Abstract The purpose of this multi-surgeon study was to assess and compare the accuracy of acetabular component placement, leg length discrepancy (LLD), and global offset difference (GOD) between six ...different surgical techniques and modes of guidance in total hip arthroplasty (THA). A total of 1980 THAs met inclusion criteria. Robotic- and navigation-guided techniques were more consistent than other techniques in placing the acetabular cup into Lewinnek's safe zone ( P <0.005 and P <0.05, respectively). Robotic-guided surgery was more consistent than other techniques in placing the acetabular component within Callanan's safe zone ( P <0.005). No statistically significant differences were found between groups in the frequency of patients with excessive LLD. Clinically significant differences between groups were not found in the frequency of patients with excessive GOD. Level of Evidence: IV
To evaluate adalimumab therapy in refractory uveitis.
Prospective case series.
A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other ...systemic immunosuppressive drug participated.
Patients received a 40 mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6).
Degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), visual acuity (logarithm of the minimal angle of resolution logMAR), and macular thickness (optical coherence tomography).
There were 61 men and 70 women (mean age, 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçet's disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82% of patients and in the vitreous cavity in 59% of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (P < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) μ at baseline versus 240 (36) μ at the 6-month visit (P < 0.001). Visual acuity improved by -0.3 logMAR in 32 of 150 eyes (21.3%) and worsened by +0.3 logMAR (-15 letters) in 5 eyes (3.3%). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (P < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 5.05 vs 5.40 4.43; P < 0.001). Six months after the initiation of the study, 111 patients (85%) were able to reduce at least 50% of their baseline immunosuppression load. Only 9 patients (6.9%) had severe relapses during the 6 months of follow-up.
Adalimumab seems to be well tolerated and helpful in decreasing inflammatory activity in refractory uveitis and may reduce steroid requirement. Further controlled studies of adalimumab for uveitis are warranted.
Delayed endothelization and late vessel remodeling might stimulate thrombus deposition and DES thrombosis especially in "real-world" situations (1-2). ...a prolonged dual antiplatelet regimen has ...been advocated in these patients (1-2). ...our findings underscore the critical role of IVUS to guide repeated procedures in this challenging setting.
Summary Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T-cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical. Herein, we describe a series of 4 ...patients with clinically, molecularly, and histopathologically annotated mycosis fungoides or Sézary syndrome whose nodal disease mimicked AITL. The patients otherwise exhibited classic clinical manifestations of mycosis fungoides/Sézary syndrome preceding the onset of lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T-cell infiltrates that coexpressed follicular helper T-cell markers and were accompanied by proliferations of high endothelial venules and arborizing CD21+ follicular dendritic cell networks. Two patients had T-cell receptor gene rearrangement studies performed on their skin, lymph node, and peripheral blood demonstrating identical polymerase chain reaction clones in all 3 tissues. A small secondary clonal B-cell population was present in 1 patient that mimicked the B-cell proliferations known to accompany AITL and persisted on successive nodal biopsies over several years. This latter phenomenon has not previously been described in CTCL. The potential for patients to be misdiagnosed with AITL for lack of consideration of advanced-stage CTCL with nodal involvement underscores the necessity of information sharing among the various pathologists and clinicians involved in the care of each patient.
Abstract Introduction Around 10% of patients with non-medullary thyroid cancer (NMTC) will have a positive family history for the disease. Although many will be sporadic, families where 3 ...first-degree relatives are affected can be considered to represent true familial non-medullary thyroid cancer (FNMTC). The genetic basis, impact on clinical and pathological features, and overall effect on prognosis are poorly understood. Methods A literature review identified articles which report on genetic, clinical, therapeutic and screening aspects of FNMTC. The results are presented to allow an understanding of the genetic basis and the impact on clincal-pathological features and prognosis in order to inform clinical decision making. Results The genetic basis of FNMTC is unknown. Despite this, significant progress has been made in identifying potential susceptibility genes. The lack of a test for FNMTC has led to a clinical definition requiring a minimum of 3 first-degree relatives to be diagnosed with NMTC. Although some have shown an association with multi-centric disease, younger age and increased rates of extra-thyroidal extension and nodal metastases, these findings are not supported by all. The impact of FNMTC is unclear with all groups reporting good outcome, and some finding an association with more aggressive disease. The role of screening remains controversial. Conclusion FNMTC is rare but can be diagnosed clinically. Its impact on prognostic factors and the subsequent role in influencing management is debated. For those patients who present with otherwise low-risk differentiated thyroid cancer, FNMTC should be included in risk assessment when discussing therapeutic options.
Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct ...molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein–protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine–cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.
Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to ...provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years 49·6–50·4, 48·2 years 47·3–49·2, 46·8 years 46·6–48·1, and 55·5 years 54·9–56·1, respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agència de Gestió d'Ajuts Universitaris i de Recerca, Marató de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.
Abstract Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are distinct clinicopathologic entities derived from small B-cells. Here we report an unusual case of simultaneous occurrence of ...CD10-negative, t ( 14 ; 18 )/ BCL2 -negative FL with rare residual germinal centers, and extranodal MZL with extensive amyloid deposition. Diagnostic challenges included a prominent nodular growth pattern and lack of expression of commonly used germinal center (GC) B-cell markers and the t ( 14 ; 18 )/ BCL2 gene rearrangement characteristic of FL in an inguinal lymph node. The corresponding chest wall mass was diagnosed as MZL with extensive amyloid deposition. Though initially diagnosed as MZL involving a lymph node corresponding to the chest wall mass, newer markers of GC B-cells, HGAL and LMO2, as well as a newly described marker of marginal zone cells, MNDA, were helpful to establish the diagnosis of FL in the inguinal lymph node. Subsequent molecular clonality studies showed two distinct clonal B-cell processes in the two sites. This case illustrates the need for integration of morphologic findings with careful choice of ancillary diagnostic tests to establish definitive diagnoses among the spectrum of lymphomas derived from small B-cells.
Background and Aims:
Intestinal microbiota is required to maintain immune homeostasis and intestinal barrier function. At the same time, intraluminal bacteria are considered to be involved in ...inflammatory bowel disease and are required for colitis induction in animal models, with the possible exception of dextran sulphate sodium DSS colitis. This study was carried out to ascertain the mechanism underlying the induction of colitis by DSS in the absence of bacteria.
Methods:
Conventional and germ-free GF Naval Medical Research Institute NMRI mice were used, plus conventional mice treated with an antibiotic cocktail to deplete the intestinal microbiota ‘pseudo-GF’ or PGF mice. The differential response to DSS was assessed.
Results:
Conventional mice developed DSS-induced colitis normally, whereas GF mice showed only minimal inflammation no colonic thickening, lower myeloperoxidase activity, IL-6, IL-17, TNF-α, and IFN-γ secretion by splenocytes and mesenteric cell cultures, etc.. However, these mice suffered enhanced haemorrhage, epithelial injury and mortality as a consequence of a weakened intestinal barrier, as shown by lower occludin, claudin 4, TFF3, MUC3, and IL-22. In contrast, PGF mice had a relatively normal, albeit attenuated, inflammatory response, but were less prone to haemorrhage and epithelial injury than GF mice. This was correlated with an increased expression of IL-10 and Foxp3 and preservation barrier-related markers.
Conclusions:
We conclude that enteric bacteria are essential for the development of normal DSS-induced colitis. The absence of microbiota reduces DSS colonic inflammation dramatically but it also impairs barrier function, whereas subtotal microbiota depletion has intermediate effects at both levels.
Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main ...etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed.
PDF
