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2.
J Oral Maxillofac Pathol ; 28(2): 192-199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157846

RESUMO

Background: Dental pulp calcifications or pulp stones are calcified structures found in dental pulp, mostly around or enclosing a blood vessel. The formation of these calcifications begins with concentric layers of calcified tissue within which remnants of necrotic and calcified cells may be present. The calcifications of thrombi in blood vessels, called phleboliths, may also serve as nidi for denticles. In metabolic diseases such as diabetes, hypertension or poor periodontal health, there are obvious changes in blood vessels and vascularization. In our study, we observed histopathological sections of dental pulp and correlated systemic diseases such as diabetes and hypertension with poor periodontal health and dental pulp stones. Aim: The aim of our study was to evaluate the histopathology of dental pulp stones, their distribution among various age groups and sexes and to identify any correlations between pulp stone formation and systemic diseases such as type II diabetes and hypertension. Materials and Methods: Samples from 100 patients with metabolic diseases such as type II diabetes and hypertension were collected. The pulp was extirpated from the teeth that were undergoing root canal treatment, and the teeth were extracted. The collected pulp sample was fixed in 10% formaline neutral buffer, subjected to routine histopathological procedures and stained with haematoxylin and eosin. The pulp of teeth extracted for orthodontic treatment was considered a control for patients with no metabolic disease. Results: There was a definite relationship between increased pulp stones and metabolic diseases such as type II diabetes and hypertension; likewise, poor periodontal health was significantly related to pulp stones.

3.
Clin Neurol Neurosurg ; 245: 108517, 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39173493

RESUMO

We present the case of a patient with leukoencephalopathy with calcifications and cysts (LCC), who experienced progressive severe hemiparesis despite multiple neurosurgical interventions of a large contralateral cyst. Bevacizumab was proposed as an ultimate treatment option based on prior case reports. While awaiting reimbursement approval for bevacizumab, major improvement occurred in both clinical and radiological disease manifestations. The disease course of LCC is variable and unpredictable; neurosurgical treatment should be reserved for severe and progressive neurological deficits. Bevacizumab has been reported as a promising alternative treatment option. Importantly, in our case the observed clinical improvement would have been attributed to the effects of bevacizumab, if started when requested. Our case underscores the need for a natural history study for LCC and the necessity of validating treatment efficacy by systematic evaluation through appropriate clinical trials rather than relying on anecdotal evidence from published case reports.

4.
Surg Endosc ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187729

RESUMO

BACKGROUND: This study aimed to determine the relationship between preoperative arterial calcifications and postoperative outcomes after Ivor Lewis esophagectomies. METHODS: This was a single-center retrospective review of Ivor Lewis esophagectomies from 2013 to 2018. Preoperative CT imaging was reviewed, and arterial calcifications were graded (absent, minor, or major) in various locations. The primary outcome included major complications (defined by the Clavien-Dindo classification III-V) and the secondary outcomes were 90-day reoperations, readmissions, and mortality. Significant associations (p < 0.05) between calcifications and outcomes on univariable analysis were evaluated using a multivariable logistic regression model (odds ratios, OR; 95% confidence intervals, CI). RESULTS: One hundred patients underwent esophagectomies from 2013 to 2018 (79% male, 90% White, median age 68 years), and 85% were classified as ASA III. Ninety-four patients had accessible preoperative imaging. Arterial calcifications in specific areas were observed: 82 in coronary arteries (major in 33 patients), 54 in the aortic valve, 78 in supra-aortic arteries, 79 in the thoracic aorta, 82 in the abdominal aorta, and 71 in common iliac. Furthermore, 60 patients exhibited celiac axis calcifications, with 40 patients classified as major. Twenty-five patients experienced major complications. Anastomotic leak occurred in two patients, and graft necrosis occurred in one patient. Ninety-day readmission was 10%, reoperation was 12%, and mortality was 4%. On univariable analysis, major coronary artery calcifications were significantly associated with major complications (OR 4.04; 95% CI 1.34-12.16; p = 0.02) and 90-day readmissions (OR 8.20; 95% CI 1.01-68.47; p = 0.04). However, no significant associations were identified between 90-day reoperations or mortality and arterial calcifications. CONCLUSIONS: This study demonstrated that preoperative coronary calcifications increase the risk of postoperative complications, as this may be a surrogate of overall health. Nonetheless, the correlation between splanchnic calcifications and postoperative outcomes needs further exploration.

5.
Front Cardiovasc Med ; 11: 1367467, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135615

RESUMO

Introduction: Myocardial calcifications (MC) represent a relatively rare pathological process, which may accompany different cardiovascular conditions and can be broadly categorized as dystrophic or metastatic. Myocardial infarction (MI) has been traditionally regarded as the main cause of MC overall; however, no updated comprehensive data on the relative incidence of different forms of MC is available. The purpose of this systematic review of the literature is to analyze the currently available evidence on MC in terms of pathophysiology, diagnosis, and clinical presentation. Methods and results: A total of 241 studies including a total of 368 patients affected by extensive MC were included in the final review. The majority of patients (69.8%) presented with dystrophic MC. Endomyocardial fibrosis (EMF) represents the single most common etiology of MC (24.2%), while sepsis/acute systemic inflammatory syndrome (SIRS) and chronic kidney disease were identified as the second and third most common causes respectively. The relative incidence of etiologies also varies across the years, with MI being more represented before 1990, and sepsis/SIRS becoming the single most common cause of MC after 1990. Multimodality imaging was used in the work-up of MC in 42.7% of cases. The most commonly employed imaging modality overall was echocardiography (51.9%), while after 1990 computed tomography scan became the most widely used tool (70.1%). Conclusion: The present systematic review provides new insights into the pathophysiology of MC. Previously thought to be mainly a consequence of ischemic heart disease, our data indicate that other diseases, namely EMF and sepsis/SIRS, are indeed the main conditions associated with MC. The importance of multimodality imaging in the work-up of MC is also highlighted.

6.
Pediatr Neurol ; 158: 49-56, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38959649

RESUMO

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.


Assuntos
Adenosina Desaminase , Agamaglobulinemia , Imunodeficiência Combinada Severa , Humanos , Adenosina Desaminase/deficiência , Pré-Escolar , Lactente , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Feminino , Masculino , Agamaglobulinemia/complicações , Estudos Prospectivos , Estudos Retrospectivos
7.
World Neurosurg ; 190: 99-112, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38968992

RESUMO

BACKGROUNDS: Labrune syndrome is a rare white matter disease characterized by angiomatous leukoencephalopathy, diffuse intracranial calcifications and supratentorial and infratentorial 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 the surgical timing, the most effective procedure, and the long-term results. METHODS: Electronic databases PubMed/MEDLINE and Google Scholar were searched for studies published up to April 2022 using the search string (Labrune syndrome OR leukoencephalopathy with calcifications and cysts OR brain calcifications OR brain cysts) AND (therapy OR surgery). RESULTS: We found 28 studies in the literature, and we added a new case from our institution, comprising 37 patients. All the patients in this series underwent surgical intervention. We reviewed all the pertinent literature to discuss clinical-radiological features and etiopathogenesis, specifically addressing the surgical options, clinical results, and prognosis. CONCLUSIONS: Leukoencephalopathy with cerebral calcifications and cysts is a rare neurodegenerative disorder for which effective medical treatment is lacking. 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 regarding which procedure is 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 satisfactory results.

9.
Cureus ; 16(6): e62844, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39036164

RESUMO

Diagnosing congenital cytomegalovirus (CMV) infection in neonates, particularly in developing countries with limited resources, can be challenging. This case report and literature review highlights the clinical presentation, diagnostic challenges, and management strategies associated with congenital CMV infection in a limited-resource setting. A female neonate born at 37 weeks and weighing 1760 grams presented with jaundice, petechial rash, and ventriculomegaly detected on prenatal ultrasound. Diagnostic workup revealed splenomegaly, thrombocytopenia, and elevated bilirubin levels, prompting suspicion of CMV infection. Serological testing confirmed CMV antibodies in the neonate, indicating severe symptomatic primary congenital infection. Imaging studies demonstrated colpocephaly with periventricular calcifications, consistent with CMV-related neurological abnormalities. Treatment with oral valganciclovir resulted in clinical improvement without adverse effects. However, follow-up was hindered by the mother's non-compliance. This case underscores the importance of considering CMV in the differential diagnosis of neonatal jaundice and neurological abnormalities. Despite its prevalence and clinical impact, there is no consensus on universal screening during pregnancy. Strengthening preventative measures and increasing awareness are crucial steps in addressing congenital CMV infection's public health implications.

10.
Cureus ; 16(6): e62733, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39036182

RESUMO

A female patient in her early 50s presented with a complaint of multiple right thigh swellings for eight years which on evaluation were found to be guinea worms. The patient had no risk factors as she was living in a rural area of Maharashtra. We performed radiological investigations which only revealed calcifications in subcutaneous planes. On exploring the excised specimen post-surgery there was a worm-like appearance which on histopathological study confirmed guinea worm disease. We highlight this unusual presentation of guinea worm disease so that surgeons can treat the condition effectively.

11.
Odontology ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951299

RESUMO

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.

12.
BMC Emerg Med ; 24(1): 116, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997628

RESUMO

BACKGROUND: At present, the diagnosis of acute coronary syndrome (ACS) can be made by emergency physicians using the usual complementary tests, since the current troponin and electrocardiogram (ECG) protocols have been extensively tested for their safety. However, the detection of coronary calcifications on CT associated with coronary obstruction may be of interest for the diagnostic strategy in the emergency department (ED). The aim of this study was to evaluate a strategy combining a non-ischemic ECG with an initial normal troponin assay and the diagnostic accuracy of chest CT in detecting coronary calcifications to rule out the presence of an acute coronary event in patients presenting with chest pain in the ED. METHODS: This was a retrospective, single-center study carried out in an ED in France and included all patients over 18 years of age presenting with chest pain between 1 June 2021 and 31 December 2021 with a non-ischemic ECG and a negative first troponin assay. The primary endpoint was the diagnostic performance of the combing strategy in ruling out ACS. The secondary endpoints were the sensitivity and specificity of calcifications in acute coronary syndrome, comparison with the diagnostic performance of a second troponin assay and the rate of reconsultation, rehospitalisation and investigations within 2 months of the ED. RESULTS: Of the 280 patients included, 141 didn't have calcifications. A total of 14 events were found with a negative predictive value for the combining strategy of 99.8% [95%CI: 98.2 - 100]. Sensitivity and specificity were 98.4% [95%CI: 83.8 - 100] and 53% [95%CI: 47 - 58.9], respectively. Among patients with no calcification, 8.2% were admitted to hospital and none suffered an acute coronary event. A total of 36 patients (12.8%) consulted a doctor within 2 months, with 23 investigations, all of which were negative in the non-calcification group. CONCLUSIONS: A strategy combining the detection of coronary calcifications on chest CT in patients with a non-ischemic ECG and a single troponin assay is effective to rule out ACS in the ED, and may perform better then ECG and troponin alone.


Assuntos
Síndrome Coronariana Aguda , Eletrocardiografia , Serviço Hospitalar de Emergência , Tomografia Computadorizada por Raios X , Humanos , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/diagnóstico , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Troponina/sangue , Dor no Peito/etiologia , Dor no Peito/diagnóstico por imagem , França , Sensibilidade e Especificidade , Calcinose/diagnóstico por imagem , Calcificação Vascular/diagnóstico por imagem
14.
Radiol Case Rep ; 19(9): 3740-3747, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38983295

RESUMO

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.

15.
J Clin Med ; 13(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38999515

RESUMO

Background: Chronic obstructive pulmonary disease has extrapulmonary manifestations, such as cardiovascular diseases and osteoporosis. The purpose of this research was to determine the relationship between the type and extent of emphysema with thoracic aorta calcification (TAC) and bone mineral density (BMD) at Th4, Th8, and L1 vertebrae. Methods: Emphysema was described by computed tomography parameters (both Fleischner classification and low attenuation value percentage, LAV%) and the clinical FEV1/FVC ratio (Tiffeneau-Pinelli index, TI, TI < 0.7; TI > 0.7). Results: Of 200 included patients (median age 64, 33% women), signs of clinical obstruction (TI) were observed in 104 patients, which had significantly lower BMD and more heavy TAC. BMD correlated negatively with LAV%, Rho = -0.16 to -0.23, while a positive correlation of aortic calcification with LAV% was observed, Rho = 0.30 to 0.33. Multiple linear regression showed that age and TI < 0.7 were independent predictors of BMD, ß = -0.20 to -0.40, and ß = -0.21 to -0.25; age and hypercholesterolemia were independent predictors of TCA, ß = 0.61 and ß = 0.19. Conclusions: Clinical TI and morphological LAV% parameters correlated with BMD and TAC, in contrast to Fleischer-graded emphysema, which showed no correlation. However, only TI was an independent predictor of BMD, while the morphologically described type and extent of emphysema could not independently predict any extrapulmonary manifestation.

16.
Cureus ; 16(5): e60265, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38872643

RESUMO

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.

17.
J Vasc Surg ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866374

RESUMO

BACKGROUND: Only a few small studies have shown the association between high ankle-brachial pressure index (ABI >1.4) and adverse cardiovascular (CV) events and mortality. Although there is abundant literature depicting the association between ABI and overall systemic atherosclerosis, it typically focuses on low ABI. Furthermore, historically, many studies focusing on peripheral artery disease have excluded high ABI participants. We aimed to study the mortality outcomes of persons with high ABI in the National Health and Nutrition Examination Survey (NHANES). METHODS: We obtained ABI from participants aged ≥40 years for survey years 1999 to 2004. We defined low a ABI as ≤0.9, normal ABI as 0.9 to 1.4, and high ABI as >1.4 or if the ankle pressures were >245 mm Hg. Demographics, various comorbidities, and laboratory test results were obtained at the time of the survey interview. Multivariable adjusted hazard ratios (HRs) along with 95% confidence intervals (CIs) were calculated for CV and all-cause mortality via Cox proportional hazards regression. Mortality was linked to all NHANES participants for follow-up through December 31, 2019, by the Centers for Disease Control and Prevention. RESULTS: We identified 7639 NHANES participants with available ABI. Of these, 6787 (89%) had a normal ABI, 646 (8%) had a low ABI, and 206 (3%) had elevated ABI. Of participants with high ABI, 50% were men, 15% were African Americans, 10% were current smokers, 56% had hypertension, 33% had diabetes, 15% had chronic kidney disease (CKD), and 18% had concomitant coronary artery disease (CAD). Diabetes (odds ratio [OR], 2.4; 95% CI, 1.7-3.2), CAD (OR, 1.6; 95% CI, 1.0-2.4), and CKD (OR, 1.5; 95% CI, 1.0-2.3) at baseline were associated with having a high ABI, respectively. A high ABI was associated independently with elevated CV (HR, 2.6; 95% CI, 2.1-3.1; P < .0001) and all-cause mortality (HR, 2.5; 95% CI, 2.2-2.8; P < .0001) after adjusting for covariates, including diabetes, CKD, CAD, current smoking, cancer, and hypertension. CONCLUSIONS: A high ABI is associated with an elevated CV and all-cause mortality, similar to patients with PAD. High ABI participants should receive the same attention and aggressive medical therapies as patients with PAD.

18.
J Imaging ; 10(6)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38921624

RESUMO

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.

19.
Cureus ; 16(5): e61058, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38915958

RESUMO

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.

20.
Anat Sci Int ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922560

RESUMO

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.

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