Tag: pubmed

JAMA Psychiatry. 2022 May 18. doi: 10.1001/jamapsychiatry.2022.1142. Online ahead of print.

ABSTRACT

IMPORTANCE: Schizophrenia is associated with major cognitive deficits and has been conceptualized as both a neurodevelopmental and a neurodegenerative disorder. However, when deficits develop and how they change over the course of illness is uncertain.

OBJECTIVE: To trace cognition from elementary school to old age to test neurodevelopmental and neurodegenerative theories of psychotic disorders.

DESIGN, SETTING, AND PARTICIPANTS: Data were taken from the Suffolk County Mental Health Project, a first-admission longitudinal cohort study of individuals with psychotic disorders. Participants were recruited from all 12 inpatient psychiatric facilities in Suffolk County, New York. This analysis concerns the 428 participants with at least 2 estimates of general cognitive ability. Data were collected between September 1989 and October 2019, and data were analyzed from January 2020 to October 2021.

EXPOSURES: Psychiatric hospitalization for psychosis.

MAIN OUTCOMES AND MEASURES: Preadmission cognitive scores were extracted from school and medical records. Postonset cognitive scores were based on neuropsychological testing at 6-month, 24-month, 20-year, and 25-year follow-ups.

RESULTS: Of the 428 included individuals (212 with schizophrenia and 216 with other psychotic disorders), 254 (59.6%) were male, and the mean (SD) age at psychosis onset was 27 (9) years. Three phases of cognitive change were observed: normative, declining, and deteriorating. In the first phase, cognition was stable. Fourteen years before psychosis onset, those with schizophrenia began to experience cognitive decline at a rate of 0.35 intelligence quotient (IQ) points per year (95% CI, 0.29-0.42; P < .001), a significantly faster decline than those with other psychotic disorders (0.15 IQ points per year; 95% CI, 0.08-0.22, P < .001). At 22 years after onset, both groups declined at a rate of 0.59 IQ points per year (95% CI, 0.25-0.94; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study, cognitive trajectories in schizophrenia were consistent with both a neurodevelopmental and neurodegenerative pattern, resulting in a loss of 16 IQ points over the period of observation. Cognitive decline began long prior to psychosis onset, suggesting the window for primary prevention is earlier than previously thought. A window for secondary prevention emerges in the third decade of illness, when cognitive declines accelerate in individuals with schizophrenia and other psychotic disorders.

PMID:35583896 | DOI:10.1001/jamapsychiatry.2022.1142

Transl Vis Sci Technol. 2022 May 2;11(5):20. doi: 10.1167/tvst.11.5.20.

ABSTRACT

PURPOSE: To determine the sensitivity of optical coherence tomography (OCT) and standard automated perimetry (SAP) for detecting glaucomatous progression in the superior and inferior hemiretina.

METHODS: We calculated contrast-to-noise ratios (CNRs) for OCT retinal nerve fiber layer (RNFL) thickness of hemiretinas and for SAP mean total deviation (MTD) of the corresponding hemifields from longitudinal data (205 eyes, 125 participants). The glaucoma stage for each hemiretina was based on the corresponding hemifield’s MTD. Contrast was defined as the difference of the parameter between two consecutive glaucoma stages, whereas noise was the measurement variability of the parameter in those stages. The higher the CNR of a parameter, the more sensitive it is to detecting progression in the transition between successive stages.

RESULTS: There were no statistically significant differences for the RNFL CNR and MTD CNR between superior and inferior hemiretinas. As the glaucoma stage of the opposite hemiretina worsened, the MTD CNR in the transition from moderate to advanced glaucoma significantly increased. The RNFL CNR in the transition from mild to moderate glaucoma significantly decreased in case of advanced glaucoma in the opposite hemiretina.

CONCLUSIONS: Similar to full retinas, detecting conversion to glaucoma in hemiretinas is more sensitive with OCT than SAP, whereas with more advanced disease, SAP is more sensitive for detecting progression. More importantly, the sensitivity for detecting progression in one hemiretina with either technique depends on the glaucoma severity in the opposite hemiretina.

TRANSLATIONAL RELEVANCE: Monitoring glaucomatous progression with either OCT or SAP partly depends on the glaucoma severity in the opposite hemiretina.

PMID:35583886 | DOI:10.1167/tvst.11.5.20

Neurol Sci. 2022 May 18. doi: 10.1007/s10072-022-06150-4. Online ahead of print.

ABSTRACT

Slowness of information processing (SIP) is frequently reported after traumatic brain injury (TBI). Previous studies point toward a pivotal role of white matter damage on speed of information processing. However, little is known about the more comprehensive and ecological assessment of SIP in TBI. Here, we combined an ecological assessment of SIP with the use of tract-based spatial statistics (TBSS) on individuals’ fractional anisotropy (FA) maps. Twenty-six moderate-to-severe patients with TBI (21 males and 5 females) participated in this study: 10 individuals were classified as not having SIP (SIP-) and 16 were classified as having SIP (SIP +). SIP + showed lower FA in bilateral anterior thalamic radiation, corticospinal tract, cingulum, and forceps, as well as in bilateral inferior fronto-occipital, inferior and superior longitudinal fasciculi and uncinate fasciculus. Overall, this result is consistent with and expands previous reports on information processing speed to a more comprehensive and ecological perspective on SIP in TBI.

PMID:35583841 | DOI:10.1007/s10072-022-06150-4

Transbound Emerg Dis. 2022 May 18. doi: 10.1111/tbed.14599. Online ahead of print.

ABSTRACT

Lumpy skin disease (LSD) is an economically important transboundary disease affecting cattle, causing large economic losses such as decreased production and trade restrictions. LSD has been a historically neglected disease since it previously caused disease limited to the African continent. Currently, the epidemiology of lumpy skin disease virus is based on how the disease is transmitted in tropical and subtropical climates. The understanding of its epidemiology in hemiboreal climates is not well understood and needs urgent attention to expand the current knowledge. In this paper, the epidemiological findings on LSD in Russia over a 6-year period are summarized and discussed. A total of 471 outbreaks were identified spanning over a 9000 km range. The outbreaks of lumpy skin disease occur primarily in small holder farms (backyard) compared to commercial farms between mid-May through mid-November including weather conditions with snow and freezing temperatures that preclude vector activity. Mortality and morbidity varied across the six years ranged from 1.19 to 61.8% and 0 to 50% respectively with a tendency to decline from 2015 to 2020. The geographic pattern of spread was assessed by means of directionality, indicated a northward movement from 2015 to 2016, with a consequent East turn in 2017 through Siberia to the Far East by 2020. All cases occurred along the border with Kazakhstan. Mathematical modelling showed that the disease tended to form statistically verified annual spatio-temporal clusters in 2016 – 2018, whereas in 2019 and 2020 such segregation was not evident. The trend of spread was mainly either from south to north or from south to a north-east direction. This article is protected by copyright. All rights reserved.

PMID:35583857 | DOI:10.1111/tbed.14599

J Cancer Res Clin Oncol. 2022 May 18. doi: 10.1007/s00432-022-04048-4. Online ahead of print.

ABSTRACT

PURPOSE: Mesenchymal-epithelial transition (MET) amplification is one of the mechanisms accounting for the resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in lung cancer patients, as well as the poor prognosis. Fluorescence in situ hybridization (FISH) is the most widely used method for MET amplification detection. However, it is inapplicable when tissue samples were unavailable. Herein, we assessed the value of droplet digital PCR (ddPCR) in MET copy number gain (CNG) detection in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKIs.

MATERIALS AND METHODS: A total of 103 cancer tissues and the paired peripheral blood samples from NSCLC patients were collected for MET CNG detection using ddPCR. In parallel, MET amplification in tissue samples was verified by FISH. Also, the relationships between MET CNG and EGFR T790M, as well as the EGFR-TKI resistance were also evaluated using Chi-square or Fisher’s exact tests.

RESULT: The concordance rate of ddPCR and FISH in detecting MET CNG in tissue samples was 100% (102/102), and it was 94.17% (97/103) for ddPCR method in detecting the MET CNG among peripheral blood and tissue samples. No statistical difference was observed between MET amplification and EGFR T790M (p = 0.65), while MET amplification rate was significantly increased in patients with resistance to third generations of EGFR-TKIs as compared with patients with resistance to first/second EGFR-TKIs (p < 0.05).

CONCLUSIONS: ddPCR is an alternative method to detect MET CNG in both tissues and peripheral blood samples, which is of worthy in clinical promotion.

PMID:35583827 | DOI:10.1007/s00432-022-04048-4

Histopathology. 2022 May 18. doi: 10.1111/his.14698. Online ahead of print.

ABSTRACT

AIMS: Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here, we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach.

METHODS AND RESULTS: PubMed, SCOPUS and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then, a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium- ICGC dataset and The Cancer Genome Atlas- TCGA program) were conducted. The core findings of 128 patients were as follows – 1) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. 2) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. 3) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (p<0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (p<0.001). 4) Survival analysis: ITPN with a “pure” branch duct involvement showed the lowest risk of recurrence.

CONCLUSIONS: ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.

PMID:35583805 | DOI:10.1111/his.14698

J Neurooncol. 2022 May 18. doi: 10.1007/s11060-022-04011-w. Online ahead of print.

ABSTRACT

PURPOSE: In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (¹⁸F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether ¹⁸F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS).

METHODS: Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus ¹⁸F-DOPA PET defined tumor.

RESULTS: Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing ¹⁸F-DOPA PET. PFS3 was 85% (95% CI 63.2-95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed.

CONCLUSION: ¹⁸F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.

PMID:35583721 | DOI:10.1007/s11060-022-04011-w

Int Arch Occup Environ Health. 2022 May 18. doi: 10.1007/s00420-022-01876-2. Online ahead of print.

ABSTRACT

PURPOSE: Occupational exposure limits (OEL) for nitrogen oxides (NO, NO₂) and diesel exhaust (EC-DPM) were reassessed by the German authorities in 2016/2017. We performed a clinical cross-sectional study among salt and potash underground workers exposed to these substances at relatively high levels to examine possible indicators of acute effects on workers’ health.

METHODS: We measured post- versus pre-shift differences in cardiovascular, inflammatory, immune, and respiratory effect biomarkers and assessed their associations with personal exposures measured during the same shift. We also compared post- versus pre-shift differences in biomarker levels between exposure groups defined based on work site and job type.

RESULTS: None of the above-ground workers exceeded the OEL for NO₂ and only 5% exceeded the OEL for EC-DPM exposure. Among underground workers, 33% of miners and 7% underground maintenance workers exceeded the OEL for NO₂; the OEL for EC-DPM was exceeded by 56% of miners and 17% of maintenance workers. Some effect biomarkers (thrombocytes, neutrophils, MPO, TNF-α, IgE, FeNO) showed statistically significant differences between pre- versus post-shift measurements; however, there were no consistent associations between pre- and post-shift differences and exposure group or personal exposure measurements during the shift.

CONCLUSIONS: We did not find evidence of associations between workplace exposure to NO, NO₂ or EC-DPM and clinically relevant indicators of acute cardiovascular, inflammatory and immune, or respiratory effects among salt and potash underground workers in Germany.

PMID:35583687 | DOI:10.1007/s00420-022-01876-2

Clin Rheumatol. 2022 May 18. doi: 10.1007/s10067-022-06206-y. Online ahead of print.

ABSTRACT

Raynaud’s phenomenon (RP) is a cardinal feature of systemic sclerosis (SSc) and manifests with pain, digital colour change, sensory symptoms, and impaired function. SSc-RP is exacerbated by cold exposure (RP ‘attacks’) but many patients report persistent symptoms of background digital ischaemia. The aim of our study was to examine the significance of RP with digital colour change with or without symptoms, and persistent colour change in between attacks. Patients with SSc responses were obtained from the Patient Survey of experiences of Raynaud’s Phenomenon (PASRAP). We enquired about symptoms associated with Raynaud’s attacks, and persistent symptoms in between attacks. Data were analysed as descriptive statistics with appropriate parametric/non-parametric testing. Relevant PASRAP survey question data from 747 evaluable SSc patients from across three continents were analysed. Isolated colour change was rare (29/484, 6%). Digital ulcers were more common in SSc-RP associated with other sensory symptoms (42.1% vs. 24.1%, P=0.057) and more readily treated with phosphodiesterase-type 5 inhibitors (22.5% vs. 10.3%%, P=0.124). Over one-third of patients (n=92/239, 38%) reported persistent colour change in between Raynaud’s attacks. Patients with persistent colour change were more likely to have pulmonary arterial hypertension (15.2% vs. 7.5%, P=0.057) and be treated with calcium channel blockers (54.3% vs. 39.0%, P=0.021). SSc-RP with colour change and other symptoms and/or or persistent decolourisation in between attacks were more likely to have vascular complications of SSc and be treated with vascular therapies. Future research should explore the judicious use of vascular therapies as a potential form of disease modification in SSc. Key Points • Isolated colour change without other symptoms is rare in SSc patients. • SSc patients often identify persistent symptoms in between attacks of RP. • SSc-RP with colour change and other symptoms, or persistent decolourisation, may have greater disease severity and be treated with vascular therapies.

PMID:35583625 | DOI:10.1007/s10067-022-06206-y

Osteoporos Int. 2022 May 18. doi: 10.1007/s00198-022-06416-9. Online ahead of print.

ABSTRACT

Duchenne muscular dystrophy is a progressive disease usually associated with loss of ambulation and progressive scoliosis. Immobilisation and glucocorticoid treatment are predisposing factors for reduced bone mineral density (BMD). Analysis of quantitative computed tomography revealed low BMD in thoracic and lumbar vertebrae in comparison to age- and sex-matched healthy controls.

INTRODUCTION: Evaluation of vertebral bone mineral density (BMD) in Duchenne Muscular Dystrophy (DMD) adolescents with untreated advanced scoliosis and comparison with the BMD values of healthy age-matched controls, based on quantitative computer tomography.

METHODS: Thirty-seven DMD adolescents (age 15.6 ± 2.5 years) with spinal deformity were evaluated clinically and radiologically prior to definite spinal fusion and compared to 31 male and age-matched healthy individuals (age 15.7 ± 2.3 years). Data related to previous medical treatment, physiotherapy and ambulatory status was also analysed. Scoliotic curves were measured on plain sitting radiographs of the spine. The BMD Z-scores of the thoracic and lumbar vertebrae were calculated with QCTpro® (Mindways Software Inc., USA), based on data sets of preoperative, phantom pre-calibrated spinal computed tomography scans.

RESULTS: A statistically significant lower BMD could be found in DMD adolescents, when compared to healthy controls, showing an average value for the lumbar spine of 80.5 ± 30.5 mg/cm³. Z-scores deteriorated from the upper thoracic towards the lower lumbar vertebrae. All but the uppermost thoracic vertebrae had reduced BMD values, with the thoracolumbar and lumbar region demonstrating the lowest BMD. No significant correlation was observed between BMD and the severity of the scoliotic curve, previous glucocorticoid treatment, cardiovascular impairment, vitamin D supplementation, non-invasive ventilation or physiotherapy.

CONCLUSION: DMD adolescents with scoliosis have strongly reduced BMD Z-scores, especially in the lumbar spine in comparison to healthy controls. These findings support the implementation of a standardised screening and treatment protocol. Level of evidence/clinical relevance: therapeutic level III.

PMID:35583603 | DOI:10.1007/s00198-022-06416-9