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Childhood obesity is a serious public health crisis and a critical factor that determines future obesity prevalence. Signals affecting adipocyte development in early postnatal life have a strong potential to trigger childhood obesity; however, these signals are still poorly understood. We show here that mitochondrial (mt)RNA efflux stimulates transcription of nuclear-encoded genes for mitobiogenesis and thermogenesis in adipocytes of young mice and human infants. While cytosolic mtRNA is a potential trigger of the interferon (IFN) response, young adipocytes lack such a response to cytosolic mtRNA due to the suppression of IFN regulatory factor (IRF)7 expression by vitamin D receptor signalling. Adult and obese adipocytes, however, strongly express IRF7 and mount an IFN response to cytosolic mtRNA. In turn, suppressing IRF7 expression in adult adipocytes restores mtRNA-induced mitobiogenesis and thermogenesis and eventually mitigates obesity. Retrograde mitochondrion-to-nucleus signalling by mtRNA is thus a mechanism to evoke thermogenic potential during early adipocyte development and to protect against obesity.

Background: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. Materials and methods: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. Results: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. Conclusions: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required. Open access funding provided by University of Szeged. This study has been funded by FEDER funds through the Competitiveness Factors Operational Program (COMPETE) and by national funds through the Foundation for Science and Technology (FCT) within the scope of project No. POCI-01–0145-FEDER-007038, as well as by project No. NORTE-01–0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020) under the Portugal 2020 Partnership Agreement through the European Regional Development Fund (FEDER).

Absztrakt Bevezetés: A kóros elhízás és az okozott társbetegségek, elsősorban a 2-es típusú diabetes prevalenciája az elmúlt évtizedekben rohamos növekedésnek indult. Miután a konzervatív kezelési módszerek (diéta, tréning) legtöbbször nem hoznak megoldást, egyre nagyobb az igény a metabolikus sebészeti beavatkozásokra. Módszer: Osztályunkon az elmúlt hat és fél évben 514 laparoszkópos Roux Y gyomorbypassműtétet (LRYGB) és 54 laparoszkópos gyomorsleeve-reszekciót (LGSR) végeztünk. Random kiválasztott 40, gyomorbypassműtéten és 15 sleeve-reszekción átesett beteg adatait dolgoztuk fel. Ismertetésre kerülnek az alkalmazott indikációs kritériumok, a pre- és posztoperatív rutineljárások, az elért eredmények, illetve a komplikációk típusa és aránya. Eredmények: Tapasztalataink alapján mindkét műtéti beavatkozás relatív alacsony szövődményráta mellett végezhető és hosszú távon is hatékony mind a testsúlycsökkenés, mind a társbetegségek javulásának vonatkozásában. Gyomorbypass után nagyobb mértékű fogyást (testsúlyfelesleg-csökkenés 88% vs. 68%) és a 2-es típusú diabetes, a hypertonia és a gastrooesophagealis reflux magasabb arányú javulását tapasztaltuk a sleeve-reszekcióhoz viszonyítva. Konklúzió: Eredményeink alapján az LRYGB-t részesítjük előnyben, sleeve-reszekciót akkor indikálunk, amikor bypass végzésére nincs, illetve csak magas rizikó mellett volna lehetőség, természetesen figyelembe véve a beteg ez irányú, egyénre szabott igényeit is.

Intubation of the tracheobronchial tree is the most common type of malposition during the placement of narrow-bore enternal tubes.In addition to other treatment components in a 65-year-old female, nasojejunal feeding was started to treat her for severe acute pancreatitis. After the placement of the narrow-bore feeding tube, she developed dyspnea and huskiness. On auscultation and X-ray investigation, the right pneumothorax was detected and the tube was found in the chest cavity. The diagnosis was confirmed by bronchoscopy. Videothoracoscopic resection and closure of the lacerated lung, using a tube thoracostomy, were performed. The patient recovered after postoperative conservative treatment for her pancreatitis.Pneumothorax and laceration of the lung-caused by the malposition of narrow-bore enternal tube-can be successfully treated by applying videothoracoscopy.

Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that allows near-real-time characterization of human tissue in vivo by analysis of the aerosol ("smoke") released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.

Dual-laser flow cytometric resonance energy transfer (FCET) is a statistically efficient and accurate way of determining proximity relationships for molecules of cells even under living conditions. In the framework of this algorithm, absolute fluorescence resonance energy transfer (FRET) efficiency is determined by the simultaneous measurement of donor-quenching and sensitized emission. A crucial point is the determination of the scaling factor α responsible for balancing the different sensitivities of the donor and acceptor signal channels. The determination of α is not simple, requiring preparation of special samples that are generally different from a double-labeled FRET sample, or by the use of sophisticated statistical estimation (least-squares) procedures. We present an alternative, free-from-spectral-constants approach for the determination of α and the absolute FRET efficiency, by an extension of the presented framework of the FCET algorithm with an analysis of the second moments (variances and covariances) of the detected intensity distributions. A quadratic equation for α is formulated with the intensity fluctuations, which is proved sufficiently robust to give accurate α-values on a cell-by-cell basis in a wide system of conditions using the same double-labeled sample from which the FRET efficiency itself is determined. This seemingly new approach is illustrated by FRET measurements between epitopes of the MHCI receptor on the cell surface of two cell lines, FT and LS174T. The figures show that whereas the common way of α determination fails at large dye-per-protein labeling ratios of mAbs, this presented-as-new approach has sufficient ability to give accurate results. Although introduced in a flow cytometer, the new approach can also be straightforwardly used with fluorescence microscopes.

Background: Minimal technologies exist that provide tissue specific molecular information to the surgeon in real-unsupervised principal components time. Rapid evaporative ionization mass spectrometry allows near real-time characterization of tissue by mass spectrometric analysis of the smoke plume released during electrosurgical dissection. Objectives: To develop and optimize a statistical strategy for the real-time recognition of cancer margin status during surgical excision of liver metastases. Methods: Fresh tissue samples from 25 patients with liver metastasis from colorectal adenocarcinoma were collected and analyzed using monopolar diathermy coupled to ion trap mass spectrometry. At the point of rapid evaporation of tissues during electrosurgical dissection, tissue specific charged particles are formed and these ionized molecular species are transferred within the diathermy plume to the mass spectrometer using Venturi air jet pump and PTFE tubing. Intense spectral profiles are produced (m/z range: 600-900) which are associated with the structural phospholipid content of tissues and vary significantly between the distinct histological tissue types. Results: The resulting dataset was analyzed by unsupervised principal components analysis for explorative analysis of similarities/differences in molecular ion composition between samples. The maximum margin criterion analysis, a supervised dimension reduction technique, was subsequently applied to extract tissue specific discriminating molecular ion patterns. The 3-nearest neighbour classification algorithm was applied on a reduced set of discriminant features and 10-fold cross validation carried out. Discrimination of healthy and malignant tissue was possible with a sensitivity of 96.8% and cross validation demonstrated the validity of the supervised methods. Conclusion: When paired with real-time data analysis, the iKnife is a viable potential method of real-time tissue identification including the intra-operative assessment of oncological resection margins.

Authors present two cases of successfully operated patients with retrohepatic inferior vena cava (IVC) injury. In the first case a 79 year old female patient suffered from multiple stab wounds in the area of the 4th segment of the right lung as well as in the retrohepatic region in close proximity to the IVC. At the time of the first surgery the IVC injury was not identified. During a second operation, however, the IVC was isolated from the liver using an anterior dissection of the parenchyma with finger-fracture technique and the injury was oversawn finally. Successful haemostasis of the liver was achieved by packing of the perihepatic space, which was removed three days later. In the second case a 25 year-old male patient had suffered blunt abdominal trauma. He underwent laparotomy and packing on the site of the hepatic injury, which had to be repeated seven more times. Later on, another urgent laparotomy was carried out for recurring intraabdominal bleeding and bile leakage, and cholecystectomy was performed due to gallbladder perforation. Another two days later a further emergency laparotomy was indicated for ongoing intraabdominal bleeding, when the bleeding source - an injury (3 mm in diameter) of the retrohepatic IVC - was oversawn. After relatively long postoperative stay both patients were fully recovered and discharged from hospital.penetrating injuries of the IVC are associated with high mortality rate of approximately 78%. Proper management of these injuries requires experience in both vascular and liver surgery. Retrohepatic IVC injury needs to be considered in the differential diagnosis of ongoing bleeding in penetrating or blunt liver trauma. Packing of the liver is a reliable haemostatic method if bleeding persists due to division of the liver parenchyma.

Absztrakt Esetismertetés: A szerzők két sikeresen operált beteg esetét ismertetik. A 79 éves anticoagulált nőbeteg többszörös mellkasi és hasi szúrt sérülést szenvedett, a jobb tüdő IV. szegmentumának és a vena cava inferior retrohepaticus szakaszának szúrt sérülését látták el. Az első műtét során a cava sérülését nem ismerték fel. A második műtét során a máj anterograd, finger-fracture technikával történt szétválasztását követően sikerült a cava sérülését feltárni és elvarrni. A máj állományának sebét perihepaticus packing módszerrel tamponálták. A 3. posztoperatív napon újabb műtét során a tampon eltávolítását végezték. A beteg meggyógyult. Egy másik, 25 éves férfi beteg tompa hasi sérülést szenvedett. Első ellátásként a májruptura tamponálása történt. Ezt követően sorozatos (7×) tamponcserékre került sor. Ismételten jelentkező hasüregi vérzés és epefolyás miatti reoperációkor az epehólyagon lévő kb. 1 mm-es perforatiós nyílás miatt cholecystectomia történt. Két nappal később ismételt vérzés miatt végzett haematomaevakuálás után a vena cava inferior retrohepaticus szakaszán lévő, kb. 3 mm-es sérülés elvarrása történt. Posztoperatív epefolyás miatt EST történt. A beteg gyógyultan otthonába távozott. Megbeszélés: Az áthatoló retrohepaticus vena cava sérülések mortalitása magas, mintegy 78%-ra tehető. A sérülés ellátása nemcsak érsebészeti, hanem májsebészeti jártasságot is igényel. A máj szúrt és tompa sérülésének ellátása során gondolni kell a vena cava inferior retrohepaticus szakaszának sérülésére is. A sérülés elvarrása gyógyuláshoz vezet. A parenchyma szétválasztása utáni vérzés perihepaticus „packing” módszerrel megbízhatóan kezelhető. A posztoperatív epefolyás EST-vel sikeresen kezelhető.

The newly developed rapid evaporative ionization mass spectrometry (REIMS) provides the possibility of in vivo, in situ mass spectrometric tissue analysis. The experimental setup for REIMS is characterized in detail for the first time, and the description and testing of an equipment capable of in vivo analysis is presented. The spectra obtained by various standard surgical equipments were compared and found highly specific to the histological type of the tissues. The tissue analysis is based on their different phospholipid distribution; the identification algorithm uses a combination of principal component analysis (PCA) and linear discriminant analysis (LDA). The characterized method was proven to be sensitive for any perturbation such as age or diet in rats, but it was still perfectly suitable for tissue identification. Tissue identification accuracy higher than 97% was achieved with the PCA/LDA algorithm using a spectral database collected from various tissue species. In vivo, ex vivo, and post mortem REIMS studies were performed, and the method was found to be applicable for histological tissue analysis during surgical interventions, endoscopy, or after surgery in pathology.

A paraesophageal hernia was diagnosed in a 67-year-old female patient suffering from epigastric pain and gastroesophageal reflux disease. The patient underwent laparoscopy. Beside the paraesophageal hernia, a Morgagni hernia was also observed, with a significant part of the omentum herniated in the sac. A 360-degree Nissen fundoplication was performed, the Morgagni hernia sac was not resected, and its closure was performed with interrupted sutures. No complications were observed in the postoperative period and on one-year follow-up the patient was free of symptoms.