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关键词： Diseases   Neuroscience   Medicine/Public Health   general   Psychiatry   Neurosciences   Behavioral Sciences   Pharmacotherapy   Biological Psychology  

摘要： Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN(-/-)) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cognitive impairments. More recently, we also demonstrated that APN deficiency increased A beta-induced microglia activation and neuroinflammatory responses in 5xFAD mice. There is compelling evidence that deregulated insulin activities or cerebral insulin resistance contributes to neuroinflammation and Alzheimer's disease (AD) pathogenesis. Here, we demonstrated that APN levels were reduced in the brain of AD patients and 5xFAD mice. We crossbred 5xFAD mice with APN(-/-) mice to generate APN-deficient 5xFAD (5xFAD;APN(-/-)). APN deficiency in 5xFAD mice accelerated amyloid loading, increased cerebral amyloid angiopathy, and reduced insulin-signaling activities. Pharmacokinetics study demonstrated adipoRon (APN receptor agonist) was a blood-brain barrier penetrant. AdipoRon improved neuronal insulin-signaling activities and insulin sensitivity in vitro and in vivo. Chronic adipoRon treatment improved spatial memory functions and significantly rescued neuronal and synaptic loss in 5xFAD and 5xFAD;APN(-/-) mice. AdipoRon lowered plaque and A beta levels in AD mice. AdipoRon also exerted anti-inflammatory effects by reducing microglial and astrocytes activation as well as suppressing cerebral cytokines levels. The microglial phagocytic activity toward A beta was restored after adipoRon treatment. Our results indicated that adipoRon exerts multiple beneficial effects providing important therapeutic implications. We propose chronic adipoRon administration as a potential treatment for AD.

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摘要： Background Administration of chemotherapy to patients with colorectal liver metastases may result in disappearing liver metastases (DLM). This poses a therapeutic dilemma due to the uncertainty of true complete (pathological) response. Objective We aimed to examine the diagnostic performance of imaging modalities in detecting true complete response in patients with DLM after chemotherapy. Methods We performed a systematic search for articles assessing the diagnostic performance of imaging modalities in evaluating DLM following chemotherapy. True complete response was defined as 1-year recurrence-free survival in non-resected patients or complete pathological response on histologic examination in resected patients. We calculated the negative predictive value (NPV) for detecting true complete response of each imaging modality using a random effects model. Results Thirteen studies comprising 332 patients with at least one DLM were included. The number of DLMs after chemotherapy was 955 with computed tomography (CT), 104 with positron emission tomography (PET), 50 with intraoperative ultrasound (IOUS), 585 with magnetic resonance imaging (MRI), and 175 with contrast-enhanced IOUS (CEIOUS). Substantial variation in study design, patient characteristics, and imaging features was observed. Pooled NPV was 0.79 (95% confidence interval [CI] 0.53-0.96), 0.73 (95% CI 0.58-0.85), 0.54 (95% CI 0.37-0.7), 0.47 (95% CI 0.34-0.61), and 0.22 (95% CI 0.11-0.39) for CEIOUS, MRI, IOUS, CT, and PET, respectively. Conclusion After chemotherapy, MRI or CEIOUS are the most accurate imaging modalities for assessment of DLM and should be used routinely in this context. Given the high NPV of these two modalities, surgical resection of visible CRLM is warranted if technically possible, even if DLM remain.

关键词： cardiac hamartoma   hamartoma of mature cardiomyocytes   cardiac mesenchymal hamartoma   hemangioma  

摘要： Hamartomas are primary, benign neoplastic lesions that most commonly derive from a single variably differentiated cell lineage. Here, we report an unusual case of a cardiac hamartoma. A 62-year-old woman presented with chest pain and palpitations. Serial imaging revealed a large slowly growing and highly vascularized left ventricular mass, which required surgical resection. Microscopically, the lesion was composed of nodular fibrovascular proliferation with haphazardly embedded muscle bundles and peripheral calcifications. Immunohistochemical studies revealed prominent muscle-specific actin positive and smooth muscle actin positive muscle fiber bundles within a disorganized fibrovascular stroma. This characterization is most consistent with cardiac mesenchymal hamartoma. Relevant differential diagnoses for this lesion include hamartoma of mature cardiac myocytes (HMCMs) and intramuscular hemangioma. The prominent smooth muscle differentiation of muscle bundles was incompatible with defining features of HMCM. Absence of S100-positive nerve and mature adipose cells distinguished this lesion from the recently defined, heterogeneous cardiac mesenchymal hamartoma. Forty-seven cases of cardiac hamartoma reported from 1970 to 2020 were reviewed to provide histopathologic context.

关键词： Thyroid   FNAC   Guidelines   Differentiated Thyroid Carcinoma   Tailored Surgery   Conservative Surgery  

摘要： A great number of surgical diagnostic procedures are performed every year for thyroid nodules that are included in undetermined cytological classes that reveal to be malignant thyroid carcinomas in one-third of cases. In the most recent guidelines, lobectomy is the most recommended surgical approach for this classes of nodules, but total thyroidectomy is the recommended treatment for undetermined nodules larger than 4 cm. The main study aim is to support or question the dimensional criteria as an independent clinical decision element for undetermined thyroid nodules management. We examined data regarding 761 patients undergoing thyroid surgery for undetermined thyroid nodules at two high-volume endocrine surgery units in Italy. Patients were divided into three groups based on the preoperative size of the nodules (N < 1, 1 < N < 4, N > 4 cm). Among the patients belonging to the different groups, we analyzed: differences in malignancy rate, histological characteristics of invasiveness and neoplastic aggressiveness, rates of recurrence and response to therapy. Nodule size (evaluated as a categorical variable and as a continuous variable) did not show any statistically significant correlation with the rate of malignancy, histopathological characteristics of tumor aggressiveness and the patient's clinical outcome. Most of the tumors found were included in the low risk class (79.2%) and only one was classified as high risk. Follow up of cancer cases showed excellent results in terms of survival, response to therapy and disease recurrence. Malignant thyroid tumors of any size resulting from a nodule identified as cytologically indeterminate are usually characterized by a low risk follicular pattern, well-differentiated and with an excellent outcome. As a result, preferring an extended surgical attitude for undetermined nodules based on tumor size, in absence of other risk factors, can lead to overtreatment in a significant percentage of cases.

关键词： Chordoid glioma   Third ventricle   Bone metaplasia   Subcommissural organ   Circumventricular organ  

摘要： Chordoid glioma (CG) is a rare WHO Grade II neoplasm of the anterior third ventricle. We report two cases of CG with new presentation in terms of histopathology and location: a case of CG with osseous metaplasia evident on imaging, and another CG, unusually located in the posterior portion of the third ventricle.

关键词： IMN   Biopsy   Pathologic   Reaming   Metastatic   Cancer  

摘要： Introduction Histologic diagnosis of the lesion is important while intramedullary nailing of a pathologic or impending fracture of a long bone. A biopsy can be performed extramedullary using a targeted sampling device such as a pituitary rongeur or intramedullary from the bone removed from the reamer during preparation of the intramedullary canal. The purpose of this study is to compare a cup pituitary rongeur vs. a reaming biopsy from the intramedullary canal during the treatment of pathologic bone lesions with an intramedullary nail. Methods An IRB approved retrospective case control study was performed on 46 consecutive patients who underwent an IMN for pathologic fracture or impending pathologic fracture with an obvious lytic lesion with a known metastatic primary. A laryngeal cup pituitary forceps' rongeur was used in 25 patients and the intramedullary reamer as it passed the lesion was used in 21 patients. Histopathology reports were assessed for (1) adequacy of bone sample (defined as containing sufficient bone and marrow-derived tissue to allow complete histological analysis) and (2) tumor tissue diagnosis. A standard approach for IMN was used. Results Twenty-three of 25 cup biopsy cases (92%) had positive pathology that corresponded to the primary cancer. Eleven of 21 reaming cases (52.4%) had positive pathology that corresponded to the primary cancer (p = 0.0117). Conclusion The use of an intramedullary cup biopsy forceps is better than reamings to diagnose pathological lesions of impending and pathological fractures in long bones caused by metastatic lesions.

关键词： Surgery