Dynamic cerebral autoregulation in acute lacunar and middle cerebral artery territory ischemic stroke

Background and Purpose - We addressed whether dynamic cerebral autoregulation (dCA) is affected in middle cerebral artery (MCA) territory (MCAS) and lacunar ischemic stroke (LS). Methods - Blood pressure (MAP) and MCA velocity (V) were measured in 10 patients with large MCAS (National Institutes of Health Stroke score, 17 +/- 2; mean +/- SEM), in 10 with LS (score, 9 +/- 1), and in 10 reference subjects. dCA was evaluated in time (delay of the MCA V-mean counter-regulation during changes in MAP) and frequency domains (cross-spectral MCA V-mean-to-MAP phase lead). Results - In reference subjects, latencies for MAP increments (5.3 +/- 0.5 seconds) and decrements (5.6 +/- 0.5 seconds) were comparable, and low frequency MCA V-mean-to-MAP phase lead was 56 +/- 5 and 59 +/- 5 degrees (left and right hemisphere). In MCAS, these latencies were 4.6 +/- 0.7 and 5.6 +/- 0.5 seconds in the nonischemic hemisphere and not detectable in the ischemic hemisphere. In the unaffected hemisphere, phase lead was 61 +/- 6 degrees versus 26 +/- 6 degrees on the ischemic side (P <0.05). In LS, no latency and smaller phase lead bilaterally (32 +/- 6 and 33 +/- 5 degrees) conformed to globally impaired dCA. Conclusions - In large MCAS infarcts, dynamic cerebral autoregulation was impaired in the affected hemisphere. In LS, dynamic cerebral autoregulation was impaired bilaterally, a finding consistent with the hypothesis of bilateral small vessel disease in patients with lacunar infarct

Settlement of blue crab postlarvae in western North Atlantic estuaries

We quantified variability in daily settlement of blue crab postlarvae (megalopae) on identical artificial settlement substrates at up to 6 sites concurrently over a broad geographic expanse (similar to 1300 km) of the western North Atlantic (Delaware-South Carolina, USA). The 4-year study encompassed the blue crab recruitment season (generally July-November) from 1989-1992. Regional settlement was characterized by: (1) constant low levels of daily settlement punctuated by significantly non-random, episodic peaks of variable duration and intensity with peaks collectively accounting for at least half the total annual settlement at a site; (2) spatial and temporal variability leading to a general lack of coherence between sites in a given year and across years within a site; (3) occasional coherence in patterns between sites during a given year, suggesting linkages in regional processes affecting settlement; and, (4) significant semilunar patterns of episodic settlement pulses at the York River and Charleston-Harbor sites over a 4-year period. Thus, regional settlement patterns exhibit both consistent (i.e., semilunar periodicity, episodic pulses) and variable (i.e., temporal and spatial variation) elements, which are likely due to a combination of stochastic and deterministic processes. Such patterns may impart an ecological advantage to crabs settling en masse (i.e., reduced encounter rate with predators through predator swamping) or at continuous low levels (i.e., below a density-dependent threshold) during the recruitment season. An identical study illustrated that settlement in Gulf of Mexico estuaries exhibited similarly episodic and highly variable patterns. Daily mean and total annual settlement were up to a hundred-fold greater for gulf than Atlantic Coast estuaries implying population limitation by post-settlement processes in the gulf and greater recruitment limitation in the Atlantic. These studies emphasize the merit of conducting research over a broad geographic range using standardized techniques to attempt meaningful ecological comparisons

Quality of Life after Venous Stenting for Post-thrombotic Syndrome and the Effect of Inflow Disease

Objective: Patients with PTS experience an impaired quality of life (QoL). We aimed to study QoL in patients stented for post thrombotic syndrome (PTS) and analyze the influence of different parameters. Methods: Patients stented for PTS after iliofemoral deep vein thrombosis were asked to complete the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) and the Short Form Health Survey (SF-36) in this cross-sectional study. All other data were collected retrospectively. Primary endpoints were median CIVIQ-20 and physical (PCS) and mental (MCS) component summary SF-36 scores. The influence of age, sex, and years between the procedure and completion of questionnaire were investigated using a multivariate linear regression model. Wilcoxon signed rank test compared the PCS and MCS with the normative. Effects of inflow from the deep femoral vein (DFV) and/or the femoral vein (FV) on QoL was analyzed in patients with patent stents. Results: The response rate was 70.3% (n = 45/64). Time period (median) from stenting to questionnaire completion was 6.6 years (IQR: 8.0). Most stents were placed unilateral left-sided (73.3%). For patients with patent stents (n = 42) median CIVIQ-20 was 35.5 (IQR: 17.3), higher than the minimum of 20.0 (P &lt; .001). Median PCS of 44.7 (IQR: 14.2) was lower (P &lt; .001), and MCS of 55.9 (IQR: 7.1) higher (P = .001) than the normative (50.0). Time since stenting and sex were not associated with QoL. Age was a significant predictor [standardized coefficient ss = .36, P = .04] for QoL using the CIVIQ-20, but not for the SF-36. Inflow disease did not impact QoL, but patients with occluded stents (n = 3) had poor functioning levels. Conclusion: Quality of life is impaired after venous stenting for PTS, particularly physical functioning, among patients with an open stent, but was similar between patients with good and impaired inflow. Patients with a permanent stent occlusion had the lowest QoL

Quality of Life after Venous Stenting for Post-thrombotic Syndrome and the Effect of Inflow Disease

Objective: Patients with PTS experience an impaired quality of life (QoL). We aimed to study QoL in patients stented for post thrombotic syndrome (PTS) and analyze the influence of different parameters. Methods: Patients stented for PTS after iliofemoral deep vein thrombosis were asked to complete the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) and the Short Form Health Survey (SF-36) in this cross-sectional study. All other data were collected retrospectively. Primary endpoints were median CIVIQ-20 and physical (PCS) and mental (MCS) component summary SF-36 scores. The influence of age, sex, and years between the procedure and completion of questionnaire were investigated using a multivariate linear regression model. Wilcoxon signed rank test compared the PCS and MCS with the normative. Effects of inflow from the deep femoral vein (DFV) and/or the femoral vein (FV) on QoL was analyzed in patients with patent stents. Results: The response rate was 70.3% (n = 45/64). Time period (median) from stenting to questionnaire completion was 6.6 years (IQR: 8.0). Most stents were placed unilateral left-sided (73.3%). For patients with patent stents (n = 42) median CIVIQ-20 was 35.5 (IQR: 17.3), higher than the minimum of 20.0 (P &lt;.001). Median PCS of 44.7 (IQR: 14.2) was lower (P &lt;.001), and MCS of 55.9 (IQR: 7.1) higher (P =.001) than the normative (50.0). Time since stenting and sex were not associated with QoL. Age was a significant predictor [standardized coefficient ß =.36, P =.04] for QoL using the CIVIQ-20, but not for the SF-36. Inflow disease did not impact QoL, but patients with occluded stents (n = 3) had poor functioning levels. Conclusion: Quality of life is impaired after venous stenting for PTS, particularly physical functioning, among patients with an open stent, but was similar between patients with good and impaired inflow. Patients with a permanent stent occlusion had the lowest QoL.</p

Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening

Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The objective of the study was to assess the morbidity, mortality, and diagnostic and therapeutic delay in children with SCID in the Netherlands in the last 15 years. These data may help to judge whether SCID should be considered to be included in our national neonatal screening program. In the period 1998–2013, 43 SCID patients were diagnosed in the Netherlands, 11 of whom were atypical SCID (presentation beyond the first year). The median interval between the first symptom and diagnosis was 2 months (range 0–1173 months). The total mortality was 42 %. In total, 32 patients were treated with HSCT of whom 8 were deceased. Nine patients died due to severe infectious complications before curative treatment could be initiated. Conclusion: Because of a high mortality of patients with SCID before HSCT could be initiated, only a national newborn screening program and pre-emptive HSCT or GT will be able to improve survival of these patients

Diagnostic testing for interstitial lung disease in common variable immunodeficiency: a systematic review

INTRODUCTION: Common variable immunodeficiency related interstitial lung disease (CVID-ILD, also referred to as GLILD) is generally considered a manifestation of systemic immune dysregulation occurring in up to 20% of people with CVID. There is a lack of evidence-based guidelines for the diagnosis and management of CVID-ILD. AIM: To systematically review use of diagnostic tests for assessing patients with CVID for possible ILD, and to evaluate their utility and risks. METHODS: EMBASE, MEDLINE, PubMed and Cochrane databases were searched. Papers reporting information on the diagnosis of ILD in patients with CVID were included. RESULTS: 58 studies were included. Radiology was the investigation modality most commonly used. HRCT was the most reported test, as abnormal radiology often first raised suspicion of CVID-ILD. Lung biopsy was used in 42 (72%) of studies, and surgical lung biopsy had more conclusive results compared to trans-bronchial biopsy (TBB). Analysis of broncho-alveolar lavage was reported in 24 (41%) studies, primarily to exclude infection. Pulmonary function tests, most commonly gas transfer, were widely used. However, results varied from normal to severely impaired, typically with a restrictive pattern and reduced gas transfer. CONCLUSION: Consensus diagnostic criteria are urgently required to support accurate assessment and monitoring in CVID-ILD. ESID and the ERS e-GLILDnet CRC have initiated a diagnostic and management guideline through international collaboration. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022276337

Development of a primary care screening algorithm for the early detection of patients at risk of primary antibody deficiency

BACKGROUND: Primary antibody deficiencies (PAD) are characterized by a heterogeneous clinical presentation and low prevalence, contributing to a median diagnostic delay of 3-10 years. This increases the risk of morbidity and mortality from undiagnosed PAD, which may be prevented with adequate therapy. To reduce the diagnostic delay of PAD, we developed a screening algorithm using primary care electronic health record (EHR) data to identify patients at risk of PAD. This screening algorithm can be used as an aid to notify general practitioners when further laboratory evaluation of immunoglobulins should be considered, thereby facilitating a timely diagnosis of PAD. METHODS: Candidate components for the algorithm were based on a broad range of presenting signs and symptoms of PAD that are available in primary care EHRs. The decision on inclusion and weight of the components in the algorithm was based on the prevalence of these components among PAD patients and control groups, as well as clinical rationale. RESULTS: We analyzed the primary care EHRs of 30 PAD patients, 26 primary care immunodeficiency patients and 58,223 control patients. The median diagnostic delay of PAD patients was 9.5 years. Several candidate components showed a clear difference in prevalence between PAD patients and controls, most notably the mean number of antibiotic prescriptions in the 4 years prior to diagnosis (5.14 vs. 0.48). The final algorithm included antibiotic prescriptions, diagnostic codes for respiratory tract and other infections, gastro-intestinal complaints, auto-immune symptoms, malignancies and lymphoproliferative symptoms, as well as laboratory values and visits to the general practitioner. CONCLUSIONS: In this study, we developed a screening algorithm based on a broad range of presenting signs and symptoms of PAD, which is suitable to implement in primary care. It has the potential to considerably reduce diagnostic delay in PAD, and will be validated in a prospective study. Trial registration The consecutive prospective study is registered at clinicaltrials.gov under NCT05310604

Diagnostic testing for interstitial lung disease in common variable immunodeficiency:a systematic review

Introduction: Common variable immunodeficiency related interstitial lung disease (CVID-ILD, also referred to as GLILD) is generally considered a manifestation of systemic immune dysregulation occurring in up to 20% of people with CVID. There is a lack of evidence-based guidelines for the diagnosis and management of CVID-ILD. Aim: To systematically review use of diagnostic tests for assessing patients with CVID for possible ILD, and to evaluate their utility and risks. Methods: EMBASE, MEDLINE, PubMed and Cochrane databases were searched. Papers reporting information on the diagnosis of ILD in patients with CVID were included. Results: 58 studies were included. Radiology was the investigation modality most commonly used. HRCT was the most reported test, as abnormal radiology often first raised suspicion of CVID-ILD. Lung biopsy was used in 42 (72%) of studies, and surgical lung biopsy had more conclusive results compared to trans-bronchial biopsy (TBB). Analysis of broncho-alveolar lavage was reported in 24 (41%) studies, primarily to exclude infection. Pulmonary function tests, most commonly gas transfer, were widely used. However, results varied from normal to severely impaired, typically with a restrictive pattern and reduced gas transfer. Conclusion: Consensus diagnostic criteria are urgently required to support accurate assessment and monitoring in CVID-ILD. ESID and the ERS e-GLILDnet CRC have initiated a diagnostic and management guideline through international collaboration. </p