Insulin Secretion in Bantu with Siderosis or Hepatoma

The IR and concomitant GTC was evaluated in 10 siderotic Bantu patients and in 11 Bantu patients suffering from hepatoma. A normal IR was found in the siderotic Bantu, occurring, however, at much higher blood glucose levels than those of the control Bantu group. This relatively low IR is ascribed to impaired secretion of the ,β-cells, due most probably to significant low deposits in the pancreas. A similar relatively low IR in the presence of elevated blood glucose levels was found in the patients suffering from hepatoma. Their IR was furthermore delayed, possibly due to impaired destruction of insulin by the damaged liver. Since these patients were seemingly not siderotic, their relatively low IR apparently cannot be ascribed to iron deposits in the pancreas. It could, however, be due to exhaustion of the ,β-cells caused by the persistent hyperglycaemia observed in the patients -with hepatoma

Biomarker profiling in plants to distinguish between exposure to chlorine gas and bleach using LC-HRMS/MS and chemometrics

Since its first employment in World War I, chlorine gas has often been used as chemical warfare agent. Unfortunately, after suspected release, it is difficult to prove the use of chlorine as a chemical weapon and unambiguous verification is still challenging. Furthermore, similar evidence can be found for exposure to chlorine gas and other, less harmful chlorinating agents. Therefore, the current study aims to use untargeted high resolution mass spectrometric analysis of chlorinated biomarkers together with machine learning techniques to be able to differentiate between exposure of plants to various chlorinating agents. Green spire (Euonymus japonicus), stinging nettle (Urtica dioica), and feathergrass (Stipa tenuifolia) were exposed to 1000 and 7500 ppm chlorine gas and household bleach, pool bleach, and concentrated sodium hypochlorite. After sample preparation and digestion, the samples were analyzed by liquid chromatography high resolution tandem mass spectrometry (LC-HRMS/MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). More than 150 chlorinated compounds including plant fatty acids, proteins, and DNA adducts were tentatively identified. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed clear discrimination between chlorine gas and bleach exposure and grouping of the samples according to chlorine concentration and type of bleach. The identity of a set of novel biomarkers was confirmed using commercially available or synthetic reference standards. Chlorodopamine, dichlorodopamine, and trichlorodopamine were identified as specific markers for chlorine gas exposure. Fenclonine (Cl-Phe), 3-chlorotyrosine (Cl-Tyr), 3,5-dichlorotyrosine (di-Cl-Tyr), and 5-chlorocytosine (Cl-Cyt) were more abundantly present in plants after chlorine contact. In contrast, the DNA adduct 2-amino-6-chloropurine (Cl-Ade) was identified in both types of samples at a similar level. None of these chlorinated biomarkers were observed in untreated samples. The DNA adducts Cl-Cyt and Cl-Ade could clearly be identified even three months after the actual exposure. This study demonstrates the feasibility of forensic biomarker profiling in plants to distinguish between exposure to chlorine gas and bleach

Masquerade of an emergency: cardiac tamponade as a deceptive presentation of primary cardiac diffuse large b-cell lymphoma-a case report

Background Primary cardiac diffuse large B-cell lymphoma (CDLBCL) is an exceptionally rare entity, estimated to represent less than 1% of all primary cardiac tumours. In this case report, we emphasize the diagnostic importance of multimodality imaging and the need for additional procedures, such as tissue biopsy, in a case with a primary cardiac lymphoma presenting with cardiac tamponade. Case summary An 80-year-old male was admitted to the emergency department with a life-threatening tamponade demanding immediate sternotomy. Pre-operative echocardiography unveiled pericardial effusion and a thickened apex. While computed tomography ruled out an aortic dissection, surgery revealed an unexpected vascular-rich mass at the right ventricle and apex, too perilous for biopsy. Post-operative imaging misinterpreted this mass as a benign haematoma. Subsequently, the patient was admitted to the intensive care unit, but after a conservative treatment strategy, the patient died. An autopsy revealed a primary CDLBCL. Discussion This case demonstrates the deceptive nature of primary CDLBCL, often complicated by cardiac tamponade. It underscores the pivotal role of pathologic assessment, even amidst the perils of sternotomy, to determine the origin of abnormal cardiac masses. A heightened awareness among physicians is imperative, for such elusive diagnoses may slip by, with potentially fatal outcomes

The evolution of trauma care in the Netherlands over 20 years

Introduction: In 1999 an inclusive trauma system was initiated in the Netherlands and a nationwide trauma registry, including all admitted trauma patients to every hospital, was started. The Dutch trauma system is run by trauma surgeons who treat both the truncal (visceral) and extremity injuries (fractures). Materials and Methods: In this comprehensive review based on previous published studies, data over the past 20 years from the central region of the Netherlands (Utrecht) was evaluated. Results: It is demonstrated that the initiation of the trauma systems and the governance by the trauma surgeons led to a region-wide mortality reduction of 50% and a mortality reduction for the most severely injured of 75% in the level 1 trauma centre. Furthermore, major improvements were found in terms of efficiency, demonstrating the quality of the current system and its constructs such as the type of surgeon. Due to the major reduction in mortality over the past few years, the emphasis of trauma care evaluation shifts towards functional outcome of severely injured patients. For the upcoming years, centralisation of severely injured patients should also aim at the balance between skills in primary resuscitation and surgical stabilization versus longitudinal surgical involvement. Conclusion: Further centralisation to a limited number of level 1 trauma centres in the Netherlands is necessary to consolidate experience and knowledge for the trauma surgeon. The future trauma surgeon, as specialist for injured patients, should be able to provide the vast majority of trauma care in this system. For the remaining part, intramural, regional and national collaboration is essentia

Glycan-dependent immunogenicity of recombinant soluble trimeric hemagglutinin

Recombinant soluble trimeric influenza A virus (IAV) hemagglutinin (sHA3) has proven an effective vaccine antigen against IAV. Here, we investigate to what extent the glycosylation status of the sHA3 glycoprotein affects its immunogenicity. Different glycosylation forms of subtype H5 trimeric HA protein (sH53) were produced by expression in insect cells and different mammalian cells in the absence and presence of inhibitors of N-glycan-modifying enzymes or by enzymatic removal of the oligosaccharides. The following sH53 preparations were evaluated: (i) HA proteins carrying complex glycans produced in HEK293T cells; (ii) HA proteins carrying Man9GlcNAc2 moieties, expressed in HEK293T cells treated with kifunensine; (iii) HA proteins containing Man5GlcNAc2 moieties derived from HEK293S GnTI(-) cells; (iv) insect cell-produced HA proteins carrying paucimannosidic N-glycans; and (v) HEK293S GnTI(-) cell-produced HA proteins treated with endoglycosidase H, thus carrying side chains composed of only a single N-acetylglucosamine each. The different HA glycosylation states were confirmed by comparative electrophoretic analysis and by mass spectrometric analysis of released glycans. The immunogenicity of the HA preparations was studied in chickens and mice. The results demonstrate that HA proteins carrying terminal mannose moieties induce significantly lower hemagglutination inhibition antibody titers than HA proteins carrying complex glycans or single N-acetylglucosamine side chains. However, the glycosylation state of the HA proteins did not affect the breadth of the antibody response as measured by an HA1 antigen microarray. We conclude that the glycosylation state of recombinant antigens is a factor of significant importance when developing glycoprotein-based vaccines, such as recombinant HA proteins

Efficacy and safety of abrocitinib in patients with severe and/or difficult-to-treat atopic dermatitis: a post hoc analysis of the randomized phase 3 JADE COMPARE trial

Background: Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200 mg and 100 mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200 mg) than dupilumab at week 2. Objective: This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a post hoc analysis of the JADE COMPARE trial. Methods: Adults with moderate-to-severe AD received once-daily oral abrocitinib 200 mg or 100 mg, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator’s Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥ 2-point improvement from baseline, ≥ 75% and ≥ 90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥ 4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days 2–15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week 16. Results: The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.01); the time to achieve this response was shorter with abrocitinib 200 mg (range 4.5–6.0 days) than abrocitinib 100 mg (range 5.0–17.0 days), dupilumab (range 8.0–11.0 days), and placebo (range 3.0–11.5 days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy. Conclusions: Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD. Trial registration:: ClinicalTrials.gov, NCT03720470

Outcome of severely injured patients in a unique trauma system with 24/7 double trauma surgeon on-call service

Background: The presence of in-house attending trauma surgeons has improved efficiency of processes in the treatment of polytrauma patients. However, literature remains equivocal regarding the influence of the presence of in-house attendings on mortality. In our hospital there is a double trauma surgeon on-call system. In this system an in-house trauma surgeon is 24/7 backed up by a second trauma surgeon to assist with urgent surgery or multiple casualties. The aim of this study was to evaluate outcome in severely injured patients in this unique trauma system. Methods: From 2014 to 2021, a prospective population-based cohort consisting of consecutive polytrauma patients aged ≥ 15 years requiring both urgent surgery (≤ 24h) and admission to Intensive Care Unit (ICU) was investigated. Demographics, treatment, outcome parameters and pre- and in-hospital transfer times were analyzed. Results: Three hundred thirteen patients with a median age of 44 years (71% male), and median Injury Severity Score (ISS) of 33 were included. Mortality rate was 19% (68% due to traumatic brain injury). All patients stayed ≤ 32 min in ED before transport to either CT or OR. Fifty-one percent of patients who needed damage control surgery (DCS) had a more deranged physiology, needed more blood products, were more quickly in OR with shorter time in OR, than patients with early definitive care (EDC). There was no difference in mortality rate between DCS and EDC patients. Fifty-six percent of patients had surgery during off-hours. There was no difference in outcome between patients who had surgery during daytime and during off-hours. Death could possibly have been prevented in 1 exsanguinating patient (1.7%). Conclusion: In this cohort of severely injured patients in need of urgent surgery and ICU support it was demonstrated that surgical decision making was swift and accurate with low preventable death rates. 24/7 Physical presence of a dedicated trauma team has likely contributed to these good outcomes

Recurrent differentiated thyroid cancer: Towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): Study protocol of a multicenter observational cohort study

Background: After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.Methods/Design: In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.Discussion: This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.Trial registration: Clinicaltrials.gov identifier: NCT01641679

Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

Background: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab. Objective: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC). Methods: Electronic survey and in-person discussion of management strategies. Results: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist. Limitations: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey. Conclusion: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 2