Proteome alterations in human autopsy tissues in relation to time after death.

Protein expression is a primary area of interest for routine histological diagnostics and tissue-based research projects, but the limitations of its post-mortem applicability remain largely unclear. On the other hand, tissue specimens obtained during autopsies can provide unique insight into advanced disease states, especially in cancer research. Therefore, we aimed to identify the maximum post-mortem interval (PMI) which is still suitable for characterizing protein expression patterns, to explore organ-specific differences in protein degradation, and to investigate whether certain proteins follow specific degradation kinetics. Therefore, the proteome of human tissue samples obtained during routine autopsies of deceased patients with accurate PMI (6, 12, 18, 24, 48, 72, 96 h) and without specific diseases that significantly affect tissue preservation, from lungs, kidneys and livers, was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the kidney and liver, significant protein degradation became apparent at 48 h. For the lung, the proteome composition was rather static for up to 48 h and substantial protein degradation was detected only at 72 h suggesting that degradation kinetics appear to be organ specific. More detailed analyses suggested that proteins with similar post-mortem kinetics are not primarily shared in their biological functions. The overrepresentation of protein families with analogous structural motifs in the kidney indicates that structural features may be a common factor in determining similar postmortem stability. Our study demonstrates that a longer post-mortem period may have a significant impact on proteome composition, but sampling within 24 h may be appropriate, as degradation is within acceptable limits even in organs with faster autolysis.

Sterile, abscess-like cerebral lesion during trastuzumab therapy after HER2 status switch in a triple negative breast cancer patient: a case report and literature review.

BACKGROUND: Breast cancer is a global health problem - it is the most common malignancy among women. Triple negative breast cancers (TNBC) account for 10-20% of female breast cancer. Most TNBC cases confer poor prognosis. Brain metastasis appears in more than 15% in the triple negative breast cancer population, which causes serious decrease in survival. Changes of immunophenotype are not uncommon in breast cancer, offering new therapeutic options in cases where targetable proteins or pathways are being identified. CASE PRESENTATION: After five lines of chemotherapy and 82 months following the first diagnosis, our patient with brain metastatic triple negative breast cancer had human epidermal growth factor receptor 2 (HER2) genetic heterogeneity in the metastatic tissue sample interpreted as HER2 status conversion. After the removal of the metastasis, we started first line therapy for metastatic HER2 positive cancer with trastuzumab and paclitaxel. After the first cycle of trastuzumab, on day 8, she had a seizure, and neurosurgical examination showed an abscess-like lesion. The punctate proved to be sterile by microbiological and pathological examination, so we continued cytostatic therapy without the anti-HER2 antibody. 3 months later, we could not identify the previous abscess-like lesion in the control computer tomography (CT) scan, and our patient had no neurological deficits. CONCLUSION: We emphasize the importance of regular tissue confirmation of predictive markers in progressive tumorous disease even if our presented case is not unequivocally a "conversion case". Tumor subtype is determined according to algorithms and definitions published in guidelines, nevertheless, use of different guidelines may lead to controversial interpretation in cases where HER2 genetic heterogeneity is present. Furthermore, we suggest that seronegative, aseptic intracranial fluid effusion after the removal of a brain metastasis may possibly be a side effect of trastuzumab.

Helicobacter pylori heteroresistance to clarithromycin in adults-New data by in situ detection and improved concept.

BACKGROUND: Clarithromycin (Cla) heteroresistance of Helicobacter pylori (H pylori) infections is commonly assessed by comparing the resistance status of antrum and corpus biopsy samples and by demonstrating the discrepancy between them (interniche heteroresistance). However, fluorescence in situ hybridization (FISH) technique is capable of showing the synchronous presence of susceptible and resistant bacteria (intraniche heteroresistance), enabling the detection of heteroresistant H pylori populations within one biopsy sample. MATERIALS AND METHODS: Antrum and corpus biopsy specimens of 305 H pylori-infected patients were investigated with an rRNA-targeted Cla-resistance FISH test. Anamnestic data were collected from the institutional electronic register. Prevalence rates of susceptible, homo- and heteroresistant cases were correlated with the anamnestic and clinicopathological data. RESULTS: Overall Cla-resistance rate was 23.9% (73 cases), consisting of 35 (11.5%) homoresistant and 38 (12.5%) heteroresistant cases. Thirty-five patients had at least one biopsy site where susceptible and resistant bacteria were present simultaneously. From this subset, 20 cases demonstrated intraniche heteroresistance on both sites. Prior Cla-based eradication attempts were more frequent in homoresistant than in susceptible and heteroresistant cases (P < .001, P < .001, respectively). Cla-containing therapy eradicated heteroresistant infections at a significantly lower rate in comparison with susceptible cases (P = .0112), but more effectively than homoresistants (P = .0393). CONCLUSIONS: The most frequent type of Cla-heteroresistance is the coexistence of susceptible and resistant H pylori bacteria in the same location (intraniche heteroresistance). A previous Cla-based eradication attempt predisposes patients to homoresistant infection. Heteroresistance is characterized by a non-eradication-related background and intermediate characteristics in many respects when compared to susceptible and homoresistant cases.

Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases.

BACKGROUND: Claudin-18 (CLDN18) is a highly specific tight junction protein of the gastric mucosa. An isoform of CLDN18, the Claudin 18.2, has recently emerged as an innovative drug target for metastatic gastric cancer. METHODS: We investigated the immunohistochemical profile of CLDN18, p53, p16, E-cadherin, MSH2, MSH6, MLH1, PSM2, HER2, and PDL-1 in a large series of 523 primary gastric carcinomas (GCs; n = 408) and gastro-oesophageal carcinomas (GECs; n = 115) and 135 matched and synchronous nodal metastases. The status of HER2 and EBER by means of chromogenic in situ hybridisation (CISH) was also evaluated. RESULTS: High membranous CLDN18 expression was present in 150/510 (29.4%) primary cases and in 45/132 (34.1%) metastases. An abnormal expression (i.e. nuclear and/or cytoplasmic) was observed in 115 (22.5%) primary cases and in 33 (25.0%) metastases. A 38.8% of the cases showed significant CLDN18 intratumoural variability among the different tissue microarray cores obtained from the same tumour. Positive membrane CLDN18 expression was statistically associated with non-antral GCs (p = 0.016), Lauren diffuse type (p = 0.009), and with EBV-associated cancers (p < 0.001). CONCLUSIONS: CLDN18 is frequently expressed in gastric and gastro-oesophageal cancers; further studies should investigate the prognostic significance of CLDN18 heterogeneity in order to implement its test into clinical practice.

A rapid and concise setup for the fast screening of FRET pairs using bioorthogonalized fluorescent dyes.

One of the most popular means to follow interactions between bio(macro)molecules is Förster resonance energy transfer (FRET). There is large interest in widening the selection of fluorescent FRET pairs especially in the region of the red/far red range, where minimal autofluorescence is encountered. A set of bioorthogonally applicable fluorescent dyes, synthesized recently in our lab, were paired (Cy3T/Cy5T; Cy1A/Cy3T and Cy1A/CBRD1A) based on their spectral characteristics in order to test their potential in FRET applications. For fast elaboration of the selected pairs we have created a bioorthogonalized platform based on complementary 17-mer DNA oligomers. The cyclooctynylated strands were modified nearly quantitatively with the fluorophores via bioorthogonal chemistry steps, using azide- (Cy1; CBRD1) or tetrazine-modified (Cy3; Cy5) dyes. Reactions were followed by capillary electrophoresis using a method specifically developed for this project. FRET efficiencies of the fluorescent dye pairs were compared both in close proximity (5' and 3' matched) and at larger distance (5' and 5' matched). The specificity of FRET signals was further elaborated by denaturation and competition studies. Cy1A/Cy3T and Cy1A/CBRD1A introduced here as novel FRET pairs are highly recommended for FRET applications based on the significant changes in fluorescence intensities of the donor and acceptor peaks. Application of one of the FRET pairs was demonstrated in live cells, transfected with labeled oligos. Furthermore, the concise installation of the dyes allows for efficient fluorescence modification of any selected DNA strands as was demonstrated in the construction of Cy3T labeled oligomers, which were used in the FISH-based detection of Helicobacter pylori.

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat.

BACKGROUND: Surgical removal of complicated liver tumors may be realized in two stages via selective portal vein ligation, inducing the atrophy of portally ligated lobes and the compensatory hypertrophy of nonligated liver lobes. Unlike morphological changes, functional aspects such as hepatic cytochrome P450 (CYP)-mediated drug metabolism remain vaguely understood, despite its critical role in both drug biotransformation and hepatic functional analysis. Our goal was the multilevel characterization of hepatic CYP-mediated drug metabolism after portal vein ligation in the rat. METHODS: Male Wistar rats (n = 24, 210-230 g) were analyzed either untreated (controls; n = 4) or 24/48/72/168/336 h (n = 4 each) following portal vein ligation affecting approximately 80% of the liver parenchyma. Besides the weights of ligated and nonligated lobes, pentobarbital (30 mg/kg)-induced sleeping time, CYP1A(2), CYP 2B(1/2), CYP2C(6/11/13), CYP3A(1) enzyme activities, and corresponding isoform mRNA expressions, as well as CYP3A1 protein expression were determined by in vivo sleeping test, CYP isoform-selective assays, polymerase chain reaction, and immunohistochemistry, respectively. RESULTS: Portal vein ligation triggered atrophy in ligated lobes and hypertrophy nonligated lobes. Sleeping time was transiently elevated (p = 0.0451). After an initial rise, CYP1A, CYP2B, and CYP3A enzyme activities dropped until 72 h, followed by a potent increase only in the nonligated lobes, paralleled by an early (24-48 h) transcriptional activation only in nonligated lobes. CYP2C enzyme activities and mRNA levels were bilaterally rapidly decreased, showing a late reconvergence only in nonligated lobes. CYP3A1 immunohistochemistry indicated substantial differences in positivity in the early period. CONCLUSIONS: Beyond the atrophy-hypertrophy complex, portal vein ligation generated a transient suppression of global and regional drug metabolism, re-established by an adaptive, CYP isoform-dependent transcriptional response of the nonligated lobes.

Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in comparison with immunohistochemistry and fluorescent in situ hybridization and strongly depends on inflammatory activity.

BACKGROUND: Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP). MATERIALS AND METHODS: We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations. RESULTS: Giemsa revealed 687 cases (23.7%), IHC 795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH (98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the nonactive cases. We found that sensitivity of Giemsa strongly depends on HP density and, accordingly, on the presence of activity. Structural alterations (intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity of the three stainings. Both IHC and FISH proved to be equally reliable HP detecting techniques whose diagnostic performance is minimally influenced by mucosal inflammatory and structural alterations contrary to conventional stainings. CONCLUSIONS: We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP.

[Molecular diagnostics of ALK-positive lung cancer]. / Az ALK-pozitív tüdõrák korszerû diagnosztikája.

ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH). In case of cytological samples FISH technique must be used as ALK diagnostics. In equivocal cases the genetic alteration of ALK can be confirmed by alternative molecular techniques such as next generation sequencing or RNAbased PCR methods. Upon administration of ALK inhibitors, acquired resistance is frequent which is mostly due to ALK amplification and/or mutation. It is evident that the diagnostics of these secondary ALK gene alterations must be done from recurrent tumors or circulating nucleic acids.

Postconditioning in major vascular surgery: prevention of renal failure.

BACKGROUND: Postconditioning is a novel reperfusion technique to reduce ischemia-reperfusion injuries. The aim of the study was to investigate this method in an animal model of lower limb revascularization for purpose of preventing postoperative renal failure. METHODS: Bilateral lower limb ischemia was induced in male Wistar rats for 3 hours by infrarenal aorta clamping under narcosis. Revascularization was allowed by declamping the aorta. Postconditioning (additional 10 sec reocclusion, 10 sec reperfusion in 6 cycles) was induced at the onset of revascularization. Myocyte injury and renal function changes were assessed 4, 24 and 72 hours postoperatively. Hemodynamic monitoring was performed by invasive arterial blood pressure registering and a kidney surface laser Doppler flowmeter. RESULTS: Muscle viability studies showed no significant improvement with the use of postconditioning in terms of ischemic rhabdomyolysis (4 h: ischemia-reperfusion (IR) group: 42.93 ± 19.20% vs. postconditioned (PostC) group: 43.27 ± 27.13%). At the same time, renal functional laboratory tests and kidney myoglobin immunohistochemistry demonstrated significantly less expressed kidney injury in postconditioned animals (renal failure index: 4 h: IR: 2.37 ± 1.43 mM vs. PostC: 0.92 ± 0.32 mM; 24 h: IR: 1.53 ± 0.45 mM vs. PostC: 0.77 ± 0.34 mM; 72 h: IR: 1.51 ± 0.36 mM vs. PostC: 0.43 ± 0.28 mM), while systemic hemodynamics and kidney microcirculation significantly improved (calculated reperfusion area: IR: 82.31 ± 12.23% vs. PostC: 99.01 ± 2.76%), and arterial blood gas analysis showed a lesser extent systemic acidic load after revascularization (a defined relative base excess parameter: 1(st) s: IR: 2.25 ± 1.14 vs. PostC: 1.80 ± 0.66; 2(nd) s: IR: 2.14 ± 1.44 vs. PostC: 2.44 ± 1.14, 3(rd) s: IR: 3.99 ± 3.09 vs. PostC: 2.07 ± 0.82; 4(th) s: IR: 3.28 ± 0.32 vs. PostC: 2.05 ± 0.56). CONCLUSIONS: The results suggest a protective role for postconditioning in major vascular surgeries against renal complications through a possible alternative release of nephrotoxic agents and exerting a positive effect on hemodynamic stability.

Improvement of small intestinal microcirculation by postconditioning after lower limb ischemia.

BACKGROUND: Major lower limb vascular surgeries may result in severe, remote injury of the gastrointestinal system, which has high mortality rates. Postconditioning is a technique with potential capability of reducing remote gastrointestinal complications. Our aim was to assess the remote macro- and micro-hemodynamic changes of the small intestine following an infrarenal aortic occlusion and to evaluate the effects of postconditioning on these alterations. METHODS: Rats underwent 3h of infrarenal aortic occlusion followed by 4h of reperfusion. In one group, postconditioning was applied. Blood pressure, superior mesenteric artery flow and mucosal microcirculation of the duodenum, jejunum and ileum were assessed. Samples were taken from each intestinal segment for histological examinations. RESULTS: Superior mesenteric artery flow, as well as microcirculation of the duodenum, jejunum and ileum showed significant impairment in the IR group, while histological damage was significantly worsened. Postconditioning was able to limit flow reduction in all three small bowel segments and in the superior mesenteric artery, and was able to significantly reduce histological damage. Strong negative correlation was found between microcirculatory values and histological damage. CONCLUSIONS: Microcirculatory impairment might be responsible for remote intestinal injury following infrarenal aortic occlusion. Postconditioning was able to reduce this remote intestinal damage.

Neural elements behind the hepatoprotection of remote perconditioning.

BACKGROUND: The ability of remote ischemic perconditioning (RIPER) to protect the liver from ischemic-reperfusion (IR) injury has been reported before; however, the mechanism behind the positive effects of RIPER remains unrevealed. Therefore, we aimed to investigate the potential role of neural elements to transfer protective signals evoked by perconditioning. MATERIALS AND METHODS: Male Wistar rats were randomly allocated into six groups (sham, IR, RIPER ± denervation; n = 7 per group). Half of the animals underwent left femoral and sciatic nerve resection. In IR and RIPER groups, normothermic, partial (70%) liver ischemia lasting for 60 min was induced; parallel animals in the RIPER groups received perconditioning treatment (4 × 5 - 5 min IR, left femoral artery clamping). Hepatic microcirculation and systemic blood pressure were monitored during the first postischemic hour. After 24 h of reperfusion, liver samples were taken for histology and redox-state analysis. Automated image analysis software was used for necrosis quantification. Serum alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were measured. RESULTS: Microcirculation and blood pressure showed significant improvement during reperfusion after perconditioning. This phenomenon was completely abolished by nerve resection (P < 0.05; RIPER versus IR, IR + denervation, and RIPER + denervation). Results of necrosis quantification showed similar pattern. Besides noncharacteristic changes in aspartate aminotransferase levels, alanine aminotransferase values were significantly lower (P < 0.05) in the RIPER group compared with the other IR groups. Mild but significant alterations were observed in liver function assessed by total bilirubin levels. Further supporting results were obtained from analysis of redox homeostasis. CONCLUSIONS: Perconditioning was able to reduce liver IR injury in our model via a mechanism most probably involving interorgan neural pathways.

Alterations in hepatic lobar function in regenerating rat liver.

BACKGROUND: Ligation of a branch of the portal vein redirects portal blood to nonligated lobes resulting in lobar hypertrophy. Although the effect of portal vein ligation on liver volume is well documented, the parallel alterations in liver function are still the subject of controversy. Our aim was to assess the time-dependent reactions of regional hepatic function to portal vein ligation by selective biliary drainage. METHODS: Male Wistar rats (n = 44) underwent 80% portal vein ligation. Before the operation as well as 1, 2, 3, 5, and 7 d after circulation, morphology and function (laboratory blood test; hepatic bile flow; plasma disappearance rate of indocyanine green; and biliary indocyanine green excretion) of the liver were examined. RESULTS: Although portal vein ligation affected liver circulation and morphology to a great extent, serum albumin levels, bilirubin levels, and total hepatic bile flow did not change significantly after the operation. Nevertheless, plasma disappearance rate and biliary indocyanine green excretion indicated a temporary impairment of total liver function with the lowest value on the second day and normalization by the fifth day. Bile production and biliary indocyanine green excretion of ligated lobes decreased rapidly after the operation and remained persistently suppressed, whereas the secretory function of nonligated lobes--after a temporary decline--showed a greater increase than the weight of the lobes. CONCLUSIONS: Portal vein ligation induced temporary impairment of total liver function, followed by rapid recovery mainly by reason of increase in the function of nonligated lobes. Functional increase in nonligated lobes was more pronounced than suggested by the degree of volume gain.

[Clinico-pathologically focused breast cancer research]. / Klinikopatológiai szemléletû emlõrákkutatások.

In the second half of the 20th century research focusing to breast carcinomas at the Semmelweis University had been mostly linked to the 2nd Department of Pathology. Nowadays, following the rapidly improving treatment modalities in breast cancer there is an increasing need for defining new predictive and prognostic markers. The modern molecular pathological approach helps tremendously in mapping the biological behavior of individual cases of breast cancers and meanwhile, it is one of the prerequisites of a more efficient treatment both in neoadjuvant and adjuvant settings, as well as in metastatic disease. We provide a brief review of the relevant results we have obtained in breast cancer research between 2000 and 2015.

Postconditioning of the small intestine: which is the most effective algorithm in a rat model?

BACKGROUND: Mesenteric ischemia is a serious clinical condition requiring immediate surgical intervention. The unavoidable ischemic-reperfusion (IR) injury may be ameliorated using the appropriate postconditioning protocol. The aim of the present study was to investigate the optimal postconditioning algorithm in a rat model of intestinal ischemic-reperfusion injury. MATERIALS AND METHODS: Male Wistar rats were randomized into five groups (n = 10), one sham-operated, one IR, and three postconditioned groups, each with different protocols. The animals were subjected to 60 min of mesenteric ischemia, followed by 60 min of reperfusion. Postconditioning was applied at the onset of reperfusion using three different algorithms. Arterial pressure and mucosal microcirculation were monitored throughout the experiment. Mesenteric pH was determined at the early phase of reperfusion. Blood and tissue samples were taken at the end of reperfusion for histologic evaluation, serum lactate dehydrogenase, serum creatine kinase, serum tumor necrosis factor-α, serum interleukin-6, detailed mucosal antioxidant, and scavenger capacity assays. RESULTS: The shorter and intermediate length cycles of postconditioning enhanced mucosal microcirculation and redox state and significantly delayed the normalization of mesenteric pH. Furthermore, milder histopathologic lesions and lower concentrations of serum necroenzymes and proinflammatory cytokines were detected compared with the IR group. The protective effect of postconditioning using longer cycles could only be seen in a tendentious manner. CONCLUSIONS: In a rat model of intestinal ischemia-reperfusion, the shorter and intermediate length cycles of postconditioning proved to be more effective than the use of longer cycles.

Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?

Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only in special circumstances or to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal. For example, molecular epidemiology studies reported different rates of deficient MMR (dMMR) and MSI in various cancer types. Additionally, direct comparisons of the two tests revealed relatively frequent discrepancies between MMR IHC and MSI tests, especially in non-colorectal and non-endometrial cancers and in cases with unusual dMMR phenotypes. There are also scattered clinical data showing that the efficacy of immune checkpoint inhibitors is different if the patient selection was based on dMMR versus MSI status of the cancers. All these observations question the current dogma that dMMR phenotype and genetic MSI status are equal predictive markers of the immunotherapies.

Local Invasion Patterns Characterized by SARIFA and Tumor Budding Differ and Have Distinct Prognostic Significance in Esophageal Adenocarcinoma and Squamous Cell Carcinoma.

Both esophageal squamous cell carcinoma (ESQCC) and adenocarcinoma (EAC) are known to have poor prognosis. We aimed to investigate the invasion front areas of 57 ESQCC and 43 EAC cases to find histological signs of metastatic progression. Tumor cell clusters with different cell counts, including tumor buds (TBs) and poorly differentiated clusters (PDCs), were assessed. The presence of the recently described Stroma AReactive Invasion Front Area (SARIFA) phenomenon, which defines a direct contact between tumor cells and adipocytes, was more frequently observed in EAC than in ESQCC (p = 0.004). In adenocarcinomas, a higher prevalence of SARIFA was observed in tumors with a higher number of small clusters (TBs and small PDCs; p < 0.001); furthermore, both the high number of TBs (p = 0.016) and the presence of SARIFA (p = 0.001) correlated with a higher pT stage. SARIFA positivity in EAC (p = 0.011) and high TB in ESQCC (p = 0.0006) were found to be independent prognostic factors for lymph node metastases. Moreover, in ESQCC, the higher absolute number of both TBs and PDCs was associated with shorter overall survival (p = 0.0269 and p = 0.0377, respectively). Our results suggest that the histological subtypes of esophageal cancer behave differently, namely, that different features of the invasion front are of prognostic significance.

Autopsy findings in cancer patients infected with SARS-CoV-2 show a milder presentation of COVID-19 compared to non-cancer patients.

COVID-19, caused by SARS-CoV-2, manifests with differing severity across distinct patient subgroups, with outcomes influenced by underlying comorbidities such as cancer, which may cause functional and compositional alterations of the immune system during tumor progression. We aimed to investigate the association of SARS-CoV-2 infection and its complications with cancer in a large autopsy series and the role of COVID-19 in the fatal sequence leading to death. A total of 2641 adult autopsies were investigated, 539 of these were positive for SARS-CoV-2. Among the total number of patients analyzed, 829 had active cancer. Overall, the cohort included 100 patients who simultaneously had cancer and SARS-CoV-2 infection. The course of COVID-19 was less severe in cancer patients, including a significantly lower incidence of viral and bacterial pneumonia, occurring more frequently as a contributory disease or coexisting morbidity, or as SARS-CoV-2 positivity without viral disease. SARS-CoV-2 positivity was more frequent among non-metastatic than metastatic cancer cases, and in specific tumor types including hematologic malignancies. COVID-19 was more frequently found to be directly involved in the fatal sequence in patients undergoing active anticancer therapy, but less frequently in perioperative status, suggesting that the underlying malignancy and consequent surgery are more important factors leading to death perioperatively than viral disease. The course of COVID-19 in cancer patients was milder and balanced during the pandemic. This may be due to relative immunosuppressed status, and the fact that even early/mild viral infections can easily upset their condition, leading to death from their underlying cancer or its complications.

Remote ischemic perconditioning protects the liver from ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR)-induced injury is a frequent sequel of major liver resections. IR injury after prolonged surgical interventions could be the source of increased risk of postoperative morbidity and mortality. Hepatoprotective effects of this new feasible method called remote ischemic perconditioning (RIPER) were investigated in our rat model of IR injury. MATERIALS AND METHODS: Male Wistar rats underwent ischemia for 60 min on two-thirds of their livers, followed by 1, 6, and 24 h of reperfusion (n = 72, 8 per group). During liver ischemia, but before reperfusion, rats in the treated groups received four cycles of brief infrarenal aortic clamping as perconditioning. Liver microcirculation was monitored by laser Doppler flowmeter parallel with mean arterial pressure measurements. Liver tissue injury and redox homeostasis were investigated. Furthermore, serum tumor necrosis factor alpha (TNF-α) levels were measured. RESULTS: In the RIPER group, compared with the IR group, serum transaminase levels were significantly lower after each reperfusion period (alanine aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.01 and aspartate aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.05). Reperfusion microcirculatory parameters significantly improved in the perconditioned group compared with those in the IR group (reperfusion area: P = 0.005; maximal plateau: P = 0.0002). Regarding TNF-α levels, significant differences were detected between the two IR injured groups (RIPER versus IR: 1 h, 34.3 ± 12.8 pg/mL versus 205.7 ± 60.9 pg/mL, P < 0.001; 6 h, 60.6 ± 11.7 pg/mL versus 110.4 ± 21.6 pg/mL, P < 0.05). Results of the histologic assessment and redox state measurements also showed favorable changes. CONCLUSIONS: Our team firstly reported the protective effects of RIPER on liver morphology, redox homeostasis, and microcirculation and proposed the changes of TNF-α expression.

Therapeutic option for managing lung injury induced by infrarenal aortic cross-clamping.

BACKGROUND: Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem. OBJECTIVES: Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated. RESULTS: Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO2 level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05). CONCLUSIONS: Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.

[Changing prevalence of Helicobacter pylori infection in the 9th district of Budapest. A retrospective endoscopic study, 1997-2012]. / A Helicobacter pylori-fertozés epidemiológiája Ferencvárosban. Retrospektív endoszkópos tanulmány, 1997-2012.

BACKGROUND: The prevalence of Helicobacter pylori infection in developed countries is decreasing. The time-frame of this process is largely unknown. AIM: The aim of the authors was to evaluate the changes in the prevalence of Helicobacter pylori infection in their endoscopic centre. METHODS: This retrospective study included 4647 patients examined between 1997 and 2012. Helicobacter pylori was determined from antral and corpus biopsies by the modified Giemsa stain and rapid urease test. The prevalence of the infection was calculated yearly for the period studied, for age decades from 18 to 85 years, birth cohorts of 10 years from 1920 to 1994 and according to diagnosis. RESULTS: The overall prevalence of Helicobacter pylori infection was 54.7%, which decreased from 71.3% in 1997 to 32.76% in 2011. Functional dyspepsia was found in 37.9%, duodenal ulcer in 25.3%, gastric ulcer in 3.8% and reflux disease in 24.2% of the patients. The mean prevalence of infection was 62.5% in birth cohorts of 10 years between 1920 and 1959, 57.4% in those between 1960 and 1969, and decreased to 39.0% and 26.7% in birth cohorts between 1970 and 1979) and between 1980 and 1989, respectively. According to age cohorts, the prevalence was 21.8% 34.9%, 46.5%, 63.7%, 63.2% and 59.2% in patients aged 18-19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years and 60-69 years, respectively. The proportion of H. pylori positive duodenal ulcers decreased from 95.9% in 1998 to 59.1% in 2011 (p = 0.001). CONCLUSIONS: The prevalence of Helicobacter pylori infection in the 9th district of Budapest is decreasing, especially in cohorts born in the late 1960s and 1970s, nearly 1.5 decades before the discovery of the bacterium.