Objective:This study evaluated the feasibility of quantitative near-infrared fluorescence imaging with indocyanine green (NIRF-ICG) to assess changes in colon perfusion induced by abdominal aortic aneurysm reconstruction. Improved perfusion assessment may support clinical decision-making in patients at risk for developing colon ischemia. Methods:NIRF-ICG recordings of the sigmoid colon from 25 patients treated at a single center were retrospectively analyzed. Time-intensity curves were extracted from the sigmoid colon and small intestine and classified as demonstrating adequate, questionable, or poor perfusion. Four curve-derived perfusion parameters (time to maximum intensity, maximum inflow rate of the normalized curve, and remaining fluorescence intensity 30 seconds and 60 seconds after maximum intensity) were compared to objectively evaluate changes in fluorescence inflow and outflow before and after aortic reconstruction. Results:Quantitative analysis was feasible in 23 patients undergoing elective procedures and in 1 patient undergoing acute surgery. Although all patients demonstrated adequate perfusion on clinical assessment, quantitative classification identified perfusion deterioration in 13 patients. All four derived perfusion parameters showed a significant decrease in sigmoid perfusion after aortic reconstruction (time to maximum intensity, P < .001; maximum inflow rate of the normalized curve, P = .019; remaining fluorescence intensity 30 seconds after maximum intensity, P = .029; remaining fluorescence intensity 60 seconds after maximum intensity, P = .021), whereas small intestinal perfusion remained unchanged (all P > .05). In two cases, severely impaired perfusion detected by NIRF-ICG imaging recovered postoperatively, as confirmed by a NIRF-ICG measurement during planned second-look surgery. Two patients classified as having poor perfusion required acute relaparotomy due to anastomotic bleeding. There were no cases of colon ischemia, and mortality was zero. Conclusions:Quantitative NIRF enables objective intraoperative assessment of sigmoid perfusion during open abdominal aortic aneurysm repair. The observed recovery from transient perfusion deficits supports heightened awareness rather than immediate bowel resection in cases suspected of malperfusion. Validation of perfusion patterns predictive of ischemia is required to establish risk stratification criteria and optimize clinical decision-making.

BACKGROUND:Lower-limb amputation remains a devastating outcome of peripheral artery disease (PAD). Over recent decades, advances in cardiovascular and PAD management, rising diabetes incidence, and population aging may have influenced amputation incidence and outcomes. This nationwide observational cohort study evaluates changes in incidence and short-term and long-term survival after PAD-related lower-limb amputation in the Netherlands between 1995-1999 and 2014-2018. METHODS:Nationwide linked registry data from the Hospital Discharge Register, Population Register, and Cause of Death Register were used. Patients >45 years undergoing PAD-related amputations were included. Patient characteristics, amputation incidences, survival and causes of death were compared between periods. RESULTS:A total of 30,400 unique patients were identified and analyzed. Over time the overall amputation incidence decreased with 16.3%, along with median age, the proportion of major amputations, and median hospital stay, whereas the proportion male patients and comorbidity burden, including diabetes, increased. Six-month survival rose from 75.6% to 83.4% (P < 0.001) with male sex, hypertension, and diabetes as strong predictors of early mortality. Long-term survival (conditional on 6 months survival) remained poor with 5-year relative survival rates between 0.51 and 0.80, depending on diabetic status, sex, and amputation level. Excess mortality was extremely high, especially among younger and diabetic patients. CONCLUSION:Short-term postamputation survival has improved over time (2014-2018 versus 1995-1999). However, long-term outcomes remain poor, particularly in younger patients with diabetes and after major amputation. Amputation continues to identify a multimorbid population with advanced systemic vascular disease, necessitating improved prevention and treatment.

Succinate dehydrogenase (SDH) gene variants are the most common cause of the neuroendocrine tumour hereditary paraganglioma, which is associated with an over 20% metastasis risk as well as significant morbidity. There are currently no relevant human tumour cell lines or mouse models, and molecular understanding of downstream tumourigenic pathways is still rudimentary despite over two decades of concerted effort worldwide. These tumours generally show extremely slow in vivo doubling times (4-12 years), presumably existing in a primarily semi-quiescent state with little cell cycling or DNA replication. This characteristic makes deriving a useful tumour cell line impractical. A better alternative would be a cell line in which cell proliferation can be turned on and off at will, allowing expansion to generate sufficient cell numbers and experimentation once tumour cells have returned to their natural semi-quiescent state. The closest models currently available, highly-proliferating rat and mouse adrenal paraganglioma cell lines, are molecularly unrelated to SDH tumours. In this pilot study, we investigated whether primary SDH-derived paraganglioma tumour cells can be made to proliferate in vitro. We successfully transduced primary paraganglioma tumour cells with a lentiviral construct, using the proven strategy of c-MYC¬T58A (c-MYC) controlled by a Tet-On doxycycline-inducible expression system. We present the first evidence that primary paraganglioma chromaffin cells can be induced to proliferate in vitro, even in later passage cultures. Without any prior selection for chromaffin tumour cells, passaged cultures were obtained with over 80% synaptophysin-expressing chromaffin tumour cells, suggesting that this highly promising strategy deserves further exploration.

BACKGROUND:To evaluate the efficacy and safety of REX-001, an autologous bone marrow-derived mononuclear cell product, in patients with chronic limb-threatening ischemia (CLTI) who had no options for revascularization. METHODS:In this multicenter, double-blind, randomized, placebo-controlled phase III clinical trial, diabetic patients with CLTI (Rutherford category 5), no revascularization options, and no urgent need for amputation were enrolled. Bone marrow (250 mL) was processed to create REX-001, and a single intra-arterial injection was administered. Primary endpoints included change in Rutherford classification (to category 4 or lower) or complete ulcer healing within 12 months. Secondary endpoints included limb TcpO2, ulcer size, quality of life, ankle-brachial index, 6-min walking test, and amputation-free survival. RESULTS:The trial was stopped early after an interim analysis of 50% of the patients due to lack of efficacy. Thirty-two patients completed the study (21 REX-001, 11 placebo). Complete ulcer healing or improvement in Rutherford category occurred in 28.6% of REX-001-treated patients and 27.3% of placebo-treated patients. No treatment-related adverse events or safety concerns were identified. Data on secondary endpoints were not available. CONCLUSION:This prematurely ended study failed to confirm REX-001's efficacy for ulcer healing. Nevertheless, the study provides valuable insights into trial design, endpoint selection, and data stewardship, guiding future regenerative therapy research in this challenging patient population.

Background: The quality of life (QoL) in patients with head and neck paragangliomas, including carotid body tumors (CBTs), is known to be reduced. Currently, there are only a few studies performed on the QoL among patients diagnosed with CBTs during follow-up and after surgery. Objective: This study aims to assess QoL in patients with CBT in follow-up and after surgery and to compare both groups with a control group. Methods: In this retrospective study, patients with CBT who underwent surgery were matched using Euclidean distance scoring with patients in follow-up based on age, gender, tumor size, tumor laterality, and follow-up duration. All matched patients completed the World Health Organization Quality of Life-Brief, Sickness Impact Profile 68, and Short-Form Survey-36 questionnaires. A control group was recruited through an open online survey distributed via public channels. Results: No statistically significant QoL differences were found between resected and non-resected patients with CBT. Comparing non-resected, resected, and control groups, the Short-Form Health Survey-36 showed significant differences in physical function, role-physical, and general health (P = .00). The Sickness Impact Profile 68 indicated a significant difference in mobility between resected and control groups, and the World Health Organization Quality of Life-Brief showed a significant difference in physical function (P < .02). Comorbidities and postoperative complications may contribute to reduced QoL in this population. Conclusions: No significant QoL differences between matched patients with CBT in follow-up and those who underwent resection. Both groups had lower QoL compared with controls in the subscales for physical function, role-physical, and general health. These findings suggest a personalized approach may be more appropriate than assuming surgery improves QoL.

Previously, we concluded that thyroid resections with multifocal, genetically distinct lesions more often showed florid chronic lymphocytic thyroiditis (CLT) than thyroids with clonally related multiple lesions. In this study, we characterized a consecutive cohort of thyroid lesions for molecular drivers and investigated the relationship between the molecular alteration type and florid CLT. Molecular diagnostic data from 414 patients (2016-2025) were retrospectively reviewed, including clinical information and histopathological evaluation. Gene fusion, somatic mutation, and chromosomal LOH/imbalance/copy-number analysis results were available for 342 cases. Eighty-eight gene rearrangements were identified across 86 patients. Most had been previously reported in thyroid neoplasia. Five well-known gene fusions revealed unusual breakpoints. Three gene fusions, previously reported only in nonthyroid malignancies (BRAF-TRIM24, SLC12A7-TERT, PVT1-MYC), were described for the first time in thyroid carcinoma. Three novel gene fusions (TRIM65-RET, FGFR2-WARS1, PPARGC1A-PPARɣ) produced in-frame translation products leading to corresponding mRNA expression. BRAF exon-skipping events were identified in treatment-naïve papillary thyroid carcinomas. Florid CLT (p = 0.002) and younger age (OR = 0.97 per year, p < 0.001) were independently associated with gene fusion-positive tumors. Sex, follicular nodular disease, and Graves' disease were not significant predictors. Our findings suggest an association between fusion-driven thyroid neoplasia and florid CLT, warranting further investigation.

Parathyroid carcinoma (PC) is most often linked to germline or somatic CDC73 mutations. Previously, we identified three CDC73-wildtype PCs with massive chromosomal losses and genome near-haploidization, with or without endoreduplication/genome doubling - features also seen in rare tumor types such as oncocytic thyroid carcinoma. To assess whether similar alterations occur in other parathyroid neoplasms, we analyzed fourteen parathyroid adenomas (PA; thirteen oncocytic), three atypical parathyroid tumors (APTs; one oncocytic), and one additional PC, the latter four all CDC73-wildtype. Histopathological diagnoses followed the 2022 WHO classification. Genome-wide SNP array analysis was performed to detect copy number variations (CNVs), imbalances and loss of heterozygosity (LOH). APTs and PC underwent somatic mutation analysis, to confirm CDC73-wildtype status. Oncocytic PAs exhibited largely stable genomes, with few or no chromosomal alterations. Patients with chromosomally altered PA had significantly higher preoperative serum calcium levels. In contrast, two of three APTs, and the included PC displayed extensive chromosomal losses and genome near-haploidization. These findings expand the recognized spectrum of chromosomal alterations in CDC73-wildtype parathyroid tumors.

Background: Ruptured abdominal aortic aneurysm (RAAA) remains a medical catastrophe. Although early outcomes improved, contemporary data integrating early and long-term survival, and postdischarge care needs across sex- and age groups is limited. Methods: This nationwide cohort included Dutch RAAA repairs between 2014 and 2023. Dutch Surgical Aneurysm Audit data were linked to Statistics Netherlands registries. Outcomes included 90-day mortality, long-term survival, and postdischarge care. Results: Of the 3642 patients, 15.2% were women, who were older (76.3 vs. 74.0 y) and more often required open repair (61.4% vs. 54.0%). Ninety-day mortality increased with age and was higher in women (39.1% vs. 29.1%), but female sex was not independently associated with early mortality after adjustment. Among 90-day survivors, absolute long-term survival was similar, but relative survival was lower in women (5-year relative survival 68.0% vs. 78.3%). Women were less often discharged home (42.4% vs. 56.7%) and more frequently required early homecare (47.7% vs. 34.7%). Reinterventions were more common after EVAR than open repair and occurred less frequently in women. Conclusion: In this nationwide linked audit-registry analysis, outcomes after RAAA repair improved substantially, despite lower estimated in-hospital turndown rates than in earlier eras. The higher early mortality in women reflected by differences in age, presentation severity, and repair type, possibly reflecting less favorable aneurysm anatomy. Female sex also associated with an increased long-term excess mortality and greater postdischarge dependency. These findings indicate that optimization of care for women with a RAAA is not confined to perioperative mortality, but extends across the entire care pathway.

Surgery is a demanding and stressful profession. Unfortunately, inappropriate behavior is still not banished from the daily surgical practice and we are dealing with the negative consequences (e.g. negative working environments or burn-out). To adequately treat this type of behavior we first have to acknowledge its existence and create a proper path to discuss it inside our own ranks. The only manner to achieve this, is through an open culture. An 'open surgical culture' is the key, as it creates an environment with psychological safety and allows all involved parties to be able to speak up without fear for retaliation. Theoretical models such as Bateson's pyramid, McClelland's iceberg, and Dweck's Growth Mindset Theory can serve as valuable sources of inspiration to addressing cultural change by approaching both individual and organizational levels. Examples of cultural change attempts can be as small as discussing inappropriate behavior through pocket cards with statements of certain behavior or during national conferences, e.g. the annual meeting of the Dutch Surgical Society (Chirurgendagen). Only together we are able to achieve an open surgical culture, in order to ban mistreatment from the surgical profession. Here a roadmap to achieving an open surgical culture is presented and discussed.

BACKGROUND AND PURPOSE:Intergenerational differences in surgery create both challenges and opportunities. While differening perspectives and expectations may deter younger generations from pursuing surgical careers, it is crucial to balance these with the core values that define the surgical profession. This narrative review was conducted to better understand how the profession needs to evolve. METHODS:A structured literature search on generational changes in surgery was conducted using PubMed and Google Scholar. Relevant search terms were employed, covering (i) surgeons/surgery, (ii) generation/cohort and (ii) culture/identity/behaviour. After independent title and abstract screening by three authors, consensus was reached to include relevant studies published in English up to November 2023. MAIN FINDINGS:Full-text evaluation led to an inclusion of 50 studies, reviewed for returning themes. Identified themes included: generations (n = 9), work engagement (n = 8), work-life balance (n = 7), training and education (n = 4) and attractiveness of the profession (n = 8). An additional 14 relevant studies were included based on reference lists and external sources. CONCLUSIONS:This review summarizes key factors contributing to surgical well-being and generational dynamics. Awareness of these factors is increasing. While generational differences exist, many distinctions may be attributed to life phases, lifestyles or systemic changes in the past decades. Addressing these topics daily can foster intergenerational dialogue and a supportive environment for future surgeons.

Objective Aneurysms at different arterial sites share similar pathophysiologic and biomechanical properties. Theoretically, an association between intracranial aneurysms and aortic aneurysms could exist as well, which might be important for screening purposes. This systematic review aims to evaluate the potential association between intracranial and aortic aneurysms. Methods A systematic search was performed to identify studies that investigated the occurrence of intracranial aneurysms in patients with aortic aneurysms (sub-question A) or vice versa (sub-question B). Methodological quality was assessed by using a modified version of the Newcastle-Ottawa Scale. Results In total, 12 studies were included in this systematic review. For sub-question A, an occurrence rate of 5% to 12% was identified for aortic aneurysms in patients with intracranial aneurysms. An occurrence rate of 5% to 22% for intracranial aneurysms was found in patients with an aortic aneurysm (sub-question B). Conclusions This systematic review suggests a potential association between intracranial and aortic aneurysms, as higher occurrences compared with the general population or controls were found. Unfortunately, very little research has been performed about the subject and because of this, a definite conclusion could not be made. Screening for aortic aneurysms in patients with intracranial aneurysms might be valuable for timely diagnosis, follow-up, treatment, and potentially be cost-effective. Screening vice versa is unclear; important factors that remain unclear include the costs and the uncertain survival benefit of detecting intracranial aneurysms in patients with an aortic aneurysm. To make a more reliable statement about this, more high-quality research must follow.

Considering that the treatment of patients with complex vascular disease requires multidisciplinary collaboration in teams and personality traits can impact team dynamics, we investigated the personality structures of vascular surgeons, cardiothoracic surgeons, and interventional radiologists using the validated big five model. A cross-sectional study utilizing the validated Big Five Inventory-2 (BFI-2) questionnaire. Corrected one-way analyses of variance were performed to compare personality domain scores between the specialist groups. Questionnaires were distributed among all Dutch general surgery departments and through the Dutch Societies for Interventional Radiology (NVIR) and Cardiothoracic Surgery (NVT). A total of 224 specialists participated: 78 interventional radiologists (mean age 48.2y, 20.5

Foot ulceration is a significant and growing health problem worldwide, particularly due to rises in diabetes mellitus (DM) and peripheral artery disease. The prediction of ulcer healing remains a major challenge. In patients with foot ulcers, medial arterial calcification (MAC) can be present as a result of concomitant DM or chronic kidney disease and is a prognostic factor for unfavorable outcome. This systematic review aimed to evaluate the prognostic reliability of bedside tests to predict ulcer healing and wound healing after minor amputation in patients prone to MAC, following PRISMA guidelines. Primary endpoints were the positive and negative likelihood ratios for ulcer healing. Methodological quality and risk of bias were assessed using the QUIPS-tool. A total of 35 studies were included, predominantly investigating transcutaneous oxygen pressure (TcPO2), followed by ankle-brachial index and toe pressure. None of these bedside tests effectively provided an acceptable trade-off between predicting healing and nonhealing. A TcPO2 below 30 mmHg was most closely associated with nonhealing of an ulcer. The same applied to wound healing after minor amputation, in which none of the bedside tests was able to sufficiently predict healing or nonhealing. To conclude, currently used bedside tests lack acceptable prognostic performance for ulcer healing and healing after minor amputation in patients prone to MAC. Future prospective studies should establish a clear definition of ulcer healing, utilize a standardized wound classification system, and minimize patient heterogeneity. A combined assessment of microvascular and macrovascular perfusion status could improve the prediction of wound healing.

Indocyanine green near-infrared fluorescence (ICG-NIRF) imaging is widely used to assess tissue perfusion, yet its subjective interpretation limits correlation with postoperative parathyroid function. To address this, the Workflow model for ICG-angiography integrating Standardization and Quantification (WISQ) was developed. This exploratory prospective multicenter study evaluated the reproducibility of WISQ in adults undergoing total thyroidectomy at two Dutch university centres. Patients with contraindications to ICG or prior neck surgery were excluded. Intraoperative imaging used standardized camera settings with blood volume-adjusted ICG dosing, and perfusion curves were analyzed using predefined regions of interest. Eighty patients were included. Significant inter-centre variability was observed in maximum fluorescence intensity, inflow slope, and outflow slope (n = 30). At the lead centre, outflow was the most promising predictor of postoperative hypoparathyroidism (HPT) (median −0.33 [IQR −0.49–−0.15] a.f.u./s for HPT vs. −0.68 [−0.91–−0.41], n = 17, p = 0.08), although no parameter significantly predicted HPT. Repeated ICG injections consistently produced lower maximal intensities irrespective of injection rate, and reproducible curves were achieved only when ICG was freshly dissolved at 0.5 mg/mL instead of 2.5 mg/mL. These findings indicate that ICG concentration and injection technique influence perfusion kinetics and underscore the need to update WISQ with standardized injection dilution to improve its clinical utility.

Assessment of tissue perfusion using near-infrared fluorescence (NIR) with indocyanine green (ICG) is gaining popularity, however reliable and objective interpretation remains a challenge. Therefore, this study aimed to establish reference curves for vital tissue perfusion across target tissues using this imaging modality. Data from five prospective study cohorts conducted in three Dutch academic medical centres between December 2018 and June 2023 was included. Quantitative analysis using time-intensity curves was performed in ten target tissues, including the colon, ileum, gastric conduit, deep inferior epigastric artery perforator (DIEP) flap, skin of the foot, trachea, sternocleidomastoid muscle (SCM), carotid artery, parathyroid gland, and skin of the neck. A total of 178 patients were included in this study, representing 303 target tissues. Three different patterns of reference curves were identified based on a subjective assessment. Seven out of ten tissues showed a reference curve with rapid inflow (median time-to-max (tmax): 13.0–17.8 s, median maximum-normalized-slope (slope norm): 10.6–12.6

Background:Patients with primary hyperparathyroidism (PHPT) often present with nonspecific neuropsychological symptoms, which remain challenging to quantify. While parathyroidectomy (PTx) recently has been recommended for asymptomatic patients, its benefit remains unclear as existing evidence relies on generic health-related quality of life (HRQoL) tools. In contrast, the disease-specific PHPQoL questionnaire offers more sensitive and clinically relevant symptom assessment. This study aims to translate and validate the PHPQoL for Dutch use and to evaluate the effect of PTx on HRQoL in both symptomatic and asymptomatic PHPT patients. Methods:In this single-center prospective study, PHPT patients with at least one surgical indication underwent either PTx or conservative treatment based on medical requirement and patient preference. Clinicians classified patients as asymptomatic if no hypercalcemia-related complaints were present. HRQoL questionnaires were assessed using the PHPQoL, SF-36, and EQ-5D questionnaires at inclusion and 3 months after treatment. Statistical significance was set at P < 0.001. Results:Of the 100 patients included (mean age: 61.5 ± 12.4 years, 77% female), 89 underwent PTx (symptomatic: n = 47, asymptomatic: n = 42), and 11 received conservative treatment. The PHPQoL demonstrated strong psychometric properties and correlated well with generic HRQoL questionnaires. Following PTx, mean PHPQoL scores improved from 52.2 to 65.9 (P < 0.001); in asymptomatic patients, scores rose from 58.3 to 71.7 (P < 0.001). Conclusion:The Dutch version of the PHPQoL is a valid and reliable tool for assessing PHPT and demonstrates significant HRQoL improvements following PTx, including in asymptomatic patients, which may be underestimated by generic instruments.

Background Traditional exploration of surgical professionals' personality traits focuses on general characteristics at the domain-level of the five-factor model. Personality has been related to clinically-relevant areas such as clinical decision-making and team effectiveness, yet there is limited insight in the personality of surgeons at the facet-level of the Big Five. Here, we performed a large-scale study examining domain- and facet-variations of personality in four surgical generations and subspecialties. Method The Big Five Inventory-2, measuring the five domains and fifteen corresponding facets of personality, was distributed among all general surgery departments in the Netherlands. Surgically-interested medical students were approached via the surgical student society. A normative sample was matched for age to the surgical population. Corrected one-way analyses of variance were performed. Results The surgical population (medical students (n = 126), surgical residents not-in-training (n = 147), surgical residents-in-training (n = 227), and surgeons (n = 539)) scored higher on open-mindedness, conscientiousness, extraversion, agreeableness, and lower on negative emotionality relative to the normative population. Higher conscientiousness (p < 0.01) and lower negative emotionality (p < 0.001) were observed to increase per generation, together with lower open-mindedness scores in surgical residents (p < 0.001). Differences at the facet-level were present in five domains, including sub-traits such as productiveness, trust, and anxiety. Across environments, personality variances were observed in surgical subspecialty (conscientiousness, negative emotionality), teaching region (open-mindedness), and academics (open-mindedness). Conclusion We delineated nuanced personality variations across generations and subspecialties in the surgical population, marking a starting point in the introduction of personality insights in the professional domain of healthcare.