Dupilumab responder types and predicting factors in patients with type 2 severe asthma: A real-world cohort study.

BACKGROUND: Severe asthma (SA) presents a considerable healthcare challenge despite optimal standard treatment. Dupilumab, which is effective in type 2 (T2) SA patients, demonstrates variable responses, categorizing patients as non-responders, partial responders, or those achieving clinical remission. However, real-world response rates remain underexplored. Additionally, understanding the characteristics of patients achieving clinical remission is crucial for predicting favourable responses to dupilumab. OBJECTIVE: To investigate responder types and identify predictors of clinical remission and non-response induced by dupilumab in a real-world cohort of SA patients. METHODS: We analyzed retrospective data from SA patients undergoing dupilumab treatment in a study conducted at Franciscus Gasthuis & Vlietland hospital. Data were collected at baseline and at a 12 to 24-months follow-up (T = 12). Response rates were evaluated at T = 12. Predictors of non-response and clinical remission were investigated using multivariate logistic regression analysis with a stepwise forward variable selection approach. RESULTS: Among the 175 patients screened, 136 met the inclusion criteria. At T = 12, 31.6 % achieved clinical remission, 47.1 % were partial responders and 21.3 % were non-responders. Predictors associated with clinical remission included high baseline blood eosinophil counts (BEC) and male sex. Conversely, younger age at baseline, low baseline total immunoglobin E (IgE) and low baseline fractional exhaled nitric oxide (FeNO) levels were identified as predictors of non-response. CONCLUSIONS: Dupilumab results in clinical disease remission in one-third of the treated patients. Clinical remission is predicted by high BEC and male sex, whereas low total IgE, low FeNO and younger age indicate a lower likelihood of response.

Anti-IL-5/5Ra biologics improve work productivity and activity in severe asthma: a RAPSODI registry-based cohort study.

INTRODUCTION: Severe asthma is associated with a serious disease burden, partially caused by limitations in activity and work impairment. AIMS AND OBJECTIVES: This study aims to relate treatment with biologics targeting IL-5/5Ra to work productivity and activity in the long term in a real-world context. MATERIAL AND METHODS: This is a registry-based multi-center cohort study evaluating data from adults with severe eosinophilic asthma included in the Dutch Register of Adult Patients with Severe Asthma for Optimal DIsease management (RAPSODI). Patients that started with anti-IL-5/5Ra biologics and completed the work productivity and activity improvement questionnaire, were included. Study and patient characteristics were compared between the employed and unemployed patients. Work productivity and activity impairment are related to accompanying improvements in clinical outcomes. RESULTS: At baseline, 91 of 137 patients (66%) were employed which remained stable throughout the follow-up period. Patients in the working age category were younger and had significantly better asthma control (p = 0.02). Mean overall work impairment due to health decreased significantly from 25.5% (SD2.6) to 17.6% (SD 2.8) during 12 months anti-IL-5/5Ra biologics treatment (P = 0.010). There was a significant association between ACQ6 and overall work improvement after targeted therapy (ß = 8.7, CI 2.1-15.4, P = 0.01). The improvement of asthma control of 0.5 points on the asthma Control Questionnaire was associated with an overall work impairment of -9%. CONCLUSIONS: Work productivity and activity in severe eosinophilic asthma improved after starting anti-IL-5/5Ra biologics. Clinically relevant improvement in asthma control was associated with an overall work impairment score of -9% in this study.

The impact of the covid-19 pandemic on diabetes care: the perspective of healthcare providers across Europe.

AIMS: Covid-19 caused changes on the delivery of diabetes care. This study aimed to explore perceptions of healthcare providers across Europe concerning 1) the impact of covid-19 on delivery of diabetes care; 2) impact of changes in diabetes care on experienced workload; 3) experiences with video consultation in diabetes care. METHODS: Cross-sectional survey among healthcare providers in the Netherlands, United Kingdom, Turkey, Ukraine and Sweden, with a focus on primary care. RESULTS: The survey was completed by 180 healthcare providers. During the COVID-19 pandemic 57.1% of respondents provided less diabetes care and 72.8% observed a negative impact on people with diabetes. More than half of respondents (61.9%) expressed worries to some extent about getting overloaded by work. Although the vast majority considered their work meaningful (85.6%). Almost half of healthcare providers (49.4%) thought that after the pandemic video-consultation could be blended with face-to-face contact. CONCLUSIONS: Less diabetes care was delivered and a negative impact on people with diabetes was observed by healthcare providers. Despite healthcare providers' feeling overloaded, mental wellbeing seemed unaffected. Video consultations were seen as having potential. Given the remaining covid-19 risks and from the interest of proactive management of people with diabetes, these findings urge for further exploration of incorporating video consultation in diabetes care.

ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

Incretin responses to oral glucose and mixed meal tests and changes in fasting glucose levels during 7 years of follow-up: The Hoorn Meal Study.

We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus.

Individual and partner's level of occupation and the association with HbA1c levels in people with Type 2 diabetes mellitus: the Dutch Diabetes Pearl cohort.

AIMS: Individual indicators of socio-economic status have been associated with glycaemic control in people with Type 2 diabetes, but little is known about the association between partner's socio-economic status and HbA1c levels. We therefore examined the cross-sectional association between individual and partner's level of occupation on HbA1c levels in people with Type 2 diabetes in the Netherlands. METHODS: We included people with Type 2 diabetes with a partner who were treated in primary, secondary and tertiary care in the Diabetes Pearl cohort. Occupational level was classified according to International Standard Classification of Occupations (ISCO)-08 skill levels. Linear regression analyses were performed stratified for sex, and corrected for age, recruitment centre and diabetes medication. RESULTS: In total, 3257 participants (59.8% men, mean 62.2±9.4 years) were included. For men, having a partner with an intermediate level of occupation was associated with lower HbA1c levels [e.g. ISCO level 3: -2 mmol/mol (95% CI -4;-1) or -0.2% (95% CI -0.4;-0.1)], compared with having a partner of the highest occupational level (ISCO level 4). In women, having an unemployed partner was associated with higher HbA1c levels [14 mmol/mol (95% CI 6; 22) or 1.3% (95% CI 0.6; 2.0)], compared with having a partner of the highest occupational level. CONCLUSIONS: Partner's occupational status provided additional information on the association between socio-economic status and HbA1c levels in people with Type 2 diabetes. Women seemed to benefit from a partner with a higher occupational status, while men seemed to benefit from a partner with a lower status. Because of the cross-sectional nature of the present study, more research is necessary to explore this association.

The Use of Antidepressants, Anxiolytics, and Hypnotics in People with Type 2 Diabetes and Patterns Associated with Use: The Hoorn Diabetes Care System Cohort.

Objective. With depression being present in approximately 20% of people with type 2 diabetes mellitus (T2DM), we expect equally frequent prescription of antidepressants, anxiolytics, and hypnotics. Nevertheless, prescription data in people with T2DM is missing and the effect of depression on glycaemic control is contradictory. The aim of this study was to assess the prevalence of antidepressants, anxiolytics, and/or hypnotics use in a large, managed, primary care system cohort of people with T2DM and to determine the sociodemographic characteristics, comorbidities, T2DM medication, and metabolic control associated with its use. Method. The prevalence of antidepressants, anxiolytics, and/or hypnotics use in the years 2007-2012 was assessed in the Hoorn Diabetes Care System Cohort from the Netherlands. Results. From the 7016 people with T2DM, 500 people (7.1%) used antidepressants only, 456 people (6.5%) used anxiolytics and/or hypnotics only, and 254 people (3.6%) used a combination. Conclusion. We conclude that in our managed, primary care system 17% of all people with T2DM used antidepressants, anxiolytics, and/or hypnotics. Users of antidepressants, anxiolytics, and/or hypnotics were more often female, non-Caucasian, lower educated, and more often treated with insulin.

A Retrospective Study looking at Admissions Characteristics of Patients admitted to an Oncology Ward in Luxembourg.

Our study set out to monitor all admissions admitted to an oncology ward over a period of 60 days between 20/10/14 and 18/12/14. We wanted to analyse the reasons for admission, in order to identify treatment related complications and other preventable causes for inpatient admission.

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

BACKGROUND: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. PATIENTS AND METHODS: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). RESULTS: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). CONCLUSION: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. TRIAL REGISTRATION: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.

Robotic transanal minimally invasive surgery for local excision of rectal neoplasms.

BACKGROUND: Robotic transanal minimally invasive surgery (TAMIS) may be an option for rectum-preserving excision of neoplasms. Recent cadaveric studies showed improved vision, control and manoeuvrability compared with use of laparoscopic instruments. This study reports the clinical application. METHODS: Consecutive patients eligible for transanal endoscopic microsurgery (TEM) or TAMIS in three participating centres were operated on using a robotic platform and transanal glove port. Patient demographics, lesion characteristics, perioperative data, complications and follow-up of all patients were recorded prospectively. RESULTS: Sixteen patients underwent robotic TAMIS for rectal lesions with a median (range) distance from the anal verge of 8 (range 3-10) cm. The median size of the resected specimen was 5·3 (0·5-21) cm(2) . The median docking time and duration of operation were 36 (18-75) and 108 (40-180) min respectively. One conversion to regular (non-robotic) TAMIS was needed owing to difficulties accessing the rectum. Glove puncture necessitated replacement in four procedures, an unstable pneumorectum arose during one operation and one patient developed a pneumoperitoneum. One patient required catheterization for urinary retention. The median hospital stay was 1·3 (0-4) days. The additional cost of the robotic approach was approximately €1000 per procedure (excluding the capital expenditure on the robotic system and its maintenance). CONCLUSION: Robotic TAMIS is feasible in patients with rectal lesions. Potential advantages over TEM and non-robotic TAMIS will need to be balanced against the cost of the robotic system.

Preclinical cadaveric study of transanal endoscopic da Vinci® surgery.

BACKGROUND: Single-port platforms are increasingly being used for transanal surgery and may be associated with a shorter learning curve than transanal endoscopic microsurgery. However, these procedures remain technically challenging, and robotic technology could overcome some of the limitations and increase intraluminal manoeuvrability. An initial experimental experience with transanal endoscopic da Vinci(®) surgery (TEdS) using a glove port on human cadavers is reported. METHODS: After initial dry laboratory experiments, the feasibility of TEdS and ideal set-up were further evaluated in human cadavers. For transanal access a glove port was constructed on-table by using a circular anal dilator, a standard wound retractor and a surgical glove. A da Vinci(®) Si HD system was used in combination with the glove port for transanal endoscopic resections. RESULTS: It was possible to perform all necessary tasks to complete a full-thickness excision and closure of the rectal wall, with cadavers in both prone and supine positions. The stable magnified view, combined with the EndoWrist(®) technology of the robotic instruments, made every task straightforward. Intraluminal manoeuvrability could be improved further by intersecting the robotic instruments. The glove port proved to be very reliable and the inherent flexibility of the glove facilitated docking of the robotic arms in a narrow confined space. CONCLUSION: Using a reliable and universally available glove port, TEdS was feasible and a preferred set-up was determined. Further clinical trials will be necessary to assess the safety and efficacy of this technique.

Incidence of small-bowel obstruction and adhesiolysis after open colorectal and general surgery.

PURPOSE: The study contained herein was undertaken to establish the incidence of small-bowel obstruction, adhesiolysis for obstruction, and additional abdominal surgery after open colorectal and general surgery. METHODS: A retrospective cohort study was performed using patient-specific Health Care Financing Administration data to evaluate a random 5 percent sample of all Medicare patients who underwent surgery in 1993. Of these, 18,912 patients had an index abdominal procedure. Two-year follow-up data documented outcomes of hospitalizations with obstruction, adhesiolysis for obstruction, and/or additional open colorectal or general surgery. RESULTS: Within two years of incision, excision, and anastomosis of intestine (International Classification of Dis eases (ICD)-9 code 45), 14.3 percent of patients had obstructions, 2.6 percent required adhesiolysis for obstructions, and 12.9 percent underwent additional open colorectal or general surgery. After other operations of intestine (ICD code 46), 17 percent of patients had obstructions, 3.1 percent required adhesiolysis for obstructions, and 20.2 percent underwent additional open colorectal or general surgery. After operations of rectum, rectosigmoid, and perirectal tissue (ICD code 48), 15.3 percent of patients had obstructions, 5.1 percent required adhesiolysis for obstructions, and 16.4 percent underwent additional open colorectal or general surgery. After other operations on the abdominal region (ICD code 54), 12.4 percent of patients had obstructions, 2.3 percent required adhesiolysis for obstructions, and 8.8 percent underwent additional open colorectal or general surgery. CONCLUSIONS: In this retrospective study of Medicare patients, we learned that bowel obstruction, adhesiolysis for obstructions, and additional abdominal surgery occurred more often after abdominal surgery than was previously published.

Complications and hospitalisation--duration after chemoembolisation for liver metastases.

In a retrospective study, all patients of the hemato-oncology department of the Centre Hospitalier who were treated from 1988 to 1997 by chemoembolisation for liver metastases were analysed for treatment-related hospitalisation duration, side effects and complications, in order to assess the treatment burden. Major side-effects were: pain in 17 of 29 patients, nausea in 8, vomiting in 7, persistent hickup in 3, fever in 12, a temporary confusional state in 4 patients. 1 patient experienced syncope, 2 patients developed homolateral pleral effusions, 1 patient suffered transient supraventricular arrhythmias. Major complications included 1 hemoperitoneum (under anticoagulant therapy), 1 hemorrhagic gastritis, 1 acute cholecystitis due to inflammatory tumoral choledochal obstruction and one iatrogenous acute pancreatic ischemic necrosis. Two patients died of post-embolic acute hepatic insufficiency, one 10 days, one 41 days after the last treatment session). In summary, chemo-embolisation of liver metastases is a complication-burdened treatment in a strictly palliative setting with inestimable efficacy. The treatment modalities have to be discussed with the patient beforehand and preferably in controlled study setting. Large randomised trials may indicate patients' subgroups for benefit.

[Cholesterol embolism: an often unknown disease; a report of two cases]. / La maladie à embols de cholestérol: une pathologie souvent méconnue; à propos de deux cas.

We report on a case of post-invasive acute renal insufficiency and a case of acute necrotizing pancreatitis, both histologically proven to have been caused by cholesterol embolisms. A survey of the literature with discussion of diagnostic and therapeutic options is given.

[Spontaneous regression of pulmonary metastases in renal cancer]. / Régression spontanée de métastases pulmonaires d'un cancer rénal.

Spontaneous regression of lung-metastases in kidney cancer (a case report) A case is reported of a 56-year old woman with renal cell carcinoma operated and treated adjuvantly for a year with Interferon alpha. Ten months thereafter the patient had histologically proven a large pulmonary metastatic disease that regressed spontaneously. Duration of the spontaneous remission was 8 months.

[New diagnostic approaches to deep venous thrombosis]. / Nouvelles approches diagnostiques des thromboses veineuses profondes.

This review summarizes a number of recent articles reconsidering the use of phlebography as the golden standard for deep venous thrombosis. Compression ultrasound and color-coded duplex doppler seem to be reasonably sensitive to provide safety in detecting lower limb thrombosis while less invasive. A clinical risk factor panel may further enhance diagnostic security.

Characterization of a basic transthyretin variant--TTR Arg 102--in the German population.

A basic transthyretin (TTR) variant, apparently non-pathogenic, has been reported in a German family. Protein analysis of this TTR variant revealed the substitution of arginine for proline at position 102 of the TTR polypeptide chain. This result was confirmed by DNA analysis of PCR amplified DNA.