Diffuse Disease Research Articles

Congenital hyperinsulinism in the Ukraine: a 10-year national study

IntroductionCongenital Hyperinsulinism (CHI) has not been previously studied in Ukraine. We therefore aimed to elucidate the genetics, clinical phenotype, histological subtype, treatment and long-term outcomes of Ukrainian patients with CHI.MethodsForty-one patients with CHI were recruited to the Ukrainian national registry between the years 2014-2023. Genetic testing (n=40), 18F-fluorodihydroxyphenylalanin and 68Ga-DOTANOC PET/CT imaging followed by surgical treatment and subsequent histological analysis (n=19) was performed through international collaboration.ResultsPathogenic variants were identified in 19/22 (86.3%) individuals with persistent CHI (p-CHI) and 8/18 (44.4%) with early remission CHI (er-CHI). Pathogenic variants in the K-ATP channel genes were the only identified genetic cause of p-CHI (ABCC8 (n=17) and KCNJ11 (n=2)) with greater genetic heterogeneity observed in those with er-CHI (ABCC8 (n=3), KMT2D (Kabuki Syndrome, n=1), Beckwith-Wiedemann syndrome (n=2) and INSR (Donohue syndrome (n=2)). Histological analysis performed on 19 children with persistent CHI confirmed focal disease in 14 (73.7%), diffuse disease in two (10.5%) and atypical histology in three (15.8%). After surgery, complete recovery was observed in all 14 with focal disease, while relapse occurred in three patients with diffuse or atypical histology.ConclusionA genetic diagnosis was achieved for 67.5% (27/40) of the cohort with a higher pick-up rate observed in those with p-CHI. The genetics and imaging studies enabled subtype-targeted treatment with surgical cure achieved in all individuals with focal disease.

Hospitalizations in patients with systemic sclerosis: Differences between limited and diffuse cutaneous subtypes

Aim: Systemic sclerosis is associated with significant morbidity and mortality. It remains unclear from the literature if there are differences between the subtypes of systemic sclerosis and the rate of hospitalization. Our study investigates the rates of all types of hospitalizations between limited and diffuse cutaneous systemic sclerosis. Methods: Patients have been collected prospectively using the European Scleroderma Trials and Research Group database at the Waikato Hospital, and were screened for inclusion criteria. Data were collected retrospectively on hospitalizations (total, acute, elective and infusion-related) for all patients. Results: Overall, 140 patients were included in the analysis with 84 (60.0%) with limited cutaneous systemic sclerosis, 40 (28.6%) with diffuse systemic sclerosis, 3 (2.1%) with systemic sclerosis sine scleroderma and 13 (9.3%) with overlap syndrome. The mean number of total hospitalizations in 12 months was 0.9 (SD 3.0) for patients with limited disease versus 1.7 (SD 3.0) for diffuse disease (p = 0.062). The mean number of acute hospitalizations in 12 months was 0.6 (SD 1.3) for limited and 1.2 (SD 2.4) for diffuse (p = 0.061). Patients with diffuse systemic sclerosis were more likely to be admitted for reasons relating to systemic sclerosis than patients with limited disease (p < 0.001). Conclusion: Diffuse and limited systemic sclerosis subtypes appear to have similar rates of hospitalizations though there is a trend in favour of diffuse disease towards more total and acute hospitalizations. There are clear differences in causes of hospitalization between the two main subgroups.

A clinical-radiomics nomogram based on automated segmentation of chest CT to discriminate PRISm and COPD patients

PurposeIt is vital to develop noninvasive approaches with high accuracy to discriminate the preserved ratio impaired spirometry (PRISm) group from the chronic obstructive pulmonary disease (COPD) groups. Radiomics has emerged as an image analysis technique. This study aims to develop and confirm the new radiomics-based noninvasive approach to discriminate these two groups. MethodsTotally 1066 subjects from 4 centers were included in this retrospective research, and classified into training, internal validation or external validation sets. The chest computed tomography (CT) images were segmented by the fully automated deep learning segmentation algorithm (Unet231) for radiomics feature extraction. We established the radiomics signature (Rad-score) using the least absolute shrinkage and selection operator algorithm, then conducted ten-fold cross-validation using the training set. Last, we constructed a radiomics signature by incorporating independent risk factors using the multivariate logistic regression model. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCA). ResultsThe Rad-score, including 15 radiomic features in whole-lung region, which was suitable for diffuse lung diseases, was demonstrated to be effective for discriminating between PRISm and COPD. Its diagnostic accuracy was improved through integrating Rad-score with a clinical model, and the area under the ROC (AUC) were 0.82(95 %CI 0.79–0.86), 0.77(95 %CI 0.72–0.83) and 0.841(95 %CI 0.78–0.91) for training, internal validation and external validation sets, respectively. As revealed by analysis, radiomics nomogram showed good fit and superior clinical utility. ConclusionsThe present work constructed the new radiomics-based nomogram and verified its reliability for discriminating between PRISm and COPD.

Clinical Significance of Aspergillus Sensitisation in Chronic Pulmonary Aspergillosis.

Aspergillus sensitisation (AS) is seen in many patients with chronic pulmonary aspergillosis (CPA). However, the clinical relevance of AS in CPA remains unclear. In this study, we assess the clinical significance of AS in CPA. We retrospectively analysed the data of CPA subjects, defining AS as Aspergillus fumigatus-IgE ≥ 0.35 kUA/L. We excluded subjects with asthma, allergic bronchopulmonary aspergillosis, chronic obstructive pulmonary disease (COPD) and diffuse parenchymal lung diseases (DPLD). The primary objective was to compare the demographic and clinical characteristics, lung functions (via spirometry) and treatment outcomes in CPA subjects with or without AS. The secondary objective was to explore the association between AS and airflow obstruction on spirometry using multivariable logistic regression analysis. We included 232 CPA subjects (119 females, 113 males) with a mean ± SD age of 42.1 ± 13.7 years. AS was present in 92 (39.7%) CPA patients (CPA-AS group). CPA-AS patients had higher SGRQ total scores, a higher prevalence of fungal ball, more frequent airflow obstruction and experienced more CPA relapses during follow-up compared to those without AS. Airflow obstruction was seen in 77/232 (33.2%) CPA patients. On multivariable logistic regression analysis, we found AS, increasing age and chronic fibrosing pulmonary aspergillosis independently associated with airflow obstruction on spirometry after adjusting for sex and other CPA categories. The relapse-free survival was significantly shorter in the CPA-AS group than in the CPA group. AS is common in CPA and is independently associated with airflow obstruction. More studies are required to confirm our findings.

Whole lung and sequential bronchoscopic lavage for pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli due to abnormal surfactant homeostasis. Since its introduction in the 1960s, whole lung lavage (WLL) has been the primary treatment for PAP. This review focuses on WLL, including its technique modifications, and sequential bronchoscopic lavage. Autoimmune PAP, which accounts for the majority of cases, occurs when antigranulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies lead to the deficiency of bioavailable GM-CSF. At present, there are no international guidelines or consensus statements for PAP treatment. Traditionally, therapeutic decisions are made based on the severity and type of PAP. Despite emerging data on GM-CSF-based therapies, WLL remains a central component in the therapeutic strategy for PAP. Although the technique of WLL has evolved over time, there is still no universally adopted, standardized protocol. However, key periprocedural aspects - such as preprocedural planning, patient evaluation, anesthetic technique, lavage protocol, and postprocedural care - remain essential to ensuring the safety and success of WLL.

Focal what focal? — The diverse entities within focal adenomyosis

Adenomyosis is a benign uterine condition defined as the presence of endometrial glands and stroma within the myometrium. Unfortunately, its pathogenesis remains uncertain. The international Morphological Uterus Sonographic Assessment (MUSA) group has published a consensus on the ultrasound features of adenomyosis in 2015. Among different adenomyosis phenotype, focal adenomyosis is a heterogeneous group of different pathogenic, histopathological and clinical entities. By using the sonographic features different types of focal adenomyosis may be identified: 1) focal adenomyosis in the outer myometrium involving the serosa, which might have a strong correlation with deep infiltrating endometriosis; 2) the presence of a focal area of direct signs of adenomyosis in the inner myometrium, most likely through direct invasion from endometrial cells from the uterine cavity; 3) the presence of a focal area of direct signs (i.e., hyperechogenic islands with or without myometrial cysts) in the middle or outer myometrium. Most likely, this lesion is part of more diffuse disease; 4) A macro-cystic lesion in the myometrium without contact with the junctional zone of myometrium; 5) Accessory and cavitated uterine mass (ACUM) in the outer myometrium, which are suggested to be a continuum of congenital uterine anomalies. Some of these entities have also been described in MRI. The scope of the present opinion paper is to describe the different entities of focal adenomyosis leading to new insights of the impact of each of these entities on both clinical symptoms (e.g. pain, bleeding, subfertility) and management options. However, the proposed concept might need amendment and should be the object of future research.

Abstract 4138477: Small Vessels, Big Challenges: Clinical and Demographic Correlates of Failure to Respond to Optimal Medical Therapy in Patients with Microvascular Angina

Background: Microvascular angina (MVA), resulting from coronary microvascular dysfunction, affects 40-50% of patients with exertional chest pain or dyspnea and a normal coronary angiogram. This condition significantly impairs quality of life and elevates the risk of major cardiac events, including myocardial infarction, stroke and death. MVA is classified as 'structural' (coronary flow reserve [CFR] <2.5&index of microcirculatory resistance [IMR] >25) or 'functional' (CFR <2.5&IMR <25). Current treatments are empirical, necessitating further investigation. Methods: This single-centre, retrospective study conducted in South Wales from 2019-24 examined MVA cases confirmed via national electronic health records. The Canadian Cardiovascular Society (CCS) angina grade was assessed at diagnosis and post optimal medical therapy (OMT) during clinic visits. Ordinal logistic regression was used to identify independent correlates of higher CCS grade, considering baseline LDL, age, diffuse epicardial disease, sex, hypertension, kidney function, smoking status and HbA1c levels as covariates. Results: Among 64 identified MVA cases (median age 69 yrs, IQR 61.3-77.8; 68.8% male), 81.3% had structural MVA, 6.3% functional MVA and 12.5% mixed disease. Coronary vessel testing was performed on 1, 2 or 3 vessels in 29.7% (n=19), 53.1% (n=34; 21 positive [+ve] in 2 vessels, 13 +ve in 1 vessel) and 17.2% (n=11; 5 +ve in 3 vessels, 5 +ve in 2 vessels, 1 +ve in 1 vessel) of cases, respectively. The LAD was most commonly affected vessel (82.8%). At diagnosis, 79.7% had CCS grade III or higher (Fig 1). Post OMT, 45.3% achieved CCS grade 0-I, 31.8% CCS grade II and 15.6% remained at CCS grade III (refractory angina). Medications included ranolazine (84.4%), beta-blockers (70.3%) and calcium channel blockers (28.1%). Ordinal logistic regression analysis (X 2 =0.27, p=0.033) identified baseline LDL (95% CI [0.16, 1.26]; p=0.011), age (95% CI [-0.12, -0.001]; p=0.045), diffuse epicardial disease (95% CI [0.016, 2.13]; p=0.047) and male sex (95% CI [0.066, 2.36]; p=0.038) as independent correlates of higher CCS grade, signifying poor response to OMT. Conclusion: MVA manifests regionally, underscoring the need for multi-territory testing. Although tailored OMT proved effective for many, 15.6% of patients continued to experience refractory symptoms (CCS grade III). This highlights the necessity for alternative therapeutic strategies to improve patient outcomes in this challenging condition.

Abstract 4137058: Clinical Characteristics and Outcomes of South Asians Presenting with Acute Coronary Syndrome

Background: Patients of South Asian descent have a higher incidence of atherosclerotic cardiovascular disease and are affected by clinically significant coronary artery disease at an earlier age when compared to the general population. As a result, they have been shown to have a higher rate of cardiovascular events. This at-risk population has not been well studied as it pertains to acute coronary syndrome. Methods: Out of 1610 patients who presented to one of two tertiary care centers between 2021-2022 with a diagnosis of acute coronary syndrome and underwent coronary angiography, 240 patients were identified as being South Asian and were included in the study. 480 non-South Asian patients were randomly selected as controls. A retrospective analysis was conducted to study the demographics, risk factors, clinical presentation, diagnostic features, and outcomes of the two groups. Results: South Asian patients who were diagnosed with acute coronary syndrome and underwent coronary angiography were significantly younger than non-South Asian patients (61 vs 65 years, p < 0.001). Though they were less likely to be smokers, they were significantly more likely to have other known risk factors including hypertension, dyslipidemia, and a history of prior myocardial infarction (p < 0.001). South Asians had mean lower HDL (p = 0.02), higher triglycerides (0.006), and higher Hgb A1C (p < 0.001). Surprisingly, rates of multivessel disease (defined as stenosis of 50% or greater in two or three vessels) were similar between the two groups. South Asians were more likely to be referred for CABG after initial coronary angiography most likely due to diffuse disease (p = 0.014). Clinical outcomes including pre-discharge LVEF, and 2-year mortality were similar between the groups. Conclusions: South Asians are a notoriously high-risk group when it comes to early-onset and more severe coronary artery disease. The pathophysiology behind this disproportionate manifestation of cardiovascular disease is not entirely understood, but several efforts to delineate this are ongoing. Our data demonstrate that this is at least in part, due to a higher prevalence of conventional modifiable and nonmodifiable risk factors in South Asian patients.

Abstract 4138424: Ring of Power: Unraveling a Rare Diagnosis in a Young Male with Palpitations

Case Description: A 36-year-old male presented for an outpatient treadmill ECG stress test for further evaluation of palpitations exacerbated by exercise. He had no ischemic ECG changes, but developed a sustained episode of polymorphic VT at 13 minutes (Figure 1a). The test was stopped and the VT self-terminated after 43 seconds. The patient was admitted for further workup. Lab workup was unremarkable; baseline ECG demonstrated no ST-T wave changes and displayed normal QT and QRS duration. TTE showed mild biventricular dysfunction. Coronary CT angiogram showed type 3 subtype of Vieussens’ arterial ring (VAR), with an absent left main and super-dominant RCA supplying both LAD and LCx. FFR-CT showed non-hemodynamically significant stenosis in the mid-distal LAD (Figure 1b). Left heart catheterization confirmed presence of VAR and mild diffuse disease in a small-caliber mid-distal LAD (Figures 1c&d). No malignant course or dynamic coronary compression was present. Cardiac MRI revealed normal biventricular function and the absence of late gadolinium enhancement. An exercise stress test, now with myocardial perfusion, was performed and was entirely normal without evidence of myocardial ischemia. Genetic testing for catecholaminergic polymorphic VT was negative. After a multidisciplinary discussion, it was decided not to pursue CABG in the absence of demonstrable ischemia at peak exercise. He underwent an ICD placement for secondary prevention and was discharged on beta blockers. Discussion: Three distinct subtypes of VAR have been described, with type 3 being the rarest. The coronary anomaly was first described by Raymond de Vieussens in 1706, and represents an embryologic remnant of the conotruncal circle. It may be diagnosed incidentally in asymptomatic patients or present with angina especially if underlying CAD, aneurysms or fistulae are present. We report the first case of exercise-induced polymorphic VT in a type 3 VAR patient, theorizing that intermittent myocardial ischemia at peak exercise may induce VT in these patients. Surgical revascularization may be considered if myocardial ischemia is demonstrated on stress testing, although its benefit in patients without such evidence of ischemia is unknown.

PATH-42. METASTATIC ADENOID CYSTIC CARCINOMA OF BREAST WITH BRAIN METASTASES AND LEPTOMENINGEAL DISEASE

Abstract INTRODUCTION Adenoid cystic carcinoma (ACC) of the breast rarely metastasizes to the brain and leptomeninges. ACC is a rare type of breast cancer, accounting for less than 0.1% of cases. It is usually triple negative, but has a good prognosis when it is confined to the breast. Lymph node involvement is uncommon, occurring in less than 2% of cases, and distant metastases to the brain are extremely rare. Leptomeningeal disease has not been reported yet. Case: In this case, we describe a 57-year-old woman diagnosed with triple-negative ACC of the right breast, which had spread to the axillary lymph nodes and distant metastases to the lung. The diagnosis was confirmed by biopsies of both metastatic sites. The patient received vinorelbine and cisplatin treatment for 11 cycles followed by right needle localized lumpectomy. While awaiting for the next steps in treatment she was admitted to the hospital for altered mental status, saddle anesthesia, and urinary incontinence. Neuraxis MRI revealed numerous hemorrhagic and non-hemorrhagic brain metastasis with diffuse leptomeningeal disease. Cerebrospinal fluid analysis confirmed leptomeningeal disease with positive cytology for atypical epithelioid malignant cells. The patient underwent whole brain radiation and focal radiation treatment to specific areas of leptomeningeal disease. Although she initially improved after the first month of radiation, her condition deteriorated rapidly, preventing the initiation of the next line of treatment with high-dose methotrexate or capecitabine. DISCUSSION Adenoid cystic carcinoma of the breast is exceedingly rare however with a very good overall prognosis. It is uncommon for ACC to spread to regional lymph nodes, and even rarer for distant metastasis. Brain metastasis is also infrequently reported. There are no documented cases of metastatic ACC with leptomeningeal disease, so there is no consensus on the best course of treatment.

Analysis of a diffusive vector-borne disease model with nonlinear incidence and nonlocal delayed transmission

Analysis of a diffusive vector-borne disease model with nonlinear incidence and nonlocal delayed transmission

RADT-35. PATTERNS OF INTRACRANIAL RESPONSE AND RELAPSE AFTER CNS-DIRECTED RADIOTHERAPY (CNS-RT) FOR PATIENTS WITH CHEMOREFRACTORY OR PROGRESSIVE SECONDARY CNS LYMPHOMA (SCNSL)

Abstract PURPOSE/OBJECTIVE Progressive SCNSL after failure of CNS-directed systemic therapy is a challenging clinical scenario. CNS-RT can effectively salvage, but its optimal role is poorly defined. METHODS We analyzed diffuse large B-cell patients who received brain RT for progressive SCNSL following 1+ line of therapy for active SCNSL (not prophylaxis). Overall survival (OS) was calculated by Kaplan-Meier and RT response was evaluated using IPCG or RANO criteria for parenchymal or leptomeningeal disease, respectively. Risk of intracranial failure assumed death as a competing risk. Pre-RT SCNSL patterns were classified as parenchymal-only versus diffuse (periventricular or leptomeningeal). Local failure was progression only of pre-RT lesion(s). RESULTS We identified 55 patients with median follow up of 3.5m. 85% had neurologic symptoms, 45% had extracranial disease. Patients received a median of 2 prior SCNSL-directed therapies (IQR 1-3); 91% received methotrexate-based regimens with median 21d between last methotrexate and RT. Median CNS-RT dose was 30 Gy in 10 fractions delivered to whole brain (n=44, 80%), partial brain (n=9, 16%), or craniospinal axis (n=2, 4%). Median OS was 3.5m. Overall response for 38 evaluable was 79% (24% complete), with median of 60d to best response. 58% were successfully bridged with CNS-RT to subsequent therapies and 12m intracranial failure risk was 37% for those bridged, and 64% for those not bridged (p=0.05). 19 had parenchymal-only disease (10 unifocal, 9 multifocal) with median largest lesion diameter 4.1cm (range 1.7–7.4). 19 had diffuse pattern (12 periventricular, 7 leptomeningeal). 7 with parenchymal-only disease failed intracranially, 5 of which were local. 8 with diffuse disease failed intracranially, only 1 of which was local (p = 0.035). CONCLUSION SCNSL patients referred for RT had symptomatic, treatment-refractory disease. While CNS-RT response rates were high, duration was often limited, suggesting RT is best used for bridging/palliation. Patients with parenchymal-only disease were enriched for local failure, suggesting potential suitability of involved site CNS-RT, though further validation is needed.

Impact of Season, Environmental Temperature, and Humidity on Raynaud Phenomenon in an Australian Systemic Sclerosis Cohort.

The aim of this study was to determine the impact of season, temperature and humidity on the severity of Raynaud phenomenon (RP) in systemic sclerosis. Data from the Australian Scleroderma Cohort Study were used to assess associations of patient-reported worsened RP in the month preceding each study visit. Mean monthly weather data were obtained from the closest weather station to the patient's address. We evaluated the relationship between worsened RP and health-related quality of life (HRQoL) measured using the Short Form 36 instrument. Among 1,972 patients with systemic sclerosis, RP was a near-universal finding, and worsened RP in the preceding month was reported in 26.7% of 9,175 visits. "Worsened RP" showed significant environmental variability. On multivariable analysis, worsened RP was associated with low mean maximum temperatures (odds ratio [OR] 0.91, 95% confidence interval [95% CI] 0.90-0.92, P < 0.001), high relative humidity (OR 1.05, 95% CI 1.04-1.05, P < 0.001) and lower mean daily evaporation (OR 0.77, 95% CI 0.73-0.81, P < 0.001). Worsened RP was strongly associated with telangiectasia, calcinosis, and digital ulceration, as well as demonstrating an association with anticentromere antibody and gastroesophageal reflux disease and a negative correlation with diffuse disease. Worsened RP was also strongly associated with worse HRQoL. Lower environmental temperature and higher relative humidity had significant associations with worsened RP in this systemic sclerosis cohort, suggesting an important role for dry warmth in managing this condition.

Modern views on the diagnosis of sarcopenia in patients with diffuse liver diseases

Currently, the term sarcopenia is primarily understood as a decrease in muscle strength as a key characteristic of sarcopenia, taking into account that the most unfavorable clinical outcomes occur in patients with a combination of impaired muscle strength and function. In particular, grip strength combined with evaluation of the end-stage liver disease (MELD) model is the best predictive model among widely used methods for diagnosing sarcopenia in patients with cirrhosis of the liver. Given that muscle mass does not always correlate well with muscle strength or function in the population of patients with cirrhosis of the liver, there is a need for a comprehensive diagnosis of sarcopenia based on a combination of functional research methods with modern instrumental methods. The presented review article highlights current information on the diagnosis of sarcopenia in patients with chronic diffuse liver diseases. Aspects of antrometric methods, functional tests, methods for evaluating muscle strength and mass, and physical performance are reflected. Special attention is paid to the advantages of modern methods of instrumental diagnosis of sarcopenia in patients with diffuse liver diseases. The advantages and disadvantages of each of the methods of instrumental diagnostics are noted.

Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French pharmacovigilance database.

Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs. This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged 18 and over. We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 [18-103] years. The most prevalent ADRs were "ILD" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). "Anti-cancer drugs" (31.2%) and "Cardiovascular drugs" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%). This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify it properly and discontinue the culprit drug urgently.

Exploring subcortical pathology and processing speed in neuromyelitis optica spectrum disorder with myelin water imaging.

Neuromyelitis optica spectrum disorder (NMOSD) affects the optic nerves and spinal cord but can also cause focal brain inflammation. Subcortical pathology may contribute to the etiology of cognitive deficits in NMOSD. Using myelin water imaging, we investigated cerebral normal-appearing white matter (NAWM) and thalamic metrics and their association with cognition in NMOSD participants compared to healthy controls (HC). Seventeen NMOSD participants and 21 HC were scanned on a 3.0-Tesla MRI scanner using a multicomponent driven-equilibrium single-pulse observation of T1 and T2 protocol. Tissue compartment and thalamic volumes (normalized to intracranial volume), T1 relaxation time, and myelin water fraction (MWF) were reported. Eleven NMOSD participants underwent the Symbol Digit Modalities Test (SDMT) for cognitive evaluation. Group comparisons were performed using Student's t-test. The association between thalamic metrics and SDMT score was assessed using multiple regression analysis with age as a covariate. Compared to HC, NMOSD participants had reduced white matter volume (-14.2%, p<.0001), increased T1 relaxation time (+2.29%, p=.022), and lower MWF (-3.64%, p=.024) in NAWM. NMOSD group had a trend for smaller thalamic volumes than HC (-5.52%, p=.082) and no differences in thalamic MWF (p=.258) or T1 (p=.714). Thalamic T1 predicted SDMT score (adjusted R2=.51, p=.04) when controlling for age. NAWM in NMOSD demonstrates diffuse abnormalities with increased water content and demyelination, suggesting a diffuse disease process overlooked by focal inflammation measures. Increased water content, as a biomarker for diffuse thalamic pathology, may partially explain cognitive impairment in NMOSD.

Sjögren's Syndrome and Ankylosing Spondylitis Association: A Case-Based Review.

Unlike restrictive pulmonary function and apical fibrobullous disease, diffuse interstitial lung disease is scarce in patients with ankylosing spondylitis (AS). We present a systematic review of the association between AS and SS. We also report a new case of SS revealed by interstitial lung disease in AS patients treated with tumor necrosis factor (TNF) inhibitors. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE and SCOPUS databases and included case reports and case series describing the association between AS and SS. There were sixty-three patients, including our case: 16 males and 47 females. The mean age was 49.2 years. The mean SpA duration was 14.1 years. The mean delay between SpA and SS was 12.8 years (0-27). SS was diagnosed after SpA in 62% of cases (n=39). It preceded SpA in 36.5% (n=23) and was concomitant with SpA in 1 case. All patients had sicca symptoms. MSGB showed focal sialadenitis grade III or grade IV in the Chisholm classification in 20 patients. Anti- nuclear antibody was positive in 75.8% of cases. Among them, anti-SSA and anti-SSB were positive in 44.4% and 35.3% of cases. Except for our patient, no patient had interstitial lung disease. SS extra glandular manifestations were reported in 12 cases. The occurrence of Sjögren's syndrome is uncommon in patients with ankylosing spondylitis. This association has been reported in the literature, suggesting a pathogenetic link between these two diseases. This association should be considered in ankylosing spondylitis patients with diffuse interstitial lung disease. Knowing this association is necessary for therapeutic adjustment. Our study has some limitations. Publication bias was the major bias in our study. Indeed, we only included case reports and case series describing the association between SpA and SS. We did not search for unpublished work. Moreover, the follow-up was not specified in most included articles.

Thirty-Day Outcomes from the Disrupt PAD BTK II Study of the Shockwave Intravascular Lithotripsy System for Treatment of Calcified Below-the-Knee Peripheral Arterial Disease

Below the knee (BTK) lesions may be particularly challenging to treat owing to length, diffuse disease, and extent of calcification. Landmark interventional clinical studies have not reached consensus on the optimal standard of care for BTK lesions, and many published trials excluded patients with moderate or severe lesion calcification. Calcium modification with intravascular lithotripsy (IVL) was shown to be superior to percutaneous transluminal angioplasty (PTA) in the femoropopliteal artery and successful in treating BTK lesions in pilot studies. The Disrupt BTK II study is a core-lab adjudicated, prospective, multi-center single-arm study of patients with moderate to severely calcified BTK lesions treated with the Shockwave Medical Peripheral IVL System. Disrupt BTK II enrolled 250 subjects with calcified infrapopliteal lesions and Rutherford category 3-5 presentation from 38 sites in the United States and Europe. The primary safety endpoint was major adverse limb events (MALE) or post-operative death (POD) at 30 days, a composite of all-cause death, above-ankle amputation of the index limb, and/or major reintervention of the index limb involving an infrapopliteal artery. The primary effectiveness endpoint was procedural success, defined as ≤50% residual stenosis for all treated target lesions without serious core lab-adjudicated serious angiographic complications. The study used independent angiographic and duplex ultrasound core laboratories, and follow-up is planned through two years. A total of 305 lesions in 250 patients were treated with a procedural success of 97.9%. Mean target lesion length was 76 ± 65mm, diameter stenosis was 78 ± 18%, and 84.8% had moderate or severe calcification as assessed by an independent angiographic core lab. After IVL, residual stenosis was reduced to 29%, and to 26% after optional post-dilatation and/or stent implantation. At 30 days, there were no deaths, MALE rate was 0.8%, and mean improvement in VascuQoL scores was 4.0 ± 5.0 (P<0.0001). Of the patients with baseline wounds, 15.8% healed and 53.4% were improved at 30 days. The Disrupt PAD BTK II study demonstrated that treatment with the Shockwave Medical Peripheral IVL System in patients with moderate-severe calcified lesions resulted in high procedural success, significant reduction in residual stenosis, improvements in patient QoL and wound healing, with minimal adverse events at 30-day follow-up.

Pediatric Diffuse Lung Disease in Infants: Imaging Findings and Histopathologic Correlation.

Childhood interstitial lung disease (chILD) encompasses a diverse group of genetic, infectious, and inflammatory conditions affecting infants and children. The recognition and understanding of these entities have highlighted the necessity for more accurate classification. This group of rare heterogeneous diseases comprises more than 200 different conditions and has a combined estimated prevalence of less than one patient per 100 000 children. Hence, a systematic diagnostic approach is crucial. This article describes a diagnostic approach for pediatric diffuse lung diseases in infancy, including an analysis of clinical presentations and imaging and histologic features to effectively distinguish among various chILD entities. Although they often have overlapping and nonspecific radiologic features, some chILD entities may exhibit typical imaging findings, resulting in a CT diagnosis or aiding in narrowing the differential diagnosis, thus guiding the clinician to the appropriate genetic tests, potentially limiting unnecessary biopsies. This approach aims to enhance the understanding and diagnosis of chILD in infants, thereby facilitating improved patient care.

Mechanisms leading to peri-procedural myocardial infarction in patients with focal versus diffuse coronary artery disease

Abstract Background PMI are characterized by an elevation in cardiac biomarkers, such as troponin, following PCI. Adherence to the 4th UDMIof PMI necessitates not only elevated cardiac biomarkers but also the presence of ECG changes, new loss of viable myocardium, or angiographic findings indicative of a procedural complication. Understanding the mechanisms underlying PMI and their associated factors is of paramount clinical significance. Our goal was to investigate the specific pathways contributing to the occurrence of PMI in stable patients undergoing PCI. Methods This prospective study was performed at 23 sites and enrolled patients with at least one epicardial lesion with an FFR≤0.80 planned to be treated by PCI. Each patient underwent a standardized physiological protocol, including manual FFR pullbacks with PPG calculation for the characterization of CAD patterns. The median PPG value (0.62) was used to divide patients into predominantly focal or diffuse disease. Troponin levels were measured after PCI, and patients exhibiting an elevation exceeding 5 times the upper limit of normal (ULN) were subject to evaluation by an independent clinical events committee. In addition, patients with large troponin elevation (&amp;gt;70 times above the ULN) were adjudicated as PMI as a standalone criterion. The primary objective was to investigate the mechanism leading to PMI in patients with focal versus diffuse CAD. Results Overall, 855 patients were included in this analysis, with 34.5% (295 patients) exhibiting a troponin elevation exceeding 5 times the ULN. Among these cases, 66 (7.7%) were adjudicated as PMI. The prevalence of secondary criteria for PMI was as follows: ECG changes at 7.6% (5/66), new loss of viable myocardium at 0%, side branch occlusion at 18.2% (12/66), and large troponin elevation at 84.8% (56/66). Diffuse disease (PPG &amp;lt; 0.62) was significantly associated with PMI (OR 1.71, 95% CI 1.03 to 2.88, p-value = 0.038). In the overall population, the occurrence of ECG changes after PCI was 0.7% in focal disease compared to 0.8% in diffuse disease (p-value=1.0). Side branch occlusion after PCI was observed in 0.7% in focal disease vs. 2.5% in diffuse disease (p-value=0.04), and large troponin elevation occurred in 4.8% in focal disease vs. 8.5% in diffuse disease (p-value=0.03). Additionally, PPG was significantly associated with the incidence of side branch occlusion (OR 1.71, 95% CI 1.03 to 2.88, p-value=0.038) and large troponin elevation after PCI (OR 1.83, 95% CI 1.06 to 3.22, p-value=0.038). Conclusion The presence of diffuse atherosclerosis, as defined by PPG, was linked to an increased risk of PMI. The mechanisms leading to PMI differed between patients with focal and diffuse disease. Patients with diffuse disease demonstrated a higher incidence of branch occlusion and large troponin elevation following PCI compared to those with focal CAD. Targeting patients with high PPG may improve outcomes after PCI.MACE by PPG