Search Results (23)

Background: The optimal timing of adjuvant chemotherapy after cytoreductive surgery in epithelial ovarian cancer remains uncertain, and perioperative wound-healing responses may transiently create a pro-tumorigenic and drug-resistant microenvironment. This study aimed to characterize time-dependent wound-induced transcriptomic alterations and to identify pharmacologic agents capable of reversing these responses. Methods: An ID8 murine ovarian cancer model was used to compare no treatment, anesthesia alone, and anesthesia plus surgical wounding mimicking futile laparotomy. Tumors were collected at baseline, 1 day (T1), 1 week (T2), and 2 weeks (T3) after intervention. RNA sequencing was performed, and wound-specific differentially expressed genes (WsDEGs) were defined by excluding anesthesia- and progression-related signatures. Functional enrichment analyses were conducted, followed by transcriptome-based drug repurposing using the REMEDY platform to identify compounds predicted to reverse wound-induced gene expression profiles. Results: Surgical wounding significantly increased tumor burden at T1. Transcriptomic analyses revealed distinct, time-dependent wound-associated programs. At T1, WsDEGs were enriched in inflammatory signaling, coagulation, angiogenesis, and immune cell migration, with Vorinostat and Homoharringtonine identified as top candidates to counteract these signatures. At T2, pathways related to cell survival, adhesion, and morphogenesis predominated, with LY-2090314, Artesunate, and Birinapant emerging as potential modulators. At T3, cell-cycle regulation and lipid metabolic pathways were dominant, and Fulvestrant, Atorvastatin, Imatinib, and ABT-737 were predicted to inhibit these processes. Conclusions: Perioperative surgical wounding induces dynamic, stage-specific transcriptomic programs that may promote ovarian cancer progression and alter drug responsiveness. These findings support time-adapted perioperative pharmacologic strategies to optimize postoperative cancer therapy. Full article

Surgical resection combined with chemotherapy offers the best chance of survival in pancreatic ductal adenocarcinoma (PDAC), but many will experience recurrence and early mortality. We examined soluble AXL (sAXL), a blood protein, for its ability to predict 6-month mortality after resection and compared it to CA19-9. Fifty-four patients with PDAC who underwent tumour resection were analyzed to assess biomarker performance and identify optimal cut-off levels. The cut-off for sAXL was 40.26 ng/mL (sensitivity 0.729; specificity 0.643), while it 253.3 U/mL for CA19-9 (sensitivity 0.591; specificity 0.621). Patients with sAXL > 40.26 ng/mL had a non-significant trend toward worse survival (log-rank p = 0.088). Univariate Cox regression revealed that high tumour grade (3 + 4) and positive resection margin significantly predicted early mortality. Multivariate Cox regression showed that sAXL > 40.26 ng/mL remained associated with 6-month mortality (hazard ratio 2.42, bootstrap 95% CI 1.15–5.65, p = 0.020), independent of high tumour grade (hazard ratio 4.02, bootstrap 95% CI 1.68–13.2, p = 0.002). These findings suggest that a preoperative blood test (sAXL) has utility for predicting futile surgery beyond the current standard, CA19-9, and can be incorporated into larger models to assist in risk stratification and follow-up planning. Full article

Background and Objectives: Advanced epithelial ovarian cancer (AEOC) often requires extensive cytoreductive surgery. Minimally invasive surgery (MIS), especially diagnostic laparoscopy, is increasingly used to assess resectability and guide treatment. This review aimed to evaluate the evidence on MIS in AEOC, focusing on its diagnostic and therapeutic roles in primary and interval debulking surgery (PDS and IDS), and its impact on perioperative and oncologic outcomes. Materials and Methods: A structured literature review was performed using PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library, including studies published between January 2000 and June 2025. Eligible studies involved laparoscopic or minimally invasive cytoreduction in PDS or IDS, reporting surgical feasibility, perioperative results, and oncologic outcomes. Data were synthesized qualitatively due to heterogeneity across studies. Results: Observational studies indicate that diagnostic laparoscopy predicts resectability, reduces futile laparotomies, and improves patient selection for primary surgery. In selected patients, non-randomized cohorts of laparoscopic PDS report R0 resection rates up to 95%, with low morbidity and short hospital stays. In IDS after neoadjuvant chemotherapy, MIS has been associated with reduced blood loss, fewer complications, and faster postoperative recovery, while showing progression-free and overall survival comparable to laparotomy in retrospective series. Conversion to open surgery was generally reported in fewer than 10% of cases when stringent selection criteria were applied. Conclusions: Diagnostic laparoscopy is a valuable tool for accurate preoperative evaluation and surgical planning in EOC. MIS, particularly for IDS, appears to offer reduced morbidity and equivalent survival outcomes when performed in experienced centers, whereas its application in PDS remains investigational and should be reserved for highly selected cases. These conclusions are limited by the predominance of retrospective evidence and the heterogeneity in patient selection and surgical expertise. Full article

Background: Studies assessing poor postoperative recovery using patient-centered metrics among older adults are scarce. We aimed to explore poor postoperative recovery in octogenarians and nonagenarians, characterized using the validated patient-centered tool ‘days alive and out of hospital’ (DAOH). Methods: This retrospective cohort study included patients aged ≥ 80 years who had non-palliative surgery at a tertiary academic center between January 2017 and July 2021. We explored the incidence of DAOH at 90 days (DAOH₉₀) ≤ 45 days as a pragmatic patient-centered marker of poor postoperative recovery. We also identified independent risk factors associated with this outcome using logistic regression models. Sensitivity analyses were performed using similar regression models. Results: Among 3683 included patients (median age 84 years), 640 patients (17%) had poor postoperative recovery. Of them, 240 patients (38%) survived the 90-day postoperative period but suffered a cumulative hospitalization period of over 45 days, and 400 patients (62%) died during the 90-day postoperative period. The most significant risk factors were ASA physical status classification (adjusted odds ratio (aOR) 3.52 [95% CI 2.55–4.87] for class 3E-5E compared to class 1–2), renal failure (aOR 3.49 [2.01–6.06] for GFR < 15 compared to GFR > 60 mL/min/1.73 m²), and high-risk surgery (aOR 1.85 [1.47–2.32]). Conclusions: We found a non-trivial rate of poor postoperative recovery in octogenarians and nonagenarians. DAOH₉₀ ≤ 45 days is a simple, clear, and intuitive tool that may enhance patient-centered research and promote communication about expected outcomes, support shared decision making, and provide personalized risk assessment aligned with older patients’ goals of care. Full article

Introduction: Non-surgical biopsy is recommended for diagnosing solid pulmonary nodules measuring >8 mm when the probability of malignancy is low to moderate. However, currently available biopsy methods do not have a sufficient diagnostic yield for nodule size <20 mm. Previous work has shown that one-lung flooding (OLF) enables complete lung sonography and good demarcation of lung nodules. Therefore, here, we report the first experiences with ultrasound-guided transthoracic core needle biopsy (USgTTcNB) under OLF for the histological diagnosis of small pulmonary nodules. Methods: In two patients with small pulmonary nodules, a transbronchial/thoracic biopsy was not indicated due to the size and location of the nodules. Following nodule detection under OLF, the USgTTcNB was performed. The biopsy cylinder was immediately examined via the frozen section procedure. After liquid draining and re-ventilation, the patients were extubated in the operation room and monitored in the intermediate care unit. Results: In both patients, a histological diagnosis was achieved. In the case of malignancy, the patient underwent lobectomy during the same session. In the case of a benign diagnosis, a futile operation was avoided. In case two, a small apical pneumothorax occurred. The hemodynamic values during and after the intervention were in the normal range. Lung function on day 2 after the intervention increased compared with that before the intervention. Conclusions: USgTTcNB under OLF is feasible and enables a histological confirmation of small pulmonary nodules. Nevertheless, this new promising technique should be evaluated in a study with a larger cohort. Full article

Background: Spontaneous intracerebral hemorrhage (ICH) has the highest case fatality of all stroke types, yet recent epidemiological and outcome data from Central and Eastern Europe remain limited. Methods: We retrospectively analyzed prospectively collected data for 601 consecutive adults with primary ICH admitted to Sibiu County Clinical Emergency Hospital, Romania (2017–2023). Demographics, Glasgow Coma Scale (GCS), CT-derived hematoma volume (ABC/2), anatomical site, intraventricular extension (IVH), treatment, comorbidities, and in-hospital death were reported with exact counts and percentages; no imputation was performed. Results: Mean age was 68.4 ± 12.9 years, and 59.7% were male. Mean hematoma volume was 30.4 mL, and 23.0% exceeded 30 mL. IVH occurred in 40.1% and doubled mortality (50.6% vs. 16.7%). Overall case fatality was 29.6% and climbed to 74.5% for brain-stem bleeds. Men, although younger than women (66.0 vs. 71.9 years), died more often (35.4% vs. 21.1%; risk ratio 1.67, 95% CI 1.26–2.21). Systemic hazards amplified death risk: Oral anticoagulation, 44.2%; chronic alcohol misuse, 51.4%; thrombocytopenia, 41.0%; chronic kidney disease, 42.3%. Conservative management (74.9%) yielded 27.8% mortality overall and ≤15 for small-to-mid lobar or capsulo-lenticular bleeds; lobar surgery matched this (13.4%) only in large clots. Thalamic evacuation was futile (82.3% mortality), and cerebellar decompression performed late still carried 54.5% mortality versus 16.6% medically. Multivariable analysis confirmed that low GCS, IVH, large hematoma volume, thrombocytopenia, and chronic alcohol use independently predicted in-hospital mortality. Limitations: This retrospective study lacked post-discharge functional outcome data (e.g., mRS at 90 days). Conclusions: This study presents the largest Romanian single-center ICH cohort, establishing national benchmarks and underscoring modifiable risk factors. Early ICH lethality aligns with Western data but is amplified by exposures such as alcohol misuse, anticoagulation, thrombocytopenia, and CKD. Priorities include preventive strategies, timely surgical access, wider adoption of minimally invasive techniques, and development of a prospective regional registry. Full article

Background: Aortic dissection is a life-threatening condition where emergent surgical repair is the standard of care. However, despite operative intervention, mortality is 10–15% in all patients. Objective markers to distinguish when surgical repair is more beneficial versus being futile are warranted. Currently, no such known measures are widely agreed upon. Since most complications from aortic dissection stem from malperfusion, serum lactate is thought to be a surrogate marker for malperfusion. This scoping review aims to examine the preoperative predictive value of lactate or lactate dehydrogenase (LDH) in assessing postoperative mortality in patients undergoing surgical repair for acute Stanford Type A aortic dissection (ATAAD). Methods: PubMed was searched for the following search terms: “Dissection, Ascending Aorta”, “Dissection, Thoracic Aorta”, or “Aortic Dissection”. Prospective and retrospective randomized controlled trials, case reports, and cohort studies were included in the initial search. Studies were first screened for inclusion of preoperative lactate or LDH level with a search of “lac” or “LDH”. Included studies consisted of patients aged 18 or older diagnosed with Stanford Type A/Debakey Type I and II aortic dissection with reported preoperative lactate or LDH levels and postoperative mortality treated within 14 days of symptom onset. Preoperative laboratory values were measured from samples collected prior to patient transfer to the operating room or before utilization of ECMO intraoperatively. Results: A comprehensive database search identified a total of 4722 articles. After a rigid screening process, 46 studies fit the inclusion criteria. These papers reported a combined 4696 participants with either preoperative lactate or LDH levels and postoperative mortality. The mean preoperative lactate level was 2.4 mmol/L, whereas the LDH level was 424.9 U/L. Postoperative mortality was 16.51%. Average creatinine, BUN, platelets, INR, PT, PTT, and hemoglobin were all within normal lab analysis limits. Conclusions: Neither lactate nor LDH should be used as a solo predictor of postoperative mortality after ATAAD due to lack of consensus on the cut-off values. Accompanying clinical signs, lab abnormalities, and radiographic findings taken together may be better predictors of prognosis. Full article

Background: Pediatric in-hospital cardiac arrest (IHCA) remains a critical health challenge with high mortality rates. Limited data from Western China prompted this study to investigate the characteristics of IHCA using the Utstein style. Methods: A retrospective analysis of 456 pediatric patients with IHCA (2018–2022) at the Children’s Hospital of Chongqing Medical University assessed demographics, arrest characteristics, outcomes and mortality risk factors. The primary outcome was survival to discharge; the secondary outcomes included return of spontaneous circulation (ROSC) > 20 min, 24 h survival, and favorable neurological outcomes. Logistic regression was used to identify the mortality risk factors. Results: ROSC > 20 min was achieved in 78.07% of cases, with 37.94% surviving to discharge (86.13% of survivors had favorable neurological outcomes). Etiological stratification identified general medical conditions (52.63%) as the predominant diagnoses, with surgical cardiac patients demonstrating superior resuscitation outcomes (ROSC > 20 min: 86.84%, discharge survival: 64.04%). Initial arrest rhythms predominantly featured non-shockable patterns, specifically bradycardia with poor perfusion (79.39%), whereas shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia) constituted only 4.17% of cases. Multivariable regression analysis identified five independent risk factors: vasoactive infusion before arrest (OR = 7.69), CPR > 35 min (OR = 13.92), emergency intubation (OR = 5.17), administration of >2 epinephrine doses (OR = 3.12), and rearrest (OR = 8.48). Notably, prolonged CPR (>35 min) correlated with higher mortality (8.96% survival vs. 48.54% for 1–15 min), yet all six survivors with CPR > 35 min had favorable neurological outcomes. Conclusions: These findings underscore the persistent challenges in pediatric IHCA management while challenging the conventional CPR duration thresholds for futility. The identified mortality risk factors inform resuscitation decision making and future studies. Full article

Biliary atresia (BA) is an obliterative disease of the bile ducts affecting between 1 in 10,000–20,000 infants with a predominance in Asian countries. It is clinically heterogeneous with a number of distinct variants (e.g., isolated, Biliary Atresia Splenic Malformation syndrome, Cat-eye syndrome, cystic BA, and CMV-associated BA). Facts about its aetiology are hard to encounter but might include genetic, developmental, exposure to an environmental toxin, or perinatal virus infection. However, the cholestatic injury triggers an intrahepatic fibrotic process beginning at birth and culminating in cirrhosis some months later. Affected infants present with a triad of conjugated jaundice, pale stools, and dark urine and may have hepatosplenomegaly upon examination, with later ascites coincident with the onset of progressive liver disease. Rapid, efficient, and expeditious diagnosis is essential with the initial treatment being surgical, typically with an attempt to restore the bile flow (Kasai portoenterostomy (KPE)) or primary liver transplantation (<5%) if considered futile. Failure to restore bile drainage or the onset of complications such as recurrent cholangitis, treatment-resistant varices, ascites, hepatopulmonary syndrome, and occasionally malignant change are usually managed by secondary liver transplantation. This issue summarises recent advances in the disease and points a way to future improvements in its treatment. Full article

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease. Full article

Background/Objectives: The change in critically ill patients makes limitation of therapeutic effort (LTE) a widespread practice when therapeutic goals cannot be achieved. We aimed to describe the application of LTE in a post-surgical Intensive Care Unit (ICU), analyze the measures used, the characteristics of the patients, and their evolution. Methods: Retrospective observational study, including all patients to whom LTE was applied in a postsurgical ICU between January 2021 and December 2022. The LTE defined were brain death, withdrawal of measures, and withholding. Withholding limitations included orders for no cardiopulmonary resuscitation, no orotracheal intubation, no reintubation, no tracheostomy, no renal replacement therapies, and no vasoactive support. Patient and ICU admission data were related to the applied LTE. Results: Of the 2056 admitted, LTE protocols were applied to 106 patients. The prevalence of LTE in the ICU was 5.1%. Data were analyzed in 80 patients. A total of 91.2% of patients had been admitted in an emergency situation, and 56.2% had been admitted after surgery. The most widespread limitation was treatment withholding (83.8%) compared to withdrawal (13.8%). No differences were found regarding who made the decision and the type of limitation employed. However, patients with the limitation of no intubation had a longer stay (p = 0.025). Additionally, the order of not starting or increasing vasopressor support resulted in a longer hospital stay (p = 0.007) and a significantly longer stay until death (p = 0.044). Conclusions: LTE is a frequent measure in critically ill patient management and is less common in the postoperative setting. The most widespread measure was withholding, with the do-not-resuscitate order being the most common. The decision was made mainly by the medical team and the family, respecting the wishes of the patients. A joint patient-centered approach should be made in these decisions to avoid futile treatment and ensure end-of-life comfort. Full article

Background: The mismatch between tricuspid valve (TV) leaflet length and annulus dilation, assessed with the septal–lateral leaflet-to-annulus index (SL-LAI), predicts residual tricuspid regurgitation (TR) following tricuspid transcatheter edge-to-edge-repair (T-TEER). When posterior leaflet grasping is required, the anterior–posterior leaflet-to-annulus index (AP-LAI) may offer additional information. Methods: This single-center retrospective cohort study included all patients referred for T-TEER with severe and symptomatic TR with high surgical risk from April 2021 to March 2024. Patients were categorized into ‘optimal result’ (<moderate TR) or ‘suboptimal result’ (≥moderate TR) groups. The SL-LAI and AP-LAI were calculated using pre-procedural transesophageal echocardiography (TEE) measurements. Results: Of the 25 patients, 12 had suboptimal post-procedural results, while 13 showed optimal outcomes. The optimal result group showed a higher prevalence of type IIIA-IIIB TV morphology (85% vs. 45%, p < 0.05), a wider SL annulus diameter (42.5 ± 5 vs. 37 ± 5 mm, p < 0.05), and a longer posterior leaflet length (28 ± 4 vs. 22 ± 5 mm, p < 0.01). The SL-LAI was lower in the optimal group (1 ± 0.2 vs. 1.2 ± 0.32, p < 0.05), while the AP-LAI was higher (0.7 ± 0.1 vs. 0.5 ± 0.2, p < 0.05). ROC curve analysis showed that the AUC for the AP-LAI was 0.769 (95% CI 0.51–0.93, p < 0.05) and Youden test identified the best cut-off value <0.5 (sensitivity 50% and specificity 100%) for a suboptimal result. The SL-LAI showed a very low AUC in predicting suboptimal results (0.245, 95% CI 0.08–0.47). Comparing the two ROC curves, we showed that AUC difference is significant with the AP-LAI showing the best association with the outcome (p = 0.01). Conclusions: The AP-LAI and SL-LAI can help in predicting post T-TEER results, ameliorating patients’ outcomes and avoiding futile procedures. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer. Full article

Arterial calcifications are present in 20–40% of patients with end-stage kidney disease and are more frequent among the elderly and diabetics. They reduce the possibility of arterio-venous fistula (AVF) formation and maturation and increase the likelihood of complications, especially distal ischemia. This review focuses on methods for detecting arterial calcifications and assessing the suitability of calcified arteries for providing inflow before the construction of an AVF. The importance of a clinical examination is stressed. A grading system is proposed for quantifying the severity of calcifications in the arteries of the arm with B-mode and Doppler ultrasound exams. Functional tests to assess the suitability of the artery to provide adequate inflow to the AVF are discussed, including Doppler indices (peak systolic velocity and resistive index during reactive hyperemia). Possible predictors of the development of distal ischemia are discussed (finger pressure, digital brachial index, acceleration and acceleration time), as well as the outcomes of AVFs placed on calcified arteries. It is concluded that a noninvasive ultrasound examination is probably the best tool for a morphologic and functional assessment of the arteries. An arterial assessment is of utmost importance if we are to create distal radiocephalic AVFs in our elderly patients whenever possible without burdening them with futile surgical attempts. Full article

Background: Frailty is highly common in older patients (pts) undergoing transcatheter aortic valve replacement (TAVR), and it is associated with poor outcomes. The selection of patients who can benefit from this procedure is necessary and challenging. The aim of the present study is to evaluate outcomes in older severe aortic valve stenosis (AS) pts, selected by a multidisciplinary approach for surgical, clinical, and geriatric risk and referred to treatment, according to frailty levels. Methods: A total of 109 pts (83 ± 5 years; females, 68%) with AS were classified by Fried’s score in pre-frail, early frail, and frail and underwent surgical aortic valve replacement SAVR/TAVR, balloon aortic valvuloplasty, or medical therapy. We evaluated geriatric, clinical, and surgical features and detected periprocedural complications. The outcome was all-cause mortality. Results: Increasing frailty was associated with the worst clinical, surgical, geriatric conditions. By using Kaplan–Meier analysis, the survival rate was higher in pre-frail and TAVR groups (p < 0.001) (median follow-up = 20 months). By using the Cox regression model, frailty (p = 0.004), heart failure (p = 0.007), EF% (p = 0.043), albumin (p = 0.018) were associated with all-cause mortality. Conclusions: According to tailored frailty management, elderly AS pts with early frailty levels seem to be the most suitable candidates for TAVR/SAVR for positive outcomes because advanced frailty would make each treatment futile or palliative. Full article