Quantitative vs. Qualitative SPECT-CT Diagnostic Accuracy in Bone Lesion Evaluation-A Review of the Literature.

(1) Background: Considering the importance that quantitative molecular imaging has gained and the need for objective and reproducible image interpretation, the aim of the present review is to emphasize the benefits of performing a quantitative interpretation of single photon emission computed tomography-computed tomography (SPECT-CT) studies compared to qualitative interpretation methods in bone lesion evaluations while suggesting new directions for research on this topic. (2) Methods: By conducting comprehensive literature research, we performed an analysis of published data regarding the use of quantitative and qualitative SPECT-CT in the evaluation of bone metastases. (3) Results: Several studies have evaluated the diagnostic accuracy of quantitative and qualitative SPECT-CT in differentiating between benign and metastatic bone lesions. We collected the sensitivity and specificity for both quantitative and qualitative SPECT-CT; their values ranged between 74-92% and 81-93% for quantitative bone SPECT-CT and between 60-100% and 41-100% for qualitative bone SPECT-CT. (4) Conclusions: Both qualitative and quantitative SPECT-CT present an increased potential for better differentiating between benign and metastatic bone lesions, with the latter offering additional objective information, thus increasing diagnostic accuracy and enabling the possibility of performing treatment response evaluation through accurate measurements.

Impact of Hormone Replacement Therapy on the Overall Survival and Progression Free Survival of Ovarian Cancer Patients: A Systematic Review and Meta-Analysis.

Background: Frequently, patients treated for Ovarian Cancer (OC) undergo menopause with subsequent symptoms. This review scrutinised the impact of Hormone Replacement Therapy (HRT) on the Overall Survival (OS) and Progression-Free Survival (PFS) of patients diagnosed with OC. Methods: A systematic literature search was conducted in the most popular English databases. Inclusion and exclusion criteria were applied to select publications that evaluate OS and PFS in these patients. End-point analysis targeted values of log(HR) and its Standard Error (SE). Results: Up to 1 September 2022, 11 studies were included in the qualitative synthesis. Eight publications, totalling 4191 patients, were included in the meta-analyses. Eight studies were considered for the OS analysis and pooled an HR of 0.66 with respective 95% CI between 0.57 and 0.76, with a p-value < 0.00001 at a Z value of 5.7, in favour of the HRT group. Results for PFS showed an overall HR of 0.73 in favour of the HRT group; CI between 0.57 and 0.95, p = 0.02 at a Z value of 2.36. Further subgroup analyses highlighted the non-inferiority of this treatment. Conclusions: Patients treated for OC that receive HRT for menopausal symptoms after various treatments appeared to have better OS than never-users.

Degenerative bony changes in the temporal component of the temporomandibular joint - review of the literature.

Temporomandibular joint (TMJ) changes are quite frequent in adults, but not all changes are degenerative. A high prevalence of bone alterations in the TMJs was reported by different research groups. Disturbed remodeling of bony articulating structures occurs because of overloading masticatory forces or because the mechanical loading in the area out-weighs the adaptive capacity of the TMJ structures. Although most of the degenerative TMJ alterations are identified at the level of the condylar process, a complete evaluation of the degenerative modifications encountered in the temporal TMJ region should not be forgotten as they are important for a comprehensive assessment and further management of the clinical situation. Several research groups have described osseous remodeling in the temporal component of the TMJ. Evidence is scarce for degenerative modifications at the level of the articular eminence and thickening of the roof of the glenoid fossa has been associated with osteoarthritis.

Morphometric study for the localization of the mental foramen in relation to the vertical reference plane.

BACKGROUND: The mental foramen (MnF) is the anatomic landmark where the mental neurovascular bundle exits the mandible. Precisely determining the position of the MnF is necessary before all dentoalveolar therapeutic procedures performed in the mandibular premolar area. MATERIALS AND METHODS: For the study, we performed two ex vivo direct morphometric determinations on dry human dentate and edentate mandibles, and two in vivo imaging morphometric determinations through cone-beam computed tomography (CBCT) and orthopantomography (OPG) in dentate human patients. The following landmarks were used to locate the MnF: the distance between the MnF and the superior border of the mandible (MnF-SB), the distance between the MnF and the inferior border of the mandible (MnF-IB), and the position of the MnF in relation to the root apices of the posterior teeth. The results obtained from these data were processed statistically using the analysis of variance (ANOVA). RESULTS: By direct morphometry on dentate mandibles, the MnF was situated closer to the IB and by direct morphometry on completely edentulous mandibles, the MnF was located closer to the SB. In both direct morphometry studies, the MnF transverse diameter was larger than the vertical one, with the MnF having an oval shape. ANOVA for both direct morphometry studies showed that the distances MnF-IB and MnF-SB significantly vary statistically with interactions and depending on age (p<0.00001). The vertical diameter of the MnF significantly varies statistically depending on age, interactions and between studies, and its transverse diameter varies statistically significantly with interactions and depending on age (p<0.00001). According to OPG and CBCT imaging studies, the MnF was located closer to the IB, and the transverse diameter of the MnF was larger than the vertical diameter; such results are similar to the direct morphometry study performed on dry dentate human mandibles. Regarding the position of the MnF in relation to the root apices, it was most frequently located inferior to the root apices in 79.45% of cases, in 19.23% of cases it was located at the root apices level and in 1.31% of cases it was located superior (coronal) to the root apices. ANOVA for both imaging morphometry studies showed that the MnF-IB distance varies statistically significantly with the interactions, the study, the sex of the patients and their age, the MnF-SB distance varies statistically significantly with the interactions, the study and the patients' age (p<0.05), and the MnF diameters vary statistically significantly with interactions and patient age (p<0.05). CONCLUSIONS: The results of this study can help dental practitioners in improving dentoalveolar surgery procedures in the posterior mandible.

Dermatological and endocrine elements in Carney complex (Review).

Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the CNC1 gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (PRKAR1A), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumors with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement.

Factors influencing the articular eminence of the temporomandibular joint (Review).

The temporomandibular joint (TMJ), the most complex and evolved joint in humans, presents two articular surfaces: the condyle of the mandible and the articular eminence (AE) of the temporal bone. AE is the anterior root of the zygomatic process of the temporal bone and has an anterior and a posterior slope, the latter being also known as the articular surface. AE is utterly important in the biomechanics of the TMJ, as the mandibular condyle slides along the posterior slope of the AE while the mandible moves. The aim of this review was to assess significant factors influencing the inclination of the AE, especially modifications caused by aging, biological sex or edentulism. Studies have reported variations in the angles of the slopes of the AE between medieval and recent human dry skulls, as well as between subjects of different racial origin. Recent articles have emphasized the significant role that tooth loss has on the flattening of the AE. Although some papers have described biological sex or age as factors which could be associated with differences in AE angulations, edentulism seems to be a significant factor impacting on the inclination of the AE.

Metformin Treatment: A Potential Cause of Megaloblastic Anemia in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Vitamin B12 (cobalamin) deficiency is a frequent cause of megaloblastic anemia, manifested through various symptoms. Screening for this deficiency can be justified in case of patients with one or more risk factors present from the following: gastric resections, inflammatory bowel disease, use of metformin over a prolonged period of time, administration of proton pump inhibitors or H2 histamine receptor blockers for more than 12 months and in case of adults over 75 years of age. One method of determining vitamin B12 deficiency is measuring its serum levels, as well as performing measurements of serum levels of methylmalonic acid and homocysteine levels, which experience an increase in the early stages of vitamin B12 deficiency. CLINICAL CASE: We bring to your attention, the case of a 62 years old patient diagnosed with Type 2 Diabetes Mellitus in 2015 that presented in the emergency room in October 2019 with an altered general condition, nausea, vomiting, abdominal pain, palpitation, and dyspnea. Treatment with metformin was initiated from the diagnosis of Type 2 Diabetes Mellitus, four years before. Investigations established the diagnosis of megaloblastic anemia by vitamin B12 deficiency. The symptoms disappeared after the injection of vitamin B12. CONCLUSION: Periodical dosing of vitamin B12 should be performed in the case of patients with Type 2 Diabetes Mellitus treated with metformin, especially if they associate anemia and/or peripheral diabetic polyneuropathy.

Long-term Risk of Malignant Neoplastic Disorders in Type 2 Diabetes Mellitus Patients with Metabolic Syndrome.

BACKGROUND: In developing countries, cancer incidence has progressively increased, becoming the second cause of mortality after cardiovascular diseases. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of malignant neoplastic disorders, especially pancreatic cancer, colorectal cancer, and breast cancer. AIM: The main aim of our study was to establish the prevalence of malignant neoplastic disorders in patients previously diagnosed with T2DM. Also, we have investigated the association between the components of the metabolic syndrome (MetS) and the different types of diagnosed malignant neoplasms. METHODS: We performed a retrospective, population-based cohort study of 1,027 patients with T2DM from the Center for Diabetes Treatment of the "Pius Brînzeu" Emergency Hospital in Timisoara, Romania. The patients were followed up every three or six months, depending on their antidiabetic treatment. The patients who developed malignant neoplasms were registered and referred to oncology centers. The potential risk factors for malignancies in patients with T2DM were evaluated using logistic regression adjusting for possible confounders. RESULTS: The prevalence of malignant neoplastic disorders in our study group was 7.1%; more precisely, we found 2.2% colon neoplasm, 2.9% mammary neoplasm, 0.7% lymphomas, 0.6% pulmonary neoplasm, 0.3% pancreatic neoplasm, and 0.4% prostate neoplasm. The presence of malignant neoplastic disorders was associated in our cohort of patients with T2DM with higher cholesterol (237.71±47.82 vs 202.52±52.16 mg/dL; p=0.005) and triglycerides levels (215.91±52.41 vs 180.75±54.32 mg/dL; p<0.001), as well as higher body mass index (33.37±3.87 vs 28.42±3.56 kg/m2; p<0.001) and abdominal circumference (110.11±14.48 vs 98.12±15.73 cm; p<0.001). Also, we found that insulin-based treatment was an independent risk factor, the patients presenting ten times higher odds of developing malignant neoplastic disorders. CONCLUSION: The prevalence of malignant neoplastic disorders in our study group was 7.1%. Also, the prevalence of malignant neoplastic disorders was higher in patients with T2DM and MetS as compared to the general population of T2DM patients.

A 2018 Italian and Romanian Survey on Subclinical Hypothyroidism in Pregnancy.

OBJECTIVES: Pregnancy induces changes in thyroid function, and thyroid dysfunction during gestation is associated with adverse outcomes. We examined the management of subclinical hypothyroidism and chronic autoimmune thyroiditis in pregnancy among Italian and Romanian endocrinologists. METHODS: Members of the Associazione Medici Endocrinologi (AME) and Romanian Society of Endocrinology (RSE) were invited to participate in a web-based survey investigating the topic. RESULTS: A total of 902 individuals participated in the survey, 759 of whom completed all sections. Among the respondents, 85.1% were aware of the 2017 American Thyroid Association guidelines about thyroid disease and pregnancy, and 82.9% declared that thyroid-stimulating hormone (TSH) screening at the beginning of pregnancy should be warranted. In a patient negative for peroxidase antibodies, 53.6% considered 2.5 mIU/L and 26.2% considered 4.0 mIU/L as the upper normal limit of TSH, and 50% would treat a patient with TSH 3.5 mIU/L with levothyroxine. About 20% did not suggest iodine supplementation. Isolated hypothyroxinemia detected in the first trimester would be treated by 40.8%. In patients undergoing ovarian stimulation, a TSH < 2.5 mIU/L would be targeted by 70%. CONCLUSIONS: Respondents globally appeared well informed about the management of thyroid autoimmunity and subclinical hypothyroidism in pregnancy. A more aggressive attitude in implementing iodine supplementation would be desirable. Most endocrinologists were convinced about an evident association between mild thyroid impairment and adverse outcomes in pregnancy, thus using a TSH value of 2.5 mIU/L as the threshold for diagnosing hypothyroidism and starting levothyroxine in pregnant women.

Morphological assessment of the mandibular canal trajectory in edentate subjects.

BACKGROUND: The mandibular canal and its content represent the vital structure, which can complicate dentoalveolar surgical procedures in the posterior region of the mandible. The purpose of the present study was to determine the path the mandibular canal takes in relation to the horizontal and the vertical anatomical reference planes in edentate subjects, in order to minimize the risk of affecting its neurovascular content during various oral surgery procedures. MATERIALS AND METHODS: Morphometric evaluations were performed on 12 dried fully edentulous human mandibles and on cone-beam computed tomography (CBCT) cross-sectional images of the mandible, from 20 patients with either partial or complete edentulism. Both methods were utilized, in three target areas (corresponding to the second premolar, to the first molar and to the second molar regions), in order to measure the distance between the mandibular canal and the following reference points: (i) the lateral (buccal) surface of the mandible (MC-BS distance); (ii) the medial (lingual) surface of the mandible (MC-LS distance); (iii) the alveolar surface of the mandible (MC-AS distance). The results were statistically processed in Stata MP/13 software package using analysis of variance (ANOVA) test. RESULTS: The mandibular canal crossed the trabecular bone from the posterior towards the anterior, and from the lingual towards the buccal, reaching the premolar region, distal to the mental foramen, where it was located in the centre of the trabecular bone, main topographic pattern encountered in 27 (84.37%) of the cases. In five (15.63%) of the cases, in the premolar region, the mandibular canal was located near the buccal cortical plate. The mandibular canal descended from the second molar region towards the premolar region, main topographic pattern found in 28 (87.5%) of the cases. In four (12.5%) cases, the mandibular canal had a descending trajectory in the molar regions and it took a slightly ascending course in the premolar region. CONCLUSIONS: According to the results, the second molar region represents the highest risk area in the accidental injury to the content of the mandibular canal, during various oral surgery procedures.

Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion from a Meckel diverticulum neuroendocrine tumor: case report.

BACKGROUND: Ectopic production of adrenocorticotropic hormone (ACTH) by neuroendocrine tumours (NET) is a rare condition, occult presentations often hampering the diagnosis. Although NET are relatively frequent in the ileon and Meckel diverticulum, we describe the first Cushing's syndrome due to ectopic adrenocorticotropic syndrome (CS-EAS) arising from a Meckel diverticulum. CASE PRESENTATION: A 44-year-old man was admitted with recent onset of diabetes, myopathy, edema and hypokalemic metabolic alkalosis consistent with Cushing's syndrome. Both basal and dynamic laboratory evaluation suggested CS-EAS. Laboratory testing also showed high serum levels of chromogranin A (CgA) and urinary 5-hydroxyindoleacetic acid (5HIAA). Pituitary and neck/thorax/abdomen/pelvis imaging proved to be normal, while somatostatin analogue ((99m)Tc-HYNIC-TOC) scintigraphy revealed increased focalized ileum uptake on the right iliac fossa. Pre-operative ketoconazole and sandostatin treatment controlled the hypercortisolism within a month. Pathological analysis of the resected submucosal 1.8 cm tumour of the Meckel diverticulum and a metastatic local lymph node confirmed a well differentiated neuroendocrine tumour (grade I), whereas immunohistochemistry was positive for ACTH, chromogranin A and synaptophysin. Post-operative clinical and biochemical resolution of Cushing's syndrome was followed by normalization of both CgA and 5HIAA, which were maintained at the 6 month follow-up. CONCLUSION: The identification, characterization and follow-up of this rare cause of ectopic ACTH secretion is important in order to assess the long-term prognostic and management.

Genetic testing for multiple endocrine neoplasia type 2.

Multiple endocrine neoplasia type 2 (MEN 2) represents a complex autosomal dominant inherited syndrome characterized by occurrence of distinct proliferative disorders of endocrine tissues. The identification of RET proto-oncogene mutations in MEN 2 and FMCT has provided a precise method for identifying gene carriers. 30 subjects (9 males, 21 females, age range 11-63 years) with multiple endocrine neoplasia type 2 have been investigated from 1998 till 2006. 20 patients were considered as index cases and 10 patients were identified after a screening programme for MEN 2. Tumoral associations permitted the MEN 2A diagnosis in 21 cases, MEN 2A with cutaneous lichen amyloidosis in 6 cases and FMCT in 3 cases. We selected 22 patients from 14 families to investigate mutations in the RET proto-oncogene. In 7 subjects no mutations could be detected in the exons 10 and 11 of the RET proto-oncogene. Heterozygous missense mutations in exon 11 were found in 15 subjects consisting of three different mutations in codon 634 (TGC --> TGG, TGC --> GGC, TGC --> CGC). We conclude that our 15 patients have the most frequent mutations described in MEN 2A families. Because the testing for exons 10 and 11 is negative for other 7 patients, the remaining 13, 14, 15 and 16 exons should be sequenced in these cases.