The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam. A small positron emission tomography (PET) system was exposed in an ocular beam of the Proton Therapy Center at MD Anderson Cancer Center to view phantoms irradiated by 3.5 × 1010protons with a kinetic energy of 75.8 MeV delivered in 101.5 ms-long spills yielding a dose rate of 164 Gy s-1. Most in-spill events were due to prompt gammas. Reconstructed post-spill tomographic events, recorded for up to 20 min, yielded quantitative imaging and dosimetric information. These findings open a new and novel modality for imaging and monitoring of FLASH proton therapy exploiting in-spill prompt gamma imaging followed by post-spill PET imaging.

Secondary bacterial infections & extensively drug-resistant bacteria among COVID-19 hospitalized patients at the University Hospital in Kraków.

INTRODUCTION: Healthcare-associated infections (HAI) and bacterial antimicrobial resistance posed a therapeutic risk during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to analyze the HAIs in COVID-19 patients in the Intensive Care Unit (ICU) and non-ICU at the University Hospital in Krakow (UHK) with an emphasis on the susceptibility of the most frequently isolated pathogens and the prevalence of extensively drug resistant (XDR) microorganisms. METHODS: This laboratory-based study was carried out at the University Hospital in Krakow in the ICU and non-ICUs dedicated to COVID-19 patients between May 2021 and January 2022. All isolates of Klebsiella pneumoniae were analyzed using PFGE protocol. RESULTS: 292 independent HAI cases were identified, with the predominance of urinary tract infections (UTI), especially in the non-ICU setting. The most common ICU syndrome was pneumonia (PNA). The prevalence of XDR organisms was 22.6% in the ICU and 14.8% in non-ICUs among all isolates. The incidence of carbapenem-resistant Enterobacteriaceae infection was 24.8 cases per 10,000 hospitalizations and the carbapenem-resistant A. baumannii infection incidence was 208.8 cases per 10,000 hospitalizations. The prevalence of XDR strains was highest in Acinetobacter spp, in PNA cases. The PFGE typing demonstrated that almost all XDR strains varied widely from each other. CONCLUSIONS: In this study, there was a high incidence of HAI in COVID-19 patients, especially when compared to Western Europe and the United States. Similarly, the prevalence of XDR microorganisms, especially XDR-A.baumannii, was also high. PFGE did not confirm the horizontal spread of any organism strains.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium-zinc-telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

The assessment of serum and diagnostic peritoneal lavage concentration of matrix metalloproteinase-2, matrix metalloproteinase-9, carbohydrate antigen 19-9, and carcinoembryonic antigen in patients with pancreatic cancer and chronic pancreatitis.

Pancreatic cancer and chronic pancreatitis are still significant diagnostic and clinical problems. A tumor marker that would eliminate the imperfection of preoperative serum carbohydrate antigen 19-9 (CA19-9) concentration is still being sought. This study aimed to conduct a comparative analysis of the concentrations in serum and peritoneal cavity of matrix metalloproteinases: metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9), CA19-9, and carcinoembryonic antigen (CEA) in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and a control group (CG). The study was performed in a group of 90 patients. Group 1 consisted of 30 patients with PC, group 2 consisted of 30 patients with CP. There was no case of pancreatic cancer in the CP group. Group 3 (CG) consisted of 30 individuals, who were recruited among patients operated for non-inflammatory cholelithiasis. The serum samples and intraperitoneal fluid, when present or samples of peritoneal lavage were taken from patients and the concentration of MMP-2, MMP-9, and CA19-9 were evaluated. The revealed intraperitoneal fluid concentrations of the MMP-2, MMP-9, and CA19-9 were significantly higher in both PC and CP groups in comparison to CG. There were no statistically significant differences between intraperitoneal fluid concentrations of the MMP2, MMP9, and CA19-9 in PC and CP groups. The revealed serum concentration of the MMP-2 and MMP-9 in the PC, CP, and CG were significantly higher compared to the intraperitoneal fluid. There was no significant correlation between serum and intraperitoneal fluid concentration of the MMP-2, MMP-9, and CA19-9 and the presence of cancer cells in the intraperitoneal fluid conventional cytological examination. The elevated preoperative intraperitoneal fluid concentration of MMP-2 and MMP-9 and serum concentration of CA19-9 and CEA showed significant sensitivity and specificity in PC prediction. The preoperative serum concentrations of MMP-2 and MMP-9, serum, and intraperitoneal fluid concentrations of CA19-9 and CEA have been shown to have a statistically significant effect on predicting cancer progression and the presence of distant metastases. Presented findings suggest the usefulness of MMP-2 and MMP-9 as a potential predictor of PC and marker of dissemination but its usefulness in the differential diagnosis between PC and CP is limited, however more studies on a large population are needed to support our result. To our knowledge, this was the first study evaluating not only MMP-2 and MMP-9 concentrations in serum but also the concentration of these metalloproteinases in peritoneal fluid in patients with PC and CP.

Vibrational microspectroscopy analysis of human lenses.

In this study we present vibrational analysis of healthy (non-affected by cataract) and cataractous human lenses by means of Raman and FTIR spectroscopy methods. The performed analysis provides complex information about the secondary structure of the proteins and conformational changes of the amino acid residues due to the formation of opacification of human lens. Briefly, the changes in the conformation of the Tyr and Trp residues and the protein secondary structure between the healthy and cataractous samples, were recognized. Moreover, the observed spectral pattern suggests that the process of cataract development does not occur uniformly over the entire volume of the lens.

Competition between Bose-Einstein Condensation and Spin Dynamics.

We study the impact of spin-exchange collisions on the dynamics of Bose-Einstein condensation by rapidly cooling a chromium multicomponent Bose gas. Despite relatively strong spin-dependent interactions, the critical temperature for Bose-Einstein condensation is reached before the spin degrees of freedom fully thermalize. The increase in density due to Bose-Einstein condensation then triggers spin dynamics, hampering the formation of condensates in spin-excited states. Small metastable spinor condensates are, nevertheless, produced, and they manifest in strong spin fluctuations.

[Diagnosis and treatment of retroperitoneal abscesses]. / Diagnostik und Therapie retroperitonealer Abszesse.

BACKGROUND: Retroperitoneal abscesses are rare but life threatening. Renal, perinephritic, and paranephritic abscesses are distinguished depending on their location and extent. They are mainly caused by ascending urologic infections of gram-negative bacteria. SYMPTOMATOLOGY: The variable symptomatology often leads to delayed diagnosis resulting in high morbidity and mortality. Typical symptoms are flank or abdominal pain, decreased appetite, weight loss, malaise, fever, and chills. Laboratory values show increased leukocytes and C­reactive protein. Creatinine levels may also be increased. CONCLUSION: If there is clinical evidence for a retroperitoneal abscess, sonography generally leads to further diagnostic via computed tomography. Small abscesses may be treated by antibiotics alone. Abscesses larger than 3 cm and those not responding to medical treatment should be percutaneously or surgically drained.

[Vascular Problem Constellations and the Operational Tactical Approaches in Post-Mortem Liver Transplantations]. / Vaskuläre Problemkonstellationen und ihre operationstaktischen Lösungsansätze im Rahmen der postmortalen Lebertransplantation.

In liver transplantation, vascular problems may occur in the donor as well as in the recipient and during the donor operation as well as during the transplantation. They have a major influence on the outcome of the transplantation. In addition to anatomic variants, arteriosclerotic vascular diseases, complications from portal hypertension, vascular lesions from mistakes during the donor operation, complications from interventions and bridging procedures need to be identified and treated. In addition to duplex sonography and contrast enhanced computed tomography, invasive vascular diagnostics (digital subtraction angiography) are established for diagnostic purposes. Problem constellations should be identified prior to transplantation and the technique of the donor operation and the transplantation should be adjusted accordingly. Problems that are diagnosed after transplantation may be treated interventionally or with open surgery. In a number of cases, vascular complications lead to loss of the transplant or death of the recipient from post-operative organ failure.

Characterisation of Atherogenic Effects of Low Carbohydrate, High Protein Diet (LCHP) in ApoE/LDLR-/- Mice.

INTRODUCTION: Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss. OBJECTIVE: The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in apoE/LDLR-/- mice and to elucidate mechanisms of proatherogenic effects of LCHP diet. MATERIALS AND METHODS: Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low Carbohydrate High Protein) diet fed mice. RESULTS: Area of atherosclerotic plaques in aortic roots or BCA from LCHP diet fed mice was substantially increased as compared to mice fed control diet and was characterized by increased lipids and cholesterol contents (ORO staining, FT-IR analysis), increased macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro-atherogenic phenotype of LCHP fed apoE/LDLR-/- mice was associated with increased plasma total cholesterol concentration, and in LDL and VLDL fractions, increased TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered acute phase response as evidence by an increased plasma concentration of haptoglobin, CRP or AGP. Finally, in long-term experiment survival of apoE/LDLR-/- mice fed LCHP diet was substantially reduced as compared to their counterparts fed control diet suggesting overall detrimental effects of LCHP diet on health. CONCLUSIONS: The pro-atherogenic effect of LCHP diet in apoE/LDLR-/- mice is associated with profound increase in LDL and VLDL cholesterol, VLDL triglicerides, liver SREBP-1 upregulation, and systemic inflammation.

Placental Schistosoma haematobium infection in a German returnee from Malawi.

Schistosomiasis is a widespread helminthic infection which sometimes may affect travelers to endemic areas. We report on a case of urogenital and placental schistosomiasis in a 28-year-old German woman who had been exposed to schistosomiasis in Lake Malawi one year earlier. She experienced painless macrohaematuria in her 21st week of pregnancy. Cystoscopy revealed vesical lesions typical for urogenital schistosomiasis. Histopathology confirmed ova of Schistosoma (S.) haematobium. The patient was treated with praziquantel 40 mg/kg/body weight/day for 3 days. After 285 days of gestation and 18 weeks post treatment, the patient delivered a healthy girl. Histopathology of placenta revealed eggs of S. haematobium in placental stroma. The infant proved negative for anti-Schistosoma spp. antibodies at the age of 15 months. This is the first report on placental schistosomiasis since 1980 and the first case occurring in a traveler.

Physicochemical and dissolution studies of simvastatin solid dispersions with Pluronic F127.

Simvastatin (SIM) solid dispersions with Pluronic F127 (PLU) obtained by kneading and fusion methods were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier Transform Infrared Spectroscopy (FTIR). DSC studies demonstrate that the SIM/PLU solid dispersions formed a simple eutectic phase diagram. FTIR spectroscopy and XRPD studies of obtained mixtures showed no interaction between the components in the solid state and confirmed the absence of terminal solid solutions. Intrinsic dissolution studies of solid dispersions in 0.5% sodium lauryl sulfate solution (SLS) indicated that the dissolution rate markedly increased in these solid dispersions systems compared with pure SIM. The increase in dissolution rate strongly depended on ratios of drug to carriers and selection of the method of preparations of mixtures. The solid dispersions prepared in the weight ratios of 60.0/40.0% and 69.9/30.1% w/w of SIM/PLU by the kneading method showed the highest improvement in wettability and dissolution rate of SIM. Approximately 100% of the drug was dissolved from these mixtures in comparison to 3.84% of pure simvastatin within 120 min.

Identification of high-risk patients with clear cell renal cell carcinoma based on interphase-FISH.

BACKGROUND: The aim of this study was to examine the prognostic value of four significant aberrations based on our previous studies by array-CGH to develop a prognostic Fluorescence-in situ-hybridisation (FISH) assay for clear cell renal cell carcinomas (ccRCC). METHODS: Fluorescence-in situ-hybridisation experiments were performed on 100 ccRCCs (52 metastasised out of 48 non-metastasised). The mean/median follow up of patients was 59/54 months. Commercially available FISH probes were used for each critical chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32). The total number of specific aberrations (TNSA) was calculated for each tumour based on the specific genomic alterations. RESULTS: Total number of specific aberrations was the best predictor of metastasis (area under the curve (AUC)=0.814) compared with single aberrations (AUC: 0.619-0.708) and to 11 different combinations of these 4 aberrations in the receiver operating characteristic curve analysis. Total number of specific aberrations, tumour grade and tumour size were independent predictors of metastasis in the multivariate analysis (P<0.001) for the whole cohort as well as for organ-confined tumours. Total number of specific aberrations and grade could also independently predict cancer-specific mortality (CSM). Total number of specific aberrations demonstrated the highest significance in COX proportional hazard models of overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). CONCLUSIONS: We identified TNSA as an independent prognostic factor which is associated with metastasis occurrence, CSM, OS, CSS and PFS in patients with ccRCCs.

Prophylactic bilateral salpingectomy (PBS) to reduce ovarian cancer risk incorporated in standard premenopausal hysterectomy: complications and re-operation rate.

PURPOSE: Hysterectomy for benign conditions can be combined with bilateral salpingectomy to prevent re-intervention for malignant or benign fallopian tube pathologies. The objective of this study was to evaluate the benefit of prophylactic bilateral salpingectomy (PBS) in standard hysterectomy in premenopausal women. METHODS: This retrospective cohort study included all premenopausal patients at our institution who underwent laparoscopically assisted vaginal hysterectomy (LAVH) without oophorectomy for benign pathologies between 2001 and 2007 [PBS group (LAVH + PBS), 2006-2007; non-PBS group (LAVH without PBS), 2001-2005]. Electronic and paper-based files as well as questionnaire responses were analyzed. In 2010, a survey on patients of a non-BRCA background with and without PBS was requested to complete a standardized questionnaire. Data were analyzed for differences between both subgroups regarding surgical outcome and adnexal pathologies as reported in the postoperative follow-up. RESULTS: Surgical outcomes of 540 patients (PBS: 127; non-PBS: 413) revealed no difference between groups. No preneoplastic or malignant lesions were diagnosed in the fallopian tubes. Follow-up (non-PBS 92 months, PBS 55 months; p < 0.01) responses from 295 (54.6 %) patients showed a higher incidence of benign adnexal pathologies in the non-PBS group (26.9 vs. 13.9 %; p = 0.02). The rate of LAVH-related surgical re-intervention was higher in the non-PBS group (12.56 vs. 4.16 %; p = 0.04). No malignant neoplasm was reported in the cohort. CONCLUSIONS: PBS did not increase the complication rate and reduced the incidence of adnexal pathologies requiring surgical re-intervention. Prospective trials should clarify the impact of PBS on cancer mortality.

Effect of nebivolol treatment on atherosclerotic plaque components in apoE-knockout mice.

Nebivolol, a third generation beta1-blocker was previously found to reduce the size of atherosclerotic lesions. The aim of this study was to assess the effect of orally administered nevibolol on the components of the atherosclerotic plaque in apoE-deficient mice. The quantitative evaluation of cross-sectioned plaques stained by histological and immunohistochemical techniques revealed that treatment with nebivolol (2.0 µol per kg b.w.) for 4 months caused a decrease in the necrotic core area (by 46%, p=0.03), density of CD68+ macrophages (by 41%, p=0.008) and CD3+ lymphocytes (by 16%, p=0.03), collagen content (by 49%, p=0.008) and the activity area of metalloproteinases (by 48%, p=0.008), as well as an increase in the smooth muscle content of the fibromuscular cap (by 46%, p=0.008). These effects suggest that nebivolol suppresses the inflammatory/immune processes in the plaque and enhances its stability.

[Evaluation of a cell block method in cytological diagnostics]. / Evaluation eines Zellblockverfahrens in der zytologischen Diagnostik.

BACKGROUND: Cell block procedures have now become an established part of cytological diagnostics. In this study a cytoblock technique based on the plasma-thrombin method was evaluated. MATERIALS AND METHODS: In total 389 consecutive cytological samples were initially analyzed by the classical procedure and then by the cell block technique. The latter was done by centrifugation of the remaining material of the cytological sample, resuspension of the cells in blood plasma followed by generation of a cell clot by the addition of thrombin. RESULTS: Analysis of material from the peritoneal cavity, ascites and pleura was successful in more than 90% of cases. In 272 samples the conventional and cell block analyses revealed concordant results according to Papanicolaou classification. In 23 cases the cell block analysis induced an upgrade. In particular, malignant processes (PAP V) or precursor lesions (PAP IV) were identified in 9 cases which were not diagnosed by conventional analysis. CONCLUSIONS: Advantages of this method include the assessment of an additional sample volume and thus reduction of sampling error, the possibility for unlimited storage and molecular testing similar to histological samples.

Effects of margarine supplemented with t10c12 and C9T11 CLA on atherosclerosis and steatosis in apoE/LDLR -/- mice.

OBJECTIVES: The objective of this study was to evaluate functional effects of margarine supplemented with individual CLA isomers trans-10, cis-12 and cis-9, trans-11 in apoE/LDLR -/- mice. DESIGN: In LONG experiment (LONG), two-month old mice with no atherosclerosis were assigned to experimental groups and fed for the next 4 months. In SHORT experiment (SHORT), four-month old mice, with pre-established atherosclerosis, were assigned to experimental groups and fed for the next 2 months. The experimental diets were: AIN-93G (margarine), AIN-93G + 0.5% trans-10, cis-12 CLA (t10c12), and AIN-93G + 0.5% cis-9, trans-11 CLA (c9t11). RESULTS: In both experiments (LONG and SHORT), liver weight was significantly (P<0.05) increased in mice fed t10c12 CLA. Hepatic steatosis was found in animals fed t10c12 diet and no signs of the steatosis was observed in mice fed c9t11 CLA. Dietary treatments with t10c12 CLA significantly increased total plasma cholesterol and plasma triacylglycerols. There were no isomer-specific effects of CLA isomers on area of atherosclerotic plaque in aortic root. CONCLUSION: In conclusion, t10c12 CLA significantly increased liver weight in mice in LONG and SHORT experiments. Our results do not support the notion that CLA isomer supplementation to the margarine possess anti-atheroclerotic effect. Therefore, no isomer-specific effects of CLA on development of atherosclerosis were observed.

Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice.

Our interest focused on an open question whether AT-(1-7), nonpeptide receptor agonist: AVE 0991, is able to ameliorate atherosclerosis. We used an apolipoprotein E (apoE) - knockout mice model of atherosclerosis. Experimental groups received the same diet as control, mixed with: AVE 0991 at a dose of 0.58 µmol/kg b.w./day, perindopril at a dose of 0.4 mg/kg b.w./day or with tiorphan at a dose of 2.5 mg/kg b.w./day. A-779 [(D-alanine)-angiotensin (1-7)] was given at a dose of 3.3 mg/kg b.w., 3 times a week i.p. Measured by "en face" method, the percentage of occupied by Sudan IV-stained surfaces were as follows: 14.2±1.9 % in control group, whereas in AVE 0991-treated as well as in perindopril-treated groups percentages were statistically significantly lower. In tiorphan group there was no change comparing to control group, whereas in A-779 group percentage was statistically significantly higher. "Cross-section" of aortic roots revealed also the difference in atherosclerotic lesions. The mean surfaces, occupied by oil red O-stained changes were: 91.213±8.123 µm(2) in control group, while in AVE 0991-treated as well as in perindopril-treated groups lesions were statistically significantly lower. In tiorphan group there was no change; however, in A-779 group lesions were statistically significantly higher. Measured by real time RT-PCR relative p22phox (submit of NADPH oxidase) expression was significantly decreased in AVE 0991-treated mice. As revealed by flow cytometry, the expression of co-stimulatory molecules: CD86, CD80 and CD40 on both dendritic cells (CD11c+) and macrophages (F4/80+) was reduced in AVE 0991-treated group, which correlated with decreased expression of CD69 activation marker on CD4+T cells. In our report we showed the beneficial effect of AVE 0991 on atherogenesis in gene-targeted mice.

Immunohistochemical marker panel differentiates between the three most common subtypes of renal cell carcinoma independent from histomorphologic criteria.

To develop a reliable immunohistochemical marker panel differentiating between the three most common renal cell carcinoma (RCC) subtypes without inclusion of histomorphologic criteria we investigated protein expression of vimentin, glutathione S-transferase alpha (GST-α), CD10, CD117 (C-KIT), carbonic anhydrase 2 (CAII), parvalbumin, alpha-methyl-CoA-racemase (AMACR), and cytokeratin-19 (CK 19) in 65 age and stage matched trios of clear cell carcinoma, papillary renal carcinoma and chromophobe renal carcinoma using tissue microarrays. All markers displayed significant differential expression among the subtypes (p < 0.001) except CAII (p = 0.192). According to positive (LR+) and negative (LR-) likelihood ratio, six markers (CD10, GST-α, AMACR, CK19, C-KIT and arvalbumin) demonstrated acceptable or good values to detect certain subtypes of RCC, but failed in terms of ruling out the respective subtypes. Based on the individual performance of these six markers, we combined them and reviewed each single case: LR+ for detection of clear cell RCC considerably increased by application of the six marker panel, but did not exceed 10. LR- was still >0.1; in case of papillary RCC LR+ rose beyond 10, but LR- remained >0.1. LR+ for recognition of chromophobe RCC rose far beyond 10, but LR- remained >0.1. Thus, the panel can reliably recognize two main RCC subtypes without inclusion of histomorphologic features. Further improvement is needed for consistent detection of clear cell RCC and for dependably ruling out all three main subtypes as well as identification of rare variants and benign lesions like oncocytoma.

[Rare differential diagnosis in a 40-year old patient with sleep apnea syndrome]. / Seltene Differenzialdiagnose bei einem 40-jährigen Patienten mit Schlafapnoe-Syndrom.

Respiratory disorders are common and important complications in acromegaly. The prevalence of sleep apnea syndrome (SAS) in this group of patients is high (20%-50%). Consequences of SAS are serious and associated with increased morbidity and mortality, mainly as a result of cardiovascular complications. The symptoms of sleep apnea are often reversible with treatment. We report on an acromegaly patient presenting with excessive snoring and severe headaches caused by sleep apnea.