Postmenopausal women with higher TSH values within the normal range present improved handgrip strength: a pilot study.

OBJECTIVE: To evaluate the possible association between thyroid function within the euthyroid range and musculoskeletal parameters as well as body composition in a sample of postmenopausal women. METHODS: This cross-sectional study included 96 postmenopausal women with serum thyroid-stimulating hormone (TSH) within the normal laboratory reference range. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Bone status and body composition were measured using Dual Energy X-ray absorptiometry (DXA). Physical activity was quantified using the International Physical Activity Questionnaire (IPAQ) index. RESULTS: Serum TSH correlated with handgrip strength (HGS, r-coefficient = 0.233, p = .025), and total body bone mineral density (BMD) T-score values (r-coefficient = 0.321, p = .003). HGS measures were associated with BMD (r-coefficient = 0.415, p < .001), with bone mineral content (BMC, r-coefficient = 0.427, p < .001), and lean mass (r-coefficient = 0.326, p = .003). Women with low muscle strength, defined as HGS < 16 kg, had lower TSH levels than women with normal muscle strength (low vs. normal muscle strength, ANCOVA 1.13 ± 0.49 mU/L vs. 1.60 ± 0.83 mU/L, p = 0.024) independently of age, BMD, percentage of body fat or absolute lean mass. Multivariable linear regression analysis showed that HGS values were associated with TSH measurements (ß-coefficient = 0.246, p = .014) and BMD T-score values (ß-coefficient = 0.306, p = .002). All models were adjusted for age, body mass index (BMI), vitamin D, low-density lipoprotein cholesterol, current smoking, physical activity, and homeostasis model assessment of insulin resistance. CONCLUSIONS: In this sample of postmenopausal women, lower serum TSH values, within normal range, were associated with lower muscle strength compared to higher normal TSH values. Further research is needed to elucidate the significance of our preliminary findings.

The Role of Novel Imaging and Biofluid Biomarkers in Traumatic Axonal Injury: An Updated Review.

Traumatic brain injury (TBI) is a leading cause of disability worldwide. Traumatic axonal injury (TAI) is a subtype of TBI resulting from high-impact forces that cause shearing and/or stretching of the axonal fibers in white matter tracts. It is present in almost half of cases of severe TBI and frequently associated with poor functional outcomes. Axonal injury results from axonotomy due to mechanical forces and the activation of a biochemical cascade that induces the activation of proteases. It occurs at a cellular level; hence, conventional imaging modalities often fail to display TAI lesions. However, the advent of novel imaging modalities, such as functional magnetic resonance imaging and fiber tractography, has significantly improved the detection and characteristics of TAI. Furthermore, the significance of several fluid and structural biomarkers has also been researched, while the contribution of omics in the detection of novel biomarkers is currently under investigation. In the present review, we discuss the role of imaging modalities and potential biomarkers in diagnosing, classifying, and predicting the outcome in patients with TAI.

Ependymomas in Children and Adults.

Ependymomas account for approximately 5% of all CNS tumors in adults and around 10% in the pediatric population. Contrary to traditional theories supporting that ependymomas arise from ependymal cells, recent studies propose radial glial cells as the cells of origin. In adults, half of the ependymomas arise in the spinal cord, whereas in the pediatric population, almost 90% of ependymomas are located intracranially. Most of the ependymomas are usually low-grade tumors except anaplastic variants and some cases of RELA-fusion-positive ependymomas, a molecular variant consisting the most recent addition to the 2016 World Health Organization (WHO) classification. Of note, the recently described molecular classification of ependymomas into nine distinct subgroups appears to be of greater clinical utility and prognostic value compared to the traditional histopathological classification, and parts of it are expected to be adopted by the WHO in the near future. Clinical manifestations depend on the location of the tumor with infratentorial ependymomas presenting with acute hydrocephalus. Gross total resection should be the goal of treatment. The prognostic factors of patients with ependymomas include age, grade, and location of the tumor, with children with intracranial, anaplastic ependymomas having the worst prognosis. In general, the 5-year overall survival of patients with ependymomas is around 60-70%.

Multi-Port Robotic-Assisted Laparoscopic Myomectomy: A Systematic Review and Meta-Analysis of Comparative Clinical and Fertility Outcomes.

BACKGROUND: Uterine fibroids are the most frequently diagnosed gynaecological tumours, and they often require surgical treatment (conventional laparoscopic myomectomy-CLM). The introduction and evolution of robotic-assisted laparoscopic myomectomy (RALM) in the early 2000s has expanded the range of minimally invasive options for the majority of cases. This study aims to compare RALM with CLM and abdominal myomectomy (AM). METHODS AND MATERIALS: Fifty-three eligible studies adhered to the pre-established inclusion criteria and were subsequently evaluated for risk of bias and statistical heterogeneity. RESULTS: The available comparative studies were compared using surgical outcomes, namely blood loss, complication rate, transfusion rate, operation duration, conversion to laparotomy, and length of hospitalisation. RALM was significantly superior to AM in all assessed parameters other than operation duration. RALM and CLM performed similarly in most parameters; however, RALM was associated with reduced intra-operative bleeding in patients with small fibroids and had lower rates of conversion to laparotomy, proving RALM as a safer overall approach. CONCLUSION: The robotic approach for surgical treatment of uterine fibroids is a safe, effective, and viable approach, which is constantly being improved and may soon acquire widespread adoption and prove to be superior to CLM in certain patient subgroups.

Stereotactic radiosurgery versus whole-brain radiotherapy after resection of solitary brain metastasis: A systematic review and meta-analysis.

Objective: The standard of care in patients with solitary brain metastasis involves surgical resection and postoperative whole-brain radiotherapy (WBRT). However, WBRT is associated with adverse effects, mainly neurocognitive deterioration. Stereotactic radiosurgery (SRS) is a more targeted form of radiation therapy that could be as effective as WBRT without the detrimental neurocognitive decline. Methods: We performed the first systematic review and meta-analysis comparing postoperative SRS versus postoperative WBRT in patients with one resected brain metastasis. PubMed, Scopus, and Cochrane library were systematically searched for studies comparing the efficacy of the two radiation modalities in terms of local and distant brain control, leptomeningeal disease control, and overall survival. Additionally, we extracted patients' neurocognitive function and quality of life after each postoperative radiation form. Results: Four studies with 248 patients (128: WBRT, 120: SRS) were included in our analysis. There was no difference between SRS and WBRT in the risk of local recurrence (RR = 0.92, CI = 0.51-1.66, p = 0.78, I2 = 0%) and leptomeningeal disease (RR = 1.21, CI = 0.49-2.98, p = 0.67, I2 = 18%), neither in the patients' overall survival (HR = 1.06, CI = 0.61-1.85, p = 0.83, I2 = 63%). Nevertheless, SRS appeared to increase the risk of distant brain failure (RR = 2.03, CI = 0.94-4.40, p = 0.07, I2 = 61%). Neurocognitive function and quality of life in the SRS group were equal or superior to the WBRT group. Conclusions: Although SRS may increase the risk of distant brain failure, it appears to be as effective as WBRT in terms of local control, risk of leptomeningeal disease, and overall survival while sparing the patients of the detrimental, WBRT-associated cognitive deterioration.

Blood biomarkers for predicting coagulopathy occurrence in patients with traumatic brain injury: a systematic review.

Purpose: The occurrence of coagulopathy in patients with traumatic brain injury (TBI) is related to severe complications. The authors performed the first systematic review to investigate whether biomarkers can predict the occurrence of hypocoagulopathy or progressive hemorrhagic injury in patients with TBI. Methods: The authors included studies that performed a receiver operating characteristics analysis for the biomarker and provided a clear value along with the respective sensitivity and specificity. Additionally, they attempted to classify each biomarker, taking into account its physiological role. Results: Twelve studies were included. All biomarkers were protein molecules, except in one study that examined the prognostic role of glucose. Copeptin had the highest sensitivity, and S100A12 had the highest specificity in predicting coagulopathy, while IL-33 had the highest sensitivity and GALECTIN-3 had the highest specificity in predicting progressive hemorrhagic injury. Conclusion: The study of the role of biomarkers in predicting the occurrence of coagulopathy in patients with TBI remains in its infancy.

Primary Intraosseous Cavernous Hemangioma of the Cranium: A Systematic Review of the Literature.

Primary intraosseous cavernous hemangioma (PICH) is a rare, benign tumor of vascular origin, typically arising in the vertebral body. Its presence in the skull is exceedingly rare, with only a few cases being reported worldwide. We carried out the first systematic review of the literature, covering the epidemiology, clinical and imaging features, management, and prognosis of cranial PICH. The literature search revealed 51 studies with 77 patients; the mean age of the patients was 32.7 years with a female predominance of 1.4:1. The majority of cranial PICHs were located in the calvarium, primarily in the frontal and parietal regions, with only a few located in the skull base. The most common initial clinical manifestation was local growth or swelling, followed by a headache. Radiographically, PICHs represented osteolytic, intradiploic masses, which in many cases displayed trabeculations, leading to the so-called "honeycomb" or "starburst" pattern. After contrast administration, PICHs typically enhance. Tumor removal, with craniectomy or en bloc resection and subsequent skull reconstruction, was selected for calvarial PICHs, whereas a transsphenoidal approach, with only partial resection, was applied for clival/sella PICHs. Preoperative embolization, aiming to minimize intraoperative blood loss, was performed in the case of large tumors. At a mean follow-up of 39 months, no patient experienced tumor recurrence, even after subtotal resection. Owing to the benign nature of the tumor, maximal safe resection is recommended as the treatment of choice for patients with cranial PICH.

The Role of Hsp27 in Chemotherapy Resistance.

Heat shock protein (Hsp)-27 is a small-sized, ATP-independent, chaperone molecule that is overexpressed under conditions of cellular stress such as oxidative stress and heat shock, and protects proteins from unfolding, thus facilitating proteostasis and cellular survival. Despite its protective role in normal cell physiology, Hsp27 overexpression in various cancer cell lines is implicated in tumor initiation, progression, and metastasis through various mechanisms, including modulation of the SWH pathway, inhibition of apoptosis, promotion of EMT, adaptation of CSCs in the tumor microenvironment and induction of angiogenesis. Investigation of the role of Hsp27 in the resistance of various cancer cell types against doxorubicin, herceptin/trastuzumab, gemcitabine, 5-FU, temozolomide, and paclitaxel suggested that Hsp27 overexpression promotes cancer cell survival against the above-mentioned chemotherapeutic agents. Conversely, Hsp27 inhibition increased the efficacy of those chemotherapy drugs, both in vitro and in vivo. Although numerous signaling pathways and molecular mechanisms were implicated in that chemotherapy resistance, Hsp27 most commonly contributed to the upregulation of Akt/mTOR signaling cascade and inactivation of p53, thus inhibiting the chemotherapy-mediated induction of apoptosis. Blockage of Hsp27 could enhance the cytotoxic effect of well-established chemotherapeutic drugs, especially in difficult-to-treat cancer types, ultimately improving patients' outcomes.

Anaplastic gangliogliomas of the spinal cord: a scoping review of the literature.

Gangliogliomas (GGs) are rare, usually low-grade tumors that account for 1-2% of all central nervous system (CNS) neoplasms. Spinal GGs are exceedingly rare (1% of all spinal tumors) and the presentation of anaplastic features in them is even rarer. According to the last World Health Organization (WHO) classification of CNS neoplasms, anaplastic GG (AGG) is classified as a malignant neoplasm (grade III). We performed a scoping review of the literature to elucidate the epidemiology, clinical features, histopathology, treatment, and outcome of primary spinal AGGs, which, to the best of our knowledge, is the first such review. Relevant studies were identified by a search of the MEDLINE and SCOPUS databases, using the following combination of search strings: (anaplastic ganglioglioma or malignant ganglioglioma or high grade ganglioglioma) AND (spine or spinal or spinal cord). We included studies related to primary or recurrent AGGs and malignant transformation of low-grade GGs. The search produced 15 eligible studies, plus two studies from the references, all of which were case reports of patients with spinal AGGs (17 studies with 22 patients). The mean age of the patients was 21.4 years and the sex ratio was 1:1, with male predominance. Motor impairment was the most common presentation, followed by sensory impairment, gait problems, urinary disturbances, and back pain. The thoracic spine was the most frequently involved area (14/22) followed by the cervical (6/22) and lumbar (5/22) spine. In terms of histology, the anaplastic features were usually predominant in the glial element, resembling high-grade astrocytomas, while the neuronal element was composed of the so-called dysplastic ganglion (neuronal) synaptophysin-positive cells, without mitotic figures. Complete surgical resection of the tumor without neurological compromise, plus adjuvant chemotherapy and radiotherapy, was the treatment protocol implemented in the two patients with the best outcome. Primary spinal AGG is an exceedingly rare entity, with only 22 cases being retrieved after an extensive literature search. They appear to affect children and young adults and tend to manifest aggressive behavior. Most studies report that only the glial component of AGGs presents high-grade malignant features, with low mitotic activity in the neuronal component. We therefore suggest that, pending novel targeted therapy, AGGs should be treated as high-grade gliomas, with an aggressive treatment protocol consisting of maximal safe resection and adjuvant chemotherapy and radiotherapy.

Repurposing Antipsychotics for Cancer Treatment.

Cancer is a leading cause of death worldwide, with approximately 19 million new cases each year. Lately, several novel chemotherapeutic drugs have been introduced, efficiently inhibiting tumor growth and proliferation. However, developing a new drug is a time- and money-consuming process, requiring around 1 billion dollars and nearly ten years, with only a minority of the initially effective anti-cancer drugs experimentally finally being efficient in human clinical trials. Drug repurposing for cancer treatment is an optimal alternative as the safety of these drugs has been previously tested, and thus, in case of successful preclinical studies, can be introduced faster and with a lower cost into phase 3 clinical trials. Antipsychotic drugs are associated with anti-cancer properties and, lately, there has been an increasing interest in their role in cancer treatment. In the present review, we discussed in detail the in-vitro and in-vivo properties of the most common typical and atypical antipsychotics, along with their mechanism of action.

Transcutaneous Vagus Nerve Stimulation (t-VNS) and epilepsy: A systematic review of the literature.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (t-VNS) has been proposed as an alternative method for the treatment of various neurological and psychiatric disorders. Contrary to the classic invasive vagus nerve stimulation (i-VNS), t-VNS does not require surgical intervention. The application of t-VNS for the treatment of epilepsy has been poorly studied. Hence, we performed a systematic review of the literature to elucidate efficacy, adverse effects and technical features of t-VNS in patients with epilepsy. MATERIAL AND METHODS: We systematically searched MEDLINE and SCOPUS databases using the following keywords: [TRANSCUTANEOUS VAGUS NERVE STIMULATION OR TRANSCUTANEOUS VAGAL NERVE STIMULATION] AND [EPILEPSY OR SEIZURES]. We searched for observational studies in English concerning the application of t-VNS for the treatment of epilepsy in humans. The full-text version of relevant studies was obtained and reviewed. Technical parameters of the stimulation, percentage of seizure frequency reduction, QOLIE-31(Quality of Life In Epilepsy-31) and LSSS (Liverpool Seizure Severity Scale) questionnaires and adverse effects were recorded and analyzed. RESULTS: A total of 10 studies with 350 patients were included. Both bilateral and unilateral placement of the electrode were applied. Stimulation frequency varied from 10-30Hz, while treatment intensity was usually adjusted according to patients' preferences and tolerance (around 1mA) and below the pain threshold. In the clinical trials included in our review, the mean seizure frequency reduction varied from 30 to 65%. Eight and four studies provided information about QOLIE-31 and LSSS questionnaires respectively. Three studies reported a statistically significant (p<0,05) improvement in patients' quality of life and two studies reported statistically significant (p<0,05) seizure severity reduction. The most common side effect was headache (8,9%), followed by skin irritation at the placement site (7,1%) and nasopharyngitis (5,1%). No serious or life-threatening side effects were reported. CONCLUSION: Due to the heterogeneity of the included studies, no safe conclusions could be extracted concerning the efficacy of t-VNS. However, the results of this review suggest that patients with epilepsy could possibly benefit from the use of t-VNS. The present study also emphasizes the limitations of previous clinical trials concerning the applications of t-VNS in people with epilepsy and thus could be a guidance for the conduction of future trials.

Extraventricular neurocytomas: a systematic review of the literature in the pediatric population.

Extraventricular neurocytomas (EVNs) are rare neuroepithelial neoplasms of the central nervous system that were first described in 1997. Most studies in patients with EVNs have incorporated mixed age groups. The tumor's clinical behavior specifically in children has not been explored in depth, while a detailed statistical analysis has never been performed in this age group. Hence, we performed a systematic review to address possible prognostic factors and the appropriate management in children with EVNs. Relevant studies were identified by searching the MEDLINE and SCOPUS databases. We included studies concerning patients 18 years of age or younger who were histologically diagnosed with EVNs. A total of 52 studies with 79 patients were included. The mean age of the patients was ~ 10 years with a male predilection (~ 2:1). Most of these tumors were located in the frontal (49%) lobe. We observed that gross total resection of the tumor was significantly lower in cases of atypical EVNs (p < 0.05). Additionally, atypical EVNs were associated with worse overall survival compared to typical EVNs (p = 0.05). Children 4 years of age or under had a worst outcome (p = 0.001). The patient's sex and the extent of the tumor's resection did not appear to affect the prognosis in a statistically significant manner. Contrary to the results of previous studies, the use of adjuvant radiotherapy or chemotherapy for the treatment of EVNs was not associated with better outcomes in the pediatric population. Thus, a less aggressive management of children with EVNs compared to the adult population is suggested.

Development and validation of analytical methodology for the quantification of aldehydes in e-cigarette aerosols using UHPLC-UV.

Aldehydes are produced in e-cigarette aerosols, as a result of the thermal decomposition of vegetable glycerin, propylene glycerol and flavorings in the atomizer. These aldehydes were collected with derivatization into 2,4-dinitrophenylhydrazine using impinger trapping. A new methodology for simultaneous quantitative analysis of aldehydes in base liquids was developed and validated. Chromatographic separation was carried out on a Jupiter Proteo 90A column, with the mobile phase consisting of 0.1% formic acid in water and acetonitrile, at a flow rate of 0.4 mL/min. Linearity was demonstrated over the range of concentrations 0.025-10 µg/mL, with correlation of determination ≥ 0.999. Intra- and inter-day % relative standard deviation and relative error were ≤ 10%. The lower limit of detection and quantification were 0.008 and 0.025 µg/mL, respectively. This method was further used for the quantification of aldehydes emitted by different base liquids. It has been shown that vegetable glycerin produces the highest percentage of aldehydes after thermal decomposition compared to propylene glycerol. We propose that it can be used for future e-liquids emissions studies.

Texture analysis of T1 - and T2 -weighted MR images and use of probabilistic neural network to discriminate posterior fossa tumours in children.

Brain tumours are the most common solid tumours in children, representing 20% of all cancers. The most frequent posterior fossa tumours are medulloblastomas, pilocytic astrocytomas and ependymomas. Texture analysis (TA) of MR images can be used to support the diagnosis of these tumours by providing additional quantitative information. MaZda software was used to perform TA on T1 - and T2 -weighted images of children with pilocytic astrocytomas, medulloblastomas and ependymomas of the posterior fossa, who had MRI at Birmingham Children's Hospital prior to treatment. The region of interest was selected on three slices per patient in Image J, using thresholding and manual outlining. TA produced 279 features, which were reduced using principal component analysis (PCA). The principal components (PCs) explaining 95% of the variance were used in a linear discriminant analysis (LDA) and a probabilistic neural network (PNN) to classify the cases, using DTREG statistics software. PCA of texture features from both T1 - and T2 -weighted images yielded 13 PCs to explain >95% of the variance. The PNN classifier for T1 -weighted images achieved 100% accuracy on training the data and 90% on leave-one-out cross-validation (LOOCV); for T2 -weighted images, the accuracy was 100% on training the data and 93.3% on LOOCV. A PNN classifier with T1 and T2 PCs achieved 100% accuracy on training the data and 85.8% on LOOCV. LDA classification accuracies were noticeably poorer. The features found to hold the highest discriminating potential were all co-occurrence matrix derived, where adjacent pixels had highly correlated intensities. This study shows that TA can be performed on standard T1 - and T2 -weighted images of childhood posterior fossa tumours using readily available software to provide high diagnostic accuracy. Discriminatory features do not correspond to those used in the clinical interpretation of the images and therefore provide novel tumour information.

Endometriosis and other benign and malignant müllerian lesions in pelvic and extrapelvic organs.

OBJECTIVE: To conduct a retrospective study on case reports found in literature across the world on benign müllerian lesions of the urogenital tract and on cases of malignant transformation from müllerian duct remnants in order to better understand these rare anatomopathologic entities and to avoid overdiagnosis and overtreatment. STUDY DESIGN: We reviewed a number of case reports on benign and malignant müllerian lesions and compared the developments associated with endometriosis, endosalpingiosis and endocervicosis. RESULTS: Our sampling of case reports confirm the suggestion that both malignant neoplasms and benign müllerian lesions can arise in foci of endometriosis in both pelvic and extrapelvic sites. CONCLUSION: The development of malignant tumors is a well-known complication of endometriosis and endosalpingiosis, but data about endocervicosis are unclear.