50 and/or DGT certificate n = 22) and n = 36 university hospitals (n = 9 autonomous clinic/department) was performed. A total of n = 2414 publications were identified, with original papers (n = 1776; 74%) and publications focussing on thoracic surgery (n = 1501; 62%) being found most frequently. The publication performance of the non-university centres was n = 599 publications (11/centre) and thus significantly lower than that of the university hospitals (n = 902; 25/clinic; p ≤ 0.001). Significantly higher publication output was confirmed for autonomous (n = 560; 62/clinic) compared to non-autonomous university thoracic surgery (n = 342; 13/clinic; p = 0.003). A 10-year trend was recorded, with almost doubling of publication output from n = 105 (university: n = 63) to n = 203 (university: n = 124) publications/year. The cumulative impact factors (IF) resulted in 2845 IF (52.7 IF/clinic) for non-university centres, 6361 IF (235.6 IF/clinic) for non-autonomous and 2931 IF (325.7 IF/clinic) for autonomous university thoracic surgery.Scientific activities have increased in non-university centres, but above all in university thoracic surgery. These positive developments are in acute danger due to the upcoming political changes (Hospital Structure Act, minimum volumes). Structural changes such as independent university thoracic surgery or cooperation models with non-university centres could offer solutions.

Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells.

Contextual fear conditioning has been shown to activate a set of "fear ensemble" cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells - the "extinction ensemble." Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.

Outcome after cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy in patients with secondary pleural metastases.

Background: The role of cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (CRS+HITOC) for patients with secondary pleural metastases has scarcely been investigated. Patients and Methods: We conducted a retrospective, multicentre study investigating the outcome of CRS+HITOC for 31 patients with pleural metastases from different primary tumours in four high-volume departments of thoracic surgery in Germany. The primary endpoint was overall survival (OS). Secondary endpoints included postoperative complications and recurrence/progression-free survival (RFS/PFS). Results: The primary tumour was non-small cell lung cancer in 12 (39%), ovarian cancer in 5 (16%), sarcoma in 3 (10%), pseudomyxoma peritonei in 3 (10%), and others in 8 (26%) patients. A macroscopic complete resection (R/1) could be achieved in 28 (90%) patients. Major postoperative complications as classified by Clavien-Dindo (III-V) were observed in 11 (35%) patients. The postoperative mortality rate was 10% (n=3). A total of 13 patients received additive chemotherapy (42%). The median time of follow up was 30 months (95% CI = 17- 43). The median OS was 39 months (95% CI: 34-44 months) with 1-month, 3-month, 1-, 3-, and 5-year survival estimates of 97%, 89%, 77%, 66%, and 41%. There was a significantly prolonged OS in patients who received additive chemotherapy compared to patients with only CRS+HITOC (median OS 69 vs 38 months; p= 0.048). The median RFS was 14 months (95% CI: 7-21 months). Conclusions: We observed that CRS+HITOC is a feasible approach with reasonable complications and prolonged survival as a part of multimodal concept for highly selected patients with secondary pleural metastases.

The Excretion of Cisplatin after Hyperthermic Intrathoracic Chemotherapy.

Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.

Diagnosis of sarcopenia on thoracic computed tomography and its association with postoperative survival after anatomic lung cancer resection.

Computer tomography-derived skeletal muscle index normalized for height in conjunction with muscle density enables single modality-based sarcopenia assessment that accounts for all diagnostic criteria and cutoff recommendations as per the widely accepted European consensus. Yet, the standard approach to quantify skeletal musculature at the third lumbar vertebra is limited for certain patient groups, such as lung cancer patients who receive chest CT for tumor staging that does not encompass this lumbar level. As an alternative, this retrospective study assessed sarcopenia in lung cancer patients treated with curative intent at the tenth thoracic vertebral level using appropriate cutoffs. We showed that skeletal muscle index and radiation attenuation at level T10 correlate well with those at level L3 (Pearson's R = 0.82 and 0.66, p < 0.001). During a median follow-up period of 55.7 months, sarcopenia was independently associated with worse overall (hazard ratio (HR) = 2.11, 95%-confidence interval (95%-CI) = 1.38-3.23, p < 0.001) and cancer-specific survival (HR = 2.00, 95%-CI = 1.19-3.36, p = 0.009) of lung cancer patients following anatomic resection. This study highlights feasibility to diagnose sarcopenia solely by thoracic CT in accordance with the European consensus recommendations. The straightforward methodology offers easy translation into routine clinical care and potential to improve preoperative risk stratification of lung cancer patients scheduled for surgery.

Tracheoesophageal Fistula Closure in a Pediatric Patient Using a Supraclavicular Artery Island Flap.

Acquired tracheoesophageal fistulas can lead to large defects with fatal complications. Surgical management is challenging but necessary to prevent respiratory infections and poor weight gain. Therefore, a reliable and pliable flap like the pedicled supraclavicular artery island flap with its wide arc of rotation and robust vascularization is needed for reconstruction. We highlight the surgical technique and postoperative measures in managing a tracheoesophageal fistula due to button battery ingestion in a 9-month-old boy with the supraclavicular artery island flap. In summary, the supraclavicular artery island flap is a safe and successful tool for closure of large acquired tracheoesophageal fistulas in pediatric patients.

Intraoperative Contrast-Enhanced Ultrasonography (Io-CEUS) in Minimally Invasive Thoracic Surgery for Characterization of Pulmonary Tumours: A Clinical Feasibility Study.

BACKGROUND: The intraoperative detection of solitary pulmonary nodules (SPNs) continues to be a major challenge, especially in minimally invasive video-assisted thoracic surgery (VATS). The location, size, and intraoperative frozen section result of SPNs are decisive regarding the extent of lung resection. This feasibility study investigates the technical applicability of intraoperative contrast-enhanced ultrasonography (Io-CEUS) in minimally invasive thoracic surgery. METHODS: In this prospective, monocentric clinical feasibility study, n = 30 patients who underwent Io-CEUS during elective minimally invasive lung resection for SPNs between October 2021 and February 2023. The primary endpoint was the technical feasibility of Io-CEUS during VATS. Secondary endpoints were defined as the detection and characterization of SPNs. RESULTS: In all patients (female, n = 13; mean age, 63 ± 8.6 years) Io-CEUS could be performed without problems during VATS. All SPNs were detected by Io-CEUS (100%). SPNs had a mean size of 2.2 cm (0.5-4.5 cm) and a mean distance to the lung surface of 2.0 cm (0-6.4 cm). B-mode, colour-coded Doppler sonography, and contrast-enhanced ultrasound were used to characterize all tumours intraoperatively. Significant differences were found, especially in vascularization as well as in contrast agent behaviour, depending on the tumour entity. After successful lung resection, a pathologic examination confirmed the presence of lung carcinomas (n = 17), lung metastases (n = 10), and benign lung tumours (n = 3). CONCLUSIONS: The technical feasibility of Io-CEUS was confirmed in VATS before resection regarding the detection of suspicious SPNs. In particular, the use of Doppler sonography and contrast agent kinetics revealed intraoperative specific aspects depending on the tumour entity. Further studies on Io-CEUS and the application of an endoscopic probe for VATS will follow.

Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression.

The cellular basis of the apparent aggressiveness in lung cancer is poorly understood but likely associated with functional or molecular features of disseminated cancer cells (DCCs). DCCs from epithelial cancers are mostly detected by antibodies directed against histogenetic markers such as cytokeratin or EpCAM. It has been argued that marker-negative metastatic founder cells might escape detection. We therefore used ex vivo sphere formation for functional detection of candidate metastasis founders. We generated cell suspensions from 199 LN samples of 131 lung cancer patients and placed them into non-adherent cell culture. Sphere formation was associated with detection of DCCs using EpCAM immunocytology and with significantly poorer prognosis. The prognostic impact of sphere formation was strongly associated with high numbers of EpCAM-positive DCCs and aberrant genotypes of expanded spheres. We also noted sphere formation in patients with no evidence of lymphatic spread, however such spheres showed infrequent expression of signature genes associated with spheres from EpCAM-positive samples and displayed neither typical lung cancer mutations (KRAS, TP53, ERBB1) nor copy number variations, but might be linked to disease progression >5 years post curative surgery. We conclude that EpCAM identifies relevant disease-driving DCCs, that such cells can be expanded for model generation and that further research is needed to clarify the functional and prognostic role of rare EpCAM-negative sphere forming cells.

Intraoperative ultrasound in minimally invasive thoracic surgery for the detection of pulmonary tumors: First intrathoracic application of TE9 and laparoscopic probe Lap 13-4cs (Mindray).

AIM: To apply intraoperative ultrasound (IO-US) for the first time using a laparascopic probe to detect malignancy-susceptible solitary pulmonary nodules (SPN) and assess macrovascularization using color-coded doppler sonography or power doppler. Description of technical feasibility. METHODS: Technical description on intrathoracic endoscopic ultrasound. A positive ethics vote from the local ethics committee and written patient consent were available. Intraoperative ultrasound was performed using a laparascopic probe (Lap 13-4cs, Mindray) on the T9 ultrasound machine (Mindray, China). B-scan was used to detect the SPN. Color-coded doppler sonography (CCS) and power doppler were used to assess macrovascularization. Primary end point was the description of the technical performance of the Io-US. Secondary endpoints were the functions of Io-US in characterizing SPN. RESULTS: Io-US was successfully applied using (n = 2) cases in video-assisted thoracic surgery. All SPN were successfully detected intraoperatively with the intrathoracically placed laparascopy probe using B-mode and examined using CCS or power Doppler (100%). Resection was sonography-guided with marking of the tumor area in all cases without complications. Histological workup revealed malignancy in both cases. CONCLUSION: Intrathoracic application of laparascopically guided Io-US was technically feasible. In addition to B-mode detection, Io-US using power doppler and color-coded doppler sonography provided initial evidence for characterization of SPN based on macrovascularization.

Surgical cytoreduction and hyperthermic intrathoracic chemotherapy for thymic tumours with pleural spread is effective on survival: results from the multicentre German hyperthermic intrathoracic chemotherapy study.

OBJECTIVES: Cytoreductive surgery and hyperthermic intrathoracic chemotherapy (HITOC) is effective on survival for patients with pleural metastatic thymic tumours. METHODS: Multicentre, retrospective analysis of patients with stage IVa thymic tumours treated with surgical resection and HITOC. Primary end point was overall survival, secondary end points were recurrence-/progression-free survival and morbidity/mortality. RESULTS: A total of n = 58 patients (thymoma, n = 42; thymic carcinoma, n = 15; atypical carcinoid of the thymus, n = 1) were included, who had primary pleural metastases (n = 50; 86%) or pleural recurrence (n = 8; 14%). Lung-preserving resection (n = 56; 97%) was the preferred approach. Macroscopically complete tumour resection was achieved in n = 49 patients (85%). HITOC was performed with cisplatin alone (n = 38; 66%) or in combination with doxorubicin (n = 20; 34%). Almost half of the patients (n = 28; 48%) received high-dose cisplatin > 125 mg/m2 body surface area. Surgical revision was required in 8 (14%) patients. In-hospital mortality rate was 2%. During follow-up, tumour recurrence/progression was evident in n = 31 (53%) patients. Median follow-up time was 59 months. The 1-, 3- and 5-year survival rates were 95%, 83% and 77%, respectively. Recurrence/progression-free survival rates were 89%, 54% and 44%, respectively. Patients with thymoma had significantly better survival compared to patients with thymic carcinoma (P-value ≤0.001). CONCLUSIONS: Promising survival rates in patients with pleural metastatic stage IVa in thymoma (94%) and even in thymic carcinoma (41%) were achieved. Surgical resection and HITOC is safe and effective for treatment of patients with pleural metastatic thymic tumours stage IVa.

Crystal Structure and NMR of an α,δ-Peptide Foldamer Helix Shows Side-Chains are Well Placed for Bifunctional Catalysis: Application as a Minimalist Aldolase Mimic.

We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before. Critically, the helix type realized places the α-residue functionalities in positions proximal enough to engage in bifunctional catalysis as demonstrated in the application of our system as a minimalist aldolase mimic.

The Promise of an Evolutionary Perspective of Alcohol Consumption.

The urgent need for medical treatments of alcohol use disorders has motivated the search for novel molecular targets of alcohol response. Most studies exploit the strengths of lab animals without considering how these and other species may have adapted to respond to alcohol in an ecological context. Here, we provide an evolutionary perspective on the molecular and genetic underpinnings of alcohol consumption by reviewing evidence that alcohol metabolic enzymes have undergone adaptive evolution at 2 evolutionary junctures: first, to enable alcohol consumption accompanying the advent of a frugivorous diet in a primate ancestor, and second, to decrease the likelihood of excessive alcohol consumption concurrent with the spread of agriculture and fermentation in East Asia. By similarly considering how diverse vertebrate and invertebrate species have undergone natural selection for alcohol responses, novel conserved molecular targets of alcohol are likely be discovered that may represent promising therapeutic targets.