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Background and Objectives: Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival., Materials and Methods: A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan-Meier survival analysis and Cox regression models were used to identify significant prognostic factors., Results: The Kaplan-Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves., Conclusions: The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

Introduction: Skin metastases arise in 10% of cancer patients, but standardized dermoscopy diagnostic criteria for skin metastases remain poor. This study's objective was to analyze the dermoscopy features of skin metastases from advanced systemic and cutaneous cancers., Methods: A retrospective study on 715 dermoscopy images of skin metastases from 33 patients with various primary cancers (breast, ovary, melanoma, non-melanoma skin cancer, and chronic leukemia) attending two academic centers between 2013 and 2023 was performed. Four independent observers blindly analyzed patterns, colors, vessels, and elementary lesions for each metastasis (30 parameters in total)., Results: The structureless white pattern was the most prominent indicator of cutaneous metastasis (81.26%, p < 0.001). Regardless of the primary tumor, colors pink, red, white, and tan were identified. Elementary lesions were infrequent, except for melanoma metastases that displayed dots (13.23%) and globules (11.11%). Breast cancer metastases presented: blue (41.48%) and red (34.32%) colors, irregular vessels (13.58%), and a blue-naevus pattern (22.22%). Melanoma metastases displayed: a blue-naevus pattern (61.38%), a blue color (85.71%), and a structureless-blue combination pattern (79.37%). Non-melanoma skin cancer metastases were characterized by vascular (42.11%) and angioma-like (31.58%) patterns, pink (57.89%) and red (57.89%) colors, irregular (57.89%), thin hairpin (47.37%), comma (47, 37%), and thick hairpin (26, 32%) vessels and a red, white and irregular vessels combination pattern (52, 63%). A pink structureless combination pattern was frequent (61.05%) in chronic leukemia metastases. Ovarian cancer metastases displayed a white and tan structureless combination pattern (100%) and frequently had dotted vessels (42.85%)., Conclusion: Papules and nodules with a white structureless pattern suggest skin metastases, regardless of the primary tumor. A blue structureless lesion is indicative of melanoma metastasis and a vascular pattern with irregular vessels indicates a non-melanoma skin cancer metastasis. Dermoscopy stands as a reliable non-invasive diagnostic method for suspected cutaneous metastases in patients with a known cancer history., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Simionescu, Petrică, Avram, Costache, Scurtu, Tudorache, Iorga and Grigore.)

Parotid gland pathology represents a web of differential diagnoses. There are many complex cases that require extensive diagnostic tests for a complete and correct final pathology diagnosis. Currently the official classification of parotid gland tumors extends over more than 40 subtypes. We performed a query of the PubMed database regarding the use of molecular biology tests in performing a better characterization of the tumors in specific cases. By using fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing, the team managing complex cases can offer a personalized therapeutic solution. We review the molecular differential diagnosis according to published articles in the last 5 years for many types of parotid gland tumors ranging from benign to borderline malign tumors to malign aggressive tumors. Mucoepidermoid carcinoma is a distinct subtype of parotid malignancy that was the subject of a consistent number of articles. However, the molecular biology diagnosis techniques helped more in excluding the diagnosis of mucoepidermoid carcinoma, and probably retrospectively limiting the number of cases with this final diagnosis. In Romania, the molecular biology diagnosis is available only in limited research facilities and should receive more consistent funding that will make it available on a larger scale. The novelty of this scoping review is that we propose an algorithm for molecular differential diagnosis of the tumors that could be encountered in the parotid gland.

Diagnosing cutaneous melanomas relies mainly on histopathological analysis, which, in selected cases, can be aided by immunohistochemical evaluation of conventional melanocytic markers. Nevertheless, these malignancies, particularly in metastatic settings, may display divergent differentiation with unusual histological and immunohistochemical features. In this context, we present the case of a 65-year-old male diagnosed with typical superficial spreading melanoma who developed recurrence and metastatic lesions featuring angiosarcomatous differentiation. The diagnosis of the initial tumour and the subsequently dedifferentiated lesions was confirmed by ample immunohistochemical analysis, which included several melanocytic markers, as well as mesenchymal and vascular markers. The recurrent tumour and lymph nodes metastases were completely negative for Melan-A and PRAME, and focally positive for SOX10. Additionally, they also displayed diffuse, intense positivity for CD10 and WT1 and focal positivity for CD99, ERB, and CD31. Thus, the diagnosis of primary cutaneous melanoma with recurrent and metastatic divergent angiosarcomatous differentiation was established. This occurrence is particularly rare and can pose important diagnostic challenges. Therefore, in addition to presenting this highly unusual case, we also performed a comprehensive review of the literature on divergent differentiation in melanomas.

Background and Objectives : Lichen planus of the lip (LPL) is a chronic inflammatory condition that resembles actinic cheilitis, discoid lupus erythematosus, graft-versus-host disease, and lichenoid reaction to dental materials or drugs. The purpose of this study was to conduct a literature review on lichen planus lip involvement and to report a retrospective observational study that characterises and explores the clinical, histopathological, and evolution of the lesions in a group of patients with unique involvement of LPL. Materials and Methods : Clinical data of patients diagnosed with LPL was retrieved from the medical charts of the patients referred to the Oral Pathology Department of the "Carol Davila" University of Medicine and Pharmacy. A concurrent electronic literature research was carried out using PubMed and Web of Science from 2003 to 2023. Results : Eleven patients diagnosed with unique LPL were analysed (male/female ratio was 1.75, mean age 63.64 years ± 12.52). All patients presented lesions of the lower lip; the clinical forms were atrophic (six cases) and erosive (five cases), and the histopathological exam confirmed the diagnosis. After topical treatment with corticosteroids, most of the patients had complete remission. The literature review revealed 24 studies (sixteen case reports and eight case series) which comprised 84 patients. Isolated lip involvement was reported in 17 studies, and five articles with concomitant oral lichen planus, while two articles did not mention this criterion. Conclusions : Our study brings new data on isolated lichen planus of the lip that primarily affects the lower lip with predominance in male patients. It was reported worldwide in patients between 22 and 75 years old. Topical corticosteroids were the main treatment prescribed and they usually brought remission of the lesions. Lichen planus of the lip is a challenging diagnosis for oral health practitioner providers as well as for dermatologists.

Introduction: Although the incidence and mortality rates of colorectal cancer exhibit significant variability, it remains one of the most prevalent cancers worldwide. Endeavors to prevent colorectal cancer development focus on detecting precursor lesions during colonoscopy. The diagnosis of endoscopically resected polyps relies on hematoxylin and eosin staining examination. For challenging cases like adenomatous polyps with epithelial misplacement, additional diagnostic methods could prove beneficial., Methods: This paper aims to underscore stromal changes observed in malignant polyps and polyps with pseudoinvasion, leveraging two-photon excitation microscopy (TPEM), a technique extensively employed in the medical field in recent years., Results and Discussions: Both the subjective and quantitative analysis of TPEM images revealed distinct distributions and densities of collagen at the invasion front in malignant polyps compared to areas of pseudoinvasion. TPEM holds potential in discerning true invasion in malignant polyps from pseudoinvasion, offering enhanced visualization of local stromal changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Florea, Eftimie, Glogojeanu, Hristu, Stanciu and Costache.)

Proliferative activity in cutaneous melanomas can be appreciated both histopathologically by counting mitotic figures and immunohistochemically through the Ki67 index, but the prognostic value of each method is still a matter of debate. In this context, we performed a retrospective study on 33 patients diagnosed with cutaneous melanomas between 2013 and 2018 in order to evaluate progression-free survival and overall survival. Multivariate Cox proportional hazards regression was performed by considering both clinical histopathological and immunohistochemical features. The mitotic rate was significantly independently associated with both outcomes, while the Ki67 index was not an independent prognostic factor. However, the Ki67 predictive accuracy could be improved by establishing both a cut-off value and a standardized protocol for evaluating its expression. Until these desiderata are met, the mitotic rate remains superior to the Ki67 index for predicting prognosis in cutaneous melanomas, as also has the advantage of being easily interpreted in a standard histopathological examination regardless of the pathologist's experience and with no further financial expenses. Importantly, this is one of very few articles that has shown perineural invasion to be an independent prognostic factor for both progression-free survival and overall survival in cutaneous melanomas. As a consequence, this parameter should become a mandatory feature in the histopathological evaluation of cutaneous melanomas as it can improve the identification of patients who are at high risk for disease progression., Competing Interests: The authors declare no conflicts of interest.

Liposarcomas are some of the most challenging soft tissue tumors and are subclassified into multiple subtypes with special histologic and molecular features. The peculiarities of each histopathological subtype influence the clinical behavior, management, and treatment of these neoplasms. For instance, well-differentiated liposarcomas are common soft tissue malignancies and usually display a favorable outcome. On the other hand, pleomorphic liposarcoma is the rarest, yet the most aggressive subtype of liposarcoma. This histopathological diagnosis may be challenging due to the scarce available data and because pleomorphic liposarcomas can mimic other pleomorphic sarcomas or other neoplasms of dissimilar differentiation. Nevertheless, the correct diagnosis of pleomorphic liposarcoma is of utmost importance as such patients are prone to develop local recurrences and metastases. Treatment usually consists of surgical excision along with radiotherapy and follow-up of the patients. Therefore, this review aims to assess the complex clinical, histological, and immunohistochemical features of liposarcomas in order to establish how these characteristics influence the management and prognosis of the patients, emphasizing the particularities of pleomorphic liposarcoma.

Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute of Pneumophthisiology, Bucharest, Romania. Our study focused on patients admitted in 2019 with non-small-cell lung carcinoma and associated pulmonary lesions identified through surgical resection specimens. Among the 314 included patients, multiple pulmonary nodules were observed on macroscopic examination, with 12% (N = 37) exhibiting nonmalignant etiologies upon microscopic examination. These findings underscore the challenge of preoperative staging. Patients with coexisting nonmalignant lesions were similar in age, smoking habits, and professional or environmental exposure by comparison with those who presented only malignant lesions. The presentation of coexisting malignant and nonmalignant lesions may pose difficulties in diagnosing and staging pulmonary cancer., Competing Interests: The authors declare no conflicts of interest.

Background and Objectives: The mainstay treatment of non-small-cell lung carcinoma is still surgery, but its impact on survival beyond nine years has never been reported/analysed in Romania. Therefore, we studied the clinical characteristics and the short- and long-term survival of a population of 1369 patients diagnosed and treated in a single institution, with the variables included in the database being collected retrospectively. Materials and Methods: In this paper, we aimed to study a number of factors that might influence prognosis and survival in non-small bronchopulmonary carcinoma. Consequently, we analysed a series of parameters such as the age of patients, their sex, the histopathological type, the tumour stage, the presence of bronchial invasion, and the completeness of surgical resection. Results: All patients underwent major lung resection for curative purposes (pneumonectomy, lobectomy, or bilobectomy) between January 2015 and January 2023. The vital status of patients included in the study was obtained by checking the DGEP (General Directorate for Persons Record) database and verifying the reporting of "non-deceased" by the hospital administrative database, as well as by telephone interviews (with patients or their relatives). On univariate analysis, predictors of worse survival were the following: male sex (the hazard of death was 1.54 times higher in men); pT (compared to pT1 tumours, pT2 tumours have a 1.60 times higher hazard of death, pT3 tumours have a 2.16 times higher hazard, and pT4 tumours have a 2.97 times higher hazard); maximum tumour size (a 10 mm increase in tumour size is associated with a 10% increase in the hazard of death); the degree of differentiation (compared to patients with G1 tumours, those with G3 tumours have a 2.16 times higher hazard of death); resectability (compared to R0, R1 B+ has a 1.84 times higher hazard of death, R1 V+ has a 1.82 times higher hazard of death, and R1 B+&V+ has a 2.40 times higher hazard of death). Conclusions: As a result, long-term survival can be achieved after complete surgery for NSCLC, and factors that classically predict overall survival suggest that both the initial tumour aggressiveness and host characteristics act beyond the period usually considered in oncology.

Lung cancer is among the most common oncological diseases regarding incidence and mortality, with most of these having epithelial origins. Pathological reporting of these tumors is conducted according to the 5th edition of the World Health Organisation (WHO) classification of thoracic tumours. This study aims to draw the pathologist's attention to four rare, atypical microscopic aspects that some of the most common types of lung malignancies reveal upon standard evaluation (hematoxylin-eosin stain) that make histopathological diagnosis challenging: acantholytic, pseudoangiosarcomatous, signet ring cell, and clear cell features. Each of these aspects was exemplified by a case diagnosed in the pathology department of the "Marius Nasta" Institute. Furthermore, we analyzed the classification dynamics of different WHO editions and used PubMed to review articles written in English and published in the last eleven years on this subject. Pathologists should be familiar with these unusual aspects to avoid misdiagnoses and to ensure the correct classification of tumors, which is extremely important because these tumor phenotypes have been associated with specific molecular alterations and a worse clinical evolution. There is a need to clarify the histogenesis and associated genetic mutations, given the fact that the rarity of these tumor phenotypes makes their study difficult. Some authors consider these to be overlapping entities; however, we do not encourage this, as they may exhibit different prognoses and various molecular alterations with important therapeutic implications. The signet ring cell feature was associated with ALK rearrangement in lung adenocarcinoma; thus, these patients can benefit from tailored therapy with ALK-tyrosine kinase inhibitors (ALK-TKI). Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.

Cutaneous melanoma (CM) is an increasingly significant public health concern. Due to alarming mortality rates and escalating incidence, it is crucial to understand its etiology and identify emerging biomarkers for improved diagnosis and treatment strategies. This review aims to provide a comprehensive overview of the multifactorial etiology of CM, underscore the importance of early detection, discuss the molecular mechanisms behind melanoma development and progression, and shed light on the role of the potential biomarkers in diagnosis and treatment. The pathogenesis of CM involves a complex interplay of genetic predispositions and environmental exposures, ultraviolet radiation exposure being the predominant environmental risk factor. The emergence of new biomarkers, such as novel immunohistochemical markers, gene mutation analysis, microRNA, and exosome protein expressions, holds promise for improved early detection, and prognostic and personalized therapeutic strategies.

Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.

Considering the increase in life expectancy in the general population and the need for a more active lifestyle, total hip arthroplasty has become an absolutely necessary surgical intervention to maintain these desired results. Along with the evolution of medicine and the increase in the quality and performance of the materials used to make prostheses, the number of patients who benefit from total hip replacement is constantly increasing, and proportionally, the number of patients who will require revision arthroplasty is increasing. Before discussing the need for hip arthroplasty revision, it is necessary to carry out a rigorous clinical and imaging examination for differential diagnosis with other pathologies such as low back pain, the presence of bone or soft tissue tumors, arterial occlusions and claudication, or other systemic diseases. One of the biggest challenges for the orthopedic surgeon in planning a hip revision is the compensation of the remaining acetabular bone defect, either as a result of the osteolysis process or following the process of removing the acetabular component, which in some cases can lead to severe bone loss that is difficult to anticipate in the preoperative planning. In this paper, we will present the short-term results of the use of reinforcement cages fixed with screws and cemented retentive acetabular cups in the case of hip revisions with extensive bone loss. The discussions that derive from the presented series of cases are related to the use of reinforcement cages, which are based on the principle of primary stability obtained with the help of screw fixation but whose risk of osteolysis and implant fixation damage is greater than in the case of implants that also associate biological integration at bone level. The use of reinforcement cages together with the retentive acetabular cup in the case of elderly patients with associated comorbidities, a moderate level of physical activity, and severe muscle insufficiency at the hip level as a result of not using the affected pelvic limb is still a viable solution that allows the patient to walk immediately after the surgery, avoiding the risk of dislocation (especially in patients who use the posterolateral approach) and avoiding morbidity induced by prolonged bed rest., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Cursaru et al.)

This study offers a thorough analysis of tibial pilon fractures, accounting for patient compliance, diverse treatment options, and soft tissue implications. The article discusses varied treatment pathways, ranging from single-stage interventions to two-stage methods for open fractures by presenting seven clinical cases. The emphasis is on the intricate interplay of trauma intensity, bone damage, and adjacent soft tissue in dictating treatment plans and patient outcomes. The challenges posed by non-compliant patients rejecting advised treatments are underscored, illuminating the inherent risks. Drawing from varied patient demographics, comorbidities, and fracture types, a comprehensive guide for clinicians emerges. The findings underscore the importance of a tailored, patient-centric approach, considering the multifaceted nature of ankle fractures, local soft tissue health, patient's overall well-being, and their adherence to the proposed treatment regimen., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Cursaru et al.)

In an effort to obtain porous scaffolds with improved mechanical properties and biocompatibility, the current study discusses nanocomposite materials based on poly(propylene fumarate)/ N -vinyl pyrrolidone(PPF/NVP) networks reinforced with polymer-modified graphene oxide (GO@PPF). The GO@PPF nanofiller was synthesized through a facile and convenient surface esterification reaction, and the successful functionalization was demonstrated by complementary techniques such as FT-IR, XPS, TGA and TEM. The PPF/NVP/GO@PPF porous scaffolds obtained using NaCl as a porogen were further characterized in terms of morphology, mechanical properties, sol fraction, and in vitro degradability. SEM and nanoCT examinations of NaCl-leached samples revealed networks of interconnected pores, fairly uniform in size and shape. We show that the incorporation of GO@PPF in the polymer matrix leads to a significant enhancement in the mechanical properties, which we attribute to the formation of denser and more homogenous networks, as suggested by a decreased sol fraction for the scaffolds containing a higher amount of GO@PPF. Moreover, the surface of mineralized PPF/NVP/GO@PPG scaffolds is uniformly covered in hydroxyapatite-like crystals having a morphology and Ca/P ratio similar to bone tissue. Furthermore, the preliminary biocompatibility assessment revealed a good interaction between PPF/PVP/GO@PPF scaffolds and murine pre-osteoblasts in terms of cell viability and proliferation.

Pancreatic heterotopy is a rare entity defined as the presence of abnormally located pancreatic tissue without any anatomical or vascular connection to the normal pancreas. Heterotopic pancreatic tissue can be found in various regions of the digestive system, such as the stomach, duodenum, and upper jejunum, with the less commonly reported location being the gallbladder. Gallbladder pancreatic heterotopia can be either an incidental finding or diagnosed in association with cholecystitis. Pancreatitis of the ectopic tissue has also been described. In this context, we report three cases of heterotopic pancreatic tissue in the gallbladder with different types of pancreatic tissue according to the Heinrich classification. One patient was a 24-year-old male who presented with acute pancreatitis symptoms and an ultrasonographical detected mass in the gallbladder, which proved to be heterotopic pancreatic tissue. The other two cases were female patients aged 24 and 32, respectively, incidentally diagnosed on histopathological examination after cholecystectomy for symptomatic cholelithiasis. Both cases displayed chronic cholecystitis lesions; one of them was also associated with low grade dysplasia of the gallbladder. Although a rare occurrence in general, pancreatic heterotopia should be acknowledged as a possible incidental finding in asymptomatic patients as well as a cause for acute cholecystitis or pancreatitis.

Purpose Secondary peritonitis is still one of the most important causes of severe sepsis in the world; therefore, it is of utmost importance to identify biomarkers that could be employed for the purpose of selecting patients at high risk for developing life-threatening complications after emergency surgery. In view of this quest, our study seeks to reveal the possible role for serum and peritoneal concentrations of selected biomarkers, specifically presepsin, procalcitonin, monocyte chemoattractant protein-1 (MCP-1), high mobility group box 1 protein (HMGB-1) and interleukins (IL-6, -8, -10), in early prediction of sepsis and septic multiorgan failure for patients with secondary peritonitis. Methods We prospectively observed 32 selected patients with secondary peritonitis that underwent emergency surgery. Blood and peritoneal fluid samples were drawn at the time of surgery (T0), and after that, blood samples were taken at 24 (T1) and 48 (T2) hours postoperatively. Cytokines concentrations were determined using a sandwich enzyme-linked immunosorbent assay (ELISA), a non-competitive variant, both in peritoneal fluid and serum. For determining whole blood concentration of presepsin and procalcitonin, PATHFAST™ assays (Polymedco, Cortlandt, New York) were used, based on the principle of non-competitive chemiluminescent enzyme immune-assay (CLEIA). The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of University Emergency Hospital Bucharest (no. 40325/6 April 2023). Results We found significant elevations in the peritoneal concentrations of interleukins 6, 8, 10, HMGB-1, and MCP-1 in all patients with secondary peritonitis at the moment of surgery; however, no clear correlation could be made based on this data with patient evolution. With regards to blood concentrations of the aforementioned serum cytokines and presepsin, procalcitonin (as already established markers of sepsis), our results showed good predictive value of presepsin for developing sepsis and septic multiorgan failure from the first hours in this patient category. All other biomarkers, despite having higher concentrations than baseline, in particular at 24-48 hours after surgery, had unpredictable dynamics that couldn't be correlated with the severity of the disease. Conclusion Cytokine production is the mainstay in developing sepsis and septic multiorgan failure in patients with secondary peritonitis; therefore, studying the dynamics of said cytokines seems of interest in finding tools to predict the development of sepsis or sepsis-related mortality. However, at the time, there seemed to be no clear correlation between the values of these cytokines and the development of complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dumitrascu et al.)

Today, the number of people affected by gonarthrosis symptoms is increasing proportionally. Total knee arthroplasty (TKA) is a successful intervention that aims to reduce pain and restore knee function. However, studies have shown that active young patients still have limitations in performing activities such as skiing, golfing, surfing, and dancing. Over the last few years, total knee arthroplasty has undergone significant changes. Most of the modern TKA implants are designed to reproduce the normal biomechanics of the knee joint, mimicking the physiological pattern with greater compliance in the medial compartment between the tibial insert and femoral condyle and less congruence on the lateral side. Unfortunately, functional outcomes are compromised in approximately half of TKA patients. This loss may be caused by the abnormal kinematics and inherent instability of many contemporary implants. The proper alignment of the femoral component during TKA is a crucial step that influences postoperative results. The position of the femoral component in the axial plane is responsible for flexion stability, knee joint kinematics, flexion alignment, and patellar tracking. The main goal when choosing a type of prosthesis is to achieve an adequate recovery that leads to an improvement in mobility and an increase in the efficiency of the quadriceps., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Cretu et al.)

Diagnosing cutaneous melanoma is usually straightforward based on these malignancies' histopathological and immunohistochemical features. Nevertheless, melanomas can imitate various other neoplasms, sometimes lacking the expression of conventional melanocytic markers and expressing non-melanocytic ones. Furthermore, divergent differentiation is more often encountered in metastatic melanomas and is still poorly described in primary cutaneous melanomas, and little is known about these patients' prognosis and therapeutic approach. Therefore, we reviewed the literature on undifferentiated/dedifferentiated cutaneous melanomas, and we discuss the histological, immunohistochemical, and molecular profiles of undifferentiated/dedifferentiated cutaneous melanomas to understand these peculiar lesions better and improve their diagnostic algorithm. In addition to this, we also discuss how different genetic mutations may influence prognosis and become potential therapeutic targets.

The number of individuals who experience the symptoms of gonarthrosis rises proportionally as life expectancy rises and the population becomes more active. The purpose of total knee arthroplasty (TKA) is to lessen pain and restore knee function, and it has a high success rate. The restoration of patellar tracking in addition to the proper alignment of the femoral and tibial components contributes to the success of the arthroplasty and the patient's happiness. Replacement of the knee is not an easy process. One of the major objectives of total knee replacement is to achieve the proper rotation of the femoral components. A critical step that affects postoperative outcomes in total knee arthroplasty is the correct alignment of the femoral component. The axial plane of the femoral component is to blame for flexion stability, knee joint kinematics, flexion alignment, and patellar tracking. The patella is the largest sesamoid bone in the human body, and its major role is to enhance the quadriceps' moment arm, which allows the knee to expand. The distribution of patellofemoral compressive pressures during knee flexion and the centralization of the quadriceps muscles' multidirectional pull during extension are both critical functions of the patella. After primary knee arthroplasty, there are 8% more cases of anterior knee discomfort than there were before. Whether or not the patella was resurfaced, patients with primary TKA experience anterior knee discomfort. Patella baja is caused by excessive joint line elevation, which causes persistent overload and discomfort. The design of the TKR might have an impact on postoperative patellofemoral problems. After TKR, patellofemoral maltracking and patellar dislocation are often caused by surgical mistakes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Iordache et al.)

Dedifferentiated liposarcoma of the deep soft tissue of the lower extremities is an infrequent finding. Myxoid liposarcoma is considered the most common soft tissue neoplasia arising in this anatomic region. Divergent differentiation usually occurs within well-differentiated liposarcoma and is exceedingly rare in a myxoid liposarcoma. We report a 32-year-old man who developed a dedifferentiated liposarcoma of the thigh on the background of a pre-existing myxoid liposarcoma. The gross examination of the surgical specimen showed a 11/7/2 cm tumour mass with solid tan-grey areas and focal myxoid degeneration. The microscopic examination revealed a malignant lipogenic proliferation, containing round cells with hyperchromatic nuclei and atypical lipoblasts, confined to the basophilic stroma with a myxoid aspect. Abrupt transition towards a hypercellular, non-lipogenic area consisting of highly pleomorphic spindle cells with atypical mitotic figures was also noted. Immunohistochemical staining was performed. Tumour cells in the lipogenic area were intensely positive for S100 and p16, and CD34 staining highlighted an arborizing capillary network. The dedifferentiated tumour areas showed positive MDM2 and CDK4 staining within neoplastic cells, with the Ki 67 proliferation marker expressed in approximately 10% of the cells. Wild-type TP53 protein expression pattern was documented. Thus, the diagnosis of a dedifferentiated liposarcoma was established. This paper aims to provide further knowledge about liposarcomas with divergent differentiation at peculiar locations, emphasizing the importance of histopathologic examination and immunohistochemical analysis for establishing the diagnosis and assessing the therapeutic response and prognosis of this condition.

Ankylosing spondylitis (AS) mainly belongs to the group of axial spondylitis. It is a chronic inflammatory disease that primarily affects the spine, but can also affect peripheral joints. It is characterized by inflammatory lower back pain and morning stiffness. Tuberculosis is still a cause of morbidity and mortality in developing countries. Management of patients with AS consists of patient education, spinal mobility exercises, non-steroidal anti-inflammatory drugs (NSAIDs), corticotherapy, and anti-tumor necrosis factor alpha (TNF-α) biological agents. Anti-TNF-α biological agents have changed the prognosis of patients with AS. They contain anti-TNF-α monoclonal antibodies (golimumab, infliximab, adalimumab, certolizumab) and the soluble TNF-α receptor (etanercept). Hip and knee involvement is common in patients with AS, as evidenced in radiographs as bone erosion and joint space narrowing. The patient may have severe pain, stiffness, and loss of mobility, and the treatment involves surgery for joint arthroplasty. We present the case of a 63-year-old patient with axial spondyloarthritis who was treated with infliximab and developed cerebral tuberculosis after three years of biological therapy. The purpose of the study is to determine the possibility of resuming biological therapy at the time of AS reactivation, given the long-term treatment and adverse reactions of cortisone therapy (aseptic necrosis of the femoral head)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Cretu et al.)

Periprosthetic joint infection (PJI) after arthroplasty is a major complication, which requires significant resources, resulting in high costs for the medical system. In recent years, significant progress has been made in the diagnosis and treatment of periprosthetic infections, the identification of the pathogen being the central element in the establishment of targeted antibiotic therapy. Next-generation sequencing (NGS) or metagenomic NGS (mNGS) represents a promising, fast alternative, with increased specificity and sensitivity compared to identification methods using conventional culture media, thus enabling an increased rate of identification of pathogenic microorganisms and antibiotic resistance genes (ARG). The purpose of this article was to highlight new molecular diagnostic methods for periprosthetic joint infections and their involvement in treatment efficiency. NGS technologies are cutting-edge techniques that may challenge the PJI diagnostic model., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Cretu et al.)

Objectives: To assess the clinicopathological characteristics of a cohort of patients with oral leukoplakia (OL) managed in a Romanian dental hospital and to evaluate the risk of malignant transformation (MT)., Materials and Methods: We conducted a hospital-based retrospective study using the clinical charts of patients diagnosed with OL that had complete clinical and histopathological evaluation followed up for 1-16 years., Results: From 120 included patients, 68 (56.7%) were females, and 71 (59.2%) were current smokers. The homogeneous form was present in 60% of cases; the buccal mucosa was the most frequently involved site. MT was observed in 9 cases, which was more common in females and in those with dysplastic leukoplakia. A significant statistical association was found between MT and dysplasia grade (χ 2 test: p = 0.007). MT occurred during a mean interval of time 75 months in both treated and non-treated patients., Conclusions: In this leukoplakia cohort, most of the lesions encountered were in smokers, clinically homogeneous and 62.5% proved histologically benign. But despite the clinically benign appearance of leukoplakia, tissue diagnosis of some cases was carcinoma. The results of the current study advocate the necessity for biopsy even in apparently homogeneous, clinically benign lesions. The malignization rate was 7.5%; two-thirds were nonhomogeneous lesions., (© 2022 Wiley Periodicals LLC.)

Background and Objectives : Melorheostosis, also referred to in the literature as Leri's disease, is an unusual mesenchymal dysplasia with the clinical appearance of benign sclerosing bone dysplasia; it frequently occurs in late adolescence. Any bone in the skeletal system can be affected by this disease, though the long bones of the lower extremities are the most common, at any age. Melorheostosis has a chronic evolution, and symptoms are usually absent in the early stages. The etiopathogenesis is still unknown, however, numerous theories have been proposed that could explain the appearance of this lesion formation. An association with other benign or malignant bone lesions is also possible, and associations with osteosarcoma, malignant fibrous histiocytoma, or Buschke-Ollendorff syndrome have also been reported. There have also been reported cases of the malignant transformation of a pre-existing melorheostosis lesion into malignant fibrous histiocytoma or osteosarcoma. The diagnosis of melorheostosis can be made only based on radiological images, but, due to its polymorphism, additional imaging investigations are often necessary and sometimes only a biopsy can establish a definite diagnosis. Because there are currently no guidelines for treatment based on scientific evidence, due to the low number of cases diagnosed worldwide, our objective was to highlight the early recognition and specific surgical treatments for better prognosis and outcomes. Materials and Methods : We conducted a review of the literature consisting of original papers, case reports, and case series and presented the clinical and paraclinical characteristics of melorheostosis. We aimed to synthesize the treatment methods available in the literature as well as determine possible future directions related to the treatment of melorheostosis. Furthermore, we presented the results of a case of femoral melorheostosis admitted to the orthopedics department of the University Emergency Hospital of Bucharest in a 46-year-old female patient with severe pain in the left thigh and limitation of joint mobility. Following the clinical examination, the patient complained of pain in the middle third of the left thigh in the antero-medial compartment; the pain appeared spontaneously and was aggravated during physical activity. The pain started about two years prior, but the patient experienced complete pain relief after the administration of non-steroidal anti-inflammatory drugs. In the last six months, the patient presented an increase in pain intensity without significant improvement following the administration of non-steroidal anti-inflammatory drugs. The patient's symptoms were mainly determined by the increase in the volume of the tumor and the mass effect on the adjacent tissues, especially on the vessels and the femoral nerve. The CT examination and bone scintigraphy showed a unique lesion in the middle third of the left femur and no oncological changes in the thoracic, abdominal, and pelvic regions; however, at the level of the femoral shaft, there was a localized cortical and pericortical bone lesion formation that surrounded approximately 180 degrees of the femoral shaft (anterior, medial, and lateral). It had a predominantly sclerotic structure but was associated with lytic areas with thickening of the bone cortex and areas of periosteal reaction. The next therapeutic gesture was to perform an incisional biopsy using a lateral approach at the level of the thigh. The histopathological result supported the diagnosis of melorheostosis. Additionally, immunohistochemical tests completed the data obtained after the microscopic examination through the classic histopathological technique The patient was discharged and included in a full medical recovery program for eight weeks in a specialized medical center, during which she also received analgesic treatment in maximum doses, but without improvement regarding her symptoms. Taking into account the chronic evolution of the pain, the complete lack of response to conservative treatment after eight weeks, and the lack of treatment guidelines in the case of melorheostosis, a surgical approach needed to be considered. The surgical option in this case, considering the circumferential location of the lesion at the level of the femoral diaphysis, was a radical resection. The surgical approach consisted of segmental resection to healthy bone tissue and reconstruction of the remaining defect with a modular tumoral prosthesis. At the 45-day postoperative control, the patient no longer complained of pain in the operated-on limb and was mobile with full support without gait difficulties. The follow-up period was one year, and the patient presented complete pain relief and a very good functional outcome. Results: In the case of asymptomatic patients, conservative treatment seems to be a good option with optimal results. However, for benign tumors, it remains unclear whether radical surgery is a viable option. Conclusions : Melorheostosis remains an incompletely understood disease, given the limited number of cases worldwide, and thus, there is a lack of clinical guidelines regarding specialized treatment.

Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma progression, we have compared gene and small non-coding RNA expression profiles from cell lines derived from primary melanoma (MelJuSo), lymph node metastasis (MNT-1) and brain metastasis (VMM1), representing distinct stages of malignant progression. Our preliminary results highlighted the aberrant regulation of molecular markers involved in several processes that aid melanoma progression and metastasis development, including extracellular matrix remodeling, migratory potential and angiogenesis. Moreover, bioinformatic analysis revealed potential targets of the microRNAs of interest. Confocal microscopy and immunohistochemistry analysis were used for validation at the protein level. Exploring the molecular landscape of melanoma may contribute to the achievement of future efficient targeted therapy, as well as better prevention, diagnosis and clinical management.

Paraneoplastic pemphigus (PNP) is a rare bullous disease with a polymorphic presentation. Diagnosis can be difficult because it can mimic other bullous diseases, while the underlying neoplasm may be completely asymptomatic. We present the case of a 19-year-old female with a four-year history of exclusively oral bullous lesions, mimicking pemphigus vulgaris, before the diagnosis of a retroperitoneal Castleman disease. While PNP is a severe and sometimes deadly condition, our patient had a mild and long evolution on minimal treatment, with complete resolution after tumor excision. Practitioners should be aware of PNP in young patients presenting with bullous disease and should conduct prompt systemic investigations in refractory or long-evolving cases, even when PNP diagnostic criteria are not fully met., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Grigore et al.)

An unusual case of a 52-year-old female with two metachronous melanomas is presented. An atypical fast-growing nodular melanoma appeared 18 months after the complete excision of an in situ melanoma and one month afterward a SARS-CoV-2 infection. Intra-nodal melanocytic proliferations were identified during lymph node assessment, raising important diagnostic and prognostic concerns. No melanoma susceptibility genes were found. This case report raises the question about the COVID-19 immunosuppression effect on the tumor microenvironment and the oncogenic potential of SARS-CoV-2. It also highlights the importance of clinical follow-up in melanoma patients, which was significantly delayed during the COVID-19 pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Avram et al.)

During the past decade, researchers have investigated the molecular mechanisms of breast cancer initiation and progression, especially triple-negative breast cancer (TNBC), in order to identify specific biomarkers that could serve as feasible targets for innovative therapeutic strategies development. TNBC is characterized by a dynamic and aggressive nature, due to the absence of estrogen, progesterone and human epidermal growth factor 2 receptors. TNBC progression is associated with the dysregulation of nucleotide-binding oligomerization domain-like receptor and pyrin domain-containing protein 3 (NLRP3) inflammasome, followed by the release of pro-inflammatory cytokines and caspase-1 dependent cell death, termed pyroptosis. The heterogeneity of the breast tumor microenvironment triggers the interest of non-coding RNAs' involvement in NLRP3 inflammasome assembly, TNBC progression and metastasis. Non-coding RNAs are paramount regulators of carcinogenesis and inflammasome pathways, which could help in the development of efficient treatments. This review aims to highlight the contribution of non-coding RNAs that support inflammasome activation and TNBC progression, pointing up their potential for clinical applications as biomarkers for diagnosis and therapy.

Magnetic materials and magnetic stimulation have gained increasing attention in tissue engineering (TE), particularly for bone and nervous tissue reconstruction. Magnetism is utilized to modulate the cell response to environmental factors and lineage specifications, which involve complex mechanisms of action. Magnetic fields and nanoparticles (MNPs) may trigger focal adhesion changes, which are further translated into the reorganization of the cytoskeleton architecture and have an impact on nuclear morphology and positioning through the activation of mechanotransduction pathways. Mechanical stress induced by magnetic stimuli translates into an elongation of cytoskeleton fibers, the activation of linker in the nucleoskeleton and cytoskeleton (LINC) complex, and nuclear envelope deformation, and finally leads to the mechanical regulation of chromatin conformational changes. As such, the internalization of MNPs with further magnetic stimulation promotes the evolution of stem cells and neurogenic differentiation, triggering significant changes in global gene expression that are mediated by histone deacetylases (e.g., HDAC 5/11), and the upregulation of noncoding RNAs (e.g., miR-106b~25). Additionally, exposure to a magnetic environment had a positive influence on neurodifferentiation through the modulation of calcium channels' activity and cyclic AMP response element-binding protein (CREB) phosphorylation. This review presents an updated and integrated perspective on the molecular mechanisms that govern the cellular response to magnetic cues, with a special focus on neurogenic differentiation and the possible utility of nervous TE, as well as the limitations of using magnetism for these applications.

The field of tissue engineering is constantly evolving due to the fabrication of novel platforms that promise to stimulate tissue regeneration in the scenario of accidents. Here, we describe the fabrication of fibrous nanostructured substrates based on fish gelatin (FG) and enriched with graphene oxide (GO) and magnetic nanoparticles (MNPs) and demonstrate its biological properties in terms of cell viability and proliferation, cell adhesion, and differentiation. For this purpose, electrospun fibers were fabricated using aqueous precursors containing either only GO and only MNP nanospecies, or both of them within a fish gelatin solution. The obtained materials were investigated in terms of morphology, aqueous media affinity, tensile elasticity, and structural characteristics. The biological evaluation was assessed against adipose-derived stem cells by MTT, LDH, Live/Dead assay, cytoskeleton investigation, and neuronal trans -differentiation. The results indicate an overall good interaction and show that these materials offer a biofriendly environment. A higher concentration of both nanospecies types induced some toxic effects, thus 0.5% GO, MNPs, and GO/MNPs turned out to be the most suitable option for biological testing. Moreover, a successful neuronal differentiation has been shown on these materials, where cells presented a typical neuronal phenotype. This study demonstrates the potential of this scaffold to be further used in tissue engineering applications.

Lung cancer ranks second worldwide after breast cancer and third in Europe after breast and colorectal cancers when both sexes and all ages are considered. In this context, the aim of this study was to emphasize the power of dual analysis of the molecular profile both in tumor tissue and plasma by NGS assay as a liquid biopsy approach with impact on prognosis and therapy modulation in NSCLC patients. NGS analysis was performed both from tissue biopsies and from cfNAs isolated from peripheral blood samples. Out of all 29 different mutations detectable by both NGS panels (plasma and tumor tissue), seven different variants (24.13%; EGFR L858R in two patients, KRAS G13D and Q61H and TP53 G244D, V197M, R213P, and R273H) were detected only in plasma and not in the tumor itself. These mutations were detected in seven different patients, two of them having known distant organ metastasis. Our data show that NGS analysis of cfDNA could identify actionable mutations in advanced NSCLC and, therefore, this analysis could be used to monitor the disease progression and the treatment response and even to modulate the therapy in real time.

Second harmonic generation microscopy (SHG) is generally acknowledged as a powerful tool for the label-free three-dimensional visualization of tissues and advanced materials, with one of its most popular applications being collagen imaging. Despite the great need, progress in super-resolved SHG imaging lags behind the developments reported over the past years in fluorescence-based optical nanoscopy. In this work, we demonstrate super-resolved re-scan SHG, qualitatively and quantitatively showing on collagenous tissues the available resolution advantage over the diffraction limit. We introduce as well super-resolved re-scan two-photon excited fluorescence microscopy, an imaging modality not explored to date.

Liver fibrosis can develop on the background of hyperglycemia in diabetes mellitus. However, xenobiotic-related factors may accelerate diabetes-associated liver fibrosis. In this study, we aimed to assess the antfibrotic effect of ADSC and HGF therapy and to establish the cellular and molecular mechanisms through in vitro and in vivo experiments. In vitro, TGF-β1-activated hepatic stellate cells (HSCs) were cocultured with ADSCs or HGF, and the expression of several fibrosis markers was investigated. The antifibrotic effect of the ADSCs, HGF, and ADSCs supplemented with HGF was further assessed in vivo on diabetic mice with liver fibrosis experimentally induced. In vitro results showed the inhibition of HSC proliferation and decrease in fibrogenesis markers. Coadministration of ADSCs and HGF on diabetic mice with liver fibrosis enhanced antifibrotic effects confirmed by the downregulation of Col I, α-SMA, TGF-β1, and Smad2, while Smad7 was upregulated. Moreover, stem cell therapy supplemented with HGF considerably attenuated inflammation and microvesicular steatosis, decreased collagen deposits, and alleviated liver fibrosis. In conclusion, the HGF-based ADSC therapy might be of interest for the treatment of liver fibrosis in diabetic patients, consecutive aggression exerts by different environmental factors.

As bone diseases and defects are constantly increasing, the improvement of bone regeneration techniques is constantly evolving. The main purpose of this scientific study was to obtain and investigate biomaterials that can be used in tissue engineering. In this respect, nanocomposite inks of GelMA modified with hydroxyapatite (HA) substituted with Mg and Zn were developed. Using a 3D bioprinting technique, scaffolds with varying shapes and dimensions were obtained. The following analyses were used in order to study the nanocomposite materials and scaffolds obtained by the 3D printing technique: Fourier transform infrared spectrometry and X-ray diffraction (XRD), scanning electron microscopy (SEM), and micro-computed tomography (Micro-CT). The swelling and dissolvability of each scaffold were also studied. Biological studies, osteopontin (OPN), and osterix (OSX) gene expression evaluations were confirmed at the protein levels, using immunofluorescence coupled with confocal microscopy. These findings suggest the positive effect of magnesium and zinc on the osteogenic differentiation process. OSX fluorescent staining also confirmed the capacity of GelMA-HM5 and GelMA-HZ5 to support osteogenesis, especially of the magnesium enriched scaffold.

Urticarial vasculitis (UV) is an uncommon condition characterized by recurrent episodes of urticarial lesions and angioedema and the pathological features of leukocytoclastic vasculitis. UV divides into two subgroups based on the level of serum complement. Usually, patients with hypocomplementemia experience internal organ involvement and an unfavorable prognosis. We report the case of a 33-year-old woman with a history of hepatitis B infection and autoimmune thyroiditis who developed hypocomplementemic urticarial vasculitis with recurrent angioedema and arthralgia. Complete remission was achieved using dapsone in monotherapy. We suggest dapsone as a potential treatment of choice for hypocomplementemic urticarial vasculitis. This clinical case emphasizes the need for urticarial vasculitis treatment guidelines., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Scurtu et al.)

(1) Background: The prevention of critical situations is a key ability in medicine. Hip ultrasound for neonates is a standard procedure to prevent later critical outcomes, such as hip dysplasia. Additionally, the SARS-CoV-2 pandemic has put worldwide stress upon healthcare units, resulting often in a lack of sufficient medical personnel. This work aims to develop solutions to ease and speed up the process of coming to a correct diagnosis. (2) Methods: Traditional medical procedures are envisaged, but they are enhanced to reduce diagnosing errors due to the movements of the neonates. Echographic noise filtering and contrast correction methods are implemented the Hyperanalytic Wavelet Transform, combined with an adaptive Soft Thresholding Filter. The algorithm is tailored to infants' structure and is tested on real ultrasounds provided by the "Victor Babes" University of Medicine and Pharmacy. Denoising and contrast correction problems are targeted. (3) Results: In available clinical cases, the noise affecting the image was reduced and the contrast was enhanced. (4) Discussion: We noticed that a significant amount of noise can be added to the image, as the patients are neonates and can hardly avoid movements. (5) Conclusions: The algorithm is personalized with no fixed reference value. Any device easing the clinical procedures of physicians has a practical medical application.

Spontaneous regression of malignant melanoma was first reported over a century ago. Clinically, areas of blue or grey colouration in lesions may be indicative of regression. Dermoscopy is a very useful tool for diagnosing regression. An important criterion is the blue-white scar. About 10-35% of excised melanomas show features of regression histopathologically. We present a case of regressing melanoma, with clinical and dermoscopic features suggesting a collision tumour, diagnosed histopathologically. This case might improve our knowledge of the potential clinical manifestations, and the biology, of regressing melanoma., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Nwabudike et al.)

Second harmonic generation (SHG) microscopy is acknowledged as an established imaging technique capable to provide information on the collagen architecture in tissues that is highly valuable for the diagnostics of various pathologies. The polarization-resolved extension of SHG (PSHG) microscopy, together with associated image processing methods, retrieves extensive image sets under different input polarization settings, which are not fully exploited in clinical settings. To facilitate this, we introduce PSHG-TISS, a collection of PSHG images, accompanied by additional computationally generated images which can be used to complement the subjective qualitative analysis of SHG images. These latter have been calculated using the single-axis molecule model for collagen and provide 2D representations of different specific PSHG parameters known to account for the collagen structure and distribution. PSHG-TISS can aid refining existing PSHG image analysis methods, while also supporting the development of novel image processing and analysis methods capable to extract meaningful quantitative data from the raw PSHG image sets. PSHG-TISS can facilitate the breadth and widespread of PSHG applications in tissue analysis and diagnostics., (© 2022. The Author(s).)

Organ-on-chips (OOCs) are microfluidic devices used for creating physiological organ biomimetic systems. OOC technology brings numerous advantages in the current landscape of preclinical models, capable of recapitulating the multicellular assemblage, tissue-tissue interaction, and replicating numerous human pathologies. Moreover, in cancer research, OOCs emulate the 3D hierarchical complexity of in vivo tumors and mimic the tumor microenvironment, being a practical cost-efficient solution for tumor-growth investigation and anticancer drug screening. OOCs are compact and easy-to-use microphysiological functional units that recapitulate the native function and the mechanical strain that the cells experience in the human bodies, allowing the development of a wide range of applications such as disease modeling or even the development of diagnostic devices. In this context, the current work aims to review the scientific literature in the field of microfluidic devices designed for urology applications in terms of OOC fabrication (principles of manufacture and materials used), development of kidney-on-chip models for drug-toxicity screening and kidney tumors modeling, bladder-on-chip models for urinary tract infections and bladder cancer modeling and prostate-on-chip models for prostate cancer modeling.

Introduction: There is an immune response after major surgery and inflammatory complications following complex surgery have a direct impact on morbidity and mortality. Currently, we do not have clinical tools to predict in which subset of patients a major complication will occur. The aim of this study was to evaluate the immediate dynamics of C-reactive protein (CRP), presepsin and procalcitonin in patients in which esophagectomy was performed either through video assisted thoracic surgery (VATS) or open approach. Methods: We conducted a prospective study on 27 patients with a mean age of 61.48 +-6.80 years, 13 patients with VATS and 14 with open approach, most of the patients were on stage III esophageal cancer (81%) and in all cases neoadjuvant treatment was performed. Results: There were increased levels of CRP, presepsin and procalcitonin after both arms of the study with significantly higher values for the open approach and with the same dynamic curves. In 3 cases there were extremely elevated levels of procalcitonin in the absence of a septic complication, in all cases a major complication occurred. Conclusion: Video assisted thoracoscopic esophageal mobilization induces a less immune response, even with the association of laparotomy. An elevated postoperative procalcitonin level can be an early indicator of a major postoperative complication., (Celsius.)

Colorectal cancer (CRC) is the second most frequently diagnosed type of cancer and a major worldwide public health concern. Despite the global efforts in the development of modern therapeutic strategies, CRC prognosis is strongly correlated with the stage of the disease at diagnosis. Early detection of CRC has a huge impact in decreasing mortality while pre-lesion detection significantly reduces the incidence of the pathology. Even though the management of CRC patients is based on robust diagnostic methods such as serum tumor markers analysis, colonoscopy, histopathological analysis of tumor tissue, and imaging methods (computer tomography or magnetic resonance), these strategies still have many limitations and do not fully satisfy clinical needs due to their lack of sensitivity and/or specificity. Therefore, improvements of the current practice would substantially impact the management of CRC patients. In this view, liquid biopsy is a promising approach that could help clinicians screen for disease, stratify patients to the best treatment, and monitor treatment response and resistance mechanisms in the tumor in a regular and minimally invasive manner. Liquid biopsies allow the detection and analysis of different tumor-derived circulating markers such as cell-free nucleic acids (cfNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) in the bloodstream. The major advantage of this approach is its ability to trace and monitor the molecular profile of the patient's tumor and to predict personalized treatment in real-time. On the other hand, the prospective use of artificial intelligence (AI) in medicine holds great promise in oncology, for the diagnosis, treatment, and prognosis prediction of disease. AI has two main branches in the medical field: (i) a virtual branch that includes medical imaging, clinical assisted diagnosis, and treatment, as well as drug research, and (ii) a physical branch that includes surgical robots. This review summarizes findings relevant to liquid biopsy and AI in CRC for better management and stratification of CRC patients., Competing Interests: Author LB was employed by company OncoTeam Diagnostic S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ginghina, Hudita, Zamfir, Spanu, Mardare, Bondoc, Buburuzan, Georgescu, Costache, Negrei, Nitipir and Galateanu.)

The extracellular matrix (ECM) consists of fibrillary and non-fibrillary components in the extracellular zone, and fulfills structural and signaling roles. Cardiac insult can lead to cardiomyocyte death, which subsequently determines dynamic changes of ECM composition and regulates cellular responses, ultimately contributing to cardiac repair. The present retrospective study on a small batch selected from the database of the Pathology Department of 'Sf. Pantelimon' Hospital aimed to determine which molecules may have a role in the dynamics of ECM using histopathology and immunohistochemistry methods. The study batch was composed of cases with cardiac ischemic conditions who died at various ages of myocardial infarcts. Tissue samples were taken from the myocardium of the left ventricle (anterior and lateral walls), and multiple series of histological sections were produced and analyzed using immunohistochemistry for collagen type I (Col-1), tenascin C (Tn-C), matrix metalloproteinase 9, CD34, and CD68. Col-1 and Tn-C showed variable patterns of fibrillar plexiform network, associated with a high micro-vascular density of newly formed capillaries revealed by CD34, and an interstitial infiltrate with histiocytes demonstrated by CD68 presence. The ECM represents therefore a polymorphic microenvironment with its own dynamics that is in continuous change, involving a large spectrum of heterogenous molecules, which play different roles in myocardium remodeling under hypoxic ischemic conditions., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

The main objective was to produce 3D printable hydrogels based on GelMA and hydroxyapatite doped with cerium ions with potential application in bone regeneration. The first part of the study regards the substitution of Ca 2+ ions from hydroxyapatite structure with cerium ions (Ca 10-x Ce x (PO 4 ) 6 (OH) 2 , xCe = 0.1, 0.3, 0.5). The second part followed the selection of the optimal concentration of HAp doped, which will ensure GelMA-based scaffolds with good biocompatibility, viability and cell proliferation. The third part aimed to select the optimal concentrations of GelMA for the 3D printing process (20%, 30% and 35%). In vitro biological assessment presented the highest level of cell viability and proliferation potency of GelMA-HC5 composites, along with a low cytotoxic potential, highlighting the beneficial effects of cerium on cell growth, also supported by Live/Dead results. According to the 3D printing experiments, the 30% GelMA enriched with HC5 was able to generate 3D scaffolds with high structural integrity and homogeneity, showing the highest suitability for the 3D printing process. The osteogenic differentiation experiments confirmed the ability of 30% GelMA-3% HC5 scaffold to support and efficiently maintain the osteogenesis process. Based on the results, 30% GelMA-3% HC5 3D printed scaffolds could be considered as biomaterials with suitable characteristics for application in bone tissue engineering.

Due to their remarkable structures and properties, three-dimensional hydrogels and nanostructured clay particles have been extensively studied and have shown a high potential for tissue engineering as solutions for tissue defects. In this study, four types of 2-hydroxyethyl methacrylate/2-acrylamido-2-methylpropane sulfonic acid/montmorillonite (HEMA/AMPSA/MMT) hydrogels enriched with sericin, and fibroin were prepared and studied in the context of regenerative medicine for soft tissue regenerative medicine. Our aim was to obtain crosslinked hydrogel structures using modified montmorillonite clay as a crosslinking agent. In order to improve the in vitro and in vivo biocompatibility, silk proteins were further incorporated within the hydrogel matrix. Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) were performed to prove the chemical structures of the modified MMT and nanocomposite hydrogels. Swelling and rheological measurements showed the good elastic behavior of the hydrogels due to this unique network structure in which modified MMT acts as a crosslinking agent. Hydrogel biocompatibility was assessed by MTT, LDH and LIVE/DEAD assays. The hydrogels were evaluated for their potential to support adipogenesis in vitro and human stem cells isolated from adipose tissue were seeded in them and induced to differentiate. The progress was assessed by evaluation of expression of adipogenic markers ( ppar-γ2 , perilipin ) evaluated by qPCR. The potential of the materials to support tissue regeneration was further evaluated on animal models in vivo. All materials proved to be biocompatible, with better results on the 95% HEMA 5% AMPSA enriched with sericin and fibroin material. This composition promoted a better development of adipogenesis compared to the other compositions studied, due the addition of sericin and fibroin. The results were confirmed in vivo as well, with a better progress of soft tissue regeneration after implantation in mice. Therefore, hydrogel 95% HEMA 5% AMPSA enriched with sericin as well as fibroin showed the best results that recommend it for future soft tissue engineering application.

Over the years, natural-based scaffolds have presented impressive results for bone tissue engineering (BTE) application. Further, outstanding interactions have been observed during the interaction of graphene oxide (GO)-reinforced biomaterials with both specific cell cultures and injured bone during in vivo experimental conditions. This research hereby addresses the potential of fish gelatin/chitosan (GCs) hybrids reinforced with GO to support in vitro osteogenic differentiation and, further, to investigate its behavior when implanted ectopically. Standard GCs formulation was referenced against genipin (Gp) crosslinked blend and 0.5 wt.% additivated GO composite (GCsGp/GO 0.5 wt.%). Pre-osteoblasts were put in contact with these composites and induced to differentiate in vitro towards mature osteoblasts for 28 days. Specific bone makers were investigated by qPCR and immunolabeling. Next, CD1 mice models were used to assess de novo osteogenic potential by ectopic implantation in the subcutaneous dorsum pocket of the animals. After 4 weeks, alkaline phosphate (ALP) and calcium deposits together with collagen synthesis were investigated by biochemical analysis and histology, respectively. Further, ex vivo materials were studied after surgery regarding biomineralization and morphological changes by means of qualitative and quantitative methods. Furthermore, X-ray diffraction and Fourier-transform infrared spectroscopy underlined the newly fashioned material structuration by virtue of mineralized extracellular matrix. Specific bone markers determination stressed the osteogenic phenotype of the cells populating the material in vitro and successfully differentiated towards mature bone cells. In vivo results of specific histological staining assays highlighted collagen formation and calcium deposits, which were further validated by micro-CT. It was observed that the addition of 0.5 wt.% GO had an overall significant positive effect on both in vitro differentiation and in vivo bone cell recruitment in the subcutaneous region. These data support the GO bioactivity in osteogenesis mechanisms as being self-sufficient to elevate osteoblast differentiation and bone formation in ectopic sites while lacking the most common osteoinductive agents.

Liquid biopsy is a promising tool for a better cancer management and currently opens perspectives for several clinical applications, such as detection of mutations when the analysis from tissue is not available, monitoring tumor mutational burden and prediction of targeted therapy response. These characteristics validate liquid biopsy analysis as a strong cancer biomarkers source with high potential for improving cancer patient's evolution. Compared to classical biopsy, liquid biopsy is a minimal invasive procedure, and it allows the real-time monitoring of treatment response. Considering that lung cancer is the most common cause of cancer-associated death worldwide and that only 15-19% of the lung cancer patients survive five years after diagnosis, there is an important interest in improving its management. Like in other types of solid cancers, lung cancer could benefit from liquid biopsy through a simple peripheral blood sample as tumor-related biomarkers, such as circulating tumor cells (CTCs), cell-free nucleic acids (cfNA) [cell-free ribonucleic acid (cfRNA) and cell-free deoxyribonucleic acid (cfDNA)], exosomes and tumor-educated platelets (TEPs) may shed into circulation because of necrosis or in an active manner. More, the detection and analysis of these biomarkers could lead to a better understanding of oncological diseases like lung cancer. The better the tumor profile is established; the better management is possible. However, this approach has currently some limitations, such as low cfNA concentration or low count of CTCs that might be overcome by improving the actual methods and technologies.

Malignant melanoma is a deadly form of skin cancer, and prompt diagnosis is a key factor in providing adequate, life-saving therapy. A 75-year-old man, with long-standing type 2 diabetes mellitus, presented with a 2- to 3-year history of right heel ulcer. He had received various therapies for a diagnosis of diabetic foot ulcer, to no avail. Physical examination showed a black, fungating ulcerated lesion on his right heel, with minimal bleeding. No inguinal lymphadenopathy was palpated. A biopsy was done, which revealed BRAF-negative malignant melanoma, with a vertical growth phase, Breslow 3.1 mm, ulceration, 11 mitoses/mm 2 , Clark level IV, no lymphatic or vascular invasion observed. Right inguinal lymph node sampling suggested no involvement, but PET-CT suggested pulmonary, right inguinal lymph node and bone involvement. The patient was referred to the oncologists. Written informed consent for publication was given by the patient. Diabetic foot ulcers are a frequently encountered, but serious complication of diabetes mellitus. Delayed healing is often seen, despite adequate therapy. The differential diagnosis of diabetic foot ulcers is vast and includes neoplasia. When a foot ulcer fails to heal, other differential diagnoses must be considered, in order for the patient to receive adequate therapy. Here specialist consultations, including dermatology consultations, could improve chances of delivering the right therapy promptly. This is a factor underlying the emphasis on a multidisciplinary approach to foot ulcer therapy. Our presentation - reported according to the CARE guidelines - also illustrates the fact that failure to reach a timely diagnosis may deny the patient the opportunity to receive adequate treatment. In such cases, "delayed therapy becomes denied (or failed) therapy", paraphrasing the old adage "Justice delayed is justice denied"., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Nwabudike et al.)

Chronic liver injuries lead to liver fibrosis and then to end-stage liver cirrhosis. Liver transplantation is often needed as a course of treatment for patients in critical conditions, but limitations associated with transplantation prompted the continuous search for alternative therapeutic strategies. Cell therapy with stem cells has emerged as an attractive option in order to stimulate tissue regeneration and liver repair. Transplanted mesenchymal stem cells (MSCs) could trans-differentiate into hepatocyte-like cells and, moreover, show anti-fibrotic and immunomodulatory effects. However, cell transplantation may lead to some uncontrolled side effects, risks associated with tumorigenesis, and cell rejection. MSCs' secretome includes a large number of soluble factors and extracellular vesicles (EVs), through which they exert their therapeutic role. This could represent a cell-free strategy, which is safer and more effective than MSC transplantation. In this review, we focus on cell therapies based on MSCs and how the MSCs' secretome impacts the mechanisms associated with liver diseases. Moreover, we discuss the important therapeutic role of EVs and how their properties could be further used in liver regeneration.