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Objectives Type I IFN (IFN-I) activation is a prominent feature of primary SS (pSS), SLE and SSc. Ultrasensitive single-molecule array (Simoa) technology has facilitated the measurement of subfemtomolar concentrations of IFNs. Here we aimed to measure IFN-α2 in serum from pSS, SLE and SSc using a Simoa immunoassay and correlate these levels to blood IFN-stimulated gene (ISG) expression and disease activity. Methods Serum IFN-α2 was measured in patients with pSS (n = 85 and n = 110), SLE (n = 24) and SSc (n = 23) and healthy controls (HCs; n = 68) using an IFN-α Simoa assay on an HD-X analyser. IFN-I pathway activation was additionally determined from serum by an IFN-I reporter assay and paired samples of whole blood ISG expression of IFI44, IFI44L, IFIT1, IFIT3 and MxA by RT-PCR or myxovirus resistance protein 1 (MxA) protein ELISA. Results Serum IFN-α2 levels were elevated in pSS (median 61.3 fg/ml) compared with HCs (median ≤5 fg/ml, P Conclusion Simoa serum IFN-α2 reflects blood ISG expression in pSS, SLE and SSc. In light of IFN-targeting treatments, Simoa could potentially be applied for patient stratification or retrospective analysis of historical cohorts.

ObjectiveIn newly diagnosed paediatric patients with moderate-to-severe Crohn’s disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment.DesignIn this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3–17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI Results100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was not significantly different (p=0.421). However, 19/46 (41%) patients in the FL-IFX group were in clinical remission on azathioprine monotherapy without need for treatment escalation vs 7/48 (15%) in the conventional group (p=0.004).ConclusionsFL-IFX was superior to conventional treatment in achieving short-term clinical and endoscopic remission, and had greater likelihood of maintaining clinical remission at week 52 on azathioprine monotherapy.Trial registration numberClinicalTrials.gov Registry (NCT02517684).

Purpose Small, hypoattenuating, indeterminate liver lesions are often encountered during staging computed tomography (CT) in patients with early-stage rectal cancer. This study aimed to determine the incidence and prognostic significance of these lesions. Methods and Materials A single institution's colorectal cancer (CRC) database was searched for patients with early-stage rectal cancer, defined as a cT1-2N0 tumor on magnetic resonance imaging (MRI). Abdominal CT scans of these patients were assessed for the presence of liver lesions and categorized according to their morphology. Preoperative MRI scans of the liver and abdominal follow-up imaging were assessed to determine whether the liver lesions found during staging CT appeared to be CRC metastases or not. Results In a consecutive cohort of 1232 patients with CRC who had undergone surgery, 84 patients with early-stage rectal cancer (cT1-2N0 on MRI) were identified. Of those 84 patients, 45 (54%) had 1 or more liver lesions on staging CT; a total of 122 liver lesions were observed, consisting of 95 indeterminate lesions (78%), 25 cysts (20%), and 2 hemangiomas (2%). Preoperative MRI of the liver and regular follow-up imaging revealed no synchronous or metachronous liver metastases in this cohort. Conclusions In this study, small, hypoattenuating, indeterminate lesions of the liver were common in patients diagnosed with early rectal cancer and seemed to have no clinical significance. Additional preoperative imaging or follow-up imaging for indeterminate liver lesions in such patients may be unnecessary.

Contains fulltext : 244716.pdf (Publisher’s version ) (Open Access) RESEARCH QUESTION: How do infertility patients, endometriosis patients and health-care providers rate virtual care as an alternative to physical consultations during the first lockdown of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands, and how does this influence quality of life and quality of care? DESIGN: Infertility patients and endometriosis patients from a university hospital and members of national patient organizations, as well as healthcare providers in infertility and endometriosis care, were asked to participate between May and October 2020. The distributed online questionnaires consisted of an appraisal of virtual care and an assessment of fertility-related quality of life (FertiQol) and patient-centredness of endometriosis care (ENDOCARE). RESULTS: Questionnaires were returned by 330 infertility patients, 181 endometriosis patients and 101 healthcare providers. Of these, 75.9% of infertility patients, 64.8% of endometriosis patients and 80% of healthcare providers rated telephone consultations as a good alternative to physical consultations during the COVID-19-pandemic. Only 21.3%, 14.8% and 19.2% of the three groups rated telephone consultations as a good replacement for physical consultations in the future. A total of 76.6% and 35.9% of the infertility and endometriosis patients reported increased levels of stress during the pandemic. Infertility patients scored lower on the FertiQol, while the ENDOCARE results care seem comparable to the reference population. CONCLUSIONS: Virtual care seems to be a good alternative for infertility and endometriosis patients in circumstances where physical consultations are not possible. Self-reported stress is especially high in infertility patients during the COVID-19-pandemic. Healthcare providers should aim to improve their patients' ability to cope.

Purpose Patient-reported outcomes (PROs) are pivotal to evaluate the efficacy of surgical management. Debate persists on the optimal surgical technique to repair incisional hernias. Assessment of PROs can guide the selection of the best management of patients with incisional hernias. The objective of this cohort study was to present the PROs after incisional hernia repair at long term follow-up. Methods Patients with a history of incisional hernia repair were seen at the out-patient clinic to collect PROs. Patients were asked about the preoperative indication for repair and postoperative symptoms, such as pain, feelings of discomfort, and bulging of the abdominal wall. Additionally, degree of satisfaction was asked and Carolina Comfort Scales were completed. Results Two hundred and ten patients after incisional hernia repair were included with a median follow-up of 3.2 years. The main indication for incisional hernia repair was the presence of a bulge (60%). Other main reasons for repair were pain (19%) or discomfort (5%). One hundred and thirty-two patients (63%) reported that the overall status of their abdominal wall had improved after the operation. Postoperative symptoms were reported by 133 patients (63%), such as feelings of discomfort, pain and bulging. Twenty percent of patients reported that the overall status of their abdominal wall was the same, and 17% reported a worse status, compared to before the operation. Ten percent of the patients would not opt for operation in hindsight. Conclusion This study showed that a majority of the patients after incisional hernia repair still report pain or symptoms such as feelings of discomfort, pain, and bulging of the abdominal wall 3 years after surgery. Embedding patients’ expectations and PROs in the preoperative counseling discussion is needed to improve decision-making in incisional hernia surgery.

The Enhanced Recovery After Surgery (ERAS) protocol reduces complications and length of stay (LOS) in colon cancer, but implementation in rectal cancer is different because of neo-adjuvant therapy and surgical differences. Laparoscopic resection may further improve outcome. The aim of this study was to evaluate the effects of introducing ERAS on postoperative outcome after rectal cancer resection in an era of increasing laparoscopic resections. Patients who underwent elective rectal cancer surgery from 2009 till 2015 were included in this observational cohort study. In 2010, ERAS was introduced and adherence to the protocol was registered. Open and laparoscopic resections were compared. With regression analysis, predictive factors for postoperative outcome and LOS were identified. A total of 499 patients were included. The LOS decreased from 12.3 days in 2009 to 5.7 days in 2015 (p = 0.000). Surgical site infections were reduced from 24% in 2009 to 5% in 2015 (p = 0.013) and postoperative ileus from 39% in 2009 to 6% in 2015 (p = 0.000). Only postoperative ERAS items and laparoscopic surgery were associated with an improved postoperative outcome and shorter LOS. ERAS proved to be feasible, safe, and contributed to improving short-term outcome in rectal cancer resections. The benefits of laparoscopic surgery may in part be explained by reaching better ERAS adherence rates. However, the laparoscopic approach was also associated with anastomotic leakage. Despite the potential of bias, this study provides an insight in effects of ERAS and laparoscopic surgery in a non-randomized real-time setting.

Aim Many of the current follow-up schedules in a watch-and-wait approach include very frequent MRI and endoscopy examinations to ensure early detection of local regrowth (LR). The aim of this study was to analyse the occurrence and detection of LR in a watch-and-wait cohort and to suggest a more efficient follow-up schedule. Method Rectal cancer patients with a clinical complete response after neoadjuvant therapy were prospectively and retrospectively included in a multicentre watch-and-wait registry between 2004 and 2018, with the current follow-up schedule with 3-monthly endoscopy and MRI in the first year and 6 monthly thereafter. A theoretical comparison was constructed for the detection of LR in the current follow-up schedule against four other hypothetical schedules. Results In all, 50/304 (16%) of patients developed a LR. The majority (98%) were detected at ≤2 years, located in the lumen (94%) and were visible on endoscopy (88%). The theoretical comparison of the different hypothetical schedules suggests that the optimal follow-up schedule should focus on the first 2 years with 3-monthly endoscopy and 3-6 monthly MRI. Longer intervals in the first 2 years will cause delays in diagnosis of LR ranging from 0 to 5 months. After 2 years, increasing the interval from 6 to 12 months did not cause important delays. Conclusion The optimal follow-up schedule for a watch-and-wait policy in patients with a clinical complete response after chemoradiation for rectal cancer should include frequent endoscopy and to a lesser degree MRI in the first 2 years. Longer intervals, up to 12 months, can be considered after 2 years.

Background: Spontaneous Haemoperitoneum in Pregnancy (SHiP) is a rare, but life-threatening complication of pregnancy that occurs predominantly in the third trimester of pregnancy and is associated with adverse pregnancy outcomes. Recently the largest case series in literature was published describing 11 Dutch cases of SHiP in women with endometriosis. Purpose: To investigate experiences, psychological impact, and quality of life after SHiP. Methods: A mixed-methods study was performed in women with a history of SHiP and their partners, including all known cases in the Netherlands between 2007 to 2015. Semi-structured in-depth interviews were organized between 2016 and 2017 and analysed thematically with a framework approach. Participants were asked to complete questionnaires investigating the impact of the event (Impact of Event Scale) and Quality of Life (RAND-36). Results: Out of a total of 11 known cases, 7 women agreed for be individually interviewed. From these, all women described a freeze response at the moment of SHiP, combined with either an anxious reaction or a survival mode mind-set. All women received psychological help after SHiP. Still, the feeling of not being heard by the medical staff was present in all women. Other themes such as postpartum period, bonding with their child, effect on daily life, reviving the event, and future pregnancies were also identified in the interviews. In regard to their partners, 3 were interviewed, hence no saturation was achieved. Finally, the questionnaires showed lower Quality of Life and an impact score of ≥ 8/10. Conclusion: SHiP had a profound impact on women and their partners. Dedicated psychological help should be offered to all women after experiencing SHiP.

Background Many studies have shown that participation in cardiac rehabilitation reduces long-term morbidity and mortality after myocardial infarction. Therefore, both American and European evidence-based guidelines recommend cardiac rehabilitation. However, it is still unclear what the optimal dose of cardiac rehabilitation is. Methodology The study is a monocenter, retrospective cohort study. We identified patients with stable ischemic heart disease, who participated in at least one phase II center-based cardiac rehabilitation session between 2010 and 2015. A total of 609 patients were included in this study. Results We retrospectively reviewed the medical records of 609 patients. Statistically significant baseline differences between the four groups were observed for index coronary artery revascularization technique, age, dual antiplatelet therapy and smoking status. A total of number of 84 patients (13.8%) had a MACE in the four-year follow-up period. After adjustment for all significant predictors in the univariate analysis, patients who attended 36 or more sessions had a 47% lower risk of MACE (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31 to 0.92), patients who attended 24 to 35 sessions had a 68% lower risk of MACE (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15 to 0.67), patients who attended 12 to 23 sessions had a 56% lower risk of MACE (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.21 to 0.92) than those who attended 1 to 11 sessions. Conclusion There is a clear clinical benefit from participating in more than 11 CR sessions. The best outcomes are achieved in patient who participated between 24 and 35 CR sessions. These results underline again the importance of improving participation and adherence to CR programmes in Europe.

Chronic interstitial nephritis in agricultural communities is a devastating kidney disease with a globally increasing prevalence. Its cause is unknown. Two predominant etiologies are hypothesised: recurrent episodes of dehydration and exposure to environmental toxins, such as agrochemicals and metals. In this review, we summarise arguments on: 1) why heat stress/dehydration is an unlikely cause of this disease and 2) why chronic interstitial nephritis in agricultural communities is to be considered a toxin-induced nephropathy. Mechanistically, we provide arguments for a putative role of pesticides on the one hand, and the calcineurin pathway on the other hand, both of which require further investigation. Finally, we summarise several important perspectives for research on chronic interstitial nephritis in agricultural communities. (C) 2020 Published by Elsevier Masson SAS on behalf of Societe francophone de nephrologie, dialyse et transplantation.

Aims Because reported mortality on veno-arterial (V-A) extracorporeal life support (ECLS) substantially varies between centres, the aim of the current analysis was to assess the outcomes between units performing heart transplantation and/or implanting ventricular assist device (HTx/VAD) vs. non-HTx/VAD units in patients undergoing V-A ECLS for cardiogenic shock.Methods and results Systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed using PubMed/MEDLINE databases until 30 November 2019. Articles reporting in-hospital/30-day mortality and centre's HTx/VAD status were included. In-hospital outcomes and long-term survival were analysed in subgroup meta-analysis. A total of 174 studies enrolling n = 13 308 patients were included with 20 series performed in non-HTx/VAD centres (1016 patients, 7.8%). Majority of patients underwent V-A ECLS for post-cardiotomy shock (44.2%) and acute myocardial infarction (20.7%). Estimated overall in-hospital mortality was 57.2% (54.9-59.4%). Mortality rates were higher in non-HTx/VAD [65.5% (59.8-70.8%)] as compared with HTx/VAD centres [55.8% (53.3-58.2%)], P Conclusions Survival after V-A ECLS differed according to centre's HTx/VAD status. Potentially different risk profiles of patients must be taken account for before definite conclusions are drawn.

Active surveillance for patients with esophageal cancer and a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) is being studied. Active surveillance requires accurate clinical response evaluations. 18F-FDG PET/CT might be able to detect local tumor recurrence after nCRT as soon as the esophagus recovers from radiationinduced esophagitis. The aims of this study were to assess the value of serial 18F-FDG PET/CT scans for detecting local recurrence in patients beyond 3 mo after nCRT and to determine when radiation-induced esophagitis has resolved. Methods: This retrospectivemulticenter study included patients who had cCR after nCRT, who initially declined surgery, and who subsequently underwent active surveillance. Clinical response evaluations included 18F-FDG PET/CT, endoscopic biopsies, and endoscopic ultrasound with fine-needle aspiration at regular intervals. SUVmax normalized for lean body mass (SULmax) was measured at the primary tumor site. The percentage change in SULmax (D%SULmax) between the last follow-up scan and the scan at 3 mo after nCRT was calculated. Tumor recurrence was defined as biopsy-proven vital tumor at the initial tumor site. Results: Of 41 eligible patients, 24 patients had recurrent disease at a median of 6.5 mo after nCRT and 17 patients remained cancer free during a median follow-up of 24 mo after nCRT. Five of 24 patients with tumor recurrence had sudden intense SULmax increases of greater than 180%. In 19 of 24 patients with tumor recurrence, SULmax gradually increased (median D%SULmax, 118%), whereas SULmax decreased (median D%SULmax, -12%) in patients with ongoing cCR (P , 0.001, independent-samples t test). In patients with ongoing cCR, SULmax was lowest at 11 mo after nCRT. Conclusion: Serial 18F-FDG PET/CT might be a useful tool for detecting tumor recurrence during active surveillance. In patients with ongoing cCR, the lowest SULmax was reached at 11 mo after nCRT, suggesting that radiation-induced esophagitis had mostly resolved by that time. These findings warrant further evaluation in a larger cohort.

We studied the three-dimensional (3-D) shape variations and symmetry of the lunate to evaluate whether a contralateral shape-based approach to design patient-specific implants for treatment of Kienböck’s disease is accurate. A 3-D statistical shape model of the lunate was built using the computed tomography scans of 54 lunate pairs and shape symmetry was evaluated based on an intraclass correlation analysis. The lunate shape was not bilaterally symmetrical in (1) the angle scaphoid surface – radius-ulna surface, (2) the dorsal side and the length of the side adjacent to the triquetrum, (3) the orientation of the volar surface, (4) the width of the side adjacent to the scaphoid, (5) the skewness in the coronal plane and (6) the curvature of bone articulating with the hamate and capitate. These findings suggest that using the contralateral lunate to design patient-specific lunate implants may not be as accurate as it is intended.

Objective: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone–standard of practice–for adverse perinatal outcome in singleton pregnancies. Design and setting: Meta-analysis based on individual participant data (IPD). Population or sample: Ten centres provided 17 data sets for 21661 participants, 18731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies. Methods: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile. Main outcome measures: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission. Results: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709–0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715–0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714–0.831). These results were consistent across all subgroups. Conclusions: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size. Tweetable abstract: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone.

Aims Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational–experimental–clinical study. Methods and results Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction 230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10–15%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34 ± 40% and 26 ± 31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation. Conclusion Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval.

Background: Accurate diagnosis and staging are crucial to ensure uniform allocation to the optimal treatment methods for non-small cell lung cancer (NSCLC) patients, but may differ among multidisciplinary tumor boards (MDTs). Discordance between clinical and pathologic TNM stage is particularly important for patients with locally advanced NSCLC (stage IIIA) because it may influence their chance of allocation to curative-intent treatment. We therefore aimed to study agreement on staging and treatment to gain insight into MDT decision-making. Research Question: What is the level of agreement on clinical staging and treatment recommendations among MDTs in stage IIIA NSCLC patients? Study Design and Methods: Eleven MDTs each evaluated the same 10 pathologic stage IIIA NSCLC patients in their weekly meeting (n = 110). Patients were selected purposively for their challenging nature. All MDTs received exactly the same clinical information and images per patient. We tested agreement in cT stage, cN stage, cM stage (TNM 8th edition), and treatment proposal among MDTs using Randolph's free-marginal multirater kappa. Results: Considerable variation among the MDTs was seen in T staging (κ, 0.55 [95% CI, 0.34-0.75]), N staging (κ, 0.59 [95% CI, 0.35-0.83]), overall TNM staging (κ, 0.53 [95% CI, 0.35-0.72]), and treatment recommendations (κ, 0.44 [95% CI, 0.32-0.56]). Most variation in T stage was seen in patients with suspicion of invasion of surrounding structures, which influenced such treatment recommendations as induction therapy and type. For N stage, distinction between N1 and N2 disease was an important source of discordance among MDTs. Variation occurred between 2 patients even regarding M stage. A wide range of additional diagnostics was proposed by the MDTs. Interpretation: This study demonstrated high variation in staging and treatment of patients with stage IIIA NSCLC among MDTs in different hospitals. Although some variation may be unavoidable in these challenging patients, we should strive for more uniformity.

ObjectivePsychosocial interventions can reduce cancer-related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta-analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention-related characteristics on the effect of psychosocial interventions on cancer-related fatigue in patients with non-metastatic breast and prostate cancer.MethodsData were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta-analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed-effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008).ResultsStatistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = -0.19 [95% confidence interval (95%CI) = -0.30; -0.08]; prostate cancer: β = -0.11 [95%CI = -0.21; -0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention-related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = -0.27 [95%CI = -0.40; -0.15]), fatigue-specific interventions (β = -0.48 [95%CI = -0.79; -0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = -0.85 [95%CI = -1.40; -0.30]).ConclusionsOur findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue.

Purpose Almost all radiolabellings of antibodies with 89Zr currently employ the hexadentate chelator desferrioxamine (DFO). However, DFO can lead to unwanted uptake of 89Zr in bones due to instability of the resulting metal complex. DFO*-NCS and the squaramide ester of DFO, DFOSq, are novel analogues that gave more stable 89Zr complexes than DFO in pilot experiments. Here, we directly compare these linker-chelator systems to identify optimal immuno-PET reagents. Methods Cetuximab, trastuzumab and B12 (non-binding control antibody) were labelled with 89Zr via DFO*-NCS, DFOSq, DFO-NCS or DFO*Sq. Stability in vitro was compared at 37 °C in serum (7 days), in formulation solution (24 h ± chelator challenges) and in vivo with N87 and A431 tumour-bearing mice. Finally, to demonstrate the practical benefit of more stable complexation for the accurate detection of bone metastases, [89Zr]Zr-DFO*-NCS and [89Zr]Zr-DFO-NCS-labelled trastuzumab and B12 were evaluated in a bone metastasis mouse model where BT-474 breast cancer cells were injected intratibially. Results [89Zr]Zr-DFO*-NCS-trastuzumab and [89Zr]Zr-DFO*Sq-trastuzumab showed excellent stability in vitro, superior to their [89Zr]Zr-DFO counterparts under all conditions. While tumour uptake was similar for all conjugates, bone uptake was lower for DFO* conjugates. Lower bone uptake for DFO* conjugates was confirmed using a second xenograft model: A431 combined with cetuximab. Finally, in the intratibial BT-474 bone metastasis model, the DFO* conjugates provided superior detection of tumour-specific signal over the DFO conjugates. Conclusion DFO*-mAb conjugates provide lower bone uptake than their DFO analogues; thus, DFO* is a superior candidate for preclinical and clinical 89Zr-immuno-PET.

Oral lichen planus (OLP) is a chronic inflammatory disease displaying ultrastructural disturbances in epithelial hemidesmosomes. The expression of several key hemidesmosomal components in OLP as well as in normal buccal mucosa is, however, unknown. The aim of the study was therefore to examine intracellular and extracellular components involved in hemidesmosomal attachment, in OLP (n = 20) and in normal buccal mucosa (n = 10), by immunofluorescence. In normal buccal mucosa, laminin-α3γ2, integrin-α6β4, CD151, collagen α-1(XVII) chain, and dystonin showed linear expression along the basal membrane, indicating the presence of type I hemidesmosomes. Plectin stained most epithelial cell membranes and remained unphosphorylated at S4642. In OLP, most hemidesmosomal molecules examined showed disturbed expression consisting of discontinuous increases, apicolateral location, and/or intracellular accumulation. Plectin showed S4642-phosphorylation at the basement membrane, and deposits of laminin-α3 and laminin-γ2 were found within the connective tissue. The disturbed expression of hemidesmosomal proteins in OLP indicates deficient attachment of the basal cell layer, which can contribute to detachment and cell death of basal keratinocytes seen in the disease.

OBJECTIVES Quality assessment is an important element in providing surgical cancer care. The main objective of this study was to develop a new composite measure ‘textbook outcome’, to evaluate and improve quality of surgical care for patients undergoing a resection for non-small-cell lung cancer (NSCLC). METHODS All patients undergoing an anatomical resection for NSCLC from 2012 to 2016 registered in the nationwide Dutch Lung Cancer Audit were included in an analysis to assess usefulness of a composite measure as a quality indicator. Based on expert opinion, textbook outcome was defined as having a complete resection (negative resection margins and sufficient lymph node dissection), plus no 30-day or in-hospital mortality, no reintervention in 30 days, no readmission to the intensive care unit, no prolonged hospital stay ( RESULTS In total, 5513 patients were included in this study. Textbook outcome was achieved in 26.4% of patients. Insufficient lymph node dissection had the most substantial effect on not realizing textbook outcome. If ‘sufficient lymph node dissection’ was not included as a criterion, textbook outcome would be 60.7%. Case-mix adjusted textbook outcome proportions per hospitals varied between 13.2% and 37.7%. CONCLUSIONS In contrast to focusing on a single aspect, the composite measure textbook outcome provides insight into comprehensive performance in NSCLC surgery. It can be used to evaluate both individual hospitals and national performance and provides the opportunity to give benchmarked feedback to thoracic surgeons.

OBJECTIVES Surgical resection is widely employed as a potential curative treatment option for patients with limited lung metastases originating from a wide range of primary tumours. However, there are no clear national or international practice guidelines and, thereby, the risk for potential practice variation exists. This study aims to define the current practice for the surgical treatment of pulmonary metastases in the Netherlands by using data from the Dutch Lung Cancer Audit for Surgery (DLCA-S). METHODS Data from the DLCA-S were used to analyse patients undergoing a parenchymal lung resection for the treatment of pulmonary metastases between 2012 and 2017. Volume of metastasectomies per hospital was calculated as a proportion of the volume of primary lung cancer resection. Studied outcomes were overall complications and postoperative mortality and complicated course. For the latter, both the national average and between-hospital variation were calculated. RESULTS A total of 2090 patients, distributed over 45 Dutch hospitals, were included for analysis. The most common primary cancer was colorectal carcinoma (N = 1087, 52.0%) followed by the urogenital carcinoma (N = 296, 14.2%). The most common type of parenchymal resection was a wedge resection (N = 1477, 70.7%) followed by a lobectomy (N = 424, 20.3%). Resection was performed minimally invasively in 1548 patients (74.1%) with a conversion rate of 3.8%. Resection of a solitary metastasis was performed in 1663 patients (79.6%). In 40 patients (1.9%), 4 or more metastases were resected. A postoperative complicated course was noted in 3.6%, and the 30-day mortality rate was 0.7%. The variety between hospitals in the volume of metastasectomies in proportion to the volume of primary lung cancer resections was 3.4–41.5%. CONCLUSIONS This analysis of the DLCA-S registry provides a unique insight into current practice on pulmonary metastasectomies in the Netherlands over a 6-year period. The rate of postoperative adverse outcome was limited, and the morbidity and mortality were lower compared to primary lung cancer resections in the DLCA-S database.

Objective: While reported mortality rates on post-cardiotomy extracorporeal membrane oxygenation vary from center to center, impact of baseline surgical status (elective/urgent/emergency/salvage) on mortality is still unknown. Methods: A systematic search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using PubMed/Medline databases until March 2018 using the keywords “postcardiotomy,” “cardiogenic shock,” “extracorporeal membrane oxygenation,” and “extracorporeal life support.” Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and baseline surgical status. The correlations between mortality and percentage of elective/urgent/emergency cases were investigated. Inference analysis of baseline status and extracorporeal membrane oxygenation complications was conducted as well. Results: Twenty-two studies (conducted between 1993 and 2017) enrolling N = 2,235 post-cardiotomy extracorporeal membrane oxygenation patients were found. Patients were mostly of non-emergency status (65.2%). Overall in-hospital/30-day mortality event rate (95% confidence intervals) was 66.7% (63.3-69.9%). There were no differences in in-hospital/30-day mortality with respect to baseline surgical status in the subgroup analysis (test for subgroup differences; p = 0.406). Similarly, no differences between mortality in studies enrolling Conclusion: Other factors than baseline surgical status may, to a higher degree, influence the mortality in patients treated with extracorporeal membrane oxygenation for post-cardiotomy cardiogenic shock. Baseline status, however, strongly influences the complication occurrence while on extracorporeal membrane oxygenation.

Introduction: The aim was assess the oncological and functional outcome of the watch-and-wait (W&W) approach in older patients with a clinical (near)complete response after neoadjuvant treatment for rectal cancer.Material and methods: Patients were included in a W&W-approach (2004-2019) when digital rectal examination, endoscopy and MRI showed a (near)clinical complete response. Patients underwent endoscopy and MRI every 3 months during the first year, and 6-monthly thereafter. Patients aged >= 75 and >= 2 years of follow-up (FU) were selected. Oncological outcomes were assessed with Kaplan-Meier curves. Functional outcome was assessed with colostomy-free rate, Vaizey incontinence score, low anterior resection syndrome-score and International Prostate Syndrome Score.Results: 43/304 (14%) of patients in a W&W-approach met the inclusion criteria. Median FU was 37 (24-109) months. 5/43(12%) developed a local regrowth. All were treated surgically, with one patient experiencing a pelvic failure. Distant metastases occurred in 3/43 patients and 4 patients died, 3 of whom not related to rectal cancer. The 3-year local regrowth-free rate was 88%, 3-year non-regrowth disease-free survival 91%, overall survival 97% and 3-year colostomy-free rate 93%. Overall, the bowel- and urinary dysfunction scores at 3, 12 and 24 months indicated good continence, no or minor LARS and moderate urinary problems.Conclusion: W&W for older patients with a clinical (near) complete response appears to be a safe alternative to a total mesorectal excision (TME), with a very high pelvic control rate, and few rectal cancer related deaths. Most patients can avoid major surgery and a definitive colostomy, and have a reasonable anorectal and urinary function. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

ObjectiveTo study survival and to characterize long-term functional impairments and health-related quality of life (HRQOL) of patients with Lambert-Eaton myasthenic syndrome (LEMS).MethodsIn this observational study, survival of patients with LEMS, separately for nontumor (NT) and small cell lung cancer (SCLC), was compared to that of the Dutch general population and patients with SCLC. Disease course in patients with LEMS was recorded retrospectively. Several scales for functional impairments and health-related quality of life were assessed.ResultsWe included 150 patients with LEMS. Survival was similar to that of the general population in 65 patients with NT-LEMS. Tumor survival was significantly longer in 81 patients with SCLC-LEMS compared to patients with non-LEMS SCLC (overall median survival 17 vs 7.0 months, p < 0.0001). At diagnosis, 39 (62%) of 63 patients with complete follow-up data were independent for activities of daily living, improving to 85% at the 1-year follow-up. The physical HRQOL composite score (55.9) was significantly lower than in the general population (76.3, p < 0.0001) and comparable to that of patients with myasthenia gravis (60.5). The mental HRQOL composite score was 71.8 in patients with LEMS, comparable to that of the general population (77.9, p = 0.19) and patients with myasthenia gravis (70.3).ConclusionsThis study shows that patients with NT-LEMS have normal survival. Patients with SCLC-LEMS have an improved tumor survival, even after correction for tumor stage. A majority of patients with LEMS report a stable disease course and remain or become independent for self-care after treatment.

The effect of orally administered hawthorn flavonoid extract (HFE) on growth, electrocardiographic waves, and cardiac parameters of pulmonary hypertensive chickens reared at high altitude (2,100 m above sea level) was examined. A total of 225 one-day-old, mixed broiler chicks (3 treatments with 5 replicates and 15 chicks per each, totally 75 birds/treatment) were assigned to 3 experimental groups: 0, 0.1, and 0.2 ml of HFE per 1 L of drinking water. Birds were administered the drinking water HFE treatments for 42 D. At an age of 28 and 42 D, electrocardiograms were undertaken and cardiac parameters such as the RV:TV, RV:BW, and TV:BW, and indicators of PHS on selected birds were measured. The final BW of chickens receiving the HFE at 0.2 ml/L was greater (2,579 ± 64 g) than that of birds receiving 0.1 ml/L (2,497 ± 62 g) and 0 ml/L (2,323 ± 57 g). Therefore, no supplemented group had a lower final BW than others (P < 0.05). Amplitudes of S and T waves in 0.1- and 0.2-ml/L HFE consumed groups at 28 and 42 D of age decreased compared with that in the control group (P < 0.05). The HFE reduced the heart weight and RV:TV, RV:BW, and TV:BW ratios when supplemented in drinking water at 0.1 and 0.2 mL/L compared with 0 mL/L (P < 0.05). In conclusion, supplementation of HFE in drinking water can reduce the PHS and incidence of cardiac disorders. Owing to the positive effect of HFE on cardiac parameters that mediated through flavonoids bioactive compounds, this product can be used to prevent complications of pulmonary hypertension and disarray of electrocardiographic waves in broiler chickens reared at high altitude.

Almost 30 years after the detection of chronic interstitial nephritis in agricultural communities (CINAC) its etiology remains unknown. To help define this we examined 34 renal biopsies from Sri Lanka, El Salvador, India and France of patients with chronic kidney disease 2-3 and diagnosed with CINAC by light and electron microscopy. In addition to known histopathology, we identified a unique constellation of proximal tubular cell findings including large dysmorphic lysosomes with a light-medium electron-dense matrix containing dispersed dark electron-dense non-membrane bound "aggregates". These aggregates associated with varying degrees of cellular/tubular atrophy, apparent cell fragment shedding and no-weak proximal tubular cell proliferative capacity. Identical lysosomal lesions, identifiable by electron microscopy, were observed in 9% of renal transplant implantation biopsies, but were more prevalent in six month (50%) and 12 month (67%) protocol biopsies and in indication biopsies (76%) of calcineurin inhibitor treated transplant patients. The phenotype was also found associated with nephrotoxic drugs (lomustine, clomiphene, lithium, cocaine) and in some patients with light chain tubulopathy, all conditions that can be directly or indirectly linked to calcineurin pathway inhibition or modulation. One hundred biopsies of normal kidneys, drug/toxin induced nephropathies, and overt proteinuric patients of different etiologies to some extent could demonstrate the light microscopic proximal tubular cell changes, but rarely the electron microscopic lysosomal features. Rats treated with the calcineurin inhibitor cyclosporine for four weeks developed similar proximal tubular cell lysosomal alterations, which were absent in a dehydration group. Overall, the finding of an identical proximal tubular cell (lysosomal) lesion in CINAC and calcineurin inhibitor nephrotoxicity in different geographic regions suggests a common paradigm where CINAC patients undergo a tubulotoxic mechanism similar to calcineurin inhibitor nephrotoxicity.

OBJECTIVES Persistent air leak (PAL; >5 days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity. Literature is contradictory about the prevention and treatment of PAL. Variation is therefore hypothesized. The aim of this study is to understand the variation in the incidence, preventive management and treatment of PAL. METHODS Data from the Dutch Lung Cancer Audit for Surgery were combined with results of an online survey among Dutch thoracic surgeons. The national incidence of PAL and case-mix corrected between-hospital variation were calculated in patients who underwent an oncological (bi)lobectomy or segmentectomy between January 2012 and December 2018. By multivariable logistic regression, factors associated with PAL were assessed. A survey was designed to assess variation in (preventive) management and analysed using descriptive statistics. Hospital-level associations between management strategies and PAL were assessed by univariable linear regression. RESULTS Of 12 382 included patients, 9.0% had PAL, with a between-hospital range of 2.6–19.3%. Factors associated with PAL were male sex, poor lung function, low body mass index, high American Society of Anesthesiologists (ASA) score, pulmonary comorbidity, upper lobe resection, (bi)lobectomy (vs segmentectomy), right-sided tumour and robotic-assisted thoracic surgery. Perioperative (preventive) management of PAL differed widely between hospitals. When using water seal compared to suction drainage, the average incidence of PAL decreased 2.9%. CONCLUSIONS In the Netherlands, incidence and perioperative (preventive) management of PAL vary widely. Using water seal instead of suction drainage and increasing awareness are potential measures to reduce this variation., Persistent or prolonged air leak (PAL) is one of the most common complications after pulmonary resection, with incidence rates reported between 8% and 26% [1–8].

Background The discovery of the Fallopian tube epithelium as origin of high grade serous ovarian cancer has brought a new option for ovarian cancer prevention. As the Fallopian tubes have no known function after completion of childbearing, they can be removed to reduce the life-time risk of ovarian cancer. Although the lifetime risk in the general population does not justify preventive surgery in itself, salpingectomy can be performed during abdominal surgery for other indications, also known as an opportunistic salpingectomy. The popularity of opportunistic salpingectomy is increasing globally, however substantial variation between gynecologists and hospitals in their advice on the opportunistic salpingectomy occurs due to remaining uncertainty of evidence. As a result, whether or not a woman is able to make her own decision depends on the hospital or gynecologist she visits. We aim to lower this practice variation by providing standardized and unbiased counseling material. Objective(s) To develop and test a patient decision aid for an opportunistic salpingectomy in women undergoing either pelvic gynecological surgery with the intention to retain the ovaries or opting for sterilization. Study Design We followed a systematic development process based on the International Patient Choice Aid Standard (IPDAS). Data were collected between June 2019 and June 2020, using both qualitative and quantitative methods. The development process which took place in collaboration with patients and healthcare professionals, was overseen by a multidisciplinary steering group, and was divided in four phases; 1. Assessment of decisional needs using individual telephone interviews and questionnaires; 2. Development of content and format based on decisional needs, current literature and guidelines; 3. Alpha-testing and first revision round; and 4. Alpha-testing and second revision round. Results An outline of the patient decision aid was developed based on decisional needs, current literature and guidelines. It became clear that the decision aid should consist of two separate paths: one with information specifically for salpingectomy in addition to abdominal surgery and one for salpingectomy as a sterilization method. Both paths contain information on the anatomy and function of ovaries and Fallopian tubes, the risk reduction of ovarian cancer and the potential benefits and risks of opportunistic salpingectomy. The sterilization path also contains information on the various sterilization methods and the risk of unwanted pregnancy. The patient decision aid was developed as an online tool that includes information chapters, a knowledge quiz, consideration statements, and a summary detailing patient’s preference and considerations. Adjustments were made following alpha-testing round one. The improved patient decision aid was subjected to usability tests (alpha-testing round two), in which it scored an ‘excellent’ in patient testing and a ‘good’ in tests with gynecologists. Furthermore, our patient decision aid met the requirements of 45 out of 49 applicable items from the International Patient Decision Aid Standards criteria. Conclusion In collaboration with patients and healthcare professionals, a patient decision aid was developed on opportunistic salpingectomy and salpingectomy as a sterilization method. Both patients and gynecologists thought it a usable aid which supports patients in making an informed decision whether to undergo an opportunistic salpingectomy, and supports the counseling process by gynecologists.

Background: Routine lymphadenectomy during metastasectomy for pulmonary metastases of colorectal cancer has been recommended by several recent expert consensus meetings. However, evidence supporting lymphadenectomy is limited. The aim of this study was to perform a systematic review of the literature on the impact of simultaneous lymph node metastases on patient survival during metastasectomy for colorectal pulmonary metastases (CRPM).Methods: A systematic review was conducted according to the PRISMA guidelines of studies on lymphadenectomy during pulmonary metastasectomy for CRPM. Articles published between 2000 and 2020 were identified from Medline, Embase and the Cochrane Library without language restriction. Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the risk of bias and applicability of included studies. Survival rates were assessed and compared for the presence and level of nodal involvement.Results: Following review of 8054 studies by paper and abstract, 27 studies comprising 3619 patients were included in the analysis. All patients included in these studies underwent lymphadenectomy during pulmonary metastasectomy for CRPM. A total of 690 patients (19.1%) had simultaneous lymph node metastases. Five-year overall survival for patients with and without lymph node metastases was 18.2% and 51.3%, respectively (p < .001). Median survival for patients with lymph node metastases was 27.9 months compared to 58.9 months in patients without lymph node metastases (p < .001). Five-year overall survival for patients with N1 and N2 lymph node metastases was 40.7% and 10.9%, respectively (p = .064).Conclusion: Simultaneous lymph node metastases of CRPM have a detrimental impact on survival and this is most apparent for mediastinal lymph node metastases. Therefore, lymphadenectomy during pulmonary metastasectomy for CRPM can be advised to obtain important prognostic value. (C) 2021 The Authors. Published by Elsevier Ltd.

Background Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology after endosonography. Confirmatory mediastinoscopy however is under debate owing its limited additional diagnostic value, its associated morbidity and its delay in the start of lung cancer treatment. The MEDIASTrial examines whether confirmatory mediastinoscopy can be safely omitted after negative endosonography in mediastinal nodal staging of NSCLC. The present work is the proposed statistical analysis plan of the clinical consequences of omitting mediastinoscopy, which is submitted before closure of the MEDIASTrial and before knowledge of any results was done to enhance transparency of scientific behaviour. Methods The primary outcome measure of this non-inferiority trial will be unforeseen N2 disease resulting from lobe-specific mediastinal lymph node dissection. For non-inferiority, the upper limit of the 95% confidence interval of the unforeseen N2 rate in the group without mediastinoscopy should not exceed 14.3% in order to probably have no negative impact on survival. Since this is a non-inferiority trial, both an intention to treat (ITT) and a per protocol (PP) analyses will be done. The ITT and the PP analyses should both indicate non-inferiority before the diagnostic strategy omitting mediastinoscopy will be interpreted as non-inferior to the strategy with mediastinoscopy. Secondary outcome measures include 30-day major morbidity and mortality, the total number of days of hospital care, overall and disease free 2-year survival, generic and disease-specific health related quality of life and cost-effectiveness and cost-utility of staging strategies with and without mediastinoscopy. Discussion The MEDIASTrial will determine if confirmatory mediastinoscopy can be omitted after tumour negative systematic endosonography in invasive mediastinal staging of patients with resectable NSCLC. Trial registration Netherlands Trial Register NL6344/NTR6528. Registered on 2017 July 06

Background Chronic pain constitutes a significant burden for the individuals affected, and is a frequent reason why patients seek health care services. While in-person psychosocial interventions can be of support to people living with chronic pain, such interventions are not always accessible. eHealth interventions may provide greater accessibility, but the evidence and use of digital self-management solutions for chronic pain are still limited and the lack of health care provider input in the development process of such solutions a concern. Therefore, the aim of the current study was to investigate health care providers’ experiences of treating patients with chronic pain, their attitudes towards, and use of, digital solutions in pain management, and their suggestions for content and design elements for a potential digital pain self-management intervention. Methods Twelve health care providers representing a variety of health care disciplines participated in semi-structured interviews. The interviews were analyzed using thematic analysis. Results The material was analyzed into three main themes: [1] Patients with chronic pain and their current use of the health care services, [2] Health care providers’ own motivation and impression of patient prerequisites for use of digital self-management interventions, and [3] Suggestions for content and design elements in a digital self-management intervention for people living with chronic pain. The challenges faced by patients living with chronic pain were described as numerous. Despite interest and positive attitudes, few of the health care providers had used or recommended eHealth solutions to their patients. A range of potential content and functionality elements were identified, including aspects of motivation and engagement and providers also emphasized the importance of easy access and positive, personal content to support existing treatment. Conclusions This study offers insights into health care providers’ considerations for the potential of digital self-management interventions supporting patients living with chronic pain. Findings indicate the need for change and a more comprehensive treatment approach to pain management. eHealth solutions may contribute to such change, and providers pointed to a need for health care provider involvement, timely support and follow-up as important factors for integrating digital pain self-management interventions into clinical care. Trial registration ClinicalTrials.gov: NCT03705104

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC. ispartof: NPJ BREAST CANCER vol:7 issue:1 ispartof: location:United States status: published

BackgroundMastitis is one of the major diseases causing economic loss to the dairy industry by reducing the quantity and quality of milk. Thus, the objective of this scientific study was to find new biomarkers based on genes for the early prediction before its severity.MethodsIn the present study, advanced bioinformatics including hierarchical clustering, enrichment analysis, active site prediction, epigenetic analysis, functional domain identification, and protein docking were used to analyze the important genes that could be utilized as biomarkers and therapeutic targets for mastitis.ResultsFour differentially expressed genes (DEGs) were identified in different regions of the mammary gland (teat cistern, gland cistern, lobuloalveolar, and Furstenberg’s rosette) that resulted in 453, 597, 577, and 636 DEG, respectively. Also, 101 overlapped genes were found by comparing 27 different expressed genes. These genes were associated with eight immune response pathways including NOD-like receptor signaling pathway (IL8, IL18, IL1B, PYDC1) and chemokine signaling pathway (PTK2, IL8, NCF1, CCR1, HCK). Meanwhile, 241 protein-protein interaction networks were developed among overlapped genes. Fifty-seven regulatory events were found between miRNAs, expressed genes, and the transcription factors (TFs) through micro-RNA and transcription factors (miRNA-DEG-TF) regulatory network. The 3D structure docking model of the expressed genes proteins identified their active sites and the binding ligands that could help in choosing the appropriate feed or treatment for affected animals.ConclusionsThe novelty of the distinguished DEG and their pathways in this study is that they can precisely improve the detection biomarkers and treatments techniques of cows’Escherichia colimastitis disease due to their high affinity with the target site of the mammary gland before appearing the symptoms.Graphical abstract

Introduction/Background* The discovery of the Fallopian tube epithelium as origin of high grade serous ovarian cancer has brought a new option for ovarian cancer prevention, the opportunistic salpingectomy (OS). The popularity of OS is increasing globally, however at present there is substantial practice variation. As a result, whether or not a woman is able to make her own decision on OS depends on the hospital or gynaecologist she visits. To lower practice variation, we developed and tested a patient decision aid (PtDA) for OS in women undergoing either pelvic gynaecological surgery with the intention to retain the ovaries or a sterilization. Methodology We followed a systematic development process based on the International Patient Choice Aid Standard (IPDAS). Data were collected between June 2019 and June 2020, using both qualitative and quantitative methods. The development process took place in collaboration with patients and healthcare professionals, was overseen by a multidisciplinary steering group, and was divided in four phases; 1. Assessment of decisional needs using individual interviews and questionnaires; 2. Development of content and format based on decisional needs, current literature and guidelines; 3. Alpha-testing and first revision round; and 4. Alpha-testing and second revision round. Result(s)* An outline of the PtDA was developed based on decisional needs, current literature and guidelines. It became clear that the PtDA should consist of two separate paths: one on salpingectomy in addition to abdominal surgery and one on salpingectomy as a sterilization method. Both paths contain information on the anatomy and function of ovaries and Fallopian tubes, the estimated risk reduction of ovarian cancer and the potential benefits and risks of OS. Adjustments were made following alpha-testing round one. The improved PtDA was subjected to usability tests (alpha-testing round two), in which it scored an ‘excellent’ in patient testing and a ‘good’ in tests with gynaecologists. Conclusion* In collaboration with patients and healthcare professionals, a PtDA was developed on OS. Both patients and gynaecologists thought it a usable aid which supports patients in making an informed decision whether to undergo an opportunistic salpingectomy, and supports the counselling process by gynaecologists.

ObjectivesElastic compression stocking (ECS) therapy is an important treatment for patients with deep venous thrombosis (DVT) and chronic venous insufficiency (CVI). This study aimed to provide insight into the structure and variability of the ECS therapy process, its effects on outcomes, and to elicit improvement themes from a multiple stakeholder perspective.DesignThirty semi-structured interviews with professionals and patients were performed. The essential functions for the process of ECS therapy were extracted to create two work-as-done models using the Functional Resonance Analysis Method (FRAM). These findings were used to guide discussion between stakeholders to identify improvement themes.SettingTwo regions in the Netherlands, region Limburg and region North-Holland, including an academic hospital and a general hospital and their catchment region.ParticipantsThe interviewees were purposely recruited and included 25 healthcare professionals (ie, general practitioners, internists, dermatologists, nurses, doctor’s assistants, occupational therapists, home care nurses and medical stocking suppliers) and 5 patients with DVT or CVI.ResultsTwo FRAM models were created (one for each region). The variability of the functions and their effect on outcomes, as well as interdependencies between functions, were identified. These were presented in stakeholder meetings to identify the structure of the process and designated variable and uniform parts of the process and its outcomes. Ultimately, six improvement themes were identified: dissemination of knowledge of the entire process; optimising and standardising initial compression therapy; optimising timing to contact the medical stocking supplier (when oedema has disappeared); improving the implementation of assistive devices; harmonising follow-up duration for patients with CVI; personalising follow-up and treatment duration in patients with DVT.ConclusionsThis study provided a detailed understanding of how ECS therapy is delivered in daily practice by describing major functions and variability in performances and elicited six improvement themes from a multistakeholder perspective.

PurposeScleritis is a potentially blinding disorder, with highly unpredictable course and outcome. We analyzed the prevalence and clinical relevance of autoantibodies and inflammatory parameters in non-infectious scleritis.MethodsRetrospective analysis of laboratory findings in all consecutive patients at the department of Ophthalmology of the Erasmus MC with non-infectious scleritis.ResultsWe included 81 patients with non-infectious scleritis. A systemic autoimmune disease was present in 46%. Positive anti-nuclear antibodies were found in 30%, anti-neutrophil cytoplasmic antibodies were positive in 19%, and the presence of rheumatoid factor was shown in 17%. The aforementioned autoantibodies, as well as inflammatory parameters, failed to show prognostic clinical value. In contrast, anti-citrullinated peptide antibodies (ACPA), found in 9% of scleritis patients, were significantly associated with the development of scleral necrosis (P = .01).ConclusionsThe presence of ACPA in patients with non-infectious scleritis was associated with the development of scleral necrosis.

Background Specific IgE (sIgE) against the peanut component Arachis hypogaea (Ara h) 2 has been shown to be the most important allergen to discriminate between peanut allergy and peanut tolerance. Several studies determined sIgE cut off values for Ara h 2, determined by singleplex measurements. However, cut off values for Ara h 2 from multiplex arrays are less well defined. The aim of this study was to evaluate the correlation between Ara h 2 sIgE determined by singleplex versus multiplex measurements and to assess the diagnostic value of the different peanut components included in Immuno Solid-phase Allergen Chip (ISAC) multiplex analysis in children with a suspected peanut allergy. Methods In this retrospective study we analyzed Ara h 2 sIgE values with singleplex Fluorescence Enzyme Immunoassay (FEIA, ImmunoCap) and multiplex microarray (ISAC) measurements in 117 children with a suspected peanut allergy. Also, other peanut components measured by ISAC were analyzed. Double blinded placebo controlled oral food challenges were used as golden standard. Results Among all studied peanut components FEIA Ara h 2 sIgE showed the highest area under the curve (AUC, 0.922), followed by ISAC Ara h 6 and Ara h 2 sIgE with AUCs of respectively 0.906 and 0.902. Best cut off values to diagnose peanut allergy were 4.40 kU/l for FEIA Ara h 2 sIgE and, 7.43 ISU and 8.13 ISU for respectively Ara h 2 and Ara h 6 sIgE in ISAC microarray. Ara h 2 sIgE determined in FEIA and ISAC showed a good correlation (r = 0.88; p Conclusion Ara h 6 and Ara h 2 sIgE in multiplex ISAC are both good predictors of clinical peanut allergy in Dutch children, and their performance is comparable to the use of Ara h 2 in singleplex FEIA. The simultaneous measurement of different peanut components using ISAC is an advantage and clinically useful to detect peanut allergic children that are Ara h 2 negative but sensitized to other peanut proteins such as Ara h 6.

Study question How do infertility patients, endometriosis patients and health care providers rate the virtual care that was provided during the first lockdown of the COVID-19 pandemic? Summary answer Patients and health care providers rate telephone- and video consultations as good alternatives during the pandemic but it cannot replace future physical consultations. What is known already Virtual alternatives to regular care such as telephone and video consultations are gaining more attention as replacement for physical consultations and are ideal for use in a social distancing situation as the COVID-19 pandemic. However, infertility and endometriosis patients often rely on physical consultations for reassurance as well as for treatments such as artificial reproductive technology and surgery. Not being able to receive these reassurances and treatments may cause stress especially as infertility patients are known to experience a high sense of urgency to obtain treatment. For patients with endometriosis, regular follow-up visits are important for continuity of care. Study design, size, duration: A cross-sectional cohort study was performed, including 555 patients and 101 health care providers in the field of infertility and endometriosis in the Netherlands. Online questionnaires were sent between May and October 2020. Participants/materials, setting, methods Patients with infertility and endometriosis patients from a university hospital and members of the respective national patients organizations, as well as health care providers in the fields of infertility and endometriosis were asked to participate. The questionnaires consisted of demographics, appraisal of telephonic and video consultations (TCs and VCs) and assessment of fertility related quality of life (FertiQoL) and patient-centeredness of endometriosis care (ENDOCARE). Main results and the role of chance The questionnaires were completed by 374 infertility patients, 181 endometriosis patients and 101 health care providers. 75.9% of the infertility patients, 64.8% of the endometriosis patients and 82.7% of the health care providers rated TCs as a good alternative for physical consultations during the COVID-19-pandemic. Only 21.3%, 14.8% and 21.3% rated TCs as a good replacement of physical consultations in general. 76.6% and 35.9% of the infertility and endometriosis patients reported to experience an increase in stress due to the altered care during the COVID-19 pandemic. 38.7% and 58.0% reported to have received sufficient information from their care givers. Infertility patients scored lower on the FertiQoL than the reference population, while the ENDOCARE results of endometriosis patients were comparable to the reference. Limitations, reasons for caution This study was limited to the Dutch population. As the organization of infertility care varies internationally, the results will not be directly applicable to other countries or health care systems. Wider implications of the findings: Virtual care options are a good alternative for infertility and endometriosis patients in situations where physical consultations are not possible. Self-reported stress is especially high in infertility patients during the COVID-19-pandemic. Health care providers should provide more information to patients in order to increase their ability to cope with stress. Trial registration number N/A

Background Tree nut-allergic individuals are often sensitised towards multiple nuts and seeds. The underlying cause behind a multi-sensitisation for cashew nut, hazelnut, peanut and birch pollen is not always clear. We investigated whether immunoglobulin E antibody (IgE) cross-reactivity between cashew nut, hazelnut and peanut proteins exists in children who are multi-allergic to these foods using a novel IMMULITE®-based inhibition methodology, and investigated which allergens might be responsible. In addition, we explored if an allergy to birch pollen might play a role in this co-sensitisation for cashew nut, hazelnut and peanut. Methods Serum of five children with a confirmed cashew nut allergy and suffering from allergic symptoms after eating peanut and hazelnut were subjected to inhibition immunoassays using the IMMULITE® 2000 XPi. Serum-specific IgE (sIgE) to seed storage allergens and pathogenesis-related protein 10 (PR10) allergens were determined and used for molecular multicomponent allergen correlation analyses with observed clinical symptoms and obtained inhibition data. Results IgE cross-reactivity was observed in all patients. Hazelnut extract was a strong inhibitor of cashew nut sIgE (46.8%), while cashew nut extract was less able to inhibit hazelnut extract (22.8%). Peanut extract showed the least inhibition potency. Moreover, there are strong indications that a birch pollen sensitisation to Bet v 1 might play a role in the observed symptoms provoked upon ingestion of cashew nut and hazelnut. Conclusions By applying an adjusted working protocol, the IMMULITE® technology can be used to perform inhibition assays to determine the risk of sIgE cross-reactivity between very different food components.

Contains fulltext : 218131.pdf (Publisher’s version ) (Open Access) Cleft lip with or without cleft palate is a congenital deformity that occurs in about 1 of 700 newborns, affecting the dentition, bone, skin, muscles and mucosa in the orofacial region. A cleft can give rise to problems with maxillofacial growth, dental development, speech, and eating, and can also cause hearing impairment. Surgical repair of the lip may lead to impaired regeneration of muscle and skin, fibrosis, and scar formation. This may result in hampered facial growth and dental development affecting oral function and lip and nose esthetics. Therefore, secondary surgery to correct the scar is often indicated. We will discuss the molecular and cellular pathways involved in facial and lip myogenesis, muscle anatomy in the normal and cleft lip, and complications following surgery. The aim of this review is to outline a novel molecular and cellular strategy to improve musculature and skin regeneration and to reduce scar formation following cleft repair. Orofacial clefting can be diagnosed in the fetus through prenatal ultrasound screening and allows planning for the harvesting of umbilical cord blood stem cells upon birth. Tissue engineering techniques using these cord blood stem cells and molecular targeting of inflammation and fibrosis during surgery may promote tissue regeneration. We expect that this novel strategy improves both muscle and skin regeneration, resulting in better function and esthetics after cleft repair.

Background. Breast cancer treatment has rapidly changed in the last few years. Particularly, treatment of patients with axillary nodal involvement has evolved after publication of several randomized clinical trials. Omitting axillary lymph node dissection in selected early breast cancer patients with one or two positive sentinel nodes did not compromise overall survival nor regional disease control in these trials. Hence, either excluding or identifying extensive axillary nodal involvement becomes increasingly important. Purpose. To evaluate whether the current diagnostic modalities can accurately identify or exclude extensive axillary nodal involvement. Evaluated modalities were axillary ultrasound, ultrasound-guided needle biopsy, MRI, and PET/CT. Methods. A literature search was performed in the Cochrane Library, EMBASE, and PubMed databases up to June 2019. The search strategy included terms for breast cancer, lymph nodes, and the different imaging modalities. Only articles that reported pathological N-stage or the total number of positive axillary lymph nodes were considered for inclusion. Studies with patients undergoing neoadjuvant systemic therapy were excluded. Conclusion. There is no evidence that any of the current preoperative axillary imaging modalities can accurately exclude or identify breast cancer patients with extensive nodal involvement. Both negative PET/CT and negative MRI scans (with gadolinium-based contrast agents) are promising in excluding extensive nodal involvement. Larger studies should be performed to strengthen this conclusion. False-negative rates of axillary ultrasound and ultrasound-guided needle biopsy are too high to rely on negative results of these modalities in excluding extensive nodal involvement.

ObjectivesOrganization and governance of national healthcare might play an important role in decision-making and outcomes in patients with lung cancer. Both Denmark and the Netherlands have a high level of healthcare but a different financial coverage, governance and level of centralization. By using both national databases we analyzed the consequences of these differences on patterns of care and outcomes with a focus on morbidity, mortality and clinical staging.Materials and methodsGeneral numbers on both healthcare systems were requested. All patients who had surgery for lung cancer from 2013 to 2016 were included. Mortality, morbidity and clinical staging were analyzed for patients with NSCLC without metastases, only one operation and no neo-adjuvant therapy.ResultsIn 2016 annual budget as share of gross national product was 10.4% for both countries. In Denmark 4 hospitals performed lung surgery in 2016, compared to 43 hospitals in the Netherlands. We included 4030 Danish and 8286 Dutch patients. In the subgroup 30-day mortality was 1.5% in Denmark compared to 1.9% in the Netherlands. The percentage of patients with a complicated course was 24.4% and 34.8% respectively (p ConclusionSurgery for lung cancer is at a high level in both countries, reflected by low mortality-rates. Centralization has been implemented successfully in Denmark, which might explain the lower rate of patients with a complicated post-operative course, although different definitions preclude firm conclusions. In both countries correct clinical staging of lung cancer remains a challenge.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has been used to deal with life-threatening complications as well as back-up or active cardiovascular support during high-risk procedures in patients undergoing transcatheter aortic valve implantation (TAVI). PubMed and MEDLINE electronic databases were searched in order to identify studies with emergency or prophylactic V-A ECMO application in association with TAVI procedures. From November 2012 to November 2017, 14 relevant studies were identified that included 5,115 TAVI patients of whom 102 (2%) required V-A ECMO (22 prophylactically, 66 as an emergency and 14 without a reported indication). The reason for emergency V-A ECMO institution was detailed in 64 patients: left ventricle free wall rupture (n = 14), haemodynamic instability (n = 12), ventricular arrhythmias (n = 7), aortic annulus rupture (n = 6), coronary obstruction (n = 6), low left ventricular output (ejection fraction

A 78-year-old woman was referred to our hospital for further investigation of a bicytopenia. She had a history of rheumatoid arthritis and Sjogren syndrome for which she was treated with methotrexate and etanercept. She had no complaints, and during physical examination, no lymphadenopathy, masses, or visceromegaly was found. Hematologic evaluation showed the following results: hemoglobin, 9.7 g/dL (reference, 12.1–16.1 g/dL); white blood cells, 1.6 × 109/L (reference, 4.0–10.0 × 109/L); and thrombocytes, 156 × 109/L (reference 150–400 × 109/L). A peripheral blood smear did not show blasts or dysplastic features of the white blood cells. The patient had normal ferritin, vitamin B12, and folic acid concentrations without evidence of hemolysis. Serum protein electrophoresis (SPE)4 and immunofixation electrophoresis (IFE) with pentavalent antiserum were performed as M-protein screening. Both techniques demonstrated a broad band in the β/γ region (Fig. 1A). Further IFE analysis, shown in Fig. 1B, identified the abnormal pattern as a broad IgG band (blue brackets) with no corresponding light chain band (red brackets). These data suggested the presence of an IgG heavy chain M protein (γ-HC). Capillary electrophoresis (CE) combined with immunosubtraction (IS) analysis (Fig. 1C) confirmed that the abnormal pattern was caused by a γ-HC. IgG-IS (Fig. 1D) illustrated that the γ region consisted of polyclonal IgG-κ and IgG-λ (green). The β2 region largely consisted of IgG not associated with light chains (γ-HC, represented in red), and the remaining fraction (blue) was a combination of polyclonal IgA, polyclonal IgG, and nonimmunoglobulins. Fig. 1. Laboratory findings associated with γ-HC. (A), SPE and the corresponding densitometry scan show an abnormal broad band bridging the β/γ region. The same abnormal dense region is observed in the pentavalent screen. (B), IFE analysis demonstrates that the abnormal dense region corresponds to IgG (blue brackets) and has no …

Objective Cardiotocography (CTG) is an important tool for fetal surveillance in severe early-onset fetal growth restriction (FGR). Assessment of the CTG is usually performed visually (vCTG). However, it is suggested that computerized analysis of the CTG (cCTG) including short term variability (STV) could more accurately detect fetal compromise. The objective of this study was to systematically review the literature on the association between cCTG and perinatal outcome and the comparison of cCTG with vCTG. Study design A systematic search was performed in MEDLINE, EMBASE and Google Scholar. Studies were included that assessed prognostic accuracy of STV or compared STV to vCTG in patients with FGR. Risk of bias and concerns about applicability were assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) instrument. Results Of the 885 records identified in the search, five cohort studies (387 patients) were included. We found no randomized studies comparing STV with visual CTG in patients with FGR. The risk of bias of all studies was generally judged as ‘low’. One small study found an association of low STV with neonatal acidosis. One study observed no association of STV with long-term outcome. Composite analysis of all five studies showed a non-significant relative risk for acidosis after a low STV of 1.4 (95% CI 0.6–3.2, N = 387). Further meta-analysis was hampered due to heterogeneity in outcome reporting and use of different thresholds. Conclusion The evidence from the included studies did not support an association of STV and short or long term outcome. However, available data are limited and heterogeneous, and influenced by management based on STV. Solid evidence from a randomized controlled trial comparing STV with vCTG including long term infant outcome is needed before STV can be used clinically for timing of delivery in patients with FGR.

Introduction Nivolumab treatment is subject to large interpatient variability in both efficacy and toxicity, which may partly be explained by differences in nivolumab exposure. Exposure–response relationships in regular healthcare have not been extensively investigated for nivolumab. Therefore, we aimed to identify possible exposure–response relationships in nivolumab-treated patients with non–small-cell lung cancer (NSCLC). Methods Patients with NSCLC who started second-line nivolumab therapy (3 mg/kg Q2W) between May 5th 2016 and August 1st 2017, and from whom serial blood samples, toxicity data and outcome data were prospectively collected, were included. Follow-up was carried out until November 1st 2017. Patients were classified according to the best overall response (BOR) based on the Response Evaluation Criteria in Solid Tumours, v1.1, and toxicities according to the Common Terminology Criteria for Adverse Events. Nivolumab trough concentrations were measured after 2, 4 and 10 weeks of treatment, excluding dose delays, and calculated geometric means were tested versus BOR or toxicity using analysis of variance and an independent samples t-test, respectively. Overall survival (OS) and progression-free survival were compared between high and low trough concentration groups. Results Seventy-six patients were evaluable for analyses. Responders (n = 15) had higher mean trough concentrations than patients with progression (n = 33): 47% higher after 2 weeks (p = 0.001), 53% higher after 4 weeks (p = 0.008) and 73% higher after 10 weeks (p = 0.002). Higher trough concentrations were associated with longer OS (p = 0.001). Conclusions This study shows that patients with NSCLC with a response to nivolumab had a higher nivolumab exposure than patients with progression, indicating a potential exposure–response relationship. Further clinical research should focus on clarifying these exposure–response relationships.

The underling pathophysiological mechanisms that cause the formation of colonic diverticula (diverticulosis) remain unclear. Connective tissue changes due to ageing that cause changes in collagen structure of the colonic wall is one theory. Alpha-1-antitrypsin (A1AT) is a protease inhibitor known to protect connective tissue in other organs. Associations between (carriers of) A1AT deficiency and the development of colonic diverticula will be the main focus of this study. A multicentre prospective case-controlled study. In total, 230 patients ≥ 60 years with acute abdominal pain undergoing an abdominal computed tomography (CT) will be included. The research group consists of patients with diverticulosis and/or diverticulitis; controls are patients without diverticula (0 to ≤ 5 diverticula). Genotype analysis for A1AT deficiency will be performed. Hypothetically, connective tissue changes, in particular related to (carriers of) A1AT deficiency, can contribute to the development of diverticula and diverticulitis. We expect to find a higher prevalence of A1AT carriers in patients with diverticulosis compared to patients without diverticulosis. Having diverticulosis does not affect the general health of these individuals per se, when asymptomatic. Once an association is found, present findings can be the basis for a second study to assess the risk of developing acute diverticulitis and its disease course in carriers of A1AT deficiency. Because a large cohort is needed in the latter, we shall first perform a pilot study to investigate the likelihood of the primary hypothesis. Netherlands Trial register, NTR6251, NL55016.094.15

BackgroundDosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I–III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.MethodsAdvanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations. A PK model was generated, covariate effects assessed and internally validated by a bootstrap procedure. PK parameters were related to overall survival (OS) and the occurrence of immune-related adverse events (irAEs).Results588 serum samples derived from 122 patients with (non-)small-cell lung cancer ([N]SCLC), malignant pleural mesothelioma (MPM), melanoma and urothelial cell cancer (UCC) were analyzed. Median follow-up was 2.2 years. A one-compartment PK model was generated: body surface area (BSA) and serum albumin had a significant effect on drug clearance (CL; covariate estimate 1.46 and −1.43, respectively), and serum lactate dehydrogenase (LDH) on the distribution volume(Vd; 0.34). A significant inverse CL–OS relationship was determined for NSCLC (HR:1.69; 95%CI1.07–2.68; p=0.024) and MPM (HR: 3.29; 95% CI 1.08 to 10.09; p=0.037), after correction for prognostic factors, which could not confirmed for melanoma (p=0.22) or UCC (p=0.34). No relationship could be determined between CL and grade >3 irAEs (p=0.70).ConclusionsHigh interpatient variability of pembrolizumab PK is determined by BSA and serum albumin (on CL) and LDH (on Vd). A strong inverse CL–OS relationship was demonstrated for NSCLC and MPM, which could not be observed for melanoma and UCC. The findings suggest that personalized dosing should be prospectively explored.

A 32-year-old male, known to have atopic eczema, presented with a 3-day history of acute pleuritic chest pain and shortness of breath. No traumatic event had occurred. The pain was described as sharp and posture dependent, and was worse when leaning backwards. The patient had no palpitations, oedema or radiated pain. Dyspnoea was present both at rest and during exercise, without the presence of wheezing, haemoptysis or purulent sputum. He had no history of fever, cold shivers, weight loss or perspiration. His nutritional state was normal and he had no symptoms of nausea, vomiting or diarrhoea. For 3 days he had experienced dysphagia during meals. The patient was working full-time as a national courier and did not visit foreign countries for his work and did not travel outside Europe. The patient owned a dog but he had no specific contact with (farm) animals. He never smoked and never consumed alcohol. His physical condition, before the start of the present symptoms, was excellent due to daily exercises. On clinical examination our patient was conscious and orientated. He had a normal temperature of 36.9 °C, a respiratory rate of 16 breaths·min−1, blood pressure of 115/75 mmHg, heart rate of 68 beats·min−1 and an oxygen saturation of 95% on room air. Both percussion and respiratory sounds were reduced over the right hemithorax, without crackles or rhonchi. He had no pitting oedema around the ankles. A chest radiograph was performed (figure 1)., Most bronchogenic cysts are found incidentally and clinicians should be aware of an atypical case presentation. Total surgical resection is the treatment of choice of a bronchogenic cyst, especially in symptomatic patients. https://bit.ly/3uQrFXo