Zealand University Hospital Køge

Abstract The functions of, and interactions between, the innate and adaptive immune systems are vital for anticancer immunity. Cytotoxic T cells expressing cell-surface CD8 are the most powerful effectors in the anticancer immune response and form the backbone of current successful cancer immunotherapies. Immune-checkpoint inhibitors are designed to target immune-inhibitory receptors that function to regulate the immune response, whereas adoptive cell-transfer therapies use CD8 + T cells with genetically modified receptors—chimaeric antigen receptors—to specify and enhance CD8 + T-cell functionality. New generations of cytotoxic T cells with genetically modified or synthetic receptors are being developed and evaluated in clinical trials. Furthermore, combinatory regimens might optimise treatment effects and reduce adverse events. This review summarises advances in research on the most prominent immune effectors in cancer and cancer immunotherapy, cytotoxic T cells, and discusses possible implications for future cancer treatment.

Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, Møller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from http://www.daltonprogram.org for a number of UNIX platforms.

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Chapter 4 TEP versus TAPP: which is better for the patient? Chapter 5 Laparoscopic surgery in complicated hernia: feasibility, risks, and benefits Chapter 6 Mesh size and recurrence: what is the optimal size? Chapter 7 Selection of mesh material Chapter 8 Cutting or not cutting of mesh: does it influence the recurrence rate? Chapter 9 Mesh fixation modalities: is there an association with acute or chronic pain? Chapter 10 Risk factors and prevention of acute and chronic pain Chapter 11 Urogenital complications associated with laparoscopic/endoscopic hernia repair Chapter 12 Intraperitoneal onlay mesh (IPOM) for inguinal hernia repair-still a therapeutic option? Chapter 13 Role for open preperitoneal mesh repair in the era of laparoscopic inguinal hernia repair Chapter 14 Sportsman hernia-diagnosis and treatment

BACKGROUND: Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. METHODS: We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. FINDINGS: We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603,838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528,908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5·1 million person-years (mean 8·5 years), in which 4768 events were recorded, and for stroke was 3·8 million person-years (mean 7·2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (≥55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1·13, 95% CI 1·02-1·26; p=0·02) and incident stroke (1·33, 1·11-1·61; p=0·002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1·30-1·42). We recorded a dose-response association for stroke, with RR estimates of 1·10 (95% CI 0·94-1·28; p=0·24) for 41-48 working hours, 1·27 (1·03-1·56; p=0·03) for 49-54 working hours, and 1·33 (1·11-1·61; p=0·002) for 55 working hours or more per week compared with standard working hours (ptrend<0·0001). INTERPRETATION: Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours. FUNDING: Medical Research Council, Economic and Social Research Council, European Union New and Emerging Risks in Occupational Safety and Health research programme, Finnish Work Environment Fund, Swedish Research Council for Working Life and Social Research, German Social Accident Insurance, Danish National Research Centre for the Working Environment, Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), US National Institutes of Health, British Heart Foundation.

Abstract Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data 1,2 . Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank 3 . This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation.

OBJECTIVE: Although the reasons for secondary loss of response to infliximab (IFX) maintenance therapy in Crohn's disease vary, dose intensification is usually recommended. This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure. DESIGN: Randomised, controlled, single-blind, multicentre study. 69 patients with secondary IFX failure were randomised to IFX dose intensification (5 mg/kg every 4 weeks) (n=36) or interventions based on serum IFX and IFX antibody levels using the proposed algorithm (n=33). Predefined co-primary end points at week 12 were proportion of patients responding (Crohn's Disease Activity Index (CDAI) decrease ≥ 70, or ≥ 50% reduction in active fistulas) and accumulated costs related to treatment of Crohn's disease, expressed as mean cost per patient, based on the Danish National Patient Registry for all hospitalisation and outpatient costs in the Danish healthcare sector. RESULTS: Costs for intention-to-treat patients were substantially lower (34%) for those treated in accordance with the algorithm than by IFX dose intensification: € 6038 vs € 9178, p<0.001. However, disease control, as judged by response rates, was similar: 58% and 53%, respectively, p=0.81; difference 5% (-19% to 28%). For per-protocol patients, treatment costs were even lower (56%) in the algorithm-treated group (€ 4062 vs € 9178, p<0.001) and with similar response rates (47% vs 53%, p=0.78; difference -5% (-33% to 22%)). CONCLUSIONS: Treatment of secondary IFX failure using an algorithm based on combined IFX and IFX antibody measurements significantly reduces average treatment costs per patient compared with routine IFX dose escalation and without any apparent negative effect on clinical efficacy. TRIAL REGISTRATION NO: NCT00851565.

Udgivelsesdato: 2010-Aug

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, Setting, and Participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main Outcomes and Measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P = .02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care. Conclusions and Relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care. Trial Registration: trialregister.nl Identifier: NTR5947.

Importance: Prosthetic mesh is frequently used to reinforce the repair of abdominal wall incisional hernias. The benefits of mesh for reducing the risk of hernia recurrence or the long-term risks of mesh-related complications are not known. Objective: To investigate the risks of long-term recurrence and mesh-related complications following elective abdominal wall hernia repair in a population with complete follow-up. Design, Setting, and Participants: Registry-based nationwide cohort study including all elective incisional hernia repairs in Denmark from January 1, 2007, to December 31, 2010. A total of 3242 patients with incisional repair were included. Follow-up until November 1, 2014, was obtained by merging data with prospective registrations from the Danish National Patient Registry supplemented with a retrospective manual review of patient records. A 100% follow-up rate was obtained. Exposures: Hernia repair using mesh performed by either open or laparoscopic techniques vs open repair without use of mesh. Main Outcomes and Measures: Five-year risk of reoperation for recurrence and 5-year risk of all mesh-related complications requiring subsequent surgery. Results: Among the 3242 patients (mean age, 58.5 [SD, 13.5] years; 1720 women [53.1%]), 1119 underwent open mesh repair (34.5%), 366 had open nonmesh repair (11.3%), and 1757 had laparoscopic mesh repair (54.2%). The median follow-up after open mesh repair was 59 (interquartile range [IQR], 44-80) months, after nonmesh open repair was 62 (IQR, 44-79) months, and after laparoscopic mesh repair was 61 (IQR, 48-78) months. The risk of the need for repair for recurrent hernia following these initial hernia operations was lower for patients with open mesh repair (12.3% [95% CI, 10.4%-14.3%]; risk difference, -4.8% [95% CI, -9.1% to -0.5%]) and for patients with laparoscopic mesh repair (10.6% [95% CI, 9.2%-12.1%]; risk difference, -6.5% [95% CI, -10.6% to -2.4%]) compared with nonmesh repair (17.1% [95% CI, 13.2%-20.9%]). For the entirety of the follow-up duration, there was a progressively increasing number of mesh-related complications for both open and laparoscopic procedures. At 5 years of follow-up, the cumulative incidence of mesh-related complications was 5.6% (95% CI, 4.2%-6.9%) for patients who underwent open mesh hernia repair and 3.7% (95% CI, 2.8%-4.6%) for patients who underwent laparoscopic mesh repair. The long-term repair-related complication rate for patients with an initial nonmesh repair was 0.8% (open nonmesh repair vs open mesh repair: risk difference, 5.3% [95% CI, 4.4%-6.2%]; open nonmesh repair vs laparoscopic mesh repair: risk difference, 3.4% [95% CI, 2.7%-4.1%]). Conclusions and Relevance: Among patients undergoing incisional repair, sutured repair was associated with a higher risk of reoperation for recurrence over 5 years compared with open mesh and laparoscopic mesh repair. With long-term follow-up, the benefits attributable to mesh are offset in part by mesh-related complications.

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.

OBJECTIVE: The aim of this study was to determine the accuracy of the diagnosis of gastro-oesophageal reflux disease (GORD) by the Reflux Disease Questionnaire (RDQ), family practitioners, gastroenterologists and a test of esomeprazole therapy. METHODS: This was a single-blind, single-arm study over 3-4 weeks from September 2005 to November 2006. Each symptom-based diagnostic assessment was made blinded to prior diagnoses. Patients were those presenting to their family practitioner with troublesome upper gastrointestinal symptoms (n=308). The RDQ was completed and a symptom-based diagnosis was made by the family practitioner. Placebo esomeprazole was started. Gastroenterologists made a symptom-based diagnosis and then performed endoscopy with 48 h oesophageal pH and symptom association monitoring to determine the presence/absence of GORD. Symptoms were recorded during treatment with 40 mg of esomeprazole for 2 weeks. The main outcome measure was RDQ scoring for the presence of GORD compared with symptom-based diagnosis by family physicians and gastroenterologists. RESULTS: GORD was present in 203/308 (66%) patients. Only 49% of the patients with GORD selected either heartburn or regurgitation as the most troublesome symptom. Sensitivity and specificity, respectively, of the symptom-based diagnosis of GORD, were 62% and 67% for the RDQ, 63% and 63% for family practitioners, and 67% and 70% for gastroenterologists. Symptom response to esomeprazole was neither sensitive nor specific for the diagnosis of GORD. CONCLUSIONS: The RDQ, family practitioners and gastroenterologists have moderate and similar accuracy for diagnosis of GORD. Symptom response to a 2 week course of 40 mg of esomeprazole does not add diagnostic precision.

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients' functional capacity and postoperative complications. METHODS/DESIGN: This international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis. DISCUSSION: Multimodal prehabilitation is expected to enhance patients' functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer. TRIAL REGISTRATION: Trial Registry: NTR5947 - date of registration: 1 August 2016.

BACKGROUND: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS: In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS: A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS: Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).

OBJECTIVE: To quantify the association between long working hours and alcohol use. DESIGN: Systematic review and meta-analysis of published studies and unpublished individual participant data. DATA SOURCES: A systematic search of PubMed and Embase databases in April 2014 for published studies, supplemented with manual searches. Unpublished individual participant data were obtained from 27 additional studies. REVIEW METHODS: The search strategy was designed to retrieve cross sectional and prospective studies of the association between long working hours and alcohol use. Summary estimates were obtained with random effects meta-analysis. Sources of heterogeneity were examined with meta-regression. RESULTS: Cross sectional analysis was based on 61 studies representing 333,693 participants from 14 countries. Prospective analysis was based on 20 studies representing 100,602 participants from nine countries. The pooled maximum adjusted odds ratio for the association between long working hours and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross sectional analysis of published and unpublished data. Odds ratio of new onset risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective published and unpublished data. In the 18 studies with individual participant data it was possible to assess the European Union Working Time Directive, which recommends an upper limit of 48 hours a week. Odds ratios of new onset risky alcohol use for those working 49-54 hours and ≥ 55 hours a week were 1.13 (1.02 to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01 to 1.25; adjusted difference in incidence 0.7 percentage points), respectively, compared with working standard 35-40 hours (incidence of new onset risky alcohol use 6.2%). There was no difference in these associations between men and women or by age or socioeconomic groups, geographical regions, sample type (population based v occupational cohort), prevalence of risky alcohol use in the cohort, or sample attrition rate. CONCLUSIONS: Individuals whose working hours exceed standard recommendations are more likely to increase their alcohol use to levels that pose a health risk.

OBJECTIVES: To test the reliability of new ultrasound (US) definitions and quantification of synovial hypertrophy (SH) and power Doppler (PD) signal, separately and in combination, in a range of joints in patients with rheumatoid arthritis (RA) using the European League Against Rheumatisms-Outcomes Measures in Rheumatology (EULAR-OMERACT) combined score for PD and SH. METHODS: A stepwise approach was used: (1) scoring static images of metacarpophalangeal (MCP) joints in a web-based exercise and subsequently when scanning patients; (2) scoring static images of wrist, proximal interphalangeal joints, knee and metatarsophalangeal joints in a web-based exercise and subsequently when scanning patients using different acquisitions (standardised vs usual practice). For reliability, kappa coefficients (κ) were used. RESULTS: Scoring MCP joints in static images showed substantial intraobserver variability but good to excellent interobserver reliability. In patients, intraobserver reliability was the same for the two acquisition methods. Interobserver reliability for SH (κ=0.87) and PD (κ=0.79) and the EULAR-OMERACT combined score (κ=0.86) were better when using a 'standardised' scan. For the other joints, the intraobserver reliability was excellent in static images for all scores (κ=0.8-0.97) and the interobserver reliability marginally lower. When using standardised scanning in patients, the intraobserver was good (κ=0.64 for SH and the EULAR-OMERACT combined score, 0.66 for PD) and the interobserver reliability was also good especially for PD (κ range=0.41-0.92). CONCLUSION: The EULAR-OMERACT score demonstrated moderate-good reliability in MCP joints using a standardised scan and is equally applicable in non-MCP joints. This scoring system should underpin improved reliability and consequently the responsiveness of US in RA clinical trials.

BACKGROUND: There is heterogeneity in the names and anatomical descriptions of regional anesthetic techniques. This may have adverse consequences on education, research, and implementation into clinical practice. We aimed to produce standardized nomenclature for abdominal wall, paraspinal, and chest wall regional anesthetic techniques. METHODS: We conducted an international consensus study involving experts using a three-round Delphi method to produce a list of names and corresponding descriptions of anatomical targets. After long-list formulation by a Steering Committee, the first and second rounds involved anonymous electronic voting and commenting, with the third round involving a virtual round table discussion aiming to achieve consensus on items that had yet to achieve it. Novel names were presented where required for anatomical clarity and harmonization. Strong consensus was defined as ≥75% agreement and weak consensus as 50% to 74% agreement. RESULTS: Sixty expert Collaborators participated in this study. After three rounds and clarification, harmonization, and introduction of novel nomenclature, strong consensus was achieved for the names of 16 block names and weak consensus for four names. For anatomical descriptions, strong consensus was achieved for 19 blocks and weak consensus was achieved for one approach. Several areas requiring further research were identified. CONCLUSIONS: Harmonization and standardization of nomenclature may improve education, research, and ultimately patient care. We present the first international consensus on nomenclature and anatomical descriptions of blocks of the abdominal wall, chest wall, and paraspinal blocks. We recommend using the consensus results in academic and clinical practice.

Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials.

BACKGROUND: Injection therapies are often considered alongside exercise for chronic midportion Achilles tendinopathy (AT), although evidence of their efficacy is sparse. PURPOSE: To determine whether eccentric training in combination with high-volume injection (HVI) or platelet-rich plasma (PRP) injections improves outcomes in AT. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 60 men (age, 18-59 years) with chronic (>3 months) AT were included and followed for 6 months (n = 57). All participants performed eccentric training combined with either (1) one HVI (steroid, saline, and local anesthetic), (2) four PRP injections each 14 days apart, or (3) placebo (a few drops of saline under the skin). Randomization was stratified for age, function, and symptom severity (Victorian Institute of Sports Assessment-Achilles [VISA-A]). Outcomes included function and symptoms (VISA-A), self-reported tendon pain during activity (visual analog pain scale [VAS]), tendon thickness and intratendinous vascularity (ultrasonographic imaging and Doppler signal), and muscle function (heel-rise test). Outcomes were assessed at baseline and at 6, 12, and 24 weeks of follow-up. RESULTS: VISA-A scores improved in all groups at all time points ( P < .05), with greater improvement in the HVI group (mean ± SEM, 6 weeks = 27 ± 3 points; 12 weeks = 29 ± 4 points) versus PRP (6 weeks = 14 ± 4; 12 weeks = 15 ± 3) and placebo (6 weeks = 10 ± 3; 12 weeks = 11 ± 3) at 6 and 12 weeks ( P < .01) and in the HVI (22 ± 5) and PRP (20 ± 5) groups versus placebo (9 ± 3) at 24 weeks ( P < .01). VAS scores improved in all groups at all time points ( P < .05), with greater decrease in HVI (6 weeks = 49 ± 4 mm; 12 weeks = 45 ± 6 mm; 24 weeks = 34 ± 6 mm) and PRP (6 weeks = 37 ± 7 mm; 12 weeks = 41 ± 7 mm; 24 weeks = 37 ± 6 mm) versus placebo (6 weeks = 23 ± 6 mm; 12 weeks = 30 ± 5 mm; 24 weeks = 18 ± 6 mm) at all time points ( P < .05) and in HVI versus PRP at 6 weeks ( P < .05). Tendon thickness showed a significant decrease only in HVI and PRP groups during the intervention, and this was greater in the HVI versus PRP and placebo groups at 6 and 12 weeks ( P < .05) and in the HVI and PRP groups versus the placebo group at 24 weeks ( P < .05). Muscle function improved in the entire cohort with no difference between the groups. CONCLUSION: Treatment with HVI or PRP in combination with eccentric training in chronic AT seems more effective in reducing pain, improving activity level, and reducing tendon thickness and intratendinous vascularity than eccentric training alone. HVI may be more effective in improving outcomes of chronic AT than PRP in the short term. Registration: NCT02417987 ( ClinicalTrials.gov identifier).

INTRODUCTION: Groin hernia repair is a commonly performed surgical procedure in the western world but large-scaled epidemiologic data are sparse. Large-scale data on the occurrence of groin hernia repair may provide further understanding to the pathophysiology of groin hernia development. This study was undertaken to investigate the age and gender dependent prevalence of groin hernia repair. METHODS: In a nationwide register-based study, using data from the Civil Registration System covering all Danish citizens, we established a population-based cohort of all people living in Denmark on December 31(st), 2010. Within this population all groin hernia repairs during the past 5 years were identified using data from the ICD 10(th) edition in the Danish National Hospital Register. RESULTS: The study population covered n = 5,639,885 persons. During the five years study period 46,717 groin hernia repairs were performed (88.6% males, 11.4% females). Inguinal hernias comprised 97% of groin hernia repairs (90.2% males, 9.8% females) and femoral hernias 3% of groin hernia repairs (29.8% males, 70.2% females). Patients between 0-5 years and 75-80 years constituted the two dominant groups for inguinal hernia repair. In contrast, the age-specific prevalence of femoral hernia repair increased steadily throughout life peaking at age 80-90 years in both men and women. CONCLUSION: The age distribution of inguinal hernia repair is bimodal peaking at early childhood and old age, whereas the prevalence of femoral hernia repair increased steadily throughout life. This information can be used to formulate new hypotheses regarding disease etiology with regard to age and gender specifications.