Sonographic characterization and surveillance of paravaginal smooth muscle tumor of uncertain malignant potential.

Sonographic characterization and surveillance of paravaginal smooth muscle tumor of uncertain malignant potential. (A1) Transvaginal ultrasound with probe placed over the right vaginal wall, showing a well-defined round mass with regular contours, a mostly hypoechoic and heterogeneous echotexture, and edge shadowing, deep to the right distal third of the right vagina. (A2) Multifrequency linear probe (9-14 MHz) placed over the right labium majus revealing hyperechoic striations (arrows on A1-A2) and central flow (arrowheads on A2). (B1) Resected solid white-tan mass of bland consistency. (B2) Hematoxylin-eosin microscopy (40X) showing fusiform cells, with mild to moderate atypia. (C1) Repeat transvaginal ultrasound six-years later showing a recurrent solid oval-shaped mass with regular contour, a mostly hypoechoic heterogeneous echotexture, and an anechoic area inside the solid mass (asterisk on C2) that could represent a focus of necrosis.

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort.

PURPOSE: Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES). METHODS: After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes. RESULTS: We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects. CONCLUSION: We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.

Anticoagulant proteins in a population of Mexican mestizo donors.

BACKGROUND: To determine the activity of antithrombin (AT), protein C (PC), and protein S (PS), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican mestizo blood donors. METHODS: AT, PC, and PS were determined from 1,502 plasma samples of healthy blood donors by using commercial kits in a coagulometer 4 STA (Diagnostica Stago, Asnières, France). RESULTS: A total of 741 women and 761 men were under study. They were divided into age range groups (18-24, 25-34, 35-44, 45-54, and 55-64 years). Activity of AT, PC, and PS was determined. For AT, activity values were specific for each age group according to gender when it had to do with PS, as well as when PC was determined. Frequencies of AT, PC, PS, and activated PC resistance activity deficiencies were obtained from reference levels (RLs) and average levels of this study. Differences were found between both frequencies for AT, PC, and PS, and the average levels obtained were used in this study. The frequencies of the activity deficiencies obtained through the values gotten in this population were: AT, 0.6%; PC, 1.06% (which is higher than the one obtained using the RLs described by commercial kits 0.33% and 0.66%, respectively); and PS, 1% (which is less than 4.5%). CONCLUSIONS: It is necessary to know the characteristics and biological behavior of the coagulation proteins in the Mexican population because the RLs used have been established for populations that are genetically different.

Risk Factors for Thrombosis Development in Mexican Patients.

BACKGROUND: To identify inherited factors: Protein C (PC), protein S (PS), antithrombin (AT), plasminogen (Plg), the activated PC resistance (APCR), prothrombin (PT) mutation G20210 A (PTG20210 A) and methylenetetrahydrofolate reductase C677 T polymorphism (MTHFR C677 T), as well as acquired-risk factors such as: diabetes mellitus, surgeries, smoking, obesity, hypertension, trauma, alcoholism, family history; and their association, in Mexican patients with diagnostic of thrombophilia. METHODS: Overall, 200 patients diagnosed with thrombophilia and 100 healthy controls. Commercial kits were used for the coagulometric tests and polymerase chain reaction, restriction fragment length polymorphism for molecular alterations. RESULTS: Alterations were found with an estimated prevalence to PC 0.65%, AT 2.04% and Plg 2.5%, APCR 2%, PT 20210 2%, and MTHFR 65%. The C677 T polymorphism of the MTHFR did not associate with acquired-risk factors so we can suppose that it is an independent risk factor. For the patients that only presented acquired-risk factors (21 of 200), the association smoking-alcoholism showed to be the cause of thrombosis with high risk. The following were also associated: smoking with AT, PC, and alcoholism; obesity with Plg; smoking with alcoholism, and PS deficiency. CONCLUSIONS: Risk factors for both primary and secondary and their association were present as a cause of thrombosis in the patients studied, and the possibility to suffer a recurrent thrombosis.

[The auditory pathway: levels of integration of information and principal neurotransmitters]. / La vía auditiva: niveles de integración de la información y principales neurotransmisores.

In this paper we studied the central auditory pathway (CAP) from an anatomical, physiological and neurochemical standpoint, from the inner ear, brainstem, thalamus to the temporal auditory cortex. The characteristics of the spiral ganglion of Corti, auditory nerve, cochlear nuclei, superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate body, and auditory cortex, including the auditory efferent pathway, are given. CAP is described as the electrical impulses, travelling through axons, allowing ions to enter a neuron and vesicles with neurotransmitters (NT) and then released into synaptic space. The NT changes the functioning of the cells; when attached to specific receptors on the next nerve cell, NT-receiver union causes input of ions through Gap sites, resulting in a postsynaptic potential that is spread over all CAP. In addition, the effects of the NT are not limited to the transmission, but as trophic agents that promote the formation of new neural networks. Even the anatomy, physiology, neurochemical aspects, and the different types of synapses are not fully understood to comprehend the organization of the CAP, but remain under investigation because of the relevance for the treatment of various central auditory disorders.

New Genetic Variants of RUNX2 in Mexican Families Cause Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 (RUNX2) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the RUNX2 gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression.

Bone Remodeling and Bone Structural Genes in Legg-Calvé-Perthes Disease: The OPG rs2073618 and IL-6 rs1800795 Are Associated with High Risk in Mexican Patients.

Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the pediatric femoral head. Bone remodeling and bone structural genes have the potential to contribute to the progression of LCPD when there is disequilibrium between bone resorption and bone formation. A case-control study was performed to search for associations of several common polymorphisms in the genes Receptor Activator for Nuclear Factor κappa B (RANK), Receptor Activator for Nuclear Factor κappa B Ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, and type 1 collagen (COL1A1) with LCPD susceptibility in Mexican children. A total of 23 children with LCPD and 46 healthy controls were genotyped for seven polymorphisms (rs3018362, rs12585014, rs2073618, rs1800795, rs1800796, rs1800012, and rs2586498) in the RANK, RANKL, OPG, IL-6, and COL1A1 genes by real-time polymerase chain reaction with TaqMan probes. The variant allele (C) of IL-6 rs1800795 was associated with increased risk of LCPD (odds ratio [OR]: 3.8, 95% confidence interval [CI]: [1.08-13.54], p = 0.033), adjusting data by body mass index (BMI) and coagulation factor V (FV), the association with increased risk remained (OR: 4.9, 95% CI: [1.14-21.04], p = 0.025). The OPG polymorphism rs2073618, specifically GC-GG carriers, was associated with a more than fourfold increased risk of developing LCPD (OR: 4.34, 95% CI: [1.04-18.12], p = 0.033) when data were adjusted by BMI-FV. There was no significant association between RANK rs3018362, RANKL rs12585014, IL-6 rs1800796, COL1A1 rs1800012, and rs2586498 polymorphisms and LCPD in a sample of Mexican children. The rs1800975 and rs2037618 polymorphisms in the IL-6 and OPG genes, respectively, are informative markers of increased risk of LCPD in Mexican children.

Enlarging 18 F-FDG-Avid Solitary Pulmonary Nodule: A Distinctly Unusual Presentation of Cytomegalovirus Infection in a Patient Receiving Chemotherapy.

ABSTRACT: Rapidly growing lung lesions, particularly in immunocompromised patients, invoke consideration of an infectious etiology. Aspergillomas, for example, can appear as round nodules with soft tissue attenuation, often associated with cavitation, and are variably 18 F-FDG avid. In contrast, cytomegalovirus, which may also evidence 18 F-FDG uptake, typically manifests as ground-glass opacities, symmetrically distributed small pulmonary nodules, or confluent consolidations, with lower lobe predilection. We describe a patient treated for lymphoma presenting with a solitary enlarging FDG-avid lung nodule, which was determined on resection to be focal cytomegalovirus infection, a distinctly uncommon presentation of this pathogen, more typical of fungal or mycobacterial disease.

Prothrombin Time and Coagulation Factor IX as Hemostatic Risk Markers for Legg- Calvé-Perthes Disease.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD. METHODS: Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration. RESULTS: After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin time↘, FV↗, FVIII↗, FIX↗, and Hcy↗. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events. CONCLUSIONS: Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.

Remote Reading and Teaching of Nuclear Medicine in the Era of COVID-19.

Community SARS-CoV-2 has profoundly affected traditional elements of learning and teaching in nuclear medicine and diagnostic radiology departments. The response of the nuclear medicine community to the challenges imposed by the COVID-19 pandemic can be described in 3 phases: accommodation, consolidation and optimization, and a return towards normalcy. Adoption of virtual communication platforms has emerged as the crucial interim tool for preservation of trainee supervision and diagnostic imaging education. Development of supplemental teaching materials, refocusing research interests, and relaxation of requirements have all contributed toward stabilization of the residency programs. As we embark on a gradual return to normalcy, many of the virtual solutions that were employed have gained a degree of enduring popularity and may find a place in the postpandemic period.

Localized Metastatic Recurrence of HCC following Distal Extremity Trauma: Bone Scintigraphy and Anatomicopathological Correlation.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with a poor median survival when left untreated. Extrahepatic metastases involving musculoskeletal tissues typically present with concomitant nonosseous metastases at the time of diagnosis. A 61-year-old male on 1-year remission, following transarterial chemoembolization of a 2.3-cm hepatic HCC 1 year before, presented with a 2-month history of left wrist pain and swelling after falling on an outstretched hand. Computed tomographic scan revealed diffuse osteolytic lesions localized in left hand and distal forearm, associated with equivocal diffuse activity on bone scan. Subsequent surgical debridement revealed metastatic hepatocellular carcinoma.

Legg-Calvé-Perthes disease overview.

BACKGROUND: Legg-Calvé-Perthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. Although LCPD was first described in the beginning of the past century, limited is known about its etiology. Our objective is to describe the main areas of interest in Legg-Calve-Perthes disease. METHODS: A review of the literature regarding LCPD etiology was performed, considering the following inclusion criteria: Studies reporting clinical or preclinical results. The research group carried out a filtered search on the PubMed and Science Direct databases. To maximize the suitability of the search results, we combined the terms ''Perthes disease" OR "LCPD" OR "children avascular femoral head necrosis" with "diagnostic" OR "treatment" OR "etiology" as either key words or MeSH terms. RESULTS: In this article been described some areas of interest in LCPD, we include topics such as: history, incidence, pathogenesis, diagnosis, treatment and possible etiology, since LCPD has an unknown etiology. CONCLUSIONS: This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved.

Association of MTHFR rs1801133 and homocysteine with Legg-Calvé-Perthes disease in Mexican patients.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is the avascular osteonecrosis of the proximal femoral epiphysis. It is a rare disease of unclear etiology in children, although alterations in coagulation or the collagen gene have been described and could be associated with its etiology. Our objective was to evaluate the following alterations: COL1A1 (rs1107946, rs2412298), COL2A1 (rs121912891 and rs387106558), MTHFR rs1801133, CBS rs115742905, and PT rs1799963 and their relationship with LCPD. METHODS: DNA was obtained and genotyped by real-time PCR with TaqMan probes. Prothrombin (FII) and homocysteine (Hcy) were determined by a coagulometric method. The variables were described as mean and standard deviation or percentages, and genotypic and allelic distributions were analyzed using the Student's t-test. The Hardy-Weinberg equilibrium and OR were also used. RESULTS: We studied 23 patients with LCPD and 46 controls. We did not find any association of the MTHFR, CBS, PT, COL1A1, and COL2A1 genetic variants with LCPD. However, when adjusting the data with the Hcy values for the MTHFR C677T polymorphism, the C/C genotypes showed an association with the recessive model (p = 0.038), with susceptibility to LCPD. CONCLUSION: No association was found with the CBS, PT, COL1A1, and COL2A1 genes. Nevertheless, our results suggest a significant link between moderately elevated Hcy levels and the MTHFR C677T polymorphism in a cohort of Mexican children with LCPD.

Association of Polymorphisms in Estrogen Receptor Genes (ESR1 and ESR2) with Osteoporosis and Fracture-Involvement of Comorbidities and Epistasis.

Single-nucleotide polymorphisms (SNPs) in the ESR1/ESR2 genes play a role in osteoporosis (OP). Our objective was to determine associations of polymorphisms in ESR genes with OP and fracture, SNP-SNP interactions, and involvement of comorbidities. We analyzed 170 Mexican osteoporotic women (FNOP), 173 with hip fracture (HFx), and 210 controls. The SNPs, ESR1 rs2234693CC, rs851982CC and rs1999805AA, were associated with reduced OP risk (odds ratios [ORs] = 0.35, 0.40 and 0.32, respectively; p < 0.05); rs2234693CC was associated with reduced fracture risk (OR = 0.24; p < 0.05). The obese/overweight carriers of rs9340799GG had a lower OP (OR = 0.15, p = 0.016) and fracture (OR = 0.12, p = 0.0057) risk. The rs9479055AA and rs3020404AA hypertensive carriers had a higher OP risk (OR = 5.96, p = 0.032; and OR = 5.29, p = 0.02, respectively). In addition, rs3020404AA had a higher risk of fracture (OR = 4.90, p = 0.045). The rs2228480GG hypertensive carriers had a higher risk of fracture (OR = 6.22, p = 0.0038). We found a synergic relation between the ESR1 rs3020331 and rs1999805 in femoral neck OP and HFx. The rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms are associated with a high risk forming a haplotype. The epistasis analysis suggests the contribution of both genes (ESR1/ESR2) to the risk of OP and fracture. Epistasis and involvement of obesity and hypertension lead to a significant modification of the risk.

Oncologic significance of unexpected osseous foci on FDG-PET without correlative CT abnormalities.

PURPOSE: Our purpose was to explore the clinical significance of unexpected osseous foci on 18F-FDG-PET without correlative CT abnormalities (FWCT) in patients referred for oncologic evaluation. The significance of FDG-avid foci without correlative CT abnormalities has been previously explored in tissues such as breast, lung, liver, and prostate; however, osseous foci without correlative CT abnormalities continue to present challenges in diagnostic interpretations. METHODS: This study is a retrospective review of 120 osseous FWCT, reported in 91 patients, and their corresponding clinical follow-up. We included only patients with at least 6 months of clinical follow-up leading to a final diagnosis, reviewing bone biopsy results, follow-up imaging, and clinical notes. We excluded those patients on active chemotherapy at the time of the scan. For reports describing > 3 foci, we only analyzed the one with highest maximum standardized uptake value (SUVmax). As a measure of uptake intensity, we obtained focus-to-liver ratios (F/L) utilizing their SUVmax and corresponding hepatic 3D SUVmean. RESULTS: Of 91 patients, 74 (81%) had biopsy-confirmed primary malignancies and 17 (19%) had suspicious findings on diagnostic imaging, but no proven primary malignancy. 50 of 120 (42%) osseous foci were malignant and 70 (58%) were benign. 49 of 120 (41%) foci were solitary and 71 (59%) were 0 with other foci (non-solitary). Malignancy resulted from 15/49 (31%) solitary foci and 35/71 (49%) non-solitary foci. Malignant lesions had a mean F/L 2.37 ± 0.397 and benign lesions a mean F/L 1.49 ± 0.169. Osseous malignancy correlated with a higher uptake intensity (Spearman = 0.408; P < 0.01) and was significantly associated with F/L ≥ 2.0 (P < 0.001). Osseous FWCT led to restaging and management modification in 12/91 (13%) patients. CONCLUSION: Osseous FWCT frequently represent early stages of malignancy. A higher index of suspicion is warranted for osseous FWCT associated with underlying myeloproliferative neoplasms, breast and lung cancer, and moderate (F/L 1.0-2.0) or high (F/L > 2.0) uptake intensity. Interpreting physicians encountering these variables can recommend interval follow-up with 18F-FDG-PET/CT or correlation with contrast-enhanced MRI or tissue biopsy. In patients with an altered biodistribution of 18F-FDG in the bone marrow (e.g., recent chemotherapy cycle), follow-up FDG-PET can be obtained at an appropriate time interval following oncologic treatment.