Assessing the Therapeutic Impacts of HAMLET and FOLFOX on BRAF-Mutated Colorectal Cancer: A Study of Cancer Cell Survival and Mitochondrial Dynamics In Vitro and Ex Vivo.

Background and Objectives: Colorectal cancer (CRC) is a major global health challenge. The BRAF V600E mutation, found in 8-12% of CRC patients, exacerbates this by conferring poor prognosis and resistance to therapy. Our study focuses on the efficacy of the HAMLET complex, a molecular substance derived from human breast milk, on CRC cell lines and ex vivo biopsies harboring this mutation, given its previously observed selective toxicity to cancer cells. Materials and Methods: we explored the effects of combining HAMLET with the FOLFOX chemotherapy regimen on CRC cell lines and ex vivo models. Key assessments included cell viability, apoptosis/necrosis induction, and mitochondrial function, aiming to understand the mutation-specific resistance or other cellular response mechanisms. Results: HAMLET and FOLFOX alone decreased viability in CRC explants, irrespective of the BRAF mutation status. Notably, their combination yielded a marked decrease in viability, particularly in the BRAF wild-type samples, suggesting a synergistic effect. While HAMLET showed a modest inhibitory effect on mitochondrial respiration across both mutant and wild-type samples, the response varied depending on the mutation status. Significant differences emerged in the responses of the HT-29 and WiDr cell lines to HAMLET, with WiDr cells showing greater resistance, pointing to factors beyond genetic mutations influencing drug responses. A slight synergy between HAMLET and FOLFOX was observed in WiDr cells, independent of the BRAF mutation. The bioenergetic analysis highlighted differences in mitochondrial respiration between HT-29 and WiDr cells, suggesting that bioenergetic profiles could be key in determining cellular responses to HAMLET. Conclusions: We highlight the potential of HAMLET and FOLFOX as a combined therapeutic approach in BRAF wild-type CRC, significantly reducing cancer cell viability. The varied responses in CRC cell lines, especially regarding bioenergetic and mitochondrial factors, emphasize the need for a comprehensive approach considering both genetic and metabolic aspects in CRC treatment strategies.

Interrater agreement between student and teacher assessments of endotracheal intubation skills in a self-directed simulation learning environment.

BACKGROUND: Practical skill assessment is an important part of the learning process to confirm competencies in acquired medical knowledge. OBJECTIVE: This study aimed to compare the assessments of endotracheal intubation skills using the HybridLab® methodology between students and teacher in terms of interobserver reliability. METHODS: Reliability analysis was performed with observational data (data are reported according to STROBE guidelines). The study was conducted in two countries, the Lithuanian University of Health Science (LUHS) and Pennsylvania State University (PSU) in the US, between 1 January and 30 June 2020. A total of 92 students (60 from LUHS and 32 from PSU) were trained in endotracheal intubation using an algorithm-driven hybrid learning method. At the end of the training session, the participants had to complete the evaluation scenario, which was assessed by one of the students and evaluated remotely by a single teacher. The student assessment of the endotracheal intubation procedure was compared with the teacher's assessment using correlation and estimation of the intraclass correlation coefficient. RESULTS: Overall, the medians of the student and teacher assessments were both 100% (0%). Spearman's correlation coefficient between the student and teacher assessments was 0.879 (p = 0.001). The intraclass correlation coefficient used for interobserver variations between the students and teacher was 0.883 (95% confidence interval from 0.824 to 0.923). CONCLUSIONS: The algorithm-driven hybrid learning method allows students to reliably assess endotracheal intubation skills to a level comparable with that of the teacher's evaluation. This learning method has the potential to be a cost-effective and efficient way to provide high-quality education while also saving human resources.

Targeting AHR Increases Pancreatic Cancer Cell Sensitivity to Gemcitabine through the ELAVL1-DCK Pathway.

The aryl hydrocarbon receptor (AHR) is a transcription factor that is commonly upregulated in pancreatic ductal adenocarcinoma (PDAC). AHR hinders the shuttling of human antigen R (ELAVL1) from the nucleus to the cytoplasm, where it stabilises its target messenger RNAs (mRNAs) and enhances protein expression. Among these target mRNAs are those induced by gemcitabine. Increased AHR expression leads to the sequestration of ELAVL1 in the nucleus, resulting in chemoresistance. This study aimed to investigate the interaction between AHR and ELAVL1 in the pathogenesis of PDAC in vitro. AHR and ELAVL1 genes were silenced by siRNA transfection. The RNA and protein were extracted for quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Direct binding between the ELAVL1 protein and AHR mRNA was examined through immunoprecipitation (IP) assay. Cell viability, clonogenicity, and migration assays were performed. Our study revealed that both AHR and ELAVL1 inter-regulate each other, while also having a role in cell proliferation, migration, and chemoresistance in PDAC cell lines. Notably, both proteins function through distinct mechanisms. The silencing of ELAVL1 disrupts the stability of its target mRNAs, resulting in the decreased expression of numerous cytoprotective proteins. In contrast, the silencing of AHR diminishes cell migration and proliferation and enhances cell sensitivity to gemcitabine through the AHR-ELAVL1-deoxycytidine kinase (DCK) molecular pathway. In conclusion, AHR and ELAVL1 interaction can form a negative feedback loop. By inhibiting AHR expression, PDAC cells become more susceptible to gemcitabine through the ELAVL1-DCK pathway.

Editorial for the Special Issue "Acute and Chronic Pancreatitis, Pancreatic Malignancies".

Pancreatic diseases, especially acute pancreatitis and pancreatic cancer, are associated with high rates of complications, difficult treatment that may not always be effective, and high mortality in complex cases [...].

A novel algorithm-driven hybrid simulation learning method to improve acquisition of endotracheal intubation skills: a randomized controlled study.

BACKGROUND: Simulation-based training is a clinical skill learning method that can replicate real-life situations in an interactive manner. In our study, we compared a novel hybrid learning method with conventional simulation learning in the teaching of endotracheal intubation. METHODS: One hundred medical students and residents were randomly divided into two groups and were taught endotracheal intubation. The first group of subjects (control group) studied in the conventional way via lectures and classic simulation-based training sessions. The second group (experimental group) used the hybrid learning method where the teaching process consisted of distance learning and small group peer-to-peer simulation training sessions with remote supervision by the instructors. After the teaching process, endotracheal intubation (ETI) procedures were performed on real patients under the supervision of an anesthesiologist in an operating theater. Each step of the procedure was evaluated by a standardized assessment form (checklist) for both groups. RESULTS: Thirty-four subjects constituted the control group and 43 were in the experimental group. The hybrid group (88%) showed significantly better ETI performance in the operating theater compared with the control group (52%). Further, all hybrid group subjects (100%) followed the correct sequence of actions, while in the control group only 32% followed proper sequencing. CONCLUSIONS: We conclude that our novel algorithm-driven hybrid simulation learning method improves acquisition of endotracheal intubation with a high degree of acceptability and satisfaction by the learners' as compared with classic simulation-based training.

Volume, but Not the Location of Necrosis, Is Associated with Worse Outcomes in Acute Pancreatitis: A Prospective Study.

Background and Objectives: The course and clinical outcomes of acute pancreatitis (AP) are highly variable. Up to 20% of patients develop pancreatic necrosis. Extent and location of it might affect the clinical course and management. The aim was to determine the clinical relevance of the extent and location of pancreatic necrosis in patients with AP. Materials and Methods: A cohort of patients with necrotizing AP was collected from 2012 to 2018 at the Hospital of Lithuanian University of Health Sciences. Patients were allocated to subgroups according to the location (entire pancreas, left and right sides of pancreas) and extent (<30%, 30−50%, >50%) of pancreatic necrosis. Patients were reviewed for demographic features, number of performed surgical interventions, local and systemic complications, hospital stay and mortality rate. All contrast enhanced computed tomography (CECT) scans were evaluated by at least two experienced abdominal radiologists. All patients were treated according to the standard treatment protocol based on current international guidelines. Results: The study included 83 patients (75.9% males (n = 63)) with a mean age of 53 ± 1.7. The volume of pancreatic necrosis exceeded 50% in half of the patients (n = 42, 51%). Positive blood culture (n = 14 (87.5%)), multiple organ dysfunction syndrome (n = 17 (73.9%)) and incidences of respiratory failure (n = 19 (73.1%)) were significantly more often diagnosed in patients with pancreatic necrosis exceeding 50% (p < 0.05). Patients with >50% of necrosis were significantly (p < 0.05) more often diagnosed with moderately severe (n = 24 (41.4%)) and severe (n = 18 (72%)) AP. The number of surgical interventions (n = 18 (72%)) and ultrasound-guided interventions (n = 26 (65%)) was also significantly higher. In patients with whole-pancreas necrosis, incidence of renal insufficiency (n = 11 (64.7%)) and infected pancreatic necrosis (n = 19 (57.6%)) was significantly higher (p < 0.05). Conclusions: The clinical course and outcome were worse in the case of pancreatic necrosis exceeding 50%, rendering the need for longer and more complex treatment.

Hyperthermia potentiates cisplatin cytotoxicity and negative effects on mitochondrial functions in OVCAR-3 cells.

The aim of this study was to determine the effects of hyperthermia, cisplatin and their combination on mitochondrial functions such as glutamate dehydrogenase (GDH) activity and mitochondrial respiration rates, as well as survival of cultured ovarian adenocarcinoma OVCAR-3 cells. Cells treated for 1 h with hyperthermia (40 and 43 °C) or cisplatin (IC50) or a combination of both treatments were left for recovery at 37 °C temperature for 24 h or 48 h. The obtained results revealed that 43 °C hyperthermia potentiated effects of cisplatin treatment: combinatory treatment more strongly suppressed GDH activity and expression, mitochondrial functions, and decreased survival of OVCAR-3 cells in comparison to separate single treatments. We obtained evidence that in the OVCAR-3 cell line GDH was directly activated by hyperthermia (cisplatin eliminated this effect); however, this effect was followed by GDH inhibition after 48 h recovery. A combination of 43 °C hyperthermia with cisplatin induced stronger GDH inhibition in comparison to separate treatments, and negative effects exerted on GDH activity correlated with suppression of mitochondrial respiration with glutamate + malate. Cisplatin did not induce uncoupling of oxidative phosphorylation in OVCAR-3 cells but induced impairment of the outer mitochondrial membrane in combination with 43 °C hyperthermia. Hyperthermia (43 °C) potentiated cytotoxicity of cisplatin in an OVCAR-3 cell line.

CT- and MRI-Based Assessment of Body Composition and Pancreatic Fibrosis Reveals High Incidence of Clinically Significant Metabolic Changes That Affect the Quality of Life and Treatment Outcomes of Patients with Chronic Pancreatitis and Pancreatic Cancer.

Background and Objectives: Both chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) may lead to cachexia, sarcopenia, and osteoporosis due to different mechanisms. Neither patient gender, age, nor body weight are good predictors of these metabolic changes having a significant negative impact on the quality of life (QOL) and treatment outcomes. The aim of this study was to evaluate radiological changes in body composition and to compare them with manifestations of exocrine and endocrine pancreatic insufficiency, body mass, and QOL among patients with CP and PDAC. Materials and Methods: Prospectively collected data of 100 patients with diagnosed CP or PDAC were used for analysis. All patients underwent dual-energy X-ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) was used to assess QOL. Diabetes and changes in fecal elastase-1 were also assessed. Results: There was no significant difference in skeletal muscle mass (SMM) among patients with CP and PDAC (p = 0.85). Significantly more underweight patients had low SMM (p = 0.002). Patients with CP had more pronounced pancreatic fibrosis (PF) (p < 0.001). Data showed a significant relationship between a high degree of PF and occurrence of diabetes (p = 0.006) and low fecal elastase-1 levels (p = 0.013). A statistically significant lower QOL was determined in patients with PF ≥ 50% and in the CP group. Conclusions: Sarcopenia and osteoporosis/osteopenia are highly prevalent among patients with chronic pancreatitis and pancreatic cancer, and CT- and MRI-based assessment of body composition and pancreatic fibrosis could be a potentially useful tool for routine detection of these significant metabolic changes.

Predictors of postoperative hypocalcemia occurring after a total thyroidectomy: results of prospective multicenter study.

BACKGROUND: Thyroid surgeries are among the most common operations performed in the world. Hypocalcemia following total thyroidectomy is a common complication that is sometimes difficult to correct. The aim of this study is to determine the risk factors for hypocalcemia following total thyroidectomy and their clinical value. METHODS: From January 2015 through to April 2017, 400 patients were included in this prospective multicenter study. All patients underwent total thyroidectomy due to various thyroid diseases. The following risk factors were analyzed: pre-operative and post-operative biochemical blood parameters, clinical effects and factors related to surgery, the patient, and the disease. RESULTS: Post-operative hypocalcemia developed in 257 patients (64.2%). Of them, 197 patients (76.7%) were diagnosed with asymptomatic hypocalcemia. Clinical symptoms were present in 60 of the 257 patients with hypocalcemia (23.3%). The statistically significant predictors of hypocalcemia were decreased calcium and ionized calcium pre-operatively (p < 0.001), parathyroid hormone on day one following surgery (p < 0.001), thyrotoxicosis <10 years before surgery (odds ratio 1.65, 95% CI 1.01-2.70, p = 0.046), the number of parathyroid glands found during surgery (odds ratio 0.52, 95% CI 0.38-0.70, p < 0.001), ligation of the trunk of the left inferior thyroid artery (odds ratio 2.04, 95% CI 1.27-3.29, p = 0.003), ligation of the trunk of the right inferior thyroid artery (odds ratio 2.37, 95% CI 1.47-3.81, p < 0.001), and the number of transplanted parathyroid glands (odds ratio 1.87, 95% CI 1.12-2.97, p = 0.015). In the multivariate analysis, age (odds ratio 1.05, 95% CI 1.01-1.09, p = 0.029) and gender (odds ratio 5.94, 95% CI 1.13-31.26, p = 0.035) were statistically significant predictors. CONCLUSIONS: This study demonstrates that there is a number of different patient (gender, age, and duration of thyrotoxicosis <10 years before surgery) and surgical (number of parathyroid glands found during surgery, decreased calcium and ionized calcium before surgery, parathyroid hormone on day one following surgery, and ligation of the trunk of the left and right inferior thyroid artery) risk factors predictive of hypocalcemia following total thyroidectomy. Optimization of the surgical technique could possibly prevent the occurrence of hypocalcemia after total thyroidectomy in some cases; in other cases, identification of known risk factors post-operatively could permit early detection and effective treatment of these patients.

Perceived changes in knowledge and confidence of doctors and midwives after the completion of the Standardized Trainings in Obstetrical Emergencies.

BACKGROUND AND OBJECTIVES: There are only few training programs in obstetric emergencies currently in use and only some of them were evaluated with an adequate sample of participants. Therefore, we present the evaluation of the novel Standardized Trainings in Obstetrical Emergencies (STrObE), conducted in Lithuania. The aim of this study was to analyze whether participants' self-reported knowledge and confidence increased after the trainings, and whether the impact of the trainings was long-lasting. MATERIALS AND METHODS: Data was collected across the majority of hospitals providing secondary and tertiary obstetrical care in Lithuania in 2015. A total of 650 obstetricians-gynecologists and midwives attended the trainings; 388 (response rate 59.7%) of them filled in the initial questionnaire before the trainings, 252 (64.9%) immediately after, 160 (41.2%) 6 weeks after, and 160 (41.2%) 6 months after the trainings, which was the final sample for the analyses. Participants used a Likert-type scale to evaluate their knowledge and confidence about management of urgent obstetrical situations: vacuum-assisted vaginal delivery, shoulder dystocia, postpartum hemorrhage, preeclampsia/eclampsia, early preterm labor, and dystocia. We assessed how participants' self-reported knowledge and confidence changed after the trainings (compared to before the trainings) and how long the effect was retained for. RESULTS: The mean score of self-reported knowledge in obstetrical emergencies increased immediately after the trainings comparing to the scores before the trainings (P<0.001) and it did not differ further between the three time points after the trainings (i.e. immediately, 6 weeks, and 6 months; P>0.05). The same pattern was observed for self-reported confidence scores. The increase in self-reported knowledge and confidence after the trainings was stable. Moreover, the self-reported knowledge and confidence gains were greater for those participants with lower work experience, although benefit was seen across all experience levels. CONCLUSIONS: STrObE improved participants' self-reported knowledge and confidence and lasting positive effects were observed for at least 6 months after the initial trainings. Moreover, the trainings were more beneficial for those with lower work experience, although they benefited all the participants.

How the changes in the system affect trauma care provision: The assessment of and implications for Lithuanian trauma service performance in 2007-2012.

OBJECTIVE: The aim of this study was to identify and assess the effects of changes in the Lithuanian trauma service from 2007 to 2012. We postulate that the implications derived from this study will be of importance to trauma policy planners and makers in Lithuania and throughout other countries of Eastern and Central Europe. MATERIALS AND METHODS: Out of 10,390 trauma admissions to four trauma centers in 2007, 294 patients (2.8%) were randomly selected for the first arm of a representative study sample. Similarly, of 9918 trauma admissions in 2012, 250 (2.5%) were randomly chosen for comparison in the study arm. Only cases with a diagnosis falling into the ICD-10 "S" and "T" codes were included. A survey of whom regarding changes in quality of trauma care from 2007 to 2012 was carried out by emergency medical service (EMS) providers. RESULTS: The Revised Trauma Score (RTS) mean value was 7.45±1.04 for the 2007 year arm; it was 7.53±0.93 for the 2012 year arm (P=0.33). Mean time from the moment of a call from the site of the traumatic event to the patient's arrival at the trauma center did not differ between the arms of the sample: 49.95min in 2007 vs. 51.6min in 2012 (P=0.81). An application of the operational procedures such as a cervical spine protection using a hard collar, oxygen therapy, infusion of intravenous fluids, and pain relief on the trauma scene was more frequent in 2012 than in 2007. Management of trauma patients in the emergency department improved regarding the availability of 24/7 computed tomography scanner facilities and an on-site radiographer. Time to CT-scanning was reduced by 38.8%, and time to decision-making was reduced by 16.5% in 2012. CONCLUSIONS: Changes in operational procedures in the Lithuanian pre-hospital care provision and management of trauma patients in emergency departments of trauma centers improved the efficiency of trauma care delivery over the 2007-2012 period.

Percutaneous Transhepatic Biliary Stenting with Uncovered Self-Expandable Metallic Stents in Patients with Malignant Biliary Obstruction - Efficacy and Survival Analysis.

BACKGROUND: The aim of this study was to assess short- and long-term outcomes of malignant biliary obstruction (MBO) treatment by percutaneous transhepatic biliary stenting (PTBS) with uncovered selfexpandable metallic stents (SEMS), and to identify predictors of survival. MATERIAL/METHODS: A nine-year, single-centre study from a prospectively collected database included 222 patients with inoperable MBO treated by PTBS with uncovered nitinol SEMS. RESULTS: Technical and clinical success rates were 95.9% and 82.4%, respectively. The total rate of postprocedural complications was 14.4%. The mean durations of the primary and secondary stent patency were 114.7±15.1 and 146.4±21.2 days, respectively. The 30-day mortality rate was 15.3% with no procedure-related deaths. The mean estimated length of survival was 143.3±20.6 days. Independent predictors increasing the risk of death included higher than 115 µmol/L serum bilirubin 2-5 days after biliary stenting (HR 3.274, P=0.019), distal (non-hilar) obstruction of the bile ducts (HR 3.711, P=0.008), Bismuth-Corlette type IV stricture (HR 2.082, P=0.008), obstruction due to gallbladder cancer (HR 31.029, P=0.012) and only partial drainage of liver parenchyma (HR 4.158, P=0.040). CONCLUSIONS: PTBS with uncovered SEMS is an effective and safe method for palliative treatment of MBO. Serum bilirubin higher than 115 µmol/L 2-5 days after the procedure has a significant negative impact on patients' survival. Lower survival is also determined by distal bile duct obstruction, Bismuth- Corlette type IV stricture, biliary obstruction caused by gallbladder cancer and when only partial liver drainage is applied.

The clinical value of adipokines in predicting the severity and outcome of acute pancreatitis.

BACKGROUND: Recent data shows that patients with severe acute pancreatic might benefit from early intensive therapy, enteral nutrition and timely transfer to specialized centers. The early prophylactic use of antibiotics in AP remains controversial. The role and need for new markers in stratification of acute pancreatitis is also uncertain. This study aims to evaluate the prognostic usefulness of adipokines in prediction of the severity and outcome of acute pancreatitis (AP). METHODS: Prospective study was conducted in four clinical centers. The diagnosis and severity assessment of AP was established according to the revised 2012 Atlanta classification. Adipokines, IL-6 and CRP levels were measured at admission and on 3rd day of hospital stay and compared with the control group. The predictive accuracy of each marker was measured by area under the receiver operating curve. RESULTS: Forty healthy controls and 102 patients were enrolled in to the study. Twenty seven (26.5 %) patients had mild, 55 (53.9 %) - moderate and 20 (19.6 %) - severe AP. Only resistin (cut-off value 13.7 ng/ml) and IL-6 (cut-off value 473.4 pg/ml) were reliable early markers of SAP. IL-6 with cut-off value of 157.0 pg/ml was a predictor of necrosis. The peripancreatic necrosis volume of 112.5 ml was a marker of SAP and 433.0 ml cut-off value could be used to predict the need of interventions. CONCLUSIONS: The prognostic value of adipokines in AP is limited. Only admission resistin levels could serve as an early predictor for SAP. The Lithuanian Regional Ethics Committee approved the study protocol (permission No. L-12-02/1/2/3/4) and all the patients and the control group provided written informed consent.

Upregulation of cugbp2 increases response of pancreatic cancer cells to chemotherapy.

PURPOSE: Altered expression and/or function of ribosomal RNA (rRNA)-binding proteins CUGBP2/CELF2 might influence post-transcriptional regulation of the HO-1- and COX-2-mediated cytoprotective pathways and represents an important therapeutic target. The aim of this study was to assess the effects of CUGBP2-mediated post-transcriptional regulation of COX-2 and HO-1 in pancreatic cancer cells in regard of response to gemcitabine (GEM) treatment. METHODS: Expression of CUGBP2, COX-2, and HO-1 was evaluated using qRT-PCR and Western blot methods. Cell viability after treatment with GEM and/or curcumin and siCUGBP2 was evaluated using MTT and crystal violet tests. RNA immunoprecipitation analysis was used to confirm COX-2 and HO-1 post-transcriptional regulation by CUGBP2 protein. RESULTS: CUGBP2 expression at the messenger RNA (mRNA) level was 2.2-fold lower (p = 0.007), but HO-1 and COX-2 expression was increased 6.9- (p = 0.023) and 2.3- (p = 0.046) fold in pancreatic cancer tissues. The median survival of patients with low CUGBP2 expression from the lowest tercile was 13.8 months. The median survival of patients in terciles of middle and high CUGBP2 expression levels was 21.9 month (p = 0.123). Induction of CUGBP2 expression by curcumin resulted in the downregulation of HO-1 and COX-2 and strongly sensitized tumor cells to GEM treatment. However, CUGBP2 silencing upregulated HO-1 and COX-2 protein expression and had a high effect on cells viability. CONCLUSION: Decreased activity of CUGBP2 could be associated with high chemoresistance and early dissemination of pancreatic cancer through the HO-1- and COX-2-mediated cytoprotective and carcinogenesis pathways. Curcumin significantly increased the effectiveness of GEM treatment in vitro via the CUGBP2-mediated post-transcriptional regulation pathway.

The influence of the extended indications for sentinel node biopsy on the identification of metastasis-free and metastatic sentinel nodes.

BACKGROUND AND OBJECTIVE: Rates of sentinel node (SN) identification and metastasis-positive SNs were compared between the group with highly selective indications for sentinel node biopsy (SNB) and the group with merely no contraindications for SNB (Groups A and B, respectively). MATERIALS AND METHODS: We performed a single-center retrospective data analysis of 471 breast cancer patients treated during 2004-2010. Data on clinical and pathologic staging, frozen section results, radiological measurements and pathologic examination results were obtained from patient records. Patients were analyzed in two groups. Group A (n=143) had SNB performed only when the patients fulfilled to the following criteria: breast tumor no greater than 3cm in diameter, unifocal disease, no pure ductal carcinoma in situ, no history of previous breast or lymph node surgery, and no neoadjuvant chemotherapy. Indications for SNB were extended in Group B (n=328) so that inflammatory breast cancer and positive lymph nodes became the only exclusion criteria. RESULTS: The rate of SN identification was 97.9% in Group A vs. 99.09% in Group B (P=0.29). SNs were metastasis positive and frozen sections false negative at comparable proportions in both groups. CONCLUSIONS: The extension of indications for SNB did not reduce the rates of SN identification or did not create any impact on the rate of metastatic SNs.

Impact of etiology on course and outcomes of severe acute pancreatitis.

BACKGROUND AND OBJECTIVE: Since the influence of etiological factors on the course and outcomes of acute pancreatitis (AP) is not fully understood yet, the aim of the study was to compare the outcomes of alcoholic and biliary severe acute pancreatitis (SAP). MATERIALS AND METHODS: We investigated 81 patients with alcoholic and biliary SAP. Demographic data, etiologic factors, severity scores, intra-abdominal pressure, imaging studies, interventions, and treatment outcomes were prospectively entered into specially maintained database and subsequently analyzed. RESULTS: No statistically significant difference was observed in the prevalence of SAP in biliary and alcoholic AP groups (P=0.429). Although, in the biliary SAP group patients were predominantly elderly women (P=0.003), the total in-hospital stay was longer in alcoholic SAP patients (P=0.021). The abdominal compartment syndrome developed more frequently (P=0.041) and necrosectomy was more frequently performed in alcoholic SAP group (not statistically significant). Although not statistically significant, a lower mortality rate among biliary SAP patients (25.0% vs. 13.5%) was observed. CONCLUSIONS: We defined a trend toward decreased incidence of infected necrosis in larger volume (≥30%) pancreatic necrosis, absence of abdominal compartment syndrome, lower rate of necrosectomies, shorter in-hospital stay, and an insignificantly reduced mortality rate in biliary SAP patients, indicating more favorable course of biliary SAP.

Microcirculatory, mitochondrial, and histological changes following cerebral ischemia in swine.

BACKGROUND: Ischemic brain injury due to stroke and/or cardiac arrest is a major health issue in modern society requiring urgent development of new effective therapies. The aim of this study was to evaluate mitochondrial, microcirculatory, and histological changes in a swine model of global cerebral ischemia. RESULTS: In our model, significant microcirculatory changes, but only negligible histological cell alterations, were observed 3 h after bilateral carotid occlusion, and were more pronounced if the vascular occlusion was combined with systemic hypotension. Analysis of mitochondrial function showed that LEAK respiration (measured in the presence of pyruvate + malate but without ADP) was not affected in any model of global cerebral ischemia in pigs. The OXPHOS capacity with pyruvate + malate as substrates decreased compared with the control levels after bilateral carotid artery occlusion, and bilateral carotid artery occlusion + hypotension by 20% and 79%, respectively, resulting in decreases in the respiratory control index of 14% and 73%, respectively. OXPHOS capacity with succinate as a substrate remained constant after unilateral carotid artery occlusion or bilateral carotid artery occlusion, but decreased by 53% after bilateral carotid artery occlusion and hypotension compared with controls (p < 0.05, n = 3-6). Addition of exogenous cytochrome c to mitochondria isolated from ischemia brains had no effect on respiration in all models used in this study. CONCLUSIONS: We found a decrease in microcirculation and mitochondrial oxidative phosphorylation activity, but insignificant neuronal death, after 3 h ischemia in all our pig models of global cerebral ischemia. Dysfunction of the mitochondrial oxidative phosphorylation system, particularly damage to complex I of the respiratory chain, may be the primary target of the ischemic insult, and occurs before signs of neuronal death can be detected.

Emergent pancreaticoduodenectomy: a dual institution experience and review of the literature.

BACKGROUND: Emergent pancreaticoduodenectomy (EPD) is an uncommon surgical procedure performed to treat patients with acute pancreaticoduodenal trauma, bleeding, or perforation. This study presents the experience of two university hospitals with EPD. METHODS: Clinical data on EPD in trauma and nontrauma patients from 2002-2012 were extracted from the hepatopancreatobiliary surgery databases at Thomas Jefferson University and Kaunas Medical University Hospitals. Data on indications, perioperative variables, morbidity, and mortality rates were evaluated. RESULTS: Ten single-stage EPD patients were identified. Five underwent a classic Whipple resection, whereas five had pylorus preservation. Seven patients had traumatic indications for pancreaticoduodenectomy: three from gunshot wounds to the abdomen and four from blunt high-energy injuries (two sustained injuries by falling from height and two by direct assaults on the abdomen). Three cases of nontrauma patients had EPD surgery for massive gastrointestinal hemorrhage. The median age of the EPD cohort was 46 y (range, 19-67 y). All 10 patients were recovered and were discharged from the hospital with a median postoperative length of stay of 24 d (range, 8-69 d). There were no perioperative mortalities. CONCLUSIONS: Despite a high morbidity rate and prolonged recovery, this dual institutional review suggests that EPD can serve as a lifesaving procedure in both the trauma and the urgent nontrauma settings.

Trends and results in treatment of gastric cancer over last two decades at single East European centre: a cohort study.

BACKGROUND: A steady decline in gastric cancer mortality rate over the last few decades is observed in Western Europe. However it is still not clear if this trend applies to Eastern Europe where high incidence rate of gastric cancer is observed. METHODS: This was a retrospective non-randomized, single center, cohort study. During the study period 557 consecutive patients diagnosed with gastric cancer in which curative operation was performed met the inclusion criteria. The study population was divided into two groups according to two equal time periods: 01-01-1994 - 31-12-2000 (Group I - 273 patients) and 01-01-2001 - 31-12-2007 (Group II - 284 patients). Primary (five-year survival rate) and secondary (postoperative complications, 30-day mortality rate and length of hospital stay) endpoints were evaluated and compared. RESULTS: Rate of postoperative complications was similar between the groups, except for Grade III (Clavien-Dindo grading system for the classification of surgical complications) complications that were observed at significantly lower rates in Group II (26 (9.5%) vs. 11 (3.9%), p = 0.02). Length of hospital stay was significantly (p = 0.001) shorter (22.6 ± 28.9 vs. 16.2 ± 17.01 days) and 30-day mortality was significantly (p = 0.02) lower (15 (5.5%) vs. 4 (1.4%)) in Group II. Similar rates of gastric cancer related mortality were observed in both groups (92.3% vs. 90.7%). However survival analysis revealed significantly (p = 0.02) better overall 5-year survival rate in Group II (35.6%, 101 of 284) than in Group I (23.4%, 64 of 273). There was no difference in 5-year survival rate when comparing different TNM stages. CONCLUSIONS: Gastric cancer treatment results remain poor despite decreasing early postoperative mortality rates, shortening hospital stay and improved overall survival over the time. Prognosis of treatment of gastric cancer depends mainly on the stage of the disease. Absence of screening programs and lack of clinical symptoms in early stages of gastric cancer lead to circumstances when most of the patients presenting with advanced stage of the disease can expect a median survival of less than 30 months even after surgery with curative intent.

Can lightweight rescuers adequately perform CPR according to 2010 resuscitation guideline requirements?

AIM: To evaluate associations between rescuers' anthropometric characteristics and chest compressions (CC) depth according to 2010 resuscitation guidelines. METHODS: 186 medical and pharmacy students, never trained in basic life support (BLS) before, underwent video self-instruction training. The participants were asked to perform a BLS test on a manikin connected to a PC for 6 min immediately after training, and the quality of the cardiopulmonary resuscitation (CPR) skills was evaluated. RESULTS: Women with body weights less than 56 kg were 6.29 times more likely to produce insufficient CCs than women weighing 56-62.7 kg, and 4.72 times more likely to produce insufficient CCs compared with women weighing more than 62.7 kg. CONCLUSIONS: Lightweight rescuers may have difficulty achieving the full compression depth of 5-6 cm required by new resuscitation guidelines. These rescuers require special attention during CPR training, with an emphasis on correct body positioning and use of body weight for CCs.