Brain abscess caused by trauma of the rhinobasis: an endoscopic challenge

Brain abscess is a rare but life-threatening infection of the brain. It often occurs as a complication of infection, trauma, or surgery. This case presents a brain abscess in a 22-month-old boy that developed after a transnasal injury with a foreign body. A minimal-invasive, transnasal, endoscopic-controlled technique was used, during which the foreign object was removed and the abscess drained. Bacteriological samples were obtained and the abscess cavity irrigated. Postoperative care included antibiotics and daily irrigation of the abscess cavity. Follow-up MRI scans showed reduction in abscess size. A spinal drain was inserted temporarily to address rhino-liquorrhoea. The patient remained asymptomatic during one-year of follow-up. This case report highlights the occurrence of a brain abscess in childhood following a transnasal injury and demonstrates a minimal-invasive, transnasal, endoscopic-controlled surgical technique. The findings underscore the importance of considering brain abscess as a potential complication in cases of head trauma, particularly in atypical presentations

Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?

INTRODUCTION: Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. MATERIAL AND METHODS: Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. RESULTS: In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (pearly = 0.02; plate = 0.005), AST (pearly = 0.02; plate = 0.004) and less DNA damage by TUNEL test (pearly = 0.05; plate = 0.034) and PAR positivity (pearly = 0.02; plate = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. CONCLUSION: Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

Background: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. Methods: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers β-catenin and E-cadherin, same as KRAS and BRAF mutations. Results: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. Conclusions: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors

HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies

Background. Although amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) is used as an indicator for response to trastuzumab, the reported response rate is low, and few patients with gastric cancer (GC) benefit from this individualized therapy. The aim of this study was to examine the expression of c-erbB-2 oncoprotein (HER2), in GC samples, using two commercial immunohistochemical (IHC) antibodies, and to validate the results by checking HER2 gene amplification by fluorescence in situ hybridization (FISH). Methods. We assessed the IHC expression of HER2 using the polyclonal antibody from Dako and CB11 clone from Leica, in 93 consecutive cases of GC samples. In all of the cases, FISH analysis was also performed using the BOND-MAX platform. Results. No significant difference was observed between the two HER2 antibodies. Of the 93 cases, 22.58% demonstrated at least focal and 1+ HER2 positivity. Seven cases (7.53%) exhibited 3+ expression, and another 7 carcinomas (7.53%) were equivocal (2+). HER2 amplification was seen in 11 cases (11.83%), 10 of which were differentiated adenocarcinomas. In 5 of the cases, 2–5 sections were examined, which proved the extremely high intratumorally/intraglandular heterogeneity. FISH heterogeneity was higher in cases with only 2+ positivity on IHC assessment, compared with those showing at least one small focus of 3+ overexpression. HER2 amplification proved to be an independent negative prognostic factor. Conclusions. Due to the highly heterogeneous aspect of GC, at least 3-4 slides should be assessed by IHC, before considering a tumor to be HER2-negative. In cases with small 3+ foci representing less than 5% of tumor and in equivocal (2+) cases, FISH analysis remains the gold standard method

Hepatic microcirculation after “early” levosimendan pretreatment.

<p>The blood flow of sham-operated (S) and “early” control group (C_E) did not change significantly. There was a decline of the flux in groups subjected to IR (IR_E; L_E). Levosimendan pretreatment (L_E) significantly improved liver microcirculation compared to the IR_E group during reperfusion. Values are expressed as means. * p<0.05 versus IR_E group. n = 5 in sham-operated (S) and control groups (C_E); n = 10 in IR (IR_E) and levosimendan pretreated groups (L_E).</p

Hepatic microcirculation after “late” levosimendan pretreatment.

<p>In the “late” control group (C_L) a reduction of blood flow was observed in comparison to sham-operated animals (S), but the difference was not significant. However, there was a significant decline of the flux in groups subjected to IR (IR_L; L_L). Levosimendan pretreatment (L_L) caused significant improvement in the microcirculation of the liver compared with the IR_L group. Values are expressed as means. * p<0.05 versus IR_L group. n = 5 in sham-operated (S) and control group (C_L); n = 10 in IR (IR_L) and levosimendan pretreated group (L_L).</p

Liver HSP72 expression.

<p><b>A:</b> Representative Western blotting for HSP72 in sham-operated group (S), control groups (C_E, C_L), IR groups (IR_E, IR_L) and levosimendan pretreated groups (L_E, L_L). <b>B:</b> Quantitative results of Western blotting. A significant increase in liver HSP72 expression was observed in the IR groups as well as in the levosimendan pretreated groups compared to the sham-operated group. Levosimendan pretreatment did not result in changes of HSP72 expression pattern. Data are presented as means+SEM, * p<0.05 versus sham-operated group. n = 5 in sham-operated (S) and control groups (C_E, C_L); n = 10 in IR (IR_L, IR_E) and levosimendan pretreated groups (L_E, L_L).</p

Microcirculatory data of the liver.

<p>S: sham-operated; C_E: “early” control; IR_E: “early” ischemia-reperfusion; L_E: “early” levosimendan pretreated; C_L: “late” control; IR_L: “late” ischemia-reperfusion; L_L: “late” levosimendan pretreated.</p>*<p>p<0.05 versus the respective IR group.</p

Serum level of ALT and AST.

<p>Ischemic-reperfusion injury of the liver led to an increase in serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).A: Serum levels of ALT significantly decreased in the levosimendan pretreated groups (L_E, L_L) compared to the corresponding IR groups (IR_L, IR_E) B: Raised AST activity in the “late” IR group (IR_L) were significantly higher than in the “early” IR group (IR_E). “Late” levosimendan pretreatment significantly reduced the serum activity of AST. Data are shown as means+SEM, * p<0.05 versus “late” IR group; ¤ <0.05 versus “early” IR group; $ p<0.05 versus “late” control group; & p<0.05 versus “early” control group; # p<0.05 versus “early” IR group. n = 5 in sham-operated (S) and control groups (C_E, C_L); n = 10 in IR (IR_L, IR_E) and levosimendan pretreated groups (L_E, L_L).</p