Prevalence of dementia subtypes: A 30-year retrospective survey of neuropathological reports.

We investigated the distribution of neuropathologically defined dementia subtypes among individuals with dementia disorder. The neuropathological reports were studied on all patients (n=524; 55.3% females; median age 80, range 39-102 years) with clinically diagnosed dementia disorder who underwent complete autopsy including neuropathological examination within the Department of Pathology at the University Hospital in Lund, Sweden, during the years 1974-2004. The neuropathological diagnosis was Alzheimer's disease (AD) in 42.0% of the cases, vascular dementia (VaD) in 23.7%, dementia of combined Alzheimer and vascular pathology in 21.6%, and frontotemporal dementia in 4.0% of the patients. The remaining 8.8% of the patients had other dementia disorders, including combinations other than combined Alzheimer and vascular pathology. The registered prevalence of dementia subtypes depends on many variables, including referral habits, clinical and neuropathological judgments and diagnostic traditions, all of these variables potentially changing over time. This, however, does not seem to obscure the delineation of the major dementia subgroups. In this material of 30 years from Lund in the south of Sweden, AD by far dominated among dementia subtypes, while cerebrovascular pathology corresponded with the dementia disorder, either entirely or partly, in almost half of the demented patients

History of depression prior to Alzheimer's disease and vascular dementia verified post-mortem.

The aim of this study was to analyze the medical history, with regards to previous remote depression, in patients with neuropathologically verified Alzheimer's disease (AD), vascular dementia (VaD) and mixed AD/VaD. The 201 patients included (115 AD, 44 VaD and 42 mixed AD/VaD) had been referred to the Psychogeriatric/Psychiatric Department, Lund University Hospital, for psychogeriatric investigation and were followed-up with clinical records and detailed information on psychiatric history prior to the onset of dementia. Depression was considered to exist when the patient had consulted a psychiatrist or physician and had been diagnosed with a "depressive episode" or "depression" and when anti-depressants and/or other specific treatments had been prescribed. Twenty patients (10%) had suffered from depression earlier in life well before the onset of dementia. Eight of the 9 AD patients with a previous diagnosis of depression had suffered from only one depressive episode and all had responded well to treatment, with complete recovery. In the VaD group, 8 out of 9 patients suffered two or more depressive episodes and only two recovered completely. Events with a possible significant relationship to depression were seen in 8 of the 9 AD patients but in only 1 of the 9 VaD patients. Psychotic symptoms were more common in VaD than in the AD group. The treatment modality of depression was similar in the groups. In conclusion, a history of depression prior to dementia is more common and more therapy-resistant in VaD than in AD

Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer : promise, controversies and ambiguities in the novel treatment paradigm

Immune checkpoint inhibitors (ICIs) have received much attention not least for melanoma since the award of the Nobel prize in 2018. Here, we review the current state of knowledge about the use of these monoclonal antibodies (mAbs) in non-small cell lung cancer (NSCLC). These drugs have generally been conditionally approved on limited early data and there are few long-term follow-up data from randomized clinical trials. The effect observed for NSCLC thus far is, on average, moderately better than that obtained with chemotherapy. Severe side-effects are more common than might have been expected. The drugs themselves are expensive and are associated with time-consuming histopathologic testing even though the predictive value of these tests can be discussed. In addition, monitoring for side-effects involves increased workload and budgetary expense for clinical chemistry laboratories. Here, we review and summarize the current knowledge, controversies and ambiguities of ICIs for the treatment of NSCLC

The Accuracy of Short Clinical Rating Scales in Neuropathologically Diagnosed Dementia.

OBJECTIVE:: The overall aim was to evaluate to what extent the diagnosis of dementia subtypes, obtained by three clinical rating scales, concurred with postmortem neuropathologic (NP) diagnosis of Alzheimer disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and mixed AD/VaD. DESIGN:: A prospective longitudinal clinical work-up with postmortem NP examination. PARTICIPANTS:: Two hundred nine patients with dementia referred for clinical evaluation and follow-up. METHODS:: The diagnostic scores in a set of three short clinical rating scales for AD, FTD, and VaD were evaluated against NP diagnoses. RESULTS:: The sensitivity and specificity of the AD scale were 0.80 and 0.87, respectively, of the FTD scale 0.93 and 0.92, respectively, and of the Hachinski Ischemic Score (HIS, VaD diagnosis) 0.69 and 0.92, respectively. Cases with mixed AD/VaD generally presented a combination of high AD and ischemic scores. A preferred cutoff score of six was identified for both the AD and FTD scales. CONCLUSIONS:: All three clinical rating scales showed a high sensitivity and specificity, in close agreement with final NP diagnosis-for the HIS a moderate sensitivity. These scales may thus be considered good diagnostic tools and are recommended for clinical and research center settings

Feasibility of EBUS-TBNA for histopathological and molecular diagnostics of NSCLC-A retrospective single-center experience

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive bronchoscopic procedure, well established as a diagnostic modality of first choice for diagnosis and staging of non-small cell lung cancer (NSCLC). The therapeutic decisions for advanced NSCLC require comprehensive profiling of actionable mutations, which is currently considered to be an essential part of the diagnostic process. The purpose of this study was to evaluate the utility of EBUS-TBNA cytology specimen for histological subtyping, molecular profiling of NSCLC by massive parallel sequencing (MPS), as well as for PD-L1 analysis. A retrospective review of 806 EBUS bronchoscopies was performed, resulting in a cohort of 132 consecutive patients with EBUS-TBNA specimens showing NSCLC cells in lymph nodes. Data on patient demographics, radiology features of the suspected tumor and mediastinal engagement, lymph nodes sampled, the histopathological subtype of NSCLC, and performed molecular analysis were collected. The EBUS-TBNA specimen proved sufficient for subtyping NSCLC in 83% and analysis of treatment predictive biomarkers in 77% (MPS in 53%). The adequacy of the EBUS-TBNA specimen was 69% for EGFR gene mutation analysis, 49% for analysis of ALK rearrangement, 36% for ROS1 rearrangement, and 33% for analysis of PD-L1. The findings of our study confirm that EBUS-TBNA cytology aspirate is appropriate for diagnosis and subtyping of NSCLC and largely also for treatment predictive molecular testing, although more data is needed on the utility of EBUS cytology specimen for MPS and PD-L1 analysis

Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer

Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the 533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135 successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH fusion positive case was missed by the NanoString assay. Stratification of the 533-sample cohort based on actionable alterations in 11 oncogenes revealed that 66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not otherwise specified harbored ≥1 alteration. In adenocarcinoma, 10.6% of patients (50.3% if including KRAS) could potentially be eligible for emerging therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1% with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are feasible in NSCLC for clinical diagnostics, identifying notable proportions of patients potentially eligible for emerging molecular therapeutics

Visby Innerstad : En användningsplan

Sedan lång tid föreligger i stort sett enighet om att bevara innerstadens bebyggelse och att anpassa eventuella nytillskott till det redan bestående. Med den inställningen har förändringsprocessen både dämpats och mildrats men ändå inte bragts att avstanna. Förändringar sker ständigt om det också huvudsakligen i smått: de många synbart så anspråkslösa byggnadsåtgärderna adderar efterhand ihop sig till något större och mer genomgripande. Långsamt, nästan omärkligt, ändrar innerstaden sitt ansikte.Ändå är det inte själva husen som förändrats mest utan användningen av dem. Ur funktionell synpunkt har 1950 - och 60-talen har varit något av en omstörtning i innerstadens historia: den har förlorat nästan hälften av de boende, en stor del av detaljhandeln och praktiskt taget helt sin gamla roll som skolcentrum. I gengäld har ytterstaden vuxit ut till ett sammanhängande kilometerbrett bälte. Till stor del av denna funktionella förändring en följd av beslutet att bevara innerstadens bebyggelse. Vad som inte fått plats inom den gamla ramen har etablerats utandör den.Föreliggande arbete vill ge en översiktlig bild av förändringsförloppen, sedda i ett långt tidsperspektiv men med tonvikt på dagsläget. Bebyggelsen tas upp till utförlig granskning men också användningen av den. Det är just samspelet mellan husen och de funtkioner, de fyller, som kan sägas utgöra bokens huvudtema. I de flesta fall är detta sammanhang hus-användning alldeles konfliktfritt och föranleder därför inte heller någon diskussion. Vad som behandlas är de relativt få problematiska fallen, hus som borde rustas upp för att fylla sin uppgift, hus som är olämpligt nyttjade eller inte använda alls. En serie sådana fall tas upp till systematisk genomgång; samtidigt berörs också de trafik - och miljömässiga konsekvenserna. Bokens syfte är alltså klart: den ger ett underlag av fakta för arbetet med att jämka samman byggnader och användningsformer. I den meningen kan skriften kallas en anvädningsplan för Visby innanför murarna.Arkitekturskolanas arbete har bedrivitis parallellt med den kommunala Innerstadskommitténs verksamhet. Något organiserat samarbete har inte förekommit med de informella kontakterna har varit både täta och goda. Att likheterna mellan Innerstadskommittén och Arkitekturskolans slutsatser blivit så pass stora, kan tillskrivas en gemensam helhetssyn.En av Arkitekturskolans elever, arkitekt Lars-Ingvar Larsson, har tidigare självständigt genomfört en undersökning av förändringar i innerstaden 1945-70- Denna studie publicerats separat och bör uppfattas som ett komplement till den hör föreliggande.Förutom de i innehållsförteckningen nämnda har ytterligare några aktivt medverkat i arbetet. Studiet av trafikfrågorna i innerstaden, i hamnen och öster om ringmuren leddes av Åke Claesson, I fältstudier och diskussioner medverkande Göran Månsson.Arkitekturskolan har fått god hjälp av ett antal initierade personer i Visby. Särskild tacksamhet är vi skyldiga byggnadsnämnden ordförande Henning Jacobson, kommunalrådet C B Stenström, stadsarkitekten Måns Hagbergm f. länsbostadsdorektören Åke Malmberg och landsantikvarien Gunnar Svahnström. I boken publiceringskostnaderna har ekonomiskt bidrag lämnats av Gotlands kommun och Riksantikvarieämbetet.Boken har redigerats av Sture Balgård och Ann Mari Westerlind med hjälp av Henrik O Andersson, Bo Ek, Göran Lindahl, Fredrik von Platen, John Sjöström Gunnar Westerlind och Hans Wetterfors.Skeppsholmen, Stockholm, sommaren 1973.Arkitekturskolans lärare och elever.Konsthögskolans arkitekturskola i Stockholm har under läsåret 1972/73 studerat bevarande - och förnyelseproblem i Visby. Staden innanför murarna har naturligt nog utgjort tyngdpunkten i arbetet - den här inte bara historiskt och estetiskt fängslande utan erbjuder också ovanliga möjligheter att tränga in i frågor, som annars sällan har en så klar och renodlad karaktär. </p