Abietic Acid as a Novel Agent against Ocular Biofilms: An In Vitro and Preliminary In Vivo Investigation.

Biofilm-related ocular infections can lead to vision loss and are difficult to treat with antibiotics due to challenges with application and increasing microbial resistance. In turn, the design and testing of new synthetic drugs is a time- and cost-consuming process. Therefore, in this work, for the first time, we assessed the in vitro efficacy of the plant-based abietic acid molecule, both alone and when introduced to a polymeric cellulose carrier, against biofilms formed by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans in standard laboratory settings as well as in a self-designed setting using the topologically challenging surface of the artificial eye. These analyses were performed using the standard microdilution method, the biofilm-oriented antiseptic test (BOAT), a modified disk-diffusion method, and eyeball models. Additionally, we assessed the cytotoxicity of abietic acid against eukaryotic cell lines and its anti-staphylococcal efficacy in an in vivo model using Galleria mellonella larvae. We found that abietic acid was more effective against Staphylococcus than Pseudomonas (from two to four times, depending on the test applied) and that it was generally more effective against the tested bacteria (up to four times) than against the fungus C. albicans at concentrations non-cytotoxic to the eukaryotic cell lines and to G. mellonella (256 and 512 µg/mL, respectively). In the in vivo infection model, abietic acid effectively prevented the spread of staphylococcus throughout the larvae organisms, decreasing their lethality by up to 50%. These initial results obtained indicate promising features of abietic acid, which may potentially be applied to treat ocular infections caused by pathogenic biofilms, with higher efficiency manifested against bacterial than fungal biofilms.

Will We Fly Again? Modeling Air Travel Demand in light of COVID-19 through a London Case Study.

The COVID-19 pandemic and associated travel restrictions have created an unprecedented challenge for the air transport industry, which before the pandemic was facing almost the exact opposite set of problems. Instead of the growing demand and need for capacity expansion warring against environmental concerns, the sector is now facing a slump in demand and the continuing uncertainty about the impacts of the pandemic on people's willingness to fly. To shed light on consumer attitudes toward air travel during and post the pandemic, this study presents an analysis that draws on recently collected survey data (April-July 2020), including both revealed and stated preference components, of 388 respondents who traveled from one of the six London, U.K., airports in 2019. Several travel scenarios considering the circumstances and attitudes related to COVID-19 are explored. The data is analyzed using a hybrid choice model to integrate latent constructs related to attitudinal characteristics. The analysis confirms the impact of consumers' health concerns on their willingness to travel, as a function of travel characteristics, that is, cost and number of transfers. It also provides insights into preference heterogeneity as a function of sociodemographic characteristics. However, no significant effects are observed concerning perceptions of safety arising from wearing a mask, or concerns over the necessity to quarantine. Results also suggest that some respondents may perceive virtual substitutes for business travel, for example video calls and similar software, as only a temporary measure, and seek to return to traveling as soon as it is possible to do so safely.

Real-Time Impedance-Based Monitoring of the Growth and Inhibition of Osteomyelitis Biofilm Pathogen Staphylococcus aureus Treated with Novel Bisphosphonate-Fluoroquinolone Antimicrobial Conjugates.

Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.

Impact of perceptions and attitudes on air travel choices in the post-COVID-19 era: A cross-national analysis of stated preference data.

The COVID-19 pandemic and the consequent travel restrictions have had an unprecedented impact on the air travel market. However, a rigorous analysis of the potential role of safety perceptions and attitudes towards COVID-19 interventions on future air passenger choices has been lacking to date. To investigate this matter, 1469 individuals were interviewed between April and September 2020 in four multi-airport cities (London, New York City, Sao Paulo, Shanghai). The core analysis draws upon data from a set of stated preference (SP) experiments in which respondents were asked to reflect on a hypothetical air travel journey taking place when travel restrictions are lifted but there is still a risk of infection. The hybrid choice model results show that alongside traditional attributes, such as fare, duration and transfer, attitudinal and safety perception factors matter to air passengers when making future air travel choices. The cross-national analysis points towards differences in responses across the cities to stem from culturally-driven attitudes towards interpersonal distance and personal space. We also report the willingness to pay for travel attributes under the expected future conditions and discuss post-pandemic implications for the air travel sector, including video-conferencing as a substitute for air travel.

Hybrid technique for postoperative ventral hernias - own experience.

INTRODUCTION: There are many techniques which may be involved in abdominal hernia repair, from classical to tension-free. Treatment of complicated hernias has undergone evolution. Many surgeons consider the laparoscopic method as a method of choice for incisional hernia repair. Sometimes miniinvasive repair of complicated hernia is not so easy to perform. We are convinced that selected patients may benefit from combined open and laparoscopic techniques. AIM: To present the operating technique and early results of treatment of 15 patients operated on using the 3 hybrid technique. MATERIAL AND METHODS: Fifteen patients suffering from recurrent incisional hernias underwent the hybrid technique for their repair between June 2012 and April 2015. The hybrid technique was performed using synthetic meshes in 14 cases and a biological implant in 1 case. RESULTS: The early postoperative period was uncomplicated in all cases. Within a maximum follow-up period of 32 months, two deep wound infections were observed. CONCLUSIONS: The hybrid technique may be used in patients with recurrent incisional hernias.

Evolution Of The Results Of 1500 Liver Transplantations Performed In The Department Of General, Transplant And Liver Surgery Medical University Of Warsaw.

UNLABELLED: Liver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects. The aim of this study was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw). MATERIAL AND METHODS: Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures. RESULTS: Increased number of transplantations performed at the site was associated with increased age of the recipients (p<0.001) and donors (p<0.001), increased rate of male recipients (p<0.001), and increased rate of piggyback operations (p<0.001), and decreased MELD (p<0.001), as well as decreased blood (p=0.006) and plasma (p<0.001) transfusions. Overall survival was 71.6% at 5 years in group 1, 74.5% at 5 years in group 2, and 85% at 2.9 years in group 3 (p=0.008). Improvement of overall survival was particularly observed for primary transplantations (p=0.004). Increased graft survival rates did not reach the level of significance (p=0.136). CONCLUSIONS: Long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.

Adenocarcinoma of the small bowel - a case report.

The paper presents a rare case of a patient with adenocarcinoma of the small intestine who reported to the hospital due to non-specific gastrointestinal symptoms. Following diagnostic examinations, the patient underwent a surgery. The post-operative period proceeded with no complications. The case presented below confirms the usefulness of imaging examinations (abdominal CT) when pathologies within the small intestine are suspected. An accurate interpretation of the result was an indication for a surgical intervention, but the final diagnosis is still established on the basis of the histopathological examination.

Evaluation of prognostic significance of circulating tumor cells detection in rectal cancer patients treated with preoperative radiotherapy: prospectively collected material data.

The aim of this study was to evaluate the prognostic value of circulating tumor cells (CTC) in nonmetastatic rectal cancer patients treated with short-term preoperative radiotherapy. In this single-center trial, 162 patients with rectal cancer after preoperative short-term radiotherapy (5 × 5 Gy) were recruited from January, 2008 to September, 2011. Clearance of CTC was determined in 91 patients enrolled in the molecular analysis. CTC presence was evaluated with real-time reverse transcription polymerase chain reaction assay (qPCR) based on the expression of three tumor genetic markers: carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), and/or cancer stem cells marker CD133 (CEA/CK20/CD133). We found that CTC detection 7 days after surgery was of prognostic significance for the local recurrence (P value = 0.006). CTC detected preoperatively and 24 hours after resection had no prognostic value in cancer recurrence; however, there was a significant relationship between CTC prevalence 24 hours after surgery and lymph node metastasis (pN1-2). We also confirmed a significant clearance of CTC in peripheral blood (PB) 24 hours after surgery. Preoperative sampling is not significant for prognosis in rectal cancer patients treated with short-term radiotherapy. Detection of CTC in PB 7 days after surgery is an independent factor predicting local recurrence in this group of patients.

Synchronous occurrence of colon and appendiceal adenocarcinoma.

The study presented two cases of synchronous occurrence of colon and appendiceal adenocarcinoma. Both patients required surgical intervention, due to acute peritonitis during the course of acute appendicitis. In case of one patient we performed abdominal CT confirming the presence of sigmoid cancer. The patient was subjected to appendectomy and Hartmann's operation. The second patient underwent an appendectomy, and colonoscopy performed two months later revealed the presence of rectal adenocarcinoma. The patient was subjected to low anterior rectal resection. The histopathological results considering both patients revealed the presence of synchronous colon and appendiceal adenocarcinoma.

18-year old patient with extrahepatic biliary duct carcinoid--case report.

Most patients with obstructive jaundice caused by an etiology other than choledocholithiasis are at risk of adenocarcinoma development. Other types of tumors are less common, although more benign. The presented study described management in case of liver hilar tumors with special regards to common hepatic duct carcinoids.

Results of liver transplantation in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw in patients with chronic hepatitis B and C viruses infection.

INTRODUCTION: Cirrhosis related to hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is the most frequent indication for liver transplantation worldwide. Progress in prophylaxis of posttransplant HBV recurrence has led to major improvements in long-term outcomes of patients after liver transplantation. Conversely, impaired posttransplant survival of patients with HCV infection was reported in several studies, mainly due to recurrence of viral infection. The purpose of this study was to compare long-term results of liver transplantation between patients with HBV monoinfection, HCV monoinfection and HBV/HCV coinfection. MATERIAL AND METHODS: A total of 1090 liver transplantations were performed in the Department of General, Transplant and Liver Surgery in cooperation with the Department of Immunology, Internal Medicine, and Transplantology at the Transplantation Institute Medical University of Warsaw between December 1994 and May 2012. After exclusion of patients with cirrhosis of non-viral etiology, patients with malignant tumors, and patients with acute liver failure, the final study cohort comprised 209 patients with HBV (HBV+/HCV- subgroup; n = 56) or HCV (HBV-/HCV+ subgroup; n = 119) monoinfection or HBV/HCV coinfection (HBV+/HCV+; n = 34). These subgroups of patients were compared in terms of long-term results of transplantations, defined by 5-year patient and 5-year graft survival estimates. RESULTS: Overall and graft survival rates after 5-years for the whole study cohort were 74.5% and 72.6%, respectively. Five-year overall survival was 70.4% for patients within the HBV+/HCV- subgroup, 77.8% for patients within the HBV-/HCV+ subgroup, and 68.5% for patients within the HBV+/HCV+ subgroup. The corresponding rates of graft survival were 67.0%, 76.3%, and 68.5% for patients within the HBV+/HCV-, HBV-/ HCV+, and HBV+/HCV+ subgroups, respectively. Observed differences were non-significant, both in terms of overall (p = 0.472) and graft (p = 0.461) survival rates. CONCLUSIONS: Both overall and graft survival rates after liver transplantations performed in the Department of General, Transplant and Liver Surgery in cooperation with the Department of Immunology, Internal Medicine, and Transplantology at the Transplantation Institute Medical University of Warsaw in patients with HBV and HCV infection are comparable to those reported by other European and American centers. In contrast to other studies, obtained results do not confirm the negative impact of HCV infection on long-term outcomes of patients.

1000 liver transplantations at the Department of General, Transplant and Liver Surgery, Medical University of Warsaw--analysis of indications and results.

THE AIM OF THE STUDY: was to analyze indications and results of the first one thousand liver transplantations at Chair and Clinic of General, Transplantation and Liver Surgery, Medical University of Warsaw. MATERIAL AND METHODS: Data from 1000 transplantations (944 patients) performed at Chair and Clinic of General, Transplantation and Liver Surgery between 1994 and 2011 were analyzed retrospectively. These included 943 first transplantations and 55 retransplantations and 2 re-retransplantations. Frequency of particular indications for first transplantation and retransplantations was established. Perioperative mortality was defined as death within 30 days after the transplantation. Kaplan-Meier survival analysis was used to estimate 5-year patient and graft survival. RESULTS: The most common indications for first transplantation included: liver failure caused by hepatitis C infection (27.8%) and hepatitis B infection (18%) and alcoholic liver disease (17.7%). Early (< 6 months) and late (> 6 months) retransplantations were dominated by hepatic artery thrombosis (54.3%) and recurrence of the underlying disease (45%). Perioperative mortality rate was 8.9% for first transplantations and 34.5% for retransplantations. Five-year patient and graft survival rate was 74.3% and 71%, respectively, after first transplantations and 54.7% and 52.9%, respectively, after retransplantations. CONCLUSIONS: Development of liver transplantation program provided more than 1000 transplantations and excellent long-term results. Liver failure caused by hepatitis C and B infections remains the most common cause of liver transplantation and structure of other indications is consistent with European data.

Results of liver transplantation for hepatocellular cancer.

BACKGROUND: Liver transplantation (LTx) for hepatocellular carcinoma (HCC) in cirrhotic liver is nowadays generally accepted treatment modality. AIM OF STUDY: Overview of the indications and results of the LTx in the patients with HCC, the first one performed in 2001. MATERIAL/METHODS: Among 357 adult liver transplant recipients in the period 1994-04.2005, in 26 (7%) the indication was HCC (16 men: 10 women, age 20-65, mean 46.5 years). HCC developed in cirrhotic liver in 25 pts. 12 (48%) were Child C, 10 (30%)--Child B and 3 (12%)--Child A patients. As underlying disease in 2 patients (8%) was alcoholic cirrhosis, in 7 (28%)--HBV cirrhosis, in 12 (48%)--HCV cirrhosis and in 4 (16%)--HBV/HCV cirrhosis. Milano criteria were met in 20 patients (77%). The mean waiting list time was 2.9 months (range 1-6 months). Seven patients underwent liver resection and 1 transarterial chemoembolization prior to LTx. 11 patients (42%) were operated on with use of veno-venous bypass, in 15 patients (58%) the piggy back technique was applied. Rapamycine based immunosuppression was preferred in post-LTx treatment. RESULTS: Operative mortality was 0.4 patients required relaparotomy for intraperitoneal bleeding. 21 patients (81%) are alive in good general condition, 19--free of the disease. 5 patients died 7-28 months after LTx (mean 16.7). The mean survival time is 20 months (range 1-38). CONCLUSIONS: Liver transplantation is safe and effective method of treatment of the selected patients with HCC in cirrhotic liver. Further investigations concerning the precise indications, timing of the transplantation and adjuvant treatment are necessary.

[Role of the pathomorphologist in diagnostic process concerning problems of ortothopic liver transplantation in adults]. / Rola lekarza patomorfologa w procesie diagnostycznym zwiazanym z ortotopowym przeszczepem watroby u doroslych.

In this paper are presented main tasks of the pathologist dealing with liver diagnosis concerning problems of its transplantation in adults. They include: pretransplant diagnosis of recipient's liver, examination of explanted liver, evaluation of donor liver (pretransplant biopsies and performed during the operation), posttransplant assessment of the graft. On the basis of our own experience, the most frequent problems in patologist's work and basic information concerning the diagnostic process in liver transplantation with posibillities and limits of the histopathological method are described. Because of the popularity of transplantation as the method of treatment of advanced liver diseases, the group of transplanted patients continously enlarges and may lead to visit to doctors of different specialties. That is why presentation of this issue seems to be very valuable.

[Amanita phalloides poisoning as an indication for liver transplantation in three family members]. / Zatrucie muchomorem sromotnikowym jako wskazanie do transplantacji watroby u trzech czlonków rodziny.

Amanita phalloides poisoning is one of the most dramatic medical invents. The course of the illness may vary from mild to the lethal, with signs of fulminant liver insufficiency with coma and multiorgan failure. When hepatic encephalopathy (III/IV degrees) occurs the prognosis is very poor. In definite cases the liver transplantation is necessary. The authors present severe Amanita phalloides poisoning in three family members, who due to fulminant hepatic failure underwent liver transplantation. The two of them (son and father) transplanted accordingly in fifth and seventh day after poisoning, survived. Mother, in whom transplantation started in ninth day after poisoning, died intraoperativel with signs of massive hemorrhage, and cardiac arrest.

[Focal fatty change (FFC) imitating liver malignancy. Own cases and review of literature]. / Ogniskowe stluszczenie watroby (focal fatty change--FFC) pod postacia guzów imitujacych chorobe nowotworowa. Spostrzezenia wlasne i przeglad literatury.

UNLABELLED: Focal fatty change (FFC) may occur in the form of a single or numerous nodules of different size, located in the liver with otherwise normal structure. These changes, especially when they are large and single, pose an important diagnostic problem as their clinical and radiological picture may imitate malignancy. In the paper we report two cases of large hepatic tumors (12 cm and 8 cm) in patients, who had no factors predisposing to fatty liver changes (such as alcohol abuse, drugs, obesity, hormone disturbances, impaired blood flow through the liver or metabolic disturbances). In microscopic examinations the nodules were diagnosed as foci of large-droplet hepatocellular steatosis. Apart from these changes the liver was normal. CONCLUSION: FFC belongs to a group of pseudotumor changes. It occurs in rare cases and should be distinguished from diffuse changes observed frequently. In the differential diagnosis, the following must also be considered: primary hepatocellular tumors with fatty change, FNH with fatty change, mesenchymal tumors containing adipose tissue, fatty macro-regenerative nodule, adipocytic pseudotumor of the Glisson's capsule.

Myoid hamartoma of the liver--a novel variant of hamartoma developing in the hilar region and imitating a malignant liver tumor.

BACKGROUND: We report here an unusual variant of hepatic mesenchymal hamartoma exhibiting a marked myoid differentiation and clinically imitating hilar malignancy. CASE REPORT: A 17-year-old patient was admitted to the hospital with the suspicion of Klatskin's tumor. Three months before he had presented with jaundice and light stools. Imaging techniques demonstrated a solid lesion (3 cm) situated in liver segment IV. Biochemical tests detected an increased level of bilirubin, alkaline phosphatase, AspAt, ALAT, and slightly increased CA19-9. Diagnosed with perihilar malignancy, the patient underwent left-sided hemihepatectomy with hepaticojejunostomy. The liver resection specimen showed an unencapsulated solid hilar tumor (5x3x3.5 cm), consisting of eosinophilic spindle-like cells with blunt-ended nuclei. Within the lesion we found numerous biliary ductules. Focally, numerous plasma cells and eosinophils were found, but no cystic spaces. There was no cellular atypia. Apart from the lesion the liver revealed intensified fibrosis of portal areas. Immunohistochemical studies demonstrated positivity of most spindle-like cells for SMActin, whereas only a few cells were CD34- and desmin-positive. Ki67 was positive in less than 5% cells. CONCLUSIONS: Given the indistinct border and heterogeneous morphology, with spindle-like myoid cells constituting most of the tissue, interspersed with biliary ductules, we suggest that this tumor is an unusual variant of mesenchymal hamartoma. As the mesenchymal component in this lesion was mainly represented by cells of muscular origin, we suggest classifying this lesion as an previously undescribed form of mesenchymal hamartoma, and propose the term, myoid hamartoma of the liver.