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By contrast, LTi cells, defined in 1997, are vital for formation of lymph nodes during embryogenesis. In the past decade, research on ILCs has defined them as important regulators of barrier immunity. However, ILC phenotype and functional characterization is complex and requires highly specific protocols for delineating ILC specific function from other well-characterized immune cells. Within this book, each chapter provides an in-depth protocol that will expand on techniques used by laboratories to study ILC development, characterization and function in mice and humans.PURPOSE OF THE REVIEW Osteochondritis dissecans (OCD) is a pathologic condition of subchondral bone most frequently occurring in the medial femoral condyle of the knee in children and adolescents. Salvage techniques are necessary when either nonoperative or typical operative treatments fail, or the OCD presents in an unsalvageable state. The purpose of this review is to describe the evaluation and management of failed OCDs. RECENT FINDINGS Thorough preoperative planning is essential to the treatment of failed OCDs. Radiographs and advanced imaging such as MRI and CT allow for a detailed assessment of subchondral bone and cartilage. Long-leg alignment radiographs are critical to assess for malalignment which may increase the contact forces on the affected condyle. Malalignment can be corrected with hemiepiphysiodesis or an osteotomy depending on the skeletal maturity of the patient. Osteochondral allografts and autologous chondrocyte implantation treat the defect in both bone and cartilage or solely cartilage and have good short to moderate term outcomes, particularly as compared to the inferior outcomes of microfracture of larger OCDs. Osteochondritis dissecans of the knee that fails to heal with initial operative measures can result in a large defect of bone and cartilage in the knee of adolescents. Treatment of the bone and cartilage defect can be accomplished with either osteochondral allograft transplantation or matrix-assisted autologous chondrocyte implantation can be performed with good outcomes. Assessment and correction of lower extremity malalignment is a critical component of treatment. Durable long-term solutions are necessary for the treatment of these difficult lesions.PURPOSE OF REVIEW The goal of this review is to introduce surgical decision-making pearls for reverse shoulder arthroplasty and describe optimization of surgical exposure for reverse shoulder arthroplasty. RECENT FINDINGS While the technology of reverse shoulder replacement and the associated prosthetic options have expanded, the principles involved in successfully exposing the humerus and glenoid in arthroplasty remain the same. Reverse shoulder replacement should be considered in arthroplasty situations with rotator cuff disease, deformity, bone loss, and instability as part of the diagnosis. Optimal exposure in reverse shoulder arthroplasty can be obtained by (1) releasing deltoid adhesions, (2) removal of humeral osteophytes, (3) generous humeral head cuts, (4) thorough humeral and glenoid capsular release and (5) optimal glenoid retractor placement. Neuromuscular paralysis can also aid glenoid exposure.PURPOSE OF REVIEW Recent advancements in surgical technology and techniques have improved functional results for operative treatment of femoroacetabular impingement syndrome (FAIS). Few studies have comprehensively evaluated the literature regarding return to sport criteria, timing, level, and rates. The purpose of this study was to review recent studies regarding return to play after surgical correction of FAIS. We will specifically evaluate the level of return to play and look to compare pre- and postoperative competition levels when available. We will also analyze timing of return to play from injury to surgery. Additionally, we will elucidate any sport-specific criteria that may determine readiness for return. RECENT FINDINGS Athletes with FAIS treated non-operatively have a low rate of return to sport and are often functionally limited in their level of performance. Surgical management of FAIS includes hip arthroscopy as well as open techniques. Current literature suggests a high rate of return to sport after contemporary surgery for FAIS at 87-93% overall. Rate of return to the same level of competition following surgery for FAIS is 55-83% in pooled studies. Limited evidence is available comparing postoperative rehabilitation protocols and timing of return among different sports. Operative treatment of FAIS results in high rates of return to sport and functional performance. The results of this study may help educate patients preoperatively in regard to the likelihood of functional return to sport and sport-specific considerations. Further research evaluating rehabilitation protocols and return criteria may better elucidate timing intervals for patients to maximize function while limiting complications.The use of temozolomide (TMZ) for the management of aggressive pituitary tumours (APT) has revolutionised clinical practice in this field with significantly improved clinical outcomes and long-term survival. Its use is now well established however a large number of patients do not respond to treatment and recurrence after cessation of TMZ is common. A number of challenges remain for clinicians such as appropriate patient selection, treatment duration and the role of combination therapy. This review will examine the use of TMZ to treat APT including mechanism of action, treatment regimen and duration; biomarkers predicting response to treatment and patient selection; and current evidence for administration of TMZ in combination with other agents.Following the introduction of combination antiretroviral therapy (cART), the morbidity and mortality from human immunodeficiency virus (HIV) infection has been drastically curtailed and HIV has now become a chronic manageable disease. Persons living with HIV (PLWH) are living longer and experiencing significant co-morbidities and conditions of aging. NeuroHIV, clinically defined as HIV-Associated Neurocognitive Disorders (HAND) and pathologically manifested by persistent inflammation in the CNS despite cART, is a significant co-morbid condition for PLWH. In the pre-cART era, HIV mediated much of the pathogenesis in the Central Nervous System (CNS); in the cART era, with low to undetectable viremia, other mechanisms may be contributing to persistent neuroinflammation. Emerging data point to the adverse effects at the cellular level of cART, independent of HIV. Astrocytes are the most abundant cells in the CNS, playing vital roles in maintaining CNS homeostasis (e.g. metabolic support to neurons, clearance of ny and disrupted metabolic homeostasis. CNS=Central Nervous System; cART=combined antiretroviral therapy; BBB=blood brain barrier.PURPOSE Differentiated thyroid cancer (DTC) patients with an unresectable primary tumor cannot benefit from curative surgery, and radioiodine treatment for locoregional and distant disease is not possible with the thyroid gland still in place. Due to local invasion, these patients cannot be included in clinical trials, so that treatment options are limited. The aim of this study was to describe the characteristics and the prognosis of patients with these locally unresectable DTC. PATIENTS AND METHODS A retrospective and multicentric analysis of consecutive cases of unresectable DTC diagnosed between 2000 and 2015 was performed. RESULTS The study population consisted in 22 patients, 13 females (59%); median age 77 years (range 52-91). Thyroid tumors were papillary in six, follicular in seven, Hürthle cell in one and poorly differentiated in eight patients. Patients were treated with external beam radiation therapy (EBRT) (57%), locoregional therapy of distant metastases (41%), cytotoxic chemotherapy (38%) and tyrosine kinase inhibitors (TKIs) (33%). TKI treatment resulted in median disease control duration of 7 months with a grade 3-4 toxicity rate of 44%. Only one patient had a total thyroidectomy after neo-adjuvant EBRT. The 1, 3 and 5-year cumulative survival rate was 81%, 27.7% and 21.5%, respectively. The cause of death was DTC in 11 cases (local progression in 7), and to other causes in 7 cases; no patient died from treatment toxicity. CONCLUSIONS Clinical trials and approved treatments are lacking for unresectable DTC. TKI treatment may allow prolonged disease control with acceptable toxicity.PURPOSE This study aimed to explore the association between low-frequency and rare variants of Wnt signaling genes and postmenopausal osteoporosis (OP) by the next generation sequencing (NGS) technology. METHODS We performed targeted NGS of nine Wnt signaling genes in 400 Chinese postmenopausal women, including 226 cases with decreased bone mineral density (BMD) and 174 controls with normal values. Proxy External Controls Association Test (ProxECAT) and logistic regression analysis were performed by data from internal cases (n = 226) and Genome Aggregation Database (gnomAD) East Asian controls (n = 9435). RESULTS The genomic region of interest (ROI) of 94 functional low-frequency and rare variants was associated with OP risk (P  less then  0.05). The LGR6 gene was associated significantly with OP risk and BMD measurements (BMD, T-score and Z-score) (adjusted-P  less then  0.05) after adjusting for confounders. The allele A of rs199693693 (K82N) in LRP6 and G of novel variant 1 202287949 (R840G) in LGR6 were associated with higher BMD, T-score, and Z-score (all adjusted-P  less then  0.05). ProxECAT showed that LGR4 was significantly different between the internal cases and the external controls (all adjusted-P  less then  0.05). Logistic regression analysis revealed that the allele G of rs765778410 (T645A) (OR = 26.16, 95% CI 4.36-156.95, adjusted-P value = 0.026) in LGR6 and A of rs61370283 (L987M) (OR = 15.39, 95% CI 2.98-79.55, adjusted-P value = 0.037) in LRP5 were associated with increased risk of postmenopausal OP. CONCLUSION The LGR4 and LGR6 genes and four potential functional rare variants associate with postmenopausal OP risk. These results highlight the significance of rare functional variants in postmenopausal OP genetics and provide new insights into the potential mutations in this field.Although the effect of the central clock system on adrenal function has been extensively studied, the role of the peripheral clock system in adrenal tumorigenesis remains largely unexplored. In this study we investigated the expression of clock-related genes in normal adrenocortical tissue and adrenocortical tumors. Twenty-seven fresh frozen human adrenal tissues including 13 cortisol secreting adenomas (CSA), seven aldosterone producing adenomas (APA), and seven adrenocortical carcinomas (ACC) were collected. CLOCK, BMAL1, PER1, CRY1, Rev-ERB, and RORα mRNA and protein expression were determined by qPCR and immunoblotting in pathological tissues and compared with the adjacent normal adrenal tissues. A significant downregulation of PER1, CRY1, and Rev-ERB compared with their normal tissue was demonstrated in CSA. All clock-related genes were overexpressed in APA compared with their normal tissue, albeit not significantly. A significant upregulation of CRY1 and PER1 and downregulation of BMAL1, RORα, and Rev-ERB compared with normal adrenal tissue was observed in ACC.
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