Organising Pneumonia - a review and results from Icelandic studies

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenOrganising pneumonia (OP) is a relatively rare interstitial lung disease. It s definition is based on a characteristic histological pattern in the presence of certain clinical and radiological features. Organising pneumonia represents also what has been called Bronchiolitis Obliterans Organising Pneumonia (BOOP). Recently it has been recommended to call OP cryptogenic organising pneumonia (COP) when no definite cause or characteristic clinical context is found and secondary organising pneumonia (SOP) when causes can be identified such as infection or it occurs in a characteristic clinical context such as connective tissue disorder. The most common clinical symptoms are dyspnea, cough, fever and general malaise. It is common that symptoms have been present for some weeks before the diagnosis is made. Patients commonly have lowered PO2 and a mildly restrictive spirometry. Radiographic features are most often patchy bilateral airspace opacities but an interstitial pattern or focal opacities can also be seen. Most of patients respond well to steroids but relapses are quite common. The aim of this paper is to present an overview of the disease and the main results from studies on OP in Iceland. The mean annual incidence for OP in Iceland was 1.97/100,000 inhabitants. Annual incidence for COP was 1.10/100,000 and 0.87/100,000 for SOP. This is higher than in most other studies. In Iceland patients with OP had a higher standardized mortality ratio than the general population despite good clinical responses. No clinical symptoms could separate between SOP and COP.Trefjavefslungnabólga er sjúkdómur í lungum, skilgreindur með klínískum einkennum, myndgreiningarrannsóknum og vefjameinafræðilegum breytingum í sameiningu. Klínísk einkenni eru hósti, mæði, hækkaður líkamshiti og almennur slappleiki. Algengt er að einkennin hafi verið til staðar í nokkrar vikur áður en greining fæst. Myndgreiningarrannsóknir geta sýnt fjölbreytt mynstur, til dæmis dreifðar millivefsíferðir, afmarkaðar lungnablöðruíferðir eða staka hnúða. Yfirleitt svarar sjúkdómurinn vel meðferð með barksterum en tekur sig upp hjá um fimmtungi sjúklinga

Chronic eosinophilic pneumonia in Iceland: clinical features, epidemiology and review

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenOBJECTIVE: The objective of the study was to describe the incidence and clinical features of chronic eosinophilic pneumonia (CEP) in Iceland and review recent literature. MATERIAL AND METHODS: Retrospective study where information was obtained from clinical charts from 1990-2004. Records, imaging studies and histopathology were evaluated. RESULTS: During the study period 10 individuals were diagnosed with CEP, 7 males and 3 females. Mean age was 58 years. None of the patients was a current smoker. The incidence of CEP during the study period was 0.23 per 100,000/year but increased to 0.54 per 100,000/year during the last 5 years of the study period. Clinical symptoms were malaise, cough, dyspnea, sweating and weight loss. Sedimentation rate was 72 mm/h and C-reactive protein (CRP) 125 mg/L. Eight of the ten patients had increase in blood eosinophils. On chest auscultation crackles were heard in seven patients and wheezing in three. Forced vital capacity (FVC) was 75% of predicted value and forced expiratory volume in one second (FEV1) was 73% of predicted. Mean PO2 was 68 mmHg. All the patients had classic diffuse bilateral opacities on chest radiograph that most commonly were peripheral. All patients were treated with corticosteroids and responded well. The average initial dose of Prednisolone was 42.5 mg per day. Seven of the patients relapsed but they all responded well to repeated treatment. CONCLUSIONS: Chronic eosinophilic pneumonia is a rare disorder but it has specific radiologic and histologic features. It is important to think of the disease in patients with diffuse infiltrates that are resistant to antibiotics. CEP responds well to corticosteroids but there is a high relapse rate, which also responds to treatment.Inngangur: Tilgangur rannsóknarinnar var að kanna nýgengi langvinnrar eósínófíl lungnabólgu á Íslandi, lýsa klínískum einkennum og veita yfirlit yfir sjúkdóminn. Efniviður og aðferðir: Aftursæ rannsókn þar sem upplýsingar voru fengnar úr sjúkraskrám árin 1990-2004. Sjúkraskrár voru yfirfarnar, kannaðar voru myndgreiningarrannsóknir og vefjafræðilegar greiningar endurskoðaðar. Niðurstöður: Á tímabilinu greindust 10 manns, sjö karlar og þrjár konur. Meðalaldur var 58 ár. Enginn sjúklinganna reykti. Nýgengi sjúkdómsins á öllu tímabilinu var 0,23 á 100.000/ári en jókst síðustu fimm árin í 0,54 á 100.000/ári. Einkenni voru slappleiki, þreyta, hósti, mæði, og megrun. Sökk var 72 mm/klst og C-reactive protein (CRP) 125 mg/L. Átta af 10 voru með aukningu eósínófíla í blóði. Við lungnahlustun heyrðist brak hjá sjö en önghljóð hjá þremur. Forced vital capacity (FVC) var 75% af áætluðu gildi og forced expiratory volume in one second (FEV1) var 73% af áætluðu gildi. Meðalhlutþrýstingur súrefnis (pO2) var 68 mmHg. Sjúklingarnir höfðu allir dæmigerðar dreifðar íferðir beggja vegna sem voru yfirleitt útlægar. Allir fengu sterameðferð og svöruðu meðferðinni fljótt og vel. Meðaltalsskammtur af prednisólon í upphafi meðferðar var 42,5 mg. Hjá sjö kom sjúkdómurinn aftur en allir svöruðu endurtekinni sterameðferð. Ályktanir: Langvinn eósínófíl lungnabólga er sjaldgæfur sjúkdómur en þó með einkennandi myndrænt og vefjafræðilegt útlit. Mikilvægt er að hafa hann í huga hjá sjúklingum með dreifðar íferðir sem svara ekki hefðbundinni sýklalyfjameðferð. Sjúkdómurinn svarar vel meðferð með barksterum sem getur þó þurft að endurtaka

Organising pneumonia in connection with Amiodarone treatment. Case reports and review

Hægt er að lesa greinina í heild sinni með því að smella á hlekkinn View/OpenOBJECTIVE: The objective of the study was to describe case reports of organising pneumonia in Iceland induced by the drug amiodarone. MATERIAL AND METHODS: Retrospective study where information was obtained from clinical charts from 1984-2003. Medical records, imaging studies and histopathology were re-evaluated. RESULTS: Described are three case reports of organising pneumonia associated with amiodarone use in two males and one female. Diagnostic methods and treatment are described and current literature is discussed. CONCLUSIONS: It is important for physicians to be aware of lung changes that amiodarone can cause and the importance of monitoring these patients.Tilgangur: Tilgangur rannsóknarinnar var að lýsa sjúkratilfellum trefjavefslungnabólgu sem tengdust notkun lyfsins amíódarón á Íslandi. Efniviður og aðferðir: Aftursæ rannsókn þar sem upplýsingar voru fengnar úr sjúkraskrám árin 1984-2003. Sjúkraskrár voru yfirfarnar og kannaðar myndgreiningarniðurstöður, vefjafræðilegar niðurstöður og meðferð sjúklinga. Niðurstöður: Lýst er þremur tilfellum trefjavefs-lungnabólgu hjá tveimur körlum og einni konu og greiningu og meðferð þeirra. Gefið er yfirlit yfir stöðu þekkingar. Ályktanir: Nauðsynlegt er fyrir lækna að vera meðvitaðir um að amíódarón getur valdið lungnabreytingum og að mikilvægt er að fylgjast vel með sjúklingum sem taka lyfið

Effect of Sex on Anterior Cruciate Ligament Injury–Related Biomechanics During the Cutting Maneuver in Preadolescent Athletes

Funding One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by the Icelandic Centre for Research (Rannís). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Publisher Copyright: © The Author(s) 2020.Background: There are 2 movement patterns associated with an anterior cruciate ligament (ACL) injury: dynamic valgus and stiff landing. Although sex-dependent differences have been identified for adults, less is known for preadolescent athletes regarding movement patterns known to load the ACL. Hypothesis: We hypothesized that girls would demonstrate greater vertical ground reaction forces and knee valgus angles. We further hypothesized that the exercise intervention would affect girls more than boys and that this would primarily be demonstrated in less sagittal plane excursions, increased vertical ground reaction forces and knee valgus moments for girls than for boys. Study Design: Controlled laboratory study. Methods: Male and female soccer and handball players (n = 288; age range, 9-12 years) were recruited. A motion capture system synchronized to a force platform was used to record 5 trials of a cutting maneuver before and after a 5-minute fatigue intervention. Linear mixed models were constructed, and analysis of variance was used to analyze differences in outcomes associated with the sex of the athletes. Results: Boys showed greater peak knee valgus moment (0.26 vs 0.22 N·m/kg, respectively; P =.048), peak knee internal rotation moment (–0.13 vs –0.10 N·m/kg, respectively; P =.021), knee rotation excursion (–7.9° vs –6.9°, respectively; P =.014), and knee extension excursion (2.7° vs 1.4°, respectively; P <.001) compared with that in girls. A significant sex × fatigue intervention interaction (F = 7.6; P =.006) was found, which was caused by a greater increase in first peak vertical ground-reaction force (vGRF) from before to after the fatigue intervention for girls (15.3 to 16.0 N/kg) compared with boys (16.4 to 16.5 N/kg). Conclusion: Differences detected for biomechanical factors during the cutting maneuver do not point to a greater ACL injury risk for prepubescent or early pubescent girls than for boys. Nonetheless, girls go on to develop more detrimental movement patterns in adolescence than those in boys in terms of biomechanical risk factors. Clinical Relevance: Early adolescence is a good target age to learn and develop muscular control; balance, strength; flexibility; and jumping, running, and landing control. This time of physical and athletic growth may therefore be an appropriate period to influence biomechanical factors and thereby task execution and the injury risk.Peer reviewe

Numerical convergence of the block-maxima approach to the Generalized Extreme Value distribution

In this paper we perform an analytical and numerical study of Extreme Value distributions in discrete dynamical systems. In this setting, recent works have shown how to get a statistics of extremes in agreement with the classical Extreme Value Theory. We pursue these investigations by giving analytical expressions of Extreme Value distribution parameters for maps that have an absolutely continuous invariant measure. We compare these analytical results with numerical experiments in which we study the convergence to limiting distributions using the so called block-maxima approach, pointing out in which cases we obtain robust estimation of parameters. In regular maps for which mixing properties do not hold, we show that the fitting procedure to the classical Extreme Value Distribution fails, as expected. However, we obtain an empirical distribution that can be explained starting from a different observable function for which Nicolis et al. [2006] have found analytical results.Comment: 34 pages, 7 figures; Journal of Statistical Physics 201

Hopes and Fears: Community cohesion and the ‘White working class’ in one of the ‘failed spaces’ of multiculturalism

Since 2001, community cohesion has been an English policy concern, with accompanying media discourse portraying a supposed failure by Muslims to integrate. Latterly, academia has foregrounded White majority attitudes towards ethnic diversity, particularly those of the ‘White working class’. Whilst questioning this categorisation, we present data on attitudes towards diversity from low income, mainly White areas within Dewsbury, West Yorkshire, a town portrayed in media discourse as one of the ‘failed spaces’ of multiculturalism. Drawing on mixed methods research, we present and discuss data that provide a complex message, seemingly confirming pessimistic analyses around ethnic diversity and predominantly White neighbourhoods but also highlighting an appetite within the same communities for greater and more productive inter-ethnic contact. Furthermore, anxieties about diversity and integration have largely failed to coalesce into broad support for organised anti-minority politics manifest in groups such as the English Defence League

X-linked serotonin 2C receptor is associated with a non-canonical pathway for sudden unexpected death in epilepsy.

Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic drive as a critical pathogenic step. Accordingly, the G protein-coupled, membrane serotonin receptor 5-HT2C inhibits forebrain and brainstem networks by exciting GABAergic interneurons, and deletion of this gene lowers the threshold for lethal evoked audiogenic seizures. Here, we characterize epileptogenesis throughout the lifespan of mice lacking X-linked, 5-HT2C receptors (loxTB Htr2c). We find that loss of Htr2c generates a complex, adult-onset spontaneous epileptic phenotype with a novel progressive hyperexcitability pattern of absences, non-convulsive, and convulsive behavioural seizures culminating in late onset sudden mortality predominantly in male mice. RNAscope localized Htr2c mRNA in subsets of Gad2+ GABAergic neurons in forebrain and brainstem regions. To evaluate the contribution of 5-HT2C receptor-mediated inhibitory drive, we selectively spared their deletion in GAD2+ GABAergic neurons of pan-deleted loxTB Htr2c mice, yet unexpectedly found no amelioration of survival or epileptic phenotype, indicating that expression of 5-HT2C receptors in GAD2+ inhibitory neurons was not sufficient to prevent hyperexcitability and lethal seizures. Analysis of human Sudden Unexpected Death in Epilepsy and epilepsy genetic databases identified an enrichment of HTR2C non-synonymous variants in Sudden Unexpected Death in Epilepsy cases. Interestingly, while early lethality is not reflected in the mouse model, we also identified variants mainly among male Sudden Infant Death Syndrome patients. Our findings validate HTR2C as a novel, sex-linked candidate gene modifying Sudden Unexpected Death in Epilepsy risk, and demonstrate that the complex epilepsy phenotype does not arise solely from 5-HT2C-mediated synaptic disinhibition. These results strengthen the evidence for the serotonin hypothesis of Sudden Unexpected Death in Epilepsy risk in humans, and advance current efforts to develop gene-guided interventions to mitigate premature mortality in epilepsy.Peer reviewe