Posttraumatic stress disorder and quality of life in patients after open thoracoabdominal aortic repair.

Background: Open thoracoabdominal aortic aneurysm (TAAA) repair is often related to significant morbidity and complications like paraplegia or acute kidney injury. Subsequently, prolonged intensive care stay is common. However, there is a lack of research on post-traumatic stress disorder (PTSD) and the perceived quality of life (QOL) in patients undergoing complex aortic procedures, such as open TAAA repair. Therefore, our study aims to determine the prevalence of PTSD and the current QOLin these patients and whether it is associated with demographic factors or complications following open thoracoabdominal aortic repair. Patients and methods: In this retrospective study, a total of 213 adult surviving patients after open thoracoabdominal aortic repair were contacted with two questionnaires one to assess PTSD and another to evaluate current QOL after open thoracoabdominal aortic repair. 61 patients returned one or both the questionnaires, and 59 patients (97%) answered all questions of the 4-item primary care PTSD section of the survey. In addition to the PTSD screening, patients were sent an SF-36 questionnaire to assess their current quality of life. 60 patients answered the SF-36 questionnaire partially or completely (98%). Results: 27% of patients (16/59) screened positive for PTSD. Electronic medical records were matched to all responding patients. Patients who were screened positive for PTSD spent more days in intensive care (OR, 1.073; 95% CI 1.02-1.13; p=0.005), had a higher frequency of tracheotomy (OR, 6.43; 95% CI 1.87-22.06; p=0.004), sepsis (OR, 5.63; 95% CI 1.56-20.33; p=0.014), as well as postoperative paraparesis (OR, 13.23; 95% CI 1.36-129.02; p=0.019). In patients with postoperative complications, a statistically significant decrease in the overall score was observed for certain categories of the SF-36. Conclusions: The prevalence of PTSD is higher, in comparison to the general population's prevalence, and the quality of life is affected following open thoracoabdominal aortic aneurysm repair, with a significant relation to postoperative complications as well as the length of ICU stay. Further research and screening for PTSD in relation to open TAAA repair is needed to assess its role in patient QOL during follow up.

The role of Proenkephalin A 119-159 in the detection of acute kidney injury after open thoracoabdominal aortic repair.

Background: Acute kidney injury (AKI) after open thoracoabdominal aortic aneurysm repairs (TAAA) is a common postoperative complication, associated with increased mortality and morbidity. Early detection and management of the kidney tissue damage remains of paramount importance. The aim of this prospectively conducted, observational trial was to evaluate the clinical applicability of Proenkephalin A 119-159 (penKid) for the detection of postoperative AKI. Patients and methods: Thirty-six patients, planned for elective open TAAA repairs from January 2019 to December 2022, were recruited in two German centres (University Hospital Aachen and Charité - University Hospital Berlin). Blood samples were collected pre-surgery (baseline), directly postoperatively and at 12, 24 and 48 hours after surgery. The penKid concentration in plasma was measured using the immunoluminometric sphingotest® assay kit and they were statistically tested for association with AKI and other clinical parameters. Results: Twenty-four patients (62%) developed moderate or severe AKI postoperatively (Stage 2 or 3 of the KDIGO classification) and they had a significantly increased risk for the development of acute respiratory distress syndrome (p=.023) or a fatal outcome (p=.035). Starting from the 12th hour after surgery, we found penKid correlating with AKI stage 2/3 (12 hour penKid mean in pmol/L: 93.9 vs. 43.1; c index .776, p=.0037) and renal replacement therapy (12 hour c index .779, p=.0035). Patients with multi-organ dysfunction syndrome had significantly increased penKid levels at all timepoints. Conclusions: We found penKid to be a promising biomarker for the early detection of postoperative AKI and in-hospital mortality after open TAAA repair, which may enable the early initiation of organ-protective strategies and reduction of further complications associated with AKI.

Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

OBJECTIVE: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. METHODS: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. RESULTS: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. CONCLUSIONS: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

Systematic Review of the Effect of Cerebrospinal Fluid Drainage on Outcomes After Endovascular Descending Thoracic/Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: This study aimed to investigate whether prophylactic use of cerebrospinal fluid (CSF) drainage in endovascular descending thoracic aortic aneurysm (DTAA) and thoraco-abdominal aortic aneurysm (TAAA) repair contributes to a lower rate of post-operative spinal cord ischaemia (SCI). DATA SOURCES: MEDLINE, Embase, and CINAHL. REVIEW METHODS: A literature review was conducted in accordance with PRISMA guidelines (PROSPERO registration no. CRD42021245893). Risk of bias was assessed through the Newcastle-Ottawa scale (NOS), and the certainty of evidence was graded using the GRADE approach. A proportion meta-analysis was conducted to calculate the pooled rate and 95% confidence interval (CI) of both early and late onset SCI. Pooled outcome estimates were calculated using the odds ratio (OR) and associated 95% CI. The primary outcome was SCI, both early and lateonset. Secondary outcomes were complications of CSF drainage, length of hospital stay, and peri-operative (30 day or in hospital) mortality rates. RESULTS: Twenty-eight observational, retrospective studies were included, reporting 4 814 patients (2 599 patients with and 2 215 without CSF drainage). The NOS showed a moderate risk of bias. The incidence of SCI was similar in patients with CSF drainage (0.05, 95% CI 0.03 ‒ 0.08) and without CSF drainage (0.05, 95% CI 0.00 ‒ 0.14). No significant decrease in SCI was found when using CSF drainage (OR 0.67, 95% CI 0.29 ‒ 1.55, p = .35). The incidence rate of CSF drainage related complication was 0.10 (95% CI 0.04 ‒ 0.19). The 30 day and in hospital mortality rate with CSF drainage was 0.08 (95% CI 0.05 ‒ 0.12). The 30 day and in hospital mortality rate without CSF drainage and comparison with late mortality and length of hospital stay could not be determined due to lack of data. The quality of evidence was considered very low. CONCLUSION: Pre-operative CSF drainage placement was not related to a favourable outcome regarding SCI rate in endovascular TAAA and DTAA repair. Due to the low quality of evidence, no clear recommendation on pre-operative use of CSF drainage placement can be made.

Targeting STAT3 prevents bile reflux-induced oncogenic molecular events linked to hypopharyngeal carcinogenesis.

The signal transducer and activator of transcription 3 (STAT3) oncogene is a transcription factor with a central role in head and neck cancer. Hypopharyngeal cells (HCs) exposed to acidic bile present aberrant activation of STAT3, possibly contributing to its oncogenic effect. We hypothesized that STAT3 contributes substantially to the bile reflux-induced molecular oncogenic profile, which can be suppressed by STAT3 silencing or pharmacological inhibition. To explore our hypothesis, we targeted the STAT3 pathway, by knocking down STAT3 (STAT3 siRNA), and inhibiting STAT3 phosphorylation (Nifuroxazide) or dimerization (SI3-201; STA-21), in acidic bile (pH 4.0)-exposed human HCs. Immunofluorescence, luciferase assay, Western blot, enzyme-linked immunosorbent assay and qPCR analyses revealed that STAT3 knockdown or pharmacologic inhibition significantly suppressed acidic bile-induced STAT3 activation and its transcriptional activity, Bcl-2 overexpression, transcriptional activation of IL6, TNF-α, BCL2, EGFR, STAT3, RELA(p65), REL and WNT5A, and cell survival. Our novel findings document the important role of STAT3 in bile reflux-related molecular oncogenic events, which can be dramatically prevented by STAT3 silencing. STA-21, SI3-201 or Nifuroxazide effectively inhibited STAT3 and cancer-related inflammatory phenotype, encouraging their single or combined application in preventive or therapeutic strategies of bile reflux-related hypopharyngeal carcinogenesis.

Onset of Adverse Abdominal Events Due to Intestinal Ischemia-Reperfusion Injury after Aortic Cross-Clamping Is Associated with Elevated HSP70 Serum Levels in the Early Postoperative Phase.

Tissue injury of the viscera during open thoracoabdominal aortic (TAA) reconstructions has been reported as the aftermath of the ischemia-reperfusion mechanism following supracoeliac aortic cross-clamping. Abdominal complications after open aortic reconstructions, although rare through the intraoperative implementation of selective visceral artery blood perfusion, are associated with high rates of reinterventions and a poor prognosis. Recent animal experiments demonstrated that provoking mesenteric ischemia in rats induces the leukocyte-mediated transcription of heat-shock protein 70 (HSP70), a chaperone belonging to the danger-associated molecular pattern proteins (DAMPs). Translating these findings clinically, we investigated the serum levels of HSP70 in patients undergoing open aortic reconstructions with supracoeliac clamping. We postoperatively observed a relevant induction of HSP70, which remained significantly elevated in cases of postoperative abdominal complications (paralytic ileus, abdominal compartment syndrome, and visceral malperfusion). The receiver-operator curve analysis revealed the reliable prognostic accuracy of HSP70 as a biomarker for these complications as soon as 12 h post-operation (AUC 0.908, sensitivity 88.9%, specificity 83.3%). In conclusion, measuring HSP70 serum levels in the early postoperative phase may serve as a further adjutant in the diagnostic decision making for both the vascular surgeon and intensivist for the timely detection and management of abdominal complications following open TAA surgery.

Pepsin Promotes Activation of Epidermal Growth Factor Receptor and Downstream Oncogenic Pathways, at Slightly Acidic and Neutral pH, in Exposed Hypopharyngeal Cells.

Pepsin refluxate is considered a risk factor for laryngopharyngeal carcinogenesis. Non-acidic pepsin was previously linked to an inflammatory and tumorigenic effect on laryngopharyngeal cells in vitro. Yet there is no clear evidence of the pepsin-effect on a specific oncogenic pathway and the importance of pH in this process. We hypothesized that less acidic pepsin triggers the activation of a specific oncogenic factor and related-signalling pathway. To explore the pepsin-effect in vitro, we performed intermittent exposure of 15 min, once per day, for a 5-day period, of human hypopharyngeal primary cells (HCs) to pepsin (1 mg/mL), at a weakly acidic pH of 5.0, a slightly acidic pH of 6.0, and a neutral pH of 7.0. We have documented that the extracellular environment at pH 6.0, and particularly pH 7.0, vs. pH 5.0, promotes the pepsin-effect on HCs, causing increased internalized pepsin and cell viability, a pronounced activation of EGFR accompanied by NF-κB and STAT3 activation, and a significant upregulation of EGFR, AKT1, mTOR, IL1ß, TNF-α, RELA(p65), BCL-2, IL6 and STAT3. We herein provide new evidence of the pepsin-effect on oncogenic EGFR activation and its related-signaling pathway at neutral and slightly acidic pH in HCs, opening a window to further explore the prevention and therapeutic approach of laryngopharyngeal reflux disease.

The in vivo preventive and therapeutic properties of curcumin in bile reflux-related oncogenesis of the hypopharynx.

Bile at strongly acidic pH exerts a carcinogenic effect on the hypopharynx, based upon recent pre-clinical studies that support its role as an independent risk factor. We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF-κB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF-κB and consequently altering the expression of genes with oncogenic function. Using Mus musculus (C57Bl/6J), we topically applied curcumin (250 µmol/L; three times per day; 10 days) to the hypopharynx, 15 minutes before, 15 minutes after or in combination with bile acids (pH 3.0). Immunohistochemical analysis and qPCR revealed that topically applied curcumin either before, after or in combination with acidic bile exposure significantly suppressed its induced NF-κB activation in regenerating epithelial cells, and overexpression of Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1 was particularly inhibited by curcumin when applied simultaneously with bile. We provide novel evidence into the preventive and therapeutic properties of topically applied curcumin in acidic bile-induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF-κB, and shaping future translational development of effective targeted therapies using topical non-pharmacologic inhibitors of NF-κB.

Postoperatively increased bioactive adrenomedullin is related to adverse outcome after complex aortic surgery.

Background: Open and endovascular thoracoabdominal aortic aneurysm repair is related to major complications and increased mortality rates. Up to now, specific biomarkers for adverse outcome are scarce, although routine usage of such biomarkers could enable an earlier and more appropriate treatment of complications during the postoperative course after complex aortic aneurysm repair. Patients and methods: In a prospective single-center study including 33 patients (48.5 % women, mean age 63.0 ± 16.2 years) undergoing elective complex open and endovascular aortic aneurysm repair, bioactive adrenomedullin (bio-ADM) was measured for 72 h perioperatively and an association with clinical endpoints, namely cardiogenic shock, death and the combined endpoint of the two aforementioned parameters was assessed. Furthermore, the association between bio-ADM and baseline characteristics and perioperative details including sepsis biomarkers score were assessed. Results: 51.5 % (n = 17) of patients developed postoperative acute kidney injury, 21.2 % (n = 7) pneumonia and 18.2 % (n = 6) sepsis. Cardiogenic shock was observed in 12.1 % (n = 4) patients. The in-hospital mortality rate was 18.2 % (n = 6), and 24.2 % (n = 8) of patients developed cardiogenic shock and/or died in hospital. A significant correlation of bio-ADM concentrations from all available time points was observed with leukocytes (r = 0.37, P < 0.0001), C-reactive protein (r = 0.56, P < 0.001) and serum creatinine levels (r = 0.52, P < 0.001). Increased bio-ADM at 12 h, 24 h, 48 h and 72 h after admission to ICU was associated with both, in-hospital death and cardiogenic shock, with an area under the curve for the combined endpoint of 0.598, 0.720, 0.880 and 0.967. Bio-ADM concentrations at 48 h and 72 h after admission to ICU were predictive for in-hospital death and cardiogenic shock (both P < 0.01). Conclusions: Bio-ADM may serve as postoperative biomarker for cardiogenic shock and death after complex open and endovascular aortic aneurysm repair, potentially enabling an earlier and by that more adequate treatment of adverse outcome after major surgery.

Non-celiac Enteropathy and Olmesartan: An Essential Consideration.

Emerging evidence has shed light on non-celiac causes of enteropathy in recent years, presenting a diagnostic challenge for clinicians. This study discusses the diagnostic challenges related to non-celiac enteropathy, specifically focusing on olmesartan-induced enteropathy (OIE). A 73-year-old lady presented to the emergency department with a six-month history of watery diarrhea exacerbated by food intake and significant weight loss. The patient at admission was found to be dehydrated with severe hypokalemia and hypocalcemia. The extensive testing that was performed was unremarkable, including celiac disease panel, enteric panel, ova and parasites, Clostridium difficile, fecal calprotectin, and computed tomography of the abdomen and pelvis. A significant electrolyte imbalance was corrected at admission, and subsequent upper endoscopy investigation with duodenal biopsies revealed moderate to severe villi blunting with a significant intraepithelial infiltrate of CD3+ lymphocytes. A colonoscopy that was performed at the same time was unremarkable, with negative biopsies for microscopic colitis. Given the suspicion of OIE, olmesartan was discontinued. One-month follow-up revealed resolution of malabsorption, with electrolyte normalization and duodenal biopsies showing improved duodenitis. This study emphasizes the importance of considering medication history and ruling out other potential causes of enteropathy. Olmesartan is an angiotensin II receptor antagonist that is commonly prescribed for hypertension. However, in rare cases, it may induce enteropathy, which often remains underdiagnosed. This rare side effect may present as chronic diarrhea, weight loss, and signs of malabsorption. Interestingly, OIE presents with overlapping clinical and histopathological features to celiac disease and, therefore, may mislead physicians to an extensive diagnostic investigation. Greater awareness of medication-related diarrheal syndromes such as OIE should be promoted, given that simple discontinuation of the medication can lead to dramatic clinical improvement.

Short-Term Outcomes and Efficacy of Percutaneous Deep Vein Arterialization for No-Option Critical Limb Ischemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Percutaneous deep vein arterialization (pDVA) is considered a treatment modality in patients with no-option critical limb ischemia. However, there is still a paucity of evidence regarding its safety and efficacy. DATA SOURCES: MEDLINE (via PubMed), Embase and Web of Science databases as well as the CENTRAL registry up to the end of June 2023. METHODS: This review adhered to the PRISMA guidelines (PROSPERO registration no. CRD42023445171). The risk of bias was assessed using the methodological index for non-randomized studies (MINORS). Primary endpoints included technical success, overall survival and limb salvage during the follow-up. Amputation-free survival at 30 days, 6 months and 1 year as well as complete wound healing, major adverse limb events and reintervention were investigated as secondary outcomes. RESULTS: Five observational studies, comprising 208 patients (142 Rutherford class 5/77 Rutherford class 6), were included. MINORS revealed a low risk of bias. The meta-analysis reached a pooled technical success rate of 96.2% (95% CI: 91.5-98.4), an overall survival of 82.8% (95% CI: 70.5-95.2) and a limb salvage rate of 77.2% (95% CI: 65.2-89.1) during the follow-up. The amputation-free survival at 30 days, 6 months and 1 year was 87.8%, 68.7% and 65.6%, respectively. Furthermore, pDVA resulted in a complete wound healing rate of 53.4% (95% CI: 30.3-76.5). The pooled reintervention rate was as high as 46.7% (37.1-56.3%). CONCLUSIONS: PDVA seems a feasible bail-out strategy for patients with no option for routine treatment of CLTI. However, due to the small number of studies, the strength of the evidence is low.

Novel non-invasive molecular signatures for oral cavity cancer, by whole transcriptome and small non-coding RNA sequencing analyses: Predicted association with PI3K/AKT/mTOR pathway.

INTRODUCTION: Identification of molecular biomarkers in the saliva and serum of oral cavity cancer patients represents a first step in the development of essential and efficient clinical tools for early detection and post-treatment monitoring. We hypothesized that molecular analyses of paired saliva and serum samples from an individual would likely yield better results than analyses of either serum or saliva alone. MATERIALS AND METHODS: We performed whole-transcriptome and small non-coding RNA sequencing analyses on 32 samples of saliva and serum collected from the same patients with oral squamous cell carcinoma (OSCC) and healthy controls (HC). RESULTS: We identified 12 novel saliva and serum miRNAs and a panel of unique miRNA and mRNA signatures, significantly differentially expressed in OSCC patients relative to HC (log2 fold change: 2.6-26.8; DE: 0.02-0.000001). We utilized a combined panel of the 10 top-deregulated miRNAs and mRNAs and evaluated their putative diagnostic potential (>87% sensitivity; 100% specificity), recommending seven of them for further validation. We also identified unique saliva and serum miRNAs associated with OSCC and smoking history (OSCC smokers vs. never-smokers or HC: log2 fold change: 22-23; DE: 0.00003-0.000000001). Functional and pathway analyses indicated interactions between the discovered OSCC-related non-invasive miRNAs and mRNAs and their targets, through PI3K/AKT/mTOR signaling. CONCLUSION: Our data support our hypothesis that using paired saliva and serum from the same individuals and deep sequencing analyses can provide unique combined mRNA and miRNA signatures associated with canonical pathways that may have a diagnostic advantage relative to saliva or serum alone and may be useful for clinical testing. We believe this data will contribute to effective preventive care by post-treatment monitoring of patients, as well as suggesting potential targets for therapeutic approaches.

Postoperative bioactive adrenomedullin is associated with the onset of ARDS and adverse outcomes in patients undergoing open thoracoabdominal aortic surgery.

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12-48 h after surgery) and the onset of ARDS (p < .001), prolonged ventilation (p = .015 at 12h after surgery), atrial fibrillation (p < .001), and mortality (p = .05 at 24h). The biomarker was also strongly associated with sepsis (p = .01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p = .02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs.

Factors Associated with Early Mortality in Acute Type A Aortic Dissection-A Single-Centre Experience.

BACKGROUND: Acute aortic dissection type A (AADA) is a surgical emergency with relevant mortality and morbidity despite improvements in current management protocols. Identifying patients at risk of a fatal outcome and controlling the factors associated with mortality remain of paramount importance. METHODS: In this retrospective observational study, we reviewed the medical records of 117 patients with AADA, who were referred to our centre and operated on between 2005 and 2021. Preoperative, intraoperative, and postoperative variables were analysed and tested for their correlation with in-hospital mortality. RESULTS: The overall survival rate was 83%. Preoperatively, factors associated with mortality were age (p = 0.02), chronic hypertension (p = 0.02), any grade of aortic valve stenosis in the patient's medical history (p = 0.03), atrial fibrillation (p = 0.04), and oral anticoagulation (p = 0.04). Non-survivors had significantly longer operative times (p = 0.002). During the postoperative phase, mortality was strongly associated with acute kidney injury (AKI) (p < 0.001), acute heart failure (p < 0.001), stroke (p = 0.02), focal neurological deficits (p = 0.02), and sepsis (p = 0.001). In the multivariate regression analysis, the onset of postoperative focal neurological deficits was the best predictor of a fatal outcome after adjusting for ARDS (odds ratio: 5.8, 95%-CI: 1.2-41.7, p = 0.04). CONCLUSIONS: In this retrospective analysis, atrial fibrillation, oral anticoagulation, hypertension, and age were significantly correlated with mortality. Postoperatively, acute kidney injury, acute heart failure, sepsis, and focal neurological deficits were correlated with in-hospital mortality, and focal neurological deficit has been identified as a significant predictor of fatal outcomes. Early detection and interdisciplinary management of at-risk patients remain crucial throughout the postoperative phase.

[Challenges and options for advanced training in surgery : An interdisciplinary position paper against the background of the hospital structural reform in Germany]. / Herausforderungen und Chancen für die chirurgische Weiterbildung : Ein fachgesellschaftsübergreifendes Positionspapier vor dem Hintergrund der Krankenhausstrukturreform.

BACKGROUND: Even now the further training in surgery faces considerable challenges. The planned hospital structural reform will result in new bureaucratic and organizational hurdles, which could lead to a considerable loss of quality in advanced surgical training across all disciplines. OBJECTIVE: The aim of this position paper is to describe the current and future challenges for advanced surgical training and to identify possible approaches and opportunities for the further development against the background of the planned hospital structural reform. MATERIAL AND METHODS: For the development of this position paper a committee of representatives of the Young Forums of the German surgical societies identified and critically discussed current problems and challenges of the present residency training system and formulated a list of demands for a sustainable residency training concept. RESULTS: The planned shift to outpatient treatment and centralization were identified as central challenges for surgical residency training. Surgical training must be considered consistently and from the outset in all political reform efforts. In addition to a transparent and cost-appropriate financing of residency training, we call for the involvement of all German surgical societies in the reform process. Furthermore, the social framework conditions for junior surgeons should be considered. CONCLUSION: The structural change in the hospital landscape in Germany, which is being forced by politicians, harbors the risk of a further loss of quality and experience in surgical treatment and training. At the same time, the planned hospital reform offers a unique opportunity to address existing problems and challenges in surgical training and to consider them as a starting point for structural changes which are fit for the future.

Endovascular repair of the aortic arch.

Objectives: The gold standard for the treatment of pathologies of the aortic arch remains the open surgical reconstruction of the affected segments. However, endovas-cular treatment options have emerged that eliminate the need for invasive open surgery. Several endograft devices - with fenestrations or branches for the supraaortic vessels - are currently available to address different pathologies and anatomical variations. Parallel-graft techniques and in situ fenestrations expand the treatment options for emergent cases. In this selective review of the literature of 2020 and 2021, we summarize the current chances and challenges of endovascular aortic repair. Content: Reported mortality rates range from 0 to 13.2 %. Although technical success rates for fenestrated and branched devices are promising (98 %), stroke rates remain a relevant issue (10 and 3 % for BTEVAR and FTEVAR respectively). The reported technical success rate for in situ fenestrations is also encouraging (94 %) and the stroke rates acceptable (5 %). Parallel-graft techniques are associated with high early and late endoleak rates (early 76 %; late 31 %), but still hold a valuable place in the treatment of emergent cases or in bail-out situations. Summary and Outlook: The endovascular repair of the aortic arch expands the range of patients with pathologies of the arch eligible for treatment to those unfit for open surgery offering a minimally invasive, yet technically challenging procedure. More data and meta-analyses are needed to define the benefits and drawbacks of this promising treatment option in an aging population with increasing co-morbidities.

The Role of PARP-1 and NF-κB in Bile-Induced DNA Damage and Oncogenic Profile in Hypopharyngeal Cells.

OBJECTIVES/HYPOTHESIS: We recently documented that acidic bile, a gastroesophageal reflux content, can cause invasive hypopharyngeal squamous cell carcinoma, by inducing widespread DNA damage and promoting nuclear factor kappa B (NF-κB)-related oncogenic molecular events. Poly or adenosine diphosphate (ADP)-ribose polymerase-1 (PARP-1), a sensitive sensor of DNA damage, may interact with NF-κB. We hypothesized that PARP-1 is activated in hypopharyngeal cells (HCs) with marked DNA damage caused by acidic bile, hence there is an association between PARP-1 and NF-κB activation or its related oncogenic profile, in this process. STUDY DESIGN: In vitro study. METHODS: We targeted PARP-1 and NF-κB(p65), using pharmacologic inhibitors, 1.0 µM Rucaparib (AG014699) and 10 µM BAY 11-7082 {3-[4=methylphenyl)sulfonyl]-(2E)-propenenitrile}, respectively, or silencing their gene expression (siRNAs) and used immunofluorescence, luciferase, cell viability, direct enzyme-linked immunosorbent assays, and qPCR analysis to detect the effect of targeting PARP-1 or NF-κB in acidic bile-induced DNA damage, PARP-1, p-NF-κB, and B-cell lymphoma 2 (Bcl-2) expression, as well as NF-κB transcriptional activity, cell survival, and mRNA oncogenic phenotype in HCs. RESULTS: We showed that (i) PARP-1 is overexpressed by acidic bile, (ii) targeting NF-κB adequately prevents the acidic bile-induced DNA double-strand breaks (DSBs) by gamma H2A histone family member X (γH2AX), oxidative DNA/RNA damage, PARP-1 overexpression, anti-apoptotic mRNA phenotype, and cell survival, whereas (iii) targeting PARP-1 preserves elevated DNA damage, NF-κB activation, and anti-apoptotic phenotype. CONCLUSION: We document for the first time that the activation of PARP-1 is an early event during bile reflux-related head and neck carcinogenesis and that NF-κB can mediate DNA damage and PARP-1 activation. Our data encourage further investigation into how acidic bile-induced activated NF-κB mediates DNA damage in hypopharyngeal carcinogenesis. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1146-1155, 2023.

Gastric cancer after Bariatric Bypass Surgery. Do they relate? (A Systematic Review).

Bariatric bypass surgery has been an effective treatment for morbid obesity. However, there is an increasing number of reported cases of gastric cancer after bypass surgery. Our systematic review showed an increasing trend of gastric cancer cases after bariatric bypass surgery in the last decade, mostly located in the excluded stomach (77%) and diagnosed in an advanced stage. In addition to known risk factors such as tobacco smoking (17%), H. pylori infection (6%), and family history of gastric cancer (3%), bile reflux, a recently proposed cancer-promoting factor, was also estimated in 18% of the cases. Our data suggest that gastric cancer risk assessment should be considered before gastric bypass surgery, and further investigations are needed to determine the value of post-operative gastric cancer surveillance.

IFABP levels predict visceral malperfusion in the first hours after open thoracoabdominal aortic repair.

Introduction: Intestinal ischemia after open thoracoabdominal aortic repairs, is a rare but devastating complication, associated with high mortality. Notoriously challenging to diagnose, visceral malperfusion necessitates immediate surgical attention. Intestinal fatty acid-binding protein (IFABP) has been proposed as a biomarker for the diagnosis of intestinal wall damage. In this prospectively conducted, observational study we evaluated the diagnostic capacity of IFABP levels in patients' serum and their correlation with visceral malperfusion. Methods: 23 patients undergoing open thoracoabdominal aortic repairs were included in this study and 8 of them were diagnosed postoperatively with visceral malperfusion-defined as a partial or complete thrombotic occlusion of the superior mesenteric artery and/or the coeliac trunk. IFABP levels and laboratory parameters often associated with intestinal ischemia (leucocytes, CRP, PCT and lactate) were measured at baseline, directly postoperatively, and at 12, 24 and 48 h after surgery. Postoperative visceral malperfusion-as revealed in CT angiography-was assessed and the predictive ability of IFABP levels to detect visceral malperfusion was evaluated with receiver-operator curve analysis. Results: Patients with visceral malperfusion had a relevant risk for a fatal outcome (p = .001). IFABP levels were significantly elevated directly postoperatively and at 12 h after surgery in cases of visceral malperfusion. High IFABP concentrations in serum detected visceral malperfusion accurately during the first 12 h after surgery, with the maximum diagnostic ability achieved immediately after surgery (AUC 1, Sensitivity 100%, Specificity 100%, p < .001). Conclusion: We conclude, that IFABP measurements during the first postoperative hours after open thoracoabdominal aortic surgery can be a valuable tool for reliable and timely detection of visceral malperfusion.

A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study.

Tobacco use is implicated in the carcinogenesis of oral squamous cell carcinoma (OSCC), which is associated with poor survival if not diagnosed early. Identification of novel noninvasive, highly sensitive, and cost-effective diagnostic and risk assessment methods for OSCC would improve early detection. Here, we report a pilot study assessing salivary and serum miRNAs associated with OSCC and stratified by smoking status. Saliva and paired serum samples were collected from 23 patients with OSCC and 21 healthy volunteers, with an equal number of smokers and nonsmokers in each group. Twenty head and neck cancer-related miRNAs were quantified by qPCR (dual-labeled LNA probes) and analyzed by Welch t test (95% confidence interval). Four saliva miRNAs, miR-21, miR-136, miR-3928, and miR-29B, showed statistically significant overexpression in OSCC versus healthy controls (P < 0.05). miR-21 was statistically significantly overexpressed in OSCC smokers versus nonsmokers (P = 0.006). Salivary miR-21, miR-136, and miR-3928, and serum miR-21 and miR-136, showed statistically significant differential expression in early-stage tumors versus controls (P < 0.05), particularly miR-21 in smokers (P < 0.005). This pilot study provides a novel panel of saliva and serum miRNAs associated with oral cancer. Further validation as a potential useful index of oral cancer, particularly miR-21 in smokers and early-stage OSCC is warranted. PREVENTION RELEVANCE: Saliva and serum miR-21, miR-136, miR-3928, and miR-29B, are potentially associated with oral cancer even at an early stage, especially miR-21 in individuals with a smoking history, a further validation in a larger cohort of subjects with premalignant and early malignant lesions need to confirm.