Leukoencephalopathy with cerebral calcifications and cysts: the neurosurgical perspective. Literature review.

PURPOSE: Labrune syndrome is a rare white matter disease characterised by angiomatous leukoencephalopathy, diffuse intracranial calcifications and supra- and infra-tentorial parenchymal cysts. The clinical worsening is often related to cyst expansion, and surgery may be advocated for symptomatic management in about one-third of cases. However, no consensus exists on surgical timing, the most effective procedure, and long-term results. MATERIAL AND METHODS: Electronic databases, such as PubMed/ MEDLINE and Google Scholar, were analysed for studies published to April 2022 using the search term "Labrune syndrome OR leukoencephalopathy with calcifications and cysts OR brain calcifications OR brain cysts AND therapy OR surgery RESULTS: We found 28 studies reported in the literature, and we added a new case we treated at our Institution, reaching a series of 37 patients. All the patients in this series underwent surgical intervention. We aimed to review all the pertinent literature to discuss clinical-radiological features and etiopathogenetic insights, addressing the specific issue of the surgical options, clinical results and prognosis. CONCLUSION: LCC is a rare neurodegenerative disorder without effective medical treatment. Surgery remains the only therapeutic option to control the disease to reduce the mass effect of growing cystic lesions. Almost half of the patients who underwent surgery required further approaches, with great concern for the associated disabilities. Several procedures have been described, with no evidence of the most effective. Individual-based surgical planning must be advocated, tailoring the approach to limit side effects. Mini-invasive neuroendoscopic approaches may be considered to achieve those satisfactory results.

A Clinical Neurological Approach to the Child With Adenosine Deaminase Deficiency.

BACKGROUND: Severe combined immunodeficiency secondary to adenosine deaminase deficiency is rare. The deficiency of this enzyme results in the accumulation of substrates in the tissues, including the brain. Clinical signs of neurological involvement may include seizures, neurodevelopmental disorders, hypotonia, and sensorineural hearing loss. Hematopoietic stem cell transplantation corrects the failure of the immune system but not the neurological involvement. OBJECTIVES: To describe the spectrum of neurological complications identified in a series of children with severe combined immunodeficiency due to adenosine deaminase deficiency. Additionally, we propose a neurological approach including electrophysiological, radiological, and neurocognitive studies to address this group of children in an efficient and timely manner. METHODS: A descriptive, observational, retro-, and prospective analysis of patients with a confirmed immunological diagnosis seen between 1996 and 2021 and referred to the Department of Neurology for neurological evaluation was conducted. RESULTS: Ten patients met the inclusion criteria. The median age at diagnosis was 4 months (range, 1-36 months). All patients had neurodevelopmental delay with hypotonia in six, language delay in three, sensorineural hearing loss in four, and spastic paraparesis in one patient. Two children developed an epileptic syndrome, consisting of generalized epilepsy in one and focal epilepsy in the other. Neuroimaging showed brain calcifications in the basal ganglia and/or centrum semiovale in four patients and enlarged subarachnoid spaces in two other patients. CONCLUSION: In this pediatric series, the rate of neurological involvement associated with abnormalities on neuroimaging was high. Although this involvement could be related to accumulation of adenosine metabolites in the central nervous system, the possibility of associated chronic infections should be ruled out. Given the neurological manifestations, it is important to involve the pediatric neurologist in the multidisciplinary follow-up team.

Characterization of stromal calcifications in odontogenic keratocyst: a multicentric study.

Odontogenic keratocysts (OKCs) are locally aggressive cysts that exhibit typical histopathological features and have a propensity for recurrence. Though histological variations are observed in OKCs, hard tissue formation and metaplastic changes are rare, and the underlying pathogenesis is not well understood. This study aimed to characterize stromal calcifications and analyze their association with odontogenic components in non-syndromic and syndrome-associated cases of OKCs. We analyzed 153 cases of OKCs from healthcare institutes in India and Japan. The epithelial and stromal features were evaluated, and the relationship of calcifications with odontogenic rests was determined. Immunohistochemistry for cytokeratin-19 and special stains including Masson Trichrome and Van Gieson, were used for identification of odontogenic rests and calcifications respectively. Stromal calcifications were observed in 29.41% OKCs. The calcification patterns included irregular dystrophic, dentinoid with linear or calcospherite-type mineralization, and psammoma calcifications. Psammoma and dentinoid calcifications were found in the proximity of cytokeratin-19-positive odontogenic rests or satellite cysts, whereas majority cases with dystrophic calcifications did not exhibit co-localization with stromal odontogenic components. Distinct patterns of calcifications were observed in OKCs. Calcifications found in proximity of the odontogenic rests were possibly indicative of an inductive or host-mediated response.

Breast calcifications on mammography from systemic amyloidosis: A case report.

Calcifications on mammography from systemic disease at times meet diagnostic criteria for histologic sampling to exclude malignancy. We present a case of bilateral groups of new calcifications on mammography that yielded amyloidosis on core biopsy. Awareness of our patient's known diagnosis of systemic light chain amyloidosis (AL) prompted use of Congo red staining to confirm the histologic diagnosis. Knowledge of systemic diseases with possible manifestations on mammography can facilitate cogent and clinically relevant radiology-pathology correlation.

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis.

BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. CONCLUSION: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.

A Rare Case of Unilateral Fetal Cataract and Coincidental Polydactyly in Congenital Toxoplasmosis.

Congenital toxoplasmosis is caused by transplacental infection of Toxoplasma gondii during pregnancy. We present a case of a congenital toxoplasma with intracranial calcifications, microcephaly, growth restriction, a unilateral cataract that developed in the third trimester, and a coincidental post-axial-polydactyly. Antenatal imaging findings are important to guide further testing and confirmation of diagnosis, it is important to know all possible associations and prognoses for timely counseling, testing, and intervention. To our knowledge, no case has been published with findings of unilateral cataract in congenital toxoplasmosis and associated coincidental polydactyly. Therefore, we wish to add this case to the current scientific literature.

Retrospective evaluation of ponticulus posticus prevalence, sella turcica types, and stylohyoid complex calcifications in a group of Turkish population.

The aim of this retrospective analysis was to assess the incidence of ponticulus posticus and stylohyoid ligament calcification and to evaluate the morphological variations of the sella turcica within the Turkish demographic using CBCT scans. Involving a retrospective review of 460 CBCT scans and utilizing the NewTom 3G system, the study analyzed high-quality CBCT images to investigate ponticulus posticus, stylohyoid ligament calcifications, and sella turcica morphology. The ponticulus posticus was examined for complete or partial formations, while the stylohyoid ligament was classified according to its elongation and calcification patterns. The sella turcica was categorized into six distinct morphological types, enhancing the understanding of structural variations in the context of the Turkish population. The calcification patterns of the styloid processes were examined on both sides of 380 individuals, revealing the highest prevalence in the 'd' and 'e' categories on the right, and similar findings on the left among 373 individuals. Symmetric calcification patterns were more common, with 68.4% symmetry observed. For the sella turcica, category 'a' was the most frequent among 363 individuals. Analysis of ponticulus posticus absence and presence showed a majority lacking this feature on both sides, with complete and partial forms less common. The study highlights the anatomical variability and bilateral symmetry of the styloid processes, sella turcica, and ponticulus posticus, illustrating that these structures do not significantly vary with gender or age. These results hold clinical significance for the diagnosis and treatment of related conditions, prompting further investigation into their impact on patient care.

Automatic Detection of Post-Operative Clips in Mammography Using a U-Net Convolutional Neural Network.

BACKGROUND: After breast conserving surgery (BCS), surgical clips indicate the tumor bed and, thereby, the most probable area for tumor relapse. The aim of this study was to investigate whether a U-Net-based deep convolutional neural network (dCNN) may be used to detect surgical clips in follow-up mammograms after BCS. METHODS: 884 mammograms and 517 tomosynthetic images depicting surgical clips and calcifications were manually segmented and classified. A U-Net-based segmentation network was trained with 922 images and validated with 394 images. An external test dataset consisting of 39 images was annotated by two radiologists with up to 7 years of experience in breast imaging. The network's performance was compared to that of human readers using accuracy and interrater agreement (Cohen's Kappa). RESULTS: The overall classification accuracy on the validation set after 45 epochs ranged between 88.2% and 92.6%, indicating that the model's performance is comparable to the decisions of a human reader. In 17.4% of cases, calcifications have been misclassified as post-operative clips. The interrater reliability of the model compared to the radiologists showed substantial agreement (κreader1 = 0.72, κreader2 = 0.78) while the readers compared to each other revealed a Cohen's Kappa of 0.84, thus showing near-perfect agreement. CONCLUSIONS: With this study, we show that surgery clips can adequately be identified by an AI technique. A potential application of the proposed technique is patient triage as well as the automatic exclusion of post-operative cases from PGMI (Perfect, Good, Moderate, Inadequate) evaluation, thus improving the quality management workflow.

Accuracy of a deep learning-based algorithm for the detection of thoracic aortic calcifications in chest computed tomography and cardiovascular surgery planning.

OBJECTIVES: To assess the accuracy of a deep learning-based algorithm for fully automated detection of thoracic aortic calcifications in chest computed tomography (CT) with a focus on the aortic clamping zone. METHODS: We retrospectively included 100 chest CT scans from 91 patients who were examined on second- or third-generation dual-source scanners. Subsamples comprised 47 scans with an electrocardiogram-gated aortic angiography and 53 unenhanced scans. A deep learning model performed aortic landmark detection and aorta segmentation to derive 8 vessel segments. Associated calcifications were detected and their volumes measured using a mean-based density thresholding. Algorithm parameters (calcium cluster size threshold, aortic mask dilatation) were varied to determine optimal performance for the upper ascending aorta that encompasses the aortic clamping zone. A binary visual rating served as a reference. Standard estimates of diagnostic accuracy and inter-rater agreement using Cohen's Kappa were calculated. RESULTS: Thoracic aortic calcifications were observed in 74% of patients with a prevalence of 27-70% by aorta segment. Using different parameter combinations, the algorithm provided binary ratings for all scans and segments. The best performing parameter combination for the presence of calcifications in the aortic clamping zone yielded a sensitivity of 93% and a specificity of 82%, with an area under the receiver operating characteristic curve of 0.874. Using these parameters, the inter-rater agreement ranged from κ 0.66 to 0.92 per segment. CONCLUSIONS: Fully automated segmental detection of thoracic aortic calcifications in chest CT performs with high accuracy. This includes the critical preoperative assessment of the aortic clamping zone.

A Case of Non-ketotic Hyperglycemic Hemichorea and Fahr Syndrome.

Non-ketotic hyperglycemic hemichorea (NHH) denotes acute hemichorea or hemiballism in patients with poorly controlled diabetes with striatal abnormalities seen on brain MRI. Here, we describe a case with diabetes mellitus and primary hypoparathyroidism who developed NHH with bilateral chorea due to the abrupt stopping of her diabetic regimen. She presented with subacute and progressive bilateral asymmetric chorea. Over the prior six months, she stopped following her diabetic regimen. Brain imaging showed features of diffuse brain calcifications suggestive of Fahr syndrome. Extensive blood investigations including genetic testing for causes of basal ganglia calcifications were unremarkable. Treatment with tetrabenazine and resumption of her diabetes medications slowly improved her chorea. This case highlights the importance of interpreting imaging findings in the context of the nature and time course of the chorea presentation. In addition, it emphasizes a systematic approach to interpreting diffuse brain calcifications with the appropriate investigations.

Cerebral Calcifications as a Result of Primary Hyperparathyroidism: A Report of a Rare Case.

Primary hyperparathyroidism (PHPT) is an extremely uncommon cause of cerebral calcification. A male patient, aged 45, was admitted to the neurosurgery clinic with a closed traumatic brain injury, namely a concussion, resulting in symptoms of headache and loss of balance. A CT scan was conducted, which detected bilateral calcifications on the basal ganglia and the tentorium. The blood tests revealed increased levels of serum calcium, phosphate, and parathyroid hormone (PTH), while vitamin D levels were within the normal range. The patient received symptomatic therapy for the cerebral concussion and was referred for further diagnostic procedures. Based on these exams, it was determined that the patient had a parathyroid adenoma, which was responsible for PHPT characterised by increased levels of calcium, phosphate, and PTH. The patient subsequently underwent a successful parathyroidectomy. Half a year following the surgical procedure, the patient remained free of any indications of neurological conditions, and the levels of PTH and calcium in their body were within the expected range. Whenever trying to identify the cause of cerebral calcification, it is important to explore several possible diagnoses. A possible cause that should be taken into account is PHTP.

Focal Seizures in a Patient With Chronic Basal Ganglia Calcifications Secondary to Idiopathic Primary Hypoparathyroidism.

Patients with hypoparathyroidism can present with concurrent basal ganglia calcifications (BGCs). The exact pathogenesis is unknown, although it is thought to relate to calcium-phosphate deposition from chronic hypocalcemia and hyperphosphatemia. We present the case of a 65-year-old man with known idiopathic primary hypoparathyroidism and concurrent extensive BGC. Thirty years after diagnosis, he presented with focal seizures despite a decade of stable intracranial calcifications on imaging. Serum calcium, phosphate, 25-hydroxyvitamin D, and parathyroid hormone levels were well controlled during this period. He was commenced on lifelong levetiracetam with subsequent seizure remission. Given the scarcity of literature surrounding focal seizures and BGC, it is essential to raise awareness in this area.

Imágenes multimodales y retromodo en la calcificación esclerocoroidea: reporte de un caso / Multimodal and retro-mode imaging in sclerochoroidal calcification: A case report

Presentamos un reporte de caso en una paciente de 70años sobre las calcificaciones esclerocoroideas, una rara condición que involucra depósitos de pirofosfato de calcio en el polo posterior del ojo. Proporcionamos un relato sobre la presentación clínica y su apariencia en imágenes multimodales, utilizando fotografías de color del fondo de ojo, tomografía de coherencia óptica de fuente de barrido (SS-OCT), ecografía ocular y la novedosa técnica de retromodo (RMI). Al examen la agudeza visual fue de 20/25 en el ojo derecho y de 20/20 en el ojo izquierdo. La fotografía de color del fondo de ojo reveló depósitos amarillentos localizados en la arcada temporal-superior de ambos ojos. SS-OCT demostró masas de origen escleral. Las ecografías oculares confirmaron la calcificación de estas masas. El RMI detectó imágenes hiperreflectivas con una marcada elevación superficial de las lesiones. El laboratorio sistémico no presentó alteraciones, lo que llevó al diagnóstico de calcificaciones esclerocoroideas bilaterales de origen idiopático.(AU)

We present a case report on sclerochoroidal calcification (SCC), a rare condition involving calcium pyrophosphate deposits in the posterior pole of the eye in a 70-year-old patient. We provide an account of the clinical presentation and its appearance in multimodal images, using color fundus photography, swept-source optical coherence tomography (SS-OCT), ocular ultrasound, and the novel retro-mode imaging (RMI) technique. Visual acuity was 20/25 in the right eye (OD) and 20/20 in the left eye (OS). Color fundus photography revealed yellowish deposits located in the upper temporal arcade of both eyes. SS-OCT demonstrated masses of scleral origin. Ocular ultrasounds confirmed the calcification of these masses. RMI detected hyper-reflective images with marked superficial elevation. Systemic laboratory results did not detect any abnormalities, leading to the diagnosis of bilateral idiopathic SCC.(AU)

Cardiovascular calcification in hemodialysis patients: A Qatar-based prevalence and risk factors study.

BACKGROUND: Patients with end-stage kidney disease on hemodialysis (HD) have an increased risk of death due to the high prevalence of cardiovascular disease. Vascular calcification (VC) is predictive of cardiovascular disease and mortality. We conducted a study to evaluate the prevalence and risk factors for VC in dialysis patients in Qatar. METHODS: This is a retrospective nationwide study including all chronic ambulatory dialysis patients in Qatar from 2020 to 2022. We used our national electronic medical record to track demographics, clinical characteristics, comorbidities, laboratory values, and diagnostic data for each patient. Calcifications were assessed by echocardiography (routinely done for all our dialysis population per national protocol), computed tomography, X-ray, and ultrasound. The study protocol was approved by the local medical research ethics committee (MRC-01-20-377). RESULTS: 842 HD patients were included in this study. Vascular calcifications (VC) were prevalent in 52.6% of patients. The main site of VC was Mitral valve calcifications in 55.5% of patients. Patients with VC were significantly older and had more prevalence of diabetes mellitus (p = 0.001 and p = 0.006, respectively). There was no statistically significant difference between patients with calcifications and patients without calcifications regarding serum calcium, phosphorus, and PTH level. In multivariate analysis, age and diabetes significantly increased the risk factor for calcification (95% CI 1.033-1.065, p < 0.0001, and 95% CI 1.128-2.272, p < 0001, respectively). Moreover, higher vitamin D levels and higher doses of IV Alfacalcidol were significant risk factors for calcifications (95% CI 1.005-1.030, p < 0.007, and 95% CI 1.092-1.270, p < 0.0001, respectively). CONCLUSION: Our study found that vascular calcification was widespread among our dialysis population in Qatar. Implementing the practice of echocardiography in dialysis patients was extremely helpful and the most productive in detecting vascular calcification. Diabetes mellitus almost doubles the risk for vascular calcifications in dialysis patients. These results are beneficial in identifying risk factors for vascular calcification, which can help stratify dialysis patients' risk of cardiovascular disease and optimize prevention efforts.

Imaging Feature of Leukoencephalopathy with Calcifications and Cysts (Labrune Syndrome).

Labrune syndrome is an uncommon central nervous system disorder characterized by leukoencephalopathy, cerebral calcifications, and cysts on brain imaging. The basic pathology is microangiopathy resulting from a mutation in the SNORD118 gene. Radiological imaging is the hallmark of the disease.

Identification and classification of pulp calcifications in posterior teeth according to dental condition using digital panoramic radiography and cone beam CT.

OBJECTIVE: To compare digital panoramic radiography (DPR) and cone beam CT (CBCT) in the detection and classification of pulp calcifications in posterior teeth in relation to tooth condition and its location. METHODS: Two hundred and fifty patients with simultaneous DPR and CBCT scans were selected from a dental image bank. For each posterior tooth, its condition was registered (healthy, restored, or decayed). The presence of calcifications was assessed and classified according to location (coronal or radicular) and type (total obliteration, partial obliteration, narrowing, and no calcification). Chi-square and McNemar tests were used to compare DPR and CBCT results, with a significance level of 5%. DPR diagnostic values were calculated using CBCT as reference. RESULTS: Decayed and restored teeth showed a significantly (P < .001) higher prevalence of pulp calcifications than healthy teeth in both imaging exams. There was a significant discrepancy between the imaging modalities in the identification of calcifications (P < .001), especially for radicular calcifications of maxillary teeth (DPR = 55.2%; CBCT = 30.9%). In the case of coronal calcifications, there was a greater discrepancy between CBCT and DPR in the mandibular teeth (10.7%) than in the maxillary teeth (7.7%). Overall, DPR presents higher sensitivity (0.855) than specificity (0.483) for pulp calcifications detection. CONCLUSION: DPR considerably overestimates pulp calcifications in posterior teeth, as compared to CBCT. A higher prevalence of pulp calcifications is related to decayed and restored teeth.

Asociación de la rigidez aórtica con calcificaciones vasculares abdominales y coronarias en pacientes con enfermedad renal crónica estadios 3 y 4 / Association of aortic stiffness with abdominal vascular and coronary calcifications in patients with stage 3 and 4 chronic kidney disease

Fundamento y objetivos: El aumento de la rigidez arterial central (aórtica) tiene repercusiones hemodinámicas con efectos nocivos cardiovasculares y renales. En la enfermedad renal crónica (ERC) puede existir un aumento de la rigidez aórtica secundaria a múltiples alteraciones metabólicas, entre ellas la calcificación de la pared vascular (CV). El objetivo de este estudio fue analizar la asociación de la rigidez aórtica y de la hemodinámica central con la presencia de CV en dos territorios: aorta abdominal (CAA) y arterias coronarias (CC). Material y métodos: Se incluyeron 87 pacientes con ERC estadios 3 y 4. Usando tonometría de aplanamiento se estudiaron la hemodinámica central y la rigidez aórtica. Esta se determinó mediante la velocidad de pulso carótida-femoral (Vpc-f). A partir de la Vpc-f se calculó el índice de la VPc-f (iVpc-f) que considera otras variables que influyen en la Vpc-f, como edad, presión arterial, sexo y frecuencia cardiaca. La presencia de CAA se valoró mediante radiografía lateral de columna lumbar calculándose el índice de Kauppila (iKauppila) y las CC mediante tomografía computarizada multidetección por el método de Agatston, calculándose su índice (iAgatston). Para el estudio de la asociación entre iVpc-f, iKauppila, iAgatston, presión aórtica central, parámetros clínicos y datos de laboratorio se usaron la regresión múltiple y la regresión logística. La capacidad discriminativa del iVpc-f para evaluar la presencia de CAA y CC se determinó mediante el área bajo la curva (ABC) de ROC (receiver-operating characteristic). Resultados: La Vpc-f y el iVpc-f fueron 11,3±2,6m/s y 10,6m/s, respectivamente. El iVpc-f fue mayor cuando la ERC coexistía con diabetes mellitus (DM). Se detectaron CAA y CC en el 77% y el 87%, respectivamente. La albuminuria (β=0,13, p=0,005) y el iKauppila (β=0,36, p=0,001) se asociaron de forma independiente con la magnitud del iVpc-f... (AU)

Rationale and objectives: Increased central (aortic) arterial stiffness has hemodynamic repercussions that affect the incidence of cardiovascular and renal disease. In chronic kidney disease (CKD) there may be an increase in aortic stiffness secondary to multiple metabolic alterations including calcification of the vascular wall (VC). The objective of this study was to analyze the association of central aortic pressures and aortic stiffness with the presence of VC in abdominal aorta (AAC) and coronary arteries (CAC). Materials and methods: We included 87 patients with CKD stage 3 and 4. Using applanation tonometry, central aortic pressures and aortic stiffness were studied. We investigated the association of aortic pulse wave velocity (Pvc-f) and Pvc-f adjusted for age, blood pressure, sex and heart rate (Pvc-f index) with AAC obtained on lumbar lateral radiography and CAC assessed by multidetector computed tomography. AAC and CAC were scored according to Kauppila and Agatston methods, respectively. For the study of the association between iPvc-f index, Kauppila score, Agatston score, central aortic pressures, clinical parameters and laboratory data, multiple and logistic regression were used. We investigated the diagnosis performance of the Pvc-f index for prediction of VC using receiver-operating characteristic (ROC). Results: Pvc-f and Pvc-f index were 11.3±2.6m/s and 10.6m/s, respectively. The Pvc-f index was higher when CKD coexisted with diabetes mellitus (DM). AAC and CAC were detected in 77% and 87%, respectively. Albuminuria (β=0.13, p=0.005) and Kauppila score (β=0.36, p=0.001) were independently associated with Pvc-f index. In turn, Pvc-f index (β=0.39, p=0.001), DM (β=0.46, p=0.01), and smoking (β=0.53; p=0.006) were associated with Kauppila score, but only Pvc-f index predicted AAC [OR: 3.33 (95% CI: 1.6–6.9; p=0.001)]. The Kauppila score was independently associated with the Agatston score (β=1.53, p=0.001)... (AU)

Intramyocardial calcification in apical hypertrophic cardiomyopathy assessed using multimodality imaging: a case series.

Apical hypertrophic cardiomyopathy (ApHCM) is an HCM variant, affecting frequently males in midlife. It is characterized by apical obliteration and persistent diastolic contraction, often resulting in microvascular ischaemia. We report five cases of ApHCM, with evidence of intramyocardial calcification on echocardiogram. On cardiac magnetic imaging (MRI), a hypointense component at early gadolinium enhancement (EGE) sequences, compatible with calcium, and a deep layer, with hyperintensity at late gadolinium enhancement (LGE) sequences, referable to fibrosis, suggest an endomyocardial fibrosis (EMF) diagnosis. EMF pathologic hallmark is endocardium and myocardium scarring, evolving to dystrophic calcification. It is found only in few ApHCM patients. Our series is the largest one described until now. Analysing patients' history, coexistent inflammatory triggers were evident in all of them, so their co-morbidities could represent a further cause of small vessel disease, in the context of ischaemic microvascular stress due to hypertrophy, leading to fibrosis and dystrophic calcification. This series could demonstrate the relation between apical fibrosis/calcification and microvascular ischaemia due to hypertrophy and inflammatory triggers.

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression.

Pathological calcifications, especially calcium phosphate microcalcifications (MCs), appear in most early breast cancer lesions, and their formation correlates with more aggressive tumors and a poorer prognosis. Hydroxyapatite (HA) is a key MC component that crystallizes in the tumor microenvironment. It is often associated with malignant breast cancer lesions and can trigger tumorigenesis in vitro. Here, we investigate the impact of additives on HA crystallization and inhibition, and how precancerous breast cells respond to minerals that are deposited in the presence of these additives. We show that nonstoichiometric HA spontaneously crystallizes in a solution simulating the tumor microenvironmental fluids and exhibits lump-like morphology similar to breast cancer MCs. In this system, the effectiveness of poly(aspartic acid) and poly(acrylic acid) (PAA) to inhibit HA is examined as a potential route to improve cancer prognosis. In the presence of additives, the formation of HA lumps is associated with the promotion or only minimal inhibition of mineralization, whereas the formation of amorphous calcium phosphate (ACP) lumps is followed by inhibition of mineralization. PAA emerges as a robust HA inhibitor by forming spherical ACP particles. When precancerous breast cells are exposed to various HA and ACP minerals, the most influential factors on cell proliferation are the mineral phase and whether the mineral is in the form of discrete particles or particle aggregates. The tumorigenic effects on cells, ranging from cytotoxicity and suppression of proliferation to triggering of proliferation, can be summarized as HA particles < HA aggregates < ACP particles < ACP aggregates. The cellular response to minerals can be attributed to a combination of factors, including mineral phase, crystallinity, morphology, surface texture, aggregation state, and surface potential. These findings have implications for understanding mineral-cell interactions within the tumor microenvironment and suggest that, in some cases, the byproducts of HA inhibition can contribute to disease progression more than HA itself.