Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation

  Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

Pierwotny maziówczak opłucnej i płuca z przerzutami do mózgu u dziecka: nietypowe objawy

Pierwotny nowotwór płuc rzadko występuje u dzieci. Najczęściej spotykane pierwotne złośliwe nowotwory płuc u dzieci to blastoma opłucnej i płuc oraz rakowiak. Maziówczak stanowi około 1% wszystkich nowotworów złośliwych występujących u dzieci. Maziówczak opłucnej i płuca jest zjawiskiem rzadkim i trudnym do rozpoznania. Mięsaki tkanek miękkich zazwyczaj posiadają dużą skłonność do przerzutów, jednak przerzuty do mózgu występują sporadycznie, nawet w zaawansowanych postaciach rozsianej choroby. Taki przebieg choroby został przedstawiony zaledwie w 3 opisach przypadków. Pierwotny maziówczak opłucnej i płuc z przerzutami do mózgu jest jeszcze rzadziej spotykany. W niniejszej pracy przedstawiono przypadek 11-letniego chłopca, u którego pojawiły się gorączka i trwający od 20 dni kaszel. Początkowo sądzono, że przyczyną jest ropień płuc, lecz po wykonaniu badań histopatologicznego, immunohistochemicznego i molekularnego rozpoznano maziówczaka. Po upływie tygodnia od pierwszej wizyty u dziecka pojawiły się objawy neurologiczne, tj. drgawki i stopniowo postępujące osłabienie siły kończyny dolnej. Wyniki tomografii komputerowej i rezonansu magnetycznego wskazywały na istnienie przerzutów do mózgu. Biorąc pod uwagę rzadkość występowania nowotworów płuc u dzieci, rozpoznanie kliniczne choroby pozostaje prawdziwym wyzwaniem. Często zdarza się, że rozpoznanie jest opóźnione, ponieważ objawy ze strony układu oddechowego mogą być przypisywane stanom zapalnym lub chorobom zakaźnym. Pierwotny maziówczak płuc i opłucnej występuje rzadko i sporadycznie wywołuje przerzuty do mózgu. Powinien być jednak brany pod uwagę przy rozpoznaniu różnicowym pierwotnych nowotworów płuc u dzieci, ponieważ przy wczesnym rozpoznaniu może być uleczalny, zaś w przypadku agresywnego przebiegu z przerzutami na przykład do mózgu, wczesne rozpoznanie jest szczególnie ważne.Pierwotny nowotwór płuc rzadko występuje u dzieci. Najczęściej spotykane pierwotne złośliwe nowotwory płuc u dzieci to blastoma opłucnej i płuc oraz rakowiak. Maziówczak stanowi około 1% wszystkich nowotworów złośliwych występujących u dzieci. Maziówczak opłucnej i płuca jest zjawiskiem rzadkim i trudnym do rozpoznania. Mięsaki tkanek miękkich zazwyczaj posiadają dużą skłonność do przerzutów, jednak przerzuty do mózgu występują sporadycznie, nawet w zaawansowanych postaciach rozsianej choroby. Taki przebieg choroby został przedstawiony zaledwie w 3 opisach przypadków. Pierwotny maziówczak opłucnej i płuc z przerzutami do mózgu jest jeszcze rzadziej spotykany. W niniejszej pracy przedstawiono przypadek 11-letniego chłopca, u którego pojawiły się gorączka i trwający od 20 dni kaszel. Początkowo sądzono, że przyczyną jest ropień płuc, lecz po wykonaniu badań histopatologicznego, immunohistochemicznego i molekularnego rozpoznano maziówczaka. Po upływie tygodnia od pierwszej wizyty u dziecka pojawiły się objawy neurologiczne, tj. drgawki i stopniowo postępujące osłabienie siły kończyny dolnej. Wyniki tomografii komputerowej i rezonansu magnetycznego wskazywały na istnienie przerzutów do mózgu. Biorąc pod uwagę rzadkość występowania nowotworów płuc u dzieci, rozpoznanie kliniczne choroby pozostaje prawdziwym wyzwaniem. Często zdarza się, że rozpoznanie jest opóźnione, ponieważ objawy ze strony układu oddechowego mogą być przypisywane stanom zapalnym lub chorobom zakaźnym. Pierwotny maziówczak płuc i opłucnej występuje rzadko i sporadycznie wywołuje przerzuty do mózgu. Powinien być jednak brany pod uwagę przy rozpoznaniu różnicowym pierwotnych nowotworów płuc u dzieci, ponieważ przy wczesnym rozpoznaniu może być uleczalny, zaś w przypadku agresywnego przebiegu z przerzutami na przykład do mózgu, wczesne rozpoznanie jest szczególnie ważne

Evaluating the Clinical Feasibility of an Artificial Intelligence-Powered, Web-Based Clinical Decision Support System for the Treatment of Depression in Adults: Longitudinal Feasibility Study.

BACKGROUND: Approximately two-thirds of patients with major depressive disorder do not achieve remission during their first treatment. There has been increasing interest in the use of digital, artificial intelligence-powered clinical decision support systems (CDSSs) to assist physicians in their treatment selection and management, improving the personalization and use of best practices such as measurement-based care. Previous literature shows that for digital mental health tools to be successful, the tool must be easy for patients and physicians to use and feasible within existing clinical workflows. OBJECTIVE: This study aims to examine the feasibility of an artificial intelligence-powered CDSS, which combines the operationalized 2016 Canadian Network for Mood and Anxiety Treatments guidelines with a neural network-based individualized treatment remission prediction. METHODS: Owing to the COVID-19 pandemic, the study was adapted to be completed entirely remotely. A total of 7 physicians recruited outpatients diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Patients completed a minimum of one visit without the CDSS (baseline) and 2 subsequent visits where the CDSS was used by the physician (visits 1 and 2). The primary outcome of interest was change in appointment length after the introduction of the CDSS as a proxy for feasibility. Feasibility and acceptability data were collected through self-report questionnaires and semistructured interviews. RESULTS: Data were collected between January and November 2020. A total of 17 patients were enrolled in the study; of the 17 patients, 14 (82%) completed the study. There was no significant difference in appointment length between visits (introduction of the tool did not increase appointment length; F2,24=0.805; mean squared error 58.08; P=.46). In total, 92% (12/13) of patients and 71% (5/7) of physicians felt that the tool was easy to use; 62% (8/13) of patients and 71% (5/7) of physicians rated that they trusted the CDSS. Of the 13 patients, 6 (46%) felt that the patient-clinician relationship significantly or somewhat improved, whereas 7 (54%) felt that it did not change. CONCLUSIONS: Our findings confirm that the integration of the tool does not significantly increase appointment length and suggest that the CDSS is easy to use and may have positive effects on the patient-physician relationship for some patients. The CDSS is feasible and ready for effectiveness studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04061642; http://clinicaltrials.gov/ct2/show/NCT04061642

Glucose-6-Phosphate Dehydrogenase Deficiency, Chlorproguanil-Dapsone with Artesunate and Post-treatment Haemolysis in African children treated for uncomplicated Malaria

Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

End-Stage Renal Disease Among HIV-Infected Adults in North America

Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Assessment of minimal residual disease in childhood acute lymphoblastic leukemia

The improving cure rate of childhood acute lymphoblastic leukemia (cALL) is considered as success story in the field of oncology. It has become possible due to progressive refinement of treatment over the period of years. Assessment of minimal residual disease (MRD) is one such tool to further refine and personalize treatment of cALL. Assessment of MRD is no longer a research tool; it has become an integral part of comprehensive management of cALL. Prognostic importance of MRD in cALL is well accepted, but translation of this new information in improving therapy has just begun especially in developing countries like ours. There is increasing understanding among clinicians regarding importance of MRD assessment in day to day clinical practice. Still, there are many issues and lack of clarity with respect to MRD assessment. We are making an attempt in this review to address such issues faced during practical implication of MRD assessment