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1.
J Am Heart Assoc ; 13(4): e032922, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38348784

ABSTRACT

BACKGROUND: Elevated cardiac troponin (cTn) is detected in 10% to 30% of patients with acute ischemic stroke (AIS) and correlates with poor functional outcomes. Serial cTn measurements differentiate a dynamic cTn pattern (rise/fall >20%), specific for acute myocardial injury, from elevated but stable cTn levels (nondynamic), typically attributed to chronic cardiac/noncardiac conditions. We investigated if the direction of the cTn change (rising versus falling) affects mortality and outcome. METHODS AND RESULTS: We retrospectively screened consecutive patients with AIS admitted to 5 stroke centers for elevated cTn at admission and at least 1 additional cTn measurement within 48 hours. The pattern of cTn was defined as rising if >20% increase from baseline, falling if >20% decrease, or nondynamic if ≤20% change in either direction. Logistic regression analyses were performed to assess the association of cTn patterns and 7-day mortality and unfavorable discharge disposition. Of 3789 patients with AIS screened, 300 were included. Seventy-two had a rising pattern, 66 falling, and 162 nondynamic. In patients with AIS with rising cTn, acute ischemic myocardial infarction was present in 54%, compared with 33% in those with falling cTn (P<0.01). Twenty-two percent of patients with a rising pattern had an isolated dynamic cTn in the absence of any ECG or echocardiogram changes, compared with 53% with falling cTn. A rising pattern was associated with higher risk of 7-day mortality (adjusted odds ratio [OR]=32 [95% CI, 2.5-415.0] rising versus aOR=1.3 [95% CI, 0.1-38.0] falling versus nondynamic as reference) and unfavorable discharge disposition (aOR=2.5 [95% CI, 1.2-5.2] rising versus aOR=0.6 [95% CI, 0.2-1.5] versus falling). CONCLUSIONS: Rising cTn is independently associated with increased mortality and unfavorable discharge disposition in patients with AIS.


Subject(s)
Ischemic Stroke , Myocardial Infarction , Humans , Ischemic Stroke/complications , Prognosis , Retrospective Studies , Myocardial Infarction/complications , Troponin , Biomarkers
2.
J Am Heart Assoc ; 12(21): e029799, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37850436

ABSTRACT

Background Cardiovascular complications after acute ischemic stroke (AIS) can be related to chronic/comorbid cardiac conditions or acute disruption of the brain-heart autonomic axis (stroke-heart syndrome). Women are known to be more vulnerable to certain stress-induced cardiac complications, such as Takotsubo cardiomyopathy. We investigated sex differences in cardiac troponin (cTn) elevation, cardiac events, and outcomes after AIS. Methods and Results We retrospectively analyzed consecutive patients with AIS from 5 stroke centers. Patients with AIS with elevated baseline cTn and at least 2 cTn measurements were included, while patients with acute comorbid conditions that could impact cTn levels were excluded. Poststroke acute myocardial injury was defined as the presence of a dynamic cTn pattern (rise/fall >20% in serial measurements) in the absence of acute atherosclerotic coronary disease (type 1 myocardial infarction) or cardiac death (type 3 myocardial infarction). From a total cohort of 3789 patients with AIS, 300 patients were included in the study: 160 were women (53%). Women were older, had a lower burden of cardiovascular risk factors, and more frequently had cardioembolic stroke and right insula involvement (P values all <0.05). In multivariate analysis, women were more likely to have a dynamic cTn pattern (adjusted odds ratio, 2.1 [95% CI, 1.2-3.6]) and develop poststroke acute myocardial injury (adjusted odds ratio, 2.1 [95% CI, 1.1-3.8]). Patients with poststroke acute myocardial injury had higher 7-day mortality (adjusted odds ratio, 5.5 [95% CI, 1.2-24.4]). Conclusions In patients with AIS with elevated cTn at baseline, women are twice as likely to develop poststroke acute myocardial injury, and this is associated with higher risk of short-term mortality. Translational studies are needed to clarify mechanisms underlying sex differences in cardiac events and mortality in AIS.


Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Heart Diseases , Ischemic Stroke , Myocardial Infarction , Stroke , Humans , Female , Male , Retrospective Studies , Biomarkers
3.
Cerebrovasc Dis ; 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37839405

ABSTRACT

Introduction Central nervous system involvement in scleroderma has traditionally been considered uncommon. Recent studies suggest that scleroderma might be associated with an increased risk of cerebrovascular disease (CBVD), independent of conventional cardiovascular risk factors. We present a case series and a systematic review to capture the spectrum of CBVD in scleroderma, through a detailed description of clinical, demographic, laboratory, and radiographical findings. Methods In our case series, we included consecutive patients with scleroderma and CBVD seen over 35 years by our group in different hospitals in the United States. We also performed a systematic review from inception to July 2022. MEDLINE/EMBASE/WoS were searched for "scleroderma", "systemic scleroderma", "systemic sclerosis", "cerebrovascular", "stroke", "cerebrovascular disorders", "cerebrovascular disease". Results Fourteen patients with scleroderma and CBVD were included in our case series (mean age 48-year, 85% female). CBVDs were ischemic stroke (64%), hemorrhagic stroke (7%), venous thrombosis (7%), ischemic optic neuropathy (7%), probable ischemic stroke (14%). Of the 110 studies identified in our systematic review (45,484 patients), 82 reports with patient level data were included for quantitative analysis (93 patients, mean age 48-year, 79% female). Despite 16 different CBVD types identified, ischemic stroke was the most common CBVD (29%), followed by vasculopathy (20%), hemorrhage (12%), vasculitis (11%), and intracranial aneurysm (11%). Discussion/Conclusion Our relatively large case series combined with a systematic review of CBVD in SCL patients shows a heterogeneous spectrum of CBVD etiology, with acute ischemic stroke being the most common in our cases and in our literature review. A complex interaction between chronic inflammation, autoimmune mechanisms, and endothelial dysfunction seems to underlie the CBVD heterogeneity in scleroderma patients. This review informs clinicians about the spectrum of CBVD related to scleroderma and raise awareness about scleroderma being a possible risk factor for early onset CBVD.

4.
Sci Rep ; 13(1): 16450, 2023 09 30.
Article in English | MEDLINE | ID: mdl-37777523

ABSTRACT

Post-operative urinary retention is a medical condition where patients cannot urinate despite having a full bladder. Ultrasound imaging of the bladder is used to estimate urine volume for early diagnosis and management of urine retention. Moreover, the use of bladder ultrasound can reduce the need for an indwelling urinary catheter and the risk of catheter-associated urinary tract infection. Wearable ultrasound devices combined with machine-learning based bladder volume estimation algorithms reduce the burdens of nurses in hospital settings and improve outpatient care. However, existing algorithms are memory and computation intensive, thereby demanding the use of expensive GPUs. In this paper, we develop and validate a low-compute memory-efficient deep learning model for accurate bladder region segmentation and urine volume calculation. B-mode ultrasound bladder images of 360 patients were divided into training and validation sets; another 74 patients were used as the test dataset. Our 1-bit quantized models with 4-bits and 6-bits skip connections achieved an accuracy within [Formula: see text] and [Formula: see text], respectively, of a full precision state-of-the-art neural network (NN) without any floating-point operations and with an [Formula: see text] and [Formula: see text] reduction in memory requirements to fit under 150 kB. The means and standard deviations of the volume estimation errors, relative to estimates from ground-truth clinician annotations, were [Formula: see text] ml and [Formula: see text] ml, respectively. This lightweight NN can be easily integrated on the wearable ultrasound device for automated and continuous monitoring of urine volume. Our approach can potentially be extended to other clinical applications, such as monitoring blood pressure and fetal heart rate.


Subject(s)
Urinary Bladder , Urinary Retention , Humans , Urinary Bladder/diagnostic imaging , Algorithms , Neural Networks, Computer , Ultrasonography/methods , Urinary Retention/diagnostic imaging
5.
Arch Phys Med Rehabil ; 104(10): 1573-1579, 2023 10.
Article in English | MEDLINE | ID: mdl-37295706

ABSTRACT

OBJECTIVE: Investigate stroke survivors' (SS) preferences for a hypothetical mHealth app for post-stroke care and to study the influence of demographic variables on these preferences. DESIGN: Mixed-methods, sequential, observational study. SETTING: Focus groups (phase 1) were conducted to identify SS perceptions and knowledge of mHealth applications (apps). Using grounded theory approach, recurring themes were identified. A multiple-choice questionnaire of 5 desired app features was generated using these themes and mailed to SS (national survey, phase 2). SS' demographics and perceived usefulness (yes/no) for each feature were recorded. In-person usability testing (phase 3) was conducted to identify areas of improvement in user interfaces of existing apps. Summative telephone interviews (phase 4) were conducted for final impressions supplementary to national survey. PARTICIPANTS: SS aged >18 years recruited from study hospital, national stroke association database, stroke support and advocacy groups. Non-English speakers and those unable to communicate were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: (1) Percentage of SS (phase 2) identifying proposed app features to be useful. (2) Influence of age, sex, race, education, and time since stroke on perceived usefulness. RESULTS: Ninety-six SS participated in focus groups. High cost, complexity, and lack of technical support were identified as barriers to adoption of mHealth apps. In the national survey (n=1194), ability to track fitness and diet (84%) and communication (70%) were the most and least useful features, respectively. Perceived usefulness was higher among younger SS (P<.001 to .006) and SS of color (African American and Hispanic) (ORs 1.73-4.41). Simple design and accommodation for neurologic deficits were main recommendations from usability testing. CONCLUSIONS: SS are willing to adopt mHealth apps that are free of cost and provide technical support. Apps for SS should perform multiple tasks and be of simple design. Greater interest for the app's features among SS of color may provide opportunities to address health inequities.


Subject(s)
Mobile Applications , Humans , Patient Preference , Focus Groups , Surveys and Questionnaires , Survivors
6.
J Am Heart Assoc ; 11(24): e026601, 2022 12 20.
Article in English | MEDLINE | ID: mdl-36533613

ABSTRACT

Perivascular spaces or Virchow-Robin spaces form pathways along the subarachnoid spaces that facilitate the effective clearance of brain metabolic by-products through intracellular exchange and drainage of cerebrospinal fluid. Best seen on magnetic resonance imaging of the brain, enlarged perivascular spaces (EPVSs) are increasingly recognized as potential imaging biomarkers of neurological conditions. EPVSs are an established subtype of cerebral small-vessel disease; however, their associations with other cerebrovascular disorders are yet to be fully understood. In particular, there has been great interest in the association between the various parameters of EPVSs, such as number, size, and topography, and vascular neurological conditions. Studies have identified cross-sectional and longitudinal relationships between EPVS parameters and vascular events, such as ischemic stroke (both clinical and silent), intracerebral hemorrhage, vascular risk factors, such as age and hypertension, and neurodegenerative processes, such as vascular dementia and Alzheimer disease. However, these studies are limited by heterogeneity of data and the lack of consistent results across studied populations. Existing meta-analyses also fail to provide uniformity of results. We performed a qualitative narrative review with an aim to provide an overview of the associations between EPVSs and cerebrovascular diseases, which may help recognize gaps in our knowledge, inform the design of future studies, and advance the role of EPVSs as imaging biomarkers.


Subject(s)
Cerebrovascular Disorders , Nervous System Diseases , Humans , Cross-Sectional Studies , Brain/diagnostic imaging , Brain/pathology , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/pathology , Magnetic Resonance Imaging/methods , Biomarkers
7.
J Stroke Cerebrovasc Dis ; 30(11): 106046, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34454302

ABSTRACT

OBJECTIVES: The Distal Motor Function (DMF) sub-score of the NIH Stroke Scale (NIHSS) was measured in the NINDS rt-PA Stroke Trials but is currently not included in the NIHSS. The correlation of DMF with the NIHSS Motor Arm Function (MAF) sub-score, the effect of IV tPA treatment on DMF, and whether adding DMF changes the utility of the NIHSS have not been analyzed. MATERIALS AND METHODS: MAF and DMF sub-scores were retrieved from the original NINDS rt-PA Stroke Trials for both sides of the body at baseline, 2 hours, 24 hours, 7-10 days, and 3 months after IV tPA treatment. MAF and DMF scores were correlated using Spearman correlation. Clustering of DMF and MAF scores was determined using a Bentler Comparative Fit Index (CFI) to estimate variation in NIHSS when adding DMF. The effect of IV tPA on DMF and MAF was assessed using a linear model comparing changes in scores from baseline to 3 months. RESULTS: MAF and DMF were highly correlated (p < 0.0001) across all time points for both dichotomous and continuous data on both sides. Intravenous tPA accounted for 21% of the change in DMF (p < 0.014, R2 = 0.0157, N = 423) and 39% of the change in MAF (p < 0.093, R2 = 0.0125, N = 547) from 0 to 3 months. On adding DMF to NIHSS, CFI decreased from 0.98 to 0.80 and DMF clustered with MAF, indicating that addition of DMF is unlikely to produce any discrepancy to NIHSS. CONCLUSIONS: Including DMF to the NIHSS does not appear to be of additional value. After IV tPA treatment, proximal and distal motor function in upper extremity strongly correlate over time but greater improvement in MAF is noted. Further research is needed on the role of IV tPA on minor strokes with deficits of DMF.


Subject(s)
Arm , Stroke , Tissue Plasminogen Activator , Administration, Intravenous , Arm/physiopathology , Fibrinolytic Agents/administration & dosage , Humans , Stroke/drug therapy , Stroke/physiopathology , Tissue Plasminogen Activator/administration & dosage , Treatment Outcome
8.
J Stroke Cerebrovasc Dis ; 30(9): 105969, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34303962

ABSTRACT

OBJECTIVES: To report a case of isolated third nerve palsy from pituitary apoplexy and perform a systematic literature review. MATERIALS AND METHODS: MEDLINE/EMBASE databases were searched up to September 2020. INCLUSION CRITERIA: Age≥18, isolated third nerve palsy from pituitary apoplexy. EXCLUSION CRITERIA: Age<18, presence of other neurological findings, no hemorrhage or infarction of pituitary. RESULTS: Case report: A 76-year-old woman presented with headache and right-sided ptosis. Right-eye exam revealed complete ptosis, absent pupillary constriction and accommodation, depressed and abducted eye on primary gaze, and -1 impaired depression, adduction, elevation, without other neurological findings. Brain MRI was suggestive of pituitary apoplexy. Pathology after transsphenoidal resection revealed an infarcted pituitary adenoma. Third nerve palsy resolved completely in 21 days. Systematic review: Twenty-three studies reporting 35 patients were selected from 182 abstracts. Twenty-nine (83%) had complete isolated third nerve palsy. Headache was reported in 31 (97%). Thirty-one had hemorrhage and 1 had infarction of pituitary. Cavernous sinus invasion occurred in 14 (50%). Twenty-eight were managed surgically (80%) and 7 medically (20%). Nerve palsy resolved completely in 27 (82%) and partially in 4 (11%). CONCLUSIONS: Pituitary apoplexy is an important differential diagnosis in patients with isolated third nerve palsy. Isolated third nerve palsy in apoplexy appears to have favorable prognosis.


Subject(s)
Adenoma/complications , Oculomotor Nerve Diseases/etiology , Oculomotor Nerve/physiopathology , Pituitary Apoplexy/etiology , Pituitary Neoplasms/complications , Adenoma/diagnostic imaging , Adenoma/pathology , Adenoma/surgery , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Oculomotor Nerve Diseases/diagnosis , Oculomotor Nerve Diseases/physiopathology , Pituitary Apoplexy/diagnostic imaging , Pituitary Apoplexy/pathology , Pituitary Apoplexy/surgery , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Predictive Value of Tests , Recovery of Function , Risk Factors , Treatment Outcome , Young Adult
9.
J Stroke Cerebrovasc Dis ; 30(5): 105680, 2021 May.
Article in English | MEDLINE | ID: mdl-33652344

ABSTRACT

INTRODUCTION: Body lateropulsion (BLP) is seen in neurological lesions involving the pathways responsible for body position and verticality. We report a case of isolated body lateropulsion (iBLP) as the presentation of lateral medullary infarction and conducted a systematic literature review. METHODS: MEDLINE and EMBASE databases were searched up to December 3, 2020. INCLUSION CRITERIA: age ≥ 18, presence of BLP, confirmed stroke on imaging. EXCLUSION CRITERIA: age < 18, qualitative reviews, studies with inadequate patient data. Statistical analysis was performed using IBM® SPSS® Statistics 20. RESULTS: A 64-year-old man presented with acute-onset iBLP. Brain MRI demonstrated acute infarction in the right caudolateral medulla. His symptoms progressed with ipsilateral Horner syndrome over the next 24 hours and contralateral hemisensory loss 10 days later. Repeat MRI showed an increase in infarct size. BLP resolved partially at discharge. Systematic review: 418 abstracts were screened; 59 studies were selected reporting 103 patients. Thirty-three patients had iBLP (32%). BLP was ipsilateral to stroke in 70 (68%) and contralateral in 32 (32%). The most common stroke locations were medulla (n = 63, 59%), pons (n = 16, 15%), and cerebellum (n = 16, 15%). Four strokes were cortical, 3 frontal and 1 temporoparietal (3%). The most common etiology was large-artery atherosclerosis (LAA) in 20 patients (32%), followed by small-vessel occlusion in 12 (19%). Seventeen (27%) had large-vessel occlusion (LVO), 12 involving the vertebral artery. Sixty (98%) had some degree of resolution of BLP; complete in 41 (70%). Median time-to-resolution was 14 days (IQR 10-21). There was no relationship between time-to-resolution and age, sex, side of BLP or side of stroke. CONCLUSION: BLP was commonly seen with medullary infarction and was the isolated finding in one-third. LAA and LVO were the most common etiologies. Recovery of BLP was early and complete in most cases.


Subject(s)
Brain Stem Infarctions/complications , Postural Balance , Sensation Disorders/etiology , Brain Stem Infarctions/diagnostic imaging , Brain Stem Infarctions/physiopathology , Diffusion Magnetic Resonance Imaging , Horner Syndrome/etiology , Horner Syndrome/physiopathology , Humans , Male , Middle Aged , Sensation Disorders/diagnosis , Sensation Disorders/physiopathology
11.
Stroke ; 51(1): 90-98, 2020 01.
Article in English | MEDLINE | ID: mdl-31766980

ABSTRACT

Background and Purpose- To test the hypothesis that covert brain infarcts (CBIs) are more likely to be located in noneloquent brain areas compared with clinical strokes and that CBI etiological subtypes carry a differential risk of vascular events compared with people without CBI. Methods- We used brain magnetic resonance imaging from 1290 stroke-free participants in the NOMAS (Northern Manhattan Study) to evaluate for CBI. We classified CBI as cardioembolic (ie, known atrial fibrillation), large artery atherosclerosis (extracranial and intracranial), penetrating artery disease, and cryptogenic (no apparent cause). CBI localized in the nonmotor areas of the right hemisphere were considered noneloquent. We then evaluated risk of events by CBI subtype with adjusted Cox proportional models. Results- At the time of magnetic resonance imaging, 236 participants (18%) had CBI (144 [61%] distal cryptogenic, 29 [12%] distal cardioembolic, 26 [11%] large artery atherosclerosis, and 37 [16%] penetrating artery disease). Smaller (per mm, odds ratio, 0.8 [0.8-0.9]) and nonbrain stem infarcts (odds ratio, 0.2 [0.1-0.6]) were more likely to be covert. During the follow-up period (10.4±3.1 years), 398 (31%) died (162 [13%] of vascular death) and 117 (9%) had a stroke (99 [85%]) were ischemic. Risks of events varied by CBI subtype, with the highest risk of stroke (hazard ratio, 2.2 [1.3-3.7]) and vascular death (hazard ratio, 2.24 [1.29-3.88]) noted in participants with intracranial large artery atherosclerosis-related CBI. Conclusions- CBI can be classified into subtypes that have differential outcomes. Certain CBI subtypes such as those related to intracranial large artery atherosclerosis have a high risk of adverse vascular outcomes and could warrant consideration of treatment trials.


Subject(s)
Brain Infarction/pathology , Brain Ischemia/pathology , Cerebral Infarction/classification , Infarction/pathology , Stroke/pathology , Aged , Atrial Fibrillation/complications , Atrial Fibrillation/pathology , Brain Infarction/complications , Brain Ischemia/etiology , Cerebral Infarction/etiology , Cerebral Infarction/pathology , Female , Humans , Infarction/diagnosis , Intracranial Arteriosclerosis/complications , Intracranial Arteriosclerosis/pathology , Male , Middle Aged , Risk Factors , Stroke/etiology
12.
Alzheimer Dis Assoc Disord ; 33(3): 194-199, 2019.
Article in English | MEDLINE | ID: mdl-31305321

ABSTRACT

BACKGROUND: Brain amyloid- positron emission tomography (PET) imaging is highly sensitive for identifying Alzheimer disease. Currently, there is a lack of insight on the association between amyloid-PET status and the widely used Montreal cognitive assessment (MoCA). Studying this relationship may optimize the clinical use of amyloid-PET imaging. OBJECTIVES: To evaluate the relationship between amyloid-PET status and MoCA scores and to identify a MoCA score cutoff that translates to amyloid-PET positivity. METHODS: Using retrospective chart review, patients from 2010 to 2017 with amyloid-PET scans (positive or negative) and MoCA test scores were included. We studied the relationship between amyloid-PET status and MoCA scores and the influence of age, sex, education, and race. A MoCA score cutoff for amyloid-PET positivity was estimated. RESULTS: Among the 684 clinic patients with dementia, 99 fulfilled inclusion criteria. Amyloid-PET positivity was associated significantly with lower MoCA scores (median=19, U=847, P=0.01). The MoCA score cutoff (25) used for minimal cognitive impairment (MCI) predicted amyloid-PET positivity suboptimally (sensitivity=94.6%, specificity=13.9%). A MoCA score cutoff of 20 patients had optimal sensitivity (64.2%) and specificity (67.4%). CONCLUSIONS: Amyloid-PET positivity is associated with lower MoCA scores. Clinical utility of amyloid-PET scan is likely to be suboptimal at the MoCA score cutoff for minimal cognitive impairment.


Subject(s)
Alzheimer Disease/diagnostic imaging , Ambulatory Care Facilities , Amyloidogenic Proteins , Mental Status and Dementia Tests/statistics & numerical data , Positron-Emission Tomography , Referral and Consultation , Aged , Cognitive Dysfunction/diagnostic imaging , Female , Humans , Male , Retrospective Studies , Sensitivity and Specificity
13.
Opt Express ; 26(23): 30523-30531, 2018 Nov 12.
Article in English | MEDLINE | ID: mdl-30469950

ABSTRACT

We demonstrate an optically pumped magnetometer (OPM) operated in a free-induction-decay (FID) configuration that is capable of tracking oscillating magnetic signals in the presence of a 50 µT static field. Excellent waveform reconstruction is demonstrated for low frequency modulations with respect to the Nyquist limited bandwidth. A 100 pT oscillation was successfully reconstructed using signal averaging, and an optimum sensitivity of 3.9 pT/Hz was measured from the spectrum of the residuals relative to the sinusoidal fit. The impact of the pump-probe repetition rate and spin depolarization on the frequency response of the sensor is investigated in detail using miniaturized vapor cell technology, with the (-3 dB) bandwidths residing beyond the Nyquist limit in each case. We also discuss technical limitations associated with the magnetometer when exposed to oscillating fields of sufficiently high amplitude or frequency. This is discussed in the context of potential distortions arising in the reproduced signals, induced by frequency modulation (FM) and aliasing artefacts.

14.
J Clin Diagn Res ; 11(8): OD17-OD18, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28969188

ABSTRACT

Primary Intestinal Lymphangiectasia (PIL) is a rare disease of unknown aetiology which presents in the paediatric age group with anasarca, diarrhoea, hypoproteinaemia, lymphoedema and chylous effusions. Tuberculosis, filariasis, chest trauma, malignancies and haematological disorders usually contribute to most cases of secondary lymphangiectasia and chylous effusions. We hereby describe a case of PIL presenting with chylous effusions which remained undiagnosed for eight years.

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