Aggressive Course Research Articles

The expression of VDACs and Bcl2 family genes in pituitary adenomas: clinical correlations and postsurgical outcomes.

Pituitary adenomas (PAs) are benign tumors with high prevalence and, occasionally, aggressive course. The tumorigenesis of these lesions is not completely understood at the molecular level. BAK1 and BAX proteins play fundamental roles in apoptosis and seem to interact with VDAC proteins, whose expressions have been markedly altered in cancer, impacting their prognosis. to evaluate the gene expression of VDAC1, VDAC2, BAK1 and BAX and their association with clinical and imaging characteristics in PA. Clinical-epidemiological data were collected from 117 tumor samples from patients affected by PA. Invasiveness was assessed by the Knosp scale. Gene expression was examined by real-time PCR. Relative expression analysis was performed by 2^(-DDCt) method. The sample was mainly composed of women (69/117 - 57.2%). Tumor subtypes observed were Non-Functioning (NF) (73/117 - 62.4%), Acromegaly (24/117 - 20.5%) and Cushing's Disease (CD) (20/117 - 17.1%). Compared to normal tissue, there was a significant reduction in VDAC1 expression in the Acromegaly (p=0.029) and NF (p=0.002) groups. BAX expression was lower in all groups (p <0.001; p=0.007; P =0.005). No difference was found in VDAC2 and BAK1 expression, compared to normal pituitary. Overexpression of VDAC2 occurred in PAs with post-surgical regrowth (p=0.042). A strongly negative correlation was observed in BAX and BAK1 expression in CD. The results indicated that downregulations of VDAC1 and BAX may be related to resistance to apoptosis. In contrast, overexpression of VDAC2 in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs.

Clinical Features and Prognosis of Primary Epithelial-Myoepithelial Carcinoma of Salivary Gland: A Surveillance, Epidemiology, and End Results Database-Based Study.

The clinical characteristics and prognosis of primary epithelial-myoepithelial carcinoma of salivary gland (EMC-SG) have not been defined well due to its rarity. The purpose of this study is to assess the proportion of EMC-SG among salivary gland cancers, describe the clinicopathological features and prognosis of this disease, further analyze the factors associated with EMC-SG survival, and establish individual survival-predicting models. Data on patients diagnosed with salivary gland malignancy between 2000 and 2020 were collected from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method and log-rank test were employed to estimate survival of EMC-SG patients. Univariable and multivariable Cox proportional hazards models were developed to determine the EMC-SG survival-associated factors. Furthermore, EMC-SG nomograms were constructed. A total of 15212 patients with salivary gland malignancy were identified. Of these, 310 cases were diagnosed with EMC-SG, representing a prevalence of 2.03% (95%CI 1.82%-2.28%). The overall survival (OS) rates for all 310 EMC-SG patients at 2-year, 5-year, and 10-year were 92.43%, 84.85%, and 73.39%, respectively. Age, primary site, and T stage were independent prognostic factors for OS, while pathological grade and the use of surgery were independent prognostic factors for cancer-specific survival (CSS). The concordance index (C-index) for the OS- and CSS-specific nomograms was 0.72 (95%CI 0.64-0.80) and 0.77 (95%CI 0.67-0.87), respectively. The calibration curve and receiver operating characteristic analysis demonstrated that the predicted values aligned well with the actual observations. Decision curve analysis indicated the superiority of the nomograms over the traditional Tumor Node Metastasis staging system. This study represents the largest cohort of EMC-SG patients used to investigate the characteristics and prognosis of this disease. EMC-SG patients often have a less aggressive course and favorable prognosis. The established nomograms provide a useful tool for clinicians to predict patient outcomes, and can assist in customizing the counseling approach for this rare disease.

Clinical Characteristics of Systemic Lupus Erythematosus in Caucasians and Latin American Hispanics: Data from a Single Tertiary Center.

Different studies report that systemic lupus erythematosus (SLE) tends to have a more aggressive course in Hispanic patients. In this study, we analysed epidemiologic, clinical, and laboratory characteristics in a cohort of Hispanic and Caucasian lupus patients in the context of Italian health service, which provides free access to care to all citizens, thus mitigating the impact of socioeconomic factors that negatively influence the course of the disease in ethnic minorities. This single-center retrospective study was conducted at the San Martino Hospital "Lupus Clinic" in Genoa, Italy. Patients ≥18 years with a confirmed diagnosis of SLE and definite ethnicity (Hispanic or Caucasian) were recruited. A total of 126 patients (90 Caucasians and 36 Hispanics) were enrolled. We compared epidemiologic characteristics, clinical features, autoantibodies profile, and treatment options without evidencing any statistically significant difference between the two groups, except for disease duration, which was higher in the Caucasian group (20.4 years versus 14.2 years in the Hispanic group, P=0.002) and SLICC damage index, which was greater in Caucasian patients (2.11 versus 1.88 in Hispanics, P=0.037), but this difference was no longer significant after correction for disease duration (P=0.096). In our cohort, Hispanic ethnicity is not associated with worse disease features and outcomes. Therefore, we speculated that socioeconomic factors, in particular, free access to healthcare, might be more relevant in influencing the course of the disease than genetic background.

COMPARATIVE ANALYSIS OF MRI, MORPHOLOGICAL AND BIOCHEMICAL FEATURES OF MALIGNANT NEOPLASM OF THE PROSTATE GLAND

Introduction. This article presents a comparative analysis of magnetic resonance imaging (MRI), transrectal ultrasound (TRUS), biopsy and biochemical studies in prostate cancer using histomorphologic grading of the tumor component according to the Gleason score. It has been shown that the level of prostate-specific antigen (PSA) often correlated with the total Gleason score. Materials and methods: In the study, 860 patients with suspected prostate cancer were examined: 530 patients (62 %) were diagnosed with prostate cancer at various stages of development, and 330 patients (38 %) were diagnosed with prostate adenoma. MRI of the prostate was performed in three sections: sagittal, frontal and vertical. The tumor component was assessed using the PI-RADS system. Patients with a PSA level of more than 4.4 ng/ml were selected for the study. The stage of cancer development was determined by the Gleason scale during histological examination. Results of own research: It was found that the MRI diagnostic method was most effective in low and moderately differentiated forms of prostate adenocarcinoma and could also be used to assess the prevalence of the tumor process. The first place among the studied cases (61%) was occupied by stage III prostate cancer, the second place – by stage IV prostate cancer (24%) and the third place – by stage II prostate cancer (15%). Hypoechoic nodular elements were detected in 30.2%, mainly 5–7 by the Gleason score, heterogeneous nodular elements – in 40.1% (8 by the Gleason score), hypointense areas, mainly in the peripheral parts of the gland, were detected in 75.2% (9–10 by the Gleason score). Changes in the vascular pattern depended on the degree of development of the tumor component. Conclusion. Our study revealed a number of features: prostate cancer is mainly characterized by highly differentiated and moderately differentiated forms of adenocarcinoma; in metastasized prostate cancer, a low-grade form of adenocarcinoma is more often detected, which can have an aggressive course and rapid spread of the tumor component.

ОСВІТНЯ КОНЦЕПЦІЯ "РУССКОГО МІРА" ЯК ЗБРОЯ РОСІЙСЬКОГО НЕОІМПЕРІАЛІЗМУ

The Russian-Ukrainian war of 2014–2024 led to the intensification of the information struggle in all spheres of life in modern society. One of the leading directions of the aggressor state's efforts was the transformation of its own education system and the spread of its influence in the international information space. At the beginning of the 21st century in the russian federation, a large-scale socio-political experiment was launched to change the worldview of its population. The declaration by the russian political establishment of its own country as a separate civilization with messianic tasks of a global scale made it necessary to search for a new educational paradigm that would ensure the successful reception of the ideology of the "russian world" by participants in the educational process. Clericalism, militarism, and xenophobia should become the new worldview coordinates of education. The final result of such an educational process should be the formation of an imperial identity among its participants. Thus, the russian neo-imperial educational concept is de facto a kind of information-psychological weapon. The implementation of its provisions will allow russia to obtain in the near future a powerful human resource for continuing an aggressive foreign policy course. Thus, there is a need to find appropriate and effective tools for countering russian influence in the educational space. The purpose of the proposed research is to reveal the peculiarities of the use of the ideology of the "russian world" as an organizational factor of the neo-imperial concept of education, which should contribute to counteracting anti-Ukrainian informational destructive influences.

Inflammatory bowel diseases: Transformation of representations. A review

The global burden of inflammatory bowel disease (IBD) is currently significant and continues to grow due to the increasing prevalence of ulcerative colitis (UC) and Crohn's disease (CD), the increasing costs of diagnosis and treatment, and the high level of disability in patients with this disease. Categories, which leads to the search for risk factors and predictors of aggressive course and extraintestinal manifestations. According to the latest data, the prevalence of UC in Russia is 16.6 per 100 000 population, the annual registered increase is 11.3%; the prevalence of CD is 5.6 per 100 000 population, and the increase is 13.7%. In the Russian population of patients with IBD, the average age of disease onset is 35.3 years for UC and 31.2 years for CD. Moreover, in 89.3% of patients with UC, it took at least 2 years to verify the diagnosis, and in CD, within 2 years from the onset of clinical symptoms, the diagnosis was established in only 72.6% of patients. One of the dominant characteristics of IBD is its multisystem nature, which leads to the development of extraintestinal manifestations (ECM), which can be observed in 50-60% of patients, while up to 25% of patients with IBD have several EMC and the most common variants are joint lesions. A higher frequency of extraintestinal manifestations is observed in CD (up to 45% of patients), in female patients, in smokers and with a longer duration of the disease. To predict clinical remission, the level of fecal calprotectin and CRP, the need for glucocorticosteroids are important, to predict endoscopic remission - the level of fecal calprotectin, and to predict histological remission, an endoscopic Schroeder index value of ≤1 is important. The absolute risk of developing colorectal cancer in IBD remains relatively low, ranging from 1.1 to 5.4% after 20 years of disease. The main risk factors for IBD are total intestinal damage, high inflammatory activity, the stricturing phenotype of CD and the presence of primary sclerosing cholangitis.

Aggressive course of atherosclerosis in hyperlipoproteinemia (a): a case series

Currently, worldwide interest in lipoprotein(a) (LP(a) as one of the most important markers of premature and aggressive atherosclerosis is steadily growing. This trend is due to both the new data on the pathogenesis of hyperlipoproteinemia (a) and the development of novel treatment methods in the near future. The variety of clinical manifestations of atherosclerosis associated with high LP(a) concentrations leads such patients to specialists of various profiles. The aim of this paper was to demonstrate, using examples from the practice of two lipid centers in Krasnodar, the diversity of clinical scenarios of atherosclerosis as a systemic disease in patients with very high LP(a) levels, as well as to highlight the current and future options for the treatment of hyperlipoproteinemia (a).

Individual approach to metastatic colorectal cancer treatment (clinical cases)

Two patients with metastatic colorectal cancer underwent R0 large bowel resection followed by surgery liver and lungs metastases, retroperitoneal lymph nodes and post-op chemotherapy. The total follow-up period of the first patient was currently 12 years, the recurrence-free period was 5 years. In the second patient, stabilization of the disease was observed for 12 years, and the total follow-up period – 18.5 years. An integrated treatment approach to metastatic CRC with active surgery for removable distant metastases or perioperative use of the most effective drug therapy for potentially resectable metastases can control the disease even with an aggressive course.

Recent advances in the treatment of triple-negative breast cancer

Triple-negative is the rarest breast cancer biological subtype of breast cancer, but has the most aggressive course. The resuls of chemotherapy, especially in advanced disease, are unsatisfactory. Numerous clinical trials have been conducted, that resulted in registrations of new drugs decreasing the risk of recurrence and improving the outcome of patients with metastatic disease. The article summarizes the data on modern therapies registered in recent years. The role of pembrolizumab in perioperative treatment in the early stage was indicated, as well as the importance of olaparib in BRCA mutation carriers. Additionally, in patients with metastatic the indication for immunotherapy (pembrolizumab and atezolizumab), sacituzumab govitecan and PARP inhibitors (olaparib and talazoparib) in BRCA mutation carriers were highlighted.

Comparative analysis of clinical and morphological data of patients of different age groups who underwent emergency surgical interventions for complicated colon cancer

The aim of the study was to conduct a comparative analysis of clinical and morphological data of patients of different age groups after emergency resection interventions for complicated colon cancer. Materials and methods. The retrospective cohort study included 227 patients who underwent emergency operations for complicated colon cancer during the period from September 2016 to December 2022. Two groups of patients were selected: group 1 – under 60 years old, group 2–60 years old and older. In the 2nd group, 2 subgroups were selected: patients aged between 60 to 74 years and patients between 75 years and older. The primary point of the study was assessment of postoperative complications according to the Clavien–Dindo classification within 30 days after surgery. The secondary point was study of oncological adequacy of the operation. Results. The study included 128 (56.4 %) women and 99 (43.6 %) men. The median age was 66 years. Forty seven (20.7 %) patients were included in the group of persons younger than 60 years; 180 (79.3 %) patients were included in the group 60 years and older. There were no differences between the groups by gender and tumor localization. Tumor perforation was more often recorded in group 2 (23.3 % and 4.3 %, p = 0.017). High comorbidity was also more often observed in group 2 (46.8 % and 100 %, p = 0.023). In group 2, the physical status mostly corresponded to ASA grade 3 and 4 (p = 0.031). The difference between the groups by T-status was revealed: in group 1, there were more cases of T2-T3 (76.6 % vs. 46.7 %), and in group 2 – of T4 (53.3 % vs. 23.4 %), p = 0.034. Most patients in group 1 had the pN2 status (68.1 %), however, the pN1 status prevailed in the 2nd group (70 %). There were more oncologically inadequate operations in group 2: 54 (30 %) compared with group 1–2 (4.3 %) (p = 0.004). The main factors influencing the radicality of the performed operation were the type of urgent complication – tumor perforation (odds ratio (OR) 1.81, 95 % CI 1.43–3.96, p = 0.002); type of surgery (the Hartmann type surgery) (OR 1.62, 95 % CI 1.22–3.83, p &lt;0.001); age OR 0.76, 95 % CI 0.54–1.33, p = 0.004); comorbidity (OR 0.61, 95 % CI 0.43–1.28, p = 0.02); physical status of patients according to ASA classification grade 3–4 at admission (OR 0.52, 95 % CI 0.30–1.49, p = 0.002); tumor localization (OR 0.43, 95 % CI 0.28–1.15, p = 0.011). Conclusion. Emergency operations for complicated colon cancer are characterized by a high risk of serious postoperative complications, especially in elderly and senile patients. In patients younger than 60 years of age, the malignant tumors are often characterized by more aggressive course with damage to regional lymph nodes (N2 status).

Clinical and histological study of follicular helper T-cell lymphomas with indolent evolution

IntroductionFollicular helper T-cell lymphomas (TFHL) have an aggressive course with a poor outcome. European and US guidelines recommend anthracycline-based chemotherapy as a first-line treatment, but the 5-year overall survival rate is still approximately 30%. We describe here the features of a cohort of TFHL patients who experienced prolonged survival despite the absence of specific treatment or the initiation of steroid-based therapy. Patients and methodsIn our study, we describe 15 adult patients who suffered from TFHL and had not received intensive chemotherapy at diagnosis for any reason. Biopsies of these cases were centrally reviewed, and the mutational pattern was determined using next-generation sequencing. ResultsThese 15 patients had the classic clinical, biological and pathological features of TFHL, angioimmunoblastic-type. TET2 mutations were found in 83% of patients; RHOA G17V, IDH2 R172 and DNMT3A mutations were found in 67%, 42% and 33% of the patients, respectively. Among the 15 patients, 8 did not receive any treatment, and 7 received steroid-based treatment. Ten patients had progression (5 in each group). Four patients died (3 of them from the progression of their lymphoma). The median follow-up in our cohort was 53 months. The 5-year OS was 66%, 100% for untreated patients and 29% for the others. In those 2 groups, the median time to treatment initiation was 22 months from diagnosis. ConclusionWe described a series of 15 well-characterized TFHL patients with an indolent outcome, suggesting that a watch-and-wait approach can be proposed in selected patients. Identifying factors predicting such evolution is warranted.

Prioritization of potential pharmacological targets for the development of anti-hepatocarcinoma drugs modulating the extrinsic apoptosis pathway: the reconstruction and analysis of associative gene networks help

Prioritization of potential pharmacological targets for the development of anti-hepatocarcinoma drugs modulating the extrinsic apoptosis pathway: the reconstruction and analysis of associative gene networks help

Primary squamous cell carcinoma of the parotid salivary gland: a clinical observation

Introduction. Malignant tumors of the salivary glands account for 3–5 % of all cases of head and neck cancer. Squamous cell carcinoma is the rarest histological variant of this pathology. It accounts for an average of 1.6 %. Among large salivary gland tumors, squamous cell carcinoma most often occurs in the parotid salivary gland.Aim. To present a clinical case of primary disseminated cancer of the parotid salivary gland with squamous cell structure.Clinical observation. A 70-year-old patient was under observation who was diagnosed with a primary squamous cell tumor of the parotid salivary gland with multiple metastases during a complex examination. He was sick for about 6 months when asymmetry of left half of the face appeared due to a painful neoplasm in the parotid salivary gland. Recently, the patient has noted increased tumor growth. Objective examination revealed peripheral paralysis of the facial nerve on the left. In the parotid-masticatory region on the left, with a transition to the zygomatic region, there is a dense painful immobile exophytic tumor with infiltration into soft tissues of the face and skin 6.5 × 5.0 cm in size with an ulcer in the center. Laterally, it reaches the tragus, and at the bottom-the angle of the lower jaw. In the submandibular region on the left, metastatic lymph nodes 2.5 × 2.0 cm in size are palpated. A biopsy was collected. Histological conclusion: non-keratinizing squamous cell carcinoma. Expression of the programmed death receptor ligand (PD-L1) in the tumor is negative. Mutations of genes Her2-neu and BRAF were not detected. According to medical imaging methods, multiple metastases were found in the lungs, liver, zygomatic bone and tumor growth in the maxillary sinus on the left. The diagnosis was established: cancer of the parotid salivary gland, stage IVC, cT4N1M1, with metastases to the liver, lungs and bones. Polychemotherapy was prescribed according to the scheme: 5-fluorouracil + cisplatin + cetuximab + bisphosphonates. After 3 cycles, a partial regression is obtained.Conclusion. The primary squamous cell carcinoma is prone to an aggressive course and has an unfavorable prognosis, especially in patients over 60 years of age with skin and facial nerve damage, as well as the presence of regional and distant metastases. Differential diagnosis is necessary to exclude the secondary nature of the tumor. The presented case is a rare example of primary squamous cell carcinoma of the parotid salivary gland with extensive metastatic lesion and regression of the pathological process after polychemotherapy in combination with targeted therapy.

Diffuse large B-cell lymphoma: strokes to the epidemiological portrait. A review

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous orphan lymphoproliferative disease with an aggressive course, which accounts for 30–40% of all non-Hodgkin lymphomas. Approximately 3,000 new cases of DLBCL are diagnosed annually in Russia. The trend towards a steady increase in DLBCL incidence worldwide and the rapidly changing treatment landscape with the introduction of innovative options require the updating of epidemiological data. Despite a deeper understanding of the lymphomagenesis and molecular heterogeneity of DLBCL, the R-CHOP regimen remains the first-line standard of care for the vast majority (74%) of patients in Russia and worldwide. The effectiveness of this approach varies greatly and depends on several clinical, biological, and genetic factors. Currently, the most effective and simple prognostic model is the International Prognostic Index (IPI), according to which approximately 20% of patients are at intermediate/high risk of early progression (IPI3-5) and require therapy modification. After the first-line standard immunochemotherapy, 60–70% of DLBCL patients achieve long-term remission with the potential for cure. However, the occurrence of relapse or refractory disease in the remaining 40% of patients is associated with an abysmal prognosis with a median overall survival of about 6 months, which tends to decrease with each subsequent line, warranting an urgent need for new innovative treatments for patients with relapsed DLBCL.

Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy

BackgroundThe incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. MethodsWe included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan–Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. ResultsA total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637–78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109–3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166–66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. ConclusionThe prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

Immune Cells in the Tumor Microenvironment of Soft Tissue Sarcomas.

Soft tissue sarcomas (STSs) are a rare heterogeneous group of malignant neoplasms characterized by their aggressive course and poor response to treatment. This determines the relevance of research aimed at studying the pathogenesis of STSs. By now, it is known that STSs is characterized by complex relationships between the tumor cells and immune cells of the microenvironment. Dynamic interactions between tumor cells and components of the microenvironment enhance adaptation to changing environmental conditions, which provides the high aggressive potential of STSs and resistance to antitumor therapy. Today, active research is being conducted to find effective antitumor drugs and to evaluate the possibility of using therapy with immune cells of STS. The difficulty in assessing the efficacy of new antitumor options is primarily due to the high heterogeneity of this group of malignant neoplasms. Studying the role of immune cells in the microenvironment in the progression STSs and resistance to antitumor therapies will provide the discovery of new biomarkers of the disease and the prediction of response to immunotherapy. In addition, it will help to initially divide patients into subgroups of good and poor response to immunotherapy, thus avoiding wasting precious time in selecting the appropriate antitumor agent.

Clinical case of giant extramedullar plasmacytoma in a patient with multiple myeloma

One possible manifestation of multiple myeloma may be extramedullary plasmacytoma, manifested by infiltration of plasma cells outside the bone marrow. In the debut of the disease, bone plasmacytomas are most often diagnosed, in contrast to extramedullary ones, which are rare. According to the literature, the presence of extramedullary plasmacytoma is an unfavorable factor characterized by an aggressive disease course, the absence of an antitumor response to standard therapy, and low overall survival rates. Therefore, the pathogenesis, clinic, diagnosis and treatment of this variant of the disease require additional study. This article presents a clinical case of an aggressive course of extensive extramedullary plasmacytoma in a patient with multiple myeloma with an assessment of various combination therapy regimens efficacy.

Primary Small Cell Neuroendocrine Carcinoma of Bladder – A Rare Diagnostic Entity

Primary small cell carcinoma of the bladder is very rare pathological entity, follows an aggressive course and carries poor prognosis. The literature carrying these articles are scarce and due to which it poses a diagnostic challenge to the radiologist and urologists. Herein, we present a case of small cell carcinoma of urinary bladder in a 75 year old male patient initially reported as poorly differentiated urothelial carcinoma on transurethral resection of bladder tumor specimen to emphasize its rarity as well as the role of immunohistochemistry to differentiate between the two.

Biomarkers of Autoimmune Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways. In CSU, two major endotypes exist based on the primary receptor activating mechanism: type I hypersensitivity (IgE-mediated, directed against auto-allergens) and type IIb (autoimmune, via IgG autoantibodies directed against IgE or the IgE-receptor). Their treatment responses vary. We discuss in vitro and in vivo biomarkers. Patients with auto-allergic CSU have clinical characteristics that can distinguish them partly from those with autoimmune CSU. Most importantly, their disease generally presents a less aggressive course, a better response to second generation (up-dosed) antihistamines and a good response to omalizumab, if necessary. Meanwhile, autoimmune CSU/CindU patients fare less well and often need immunosuppressive drugs. Biomarkers that might help endotype CSU/CindU patients and select the most appropriate treatment, dose, and duration, e.g., for autoallergic CSU, high total IgE and IgE against auto-allergens; for autoimmune CSU, low IgE, basopenia, and IgG against autoantigens like thyroid peroxidase and a positive autologous serum skin test (but sometimes also positive in autoallergy). Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic.

Epidemiology, site-specific characteristics and survival of carcinosarcoma: a retrospective study based on SEER database

ObjectivesCarcinosarcoma (CS) is a rare and biphasic malignancy characterised by a highly invasive biological nature and poor prognosis. This study explored the epidemiology, site-specific characteristics and survival outcome of CS.DesignWe...