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1.
J Clin Med ; 13(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38610871

ABSTRACT

Background: The diagnostics and treatment of attention-deficit/hyperactivity disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period, and (peri)menopause are neglected, even though they impact ADHD symptoms and associated mood disorders. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. Methods: We describe the group programme and underlying rationale, offering a qualitative analysis of the participants' evaluation. Results: The seven bi-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47 years) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable, and the structure suited them well. Completing the premenstrual calendar augmented the awareness and recognition of individual cyclical symptoms. A lifespan approach increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care. Conclusions: Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

2.
Sci Rep ; 14(1): 3015, 2024 02 12.
Article in English | MEDLINE | ID: mdl-38346983

ABSTRACT

Anthropogenic factors have impacted the diversity and evolutionary trajectory of various species. This can be through factors such as pressure on population size or range, habitat fragmentation, or extensive manipulation and translocation. Here we use time-calibrated data to better understand the pattern and processes of evolution in the heavily manipulated European fallow deer (Dama dama). During the Pleistocene, fallow deer had a broad distribution across Europe and were found as far north as Britain during the Eemian interglacial. The last glacial period saw fallow deer retreat to southern refugia and they did not disperse north afterwards. Their recolonisation was mediated by people and, from northern Europe and the British Isles, fallow deer were transported around the world. We use ancient and modern mitochondrial DNA (mtDNA) and mitogenomic data from Eemian Britain to assess the pattern of change in distribution and lineage structure across Europe over time. We find founder effects and mixed lineages in the northern populations, and stability over time for populations in southern Europe. The Eemian sample was most similar to a lineage currently in Italy, suggesting an early establishment of the relevant refuge. We consider the implications for the integration of anthropogenic and natural processes towards a better understanding of the evolution of fallow deer in Europe.


Subject(s)
Deer , Humans , Animals , Deer/genetics , Population Dynamics , Europe , DNA, Mitochondrial/genetics , United Kingdom
3.
Clin Transl Radiat Oncol ; 44: 100696, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37965060

ABSTRACT

Background: Elective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life. Methods/design: This is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment. Discussion: If this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care.

4.
Front Psychiatry ; 14: 1306194, 2023.
Article in English | MEDLINE | ID: mdl-38152361

ABSTRACT

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition which is underdiagnosed and undertreated in women. For decades, the ADHD field has called for more insight into female-specific therapy. Preliminary findings postulate that changes in sex hormones during the menstrual cycle may influence the effectiveness of psychostimulant medication. Yet, pharmacotherapeutic interventions tailored to women with ADHD remain scarce. Previously, our group showed an increase in mood symptoms in the premenstrual week in women with ADHD. Premenstrual worsening of depressive and ADHD symptoms represent a treatment challenge. In our adult ADHD clinic, we noted several women describing exacerbation of their ADHD and depressive symptoms in the premenstrual week and/or insufficient effect of their established dosage of psychostimulant. We responded to the need expressed by these women by increasing their stimulant dosage in the premenstrual week, while monitoring the response and side effects. Methods: This community case study of nine consecutive women being treated for ADHD and co-occurring conditions (including depression and premenstrual dysphoric disorder), reports our local experience of increasing the individually prescribed psychostimulant dosage during the premenstrual period. We methodically monitored the effect of this increased dosage on ADHD symptoms, mood and somatic symptoms for the following 6-24 months. Results: With premenstrual dose elevation, all nine women experienced improved ADHD and mood symptoms with minimal adverse events. Premenstrual inattention, irritability and energy levels improved, and now resembled the other non-premenstrual weeks more closely. All women decided to continue with the elevated premenstrual pharmacotherapy. Discussion: Our preliminary results demonstrate potential benefits of increasing premenstrual psychostimulant dosage in women with ADHD, experiencing premenstrual worsening of ADHD and mood symptoms. The results concur with previous findings of diminished response to amphetamines in the late luteal phase. Increased dosage may help combat premenstrual worsening of cognitive and emotional symptoms in women with ADHD, with significant clinical implications. Better management of premenstrual ADHD and mood symptoms in vulnerable women can improve treatment outcome and meet an unmet need. However, implementation should be individually explored. Further investigation of luteal phase psychostimulant dose adjustment is required for safe, optimal and individualised treatment for women with ADHD.

5.
Ann R Coll Surg Engl ; 105(7): 632-638, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37652084

ABSTRACT

INTRODUCTION: Lymph node (LN) metastases in papillary thyroid microcarcinomas (microPTCs) are common. The lymph node ratio (LNR) has been proposed as a risk factor for recurrence in papillary thyroid cancer. However, its relevance in microPTC is undetermined. METHODS: Patients who underwent resection of their microPTC with concomitant LN clearance between 2005 and 2018 were identified. The LNR was calculated as the ratio of positive LNs to the total number of LNs. RESULTS: Data on 50 patients (36 female [72%]; median age 47 years [range: 19-84]) who underwent LN clearance (28 central [56%] vs 22 central + lateral [44%]) were analysed. Positive LNs were found in over two-thirds of the patients (n = 34; 68%). After a median follow-up of 61 months, 14 patients (28%) had developed recurrence. Positive LNs were not found to impact recurrence-free survival; extranodal extension and an LNR ≥ 0.26 were found to significantly increase the risk of recurrence on unadjusted analyses (p < 0.05). CONCLUSIONS: LN metastases are frequent among patients with microPTC. A higher LNR seems to be associated with recurrence. Additional studies are needed to further clarify these findings and to assess the possible role of LNR in treatment and surveillance.


Subject(s)
Carcinoma, Papillary , Lymph Node Ratio , Thyroid Neoplasms , Thyroid Cancer, Papillary/surgery , Recurrence , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Lymphatic Metastasis/pathology , Neoplasm Recurrence, Local , Biopsy, Fine-Needle , Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over
6.
Commun Earth Environ ; 4(1): 181, 2023.
Article in English | MEDLINE | ID: mdl-37250099

ABSTRACT

Understanding the variability of the Atlantic Meridional Overturning Circulation is essential for better predictions of our changing climate. Here we present an updated time series (August 2014 to June 2020) from the Overturning in the Subpolar North Atlantic Program. The 6-year time series allows us to observe the seasonality of the subpolar overturning and meridional heat and freshwater transports. The overturning peaks in late spring and reaches a minimum in early winter, with a peak-to-trough range of 9.0 Sv. The overturning seasonal timing can be explained by winter transformation and the export of dense water, modulated by a seasonally varying Ekman transport. Furthermore, over 55% of the total meridional freshwater transport variability can be explained by its seasonality, largely owing to overturning dynamics. Our results provide the first observational analysis of seasonality in the subpolar North Atlantic overturning and highlight its important contribution to the total overturning variability observed to date.

7.
J Laryngol Otol ; 137(6): 685-690, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35871793

ABSTRACT

OBJECTIVE: To evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour-node stage T2N0 glottic carcinoma, stratified for tumour extension. METHODS: A cross-sectional study was performed on patients who were treated with radiotherapy for T2N0 glottic carcinoma. Four questionnaires were used to measure different aspects of functional outcome. In addition, objective evaluation and perceptual analysis were performed. RESULTS: Fourteen patients were included in this study. The median time between the start of radiotherapy and assessment was 42 months (range, 26-143 months). Patients reported high-level functioning, with low symptom scores and good swallowing function, and showed a median dysphonia grade of 1.5. The median Voice Handicap Index-30 score was 17.5. CONCLUSION: Patients with T2N0 glottic carcinoma treated with radiotherapy had good long-term quality of life, with low symptom scores, good swallowing functioning and slightly elevated voice outcome parameters.


Subject(s)
Carcinoma , Dysphonia , Laryngeal Neoplasms , Humans , Quality of Life , Cross-Sectional Studies , Treatment Outcome , Dysphonia/etiology , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/pathology , Carcinoma/pathology , Glottis/pathology , Radiotherapy/adverse effects
8.
Updates Surg ; 75(2): 281-290, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35962278

ABSTRACT

BACKGROUND: Gastrectomy with lymph node dissection is the cornerstone of curative treatment of gastric cancer. Extent of lymphadenectomy may differ depending on T-stage, as the rate of lymph node metastases may differ. The objective of this systematic review is to investigate and compare the prevalence of nodal metastases in the individual lymph node stations between different T-stages. METHODS: Data reporting and structure of this systematic review follows the PRISMA checklist. The Medline and PubMed databases were systematically searched. The search included the following Mesh terms: "Stomach Neoplasms", "Lymphatic Metastasis" and "Lymph Node Excision". The primary outcome was the highest prevalence of nodal metastases per T-stage. RESULTS: The initial search resulted in 175 eligible articles. Five articles met the inclusion criteria and were accordingly analyzed. Concerning the lymph node stations 1 to 7, the lymph nodes along the lesser gastric curvature (station 3) show the highest metastases rate (T1: 5.5%, T2: 21.9%, T3: 41.9%, T4: 71.0%). Concerning the lymph node stations 8 to 20, the lymph nodes around the common hepatic artery (station 8) show the highest metastases rate (T1: 0.8%, T2: 7.9%, T3: 14.0%, T4: 28.2%). CONCLUSION: An overall low prevalence of nodal metastases in the individual lymph node stations in early, T1 gastric carcinomas and an overall high prevalence in more advanced, T3 and T4 gastric carcinomas endorse a more tailored approach based on the different gastric T-stages. In addition, a less extensive lymphadenectomy seems justified in early T1 carcinoma. SYNOPSIS: This systematic review provides an overview of the prevalence of nodal metastases for the individual lymph node stations between different T-stages, showing an overall low prevalence in early, T1 gastric carcinomas and an overall high prevalence in the more advanced, T3 and T4 gastric carcinomas.


Subject(s)
Carcinoma , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Prevalence , Lymph Nodes/surgery , Lymph Nodes/pathology , Lymph Node Excision , Lymphatic Metastasis/pathology , Gastrectomy/methods , Neoplasm Staging , Carcinoma/surgery
10.
Ann R Coll Surg Engl ; 104(9): 703-709, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35446717

ABSTRACT

BACKGROUND: Fine-needle aspiration cytology (FNAC) is an integral part of thyroid nodule assessment. Nodules with an indeterminate cytology (THY3a-f) require formal histological assessment to confirm benign or malignant pathology. This study aimed to provide data for an evidence-based approach for management of patients with THY3f nodules. METHODS: Retrospective review of patients who had a thyroid FNAC reported as suspicious of follicular neoplasm (THY3f) or showing atypia (THY3a) were identified, and clinical, operative and outcomes data were analysed. RESULTS: Between 2018 and 2020, 200 patients (167F:33M, median age 51 years (range:18-86 years)) had a THY3f cytology. Most presented with a palpable nodule (n=104; 68.4%). Overall, 152 (76.0%;130F:23M) underwent surgery and 31 (20.4%) were found to have a thyroid carcinoma (22 follicular carcinomas, 7 papillary carcinomas, 1 medullary thyroid carcinoma and 1 metastatic renal carcinoma). An additional incidental carcinoma (size: 0.7-13mm) was found in seven (4.6%). Among those with cancer, a completion thyroidectomy and radioactive iodine treatment was indicated in nine (<6% of the entire cohort). Previously suggested risk factors for malignancy, eg male gender, large tumour size (>4cm) or age, were not found to be associated with increased risk. During the same period, THY3a cytology was reported in 53 patients, of whom 29 underwent diagnostic surgery and 4 patients were found to have a thyroid cancer (follicular, n=3 and medullary, n=1). CONCLUSION: One in five patients with features suspicious of a follicular neoplasm (THY3f) has a thyroid carcinoma. This risk is much lower for THY3a. This study reinforces the current recommendation for thyroid surgery in all patients with a reliable THY3f cytology, as no further stratifying risk factors could be identified.


Subject(s)
Adenocarcinoma, Follicular , Carcinoma, Neuroendocrine , Thyroid Neoplasms , Thyroid Nodule , Humans , Male , Middle Aged , Thyroid Nodule/diagnosis , Thyroid Nodule/surgery , Thyroid Nodule/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Iodine Radioisotopes , Ultrasonography , Adenocarcinoma, Follicular/diagnosis , Adenocarcinoma, Follicular/surgery , Adenocarcinoma, Follicular/pathology , Retrospective Studies
11.
J Hosp Infect ; 124: 72-78, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35288252

ABSTRACT

BACKGROUND: Healthcare workers (HCWs) are at risk for coronavirus disease 2019 (COVID-19), and for spreading severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) amongst colleagues and patients. AIM: To study the presence of SARS-CoV-2 RNA and possible onward transmission by HCWs upon return to work after COVID-19, and association with disease severity and development of antibodies over time. METHODS: Unvaccinated HCWs with positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) were recruited prospectively. Data on symptoms were collected via telephone questionnaires on days 2, 7, 14 and 21 after a positive test. Upon return to work, repeat SARS-CoV-2 RT-PCR was performed and serum was collected. Repeat serum samples were collected at weeks 4, 8, 12 and 16 to determine antibody dynamics over time. Phylogenetic analysis was conducted to investigate possible transmission events originating from HCWs with a positive repeat RT-PCR. FINDINGS: Sixty-one (84.7%) participants with mild/moderate COVID-19 had a repeat SARS-CoV-2 RT-PCR performed upon return to work (median 13 days after symptom onset), of which 30 (49.1%) were positive with a median cycle threshold (Ct) value of 29.2 (IQR 26.9-29.9). All HCWs developed antibodies against SARS-CoV-2. No significant differences in symptomatology and presence of antibodies were found between repeat RT-PCR-positive and -negative HCWs. Eleven direct colleagues of six participants with a repeat RT-PCR Ct value <30 tested positive after the HCW returned to work. Phylogenetic and epidemiologic analysis did not indicate onward transmission through HCWs who were SARS-CoV-2 RNA positive upon return to work. CONCLUSIONS: HCWs regularly return to work with substantial SARS-CoV-2 RNA loads. However, this study found no evidence for subsequent in-hospital transmission.


Subject(s)
COVID-19 , SARS-CoV-2 , Health Personnel , Humans , Phylogeny , RNA, Viral , Return to Work
13.
J Nucl Cardiol ; 29(5): 2487-2496, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34318395

ABSTRACT

BACKGROUND: Calcification and inflammation are atherosclerotic plaque compositional biomarkers that have both been linked to stroke risk. The aim of this study was to evaluate their co-existing prevalence in human carotid plaques with respect to plaque phenotype to determine the value of hybrid imaging for the detection of these biomarkers. METHODS: Human carotid plaque segments, obtained from endarterectomy, were incubated in [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt), targeting Leukocyte Function-associated Antigen-1 (LFA-1) on leukocytes. By performing SPECT/CT, both inflammation from DANBIRT uptake and calcification from CT imaging were assessed. Plaque phenotype was classified using histology. RESULTS: On a total plaque level, comparable levels of calcification volume existed with different degrees of inflammation and vice versa. On a segment level, an inverse relationship between calcification volume and inflammation was evident in highly calcified segments, which classify as fibrocalcific, stable plaque segments. In contrast, segments with little or no calcification presented with a moderate to high degree of inflammation, often coinciding with the more dangerous fibrous cap atheroma phenotype. CONCLUSION: Calcification imaging alone can only accurately identify highly calcified, stable, fibrocalcific plaques. To identify high-risk plaques, with little or no calcification, hybrid imaging of calcification and inflammation could provide diagnostic benefit.


Subject(s)
Calcinosis , Carotid Artery Diseases , Plaque, Atherosclerotic , Biomarkers , Calcinosis/diagnostic imaging , Calcinosis/pathology , Carotid Artery Diseases/diagnostic imaging , Humans , Indium Radioisotopes , Inflammation/complications , Inflammation/diagnostic imaging , Lymphocyte Function-Associated Antigen-1 , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Single Photon Emission Computed Tomography Computed Tomography
14.
J Crohns Colitis ; 16(4): 606-615, 2022 May 10.
Article in English | MEDLINE | ID: mdl-34636839

ABSTRACT

INTRODUCTION: Intestinal ultrasound [IUS] is useful for assessment of inflammation, complications, and treatment follow-up in inflammatory bowel disease [IBD] patients. We aimed to study outcomes and impact on disease management for point-of-care [POC] IUS in IBD patients. METHODS: Two patient cohorts undergoing POC IUS [January 2016-July 2018 and October 2019-December 2019] were included retrospectively. Disease management after IUS was analysed and IUS outcomes were compared with symptoms, biomarkers, and additional imaging within 8 weeks from IUS. To study differences in use of IUS over time, cohorts were compared. RESULTS: In total, 345 examinations (280 in Crohn's disease [CD]/65 in ulcerative colitis [UC]) were performed. Present inflammation on IUS was comparable between symptomatic and asymptomatic CD [67.6% vs 60.5%; p = 0.291]. In 60%, IUS had impact on disease management with change in medication in 47.8%. Additional endoscopy/magnetic resonance imaging [MRI] was planned after 32.8% examinations, showing good correlation with IUS in 86.3% [ρ = 0.70, p <0.0001] and 80.0% [ρ = 0.75, p <0.0001] of cases, respectively. Faecal calprotectin was higher in active versus inactive disease on IUS [664 µg/g vs 79 µg/g; p <0.001]. Over the years, IUS was performed more frequently to monitor treatment response and the use of MRI was reduced within the cohort. CONCLUSIONS: POC IUS affects clinical decision making and could detect preclinical relapse in CD patients, with potential to reduce additional endoscopy or MRI. In addition, the paradigm expands towards monitoring treatment and close follow-up for IUS. Based on our results, we propose a POC IUS algorithm for follow-up of IBD patients.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Algorithms , Chronic Disease , Colitis, Ulcerative/diagnostic imaging , Colitis, Ulcerative/drug therapy , Crohn Disease/complications , Crohn Disease/diagnostic imaging , Disease Management , Feces , Humans , Inflammation/complications , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/diagnostic imaging , Point-of-Care Systems , Retrospective Studies
15.
J Antimicrob Chemother ; 76(11): 2941-2949, 2021 10 11.
Article in English | MEDLINE | ID: mdl-34337660

ABSTRACT

BACKGROUND: The advocated pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin, AUC/MIC ≥ 400 mg·h/L, may not be reached with a conventional fixed starting dose of 1000 mg in critically ill patients, but increasing the dose may cause nephrotoxicity. OBJECTIVES: To evaluate the effect of a weight-based loading dose of 25 mg/kg vancomycin on PK/PD target attainment in the first 24 h (AUC0-24) in critically ill patients and to evaluate whether this increases the risk of acute kidney injury (AKI). PATIENTS AND METHODS: A prospective observational before/after study was performed in ICU patients, comparing the percentage of vancomycin courses with AUC0-24 ≥ 400 mg·h/L and the incidence of AKI, defined as worsening of the risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE) score. The conventional dose group received 1000 mg of vancomycin as initial dose; the loading dose group received a weight-based loading dose of 25 mg/kg. A population PK model developed using non-linear mixed-effects modelling was used to estimate AUC0-24 in all patients. RESULTS: One hundred and four courses from 82 patients were included. With a loading dose, the percentage of courses achieving AUC0-24 ≥ 400 mg·h/L increased significantly from 53.8% to 88.0% (P = 0.0006). The percentage of patients with new-onset AKI was not significantly higher when receiving a 25 mg/kg loading dose (28.6% versus 37.8%; P = 0.48). However, the risk of AKI was significantly higher in patients achieving AUC0-24 > 400 mg·h/L compared with patients achieving AUC < 400 mg·h/L (39.0% versus 14.8%; P = 0.031). CONCLUSIONS: A weight-based loading dose of 25 mg/kg vancomycin led to significantly more patients achieving AUC0-24 ≥ 400 mg·h/L without increased risk of AKI. However, some harm cannot be ruled out since higher exposure was associated with increased risk of AKI.


Subject(s)
Acute Kidney Injury , Vancomycin , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Anti-Bacterial Agents/adverse effects , Critical Illness , Humans , Incidence , Retrospective Studies , Vancomycin/adverse effects
16.
Nat Commun ; 12(1): 3002, 2021 05 24.
Article in English | MEDLINE | ID: mdl-34031423

ABSTRACT

Changes in the Atlantic Meridional Overturning Circulation, which have the potential to drive societally-important climate impacts, have traditionally been linked to the strength of deep water formation in the subpolar North Atlantic. Yet there is neither clear observational evidence nor agreement among models about how changes in deep water formation influence overturning. Here, we use data from a trans-basin mooring array (OSNAP-Overturning in the Subpolar North Atlantic Program) to show that winter convection during 2014-2018 in the interior basin had minimal impact on density changes in the deep western boundary currents in the subpolar basins. Contrary to previous modeling studies, we find no discernable relationship between western boundary changes and subpolar overturning variability over the observational time scales. Our results require a reconsideration of the notion of deep western boundary changes representing overturning characteristics, with implications for constraining the source of overturning variability within and downstream of the subpolar region.

17.
Neth Heart J ; 29(7-8): 394-401, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33675521

ABSTRACT

INTRODUCTION: Circulatory extracorporeal life support (ECLS) has been performed at the University Medical Centre Utrecht for 12 years. During this time, case mix, indications, ECLS set-ups and outcomes seem to have substantially changed. We set out to describe these characteristics and their evolution over time. METHODS: All patients receiving circulatory ECLS between 2007 and 2018 were retrospectively identified and divided into six groups according to a 2-year period of time corresponding to the date of ECLS initiation. General characteristics plus data pertaining to comorbidities, indications and technical details of ECLS commencement as well as in-hospital, 30-day, 1­year and overall mortality were collected. Temporal trends in these characteristics were examined. RESULTS: A total of 347 circulatory ECLS runs were performed in 289 patients. The number of patients and ECLS runs increased from 8 till a maximum of 40 runs a year. The distribution of circulatory ECLS indications shifted from predominantly postcardiotomy to a wider set of indications. The proportion of peripheral insertions with or without application of left ventricular unloading techniques substantially increased, while in-hospital, 30-day, 1­year and overall mortality decreased over time. CONCLUSION: Circulatory ECLS was increasingly applied at the University Medical Centre Utrecht. Over time, indications as well as treatment goals broadened, and cannulation techniques shifted from central to mainly peripheral approaches. Meanwhile, weaning success increased and mortality rates diminished.

18.
Mucosal Immunol ; 14(3): 594-604, 2021 05.
Article in English | MEDLINE | ID: mdl-33542495

ABSTRACT

Human bronchial epithelial (HBE) cells play an essential role during bacterial infections of the airways by sensing pathogens and orchestrating protective immune responses. We here sought to determine which metabolic pathways are utilized by HBE cells to mount innate immune responses upon exposure to a relevant bacterial agonist. Stimulation of HBE cells by the bacterial component flagellin triggered activation of the mTOR pathway resulting in an increased glycolytic flux that sustained the secretory activity of immune mediators by HBE cells. The mTOR inhibitor rapamycin impeded glycolysis and limited flagellin-induced secretion of immune mediators. The role of the mTOR pathway was recapitulated in vivo in a mouse model of flagellin-triggered lung innate immune responses. These data demonstrate that metabolic reprogramming via the mTOR pathway modulates activation of the respiratory epithelium, identifying mTOR as a potential therapeutic target to modulate mucosal immunity in the context of bacterial infections.


Subject(s)
Bronchi/pathology , Epithelial Cells/immunology , Klebsiella Infections/immunology , Klebsiella pneumoniae/physiology , Pseudomonas Infections/immunology , Pseudomonas aeruginosa/physiology , TOR Serine-Threonine Kinases/metabolism , Animals , Cells, Cultured , Cellular Reprogramming , Disease Models, Animal , Female , Flagellin/metabolism , Glycolysis , Humans , Immunity, Innate , Mice , Mice, Inbred C57BL
19.
Eur J Surg Oncol ; 47(8): 2016-2022, 2021 08.
Article in English | MEDLINE | ID: mdl-33583629

ABSTRACT

INTRODUCTION: The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer. MATERIALS AND METHODS: Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses. RESULTS: In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8-61.5 months), 58% (95% CI 48-66), and 49% (95% CI 40-57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31-48), and 45% (95% CI 36-54). Three- and five-year risk of LRR were 26% (95% CI 19-33), and 30% (95% CI 22-38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached). CONCLUSION: In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/methods , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Neoplasm Recurrence, Local/epidemiology , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Cisplatin/therapeutic use , Disease-Free Survival , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Esophagectomy , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/therapy , Netherlands , Paclitaxel/administration & dosage , Progression-Free Survival , Radiotherapy , Retrospective Studies , Salvage Therapy , Time Factors
20.
BJS Open ; 5(1)2021 01 08.
Article in English | MEDLINE | ID: mdl-33609384

ABSTRACT

BACKGROUND: Adrenocortical carcinomas (ACCs) carry a poor prognosis. This study assessed the comparative performance of existing nomograms in estimating the likelihood of survival, along with the value of conditional survival estimation for patients who had already survived for a given length of time after surgery. METHODS: This was an observational study based on a prospectively developed departmental database that recorded details of patients operated for ACC in a UK tertiary referral centre. RESULTS: Of 74 patients with ACC managed between 2001 and 2020, data were analysed for 62 patients (32 women and 30 men, mean(s.d.) age 51(17) years) who had primary surgical treatment in this unit. Laparoscopic (9) or open adrenalectomies (53) were performed alone or in association with a multivisceral resection (27). Most of the tumours were left-sided (40) and 18 were cortisol-secreting.Overall median survival was 33 months, with 1-, 3- and 5-year survival rates of 79, 49, and 41 per cent respectively. Age over 55 years, higher European Network for Study of Adrenal Tumours stage, and cortisol secretion were associated with poorer survival in univariable analyses. Four published nomograms suggested widely variable outcomes that did not correlate with observed overall survival at 1, 3 or 5 years after operation. The 3-year conditional survival at 2 years (probability of surviving to postoperative year 5) was 65 per cent, compared with a 5-year actuarial survival rate of 41 per cent calculated from the time of surgery. CONCLUSION: Survival of patients with ACC correlates with clinical parameters but not with published nomograms. Conditional survival might provide a more accurate estimate of survival for patients who have already survived for a certain amount of time after resection.


Subject(s)
Adrenal Cortex Neoplasms/mortality , Adrenalectomy , Adrenocortical Carcinoma/mortality , Nomograms , Survival Rate/trends , Adrenal Cortex Neoplasms/surgery , Adrenocortical Carcinoma/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Tertiary Care Centers , Treatment Outcome , United Kingdom
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