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1.
Ann Surg ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38747145

ABSTRACT

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

2.
Birth ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39140615

ABSTRACT

BACKGROUND: Research has shown caseload midwifery to increase the chance of vaginal birth, but this may not be the case in settings with high vaginal birth rates in standard care. This study investigated the association between caseload midwifery and birth mode, labor interventions, and maternal and neonatal outcomes at a large obstetric unit in Denmark. METHODS: Cohort study including medical records on live, singleton births fr om June 2018 until February 2022. Exposure was caseload midwifery care compared with standard midwifery care. The primary outcome was birth mode, and secondary outcomes were other outcomes of labor. Adjusted risk ratios (aRR) with 95% confidence intervals (CI) were estimated by log-binomial regression. RESULTS: Among 16,110 pregnancies, 3162 pregnancies (19.6%) received caseload midwifery care. Caseload midwifery was associated with fewer planned cesareans (aRR 0.63 [95% CI 0.54-0.74]) and emergency cesareans (aRR 0.86 [95% CI 0.75-0.95]). No differences in labor induction, use of epidural analgesia, oxytocin augmentation, or anal sphincter tears were observed. Caseload midwifery performed more amniotomies (aRR 1.14 [95% CI 1.02-1.27]) and tended to perform more episiotomies (aRR 1.19 [95% CI 0.96-1.48]). Postpartum hemorrhage (aRR 0.90 [95% CI 0.82-0.99]) and low Apgar score were less likely (aRR 0.54 [95% CI 0.37-0.77]), and early discharge more likely (aRR 1.22 [95% CI 1.17-1.28]) in caseload midwifery. CONCLUSION: In caseload midwifery care, a higher vaginal birth rate was observed with no increase in adverse outcomes, mainly due to a lower likelihood of planned cesarean. Also, fewer children were born with low Apgar scores.

3.
Surg Endosc ; 37(4): 2729-2748, 2023 04.
Article in English | MEDLINE | ID: mdl-36471061

ABSTRACT

BACKGROUND: Currently, no generally accepted curriculum for operating room nurses (OR nurses) working with robotic-assisted surgery (RAS) exists. OR nurses working with RAS require different competencies than regular OR nurses, e.g. knowledge of the robotic system and equipment and specific emergency undocking procedures. The objective of this study was to identify learning goals for a curriculum for OR nurses working with RAS and to investigate which learning methods should be used. METHODS: A three-round Delphi approach, with an additional survey, was used in this study. Four OR nurses from every department in gynecology, urology, and surgical gastroenterology doing RAS in Denmark were invited to participate. RESULTS: The response rates were 93%, 81%, and 79%, respectively, in the three rounds of the Delphi survey and 68% in the additional survey. After the processing of data, a list of 57 learning goals, sorted under 11 domains, was produced. 41 learning goals were rated Relevant, Very relevant, or Essential spread over 10 of the 11 domains. The top 3 learning goals rated as Essential: Identify the most common injuries related to patient positioning during robotic-assisted surgery and know how to avoid them, Connect, calibrate and handle the scope, Perform an emergency undocking procedure. The panel rated Supervised training during surgery on patients as the most relevant learning method, followed by Dry lab and Team training. CONCLUSIONS: The learning goals identified in this study, can be used as the basis for a curriculum for OR nurses working with RAS. During the processing, it became clear that there is a need to further investigate issues such as communication challenges, awareness of emergency procedures, and differences in the skills required depending on the role of the RAS nurse.


Subject(s)
Robotic Surgical Procedures , Humans , Delphi Technique , Operating Rooms , Curriculum , Learning , Clinical Competence
4.
Scand J Gastroenterol ; 57(10): 1149-1157, 2022 10.
Article in English | MEDLINE | ID: mdl-35514215

ABSTRACT

Background and objectives: Over the last decade our understanding of the pathophysiology of portal hypertension has increased. Novel diagnostic technologies have facilitated and improved the diagnosis and treatment of hepatic fibrosis and cirrhosis. With this review we aim to provide an overview of contemporary diagnostic principles of portal hypertension and indications for measuring portal pressure in cirrhosis.Methods: By review of current literature, we assessed new and old principles of measuring portal hypertension and the diagnostic values of the methods.Results: Invasive measurement of the portal pressure is still the gold standard to quantitate portal hypertension and to assess response to vasoactive treatment. The size of the portal pressure is important to assess since it contains information on the course of the disease and risk of developing hepatic decompensation, hepatocellular carcinoma, and mortality. Reliable non-invasive Elastography techniques are emerging that adequately assess portal pressure, but the available methods are not yet sufficiently accurate.Conclusion: Although elastography techniques provide valuable information and are good monitoring tools, liver vein catheterization remains valuable in diagnosing and monitoring portal hypertension, especially in combination with a trans-jugular liver biopsy.


Subject(s)
Elasticity Imaging Techniques , Hypertension, Portal , Elasticity Imaging Techniques/methods , Fibrosis , Humans , Hypertension, Portal/complications , Hypertension, Portal/diagnosis , Liver/pathology , Liver Cirrhosis/pathology , Portal Pressure/physiology
5.
Colorectal Dis ; 24(10): 1128-1139, 2022 10.
Article in English | MEDLINE | ID: mdl-35639396

ABSTRACT

AIM: Living with a stoma can greatly influence quality of life. The purpose of this systematic review was to identify all patient reported outcome measures (PROMs) assessing health related quality of life (HRQoL) or similar constructs related to an intestinal stoma and to evaluate their level of validation. METHODS: The study was reported in line with PRISMA guidelines. The protocol was registered in PROSPERO prior to the study. Eligible studies were any study investigating psychometric properties of a stoma-specific PROM. The databases MedLine, Embase, CINAHL and Cochrane Libraries were searched for eligible studies. Studies were screened on title and abstract, then full-text for eligibility. Data extraction on the study populations, PROM characteristics, psychometric properties as well as quality assessment using the COSMIN Risk of Bias checklist was performed. RESULTS: In total, 40 studies were included concerning the development and/or validation of 21 PROMs. For most PROMs, few psychometric properties were assessed. In general, quality of content validity was poor, quality of construct validity and reliability was good. Assessment of responsiveness was lacking. CONCLUSION: This systematic review offers an overview of existing PROMs measuring stoma-related HRQoL and their psychometric properties. A large number of PROMs exist and their measures overlap considerably. The PROMs generally have a low level of validation, emphasizing the need for future studies to further validate existing PROMs, rather than developing new ones.


Subject(s)
Patient Reported Outcome Measures , Quality of Life , Humans , Reproducibility of Results , Psychometrics
6.
Colorectal Dis ; 24(6): 773-781, 2022 06.
Article in English | MEDLINE | ID: mdl-35090085

ABSTRACT

OBJECTIVE: To test the reliability and validity of the Chinese version of the colostomy impact score (CIS) among patients with a permanent colostomy in China. METHODS: A total of 218 patients completed the survey either in the clinic or remotely and mailed their responses. Reliability was estimated based on test-retest reliability. Validity was evaluated based on content validity, construct validity, and discriminative validity. The sensitivity and specificity of the score were analysed. The area under the curve was analysed by drawing the receiver-operating characteristic (ROC) curve; the optimal cutoff point was calculated to assess the impact of a stoma on domestic patients. RESULTS: The test-retest reliability of the CIS was 0.967. The content validity was 0.98, and the construct and discriminative validities were good; sensitivity, specificity, and area under the ROC curve were 100, 48.53, and 0.806%, respectively. The optimal cutoff point for the Chinese version of the Colostomy Impact Score was 11.5. CONCLUSIONS: The Chinese version of the CIS indicated good reliability and validity, making it suitable for the evaluation of the impact of a permanent colostomy.


Subject(s)
Colostomy , Rectal Neoplasms , China , Humans , Psychometrics , Rectal Neoplasms/surgery , Reproducibility of Results , Surveys and Questionnaires
7.
Support Care Cancer ; 30(11): 8969-8979, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35930059

ABSTRACT

PURPOSE: Stoma-related problems are known to be important to patients and potentially affect everyday life. The prevalence of stoma-related problems in rectal cancer survivors remains undetermined. This study aimed to examine aspects of life with a long-term stoma, stoma management, and stoma-related problems and explore the impact of stoma-related problems on daily life. METHODS: In total, 2262 patients from 5 European countries completed a multidimensional survey. Stoma-related problems were assessed using the Colostomy Impact score. Multivariable regression analysis, after adjusting for potential confounding factors, provided odds ratio (OR) and 95% confidence intervals (CI) for stoma-related problems' association with restrictions in daily life. RESULTS: The 2262 rectal cancer survivors completed the questionnaire at a median of 5.4 years (interquartile range 3.8-7.6) after stoma formation. In the total sample, leakage (58%) and troublesome odour (55%) were most prevalent followed by skin problems (27%) and pain (21%). Stoma-related problems were more prevalent in patients with parastomal bulging. A total of 431 (19%) reported feeling restricted in daily activities in life with a stoma. Leakage, odour, skin problems, stool consistency, and frequent appliance changes were significantly associated with restrictions in daily life. The highest risk of experiencing restrictions was seen for patients having odour (OR 2.74 [95% CI: 1.99-3.78]) more than once a week and skin problems (OR 1.77 [95% CI: 1.38-2.27]). CONCLUSION: In this large cohort with rectal cancer, stoma-related problems were highly prevalent and impacted daily life. Supportive care strategies should entail outreach to patients with a long-term stoma.


Subject(s)
Cancer Survivors , Rectal Neoplasms , Surgical Stomas , Humans , Cross-Sectional Studies , Surgical Stomas/adverse effects , Colostomy , Rectum , Rectal Neoplasms/surgery , Quality of Life
8.
Colorectal Dis ; 23(7): 1866-1877, 2021 07.
Article in English | MEDLINE | ID: mdl-33725386

ABSTRACT

AIM: Optimal oncological resection in cancers of the lower rectum often requires a permanent colostomy. However, in some patients a colostomy may have a negative impact on health-related quality of life (HRQoL). The Colostomy Impact (CI) score is a simple questionnaire that identifies patients with stoma dysfunction that impairs HRQoL by dividing patients into 'minor' and 'major' CI groups. This aim of this study is to evaluate construct and discriminative validity, sensitivity, specificity and reliability of the CI score internationally, making it applicable for screening and identification of patients with stoma-related impaired HRQoL. METHOD: The CI score was translated in agreement with WHO recommendations. Cross-sectional cohorts of rectal cancer survivors with a colostomy in Australia, China, Denmark, the Netherlands, Portugal, Spain and Sweden were asked to complete the CI score, the European Organization for Research and Treatment of Cancer (EORTC) quality of life 30-item core questionnaire, the stoma-specific items of the EORTC quality of life 29-item colorectal-specific questionnaire and five anchor questions assessing the impact of colostomy on HRQoL. RESULTS: A total of 2470 patients participated (response rate 51%-93%). CI scores were significantly higher in patients reporting reduced HRQoL due to their colostomy than in patients reporting no reduction. Differences in EORTC scale scores between patients with minor and major CI were significant and clinically relevant. Sensitivity was high regarding dissatisfaction with a colostomy. Regarding evaluation of discriminative validity, the CI score relevantly identified groups with differences in HRQoL. The CI score proved reliable, with equal CI scores between test and retest and an intraclass correlation coefficient in the moderate to excellent range. CONCLUSION: The CI score is internationally valid and reliable. We encourage its use in clinical practice to identify patients with stoma dysfunction who require further attention.


Subject(s)
Colostomy , Rectal Neoplasms , Cross-Sectional Studies , Humans , Quality of Life , Rectal Neoplasms/surgery , Reproducibility of Results , Surveys and Questionnaires , Translations
9.
J Pediatr Nurs ; 61: 40-46, 2021.
Article in English | MEDLINE | ID: mdl-33744621

ABSTRACT

PURPOSE: To explore children's, parents', and healthcare professionals', experiences of anesthesia related to pediatric oncological treatment performed at the pediatric oncology ward. DESIGN AND METHODS: The study was a qualitative study. 11 children and 12 parents were recruited for individual or dyadic interviews and two focus groups with a total of 12 healthcare professionals were recruited through purposeful and convenience sampling procedures. RESULTS: Thematic analysis generated one main theme, the familiar in the unfamiliar, and two subthemes, the room creates an atmosphere and relational continuity. CONCLUSIONS: Changing the physical environment and composition of the team positively influenced the experience of anesthesia in pediatric cancer treatment for both children, parents, and healthcare professionals. Familiarity was important for all involved and familiarity was associated with continuity related to the physical environment, as well as the relational and procedural professional continuity. Parents expressed that they never felt good about anesthesia as there were feelings of leaving your child's life into the hands of others. However, familiarity in trusting relationships with healthcare professionals helped to moderate these aspects. PRACTICE IMPLICATIONS: Familiarity should be considered important with continuity in trusting relations and collaborations between nurses and families, as well as between healthcare staff. Pediatric oncology ward is a preferred safe familiar setting for procedure-related anesthesia. Parents and children value individualized flexible nursing care, that takes the child's and parents habits and preferences into account during procedure-related anesthesia in pediatric oncological treatment.


Subject(s)
Anesthesia , Parents , Child , Delivery of Health Care , Health Personnel , Humans , Qualitative Research
10.
Am J Pathol ; 189(12): 2377-2388, 2019 12.
Article in English | MEDLINE | ID: mdl-31539518

ABSTRACT

miR-615-3p has previously been described as up-regulated in prostate cancer (PC) tissue samples compared with nonmalignant controls; however, its prognostic potential and functional role in PC remain largely unknown. In this study, we investigated the clinical and biological relevance of miR-615-3p in PC. The expression of miR-615-3p was measured in PC tissue specimens from 239 men who underwent radical prostatectomy (RP), and it was investigated if miR-615-3p could predict postoperative biochemical recurrence (BCR). These findings were subsequently validated in three independent RP cohorts (n = 222, n = 273, and n = 387) and functional overexpression studies conducted in PC cells (PC3M). High miR-615-3p expression was significantly associated with BCR in four independent PC patient cohorts (P < 0.05, log-rank test). In addition, high miR-615-3p expression was a significant predictor of PC-specific survival in univariate (hazard ratio, 3.75; P < 0.001) and multivariate (hazard ratio, 2.66; P = 0.008) analysis after adjustment for the Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) nomogram in a merged RP cohort (n = 734). Moreover, overexpression of miR-615-3p in PC cells (PC3M) significantly increased cell viability, proliferation, apoptosis, and migration. Together, our results suggest that miR-615-3p is a significant predictor of postoperative BCR and PC-specific survival and has oncogenic functions in PC cells.


Subject(s)
Biomarkers, Tumor/genetics , Cell Movement , Cell Proliferation , MicroRNAs/genetics , Neoplasm Recurrence, Local/mortality , Prostatectomy/mortality , Prostatic Neoplasms/mortality , Adult , Aged , Cohort Studies , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Prognosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Survival Rate , Tumor Cells, Cultured
11.
Int J Cancer ; 145(12): 3445-3452, 2019 12 15.
Article in English | MEDLINE | ID: mdl-31125115

ABSTRACT

Improved prognostic biomarkers are needed to guide personalized prostate cancer (PC) treatment decisions. Due to the prominent molecular heterogeneity of PC, multimarker panels may be more robust. Here, 25 selected top-candidate miRNA and methylation markers for PC were profiled by qPCR in malignant radical prostatectomy (RP) tissue specimens from 198 PC patients (Cohort 1, training). Using GLMnet, we trained a novel multimarker model (miMe) comprising nine miRNAs and three methylation markers that predicted postoperative biochemical recurrence (BCR) independently of the established clinicopathological CAPRA-S nomogram in Cox multivariate regression analysis in Cohort 1 (HR [95% CI]: 1.53 [1.26-1.84], p < 0.001). This result was successfully validated in two independent RP cohorts (Cohort 2, n = 159: HR [95% CI]: 1.35 [1.06-1.73], p = 0.015. TCGA, n = 350: HR [95% CI]: 1.34 [1.01-1.77], p = 0.04). Notably, in CAPRA-S low-risk patients, a high miMe score was associated with >6 times higher risk of BCR, suggesting that miMe may help identify PC patients at high risk of progression despite favorable clinicopathological factors postsurgery. Finally, miMe was a significant predictor of cancer-specific survival (p = 0.019, log-rank test) in a merged analysis of 357 RP patients. In conclusion, we trained, tested and validated a novel 12-marker panel (miMe) that showed significant independent prognostic value in three RP cohorts. In the future, combining miMe score with existing clinical nomograms may improve PC risk stratification and thus help guide treatment decisions.


Subject(s)
Biomarkers, Tumor/genetics , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Adult , Aged , Cohort Studies , Disease Progression , Humans , Kaplan-Meier Estimate , Male , Methylation , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Nomograms , Prognosis , Prostate/pathology , Prostate-Specific Antigen/genetics , Prostatectomy/methods , Prostatic Neoplasms/pathology , Risk Factors
12.
Acta Oncol ; 58(5): 566-572, 2019 May.
Article in English | MEDLINE | ID: mdl-30696323

ABSTRACT

Background: Formation of a fecal stoma may be necessary to ensure radical resection in colorectal cancer (CRC) patients but will substantially impact the health-related quality of life (HRQoL) in about 20% of cases. Little is known about patient-related risk factors for reduced HRQoL in patients with a permanent stoma. We, therefore, reviewed the current literature on how demographic and socioeconomic factors affect HRQoL in CRC survivors with a stoma. Material and methods: The databases Pubmed, Embase, CINAHL, and PsycINFO were systematically searched. Two independent reviewers extracted and quality-assessed eligible publications. Studies assessing HRQoL using a validated questionnaire at least 6 months after surgery for CRC were included if data on the impact of demographic and/or socioeconomic, factors on HRQoL were analyzed and presented. Results: Eligible studies predominantly presented small cross-sectional cohorts. Age showed equivocal results; hence, some studies found younger patients had inferior HRQoL compared with older patients, and others found no difference. Subdivision into age groups differed widely. Several studies found that both generic and stoma-specific HRQoL was lower in females compared with males. Most studies found that socioeconomic factors did not affect HRQoL while one study found lower education correlated to reduced HRQoL. Categorization of these factors also varied widely. Conclusions: This is to our knowledge the first systematic review on the impact of patient-related factors on HRQoL in long-term CRC survivors. We found that a stoma had more impact in younger ostomates than older and that HRQoL in females was reduced more than in males. Conclusions regarding other factors were difficult due to few studies and contradictory results. Further research in this subject is much needed in order to target preventive measures when planning surgery in patients in high risk of reduced HRQoL.


Subject(s)
Colorectal Neoplasms/surgery , Ostomy , Quality of Life , Aged , Cancer Survivors , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Socioeconomic Factors
14.
J Pediatr Nurs ; 46: e77-e85, 2019.
Article in English | MEDLINE | ID: mdl-30935724

ABSTRACT

PURPOSE: Hospital clowns are widely used as a means of non-pharmacological intervention in the treatment of hospitalized children. However, little research has examined the impact of clowns on common painful needle-related procedures. This study explored children's pain experience and their ability to cope during a venipuncture while interacting with a clown in the acute admission unit. DESIGN AND METHODS: An ethnographic fieldwork study was conducted. Data were collected over a 10-month period through participant observation and informal interviews, supplemented by video recordings. The participants comprised 38 acutely admitted children aged 4 to 15 years undergoing a venipuncture in the presence of a hospital clown. Analysis was structured in three stages: before venipuncture; during venipuncture; and after venipuncture. RESULTS: The development of a responsive interaction between child and clown, identified as a WE, was found to be beneficial to the child during venipuncture procedure. The WE was characterized by three themes "How do WE do this together?"; "WE are together"; and "I/WE did it!" CONCLUSIONS: The study emphasizes the importance of a WE established between child and hospital clown from the first encounter until a final evaluation. This WE was verbalized repeatedly by the clown and the child and was essential in shaping a tailored approach which met the needs of each child. This approach seemed to strengthen the child's competence in pain management and ability to cope, thus building competence for future venipunctures. PRACTICE IMPLICATIONS: Establishing a WE might advance the psychosocial care of hospitalized children undergoing acute painful procedures.


Subject(s)
Laughter Therapy , Pain Management/methods , Phlebotomy/adverse effects , Adolescent , Child , Child, Hospitalized , Child, Preschool , Data Collection/methods , Female , Humans , Male
15.
Int J Mol Sci ; 20(5)2019 Mar 07.
Article in English | MEDLINE | ID: mdl-30866497

ABSTRACT

Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, DOCK2, FBXO30, GRASP, HIF3A, MOB3B, PFKP, and TPM4) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75⁻94%) and specificity (84⁻100%) for PCa. Furthermore, DOCK2, GRASP, HIF3A and PKFP hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. DOCK2 is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24⁻3.10), adjusted p = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Carrier Proteins/genetics , DNA Methylation , Guanine Nucleotide Exchange Factors/genetics , Membrane Proteins/genetics , Phosphofructokinase-1, Type C/genetics , Prostatic Neoplasms/diagnosis , Aged , Aged, 80 and over , Apoptosis Regulatory Proteins , Biomarkers, Tumor/genetics , Epigenesis, Genetic , GTPase-Activating Proteins , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Promoter Regions, Genetic , Prostatic Neoplasms/genetics , Repressor Proteins , Sensitivity and Specificity , Survival Analysis
16.
Chembiochem ; 18(1): 5-49, 2017 Jan 03.
Article in English | MEDLINE | ID: mdl-27748555

ABSTRACT

Inhibition of histone deacetylase (HDAC) enzymes has emerged as a target for development of cancer chemotherapy. Four compounds have gained approval for clinical use by the Food and Drug Administration in the US, and several are currently in clinical trials. However, none of these compounds possesses particularly good isozyme selectivity, which would be a highly desirable feature in a tool compound. Whether selective inhibition of individual HDAC isozymes will provide improved drug candidates remains to be seen. Nevertheless, it has been speculated that using macrocyclic compounds to target HDAC enzymes might hold an advantage over the use of traditional hydroxamic-acid-containing inhibitors, which rely on chelation to the conserved active-site zinc ion. Here we review the literature on macrocyclic HDAC inhibitors obtained from natural sources and on structure-activity relationship studies inspired by these molecules, as well as on efforts aimed at fully synthetic macrocyclic HDAC inhibitors.


Subject(s)
Biological Products/chemistry , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylases/metabolism , Macrocyclic Compounds/chemistry , Binding Sites , Biological Products/chemical synthesis , Biological Products/metabolism , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylase Inhibitors/metabolism , Histone Deacetylases/chemistry , Macrocyclic Compounds/chemical synthesis , Macrocyclic Compounds/metabolism , Molecular Docking Simulation , Peptides, Cyclic/chemical synthesis , Peptides, Cyclic/chemistry , Peptides, Cyclic/metabolism , Structure-Activity Relationship
17.
Surg Endosc ; 31(6): 2596-2601, 2017 06.
Article in English | MEDLINE | ID: mdl-27699518

ABSTRACT

BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging procedure in the treatment of esophageal achalasia, a primary motility disorder. However, the long-term outcome of POEM in patients, who have previously undergone a Heller myotomy, is unknown. METHODS: Using a local database, we identified patients with esophageal achalasia, who underwent POEM. We compared patients with a previous Heller myotomy to those, who had received none or only non-surgical therapy prior to the POEM procedure. We conducted follow-up examinations at 3, 12, and 24 months following the procedure. RESULTS: We included 66 consecutive patients undergoing POEM for achalasia, of which 14 (21.2 %) had undergone a prior Heller myotomy. In both groups, the preoperative Eckardt score was 7. Postoperatively, the non-Heller group experienced a more pronounced symptom relief at both 3-, 12-, and 24-month follow-up compared with the Heller group, and there was a tendency for the effect of POEM to reduce over time. We suggest that there is a correlation between preoperative measurements of gastroesophageal sphincter pressures and the chance of a successful POEM. CONCLUSIONS: POEM has a place in the treatment of esophageal achalasia in patients with a prior Heller myotomy and persistent symptoms as it is a safe procedure with acceptable long-term results.


Subject(s)
Esophageal Achalasia/surgery , Esophageal Sphincter, Lower/surgery , Natural Orifice Endoscopic Surgery , Adult , Aged , Female , Heller Myotomy , Humans , Male , Middle Aged , Reoperation , Treatment Outcome , Young Adult
18.
Scand J Gastroenterol ; 49(11): 1285-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25225846

ABSTRACT

INTRODUCTION: Peroral endoscopic myotomy (POEM) has been introduced as a new treatment of achalasia, and studies are emerging on POEM treatment of other esophageal motility disorders. The effects of medical treatment, botox injections and dilatations are often limited in patients with severe nutcracker esophagus (NE). We therefore decided to perform POEM in three patients with severe NE. MATERIAL AND METHODS: Informed consent was provided. POEM was performed under general anesthesia on the distal esophagus and upper stomach. At 3 months, 6 months and 1 year postoperatively all patients had clinical follow-up, barium swallow and high-resolution manometry. RESULTS: All patients displayed marked improvement with a significant reduction in Eckardt score at follow-up after 1 year, from 10, 10 and 11 to 3, 1 and 1, respectively. During follow-up, the patients were diagnosed with increased reflux index and one patient was diagnosed with gastroparesis. CONCLUSION: Considering our results, treating severe NE with POEM has to be considered in the future; however, further studies have to confirm this.


Subject(s)
Esophageal Motility Disorders/surgery , Esophageal Sphincter, Lower/surgery , Natural Orifice Endoscopic Surgery/methods , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mouth , Time Factors
19.
EJHaem ; 4(1): 18-25, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36819175

ABSTRACT

When screening for α-thalassemia in children, adult cut-offs for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) are generally applied to guide genetic evaluation. However, the normal ranges for MCV and MCH are lower in children than in adults, so we hypothesized that using age-matched cut-offs could lead to a more rational diagnostic strategy. The aim of this study was to evaluate if age-matched cut-offs could be applied advantageously. Data on children referred to a hemoglobin fractionation at the Department of Clinical Biochemistry, Aarhus University Hospital between 2016-2021 were identified in the laboratory information system. α-globin gene (HBA1/HBA2) genotyping was performed using multiplex gap-polymerase chain reaction. A total of 387 children were identified. HBA1/HBA2-genotyping was performed in 207 children (53%), and α-thalassemia was diagnosed in 47 children (23%) with -α3.7/αα being the predominant genotype (13%). We found that 23 children had MCV and MCH levels in the normal age-matched range, and two of these children (9%) were α+ thalassemia carriers with three functional α-globin genes. Using age-specific cut-off levels resulted in a reduction of 23 (11%) genotypes performed. In conclusion, applying age-matched cut-offs for MCV and MCH when screening children for α-thalassemia lead to 11% fewer genotypes performed while 9% carriers of α+ thalassemia (of the medically innocuous genotype -α3.7/αα) would have been overlooked.

20.
Glob Qual Nurs Res ; 10: 23333936231186599, 2023.
Article in English | MEDLINE | ID: mdl-37538194

ABSTRACT

Hospital clowns are widely used in pediatric settings. However, the field of pain and pain experience in children is complex and multifaceted. Therefore, the aim of this study was to expand knowledge on the impact and influence of hospital clowns on 4 to 15-year-old children's experiences of managing painful procedures and conditions. A convergent mixed method study was conducted integrating findings from three individual studies: a prospective non-blinded study and two focused ethnographic studies. The findings illuminated a child-clown interaction characterized by a close relationship evolving during a continuous, mutually focused attention, conceptualized as WE. This WE represent a responsive interaction between child and clown, which supported the child during the procedures, and generated three integrated findings: an age-differentiated approach; understanding the child's condition; and previous experiences as a part of the child's history. The WE approach strengthened the child's competences and ability to manage during painful procedures.

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