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In December 2019, the new coronavirus infection (COVID-19) was declared a pandemic by the World Health Organization after rapidly spreading over the world in just a few months. All elective operations and nonemergency treatments have been postponed worldwide. However, some patients require surgical therapy as well, and the time spent waiting should not have a negative impact on the surgical outcome or disease course. Following the initial onset of the COVID-19 epidemic, instructions for proper and safe surgery for healthcare staff and patients should develop. Thyroid surgeries have decreased during the COVID-19 pandemic. Most of them can be postponed for a long time. Assessment of thyroid nodules recommends clinical examination, imaging studies, fine needle aspiration (FNA) and vocal cord examination. All these procedures are necessary, and sometimes they cannot be postponed. To determine the best timing, a thorough preoperative assessment should be undertaken, taking into account both oncological and anatomical features. Furthermore, COVID-19 status must be negative prior to any intervention, and hospital infrastructure must be ready to deal with the demanding situation.

Objectives Surgery of the thyroid takes place in a body part with complicated anatomy and several vital physiologic functions. Thyroidectomy is rarely associated with mortality but can be followed by significant complications, (i.e. hypoparathyroidism, hemorrhage, upper airway obstruction, laryngeal nerve injuries and thyrotoxic storm). This review aims to indicate surgical tips and techniques to sustain a low level of complications. Content MEDLINE database (PubMed) platform was used as a search engine and the articles related to the topic were selected using the keywords combination “thyroid surgery and complications”. Summary and Outlook The most common complication of total thyroidectomy with an occurrence ranging between 0.5 and 65% is hypoparathyroidism. Damage to recurrent laryngeal nerves can be temporary or permanent, unilateral or bilateral; bilateral lesion is associated with severe episodes of breathlessness. Thus, intraoperative monitoring of nerve function is essential to prevent damage. Ιn addition, hematoma formation can lead to breathing difficulties due to airway obstruction; preventive hemostasis during surgery is essential. The surgeon must have a complete anatomical understanding of not only the normal anatomy of the central visceral compartment of the neck, but also the common variations of the laryngeal nerves and parathyroid glands in order to keep the complication rate at a very low level.

Purpose This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up and therapeutic approach of ocular toxoplasmosis focusing mainly on the postnatally acquired form of the disease. Methods A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. Results Ocular toxoplasmosis is one of the most frequent infectious etiologies of posterior uveitis. It typically presents with retinochoroiditis. Setting an accurate diagnosis depends to a considerable degree on detecting characteristic clinical characteristics. In addition to the evaluation of clinical features, the diagnosis of toxoplasmosis relies at a large degree on serologic testing. The detection of the parasite DNA in the aqueous or vitreous humor can provide evidence for a definitive diagnosis. The current mainstay for the treatment, if necessary, is the use of oral antibiotic with systemic corticosteroids. Recent evidence suggests other therapeutic approaches, such as intravitreal antibiotics can be used. Conclusion Recent developments in the diagnostic and therapeutic approach have contributed to preventing or limiting vision loss of patients suffering from ocular toxoplasmosis. Further studies are required to provide a better understanding of epidemiology, pathogenesis, diagnosis, and treatment with a significant impact on the management of this challenging clinical entity.

This review aims to present the state of the art to understand the pathophysiology of ocular toxoplasmosis (OT), providing further foundations that would help to improve the future treatment and prognosis of this potentially blinding disease.A thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items.Toxoplasma gondii ocular infection is one of the most frequent causes of posterior uveitis. Despite the ocular barriers, the parasite reaches the eye through different mechanisms. Once inside, it remains encysted livelong within the retina, and recurrences cannot be completely avoided. The complexity of host-parasite interactions, leading to the success of this parasite, encompasses host factors such as genetic predisposition, immune status, and age; and parasite factors such as strain diversity, virulence, phylogenetic origin, and geographical distribution. These factors influence the clinical presentation, course, and progression of the disease. Additional elements, such as pregnancy, eating behavior, and environmental, social, and cultural factors may also contribute to this complex balance.The host-parasite interaction in OT is a complex and multifactorial relationship, with the parasite always on the driving edge of the game. There are still multiple incompletely understood fields to be investigated. Future research would permit further insight into the immune-biology of the parasite and recognition of the host-parasite interplay to improve the diagnostic and management performance.

Objectives The great saphenous vein is the lower limb’s longest and thickest-walled superficial vein. Its anatomy is complex, while its anatomical variations are widespread. This study aimed to illustrate the anatomy and variations of the great saphenous vein at the saphenofemoral junction. Methods The study was conducted on 75 fresh-frozen cadaveric lower limbs. Cadavers with evidence of prior leg surgery or trauma and any congenital abnormality or gross deformity were excluded. The saphenofemoral junction was studied in detail with emphasis on the number, incidence, draining pattern of tributaries, and duplication of the great saphenous vein. Results Out of the 75 cadaveric lower limbs, 57.3% were obtained from males, and 42.7% were obtained from females. The mean age of the cadaveric lower extremities was 66.6 years (range 42–91). The number of tributaries at the saphenofemoral junction varied from 0 to 7, with a mean of 3.8. The most frequent number of branches was 4–5 in 61.3% of cases. The most consistent tributary was the superficial external pudendal vein, while the posterior accessory great saphenous vein was the least frequent tributary. 80% of the branches drained into the saphenofemoral junction directly (53.3%) or by a common trunk (26.7%%). The most frequent common trunk was the superficial epigastric and superficial circumflex iliac vein (10.7%). The rest 20% of the tributaries drained directly into the common femoral vein. The commonest branch reaching the common femoral vein was the superficial external pudendal vein (10.7%). Duplication of the great saphenous vein was observed in 2.7% of the cases. Conclusions There is a significant variation of tributaries at the saphenofemoral junction regarding the number, incidence, draining pattern of branches, and duplication of the great saphenous vein.

Summary. Phlebosclerosis is a venous wall degenerative disease which has gained little popularity in the literature due to its uncertain clinical significance. The objective of this review is to evaluate the epidemiology, etiology and clinical significance of phlebosclerosis in lower extremities veins, particularly the effect of preexisting phlebosclerosis of the great saphenous vein on vein graft patency. Medline was searched from inception until November 1, 2019. Reference lists of included studies were scanned. Only articles published after 1949 were included. Two reviewers independently screened titles/abstracts and full-text papers for any study design in relation to phlebosclerosis in lower extremities veins and abstracted data. A total of 16 Cohort studies and one case-control study (3708 participants, mean age 61.8 years, 59.3 % men, and 40.7 % women) were included after screening 317 titles and abstracts, and 80 full-text articles. The incidence of phlebosclerosis ranged from 1.5–9.7 % depending on the radiological features. On the contrary, the incidence of the phlebosclerotic great saphenous vein prior to its use as a vein graft was 26.9–91 % on histological examination. The small saphenous vein was the most common location of phlebosclerosis followed by the great saphenous vein. There is a link between phlebosclerosis and age, venous insufficiency and haemodialysis. As for the vein graft patency seven studies demonstrated a correlation between preexisting phlebosclerosis and vein graft stenosis, whereas three studies failed to prove any association. In conclusion, the radiological incidence of phlebosclerosis depended on the ultrasound findings. Its presence in the great saphenous vein prior to its use as a vein graft is established on histological examination. The small saphenous vein is mainly affected. Risk factors included age, haemodialysis, and venous insufficiency. Preexisting wall thickness of the great saphenous vein graft seemed to affect negatively its patency in bypass surgery.

Adamantinoma is a biphasic tumor, with a low potential for malignancy, characterized by clusters of epithelial cells surrounded by a relatively bland spindle-cell osteofibrous component. The aim of the present study was to review the updated data regarding epidemiology; pathogenesis; clinical presentation; radiological, histopathological and ultrastructural findings; and treatment options of adamantinoma. In X-ray, it is usually seen as an eccentric and sometimes central, lobular, lytic lesion with sclerotic margins of overlapping radiolucency, and a characteristic 'soap-bubble' appearance. Magnetic resonance imaging seems to be the most appropriate examination for differential diagnosis between adamantinoma and other skeletal tumors. Histologically, adamantinoma is identified as classic adamantinoma or osteofibrous-like adamantinoma. Classic adamantinoma is classified into four patterns of growth: Basaloid, tubular, spindle cell, and squamous. The preferable treatment of this tumor type is en bloc resection within wide operative margins, which may include suspicious regional lymph nodes, with limb reconstruction and limb salvage.

Chronic liver injury, regardless of the underlying disease, results in gradual alteration of the physiological hepatic architecture and in excessive production of extracellular matrix, eventually leading to cirrhosis Liver cellular architecture consists of different cell populations, among which hepatic stellate cells (HSCs) have been found to play a major role in the fibrotic process. Under normal conditions, HSCs serve as the main storage site for vitamin A, however, pathological stimuli lead to their transdifferentiation into myofibroblast cells, with autophagy being the key regulator of their activation, through lipophagy of their lipid droplets. Nevertheless, the role of autophagy in liver fibrosis is multifaceted, as increased autophagic levels have been associated with alleviation of the fibrotic process. In addition, it has been found that HSCs receive paracrine stimuli from neighboring cells, such as injured hepatocytes, Kupffer cells, sinusoidal endothelial cells, which promote liver fibrosis. These stimuli have been found to be transmitted via exosomes, which are incorporated by HSCs and can either be degraded through lysosomes or be secreted back into the extracellular space via fusion with the plasma membrane. Furthermore, it has been demonstrated that autophagy and exosomes may be concomitantly or reciprocally regulated, depending on the cellular conditions. Given that increased levels of autophagy are required to activate HSCs, it is important to investigate whether autophagy levels decrease at later stages of hepatic stellate cell activation, leading to increased release of exosomes and further propagation of hepatic fibrosis.

Gestational trophoblastic diseases (GTDs) are a heterogeneous group of lesions, the most frequent being the hydatidiform mole (HM). HMs are usually cured after surgical treatment or after chemotherapy in the case of a persistent trophoblastic activity. Immunotherapy could be an interesting alternative as a first-line or second-line treatment. However, only a few studies have explored the immune microenvironment of HMs. In the present retrospective study including 19 complete and 17 partial moles, we examined the composition of the immune cell microenvironment by immunohistochemistry using the following antibodies: CD4, CD8, CD56, PD-L1, S100, CD83, CD207, CD123, CD1a, CD11c, CD163, PAX5, and MUM1. In the decidual cells compartment, CD11c+ cells were the predominant population, followed by CD4+ cells, CD56+ NK cells, CD163+ macrophages, and CD8+ T lymphocytes.In the endometrial glands compartment, CD11c+ cells were the predominant population, followed by CD4+ cells, CD56+ NK cells, and CD8+ T lymphocytes. In the villi compartment, the predominant immune cells were CD4+ cells, followed by CD163+ macrophages and CD11c+ cells. Statistically significant differences were observed between partial and complete moles in all three compartments. The immune microenvironment of HMs is immunosuppressive, but it differs between complete and partial moles, the latter having a higher infiltrate of cells with phenotypes suggestive of immunosuppressive activities.

Autophagy and cellular senescence are interrelated cellular stress responses important for cellular homeostasis and they have been implicated in the pathogenesis of classical Hodgkin lymphoma (cHL). However, the presence of autophagy and cellular senescence and their relation with clinical and laboratory parameters needs further elucidation. Thus, autophagy (LC3B and p62 immunohistochemical expression) and cellular senescence (p16 immunohistochemical expression and SenTraGor™ staining) were studied in tissue sections from 59 patients with cHL. Autophagy and cellular senescence-associated markers were detected in variable proportions of Hodgkin and Reed-Sternberg (HRS) cells in cHL cases. High nuclear p62 immunohistochemical expression in HRS cells showed significant positive correlation with relapse of the disease (p = 0.037). Heterogeneous autophagy and cellular senescence patterns were revealed in HRS cells suggesting biological heterogeneity of cHL. The detection of high nuclear p62 expression in HRS cells may identify a subset of cHL with more aggressive clinical behavior.

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Background We investigated serous effusions occurring during the course of an already known hematologic neoplasia or as a first manifestation of it. We correlated cytology results with flow cytometry results, when available. In the absence of flow cytometry, our correlation was based on clinical follow up information obtained retrospectively. We evaluated our results in relation to the data of the literature and we considered some new suggestions for the improvement of cytology service. Methods Serous effusions in hematologic patients were retrieved from the files of the Department of Cytology, Laiko Hospital, for a period of 2 years. All patients had enrolled either a previous hematologic history, or a suspicious clinical and imaging status. Seventy-three serous effusions were included. Cytology reports consisting of morphology and immunocytochemistry assessment were correlated to flow cytometry results and, occasionally, to clinical follow-up. Results In the group of patients with previous history, sensitivity was 82.76%, positive predictive value was 100%, specificity 100%, and negative predictive value was 58.33%. In the group of patients without previous history, sensitivity and positive predictive value were both 91%, whereas specificity and negative predictive value could not be estimated. Conclusion We provide evidence that the diagnostic accuracy of cytology with the adjunct of immunocytochemistry is high compared to flow cytometry for detecting hematologic malignancies. In order to improve clinical performance, it is suggested that a cytology triage of serous effusions in all patients with hematologic malignancy must be implemented.

Osteoid osteoma, the third most common benign bone tumor, usually occurs in the cortex of long bones. It consists of a radiolucent nidus surrounded by reactive osteosclerosis. Generally, osteoid osteoma affects young males. Nocturnal pain that eases with salicylates or nonsteroidal anti-inflammatory drugs (NSAID) is the typical clinical presentation. Sometimes, it remains undiagnosed for a long time. Plain radiography and computed tomography are usually sufficient for the diagnosis of osteoid osteoma. Initial treatment includes salicylates and NSAID because the tumor often regresses spontaneously over 2-6 years. Surgical treatment is indicated in case of unresponsive pain to medical therapy, no tolerance of prolonged NSAID therapy due to side effects, and no willingness to activity limitations. Nowadays, minimally invasive techniques have replaced open surgery and are considered the gold standard of surgical treatment. Although cryoablation seems superior in terms of the nerve damage and immunotherapy effect, radiofrequency ablation is the preferred technique.

Osteoid osteoma, the third most common benign bone tumor, usually occurs in the cortex of long bones. It consists of a radiolucent nidus surrounded by reactive osteosclerosis. Generally, osteoid osteoma affects young males. Nocturnal pain that eases with salicylates or nonsteroidal anti-inflammatory drugs (NSAID) is the typical clinical presentation. Sometimes, it remains undiagnosed for a long time. Plain radiography and computed tomography are usually sufficient for the diagnosis of osteoid osteoma. Initial treatment includes salicylates and NSAID because the tumor often regresses spontaneously over 2-6 years. Surgical treatment is indicated in case of unresponsive pain to medical therapy, no tolerance of prolonged NSAID therapy due to side effects, and no willingness to activity limitations. Nowadays, minimally invasive techniques have replaced open surgery and are considered the gold standard of surgical treatment. Although cryoablation seems superior in terms of the nerve damage and immunotherapy effect, radiofrequency ablation is the preferred technique.

One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as “lipofuscin,” “ceroid,” or “age pigment” is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe2+) (“labile iron”), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO•) or alcoxyl (RO•) radicals. If the oxidized materials remain unrepaired for extended periods of time, they can be further oxidized to generate ultimate over-oxidized products that are unable to be repaired, degraded, or exocytosed by the relevant cellular systems. Additionally, over-oxidized materials might inactivate cellular protection and repair mechanisms, thus allowing for futile cycles of increasingly rapid lipofuscin accumulation. In this review paper, we present evidence that the modulation of the labile iron pool distribution by nutritional or pharmacological means represents a hitherto unappreciated target for hampering lipofuscin accumulation and cellular ageing.

Background/Aim: The mechanisms underlying the contribution of the heparan sulfate proteoglycan syndecan-1 to liver tissue injury and to crucial biological processes, such as fibrogenesis, remain to be elucidated. Therefore, we investigated the immunohistochemical expression of syndecan-1 in chronic liver diseases (CLDs) and its probable role in hepatic fibrosis. Materials and Methods: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections of biopsy material obtained from 128 patients diagnosed with CLDs. The correlation between syndecan-1 expression and the stage of fibrosis was investigated. Results: According to the severity of fibrosis, cases were categorized into three groups: early fibrosis; intermediate fibrosis; advanced fibrosis. Syndecan-1 expression was significantly enhanced in advanced fibrosis compared to early (p

Apart from triglycerides, olive oil contains low quantities of polar compounds, such as polyphenols, which are believed to be relevant for maintaining human health. In this presentation, we will discuss potential molecular mechanisms by which specific phenolic compounds present in olive oil can exert cytoprotective and cell signal modulating effects, through chelation of intracellular labile (redox-active) iron. Iron chelation by specific polyphenols can prevent or relocalize the interaction of iron with hydroperoxides produced in the cells and the formation of extremely reactive species. The latter are able, either to induce uncontrolled oxidation of basic cell components or to modulate redox signaling. It is proposed that olive oil–contained polyphenols can influence the outcome of cell responses in conditions of increased oxidative stress mainly by this way.

A healthy pregnancy requires the development of maternal-fetal immune tolerance against the semi-allogeneic fetus. The interactions between the trophoblastic cells and the maternal immune cells (p.e., natural killer cells, T cells, macrophages, dendritic cells and B-cells) are important for the development of the maternal-fetal immune tolerance and the placental growth and function. These interactions are mediated by cell to cell contact and secreted molecules such as cytokines, chemokines, angiogenic factors and growth factors. The maternal immune cells are present in normal non-pregnant and pregnant endometrium and there are several lines of evidence based on immunohistochemical and RNA sequencing data that the decidual immune cells and immune-related pathways display alterations in GTD, which may have pathogenetic and clinical significance. The present review focuses on the usefulness of the immunohistochemical analysis which provides multiparametric in situ information regarding the numbers, the immunophenotypes and the immunotopographical distributions of the decidual immune cells in tissue sections from normal pregnancy and GTD. We also discuss the significance of the immunohistochemical information in order to gain insight in the putative mechanisms explaining the alterations of the decidual immune cells in GTD and the potential implications of these alterations in the pathogenesis and the clinical behavior of GTD.

The human thymus is a primary lymphoepithelial organ which supports the production of self-tolerant T cells with competent and regulatory functions. Paradoxically, despite the crucial role that it exerts in T cell-mediated immunity and prevention of systemic autoimmunity, the thymus is the first organ of the body that exhibits age-associated degeneration/regression, termed “thymic involution.” A hallmark of this early phenomenon is a progressive decline of thymic mass as well as a decreased output of naïve T cells, thus resulting in impaired immune response. Importantly, thymic involution has been recently linked with cellular senescence which is a stress response induced by various stimuli. Accumulation of senescent cells in tissues has been implicated in aging and a plethora of age-related diseases. In addition, several lines of evidence indicate that oxidative stress, a well-established trigger of senescence, is also involved in thymic involution, thus highlighting a possible interplay between oxidative stress, senescence, and thymic involution.

The purpose of this cadaveric study is to determine safe zones utilizing volar portals for wrist arthroscopy, by quantitatively describing the neurovascular relationships of a volar radial and a volar ulnar wrist arthroscopy portals in comparison with those of a newly described volar central portal (7) , considering the advantages in visualization of volar portals for wrist arthroscopy over the standard dorsal (19) . The neurovascular structures and the tendons of nine frozen human cadaveric upper limbs were exposed, while the aforementioned volar portal sites were pointed out with pins. The horizontal distance between the portals and the closest neurovascular branch or tendon was measured with a digital caliper, followed by statistical analysis of the data. The median interquartile range distances from portals to structures at risk were measured and safe zones around each portal were established. This study provides a safe approach to the volar radial and ulnar aspects of the radiocarpal and midcarpal joints, while volar radial and ulnar portals should be considered for inclusion in the arthroscopic examination of any patient with radial and ulnar sided wrist pain respectively (17,18) . Regarding the volar central portal, it is reproducible, safe and both the above joints can be inspected through one single incision (7) .

Background/aim Since most cancers are associated with alterations of the p53 and Rb pathways, the expression of p53, p21, Rb, p16, p27, cyclin D1, cyclin A, cyclin B1 and Ki67 proteins were analyzed in bladder urothelial carcinomas (BUC). Materials and methods One hundred twenty-two cases of BUC were studied by immunohistochemistry. Results The pathways p53/p21 and Rb/p16/cyclin D1 exhibited alterations in 81/115 and 63/84 cases, respectively. Alterations of the p53/p21 and Rb/p16/cyclin D1 pathways were positively correlated with high cyclin A expression. High expression of p53, Ki67, cyclin A and cyclin B1 was inversely correlated with the papillary morphology of the tumor and positively with tumor grade and T-stage. Conclusion The results showed that a) alterations of the p53 and Rb pathways are associated with high proliferation of tumor cells in BUC and b) high expression of cell-cycle proteins is associated with adverse histopathological parameters of these tumors.

Cellular senescence, an age-related process in response to damage and stress, also occurs during normal development and adult life. The thymus is a central lymphoepithelial organ of the immune system that exhibits age-related changes termed thymic involution. Since the mechanisms regulating thymic involution are still not well elucidated, we questioned whether cellular senescence is implicated in this process. We demonstrate, for the first time in situ, that cellular senescence occurs during human thymic involution using SenTraGor™, a novel chemical compound that is applicable in archival tissue material, providing thus further insights in thymus histophysiology.

Since syndecan-1 is an adhesion molecule involved in tumor invasion and metastasis, we evaluated the relationship between syndecan-1 expression and histopathological features of gastric carcinomas.Syndecan-1 expression was evaluated in 104 gastric carcinomas using immunohistochemistry.High, moderate and low syndecan-1 expression in carcinoma cells was observed in 17/104, 25/104 and 62/104 cases, respectively. High, moderate and low syndecan-1 expression in stromal cells was observed in 5/104, 22/104 and 77/104 cases, respectively. Low epithelial syndecan-1 expression was significantly associated with increased depth of invasion (p=0.034) and lymph vessel invasion (p=0.035). Low stromal syndecan-1 expression was significantly associated with histologic type (intestinal vs diffuse/mixed; p=0.04), increased histologic grade (p=0.04) and large tumor size (p=0.026).Low levels of tumor and stromal syndecan- 1 expression were associated with adverse histopathological parameters in gastric carcinoma. This suggests that syndecan-1 expression may be helpful for assessing the aggressiveness of gastric carcinomas.

Juvenile idiopathic arthritis is a heterogeneous group of conditions encompassing all forms of unknown origin arthritis before the age of 16 years that persist for more than 6 weeks. It is the most common rheumatic disease in young patients and causes severe disabilities, thus an early initiation of the appropriate treatment modalities is necessary. First therapeutic options are nonsteroidal anti-inflammatory drugs, corticosteroids, and conventional non-biologic disease-modifying anti-rheumatic drugs, such as methotrexate. Insufficiency of these drugs led to the introduction of new biological medications that selectively target specific cytokines with an objective to suppress the disease. Despite the success in treatment and physical therapy, some of the patients develop advanced arthritis that can result in severe pain and disability. In such cases, surgical intervention is required to improve quality of life. The surgical methods include soft tissue release, osteotomies, synovectomies, and arthrodesis. Total joint replacement is the last option for endstage degenerative conditions (patients with deformity, poor motion, and severe pain). Deep infections, bone perforation, acetabular protrusion, postoperative dislocations, and the need for re-operation are some of the complications of total joint arthroplasty. This review summarizes published studies of the treatment of juvenile idiopathic arthritis focusing mainly on surgical treatment. Our purpose is to evaluate the general trends in treatment of juvenile idiopathic arthritis, focusing on methods, therapeutic advances, and outcomes of the intervention applied.

Introduction An awareness of the anatomical parameters of the foot such as the position and orientation of the sesamoid bones can be of great value for the etiology and diagnostic approach to patients with hallux valgus (HV). The purpose of this study was to evaluate the basic anatomical features and measurements related to the characteristics of HV in cadaveric material. Materials and methods The study sample included 12 cadaveric limbs with HV and 10 cadaveric limbs without HV as a control group. We measured the HV angle (HVA), the first to second intermetatarsal angle (IMA), and the first to fifth IMAs of all samples. We also recorded the shape of the first metatarsal head and the position/orientation of the sesamoid bones. Results The mean values of the HVA (p = 0.000), the first to second IMA (p = 0.000), and the first to fifth IMA (p = 0.000) differed between the HV and non-HV group. The position of the sesamoid ossicles between the HV and the non-HV group was statistically significant (p = 0.001). While we noted the round shape of the first metatarsal head was predominant in HV samples, we found no statistically significant difference in the first metatarsal head shape between the test and control groups. Conclusion The HVA, the first to second IMA, the first to fifth IMA, and the orientation of the sesamoid ossicles differed significantly between cadaveric samples with HV and those without HV.

To review the role of antigen-presenting cells (APC) in the pathogenesis of ocular surface diseases (OSD). A thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items. APCs have the ability to initiate and direct immune responses and are found in most lymphoid and non-lymphoid tissues. APCs continuously sample their environment, present antigens to T cells and co-ordinate immune tolerance and responses. Many different types of APCs have been described and there is growing evidence that these cells are involved in the pathogenesis of OSD. OSD is a complex term for a myriad of disorders that are often characterized by ocular surface inflammation, tear film instability and impairment of vision. This review summarizes the current knowledge concerning the immunotopographical distribution of APCs in the normal ocular surface. APCs appear to play a critical role in the pathology of a number of conditions associated with OSD including infectious keratitis, ocular allergy, dry eye disease and pterygium.

Primary vitreoretinal lymphoma (PVRL) is a rare ocular lymphoid malignancy, which consists a subset of primary central system lymphoma (PCNSL) and the most common type of intraocular lymphoma. The involvement of eyes is estimated to be approximately 20% of PCNSL, but the brain involvement may be up to 80% of PVRL. Typically, PVRL is a high grade B-cell malignancy of the retina and needs to be assorted from choroidal low-grade B-cell lymphomas. Very often PVRL masquerades and can be erroneously diagnosed as chronic uveitis, white dot syndromes or other neoplasms. Establishing an accurate diagnosis may involve cytology/pathology, immunohistochemistry, flow cytometry, molecular pathology and cytokine profile analysis. There is inadequate information about PVRL’s true incidence, ethnic/geographical variation and pathogenetic mechanisms. The therapeutic approach of PVRL involves aggressive chemotherapy and radiation therapy. Although PVRL tends to have a good response to the initial treatment, the prognosis is poor and the survival restricted due to the high relapse rates and CNS involvement. Keywords: B-cell lymphoma, Primary vitreoretinal lymphoma, Intraocular lymphoma, Primary CNS lymphoma, Masquerade syndrome

Most primary cutaneous B-cell lymphomas (PCBCL) are CD5 negative, and only a few cases were found to express CD5. We report the first well-documented CD5+ primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT). A 71-year-old woman with a history of Multiple Sclerosis was admitted because of a nodule at the left thigh. Histological examination of the skin biopsy disclosed a diffuse dermal infiltration by large lymphoid cells. Immunohistochemistry revealed that these large cells were positive for CD5, CD20, CD79a, MUM1/IRF4, Bcl6, Bcl2, and cytoplasmic IgM/λ, whereas CD3, CD56, CD23, CD21, CD10, CD30, cyclin D1, CD68, lysozyme, myeloperoxidase, and CD34 were not detected. Thus, the diagnosis of a CD5+ PCDLBCL-LT was made. Despite treatment, the patient died 11 months after initial diagnosis.

The objective of this study was to evaluate the contribution of the medial retinaculum to the stability of the patella, for several angles of knee flexion. For six cadaveric knees, the patella and patella retinaculum were exposed, and the force required to dislocate the patella laterally by 5 mm was measured, in 0, 45 and 90 degrees of knee flexion, preserving and dissecting the medial retinaculum. Wilcoxon singed rank test (SPSS, version 23, Chicago, USA) was used for data analysis. A p value of0.05 was considered as statistically significant. The force required to displace the patella laterally is smaller with the medial retinaculum dissected than intact, in 0, 45 and 90 degrees (p = 0.028, p = 0.046, p = 0.027 respectively). The lateral displacement force is greater as the flexion angle increases, with medial retinaculum intact or dissected (p = 0.028). Thus, an intact medial retinaculum provides more stability against lateral displacement forces to the patella, especially in lower flexion angles. Consequently, surgical methods reinforcing the medial retinaculum combined or not with lateral retinaculum release, are of great importance in the plan of the orthopedic surgeons. The engagement of the bones during flexion of the knee contributes significantly to the stability of the patella.

Long-standing scapholunate instability frequently leads to progressive deterioration of the adjacent joint cartilages in a consistent repetitive sequence of arthritis. The purpose of this study was to investigate whether the capitate-triquetrum distance is related with the occurrence of carpal collapse in cases of static scapholunate instability. In this retrospective study, 41 patients formed two groups based on the capitate-triquetrum distance; twenty-four with distance of less than 5mm and 17 with distance of 5mm or more. No significant difference was detected with respect to age, sex distribution, dominant hand involvement, initial treatment and time from injury to final x-rays. Three patients (3/24, 12.5%) of the C-T5mm group and 10 patients (10/17, 58.8%) of the C-T ≥ 5mm group had no sign of carpal collapse. This difference was statistically significant (p=0.017). Capitate-triquetrum distance could reliably contribute in the decision making process in difficult cases of static scapholunate instability.

The activator protein-1 (AP-1) is a dimeric transcription factor composed of proteins belonging to the Jun (c-Jun, JunB and JunD), Fos (c-Fos, FosB, Fra1 and Fra2) and activating transcription factor protein families. AP-1 is involved in various cellular events including differentiation, proliferation, survival and apoptosis. Deregulated expression of AP-1 transcription factors is implicated in the pathogenesis of various lymphomas such as classical Hodgkin lymphomas, anaplastic large cell lymphomas, diffuse large B cell lymphomas and adult T cell leukemia/lymphoma. The main purpose of this review is the analysis of the expression patterns of AP-1 transcription factors in order to gain insight into the histophysiology of lymphoid tissues and the pathology of lymphoid malignancies.

Senescence and apoptosis constitute types of cellular responses that normally ensure homeostasis, when endogenous or exogenous signals occur. Their deregulation is often observed in various pathologies, such as age and non-age related diseases including cancer. Although epithelial cells and fibroblasts are capable to exert both functions, under a plethora of insults, the fact that they exhibit notable intrinsic differences in cell/tissue homeostasis properties, might be a crucial determinant of the mode of response to a certain stress signal. Sparse evidence in the literature reveals that in the same tissue/organ context and under the same conditions, the cell type seems to drive the differential counteraction between epithelia and fibroblasts. Based on the above notion we propose that, upon stress insults, human fibroblasts seem to predominantly respond via senescence, while epithelial cells prefer to exert apoptosis. We suggest that considering the tissue as a whole (epithelium and stroma) would benefit research into new therapeutic strategies for chronic diseases and cancer.

Objective: To evaluate the correlation between the Manchester Grading Scale and the American Orthopaedic Foot and Ankle Society (AOFAS) score in patients with a hallux valgus deformity. Subjects and Methods: The study sample included 181 feet of 122 patients with hallux valgus and 424 feet of 212 individuals without hallux valgus deformity as the control group. The severity of hallux valgus, utilizing a relative nonmetric scale, the Manchester Grading Scale, and the metric AOFAS score, was determined for all individuals in the hallux valgus and control groups. SPSS version 18 (Chicago, Ill., USA) was used for data analysis. Results: According to the Manchester Grading Scale, the 424 feet of the normal group were classified as ‘no deformity'. In the hallux valgus group, 85 feet were classified as ‘mild deformity', 67 as ‘moderate deformity' and 29 as ‘severe deformity'. The AOFAS total score in the control group was 99.14. In the hallux valgus group, patients with mild or moderate deformity had total scores of 86.20 and 68.19, respectively. For those with severe hallux valgus, the total score was 44.69 and the differences were statistically significant (p = 0.000). Using the Pearson correlation, strong negative correlations were found between the AOFAS score and the hallux valgus angle (HVA; r = -0.899, p = 0.000). Strong negative correlations were demonstrated between the AOFAS score and the first intermetatarsal angle (IMA) as well (r = -0.748, p = 0.000). Conclusions: The AOFAS score was negatively associated with the Manchester Grading Scale, HVA and first IMA. As the severity of hallux valgus increased, the AOFAS score seemed to decrease.

We report 2 rare variants in the spectrum of human herpesvirus 8 (HHV8)/Epstein-Barr virus (EBV)-copositive lymphoproliferations arising in HIV-seronegative patients, including a large B-cell lymphoma arising in the setting of multicentric Castleman disease and a germinotropic lymphoproliferative disorder. In the first case, histology revealed features of multicentric Castleman disease and a proliferation of large lymphoid cells forming clusters or arcs or rings replacing the periphery of follicles or sheets of frank lymphoma outside the follicles. In the second case, a proliferation of large lymphoid cells totally or partially invaded follicle germinal centers. In both cases, the large cells were positive for EBV-encoded small RNA, HHV8 (LANA-1), MUM1/IRF4, and CD38 and negative for CD45, CD79a, CD10, BCL6, and CD138. In the large B-cell lymphoma, the large cells did not express detectable cytoplasmic immunoglobulin light- and heavy-chains, whereas in the germinotropic lymphoproliferative disorder, the large cells expressed μ heavy chain. The present cases broaden the spectrum of HHV-EBV--copositive lymphoproliferations.

Background: The aim of this study was to analyse the biomechanical role of medial retinaculum, as a stabilising factor against lateral patellar dislocation. Materials and methods: This cadaveric-biomechanical study included the patellae of 10 cadaveric knees, which were surgically exposed and the medial retinaculum of each one was located. A stable 24.51 N force was applied to the four parts of the quadriceps, and an increasing lateral displacing force was applied to the patella, up to 5 mm dislocation. The study was repeated for 0o, 45o, and 90o of knee flexion, with the medial retinaculum intact and dissected. The Wilcoxon signed rank test was used for data analysis. A p value < 0.05 was considered as statistical significant. Results: After the dissection of medial retinaculum, the lateral displacement force was lower at every angle of knee flexion (p = 0.005, p = 0.007, p = 0.005, respectively). The lateral displacement force increased as the flexion angle increased (p = 0.005), regardless of medial retinaculum integrity. Conclusions: Medial retinaculum acts as a stabilising factor for the patella, against its lateral dislocation in lower flexion angles. Therefore, methods of surgical reinforcement or repair of medial retinaculum could provide protection against recurrent patellar dislocation.

We analyzed the expression of Jun family in relation to CD30 expression, cell proliferation and B-cell differentiation immunophenotypes [Germinal Center and non-Germinal Center] in diffuse large B-cell lymphomas (DLBCL). Expression and high expression of phosphorylated-c-Jun (p-c-Jun), JunB, JunD and CD30 (cut-off scores 20% and 50%, respectively) was found in 18/103, 49/103, 72/101 and 26/102 cases, respectively, and in 6/103, 27/103, 60/101 and 21/102 cases, respectively. The following significant positive correlations were observed: (a) JunB with cyclin A (p = 0.046), cyclin B1 (p = 0.033), cyclin E (p = 0.003), MUM-1 (p = 0.002) and CD30 (p < 0.001), (b) JunD with Ki67 (p = 0.002) and cyclin E (p = 0.014), (c) p-c-Jun with CD30 (p = 0.015), and (d) high p-c-Jun with cyclin A (p = 0.034). The positive correlation between expression of JunB, JunD and p-c-Jun and tumor cell proliferation in DLBCL, suggests that increased JunB, JunD and p-c-Jun expression may be involved in the pathogenesis of DLBCL by increasing tumor cell proliferation.

Ocular adnexal lymphomas are a group of heterogeneous neoplasms representing approximately 1–2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. The incidence of primary ocular adnexal lymphoid tumors has raised over the last decades, and this could be probably attributed to the more sophisticated diagnostic techniques. Due to the wide spectrum of clinical manifestations, ocular tissue biopsy is important in order to set a precise diagnosis based on histological, immunophenotypical and, in some cases, molecular findings. The most common subtype, which may account for up to 80% of primary ocular adnexal lymphomas, is extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue. This lymphoma is usually asymptomatic in the early phase of the disease causing a delay in the final diagnosis and prompt therapy. The pathogenesis of a proportion of these tumors has been linked to chronic inflammatory stimulation from specific infectious factors (e.g., Chlamydia psittaci) or to autoimmunity. The further improvement in diagnostic methods and the further understanding of the pathogenesis of ocular adnexal EMZL may contribute to the establishment of a more successful multidisciplinary therapeutic planning.

Purpose IL-13, TNF-α and IL-1β have various effects on lung cancer growth and death, but the signaling pathways mediating these effects have not been extensively analyzed. Therefore, the effects of IL-13, TNF-α and IL-1β alone, and in combination with Fas, on cell viability and death as well as major signaling pathways involved in these effects were investigated in A549 lung carcinoma cells. Results Using MTT and flow cytometry, IL-13, TNF-α and IL-1β pretreatment decreased Fas-induced cell death. These anti-cell death effects were attenuated by pretreatment with inhibitors of Nuclear factor-κB [NF-κB], Phoshatidylinositole-3 kinase [PI3-K], JNK, p38 and ERK1/2 pathways. Using Western blot, IL-13, TNF-α and IL-1β treated cells showed time-dependent expression of p-ERK1/2, p-p38, p-JNK, p-Akt and p-IκBα proteins, decreased IκBα protein expression, no cleavage of Caspase-3 and PARP1 proteins and no notable alterations of Fas protein. IL-13 and TNF-α treated cells showed time-dependent increase of FLIP L expression. Conclusion IL-13, TNF-α and IL-1β attenuate the pro-cell death effects of Fas on A549 cells, at least partially, by pathways involving the NF-κB, PI3-K and MAP kinases, but not by alterations of Fas protein expression. The IL-13 and TNF-α cell survival effects may also be due to increased expression of FLIP L protein.