Next-Generation Sequencing of microRNAs in Small Abdominal Aortic Aneurysms: MiR-24 as a Biomarker.

BACKGROUND: Small abdominal aortic aneurysms (AAAs) are asymptomatic but can potentially lead to rupture if left undetected. To date, there is a lack of simple nonradiologic routine tests available for diagnosing AAAs. MicroRNAs (miRNAs) have been proven to be good-quality biomarkers in several diseases, including AAA. METHODS: An attempt to identify a panel of circulating miRNAs with differential expression in AAAs via next-generation sequencing (NGS) was performed in serum samples: small AAAs (n = 3), large AAAs (n = 3), and controls (n = 3). For miR-24, validation with real-time polymerase chain reaction (PCR) was undertaken in a larger group (n = 80). RESULTS: In the NGS study, 23 miRNAs were identified as differentially expressed (with statistical significance) in small AAAs in comparison with controls. Among them, miR-24 showed the largest upregulation with 23-fold change (log2FC 4.5, P = 0.024). For large AAAs compared with controls, and small AAAs compared with large AAAs, a panel of 33 and 131 miRNAs showed statistically significant differential expression, respectively. Based on the results of the NGS stage, a literature search was performed, and information regarding AAA pathogenesis, coronary artery disease, and peripheral arterial disease was documented where applicable: miR-24, miR-103, miR-193a, miR-486, miR-582, and miR-3663. Of these 6 miRNAs, miR-24 was chosen for further validation with real-time PCR. Additionally, in the NGS study analysis, 17 miRNAs were common between the small-large AAAs, small AAAs-controls, and large AAAs-controls comparisons: miR-7846, miR-3195, miR-486-2, miR-3194, miR-5589, miR-1538, miR-3178, miR-4771-1, miR-5695, miR-6504, miR-1908, miR-6823, miR-3159, miR-23a, miR-7853, miR-496, and miR-193a. Interestingly, in the validation stage with real-time PCR, miR-24 was found downregulated in small and large AAAs compared with controls (fold-changes: 0.27, P = 0.015 and 0.15, P = 0.005, respectively). No correlation was found between average Ct values, aneurysm diameter, and patients' age. CONCLUSIONS: Our findings further highlight the importance of miR-24 as a potential biomarker as well as a therapeutic target for abdominal aneurysmal disease. Future research and validation of a panel of miRNAs for AAA would aid in diagnosis and discrimination between diseases with overlapping pathogeneses.

Circulating miRNAs as Biomarkers for Diagnosis, Surveillance, and Postoperative Follow-Up of Abdominal Aortic Aneurysms.

BACKGROUND: To provide a summary of the current state of research in English medical literature on circulating miRNAs as biomarkers for abdominal aortic aneurysm (AAA). Additionally, for the most commonly mentioned circulating miRNAs in the literature, to attempt a documentation of the biological mechanisms underlying their role in AAA development. METHODS: A literature search was undertaken in the MEDLINE database. Only reports that involved peripheral blood samples (whole blood, plasma, and serum) were included. The following terms were used in combination: microrna, mirna, AAA, human, circulating, plasma, serum, endovascular, and endovascular aneurysm repair (EVAR). RESULTS: A total of 25 reports, published from 2012 to 2022 were included with a total of 1,259 patients with AAA, predominantly men (N = 1,040, 90%). Six of these reports recruited healthy donors who underwent ultrasound screening for AAA as control samples. The majority of studies were undertaken in plasma samples and the most preferred microRNA profiling method was real - time quantitative polymerase chain reaction (qRT-PCR). The following 9 miRNAs (out of a total of 76) were studied in more than 2 references: miR-145, miR-24, miR-33, miR-125, let-7, miR-15, miR-191, miR-29, and miR-133. CONCLUSIONS: The 9 miRNAs described in this study, are implicated in known pathogenetic mechanisms of AAA, such as atherosclerosis, vascular smooth muscle cell (VSMCs) phenotype switch and apoptosis, vascular inflammation, extracellular matrix (ECM) degradation, and lipid metabolism. Identifying disease-specific miRNAs, in combination with other clinical parameters, as indicators of AAA, is crucial for early diagnosis as well as follow-up of AAAs. For future research on miRNAs as AAA biomarkers, strict case and control group definitions, sample acquisition protocols, and miRNA expression profiling techniques are warranted.

Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats.

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.

Postoperative hypofractionated-accelerated radiotherapy (HypoAR) for locally advanced rectal cancer.

BACKGROUND: despite the advances in preoperative hypofractionated-accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46-50 Gy in 5 weeks) remains a standard adjuvant schedule. The role of hypofractionated-accelerated radiotherapy in a postoperative setting remains largely unexplored. METHODS: eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated-accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12 days. The follow-up of patients alive at the time of analysis ranges from 12-120 months (median 48). RESULTS: mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P = 0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P = 0.23). CONCLUSION: postoperative hypofractionated-accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated-accelerated radiotherapy.

Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies.

BACKGROUND: Despite considerable progress in surgical techniques, anastomotic leak (AL) is a common complication after gastrointestinal surgery. Stem cells are a promising therapy to improve healing and have been used in gastrointestinal anastomoses. In this study, we perform a systematic review and meta-analysis to evaluate the efficacy of stem cell therapies in preventing ALs among animal studies. METHODS: A systematic review of the literature was performed by searching PubMed, Web of Science, and the Cochrane Library. We considered all anastomoses of the gastrointestinal tract (excl. biliary) from the esophagus to the rectum. Outcomes included AL rates on postoperative day (POD) 7 and the latest time point reported. RESULTS: Fourteen studies were identified, evaluating stem cells in gastrointestinal anastomoses, of which 1 was on esophageal, 2 on gastric, 2 on small intestinal, and 9 on colorectal anastomoses. Meta-analysis did not show significant differences in AL rates on POD 7 (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.04-3.15, p = 0.248, I2 = 34.1%, 95% CI: 0-75.2%, Q = 6.07, df = 4, p = 0.194), but there was a nonsignificant trend for lower AL rates at the latest time point reported (OR 0.28, 95% CI: 0.08-1.01, p = 0.052, I2 = 34%, 95% CI: 0-70.8%, Q = 10.6, df = 7, p = 0.157). CONCLUSION: Stem cell therapy may be associated with lower AL rates in gastrointestinal anastomoses, though meta-analysis is severely inhibited by heterogeneous study design. More studies are needed to determine the therapeutic potential of stem cells.

Career barriers for women in surgery.

BACKGROUND: Despite the increasing numbers of female medical students, surgery remains male-dominated. PURPOSE: To highlight the principal career obstacles experienced by aspiring female surgeons. METHODS: A narrative review of literature on the position and career barriers of female surgeons has been conducted, using the MEDLINE and EMBASE databases. MAIN FINDINGS: Implicit and even explicit biases against female surgeons remain prevalent, negatively impacting their training performance and overall professional trajectory. Female surgeons are globally underrepresented in leadership positions and senior academic rankings, especially that of a full professor. They feel hampered by lack of effective mentorship, whose value for a successful career has been acknowledged by all medical students, surgeons and surgical leaders. Their work-life imbalance is sometimes expressed as lower likelihood than their male contemporaries of getting married or having children and may be attributed to their conventional association with the role of caretaker, their personal desire to accommodate occupational and family duties and the inadequate implementation of parental leave and childcare policies. Female surgeons' "infertility" may be further explained by direct and indirect pregnancy-related difficulties. Female surgeons are also financially undercompensated compared to their male contemporaries. Finally, specialty-specific challenges should not be overlooked. CONCLUSIONS: While encouraging steps have been made, women in surgery feel still hindered by various obstacles. The qualitative, interview-based nature of current literature requires more meticulous studies on these barriers with a more quantitative and objective approach. Attenuation of gender imbalance in surgical specialties requires further changes in mentality and more targeted modifications in relevant policies.

Effects of the Antioxidant Quercetin in an Experimental Model of Ulcerative Colitis in Mice.

Background and Objectives: Quercetin, a member of the flavanol family found in many fruits, vegetables, leaves and grains has been found to have a wide range of biological effects on human physiology. The aim of this study was to investigate the effects of quercetin, when administered orally in the form of the water-soluble inclusion complex with hydroxypropyl-b-cyclodextrin (Que-HP-ß-CD), in an experimental model of ulcerative colitis in mice. Materials and Methods: Animals received either Dextran Sodium Sulphate (DSS), to induce colitis, + Que-HP-ß-CD (Group A), DSS alone (Group B) or no intervention (control, Group C) for 7 days. All animals were weighed daily, and evaluation of colitis was performed using the Disease Activity Index (DAI). On day 7 a blood sample was taken from all animals, they were then euthanised, the large intestine was measured, and histological and immunochemical analyses were performed. Results: The DAI demonstrated an increase over time for the groups receiving DSS (Groups A and B) compared with the control group (Group C), with a significant degree of protection being observed in the group that also received quercetin (Group A): The DAI over time slope for Group B was higher than that for Group A by 0.26 points/day (95% Cl 0.20−0.33, p < 0.01). Weight calculations and immunohistochemistry results validated the DAI findings. Conclusions: In conclusion, the administration of quercetin in an ulcerative colitis model in mice presents a therapeutic/prophylactic potential that warrants further investigation.

The medical futility experience of nursing professionals in Greece.

BACKGROUND: Providing futile medical care is an ever-timely ethical problem in clinical practice. While nursing personnel are very closely involved in providing direct care to patients nearing the end of life, their role in end-of-life decision-making remains unclear. METHODS: This was a prospective qualitative study conducted with experienced nursing professionals from December 2020 through May 2021. Individual in-depth qualitative interviews were conducted with sixteen participants. We performed a thematic analysis of the data. RESULTS: Importantly, many participants were half-hearted in their attitude towards accepting or defining futile medical care. Furthermore, interestingly, a list of well-described circumstances emerged, under which the dying process is most likely to be a "bad and undignified" process. These circumstances reflected situations revolving around a) pain and suffering, b) treating patients with respect, c) the appearance and image of the patient body, and d) the interaction between patients and their relatives. Fear of legal action, the lack of a regulatory framework, physicians being pressured by (mostly uninformed) family members and physicians' personal motives were reported as important reasons behind providing futile medical care. The nursing professional's role as a participant in decisions on futile care and as a mediator between physicians and patients (and family members) was highlighted. Furthermore, the patient's role in decisions on futile care was prioritized. The patient's effort to keep themselves alive was also highlighted. This effort impacts nursing professionals' willingness to provide care. Providing futile care is a major factor that negatively affects nursing professionals' inner attitude towards performing their duties. Finally, the psychological benefits of providing futile medical care were highlighted, and the importance of the lack of adequately developed end-of-life care facilities in Greece was emphasized. CONCLUSIONS: These findings enforce our opinion that futile medical care should be conceptualized in the strict sense of the term, namely, as caring for a brain-dead individual or a patient in a medical condition whose continuation would most likely go against the patient's presumed preference (strictly understood). Our findings were consistent with prior literature. However, we identified some issues that are of clinical importance.

Risk factors for cardiovascular mortality in patients with colorectal cancer: a population-based study.

BACKGROUND: Patients with colorectal cancer are at increased risk of cardiovascular mortality compared to the general population. The purpose of this study is to identify risk factors of cardiovascular mortality in patients with colorectal cancer. METHODS: A retrospective review of the Surveillance Epidemiology and End Results (SEER) database was performed between 2010 and 2014. Standardized Mortality Ratios (SMRs) for cardiovascular mortality were calculated by comparing the number of expected deaths in the United States according to the National Center for Health Statistics (ICD-10 codes I00-I99) to the number of observed deaths in the database. Logistic regression was used to identify independent risk factors. RESULTS: Overall, 164,719 patients were identified (mean age at diagnosis 67 ± 13.9 years, 52.7% males, 47.3% females), of which 4854 (2.9%) died from cardiovascular disease. The majority of cardiovascular deaths occurred during the first year after diagnosis (2658, 54.8%). SMRs for cardiovascular mortality were 11.7 (95% CI 11.3-12) among all patients, 12.1 (95% CI 11.7-12.6) for male patients and 11.1 (95% CI 10.6-11.6) for female patients, with SMRs being higher for younger patients. Older age, male sex, African-American race, elevated CEA and not undergoing curative surgery were independent risk factors of cardiovascular mortality in patients with colorectal cancer. CONCLUSION: Patients with colorectal cancer are associated with an increased risk of cardiovascular death, especially during the first year after diagnosis. Older age, male sex, African-American race, elevated CEA and not undergoing curative surgery are independent risk factors of cardiovascular death.

Predictors of lymph node metastasis in patients with gastrointestinal stromal tumors (GISTs).

BACKGROUND: Lymph node metastasis is not common among patients with gastrointestinal stromal tumors (GISTs) and its prognostic value is controversial. The purposes of this study are to identify predictors of lymph node metastasis and determine its prognostic associations. METHODS: A retrospective analysis of the surveillance, epidemiology and end results (SEER) database was performed. Patients with GISTs that underwent surgery and pathologic nodal staging were identified. Logistic regression and Cox regression were performed to identify independent predictors and prognostic factors, respectively. RESULTS: Of 1430 patients (age: 61.5 ± 14.5 years, 52% males), 140 (9.8%) had lymph node metastasis. On multivariable analysis, distant metastasis was the only independent predictor of lymph node metastasis (OR 4.95, 95% CI: 2.43-10.08, p < 0.001). In the entire cohort, lymph node metastasis did not reflect a worse overall survival (OS, HR 1.12, 95% CI: 0.49-2.58, p = 0.794) or disease-specific survival (DSS, HR 0.95, 95% CI: 0.31-2.88, p = 0.924), but was an independent predictor of worse OS in 51 patients (25.4% of 201 patients) who presented with both lymph node metastasis and synchronous distant metastasis (HR 2, 95% CI: 1.25-3.21, p = 0.004). Lymph node metastasis was also independently associated with worse survival among patients with small intestinal (OS: HR 1.88, 95% CI: 1.15-3.1, p = 0.013) and colorectal tumors (OS: HR 3.41, 95% CI: 1.56-7.46, p = 0.002, DSS: HR 3.58, 95% CI: 1.27-10.06, p = 0.016). CONCLUSIONS: Metastatic disease is an independent predictor of lymph node metastasis in patients with GISTs. Lymph node metastasis is also associated with worse overall survival in patients with metastatic GISTs.

Regenerated Nerve Defects with a Nerve Conduit Containing Dental Pulp Stem Cells in Pigs: An Immunohistochemical and Electrophysiological Evaluation.

BACKGROUND: Dental pulp stem cells (DPSCs) present an exciting new tool in the field of peripheral nerve regeneration due to their close embryonic origin. In this study, we examined their potential in pigs, using biodegradable collagen conduits filled with DPSCs. To our knowledge, this is the first time DPCSs are tested for peripheral nerve regeneration in such large animal model. MATERIALS AND METHODS: The second lateral incisor was extracted from every animal's lower jaw and stem cells were isolated and cultured. The collagen nerve conduits containing the DPSCs were subsequently transplanted into the transected fifth and sixth intercostal nerves, while the seventh intercostal nerve was used as a control and no stem cells were added on the respective collagen conduit. RESULTS: A histological examination was performed on the 3rd and 6th postoperative months and showed the gradual development of neural tissue and immunohistochemical expression of neuron-specific enolase. An electrophysiological study was performed on the 6th postoperative month and showed similar potentials between the stem cell infusion region (5 ± 0.04 units) and their proximal stumps (5 ± 0.05 units) and slightly smaller potentials in the respective distal stumps (4 ± 0.045 units). CONCLUSION: The nerves where DPSCs were injected exhibited morphological and functional recovery, in contrast to the control nerves where no recovery was detected; thus, there is a first evidence of the therapeutic potential of DPSCs in peripheral nerve regeneration.

Extending the concept of moral distress to parents of infants hospitalized in the NICU: a qualitative study in Greece.

BACKGROUND: The hospitalization of infants in the neonatal intensive care unit (NICU) is an ethically challenging situation. A limited number of studies have extended the concept of moral distress to parents of infants hospitalized in the NICU. This topic requires further investigation. METHODS: The present prospective qualitative study was conducted from February 2023 to May 2023. Data were collected through semistructured in-depth interviews, which were conducted in-person with fifteen parents of infants who were hospitalized in the NICU at the time of the interviews. Purposive sampling was used. The data were classified and analyzed using thematic analysis. RESULTS: Three themes emerged from the data analysis performed for this empirical study. One intrapersonal dimension featuring two aspects (one dynamic and one static) and another interpersonal dimension focusing on parental moral distress emerged from the data analysis. Furthermore, seven subthemes emerged across these themes: (1) self-directed negative feelings were experienced by parents due to their inability to fulfill their caregiving/parental roles; (2) intense internal conflict was experienced by parents in response to a moral dilemma that was difficult, which was perceived as irresolvable; (3) objectively unjustified, self-directed negative feelings of guilt or failure were experienced by parents; (4) parents experienced moral distress due to the poor image of the ill infants; (5) inadequate information may predispose parents to experience moral distress (6) neonatologists' caring behaviors were unduly perceived by parents as paternalistic behaviors; (7) reasonable or justified institutional rules were unduly perceived by parents as constraint. CONCLUSIONS: In general, the results of this study support the integrated definition of parental moral distress proposed by Mooney-Doyle and Ulrich. Furthermore, the present study introduces new information. The study distinguishes between the dynamic and static aspects of the intrapersonal dimension of the phenomenon of parental moral distress. Moreover, participants experienced moral distress because they unduly perceived certain situations as causing moral distress. In addition, inadequate information may predispose parents to experience moral distress. The findings of this study may contribute promote family-centered care in the NICU context.

Understanding the Ethical Issues of Brain-Computer Interfaces (BCIs): A Blessing or the Beginning of a Dystopian Future?

In recent years, scientific discoveries in the field of neuroscience combined with developments in the field of artificial intelligence have led to the development of a range of neurotechnologies. Advances in neuroimaging systems, neurostimulators, and brain-computer interfaces (BCIs) are leading to new ways of enhancing, controlling, and "reading" the brain. In addition, although BCIs were developed and used primarily in the medical field, they are now increasingly applied in other fields (entertainment, marketing, education, defense industry). We conducted a literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to provide background information about ethical issues related to the use of BCIs. Among the ethical issues that emerged from the thematic data analysis of the reviewed studies included questions revolving around human dignity, personhood and autonomy, user safety, stigma and discrimination, privacy and security, responsibility, research ethics, and social justice (including access to this technology). This paper attempts to address the various aspects of these concerns. A variety of distinct ethical issues were identified, which, for the most part, were in line with the findings of prior research. However, we identified two nuances, which are related to the empirical research on ethical issues related to BCIs and the impact of BCIs on international relationships. The paper also highlights the need for the cooperation of all stakeholders to ensure the ethical development and use of this technology and concludes with several recommendations. The principles of bioethics provide an initial guiding framework, which, however, should be revised in the current artificial intelligence landscape so as to be responsive to challenges posed by the development and use of BCIs.

The role of apigenin in an experimental model of acute pancreatitis.

AIM: The aim of the present study is to evaluate pathologic changes in the pancreatic parenchyma in an experimental model of acute pancreatitis (AP) following bilio-pancreatic duct ligation. An effort was made to clarify the role of apigenin, a substance that is well-known for its antioxidant and anti-inflammatory role and its likely beneficial activity to the pancreatic parenchyma following AP in rats. MATERIAL AND METHOD: One hundred twenty-six male Wistar rats 3-4 mo old and weighing 220-350 g were used. At time 0, the following groups were randomly assigned: group sham: rats were subjected to virtual surgery; group control: rats were subjected to surgery for induction of AP, by ligation of the bilio-pancreatic duct; group apigenin: rats were subjected to surgery for induction of AP and enteral feeding with apigenin. Pathologic changes of the pancreatic parenchymal and myeloperoxidase activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h. RESULT: From the pathologic reports, by comparing the control group with the apigenin group, an improvement of pancreatic tissue architecture following apigenin administration was observed. Inflammatory infiltration, edema, ductal dilation, and necrosis were reduced following apigenin administration over time (P = 0.049, P = 0.228, P = 0.387, P = 0.046). Treatment with apigenin significantly reduced the bilio-pancreatic duct ligation and evoked an increase in pancreatic myeloperoxidase activity (P = 0.030). CONCLUSION: Oral apigenin administration in rats, following experimentally induced pancreatitis, seems to protect the pancreatic tissue. Thus, apigenin administration to humans could potentially ameliorate the damages to the pancreas.

Limitation of Non-Beneficial Interventions and their Impact on the Intensive Care Unit Costs.

Introduction: Using a plan to limit non-beneficial life support interventions has significantly reduced harm and loss of dignity for patients at the end of life. The association of these limitations with patients' clinical characteristics and health care costs in the intensive care unit (ICU) needs further scientific evidence. Aim of the study: To explore decisions to limit non-beneficial life support interventions, their correlation with patients' clinical data, and their effect on the cost of care in the ICU. Material and Methods: We included all patients admitted to the general ICU of a hospital in Greece in a two-year (2019-2021) prospective study. Data collection included patient demographic and clinical variables, data related to decisions to limit (withholding, withdrawing) non-beneficial interventions (NBIs), and economic data. Comparisons were made between patients with and without limitation decisions. Results: NBIs were limited in 164 of 454 patients (36.12%). Patients with limitation decisions were associated with older age (70y vs. 62y; p<0,001), greater disease severity score (APACHE IV, 71 vs. 50; p<0,001), longer length of stay (7d vs. 4.5d; p<0,001), and worse prognosis of death (APACHE IV PDR, 48.9 vs. 17.35; p<0,001). All cost categories and total cost per patient were also higher than the patient without limitation of NBIs (9247,79€ vs. 8029,46€, p<0,004). The mean daily cost has not differed between the groups (831,24€ vs. 832,59€; p<0,716). However, in the group of patients with limitations, all cost categories, including the average daily cost (767.31€ vs. 649.12€) after the limitation of NBIs, were reduced to a statistically significant degree (p<0.001). Conclusions: Limiting NBIs in the ICU reduces healthcare costs and may lead to better management of ICU resource use.

Pedunculated Focal Nodular Hyperplasia: When in Doubt, Should We Cut It Out?

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor and can rarely present as an exophytic solitary mass attached to the liver by a stalk. Most FNH cases are usually detected as incidental findings during surgery, imaging or physical examination and have a high female predominance. However, the pedunculated forms of FNH are particularly rare and commonly associated with severe complications and diagnostic challenges. Hence, our study aims to provide a comprehensive summary of the available data on the pedunculated FNH cases among adults and children. Furthermore, we will highlight the role of different therapeutic options in treating this clinical entity. The use of imaging techniques is considered a significant addition to the diagnostic toolbox. Regarding the optimal treatment strategy, the main indications for surgery were the presence of symptoms, diagnostic uncertainty and increased risk of complications, based on the current literature. Herein, we also propose a management algorithm for patients with suspected FNH lesions. Therefore, a high index of suspicion and awareness of this pathology and its life-threatening complications, as an uncommon etiology of acute abdomen, is of utmost importance in order to achieve better clinical outcomes.

Tumor-infiltrating lymphocytes, PD-L1, and MMR-deficiency combined characterization may identify subgroups of rectal cancer patients who would benefit from immunotherapy.

INTRODUCTION: Mismatch repair deficiency, immunological fertility, and PD-L1 expression status are key histopathological and molecular features defining tumor responsiveness to immunotherapy and, eventually, prognosis. These were investigated in a series of locally advanced rectal cancer patients treated with postoperative chemotherapy and radiotherapy. MATERIALS AND METHODS: Tumor-infiltrating lymphocyte (TIL) density was assessed in hematoxylin-eosin tissue sections. PD-L1 expression and the expression of MMR proteins (MLH1, PSM2, MSH2, and MSH6) were assessed with immunohistochemistry. Their association with histopathological variables (node involvement and tumor budding) and prognosis was assessed. RESULTS: The TIL-density was significantly higher in the invading tumor front and was inversely related to tumor budding and directly with better overall survival (OS) and distant metastasis-free survival (DMFS) (p = 0.02 and 0.02, respectively). Cancer cell PD-L1 expression was related to high TIL-density (p < 0.01) but not to prognosis, although its overexpression defined a trend for poorer OS in patients with high TIL-density. High PD-L1 expression by stroma infiltrating immune cells was linked with better OS and DMFS (p = 0.007 and 0.001, respectively. MMR deficiency was recorded in 26.2 % of cases, and this was linked with higher TIL-density, but not with prognosis. CONCLUSIONS: Dense intratumoral lymphocytic infiltration relates to a better prognosis in rectal cancer, although it is also linked with PD-L1 expression that may adversely modulate the anti-tumor effects of TILs. This latter subgroup of patients (high TIL-density/high cancer cell PD-L1 expression) could be an additional target for anti-PD-1/PD-L1 immunotherapy, along with the established subgroup of MMR deficient patients.

Predictive Factors for Anastomotic Leakage Following Colorectal Cancer Surgery: Where Are We and Where Are We Going?

Anastomotic leakage (AL) remains one of the most severe complications following colorectal cancer (CRC) surgery. Indeed, leaks that may occur after any type of intestinal anastomosis are commonly associated with a higher reoperation rate and an increased risk of postoperative morbidity and mortality. At first, our review aims to identify specific preoperative, intraoperative and perioperative factors that eventually lead to the development of anastomotic dehiscence based on the current literature. We will also investigate the role of several biomarkers in predicting the presence of ALs following colorectal surgery. Despite significant improvements in perioperative care, advances in surgical techniques, and a high index of suspicion of this complication, the incidence of AL remained stable during the last decades. Thus, gaining a better knowledge of the risk factors that influence the AL rates may help identify high-risk surgical patients requiring more intensive perioperative surveillance. Furthermore, prompt diagnosis of this severe complication may help improve patient survival. To date, several studies have identified predictive biomarkers of ALs, which are most commonly associated with the inflammatory response to colorectal surgery. Interestingly, early diagnosis and evaluation of the severity of this complication may offer a significant opportunity to guide clinical judgement and decision-making.

Parental Home Safety Practices for Domestic Accident Prevention: How Prepared Were Parents for COVID-19 Confinement? A Cross-Sectional Study.

(1) Background: Children are susceptible to home injuries. How prepared parents were to protect their children from accidents before and during the COVID-19 quarantine is uncertain. (2) Methods: We conducted a community-based, cross-sectional study in Greece between November and December 2021. We asked parents to complete an anonymous questionnaire voluntarily. Questions focused on accident-preventive measures taken at home during the COVID-19 quarantine. (3) Results: A greater proportion of parents took protective measures for a safer home before the lockdown than during the quarantine, while an interesting percentage of parents never utilized preventive measures for their children. Slightly more than half (58.6%) of parents did not seem to worry about a possible increase in domestic accidents during the quarantine. It was observed that those who had one or two children took more protective measures than those with more than two children. Older parents seemed to explain to their children how to access emergency services more often. Mothers stayed at home with the children more often, and their education affected the presence of some of the assessed measures. In our logistic regression modeling, parental concern about accidents was more related to the incidence of an accident during the pandemic and attendance at seminars. (4) Conclusions: Although the COVID-19 lockdowns disorganized family life, parents were aware of the importance of their parenting role in creating a safe environment for children, but according to the study, there is room for improvement.