Importance of Follow-Up Biopsies in the Prediction of Renal Allograft Survival Following Polyomavirus-Associated Nephropathy.

OBJECTIVES: Allograft biopsy is the gold standard for diagnosing polyomavirus-associated nephropathy. We aimed to establish the effects of histopathologic findings proposed by the Banff Polyomavirus Working Group on graft outcome. We also aimed to understand the clinical importance of follow-up biopsies for patients with polyomavirus-associated nephropathy. MATERIALS AND METHODS: Our study included 22 patients with polyomavirus-associated nephropathy. All biopsies were classified according to the latest Banff Polyomavirus Working Group classification. Follow-up biopsies of all patients were evaluated in detail. RESULTS: The mean interval between polyomavirus-associated nephropathy and transplant was 10 ± 1.6 months. Of 22 patients, biopsy revealed stage 1 in 3 (13.6%), stage 2 in 17 (77.3%), and stage 3 in 2 patients (9.1%). Fourteen patients (63.6%) had polyomavirus viral load 3, 5 (22.7%) had polyomavirus viral load 2, and 3 had polyomavirus viral load 1. Among patients included in analyses, 18.2% had antibody-mediated rejection and 27.2% had T-cell-mediated rejection simultaneously with polyomavirus-associated nephropathy. Graft loss increased with increasing polyomavirus-associated nephropathy class and polyomavirus viral load (P = .015 and P = .002, respectively). The mean time of graft survival decreased with increasing degree of tubulitis, interstitial inflammation, plasma infiltration, and neutrophil infiltration. Patients with interstitial fibrosis, glomerular polyoma, and cortical plus medullar involvement showed earlier graft loss. Follow-up biopsies showed that diffuse interstitial fibrosis or persistent inflam-mation negatively influenced graft loss. CONCLUSIONS: The Banff Polyomavirus Working Group's schema significantly correlated with graft outcome. Early detection of polyomavirus-associated nephro-pathy and subsequent detection of persistent inflammation and interstitial fibrosis and tubular atrophy in follow-up biopsies and modification of immunosuppressive therapy can successfully prevent graft loss.

The role of chest X-ray in coronavirus disease 2019 (COVID-19) infection: findings and correlation with clinical outcome.

OBJECTIVE: It is possible to diagnose coronavirus disease 2019 (COVID-19) faster and more accurately with chest X-ray (CXR) and chest computed tomography (CT) than with reverse transcriptase PCR (RT-PCR) tests. The aim of this study was to verify the possibility of reducing the use of CT in diagnosis and follow-up of COVID-19 infection by using CXR. PATIENTS AND METHODS: A total of 326 COVID-19 patients who were hospitalized in Ankara City Hospital were included in this retrospective study. RESULTS: A total of 326 patients were RT-PCR positive for COVID-19 infection; 178 were male (54.6%) and 148 were female (45.4%), with a median age of 45. Considering the results, the baseline CXR sensitivity in our experience was approximately 72%. The CXRs of 113 patients with abnormal CT were divided into 2 groups, the CXR normal and abnormal groups, and were then compared. In the 1st group with abnormal CXR, the mean age, the number of patients over 65 years old, and the comorbidity rate were higher. Additionally, it was determined that the number of patients requiring respiratory support and intensive care unit (ICU) admission in this 1st group was higher than in the 2nd group (with normal CXR). Most of the patients who died (91%, 10/11) were in Group 1. In the group with normal CXR, no patients in the critically ill category needed invasive or non-invasive mechanical ventilators. CONCLUSIONS: CXR can help in detecting clinically moderate and severe cases of COVID-19. CXR can assist clinicians in patient management and treatment planning regarding the clinical course, respiratory support, ICU need, and mortality and can help them prepare for potential negative outcomes.

The impacts of the COVID-19 pandemic on patients with viral hepatitis B infection: follow-up, compliance with antiviral treatment, and vaccine preferences.

OBJECTIVE: Elimination programs and interventions for patients with viral hepatitis B (HBV) have been disrupted during the COVID-19 pandemic. This study aimed to evaluate the effects of the COVID-19 pandemic on patients with HBV infection in terms of COVID-19 vaccine preferences, follow-up visits, and antiviral treatment compliance. PATIENTS AND METHODS: In this retrospective single-center cross-sectional study, 129 patients with viral hepatitis B infection were evaluated. The patients were surveyed at the time of admission. A special form was created for patients with viral hepatitis B infection, and the form contained information about the patients at admission to collect the study data. RESULTS: A total of 129 participants were included in the study. Of the participants, 49.6% were males and the median age was 50 years. In total, 73 (56.6%) patients had their follow-up visits disrupted because of the COVID-19 pandemic. No newly diagnosed case of HBV infection was detected. Among the 129 patients, 46 had inactive hepatitis B, and 83 had chronic hepatitis B infection and were receiving antiviral treatment. None of the patients had trouble reaching antiviral treatments during the COVID-19 pandemic. A liver biopsy was recommended for 8 patients. Half of these 8 patients did not have follow-up visits during the COVID-19 pandemic. Most of the patients (123/129, 95.3%) received the COVID-19 vaccine and the most frequent vaccine that was used was the Pfizer-BioNTech (n: 92, 71.3%) vaccine. Serious side effects of the COVID-19 vaccines were not detected. Mild side effects were found in 41.9% (13/31) of the patients. The COVID antibody level was found to be statistically and significantly higher in the patients who received the Pfizer-BioNTech vaccine than in those that received the CoronoVac vaccine. CONCLUSIONS: It was reported that elimination programs and interventions for HBV infection decreased or stopped because of the COVID-19 pandemic. In the present study, no newly diagnosed case of HBV infection was detected. Most of the patients had their follow-up visits disrupted. There were no patients who could not receive antiviral treatment, the vaccination rate of the patients was high, and the vaccines were well tolerated.

The prognostic significance of tumor budding and the expression of focal adhesion kinase and survivin in lung adenocarcinoma.

OBJECTIVES: Adenocarcinoma is the tumor group with the highest incidence among lung cancers with poor prognosis. Tumor budding (TB) is the migration of single tumor cells or small clusters of cells from the neoplastic epithelium to the invasive front of the tumor. Focal adhesion kinase (FAK) and survivin are considered as poor prognostic factors in several tumors. Hence, we investigated TB, FAK, and survivin expression in lung adenocarcinoma. METHODS: The study included 103 cases of lung adenocarcinoma in the resection materials. In tumoral tissues; TB was counted and scored in one high-power field (HPF), as low if <5 in 1 HPF and high if ≥5 in 1 HPF. FAK and survivin were studied immunohistochemically. RESULTS: The mean number of TB in 1 HPF is 3.96 ± 2.8. Low-grade TB was observed in 45 (43.7 %) and high-grade TB was observed in 58 (56.3 %) patients. There was a positive correlation between TB and pT stage (p = 0.017), clinical stage (p = 0.002), lymphovascular invasion (p = 0.001), and perineural invasion (p = 0.045). The 4-year survival rate in patients was 90 % in those with low-grade TB and 60 % in those with high-grade TB (p = 0.001). FAK and survivin expressions were significantly increased in tumors with high-grade TB (p < 0.05). CONCLUSION: A significant correlation was found between the grade of TB and pT stage, clinical stage, lymphovascular and perineural invasion in lung adenocarcinoma. TB can be considered as a histological parameter showing poor prognosis. It is thought that high expression of FAK and survivin also affect the prognosis in these patients by increasing TB.

Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging and machine learning in an experimental model for minimally invasive esophagectomy.

INTRODUCTION: Esophagectomy is the mainstay of esophageal cancer treatment, but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome. Therefore, the objective of this work was to optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis. MATERIAL AND METHODS: A live porcine model (n = 58) for MIE was used with gastric conduit formation and simulation of linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and simulation of anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic simulation site was evaluated using HSI and was validated with histopathology. RESULTS: The tissue oxygenation (ΔStO2) after the anastomotic simulation remained constant only for the short stapler in caudal position (-0.4 ± 4.4%, n.s.) while it was impaired markedly in the other groups (short-cranial: -15.6 ± 11.5%, p = 0.0002; long-cranial: -20.4 ± 7.6%, p = 0.0126; long-caudal: -16.1 ± 9.4%, p < 0.0001). Tissue samples from avascular stomach as measured by HSI showed correspondent eosinophilic pre-necrotic changes in 35.7 ± 9.7% of the surface area. CONCLUSION: Tissue oxygenation at the site of anastomotic simulation of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the simulated anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. The experimental model with HSI and ML allow for systematic optimization of gastric conduit perfusion and anastomotic technique while clinical translation will have to be proven.

Tumor Microenvironment: Necroptosis Switches the Subtype of Liver Cancer While Necrosis Promotes Tumor Recurrence and Progression.

Liver cancer is a heterogeneous group of solid tumors that include mainly epithelial tumors. As with other solid carcinomas, tumor development results from an accumulation of genetic and epigenetic alterations. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma, derived from malignant transformation of hepatocytes and cholangiocytes, respectively, are 2 primary types of liver cancers. However, it has been shown that the same kind of cell can give rise to different types of cancer, depending on manner of cell death in the tumor microenvironment. In a recent animal study, hepatocytes gave rise to both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Oncogenically activated hepatocytes were shown to give rise to intrahepatic cholangiocarcinoma or hepatocellular carcinoma depending on cell death type of neighboring cells. Hepatocytes within the necroptotic microenvironment gave rise to intrahepatic cholangiocarcinoma; however, hepatocytes harboring the same oncogenic driver gave rise to hepatocellular carcinoma within the apoptotic microenvironment. The hepatic cytokine microenvironment structured by the necroptosis can also switch hepatocellular carcinoma to intrahepatic cholangiocarcinoma independently of the oncogenic drivers. Cell death by necrosis in damaged livers can also lead to development of carcinoma. Cancer cells are known to be resistant to apoptosis as a result of p53 mutation. Therefore, necrosis is the primary cell death pathway in cancer therapy. Necrosis is associated with high levels of angiogenesis, tumor-associated macrophages, and increased inflammation in the tumor microenvironment. Patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma characterized by necrosis and tumor-associated macrophages have reduced overall survival and recurrence-free survival. Cytotoxicity from anticancer therapy can also lead to accelerated necrosis. The content of cells undergoing necrosis triggers cytokine secretion, which designs cancer progression via inflammatory and noninflammatory pathways. Thus, the tumor microenvironment and manner of cell death (necrosis, apoptosis, or necroptosis) are crucial factors in the development of primary liver cancers and tumor progression.

Comparison of Biochemical Parameters in Patients with Hepatitis B, C, and Dual Hepatitis B and C in Northwest Pakistan.

The leading causes of hepatitis are viral infections, Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Millions of people have been infected with these deadly viral infections worldwide, and in Pakistan, every tenth person is infected with these viruses. Different populations respond with different rates to infectious diseases due to host genomic differences. To evaluate and compare the biochemical parameters in different types of hepatitis (Hepatitis B, C, and Co-infection) and different ethnic groups, a total of 200 pre-screened patients were recruited from District Headquarters Teaching Hospital Dera Ismail Khan and Tank. Blood samples (5ml) were taken from patients and were assayed for biochemical parameters, including four liver function tests (LFTs) and two renal function tests (RFTs). In 200 patients, the mean scores of Alanine transaminase (ALT) were 376±335, 315±265, and 478±519 IU/L in HBV, HCV, and co-infected patients, respectively. Moreover, the mean score of ALT was 31±7.2 IU/l in the normal control group. All other biochemical parameters demonstrated elevated levels in co-infection, HBV, and HCV, respectively, except total proteins. The RFTs showed a threshold or upper normal limit (UNL); nonetheless, when compared to normal control subjects, RFTs parameters were high in infected patients, as compared to normal control. Ethnicity wise comparison of parameters indicated that Pushtoon ethnic group indicated a high degree of severity of HBV infection and co-infection, as compared to Saraiki and Rajpoot ethnic groups, while Saraiki ethnic group showed a higher severity of HCV than both of Pushtoon and Rajpoot. Rajpoot ethnic group was least affected than both Pushtoon and Saraiki ethnic groups. Co-infected patients were more severely affected, as compared to HBV and HCV patients. The ethnicity-wise study provided evidence that different ethnic groups showed different degrees of severity. There may be some genetic background involved in hepatitis B and C viral infection due to which all three ethnic groups showed different degrees of severity. In gender-wise comparisons, male patients were more affected than female patients.

The effect of erosive beverages and polishing systems on the surface properties of nanohybrid composite resin.

Aims and Background: The aim of this study is to evaluate the surface microhardness and roughness of composites treated with three different polishing systems exposed to two different corrosive beverages. Material and Methods: Ninety-six composite resin disks were randomly divided into four groups, one of which was the control group. The surface roughness and microhardness values were measured after 24 h in the polishing process. The samples were divided into three subgroups and kept in distilled water, cola, and ice tea for 20 min a day for 14 days. Then, the roughness and microhardness measurements of the samples were taken again. Two samples randomly selected from each group were examined using a scanning electron microscope (SEM) and analyzed statistically using the two way anova (ANOVA) and Duncan tests. Results: A statistically significant difference was found between the roughness and hardness values at the end of 24 h and 14 days. Onegloss (OG), Dentoflex (DF), and Super-snap (SNP) polish systems showed the highest roughness in the cola group, respectively. Microhardness values: The unpolished group had the lowest significant microhardness in the coke group (P < 0.05). Conclusion: In this study, it was seen that the lowest success rate was the OG polishing system.

How Exercise Affects the Development and Progression of Hepatocellular Carcinoma by Changing the Biomolecular Status of the Tumor Microenvironment.

A sedentary lifestyle contributes to the development of nonalcoholic fatty liver disease. This disease is associated with hepatocellular carcinoma, even in the absence of cirrhosis. Nonalcoholic steatohepatitis mouse models have shown the benefits of regular exercise on hepatocellular carcinoma development. These models showed that total tumor volume per liver and tumor cell proliferation were reduced by exercise. Exercise also decreased the Ki-67-positive hepatocytes and increased p53 activity in the liver. In addition, an increased expression of Bcl-xL and the striking upregulation of p27 related to p53 activity were found in the liver. These findings suggest that p53 activation and resultant p27 expression are possible pathways by which exercise decreases hepatocyte proliferation and the development of tumor growth. Exercise could counteract hepatocellular carcinoma progression by activating adenosine monophosphate-activated protein kinase and thereby impairing mTORC1 activity. Impaired mTORC1 activity results in inhibition of cell proliferation in response to growth factors. The tumor suppressor PTEN was identified as a target of exercise by presenting increased expression in tumors of exercised rats. Loss of PTEN is shown to result in cell proliferation, growth, and invasion; therefore, increased expression of PTEN in a tumor will abate the cell proliferation and tumor growth. In addition, STAT3, a downstream factor of the mechanistic target of rapamycin that plays a role in tumor angiogenesis and metastasis, has been shown to be decreased in exercised rats. Thus, prevention of its activation will inhibit growth of hepatocellular carcinoma. In clinical studies, exercise was positively associated with improved recurrence-free survival in patients with hepatocellular carcinoma. Exercise may slow cancer progression by direct action on tumor-intrinsic factors and signaling pathways, thus possibly improving the efficacy of the anticancer treatment. This review explains the potential anticancer benefits of exercise by highlighting the tumor-intrinsic factors and signaling pathways of hepatocellular carcinoma associated with exercise.

COVID-19 outcomes in patients with antiphospholipid syndrome: a retrospective cohort study.

BACKGROUND: Aim of this study is to investigate COVID-19 outcomes in patients with antiphospholipid syndrome (APS). METHODS: A retrospective cohort was formed from APS patients. Patients were screened for a record of positive SARS-CoV 2 PCR. In PCR­positive patients, clinical data and information regarding COVID-19 outcomes were collected from medical records. RESULTS: A positive PCR test was detected in 9/53 APS patients, while 66.7 %, 33.3 % and 11.1 % of APS patients with COVID-19 were under hydroxychloroquine, LMWH or warfarin, and acetylsalicylic acid, respectively. There were 3/9 patients found to be hospitalized and one died. No new thrombotic event was reported in any of the patients during COVID-19 infection. CONCLUSION: Baseline use of hydroxychloroquine, antiaggregants and anticoagulants may be associated with an absence of new thrombotic event (Tab. 2, Ref. 33).

Bioactivity of EtOH and MeOH Extracts of Basidiomycetes Mushroom (Stereum hirsutum) on Atherosclerosis.

Mushrooms are cosmopolitan organisms living on different substrates and have different pharmacological properties, such as antioxidant, antimicrobial, and anti-inflammatory effects thanks to many bioactive compounds. Edible and medicinal higher fungi have been used by humankind for millennia. They are collected and used directly not only for their nutritional values as a main source of food or as a part of a regular diet but also for their medicinal purpose as a source of powerful new bioactive compounds. Antioxidative and anti-inflammatory functions and therefore lipid-lowering effects correlate with antiatherogenic effects. This study determined the total antioxidant capacity (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), 1-diphenyl-2-picrylhydrazyl (DPPH) activity, and antimicrobial activity of ethanolic and methanolic extracts of Stereum hirsutum (Willd.) Pers. Moreover, the effects on atherosclerosis are discussed according to the antioxidant activity of the mushroom. The TAS, TOS, and OSI values of S. hirsutum were determined using Rel Assay kits. According to the results, the TAS, TOS, and OSI values were determined at 5.289&plusmn;0.113 mmol/L, 20.540&plusmn;0.416 &mu;mol/L, and 0.389&plusmn;0.012. Furthermore, free radical scavenging activity was determined by the DPPH method. The ethanol (EtOH) extracts of S. hirsutum showed higher DPPH activity than methanol extracts. The EtOH extracts at a concentration of 2 mg/mL showed a DPPH inhibition of 45.84&plusmn;0.81%. Antimicrobial activities were tested on 9 standard bacterial and fungal strains, including Staphylococcus aureus, S. aureus MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida albicans, C. krusei,and C. glabrata using a modified agar dilution method. Extracts showed high activity against S. aureus, S. aureus MRSA, and A.baumannii. In conclusion, it was suggested that S. hirsutum can be used as a natural source related to the effects on atherosclerosis due to its antioxidant and antimicrobial activities.

Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy but frequently cause immune-related adverse events (irAEs). Description of late-onset and duration of irAEs in the literature is often incomplete. METHODS: To investigate reporting and incidence of late-onset and long-lasting irAEs, we reviewed all registration trials leading to ICI's approval by the US FDA and/or EMA up to December 2019. We analysed real-world data from all lung cancer (LC) and melanoma (Mel) patients treated with approved ICIs at the University Hospital of Lausanne (CHUV) from 2011 to 2019. To account for the immortal time bias, we used a time-dependent analysis to assess the potential association between irAEs and overall survival (OS). RESULTS: Duration of irAEs and proportion of patients with ongoing toxicities at data cut-off were not specified in 56/62 (90%) publications of ICIs registration trials. In our real-world analysis, including 437 patients (217 LC, 220 Mel), 229 (52.4%) experienced at least one grade ≥2 toxicity, for a total of 318 reported irAEs, of which 112 (35.2%) were long-lasting (≥6 months) and about 40% were ongoing at a median follow-up of 369 days [194-695] or patient death. The cumulative probability of irAE onset from treatment initiation was 42.8%, 51.0% and 57.3% at 6, 12 and 24 months, respectively. The rate of ongoing toxicity from the time of first toxicity onset was 42.8%, 38.4% and 35.7% at 6, 12 and 24 months. Time-dependent analysis showed no significant association between the incidence of irAEs and OS in both cohorts (log Rank p = 0.67 and 0.19 for LC and Mel, respectively). CONCLUSIONS: Late-onset and long-lasting irAEs are underreported but common events during ICIs therapy. Time-dependent survival analysis is advocated to assess their impact on OS. Real-world evidence is warranted to fully capture and characterise late-onset and long-lasting irAEs in order to implement appropriate strategies for patient surveillance and follow-up.

Correlation of C-Reactive Protein and Serum Iron Levels with Syntax Score.

Cardiovascular disease is one of the most common causes of morbidity and mortality in the world. Atherosclerosis is an inflammatory process, and serum C-reactive protein (CRP) is an acute-phase protein rising in response to inflammation. Serum iron (Fe) is one of the essential metals for the human body. Inflammation and infection are characterized by changes in Fe metabolism. Since atherosclerosis is an inflammatory process, changes in CRP and serum Fe levels are expected. However, the distribution of the disease in the coronary arteries is important for mortality and morbidity. The distribution of the disease can be determined by the syntax score. This study included 407 patients with a mean age of 56.4&plusmn;10.7 years. The majority of the patients were male (51.4%). In this study, 53 and 354 patients had critical and no critical lesions, respectively. According to the baseline coronary angiograms, the syntax score was calculated in all patients. The laboratory variables, including hemoglobin levels, blood glucose, creatinine, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, Fe, and CRP were also evaluated in this study. Regarding the laboratory parameters of all groups, the mean CRP levels, Fe levels, and syntax score were estimated at 0.75&plusmn;1.8 mg/dl, 80.4&plusmn;27.5 mg/dl, and 1.5&plusmn;4.8, respectively. Furthermore, a high syntax score correlated with Fe and CRP levels. Based on the findings of the present study, elevated serum Fe and CRP concentrations were associated with increased syntax score and atherosclerosis severity.

Association between focal adhesion kinase and matrix metalloproteinase-9 expression in prostate adenocarcinoma and their influence on the progression of prostatic adenocarcinoma.

Focal adhesion kinase (FAK), a member of the non-receptor cytoplasmic tyrosine kinase family, is associated with the development and progression of cancer. Matrix metalloproteinase-9 (MMP-9) is directly involved in the degradation of the extracellular matrix, and basement membrane components promote cancer cell migration and invasion. There is a functional interaction among FAK, MMP-9 and vascular endothelial growth factor (VEGF), which leads to enhanced cancer angiogenesis, cancer cell invasion and progression of malignancy. FAK, MMP-9, VEGF and CD34-positive microvessel density (MVD) were examined in 100 patients with prostate adenocarcinoma using immunohistochemistry. The relationship among these proteins and their impact on angiogenesis and clinicopathological parameters were also evaluated. The FAK expression was found to be positively correlated with the Gleason score, WHO grade group, tumour stage, extracapsular extension and perineural invasion. The MMP-9 expression was positively correlated with the WHO grade group, tumour stage, extracapsular extension, positive surgical margin and lymphovascular and perineural invasion. The FAK expression was also positively correlated with MMP-9 expression and MVD. However, no correlation between FAK and VEGF expression was identified. The MMP-9 expression was positively correlated with FAK expression and MVD. Strong MMP-9 expression was associated with shorter disease-free survival. These results suggest that strong MMP-9 and FAK expressions play an essential role in the progression of prostate adenocarcinoma. Further investigations should be conducted to determine the importance of these proteins as therapeutic targets for patients with prostate adenocarcinomas.

Controversy about the protective role of volume in the frontal sinus after severe head trauma: larger sinus equates with higher risk of death.

The "crumple zone" hypothesis suggests that the paranasal sinuses protect the brain as a zone to distribute and absorb energy after trauma to the head. We investigated the relation between the size of the frontal sinus and mortality in patients with cranial trauma. All patients with head trauma admitted to the ICU between 1 January 2016 and 20 December 2017 were reviewed retrospectively. They were divided into two groups (according to their outcome) : died and survived. The volumes of the frontal sinuses and other trauma-related variables were assessed on computed tomographs (CT) on admission. Admission CT of 33 patients (24 male, and nine female, aged between 18-92 years, mean 43) were obtained. Male patients had significantly larger frontal sinuses than female (10.24 compared with 6.6cm3). Larger sinuses were significantly associated with a worse outcome (p=0.005). The size of the frontal sinus correlates with mortality after cranial trauma. Our findings do not confirm the "crumple zone" hypothesis, and suggest that the larger the sinus, the greater the risk of death. To our knowledge this is a new finding that warrants further validation.

Gender medicine and oncology: report and consensus of an ESMO workshop.

BACKGROUND: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018. DESIGN: Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here. RESULTS: Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy. CONCLUSION: Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.

Evaluation of New Baskent University Preservation Solution for Kidney Graft During Cold Ischemia: Preliminary Experimental Animal Study.

OBJECTIVES: Organ damage due to long cold ischemia time remains a hurdle in transplantation. In this preliminary animal study, we compared the new Baskent University Preservation Solution (BUPS) with the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions. MATERIALS AND METHODS: BUPS composition included electrolytes, raffinose, mannitol, N-acetylcysteine, taurine, adenosine, and ascorbic acid. In experiment 1, kidneys from 50 male Sprague-Dawley rats were placed into BUPS, HTK, or UW solution to assess cold ischemia injury, with biopsies taken at different time points for pathologic evaluation. In experiment 2, to investigate ischemia-reperfusion injury, 5 rats were renal transplant donors to 10 rats and 6 pigs were used as transplant donors-recipients among each other. RESULTS: In experiment 1, no significant cellular injury was shown at up to 3 hours of perfusion with any solution. At 6- to 48-hour perfusion, tubular injury was shown, with lowest injury in BUPS and HTK versus UW and control groups (P < .01). The BUPS group showed more moderate degree of tubular apoptosis and cytoskeletal rearrangement than the HTK and UW groups at 12-, 24-, and 48-hour perfusion (P < .01). In experiment 2, after ischemia-reperfusion injury, no significant differences were found between HTK and BUPS groups regarding tubular damage. Although no significant differences were shown regarding tubular cytoskeletal rearrangment and apoptosis in pig reperfusion group with BUPS versus HTK, significant differences were shown with these solutions in other groups. CONCLUSIONS: Tubular damage during ischemia-reperfusion injury (cytoskeletal disruption, increased apoptosis) were lower with BUPS. BUPS can be a cost-effective perfusion solution in transplantation.