Attitudes toward genetic testing, family planning and preimplantation genetic testing in families with a germline CDKN2A pathogenic variant.

Individuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, and preimplantation genetic testing (PGT) in confirmed CDKN2A PV carriers and individuals with a 50% risk of the PV (at-risk carriers) using of a one-time questionnaire.A total of 537 individuals were screened for eligibility, of whom 208 of 366 (57%) confirmed carriers (56% female, median age 54 years [IQR 46-63]) and 39 of 171 (23%) at-risk carriers (59% female, median age of 26 years [IQR 22-32]) participated in the study. Primary motivations for genetic testing were to gain control over their personal and children's cancer risk, as well as increasing cancer surveillance practices. In contrast, concerns about obtaining a mortgage and life insurance were frequently cited as reasons for postponing genetic testing. Family planning decisions remained largely unaffected in both confirmed and at-risk carriers; however, the majority of confirmed carriers were still unaware of their familial or personal cancer risk when starting a family. More than 60% of the participants were unfamiliar with PGT and only a minority (19% of confirmed carriers and 10% of at-risk carriers) would be open to considering PGT as a reproductive option. This study found different attitudes toward genetic testing, family planning, and PGT among individuals affected by the CDKN2A PV. Understanding these different attitudes can help clinicians to address the complexities surrounding these issues, especially for younger individuals facing difficult decisions about the timing of genetic testing, family planning, and the potential use of assisted reproductive options.

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma.

BACKGROUND: The antibody-drug conjugates sacituzumab govitecan (SG) and enfortumab vedotin (EV) are standard monotherapies for metastatic urothelial carcinoma (mUC). Given the different targets and payloads, we evaluated the safety and efficacy of SG + EV in a phase I trial in mUC (NCT04724018). PATIENTS AND METHODS: Patients with mUC and Eastern Cooperative Oncology Group performance status ≤1 who had progressed on platinum and/or immunotherapy were enrolled. SG + EV were administered on days 1 + 8 of a 21-day cycle until progression or unacceptable toxicity. Primary endpoint was the incidence of dose-limiting toxicities during cycle 1. The number of patients treated at each of four pre-specified dose levels (DLs) and the maximum tolerated doses in combination (MTD) were determined using a Bayesian Optimal Interval design. Objective response, progression-free survival, and overall survival were secondary endpoints. RESULTS: Between May 2021 and April 2023, 24 patients were enrolled; 1 patient never started therapy and was excluded from the analysis. Median age was 70 years (range 41-88 years); 11 patients received ≥3 lines of therapy. Seventy-eight percent (18/23) of patients experienced grade ≥3 adverse event (AE) regardless of attribution at any DL, with one grade 5 AE (pneumonitis possibly related to EV). The recommended phase II doses are SG 8 mg/kg with EV 1.25 mg/kg with granulocyte colony-stimulating factor support; MTDs are SG 10 mg/kg with EV 1.25 mg/kg. The objective response rate was 70% (16/23, 95% confidence interval 47% to 87%) with three complete responses; three patients had progressive disease as best response. With a median follow-up of 14 months, 9/23 patients have ongoing response including 6 responses lasting over 12 months. CONCLUSIONS: The combination of SG + EV was assessed at different DLs and a safe dose for phase II was identified. The combination had encouraging activity in patients with mUC with high response rates, including clinically significant complete responses. Additional study of this combination is warranted.

Compliance with a novel hand hygiene protocol tailored to non-sterile healthcare workers in the operating theatre.

BACKGROUND: Observing hand hygiene compliance (HHC) among non-sterile healthcare workers (HCWs) in the operating theatre (OT) is challenging as there are no tailored protocols or observation tools. AIM: To develop and test a hand hygiene protocol tailored to non-sterile HCWs in the OT. METHODS: In this prospective observational study, nine hospitals in the Rotterdam-Rijnmond region provided input on a draft protocol on hand hygiene in the OT, resulting in a new consensus protocol for the region. An observation tool based on the protocol was developed and tested. HHC rates with 95% confidence intervals (CI) were calculated by type of hospital and type of HCW. FINDINGS: The protocol has three sections: (1) written general hand hygiene rules; (2) written hand hygiene rules specific for anaesthesia and surgery; and (3) visual representation of the OT, divided into four hand hygiene areas. Hand hygiene should be applied when changing area. Average HHC of 48.0% (95% CI 45.2-61.2%) was observed in OTs across all hospitals. HHC was highest in the two specialized hospitals (64.0%, 95% CI 30.6-89.8%; 76.7%, 95% CI 62.8-84.5%) and lowest in the academic teaching hospital (23.1%, 95% CI 0.0-45.8%). In terms of type of HCW, HHC was lowest among anaesthesiologists (31.6%, 95% CI 19.2-62.4%) and highest among OT assistants (57.4%, 95% CI 50.1-78.2%). CONCLUSION: This uniform way of observing HHC in the OT enables evaluation of the effectiveness of interventions in the OT and facilitates friendly competition. In the Rotterdam-Rijnmond region, HHC in the OT was below 50%; this needs to be addressed, particularly in teaching hospitals and among physicians.

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Transthyretin amyloid deposits in lumbar spinal stenosis and assessment of signs of systemic amyloidosis.

BACKGROUND: Wild-type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy. OBJECTIVE: To study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis. MATERIALS AND METHODS: A total of 250 patients, aged 50-89 (57% women), none with known cardiovascular disease, were included. Ligaments were investigated microscopically for amyloid. ATTR type was determined by immunohistochemistry and fibril type by Western blot. The amount of amyloid was graded 0-4. All patients with grade 3-4 ATTR deposits were offered cardiac investigation including ECG, cardiac ultrasound, plasma NT-proBNP and cardiac magnetic resonance (CMR), including modern tissue characterization. RESULTS: Amyloid was identified in 221 of the samples (88.4%). ATTR appeared in 93 samples (37%) of whom 42 (17 women and 25 men) were graded 3-4; all had fibril type A (mixture of full-length TTR and fragmented TTR). Twenty-nine of 42 patients with grade 3-4 ATTR deposits accepted cardiovascular investigations; none of them had definite signs of cardiac amyloidosis, but five men had a history of carpal tunnel syndrome. CONCLUSIONS: The prevalence of ATTR deposits in ligamentum flavum in patients with lumbar spinal stenosis was high but not associated with manifest ATTR cardiac amyloidosis. However, the findings of fibril type A, the prevalence of previous carpal tunnel syndrome and ATTR amyloid in surrounding adipose and vascular tissue indicate that amyloid deposits in ligamentum flavum may be an early manifestation of systemic ATTR disease.

Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer: Aggregate data and individual patient data meta-analyses.

PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.

Correction to: Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme.

In the published version, the Acknowledgements section was missing a funding note of co-author Dr C Verrill. The corrected version should read as follows.

Copeptin and mid-regional pro-atrial natriuretic peptide in women with suspected or confirmed pre-eclampsia: comparison with sFlt-1/PlGF ratio.

OBJECTIVES: Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) may contribute to the pathogenesis of pre-eclampsia (PE), but their role remains to be elucidated. Our aims were to evaluate the surrogates of AVP and ANP, C-terminal pro-AVP (copeptin) and mid-regional pro-ANP (MR-proANP), as biomarkers for the prediction of PE-related pregnancy complications and whether they are associated with angiogenic markers and/or clinical manifestations of PE. METHODS: This was a retrospective analysis of a prospective cohort study that enrolled pregnant women with suspected or confirmed PE, between December 2013 and April 2016. From each patient, a blood sample was obtained at study entry and serum levels of copeptin, MR-proANP, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured. We evaluated the ability of sFlt-1, PlGF, sFlt-1/PlGF ratio, copeptin and MR-proANP, assessed either alone or combined with traditional predictors (gestational age, parity, diastolic blood pressure and proteinuria), to predict maternal complications and fetal/neonatal complications. Models were compared using concordance statistic (C-index). RESULTS: A total of 526 women were evaluated in the study. Women with confirmed PE displayed elevated serum copeptin and MR-proANP levels in comparison to those with suspected PE but no hypertensive disease of pregnancy. When combined with traditional predictors, the sFlt-1/PlGF ratio displayed a higher C-index than copeptin and MR-proANP (0.76, 0.63 and 0.67, respectively, vs 0.60 for the traditional predictors alone) for the prediction of maternal complications. Similarly, for the prediction of fetal/neonatal complications, the sFlt-1/PlGF ratio displayed a higher C-index than copeptin and MR-proANP when added to the traditional model (0.83, 0.79 and 0.80, respectively, vs 0.79 for the traditional predictors alone). When subdividing women according to sFlt-1/PlGF ratio (≥ 85 vs < 85), no differences in copeptin levels were observed, while MR-proANP level was elevated in women with sFlt-1/PlGF ratio ≥ 85. Multiple regression analysis revealed that copeptin and MR-proANP were independent determinants of proteinuria. CONCLUSIONS: Copeptin and MR-proANP have limited value in predicting PE-related complications when compared with the sFlt-1/PlGF ratio. However, both copeptin and MR-proANP were associated with proteinuria, with copeptin exerting this effect independently of the sFlt-1/PlGF ratio. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Penile Paget's Disease: A Case Report and Review of the Literature.

Extramammary Paget's Disease (EMPD) is a rare cutaneous, slow growing, intraepithelial adenocarcinoma that can be either primary (intraepithelial arising within the epidermis) or secondary (intraepithelial spread of a visceral carcinoma). Here we present the case of a 63-year-old male with EMPD of the glans penis stemming from underlying urothelial carcinoma. Our treatment decision elected for management with chemotherapy and local treatment with radiation therapy. Subsequent, review of the literature demonstrated a rare disease with a variety of underlying malignancies causing this secondary pathology. Caregivers should be aware of the association of Paget's disease and urothelial cancer and should have a high index of suspicion that erythematous penile lesions may represent Paget's disease and that penile biopsies should be performed early in this setting.

Relationship between wetting and capillary pressure in a crude oil/brine/rock system: From nano-scale to core-scale.

HYPOTHESIS: The wetting behaviour is a key property of a porous medium that controls hydraulic conductivity in multiphase flow. While many porous materials, such as hydrocarbon reservoir rocks, are initially wetted by the aqueous phase, surface active components within the non-wetting phase can alter the wetting state of the solid. Close to the saturation endpoints wetting phase fluid films of nanometre thickness impact the wetting alteration process. The properties of these films depend on the chemical characteristics of the system. Here we demonstrate that surface texture can be equally important and introduce a novel workflow to characterize the wetting state of a porous medium. EXPERIMENTS: We investigated the formation of fluid films along a rock surface imaged with atomic force microscopy using ζ-potential measurements and a computational model for drainage. The results were compared to spontaneous imbibition test to link sub-pore-scale and core-scale wetting characteristics of the rock. FINDINGS: The results show a dependency between surface coverage by oil, which controls the wetting alteration, and the macroscopic wetting response. The surface-area coverage is dependent on the capillary pressure applied during primary drainage. Close to the saturation endpoint, where the change in saturation was minor, the oil-solid contact changed more than 80%.

Primary immunodeficiency in Africa - a review.

BACKGROUND: Efforts have been made worldwide to improve awareness and treatment of primary immunodeficiency (PID). This has also gained momentum on the African continent albeit at a slower pace. Objective. This review reports on the current status of PID on the African continent regarding its prevalence, distribution, genetic mutations and challenges in diagnosis and treatment of affected patients. Method. We evaluated all studies published from the African continent in the field of PID dealing with prevalence, epidemiology, case reports and genetic findings. Results. The prevalence of PID on the African continent has been estimated to be as high as 902 631 individuals. PID still is mostly underdiagnosed in Africa and although progress has been made in parts of the continent many challenges still remain regarding awareness, diagnosis, registration and care of these patients. Conclusion. Given the unique genetic mutations reported in PID patients on the African continent and the feasibility of hematopoietic stem cell transplantation and gene therapy, increased awareness should be encouraged and new therapeutic options considered.

Activated platelet aggregation is transiently impaired also by a reduced dose of protamine.

Objectives: Protamine reduces platelet aggregation after cardiopulmonary bypass (CPB). We studied the inhibitory effect of a reduced protamine dose, the duration of impaired platelet function and the possible correlation to postoperative bleeding. Design: Platelet function was assessed by impedance aggregometry in 30 patients undergoing cardiac surgery with CPB at baseline, before protamine administration, after 70% and 100% of the calculated protamine dose, after 20 minutes and at arrival to the intensive care unit. Adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used as activators. Blood loss was measured during operation and three hours after surgery. Results are presented as median (25th-75th percentile). Results: Platelet aggregation decreased markedly after the initial dose of protamine (70%) with all activators; ADP 89 (71-110) to 54 (35-78), TRAP 143 (116-167) to 109 (77-136), both p < .01; AA 25 (16-49) to 17 (12-24) and COL 92 (47-103) to 60 (38-81) U, both p < .05. No further decrease was seen after 100% protamine. The effect was transient and after twenty minutes platelet aggregation had started to recover; ADP 76 (54-106), TRAP 138 (95-158), AA 20 (10-35), COL 70 (51-93) U. Blood loss during operation correlated to aggregometry measured at baseline and after protaminization. Conclusions: Protamine after CPB induces a marked decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1. The impairment seems to be transient and recovery had started after 20 minutes.

Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme.

PURPOSE: This article describes the development of a new reproductive tissue cryopreservation clinical service for children at high risk of infertility in the NHS during times of severe financial constraints in the health service. METHOD: A development plan with two phases was drawn up. Phase 1 restricted the service to childhood cancer patients referred to the Oxford Paediatric Oncology and Haematology Principle Treatment Centre. It was estimated that there would be 10 patients/year and used existing staff and facilities from paediatric oncology, surgery, anaesthetics radiology, pathology, psychology, teenage-young adult gynaecology, and an existing Human Tissue Authority tissue bank with a licence for storage of tissue under a Human Sector Licence. Phase 2 extended the service to include children and young adults across England, Wales and Ireland-patients from Scotland having access to a research programme in Edinburgh. The main challenge in phase 2 being resources and the need for patients to be able to be treated as close to home as safely as possible. RESULTS: The Oxford team developed information resources and eligibility criteria based on published best practice, referral and treatment pathways, multidisciplinary team meetings, a network of third party sites, and a dedicated case management and database. As the programme expanded, the Oxford team was able to justify to management the need for a dedicated theatre list. Patient feedback through questionnaires, qualitative work conducted as part of a Ph.D. thesis as well as direct patient stories and interviews in TV, and radio features underpins the positive impact the programme has on patients and their families. CONCLUSION: The Oxford Reproductive Cryopreservation programme delivers fertility preservation treatment to children and young adults at high risk of infertility safely, effectively and as close to home as possible. The onward view is to apply for national funding for this programme for recognition and sustainability.

Effects of bariatric surgery on telomere length and T-cell aging.

BACKGROUND: Obesity adversely affects health and is associated with subclinical systemic inflammation and features of accelerated aging, including the T-cell immune system. The presence of metabolic syndrome (MetS) may accelerate, while bariatric surgery might reverse these phenomena. To examine the effects of MetS and bariatric surgery on T-cell aging, we measured relative telomere length (RTL) and T-cell differentiation status in obese patients before and after bariatric surgery. METHODS: WHO II/III classified obese patients scheduled for bariatric surgery were included: 41 without MetS and 67 with MetS. RTL and T-cell differentiation status were measured in circulating CD4+ and CD8+ T cells via flow cytometry. T-cell characteristics were compared between patients with and without MetS prior to and at 3, 6, and 12 months after surgery considering effects of age, cytomegalovirus-serostatus, and weight loss. RESULTS: Thymic output, represented by numbers of CD31-expressing naive T cells, showed an age-related decline in patients with MetS. MetS significantly enhanced CD8+ T-cell differentiation. Patients with MetS had significant lower CD4+ RTL than patients without MetS. Within the first 6 months after bariatric surgery, RTL increased in CD4+ T cells after which it decreased at month 12. A decline in both thymic output and more differentiated T cells was seen following bariatric surgery, more pronounced in the MetS group and showing an association with percentage of body weight loss. CONCLUSIONS: In obese patients, MetS results in attrition of RTL and accelerated T-cell differentiation. Bariatric surgery temporarily reverses these effects. These data suggest that MetS is a risk factor for accelerated aging of T cells and that MetS should be a more prominent factor in the decision making for eligibility for bariatric surgery.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Pro-IGF2-induced hypoglycaemia associated with hepatocellular carcinoma.

We present a patient (87 years, female) who was admitted to the emergency department because of loss of consciousness. Previous medical history included advanced-stage hepatocellular carcinoma and associated weight loss. She was found on the ground in an unresponsive state by her daughter and was determined to be hypoglycaemic. Upon bolus administration of 100 mL intravenous glucose (10%), glucose levels increased to 2.9 mmol/L and the patient regained full consciousness. She was admitted to the hospital for further examination, and treatment and continuous intravenous glucose infusion was initiated. As the patient was known to suffer from advanced-stage hepatocellular carcinoma, tumour-associated hypoglycaemia was suspected. Insulin, c-peptide and IGF1 concentrations were indeed low, cortisol concentration was high and IGF2 and Pro-IGF2 were borderline low and borderline high normal respectively. IGF2:IGF1 ratio was 23, confirming the diagnosis of non-islet cell tumour hypoglycaemia. During the initial phase of treatment, euglycaemia was maintained by continuous variable glucose infusion (5%, varying between 1 and 2 L/24 h), and the patient was advised to eat small snacks throughout the day. After euglycaemia was established and the diagnosis was confirmed, prednisolone was started (30 mg, 1 dd) and glucose infusions were halted. Under prednisolone treatment, glucose levels were slightly increased and no further hypoglycaemic episodes occurred. At her request, no surgery was performed. After 19 days, the patient was discharged to a hospice and died 3 weeks later. LEARNING POINTS: Hepatocellular carcinoma may be associated with non-islet cell tumour hypoglycaemia (NICTH).NICTH-induced hypoglycaemia is associated with low insulin and IGF1.Measurement of IGF2 only (without measurement of Pro-IGF2 and IGF1) may be insufficient to prove NICTH.

Physical activity increases survival after heart valve surgery.

OBJECTIVES: Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient Register and The Danish Civil Registration System of 742 eligible patients. Physical activity was quantified with the International Physical Activity Questionnaire and analysed using Kaplan-Meier analysis and Cox regression and logistic regression methods. RESULTS: Patients with a moderate to high physical activity level had a reduced risk of mortality (3 deaths in 289 patients, 1%) compared with those with a low physical activity level (13 deaths in 235 patients, 5.5%) with a fully adjusted HR of 0.19 (95% CI 0.05 to 0.70). In contrast, physical activity level was not associated with the risk of hospital readmission. Patients who participated in exercise-based cardiac rehabilitation (n=297) were more likely than the non-participants (n=200) to have a moderate or high physical activity level than a low physical activity level (fully adjusted OR: 1.52, 95% CI 1.03 to 2.24). CONCLUSIONS: Moderate to high levels of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation.

Exercise-based cardiac rehabilitation after heart valve surgery: cost analysis of healthcare use and sick leave.

BACKGROUND: Owing to a lack of evidence, patients undergoing heart valve surgery have been offered exercise-based cardiac rehabilitation (CR) since 2009 based on recommendations for patients with ischaemic heart disease in Denmark. The aim of this study was to investigate the impact of CR on the costs of healthcare use and sick leave among heart valve surgery patients over 12 months post surgery. METHODS: We conducted a nationwide survey on the CR participation of all patients having undergone valve surgery between 1 January 2011 and 30 June 2011 (n=667). Among the responders (n=500, 75%), the resource use categories of primary and secondary healthcare, prescription medication and sick leave were analysed for CR participants (n=277) and non-participants (n=223) over 12 months. A difference-in-difference analysis was undertaken. All estimates were presented as the means per patient (95% CI) based on non-parametric bootstrapping of SEs. RESULTS: Total costs during the 12 months following surgery were €16 065 per patient (95% CI 13 730 to 18 399) in the CR group and €15 182 (12 695 to 17 670) in the non-CR group. CR led to 5.6 (2.9 to 8.3, p<0.01) more outpatient visits per patient. No statistically significant differences in other cost categories or total costs €1330 (-4427 to 7086, p=0.65) were found between the groups. CONCLUSIONS: CR, as provided in Denmark, can be considered cost neutral. CR is associated with more outpatient visits, but CR participation potentially offsets more expensive outpatient visits. Further studies should investigate the benefits of CR to heart valve surgery patients as part of a formal cost-utility analysis.

High readmission rate after heart valve surgery: A nationwide cohort study.

BACKGROUND: After heart valve surgery, knowledge on long-term self-reported health status and readmission is lacking. Thus, the optimal strategy for out-patient management after surgery remains unclear. METHODS: Using a nationwide survey with linkage to Danish registers with one year follow-up, we included all adults 6-12 months after heart valve surgery irrespective of valve procedure, during Jan-June 2011 (n = 867). Participants completed a questionnaire regarding health-status (n = 742), and answers were compared with age- and sex-matched healthy controls. Readmission rates and mortality were investigated. RESULTS: After valve surgery, the self-reported health was lower (Short Form-36 (SF-36) Physical Component Scale (PCS): 44.5 vs. 50.6 and Mental Component Scale (MCS): 51.9 vs. 55.0, p < 0.0001) and more were physically sedentary compared with healthy controls (11.1% vs. 15.2%). Clinical signs of anxiety and depression were present in 13.6% and 13.8%, respectively (Hospital Anxiety and Depression Scale score ≥ 8). Twelve months following discharge, 483 persons (56%) were readmitted. Readmission was associated with lower self-reported health (SF-36 PCS: 46.5 vs. 43.9, and MCS 52.2 vs. 50.7). Higher age (hazard ratio (95% CI): 1.3 (1.0-1.6)), male sex (1.2 (1.0-1.5)), mitral valve surgery (1.3 (1.0-1.6)), and infective endocarditis after surgery (1.8 (1.1-3.0), p: 0.01) predicted readmission, whereas higher age (2.3 (1.0-5.4)), higher comorbidity score (3.2 (1.8-6.0)), and infective endocarditis after surgery (3.2 (1.2-8.9)) predicted mortality. CONCLUSIONS: 6-12 months after heart valve surgery the readmission rate is high and the self-reported health status is low. Readmission is associated with low self-reported health. Therefore, targeted follow-up strategies post-surgery are needed.