Safety of systemic anti-cancer treatment in oncology patients with non-severe COVID-19: a cohort study.

BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

[The rise, fall, and possible rise of LSD]. / De opkomst, val en mogelijke opkomst van lsd.

BACKGROUND: lsd and other hallucinogens or psychedelics have been therapeutically used in psychiatry in the period between the Second World War and the late 1980s. In the past years renewed interest in the medical sciences for research and therapeutic use of these substances has evolved.
AIM: A discussion of contemporary lsd research in the context of earlier research.
METHOD: A systematic survey of the literature on the psychiatric use of lsd and the reactions towards lsd use in society.
RESULTS: Since 1947 lsd has been therapeutically used in the treatment of anxiety, depression, addiction, post traumatic disorders, and other conditions. Since the early 1960s this use has been criticized because of the danger of evoking psychoses in patients, and because of the rise of a widespread non-medical use. However, there is no consolidated evidence-base for either the positive or the negative outcomes of lsd therapy.
CONCLUSION: At this moment it is unpredictable whether lsd will make a comeback in psychiatry. Contemporary research attempts to evade all public controversy and to build up a solid evidence-base. Nevertheless it demonstrates a direct continuity with earlier research.

[Management of adult bronchiectasis]. / Prise en charge des bronchectasies de l'adulte.

Non-cystic fibrosis bronchiectasis has been the subject of renewed interest over recent years. It is usually part of the evolutionary process of many infectious, autoimmune, genetic, developmental or allergic diseases. Its presentation and prognosis are heterogeneous and it causes significant morbidity and mortality with a real impact on the health care system. Thanks to increasingly available guidelines, it is now possible to define the optimal management that will include various therapeutic objectives : airway clearance, prevention and eradication of bacterial colonization, reduction of airway inflammation and exacerbations and improvement of quality of life.

Les bronchectasies non liées à la mucoviscidose font l'objet d'un regain d'intérêt. Elles font généralement partie du processus évolutif de nombreuses pathologies infectieuses, auto-immunes, génétiques, développementales ou allergiques. Leur présentation et leur pronostic sont hétérogènes et elles sont à l'origine d'une morbi-mortalité significative avec un impact important sur le système de soins de santé. Grâce à de récentes recommandations de bonne pratique, il est main¬tenant possible de définir une prise en charge optimale qui comportera différents objectifs thérapeutiques : le drainage des voies respiratoires, la prévention et l'éradication d'une colonisation bactérienne, la diminution de l'inflammation bronchique, la réduction des exacerbations et l'amélioration de la qualité de vie du patient.

[Forensic assessments from the Netherlands Institute of Forensic Psychiatry and Psychology in retrospect; applications of genetics and neuroscience, in 2000 and 2009]. / Rapportages pro Justitia van het Nederlands Instituut voor Forensische Psychiatrie en Psychologie in retrospectief; toepassingen van genetische en neurowetenschappelijke inzichten, in 2000 en 2009.

BACKGROUND: Developments in neurosciences and genetics are relevant for forensic psychiatry. AIM: To find out whether and how genetic and neuroscientific applications are being used in forensic psychiatric assessments, and, if they are, to estimate to what extent new applications will fit in with these uses. METHOD: We analysed 60 forensic psychiatric assessments from the Netherlands Institute of Forensic Psychiatry and Psychology, Pieter Baan Center, and 30 non-clinical assessments from 2000 and 2009. RESULTS: We found that (behavioral) genetic, neurological and neuropsychological applications played only a modest role in forensic psychiatric assessment and they represent different phases of the implementation process. Neuropsychological assessment already occupied a position of some importance, but needed to be better integrated. Applications from neurology were still being developed. Clinical genetic assessment was being used occasionally in order to diagnose a genetic syndrome with behavioral consequences. CONCLUSION: If further validated information becomes available in the future, it should be possible to integrate new research methods more fully into current clinical practice.

Estimation of renal function immediately after cessation of continuous renal replacement therapy at the ICU.

Estimating glomerular filtration (eGFR) after Continuous Renal Replacement Therapy (CRRT) is important to guide drug dosing and to assess the need to re-initiate CRRT. Standard eGFR equations cannot be applied as these patients neither have steady-state serum creatinine concentration nor average muscle mass. In this study we evaluate the combination of dynamic renal function with CT-scan based correction for aberrant muscle mass to estimate renal function immediately after CRRT cessation. We prospectively included 31 patients admitted to an academic intensive care unit (ICU) with a total of 37 CRRT cessations and measured serum creatinine before cessation (T1), directly (T2) and 5 h (T3) after cessation and the following two days when eGFR stabilized (T4, T5). We used the dynamic creatinine clearance calculation (D3C) equation to calculate eGFR (D3CGFR) and creatinine clearance (D3Ccreat) between T2-T3. D3Ccreat was corrected for aberrant muscle mass when a CT-scan was available using the CRAFT equation. We compared D3CGFR to stabilized CKD-EPI at T5 and D3CCreat to 4-h urinary creatinine clearance (4-h uCrCl) between T2-T3. We retrospectively validated these results in a larger retrospective cohort (NICE database; 1856 patients, 2064 cessations). The D3CGFR was comparable to observed stabilized CKD-EPI at T5 in the prospective cohort (MPE = - 1.6 ml/min/1.73 m2, p30 = 76%) and in the retrospective NICE-database (MPE = 3.2 ml/min/1.73 m2, p30 = 80%). In the prospective cohort, the D3CCreat had poor accuracy compared to 4-h uCrCl (MPE = 17 ml/min/1.73 m2, p30 = 24%). In a subset of patients (n = 13) where CT-scans were available, combination of CRAFT and D3CCreat improved bias and accuracy (MPE = 8 ml/min/1.73 m2, RMSE = 18 ml/min/1.73 m2) versus D3CCreat alone (MPE = 18 ml/min/1.73 m2, RMSE = 32 ml/min/1.73 m2). The D3CGFR improves assessment of eGFR in ICU patients immediately after CRRT cessation. Although the D3CCreat had poor association with underlying creatinine clearance, inclusion of CT derived biometric parameters in the dynamic renal function algorithm further improved the performance, stressing the role of muscle mass integration into renal function equations in critically ill patients.

GFR estimation is complicated by a high incidence of non-steady-state serum creatinine concentrations at the emergency department.

BACKGROUND: Acquiring a reliable estimate of glomerular filtration rate (eGFR) at the emergency department (ED) is important for clinical management and for dosing renally excreted drugs. However, renal function formulas such as CKD-EPI can give biased results when serum creatinine (SCr) is not in steady-state because the assumption that urinary creatinine excretion is constant is then invalid. We assessed the extent of this by analysing variability in SCr in patients who visited the ED of a tertiary care centre. METHODS: Data from ED visits at the University Medical Centre Utrecht, the Netherlands between 2012 and 2019 were extracted from the Utrecht Patient Oriented Database. Three measurement time points were defined for each visit: last SCr measurement before visit as baseline (SCr-BL), first measurement during visit (SCr-ED) and a subsequent measurement between 6 and 24 hours during admission (SCr-H1). Non-steady-state SCr was defined as exceeding the Reference Change Value (RCV), with 15% decrease or 18% increase between successive SCr measurements. Exceeding the RCV was deemed as a significant change. RESULTS: Of visits where SCr-BL and SCr-ED were measured (N = 47,540), 28.0% showed significant change in SCr. Of 17,928 visits admitted to the hospital with a SCr-H1 after SCr-ED, 27,7% showed significant change. More than half (55%) of the patients with SCr values available at all three timepoints (11,054) showed at least one significant change in SCr over time. CONCLUSION: One third of ED visits preceded and/or followed by creatinine measurement show non-stable serum creatinine concentration. At the ED automatically calculated eGFR should therefore be interpreted with great caution when assessing kidney function.

The value of endoscopic ultrasound after bronchoscopy to diagnose thoracic sarcoidosis.

A clinicoradiological presentation of thoracic sarcoidosis requires histopathology in order to establish the diagnosis. Flexible bronchoscopy has a reasonable diagnostic yield and is the procedure of first choice for diagnosis. Endoscopic ultrasound (endoscopic ultrasound-guided fine needle aspiration/endobronchial ultrasound-guided transbronchial needle aspiration) can help in the diagnosis of sarcoidosis. An implementation strategy of endoscopic ultrasound for the diagnosis of sarcoidosis following negative flexible bronchoscopy results was examined prospectively in 15 clinics. A total of 137 patients (92 males; median age 43 yrs) were included, and sarcoidosis was found in 115 (84%). Alternative diagnoses were tuberculosis, lymphangitis carcinomatosa, pneumoconiosis and alveolitis. All patients were sent for flexible bronchoscopy, which was performed in 121 (88%), resulting in a definite diagnosis in 57 (42%). A total of 80 patients were sent for endoscopic ultrasound, which could be performed in 72 (90%), yielding a definite diagnosis in 47 (59%). Endoscopic ultrasound following negative flexible bronchoscopy avoided a surgical procedure in 47 out of 80 patients. The sensitivity of flexible bronchoscopy for sarcoidosis was 45% (95% confidence interval 35-54%), but 62% (50-72%) if biopsy specimens were taken. The sensitivity of endoscopic ultrasound following negative flexible bronchoscopy results was 71% (58-82%). With this strategy, 97 out of 115 (84% (76-90%)) of proven sarcoidosis was diagnosed using endoscopy. This large prospective implementation study (trial number NCT00888212; ClinicalTrials.gov) shows that endoscopic ultrasound is valuable for diagnosing sarcoidosis after negative flexible bronchoscopy results.

[Pharmacotherapy in patients with loss of renal function]. / Farmacotherapie bij nierfunctieverlies.

When dosing renally excreted drugs in patients with kidney disease, it is important to have a reliable estimate of renal function. The estimated glomerular filtration rate (eGFR) is often used in the clinic, although this measure can be inaccurate in certain situations. Choosing the appropriate drug and dosage should therefore not be solely based on the eGFR. In this review, we discuss the physiology behind renal function estimation and drug dosing and propose a step by step approach to dosing renally excreted drugs in patients with kidney disease.

Efficacy of yoga, tai chi and qi gong on the main symptoms of chronic obstructive pulmonary disease: A systematic review.

INTRODUCTION: The aim of this systematic review was to summarize the effects of yoga, qi gong or tai chi in COPD patients. METHODS: Studies evaluating effects of the selected complementary therapies on lung function, dyspnea, quality of life or functional exercise capacity in COPD patients were identified and reviewed from three databases. RESULTS: Eighteen studies were included. Six studies evaluated the effects of yoga and the others focused on tai chi or qi gong separately or combined. The duration of the programs ranged from 6 weeks to 6 months and the frequency from 2 to 7 times a week. Each session reached 30 to 90 minutes. Benefits were observed on lung function and functional exercise capacity but benefit was clearly stated neither on quality of life nor on dyspnea. CONCLUSION: This systematic review highlights the potential of these therapies as complementary therapeutic approach in COPD patients.

[Development of concepts of disease, diagnostics and neurosurgical treatment of brain tumours in The Netherlands (1890-1950)]. / Ontwikkeling van ziekteconcept, diagnostiek en neurochirurgische behandeling van hersentumoren in Nederland (1890-1950).

The history of the treatment ofbrain tumours in the Netherlands begins around 1890. From this time up to 1950, following other European countries and later the United States, the conceptualization, diagnostics, and surgical treatment of brain tumours changed dramatically. New morphological classifications were introduced, as well as technical innovations in the fields ofimaging diagnostics and surgical methods. At the same time, the common view ofclinical signs ofbrain tumours changed into the concept that symptoms were caused by increased intracranial pressure. As is the case today, the innovations in Dutch neurosurgery in the first half of the 20th century were based on the interaction between techniques, knowledge and clinical experiences.

[Increased serum CA 19.9 in bronchiectasis]. / Elévation du CA 19.9 sérique et bronchectasies.

INTRODUCTION: CA 19.9 is considered the most specific and sensitive serological marker of pancreatic adenocarcinoma. However, serum CA 19.9 can be raised in several non-neoplastic disorders, particularly in various benign pulmonary diseases. An increase in serum CA 19.9 in bronchiectasis remains exceptional. CASE REPORT: We report the case of a 67 year old woman in whom a serum level of more than 1500 U/ml (normal value less than 37 U/ml) was found incidentally. Exhaustive investigation and clinical evolution excluded a neoplastic digestive disorder but positron emission tomography revealed a distinct hypermetabolic focus in the area of the hilum of the right lung. A complementary work-up (CT scan and fibreoptic bronchoscopy) demonstrated bilateral bronchiectasis colonised with Haemophilus influenzae. Antibiotic therapy with amoxicillin-clavulanic acid brought about a decrease in the serum CA 19.9 but level of the tumour marker remained abnormal after more than 2 years. CONCLUSION: This case report emphasises the uselessness of tumour markers as screening tests as a serum level of CA 19.9 up to 50 times normal may be found in benign respiratory disorders such as bronchiectasis.

[Medical perception of the hereditary aspects of cancer in The Netherlands, 1900-1980]. / Medische omgang met erfelijke aspecten van kanker in Nederland, 1900-1980.

Since at least the 18th century doctors have drawn connections between cancer and heredity in the hope of making progress in diagnosis, treatment and opportunities for prevention. From 1910 to 1980, the relationship between cancer and heredity was hardly discussed publicly in the Netherlands. This facilitated the development of models of public prevention and individual predisposition for certain cancers, such as retinoblastoma, after the Second World War. Historical experience shows that the perception of the relationship between cancer and heredity is influenced by more than just rational factors. The fear of creating 'cancerphobia' has hindered this perception in the past; fatalism ('it makes no difference anyway') and stigmatisation (familial and societal pressure) may negatively influence participation in early detection and prevention. This remains a problematic issue today.

[Contributions of the Netherlands and its colonies to the knowledge of the cause of leprosy in the 19th century]. / Bijdragen van Nederland en zijn koloniën aan de kennis over de oorzaak van lepra in de 19e eeuw.

OBJECTIVE: To determine the Dutch contributions to the formulation of the concept that leprosy is an infectious disease. DESIGN: Literature study. METHOD: A search for relevant publications was made in the Nederlands Tijdschrift voor Geneeskunde (Dutch journal of Medicine; NTvG) and the Geneeskundig Tijdschrift voor Nederlandsch-Indië (Medical Journal of the Dutch Indies; GTNI) with the aid of the search terms 'lepra [leprosy]', 'lepra Arabum [Arab leprosy]', 'melaatsheid [leprosy]' and 'elephantiasis Graecorum [Greek elephantiasis]'. In addition, on the basis of references in the publications in the NTvG and the GTNI, as well as via searches in the catalogues of the Royal Library in The Hague and the libraries of Dutch universities, an inventory was made of the Dutch medical dissertations and other monographs on leprosy, as well as the medical historical review articles, from the 19th century. RESULTS: For a long time, physicians described the aetiology of leprosy in terms of 'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed. From the middle of the 19th century onwards, this explanatory model with multiple possible solutions gave way to a controversy between two explanatory models: heredity as an 'anti-contagious' principle versus contagiosity. These two explanatory models were mutually exclusive in their universal aspirations. The debate in the Netherlands took place in the field of tension between European concepts on the one hand and on the other hand ideas and practices resulting from the interaction between the Netherlands and its colonies. Inspired in part by the writings of the Dutch physician C L Drognat Landré, who based his contagion theory on observations in Surinam, the Norwegian G. H. A. Hansen discovered the leprosy bacillus in 1873. It was not until 1897, at the international leprosy conference in Berlin, however, that consensus was to be reached on leprosy being an infectious disease. CONCLUSION: An essential contribution to the development of the contemporary ideas as to the cause of leprosy was made from the Netherlands.

Targeting BET proteins improves the therapeutic efficacy of BCL-2 inhibition in T-cell acute lymphoblastic leukemia.

Inhibition of anti-apoptotic BCL-2 (B-cell lymphoma 2) has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia (T-ALL) as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET (bromodomain and extraterminal) bromodomain inhibitor JQ1. Notably, this drug synergism was confirmed in vivo using T-ALL cell line and patient-derived xenograft models. Moreover, the therapeutic benefit of this drug combination might, at least in part, be mediated by an acute induction of the pro-apoptotic factor BCL2L11 and concomitant reduction of BCL-2 upon BET bromodomain inhibition, ultimately resulting in an enhanced binding of BIM (encoded by BCL2L11) to BCL-2. Altogether, our work provides a rationale to develop a new type of targeted combination therapy for selected subgroups of high-risk leukemia patients.

[Mycobacterium avium tumoral infection mimicking a lung adenocarcinoma: A potential diagnostic pitfall]. / Infection à Mycobacterium avium simulant un adénocarcinome pulmonaire : un potentiel piège diagnostique.

INTRODUCTION: The incidence of atypical mycobacterial infection in Europe is estimated at one case per 100,000 persons/year. Despite the low incidence of Mycobacterium avium infection, it can result in a nodular lesion simulating lung cancer. We report a case of atypical mycobacteriosis, mimicking lung cancer, which led to a lobectomy. CASE REPORT: It was a right pulmonary upper lobe nodule found in a 63-year-old COPD patient, partially nephrectomized for renal carcinoma, and weekly treated by methotrexate for rheumatoid arthritis. FDG uptake was weakly positive on PET-CT (SUV=2.2) in the upper fissure. Bronchoscopy yielded no lesions and no bacteriological findings. Percutaneous transthoracic lung biopsy revealed lung adenocarcinoma stage T1 (a) N0M0. An upper lobectomy with lymphadenectomy was performed. Histological examination revealed epithelioid granuloma surrounded by giant cells suggestive of tuberculomas. The bronchial washing fluid culture was positive for Mycobacterium avium after 7 weeks. CONCLUSION: In pseudo-neoplastic forms of atypical mycobacteriosis, the presence of alveolar, inflammatory cytonuclear abnormalities can mimic an adenocarcinoma. Making the difference between the cytonuclears defects related to inflammation or neoplasia remains a daily challenge in histopathology.

Compliance with nasal CPAP in obstructive sleep apnea patients.

Continuous positive airway pressure (CPAP) is currently the treatment of choice for the majority of patients with obstructive sleep apnea (OSA). After a CPAP trial, the initial acceptance rate is 70-80%. Patients who derive no subjective benefit from such a trial are poor candidates for home treatment with CPAP because they are likely to exhibit lower adherence and compliance rates. About 90% of OSA patients provided with CPAP apparatus will adhere to long-term CPAP treatment. Patients abandoning CPAP do so during the first few months of home therapy, a period during which close monitoring and support is warranted. Because of the strong correlation between the machine run time and effective pressure delivered at the nasal mask (90-95%), the time-counter of the CPAP device is sufficient to monitor compliance in clinical practice, allowing for early intervention in cases of suboptimal use. Longterm acceptors of CPAP display a satisfactory compliance (5-6.5 h of average daily use) which compares favourably with compliance with treatment in other chronic diseases. Lower acceptance and compliance rates have been reported in North America as compared to Europe. This could be related to cultural differences or different routines of prescription and follow-up.

Effects of Breathe Right on snoring: a polysomnographic study.

The nasal vestibule is a major site of resistance to airflow in healthy subjects. A high nasal resistance may increase snoring. Activation of the alae nasi and alar retraction reduce resistance to airflow and improve ventilation. The Breathe Right (BR) device has been proposed to reduce or eliminate snoring by improving nasal breathing. We assessed the efficacy of BR on sleep quality and snoring during 2 full-night polysomnographies, the first without and the second with BR. Ten non-apnoeic snorers were studied. Snoring was present during 22-98% of total sleep time during the control night. Ear-nose-throat examination disclosed a nasal valve anomaly in five subjects, objectivated by anterior and posterior rhinomanometry. Quality of sleep and snoring were not influenced by BR, even when different sleep stages were analysed separately. No difference in snoring index was found between snorers with or without nasal valve anomaly. We conclude that BR is ineffective in relieving snoring in non-apnoeic snorers.

Non-specific interstitial pneumonia showing a "crazy paving" pattern on high resolution CT.

Non-specific interstitial pneumonia is characterized pathologically by uniform interstitial inflammation and fibrosis. This disease is most commonly demonstrated on high resolution CT as subpleural ground-glass opacity mixed with irregular linear opacities. The authors report a case of non-specific interstitial pneumonia with high resolution findings consistent with a "crazy paving pattern". This appearance, represented by smoothly thickened interlobular septa with a background of geographic areas of ground-glass opacity, is unusual for non-specific interstitial pneumonia and was indistinguishable from other interstitial or alveolar lung diseases.

Hemidiaphragmatic paralysis, an unusual presentation of Parsonage-Turner syndrome.

A previously healthy 38-year-old man presented a typical Parsonage-Turner syndrome (PTS) three weeks after a cold and unusual muscular exercise. In addition to the motor and sensory defects of the upper limbs, a right hemidiaphragmatic paralysis occurred, which proved to be reversible after several months. A brief review of the hemidiaphragmatic injury in PTS is presented.

Persistent pneumomediastinum and dermatomyositis: a case report and review of the literature.

We describe a 42-year-old man with dermatomyositis and interstitial lung disease who presented with anterior neck pain and dyspnoea. Chest radiographs showed subcutaneous emphysema, pneumomediastinum and diffuse reticulonodular infiltration in both lungs. After the administration of high doses of prednisolone, an improvement of pulmonary function and respiratory symptoms was observed but the pneumomediastinum persists 12 months after diagnosis, and without any complication. We review the cases that have been reported thus far of pneumomediastinum associated with dermatomyositis and discuss the possible mechanisms involved. We conclude that pneumomediastinum is not an uncommon complication of dermatomyositis and that its aetiopathogenesis remains very unclear.