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Abstract The coronavirus disease 2019 pandemic had a major impact on most medical services. Our aim was to assess the outcome of acute cholecystitis during the nationwide lockdown period. All patients admitted to our emergency department for AC were analysed. Patient characteristics, performance status, AC severity, treatment modality and outcome of AC were assessed during the lockdown period (Period II: 1 April 2020–30 November 2021) and compared to a historical control period (Period I: 1 May 2017–31 December 2018). AC admissions increased by 72.8% in Period II. Patients were younger (70 vs. 74 years, p = 0.017) and greater in number in the CCI 1 group (20.4% vs. 11.2%, p = 0.043) in Period II. The unplanned readmission rate (6.3 vs. 0%, p = 0.004) and the gallbladder perforation (GP) rate was higher (18.0 vs. 7.3%, p = 0.006) in Period II. Percutaneous transhepatic gallbladder drainage (PTGBD) was more frequent (24.1 vs. 12.8%, p = 0.012) in Period II. In addition to a drop in patient age and CCI, a significant rise in the prevalence of acute cholecystitis, GP and unplanned readmissions was observed during the nationwide lockdown due to the COVID-19 pandemic. PTGBD was more frequent during this period, whereas successful conservative treatment was less frequent.

Firn from an ice cave in the highest mountain of Greece, Mount Olympus, was sampled and analyzed to determine the tritium content in order to estimate rates of accumulation and to date the ice plug. The presence of a sharp raise of tritium content indicating the nuclear testing era was expected to be preserved into ice beds. Tritium concentrations were found to vary from 0.9 to 11 TU. This peak did not appear in the analyzed samples, providing an upper age limit of less than 50 years for the oldest sampled layer. It is suggested that the rate of melting is responsible for the absence of older firn layers.

Hydrogen may represents a good alternative fuel that can be used to fuel internal combustion engines in order to ameliorate energetic and emissions performance. The paper presents some experimental aspects registered at hydrogen use to fuel a diesel engine, different substitute ratios being use in the area of 18–34%, at 40% engine load and speed of 2000 rev/min. The engine is equipped with an open ECU and the control of the cyclic dosses of diesel fuel and hydrogen are adjusted in order to maintain the engine power performance. The in-cylinder pressure diagrams show the increase of the maximum pressure with 17%, from 78.5 bar to 91.8 bar for the maximum substitute ratio. Also, values of maximum pressure rise rate start to increase for hydrogen addition, in correlation with the increase of fuel amount burned into the premixed stage, without exceed the normal values with assure the normal and reliable engine operation. Higher Lower Heating Value and combustion speed of hydrogen assure the increase in thermal efficiency, the brake specific energy consumption decreases with 5.4%–7.8% at substitute ratios of 20–27%. The CO2 emission level decreases with 20% for maximum hydrogen cyclic dose. In terms of pollutant emission level, at hydrogen use the emission level of the NOx decreases with 50% and the smoke number decreases with 73.8% comparative to classic fuelling at the maximum hydrogen cyclic dose.

We investigate a non-supersymmetric SO(10)×U(1)PQ axion model in which the spontaneous breaking of U(1)PQ occurs after inflation, and the axion domain wall problem is resolved by employing the Lazarides-Shafi mechanism. This requires the introduction of two fermion 10-plets, such that the surviving discrete symmetry from the explicit U(1)PQ breaking by QCD instantons is reduced from Z12 to Z4, where Z4 coincides with the center of SO(10) (more precisely Spin(10)). An unbroken Z2 subgroup of Z4 yields intermediate scale topologically stable strings, as well as a stable electroweak doublet non-thermal dark matter candidate from the fermion 10-plets with mass comparable to or somewhat smaller than the axion decay constant fa. We present an explicit realization with inflation taken into account and which also incorporates non-thermal leptogenesis. The fermion dark matter mass lies in the 3×108−1010GeV range and its contribution to the relic dark matter abundance can be comparable to that from the axion.

Abstract Background The optimal prehospital fluid for the treatment of hypotension is unknown. Hypertonic fluids may increase circulatory volume and mute the pro-inflammatory response of the body to injury and illness. The purpose of this systematic review is to determine whether in patients presenting with hypotension in the prehospital setting (population), the administration of hypertonic saline (intervention), compared to an isotonic fluid (control), improves survival to hospital discharge (outcome). Methods Searches were conducted in Medline, Embase, CINAHL, and CENTRAL from the date of database inception to November, 2016, and included all languages. Two reviewers independently selected randomized control trials of hypotensive human participants administered hypertonic saline in the prehospital setting. The comparison was isotonic fluid, which included normal saline, and near isotonic fluids such as Ringer’s Lactate. Assessment of study quality was done using the Cochrane Collaborations’ risk of bias tool and a fixed effect meta-analysis was conducted to determine the pooled relative risk of survival to hospital discharge. Secondary outcomes were reported for fluid requirements, multi-organ failure, adverse events, length of hospital stay, long term survival and disability. Results Of the 1160 non-duplicate citations screened, thirty-eight articles underwent full-text review, and five trials were included in the systematic review. All studies administered a fixed 250 ml dose of 7.5% hypertonic saline, except one that administered 300 ml. Two studies used normal saline, two Ringer’s Lactate, and one Ringer’s Acetate as control. Routine care co-interventions included isotonic fluids and colloids. Five studies were included in the meta-analysis (n = 1162 injured patients) with minimal statistical heterogeneity (I 2 = 0%). The pooled relative risk of survival to hospital discharge with hypertonic saline was 1.02 times that of patients who received isotonic fluids (95% Confidence Interval: 0.95, 1.10). There were no consistent statistically significant differences in secondary outcomes. Conclusions There was no significant difference in important clinical outcomes for hypotensive injured patients administered hypertonic saline compared to isotonic fluid in the prehospital setting. Hypertonic saline cannot be recommended for use in prehospital clinical practice for the management of hypotensive injured patients based on the available data. PROSPERO registration # CRD42016053385 .

The theory that we shall seek to elaborate here puts considerable emphasis on technological features of China’s steel production, its emergence as the world’s most significant steel producer and main manufacturing base, and the transitory decline in steel demand related to the international financial crisis. The purpose of this article is to gain a deeper understanding of the global incorporation of China’s steel enterprises, its portion of worldwide steel consumption, and its industrial policy scheme for the steel sector. This research makes conceptual and methodological contributions to the steel products supply chain in China, the deficiencies of production overcapacity and atomization in China’s steel industry, and market chances for the Chinese steel sector.

The aim of the present research is to examine and evaluate the swift growth in surplus steel production capacity and international supply chain integration, the effects of steel manufacturing on U.S. employment, raising imports of unfairly traded steel and steel goods, and the global steel sector’s structural overcapacity. This paper contributes to the literature by providing evidence on the mechanisms forming the foundation of the first-rate productivity growth in the U.S. steel industry, models of growth in the international steel supply chains, and the advantages of adequate trade remedy implementation for the U.S. steel sector.

The documentation surrounding ISO 9000 in education indicates that the application of this quality management system to education is debatable; the implementation process is time-consumming. The application of ISO 9000 in education is difficult because of interpretation problems. SR ISO IWA 2: Quality management systems - Guidelines for the application of ISO 9001:2000 in education, made the standard easier to understand and implement by the education sector.

The objective of this study was to examine the alkaline, acidic phosphatase and nonspecific esterase activity in the epithelial cells of oviducts after exposure to polychlorinated biphenyls (PCBs) at the time of puerperium. PCBs were administered in the last days of pregnancy and during early puerperium. Animals in the experimental group were exposed to Delor 105 at a dose of 100 μg/kg/day and were euthanised on Day 17 postpartum (n = 4), i.e. 5 days after the termination of 30-day PCB administration; on Day 25 postpartum (n = 5), i.e. 17 days from the last PCB administration and on Day 34 postpartum (n = 5), which corresponded to Day 28 from the completion of PCB administration. Ewes in the control group were euthanised on Day 17 (n = 3), Day 25 (n = 4) and Day 34 (n = 4) postpartum. The authors demonstrated the inhibitory effect of PCB on the enzymatic system of the oviduct during the puerperal period. The alkaline phosphatase, acidic phosphatase and nonspecific esterase activity in the oviductal epithelial cells during a 34-day observation period exhibited a rising trend (P < 0.001 vs. P < 0.001 vs. P < 0.01) in the control group of animals. Experimental animals exposed to the 30-day PCB administration (Delor 105) showed a stagnant tendency (P > 0.05) in alkaline phosphatase while acidic phosphatase and nonspecific esterase activity (P > 0.05) dropped even below the level of their activity values in the control group. It is essential to continue to monitor the effect of pollutants in exposed industrial areas on reparative and regenerative processes in puerperium and their possible impact on reproductive performance.

Purpose: Men with metabolic syndrome (MetS) have an increased prevalence of erectile dysfunction (ED). Large artery stiffness is a marker of vascular wall changes associated with MetS. Aim of the study was to investigate associations between MetS, ED and changes in large artery properties. Methods: 179 consecutive men with ED were evaluated for penile vascular disease severity by Doppler ultrasonography. Lower Doppler velocities indicate impaired arterial function and vice versa. A mean PSV below 25cm/sec was considered to indicate severe arterial insufficiency (SAI). Large artery stiffness was evaluated with carotid-femoral pulse wave velocity (PWV) using high-fidelity pulse wave analysis. Results: Patients with SAI (n=56) compared to patients with non arteriogenic ED (PSV>25cm/s, n=123) had increased prevalence of MetS (49 vs.32 % respectively, P

Se realizó un experimento en invernadero para evaluar en trigo el efecto de la inoculación con las rizobacterias Sinorhizobium meliloti, Azospirillum zeae y Azospirillum canadense, y con el hongo Trichoderma harzianum. El diseño experimental fue completamente aleatorizado, con cuatro réplicas y cinco plantas por tratamiento. Se utilizó un tratamiento fertilizado con NH4NO3 (150 ppm/kg de suelo), un control absoluto y 13 tratamientos inoculados. Se evaluó el peso seco aéreo, el peso seco radical, la longitud del tallo, la germinación y el contenido de clorofila foliar. La aplicación de Trichoderma por separado tuvo un efecto positivo en la longitud del tallo (5,58 cm); pero su presencia directa en algunas combinaciones con las bacterias rizosféricas no fue positiva ni mostró resultados uniformes en las variables en el momento de la siembra, o posterior a esta. Sin embargo, se destacó el tratamiento Trichoderma + NRG34-DS2 5d en el peso seco radical (0,45 g/planta) y en el peso seco aéreo (0,58 g/planta); así como el tratamiento A2-N7, en el contenido de clorofila (40,35 spads/planta) y la longitud del tallo (5,50 cm). Se concluye que la aplicación simple de Trichoderma no ejerció un efecto positivo en la mayoría de las variables ni los tratamientos influyeron positivamente en la germinación. Se recomienda evaluar Trichoderma + NRG34-DS2 5d y A2-N7 en experimentos de campo.

Background: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking., Aims: To examine the usability of darvadstrocel therapy in managing perianal CD., Methods: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression., Results: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported., Conclusion: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

For early-stage non-small cell lung cancer, surgical resection remains the best treatment option. Currently, sublobar resection, including segmentectomy, is recommended in these cases, as it provides a better quality of life with the same oncological outcomes; however, is requires adequate resection margins. Accurate preoperative planning and proper identification of the intersegmental planes during thoracic surgery are crucial for ensuring precise surgical management and adequate resection margins. Three dimensional computed tomography reconstruction and near-infrared-guided intersegmental plane identification can greatly facilitate the surgical procedures. Three-dimensional computed tomography reconstruction can simulate both the resection and resection margins. Indocyanine green is one of the most frequently used and affordable fluorophores. There are two ways to identify the intersegmental planes using indocyanine green: intravenous and transbronchial administration. Intravenous application is simple; however, its effectiveness may be affected by underlying lung disease, and it requires the isolation of segmental structures before administration. Transbronchial use requires appropriate bronchoscopic skills and preoperative planning; however, it also allows for delineation deep in the parenchyma and can be used for complex segmentectomies. Both methods can be used to ensure adequate resection margins and, therefore, achieve the correct oncological radicality of the surgical procedure. Here, we summarise these applications and provide an overview of their different possibilities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Libor, Pécsy, Szűcs, Lantos, Bakos, Lázár and Furak.)

Introduction: Patients undergoing thoracic surgery are at increased risk of developing, long-lasting pain. Beyond the non-surgical factors, the type of operation, including the number of incisions, and the anesthetic assessment seemed to be important factors, although some studies are controversial. The aim of our study was to examine the presence of chronic postoperative pain after non-intubated uniportal VATS lobectomy. We examined the difference between the intubated, relaxed and non-intubated spontaneous ventilation surgical approaches in patients who underwent video-assisted thoracoscopic (VATS) uniportal lobectomy., Methods: Demographic and postoperative data were retrospectively collected and analyzed, focusing on the use of pain medications, in 67 patients of the 140 patients selected by propensity score matching who underwent intubated (iVATS) or non-intubated (NITS) uniportal VATS lobectomy. This study focused on the use of analgesic medications 3, 6, and 12 months after surgery., Results: Thirty-five intubated and 32 non-intubated patients were compared. Although the analgesic consumption was nearly 2% higher among the iVATS patients during the follow-up period, there were no statistically significant differences at 3 months (15.6 vs. 17.1%) ( p  = 0.868), at 6 months (9.4 vs. 12.4%) ( p  = 0.785), and at 12 months (3.3 vs. 5.9%) ( p  = 0.633) between the NITS and iVATS groups, respectively. More female than male patients reported chronic pain, but the difference was not statistically significant ( p  = 0.616). Diabetes mellitus was a statistically significant cofactor associated with chronic pain ( p  = 0.03), while cardiac disease ( p  = 0.6), perioperative morbidity ( p  = 0.228), prolonged air leak ( p  = 0.057), and repeat drainage ( p  = 0.626) were not., Conclusion: Our study suggests that after non-intubation VATS lobectomies, the postoperative pain was less at 3, 6, and 12 months in NITS patients compared to iVATS patients. The 2% difference was not significant, so it may not be appropriate to claim the advantages of NITS in terms of postoperative pain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Farkas, Csókási, Fabó, Szabó, Lantos, Pécsy, Lázár, Rárosi, Kecskés and Furák.)

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining-from biopsy samples taken before treatment-the effectiveness of neoadjuvant chemotherapy.

Introduction: The effect of platinum-based chemotherapy (Chem.) and second- or multiple- line immune checkpoint PD-1 blocking therapy by Nivolumab or Pembrolizumab (ICI) was assayed in the peripheral blood of non-small cell lung cancer (NSCLC) patients., Methods: Flow cytometry was used to detect NSCLC-related antigen binding IgG antibodies. The Luminex MagPix multiplex bead-based cytokine/chemokine detecting system was used to quantitatively measure 17 soluble markers in the plasma samples. Single-cell mass cytometry was applied for the immunophenotyping of peripheral leukocytes., Results: The incubation of patient derived plasma with human NSCLC tumor cell lines, such as A549, H1975, and H1650, detected NSCLC-specific antibodies reaching a maximum of up to 32% reactive IgG-positive NSCLC cells. The following markers were detected in significantly higher concentration in the plasma of Chem. group versus healthy non-smoker and smoker controls: BTLA, CD27, CD28, CD40, CD80, CD86, GITRL, ICOS, LAG-3, PD-1, PD-L1, and TLR-2. The following markers were detected in significantly higher concentration in the plasma of ICI group versus healthy non-smoker and smoker controls: CD27, CD28, CD40, GITRL, LAG-3, PD-1, PD-L1, and TLR-2. We showed the induction of CD69 and IL-2R on CD4+ CD25+ T-cells upon chemotherapy; the exhaustion of one CD8+ T-cell population was detected by the loss of CD127 and a decrease in CD27. CD19+CD20+, CD79B+, or activated B-cell subtypes showed CD69 increase and downregulation of BTLA, CD27, and IL-2R in NSCLC patients following chemotherapy or ICI., Discussion: Peripheral immunophenotype caused by chemotherapy or PD-1 blocking was shown in the context of advanced NSCLC., Competing Interests: LP is the CEO of Avidin Ltd. and GS an employee of CS-Smartlab-Devices Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Neuperger, Szalontai, Gémes, Balog, Tiszlavicz, Furák, Lázár, Puskás and Szebeni.)

The coronavirus disease 2019 pandemic had a major impact on most medical services. Our aim was to assess the outcome of acute cholecystitis during the nationwide lockdown period. All patients admitted to our emergency department for AC were analysed. Patient characteristics, performance status, AC severity, treatment modality and outcome of AC were assessed during the lockdown period (Period II: 1 April 2020-30 November 2021) and compared to a historical control period (Period I: 1 May 2017-31 December 2018). AC admissions increased by 72.8% in Period II. Patients were younger (70 vs. 74 years, p = 0.017) and greater in number in the CCI 1 group (20.4% vs. 11.2%, p = 0.043) in Period II. The unplanned readmission rate (6.3 vs. 0%, p = 0.004) and the gallbladder perforation (GP) rate was higher (18.0 vs. 7.3%, p = 0.006) in Period II. Percutaneous transhepatic gallbladder drainage (PTGBD) was more frequent (24.1 vs. 12.8%, p = 0.012) in Period II. In addition to a drop in patient age and CCI, a significant rise in the prevalence of acute cholecystitis, GP and unplanned readmissions was observed during the nationwide lockdown due to the COVID-19 pandemic. PTGBD was more frequent during this period, whereas successful conservative treatment was less frequent., (© 2023. The Author(s).)

Introduction: The aim of our prospective study was to confirm validity and diagnostic accuracy of the modified Alvarado score, which was developed at the Department of Surgery, University of Szeged, on patients presenting with symptoms suggestive of acute appendicitis (right lower quadrant complaints) at the A&E department., Patient Population, Methods: 138 patients were included in our study between 01.01.2019 and 01.01.2020. For patients attending A&E, the first medic calculated and recorded the modified Alvarado score before surgical consultation. The consulting surgeon decided on further treatment without knowing the score. Validation of the score was based on the pathology report of the removed appendix (whether the operation was warranted, and if the score also supported indication for surgery), if there was readmission or surgery due to worsening symptoms after discharge from A&E. We also examined if there was any connection between the value of the Alvarado score and the severity of inflammation. Our aim was to prove that using modified Alvarado score at the A&E Units helps to reduce patient's waiting time and avoid unnecessary surgical consultations. Furthermore our study included measuring the diagnostic accuracy of the ultrasound examination (specificity, sensitivity)., Results: Based on the results, patients presenting at A&E had a mean modified Alvarado score of 6.5. Comparing the score to histological results showed that the specificity of the modified Alvarado score was 100%, and its sensitivity was 80.7%. Based on Spearman's rank correlation (0.796) and ROC analysis (AUC 0.968), the modified Alvarado score has an excellent predictive value in diagnosing acute appendicitis. When comparing the patients' waiting times with the use of modified Alvarado score and without it we found that there was a significant difference in group also in group under 4 points and in group over 7 points when using modified Alvarado score, so the diagnostic and therapeutic algorithm should be much quicker with the help of the score. We found a correlation between the severity of inflammation based on the Fisher's exact test. Rank correlation of the same question also showed a significant connection. All patients had an US examination during their diagnostic course, its sensitivity was 82.6%, specificity was 87%. Based on this, we can conclude that the predictive value of the imaging method is good., Conclusions: We can conclude according to our results that the predictive value of the modified score is excellent, and it can be safely applied by non-surgeons in urgent care in the differential diagnosis of acute appendicitis. The new score incorporates the results of an easily obtainable, ionising radiation free imaging method, the ultrasound, which was not included in previous scores. With the help of the new score, the number of unnecessary surgical referrals and waiting times for patients are reduced, excess examinations will become avoidable., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Epithelial ion and fluid secretion determine the physiological functions of a broad range of organs, such as the lung, liver, or pancreas. The molecular mechanism of pancreatic ion secretion is challenging to investigate due to the limited access to functional human ductal epithelia. Patient-derived organoids may overcome these limitations, however direct accessibility of the apical membrane is not solved. In addition, due to the vectorial transport of ions and fluid the intraluminal pressure in the organoids is elevated, which may hinder the study of physiological processes. To overcome these, we developed an advanced culturing method for human pancreatic organoids based on the removal of the extracellular matrix that induced an apical-to-basal polarity switch also leading to reversed localization of proteins with polarized expression. The cells in the apical-out organoids had a cuboidal shape, whereas their resting intracellular Ca 2+ concentration was more consistent compared to the cells in the apical-in organoids. Using this advanced model, we demonstrated the expression and function of two novel ion channels, the Ca 2+ activated Cl - channel Anoctamin 1 (ANO1) and the epithelial Na + channel (ENaC), which were not considered in ductal cells yet. Finally, we showed that the available functional assays, such as forskolin-induced swelling, or intracellular Cl - measurement have improved dynamic range when performed with apical-out organoids. Taken together our data suggest that polarity-switched human pancreatic ductal organoids are suitable models to expand our toolset in basic and translational research., (© 2023. The Author(s).)

Different applications of near-infrared fluorescence-guided surgery are very promising, and techniques that help surgeons in intraoperative guidance have been developed, thereby bridging the gap between preoperative imaging and intraoperative visualization and palpation. Thus, these techniques are advantageous in terms of being faster, safer, less invasive, and cheaper. There are a few fluorescent dyes available, but the most commonly used dye is indocyanine green. It can be used in its natural form, but different nanocapsulated and targeted modifications are possible, making this dye more stable and specific. A new active tumor-targeting strategy is the conjugation of indocyanine green nanoparticles with antibodies, making this dye targeted and highly selective to various tumor proteins. In this mini-review, we discuss the application of near-infrared fluorescence-guided techniques in thoracic surgery. During lung surgery, it can help find small, non-palpable, or additional tumor nodules, it is also useful for finding the sentinel lymph node and identifying the proper intersegmental plane for segmentectomies. Furthermore, it can help visualize the thoracic duct, smaller bullae of the lung, phrenic nerve, or pleural nodules. We summarize current applications and provide a framework for future applications and development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Géczi, Simonka, Lantos, Wetzel, Szabó, Lázár and Furak.)

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mátrai, Kelemen, Kósa, Maráz, Paszt, Pavlovics, Sávolt, Simonka, Tóth, Kásler, Kaprin, Krivorotko, Vicko, Pluta, Kolacinska-Wow, Murawa, Jankau, Ciesla, Dyttert, Sabol, Zhygulin, Avetisyan, Bessonov and Lázár.)

Regardless of its aetiology, sustained intracellular Ca 2+ overload is a well-known hallmark of acute pancreatitis (AP). Toxic Ca 2+ elevation induces pancreatic ductal cell damage characterized by impaired ion and fluid secretion - essential to wash out the protein-rich fluid secreted by acinar cells while maintaining the alkaline intra-ductal pH under physiological conditions - and mitochondrial dysfunction. While prevention of ductal cell injury decreases the severity of AP, no specific drug target has yet been identified in the ductal cells. Although Orai1, a store-operated Ca 2+ influx channel, is known to contribute to sustained Ca 2+ overload in acinar cells, details concerning its expression and function in ductal cells are currently lacking. In this study, we demonstrate that functionally active Orai1 channels reside predominantly in the apical plasma membrane of pancreatic ductal cells. Selective CM5480-mediated Orai1 inhibition impairs Stim1-dependent extracellular Ca 2+ influx evoked by bile acids or ethanol combined with non-oxidative ethanol metabolites. Furthermore, prevention of sustained extracellular Ca 2+ influx protects ductal cell secretory function in vitro and decreases pancreatic ductal cell death. Finally, Orai1 inhibition partially restores and maintains proper exocrine pancreatic secretion in in vivo AP models. In conclusion, our results indicate that Orai1 inhibition prevents AP-related ductal cell function impairment and holds the potential of improving disease outcome. KEY POINTS: Sustained intracellular Ca 2+ overload in pancreatic acinar and ductal cells is a hallmark of biliary and alcohol-induced acute pancreatitis, which leads to impaired ductal ion and fluid secretion. Orai1 is a plasma membrane Ca 2+ channel that mediates extracellular Ca 2+ influx upon endoplasmic reticulum Ca 2+ depletion. Results showed that Orai1 is expressed on the luminal plasma membrane of the ductal cells and selective Orai1 inhibition impaired Stim1-dependent extracellular Ca 2+ influx evoked by bile acids or ethanol combined with non-oxidative ethanol metabolites. The prevention of sustained extracellular Ca 2+ influx protected ductal cell secretory functions in in vitro models and maintained exocrine pancreatic secretion in in vivo acute pancreatitis models. Orai1 inhibition prevents the bile acid- and alcohol-induced damage of the pancreatic ductal secretion and holds the potential of improving the outcome of acute pancreatitis., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

The coronavirus disease 2019 (COVID-19) outbreak emerged in December 2019 in China and rapidly spread worldwide. Inflammatory bowel disease (IBD) patients are likely to be more susceptible to viral infections, and this is significantly influenced by the type of therapy they receive. Thus, issues specifically concerning the medical treatment of IBD patients were shortly addressed at the beginning of the pandemic. However, recently available data on the occurrence and outcome of SARS-CoV-2 infection in IBD patients does not address the concerns raised at the beginning of the pandemic. Growing evidence and the rapid changes happening over the past few weeks have helped elucidate the current situation, contribute to our understanding of the disease, and many previously raised questions could now be answered. We hereby summarise available evidence regarding viral infections and IBD, focusing on SARS-CoV infections, and we provide practical recommendations related to patient management during the COVID-19 pandemic era., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: Our aim is to determine the relationships among patient demographics, patient history, surgical experience, and conversion rate (CR) during elective laparoscopic cholecystectomies (LCs)., Methods: We analyzed data from patients who underwent LC surgery between 2005 and 2014 based on patient charts and electronic documentation. CR (%) was evaluated in 4013 patients who underwent elective LC surgery. The relationships between certain predictive factors (patient demographics, endoscopic retrograde cholangiopancreatography (ERCP), acute cholecystitis (AC), abdominal surgery in the patient history, as well as surgical experience) and CR were examined by univariate analysis and logistic regression., Results: In our sample (N = 4013), the CR was 4.2%. The CR was twice as frequent among males than among females (6.8 vs. 3.2%, p < 0.001), and the chance of conversion increased from 3.4 to 5.9% in patients older than 65 years. The detected CR was 8.8% in a group of patients who underwent previous ERCP (8.8 vs. 3.5%, p < 0.001). From the ERCP indications, most often, conversion was performed because of severe biliary tract obstruction (CR: 9.3%). LC had to be converted to open surgery after upper and lower abdominal surgeries in 18.8 and 4.8% cases, respectively. Both AC and ERCP in the patient history raised the CR (12.3%, p < 0.001 and 8.8%, p < 0.001). More surgical experience and high surgery volume were not associated with a lower CR prevalence., Conclusions: Patient demographics (male gender and age > 65 years), previous ERCP, and upper abdominal surgery or history of AC affected the likelihood of conversion. More surgical experience and high surgery volume were not associated with a lower CR prevalence.

Background: Leiomyoma is the most common benign oesophageal tumour. Half of all leiomyoma patients have oesophagus-associated complaints, such as dysphagia and epigastric pain, and the other 50% are asymptomatic with a diagnosis made on incidental discovery. Endoscopic ultrasonography is essential for an accurate preoperative workup and can enable guided-tissue acquisition for immunohistochemistry in certain cases. Smaller tumours are amenable to traditional and novel endoscopic removal in specialized centres, but some complex cases require surgical enucleation with a minimally invasive approach., Case Presentation: An asymptomatic 60-year-old woman was accidentally diagnosed with a bifocal oesophageal mass, which was discovered by chest computed tomography. We report a rare case of a duplicated lower-third oesophageal leiomyoma, which was completely removed via the laparoscopic transhiatal approach. The patient has recovered successfully from the surgery. She has been followed up for six months with a normal oesophagram, adequate oesophageal function and no complaints observed. Pathological examination confirmed the diagnosis of leiomyoma in both lesions., Conclusions: To the best of our knowledge, this is the first reported case of duplex oesophageal leiomyomas removed laparoscopically. Using the minimally invasive abdominal technique, the lower oesophagus can be mobilised to the mediastinum without pleura injury and offers a good alternative to the thoracoscopic approach in patients with possible intrathoracic difficulties. At experienced centres, laparoscopic transhiatal enucleation of lower oesophageal leiomyomas and other benign tumours with a combination of intraoperative oesophagoscopy is a safe, fast and effective operation.

Introduction: We have analyzed the short- and long-term results of various surgical therapies for achalasia, especially changes in postoperative esophageal function., Patients and Methods: Between January 1, 2008 and December 31, 2017, 54 patients with esophageal achalasia were treated in our institution. Patients scheduled for surgery underwent a comprehensive gastroenterological assessment pre- and post-surgery. Forty-eight of the elective cases involved a laparoscopic cardiomyotomy with Dor's semifundoplication, while two cases entailed an esophageal resection with an intrathoracic gastric replacement for end-stage achalasia. Torek's operation was performed on two patients for iatrogenic esophageal perforation, and two others underwent primary suture repair with Heller-Dor surgery as an emergency procedure. The results of the different surgical treatments, as well as changes in the patients' pre- and post-operative complaints were evaluated., Results: No intra-operative complications were observed, and no mortalities resulted. During the 12 to 24-month follow-up period, recurrent dysphagia was observed mostly in the spastic group (TIII: 33%; diffuse esophageal spasm: 60%), while its occurrence in the TI type did not change significantly (14.5%-20.8%). As a result of the follow-up of more than two years, good symptom control was achieved in 93.7% of the patients, with only four patients (8.3%) developing postoperative reflux., Conclusions: The laparoscopic Heller-Dor procedure provides satisfactory long-term results with low morbidity. In emergency and advanced cases, traditional surgical procedures are still the recommended therapy., (© 2021 by SLS, Society of Laparoscopic & Robotic Surgeons.)

The surgical treatment is still the most effective method in curing of early breast cancer. Breast preservation and the application of oncoplastic principles became generally accepted, the sentinel lymph node biopsy in the surgical treatment of the axilla is primary, and the indication for axillary block dissection (ABD) is narrowing further. The neoadjuvant oncological treatment that is applied more and more widely presented surgery with new challenges. Hereunder we summarise our recommendations on the surgical treatment of breast cancer based on the content of the 3rd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.

Background: Treating hernias is one of the oldest challenges in surgery. The gallbladder as content in the case of abdominal hernias has only been reported in a few cases in the current literature. Cholecyst has only been described in the content of an inguinofemoral hernia in one case to date., Case Presentation: A 73-year-old female patient was admitted to the Emergency Department due to complaints in the right inguinal area, which had started 1 day earlier. The patient complained of cramp-like abdominal pain and nausea. Physical examination confirmed an apple-sized, irreducible hernia in the right inguinal region. Abdominal ultrasound confirmed an oedematous intestinal loop in a 70-mm-long hernial sac, with no circulation detected. Abdominal X-ray showed no signs of passage disorder. White blood cell count and C-reactive protein level were elevated, and hepatic enzymes were normal in the laboratory findings. Exploration was performed via an inguinal incision on the right side, an uncertain cystic structure was found in the hernial sac, and several small abnormal masses were palpated there. The abdominal cavity was explored from the middle midline laparotomy. During the exploration, the content of the hernial sac was found to be the fundus of the significantly ptotic, large gallbladder. Cholecystectomy and Bassini's repair of the inguinal hernia were performed safely., Conclusions: Following a review of the literature, it can be concluded that the finding of incarcerated gallbladder in the content of an inguinal hernia is a rare finding. No other similar emergency case and successful surgical intervention have been reported before.

Backgrounds: The number of appendectomies and cholecystectomies performed is gradually increasing worldwide. An increasing incidence of colorectal cancer (CRC) after appendectomy and cholecystectomy has been reported, but the location of tumors in certain segments of the colon and rectum after appendectomy and cholecystectomy is still uncertain. We aimed to evaluate the distribution of the locations of colorectal cancer after appendectomy and/or cholecystectomy in patients who underwent CRC surgery., Methods: We reviewed the medical records of patients who had undergone CRC surgery between 2015 and 2017 for the presence of previous appendectomy/cholecystectomy. Data were collected from the Colorectal Data Base of the University of Szeged, Department of Surgery., Results: Surgery for CRC was performed in 640 patients during the study period. Data of 604 patients were analyzed. Appendectomy was performed in 100 patients (16.6%), cholecystectomy in 65 (10.8%), and both interventions in 18 (3%) before the CRC surgery. Out of those patients who underwent appendectomy alone, 92 (92%) had undergone appendectomy more than 10 years before the CRC surgery. Also in these 100 patients, the prevalence of right-sided colon cancer (CC) was 35% (n = 35), in comparison with the prevalence among the 504 other patients (20.4%, n = 103). The prevalence of right-sided CC among patients who underwent cholecystectomy alone was 36.9% (n = 24), in comparison with 21.2% (n = 114) of the 539 other patients., Conclusions: A significant left to right side shift in CRC was noted among patients who had previously undergone appendectomy/cholecystectomy. Because right-sided CC has a worse prognosis, the role of incidental appendectomy and routine cholecystectomy seems that need re-evaluation.

Background: The major limitations of widespread use of non-intubated thoracic surgery (NITS) is the fear of managing complications. Here we present our practice of converting from uniportal video-assisted thoracic surgery (VATS) NITS to open NITS in cases of surgical complications., Methods: The study period was from January 26, 2017, to November 30, 2018. Total intravenous anesthesia was provided with propofol guided by bispectral index, and the airway was maintained with a laryngeal mask with spontaneous breathing. Local anesthesia with 2% lidocaine at the skin incision, and intercostal and vagus nerve blockades were induced using 0.5% bupivacaine. For conversion with surgical indications, a thoracotomy was performed at the incision without additional local or general anesthetics., Results: In 160 complete NITS procedures, there were 145 VATS NITS and 15 open NITS (9 conversions to open NITS and 6 intended NITS thoracotomies). In the 15 open NITS cases (2 pneumonectomies, 1 bilobectomy, 1 sleeve lobectomy, 7 lobectomies, 3 sublobar resections, 1 exploration), the mean operative time was 146.7 (105-225) and 110 (75-190) minutes in the converted and intended open NITS groups, respectively. There were no significant differences between systolic blood pressure (P=0.316; 95% CI, -10.469 to 3.742), sat O2% (P=0.27; 95% CI, -1.902 to 0.593), or propofol concentration in the effect site (P=0.053; 95% CI, -0.307 to 0.002) but significant differences in pulse (P=0.007; 95% CI, -10.001 to -2.72), diastolic blood pressure (P=0.013; 95% CI, -9.489 to -1.420) and in end-tidal CO2 (P=0.016; 95% CI, -7.484 to -0.952) before versus after thoracotomy, but there was no clinical relevance of the differences., Conclusions: For conversion with surgical indications during the VATS-NITS procedure, NITS thoracotomy can be performed safely at the site of the utility incision without the need for additional drugs, and the major lung resections can be performed through this approach., Competing Interests: Conflicts of Interest: Al authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-19-3830). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)