Skin Ultrasound Assessment of Patients with Systemic Scleroderma-An Observational Study.

This study aims to analyze the changes in dermal thickness in patients with systemic scleroderma (SSc) in comparison with normal skin and also compare clinical forms with diffuse and limited cutaneous involvement. The study group consisted of female patients diagnosed with SSc with a disease history not exceeding 5 years. The areas of interest for ultrasound examination included the proximal phalanx of the third finger, the second intermetacarpal space, and the extension surface of the lower third of the forearm. The study included 20 patients diagnosed with SSc and 14 controls. SSc patients were subdivided into two subgroups based on the clinical form. Compared to the control group, patients with SSc had higher mean measurements in all three skin areas, with statistically significant differences in the hand and forearm areas. Patients with diffuse SSc displayed, on average, higher skin thickness compared to limited SSc in all skin areas examined, with a statistically significant difference only in the forearm area. Based on disease manifestations, significant differences were observed only with regard to the presence of pulmonary hypertension in the diffuse SSc group. In conclusion, skin ultrasound is a useful and accessible imaging method for diagnosing and quantifying dermal fibrosis in systemic scleroderma.

Polymyalgia rheumatica: An update (Review).

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness, predominantly of the neck muscles, hip and shoulder girdle. Usually, patients with this disease are >50 years of age and biological inflammatory syndrome is present with an increase in both the erythrocyte sedimentation rate and C-reactive protein levels, aspects similar to giant cell arteritis. The aim of the present review was to depict the current pathogenic hypothesis, diagnostic and treatment approach for patients with PMR, and novelties since the development of the currently used 2012 European League Against Rheumatism and American College of Rheumatology provisional classification criteria. PMR is a prevalent disease that can occasionally prove difficult to diagnose and treat. Possibly, the most abundant type of evidence and data revealed over the past decade have been acquired through musculoskeletal imaging, with implications in diagnosis, disease monitoring and relapse, prognosis and changes with treatment. Further research on pathophysiology is required to gain a deeper understanding of the underlying processes, which will serve as the foundation for future personalized treatments. In addition, there is an increasing demand for improved diagnostic techniques, which should include a further development of various imaging modalities, in order to provide accurate diagnosis and appropriate therapy.

Microbiota-Accessible Boron-Containing Compounds in Complex Regional Pain Syndrome.

The microbiota-gut-brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota-gut-brain axis, offering hope for improved management of this challenging condition.

Novel Biomarkers Predictive of Diabetic Charcot Foot-An Overview of the Literature.

Background: Although Charcot diabetic foot (CDF) is a frequent complication of diabetic neuropathy, less is known about the possibility of its early prevention. Methods: A review of the original articles published in English, using the "biomarkers AND Charcot's foot" criterion, resulted in 33 articles from the PubMed database and seven articles from the Web of Science database. The five duplicates were eliminated, and two independent reviewers selected the most relevant articles, leaving a total of 21 articles. Results: The biomarkers identified are exhaustively described, related to the system of advanced glycation end products (AGEs) and their soluble receptors (sRAGE), inflammatory cascade, osteoclastogenesis, and, respectively, osteoblastic activity. Conclusions: This article highlights the importance of potential early identifiable biomarkers that can lead to microstructural changes in the affected bones.

Anti-MDA5 Amyopathic Dermatomyositis-A Diagnostic and Therapeutic Challenge.

Clinically amyopathic Dermatomyositis (CADM) is a rare subtype of idiopathic inflammatory myositis, associated with no muscular manifestations, which is more frequent in Asian women. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are a recently discovered type of specific autoantibodies associated with myositis. The anti-MDA5 DM was initially described in Japan and later it was discovered that the target antigen was a protein implicated in the innate immune response against viruses, that is encoded by the melanoma differentiation-associated gene 5. Anti-MDA5 DM is characteristically associated with distinguished mucocutaneus and systemic manifestations, including skin ulcerations, palmar papules, arthritis, and interstitial-lung disease. Patients with anti-MDA5 positivity have a high risk of developing rapid progressive interstitial-lung disease (RP-ILD), with a poor outcome. As a result, despite high mortality, diagnosis is often delayed, necessitating increased awareness of this possible condition. Despite a severe course of lung disease and an increased mortality rate, there is currently no standard treatment. Recent insights based on observational studies and case reports support combined therapy with immunosuppressive drugs and corticotherapy, as soon as the symptoms appear. The aim of this paper is to describe anti-MDA5 DM, focusing on the recent literature about the unique clinical manifestations and therapeutic options, starting from a severe clinical case diagnosed in our Rheumatology Department.

A Study on Dermatomyositis and the Relation to Malignancy.

The idiopathic inflammatory myopathies (IIM) are a group of heterogeneous systemic diseases which include as main subtypes: polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). The key feature of IIMs is the muscle weakness, accompanied by a characteristic skin rash in DM patients. The overall risk for malignancy in IIM is higher compared to the age-and sex-matched general population. Most epidemiologic studies have included only PM and DM patients and reported consistently higher rates of malignancy in DM. Most common types of cancer in DM are adenocarcinoma of the lung, ovary or gastrointestinal tract, melanoma and non-Hodgkins lymphoma. The highest risk for malignancy is seen in the first year after DM diagnosis. Multiple disease features have been linked to the development of cancer in DM. These include: older age, male sex, skin necrosis, Gottron sign, heliotrope rash, dysphagia, low complement C4, lymphocytosis, poor response to corticosteroids and rapid disease progression. Our study included 23 patients with DM, divided into two groups based on the association of malignancy, in order to compare clinical and demographic features, laboratory markers and analyze characteristic of cancer development.

Complex regional pain syndrome as a paraneoplastic disorder associated with metatypical basal cell carcinoma.

Metatypical basal cell carcinoma (MTBCC) is a rare form of tumor, which associates the clinical and histopathological (HP) characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with a 5% chance for the development of metastases. The reference diagnosis remains the HP confirmation from the lesional tissue. The current report illustrates the case of a 74-year-old patient, diagnosed with MTBCC consequently to the biopsy from the clinically malignant lesion with HP and immunohistochemical examination, currently in clinical remission following surgical treatment. The musculoskeletal symptoms represent the patient's admission reason to the Clinic of Rheumatology, where he was diagnosed with paraneoplastic type I complex regional pain syndrome (CRPS-I). The onset was six weeks prior with intense pain in the upper limb, burning sensation and nondermatomal distribution, exacerbated by lowering the position of the upper limb. The clinical evaluation revealed vasomotor disorders: color changes on the skin of the upper limb, venous turgescence on the back of the hands, and local increased temperature. Also, there were evident sudomotor modifications with hyperspiration and fluffy edema. The presence of clinical manifestations associated with the HP confirmation of MTBCC and the information provided by the imaging tests regarding the evaluation of tumor extension advocates for the diagnosis of paraneoplastic CRPS, consequently to both the primary tumor and the pulmonary metastasis. Diagnosis of CRPS-I is generally established on the basis of clinical criteria after excluding other conditions that may explain the degree of pain and the existing dysfunction. The therapist should be aware of the clinical manifestation of CRPS, as early recognition and aggressive treatment often leads to the best response.

Streptococcal tonsillitis related reactive arthritis - clinical, ultrasound imaging and immunohistochemical study.

In clinical practice and literature studies, the most common condition associated to streptococcal tonsillitis used to be acute rheumatic fever (ARF). Several publications in the late years report a more frequent and distinctive entity from ARF following ß-hemolytic group A streptococcus infection in patients with post-infectious arthritis, that do not fulfill the modified Jones criteria, the so-called post-streptococcal reactive arthritis (PSRA). A distinctive pattern of clinical framing and biological profile in patients with PSRA following streptococcal tonsillitis is described, with a non-migratory, additive, recent onset (7-10 days) arthritis that affects small and large joints as well, with a bimodal peak of incidence at 8-14 and 21-37 years of age, with variate response to non-steroidal anti-inflammatory drugs and has a tendency for recurrence and persistence. Sacroiliitis, although rare, is described in human leukocyte antigen (HLA)-B27 positive PSRA patients. The main objective of the current study was to evaluate various immunohistochemical patterns of streptococcal tonsillitis in patients with PSRA and find possible correlations with the clinical, biological and ultrasound profile.

Difficulty in positive diagnosis of ascites and in differential diagnosis of a pulmonary tumor.

Ascites is the most frequent complication of cirrhosis and occurs only when the portal hypertension has already installed but ascites is caused by neoplasms, heart failure, tuberculosis, pancreatic illnesses, as well as other kind of affections. We describe the case of a 67-year-old patient, a retired person, without significant personal or familial history, nonsmoker, infrequent alcohol and coffee consumer with following chief complaints at onset: loss of appetite, weight loss, serious physical asthenia, delayed intestinal transit, diffuse abdominal pain and increase of abdominal circumference. Initially was misdiagnosed with liver cirrhosis. After discharged from our Clinic, suspicion of diagnosis was mesothelioma as well as after first thoracoscopy and pleural biopsy performed in a Clinic of Thoracic Surgery. Several pleural fragments collected by biopsy were sampled for the histopathological exam. The stainings used were Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) for the mucopolysaccharides. For the immunohistochemistry was used the labeled Streptavidin-Biotin (LSAB)-Horseradish peroxidase (HRP) method, as well as the antibodies: cytokeratin (CK) cocktail (AE1÷AE3), vimentin, calretinin, CK7, CK5÷6, CK20, epithelial specific antigen/epithelial cell adhesion molecule (Ep-CAM) (BerEP4), thyroid transcription factor-1 (TTF-1), E-cadherin, CDX2, carcinoembryonic antigen (CEA) and the Hector Battifora mesothelial antigen-1 (HBME-1). The aspect at immunohistochemistry establishes a positive diagnostic of poorly differentiated mucinous pulmonary adenocarcinoma, with "signet ring" cells. The rapid and accurate determination of the diagnostics will allow not only for a decrease in the expenses for inefficient treatments, but also for the guidance of the patients towards clinics or centers able to provide and supervise these treatments.

Histopathological and immunohistochemical profile in primary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by hypofunction of the salivary and lachrymal glands. Main clinical features of SS are sicca symptoms, due to the altered glandular function. Also, in advanced stages, bilateral swelling of the parotid glands can be noted, indicative of severe glandular involvement. Phenotypic expression of various mononuclear cells present in the affected tissue offers additional insight into cellular proliferation, survival, migration, antibody secretion and also the potential of forming tertiary lymphoid tissue, i.e., germinal centers. The main objective of the present study was to evaluate various autoimmune activity patterns present in salivary glands by means of immunohistochemistry (IHC) analysis. The study group comprised of 10 primary SS patients, with various degrees of lymphocytic infiltrates confirmed on minor salivary gland (MSG) biopsy. We could identify both morphological changes, i.e., ductal system abnormalities or increased interstitial fibrosis, and immunological patterns associated with SS pathogenesis. CD3+ T-cells displayed a more intense reaction in specimens with mild to intermediate focus score (FS) grade. Specimens with important CD20+ B-cell component of lymphocytic infiltrate were associated with intermediate and severe FS grade. Specimens showed varying degrees of CD68+ cells, with more intense IHC reactions in slides displaying a more advanced mononuclear infiltration. Immunoreactivity was strong for both MMP-2 and MMP-8 matrix metalloproteinases, throughout the gland, in areas of acini, without it being linked with proximity of mononuclear cell infiltration. We could also establish some correlations between the degree of lymphocytic infiltration and clinical profile.

Study on cognitive decline in patients diagnosed with brain tumors.

AIM: The purpose of our study was to assess the cognitive performance in patients with primitive brain tumors and to analyze the cognitive status of these patients, correlated with histological type of brain tumors. PATIENTS, MATERIALS AND METHODS: The study enrolled 52 patients diagnosed with primitive brain tumors, hospitalized in Neuropsychiatry Hospital of Craiova, Romania, from December 2013 to December 2015. According to the histological type of tumors, the patients were classified into three groups: Group A included 22 patients with meningioma, Group B composed of 16 patients diagnosed with glioblastoma, and Group C including 14 patients diagnosed with diffuse astrocytoma. Neurological examination, neuroimaging assessment [computed tomography (CT) or magnetic resonance imaging (MRI) for skulls] to diagnose primitive brain tumors, then the confirmation of clinical and histopathological diagnoses were performed for these patients. For cognitive assessment performed before surgery, Montreal Cognitive Assessment (MoCA) and Cambridge Cognitive Examination (CAMCOG) scales were used. The results were statistically analyzed using the Student's t-test; p-values less than 0.05 were considered statistically significant. RESULTS: In terms of age, we did not observe statistically significant differences between the three groups of patients. The group of patients with diffuse astrocytoma presented a higher educational level compared to patients with glioblastoma or meningioma. MoCA score obtained in glioblastoma group was 21.7 points, while in the group of patients with diffuse astrocytoma was 23.5 points, and in the group of patients with meningioma 24.2 points. The cognitive assessment using CAMCOG scale led to the following results: group of patients diagnosed with glioblastoma showed an average score of 83.5 points, the diffuse astrocytoma group had an average score of 88.9 points and the group with meningioma an average score of 90.1 points. CONCLUSIONS: Patients diagnosed with glioblastoma showed a statistically significant cognitive decline in comparison to patients diagnosed with diffuse astrocytoma (p<0.05). We did not notice statistically significant differences in the cognitive decline of patients with meningioma compared to those diagnosed with diffuse astrocytoma (p>0.05).

Cervical adenocarcinoma generator of procoagulant status and ischemic stroke.

The procoagulant status of neoplastic patients is well known in medical literature, but in the last years there is attempted a correlation between the histological types of neoplasia and the risk for thrombotic strokes. We present the case of a 44-years-old patient undergoing early menopause, who was diagnosed with cervical tumor of the serous adenocarcinoma type. The patient underwent external radiotherapy, and, in the seventh day of treatment, she suffered a frontal-temporal-parietal ischemic stroke with left hemiplegia. The blood testing highlighted procoagulant products (double fibrinogen compared to normal values, deficit of antithrombin and a high number of thrombocytes). The patient received neurological and rehabilitation treatment, at first with Heparin, followed by the administration of an antiaggregant. During this treatment, the deficit remained unchanged. She continued the neurological and rehabilitation treatment, followed by radiotherapy, with a good evolution. Six months after the stroke, it was decided the surgical tumor ablation of cytoreduction. The post-surgery histological examination highlighted specific changes due to post-surgery radiotherapy, without the presence of any neoplastic cells. The imagistic evaluation, computed tomography (CT) every three months after surgery, did not highlight any suggestive dissemination elements. The occurrence of an ischemic stroke in a patient with endocervical neoplasm of the adenocarcinoma type during radiotherapy imposed the discharge of chemotherapy, with subsequent imaging, biological and histopathological monitoring after surgery. The cause of stroke in this case is determined by the hypercoagulant status in the context of the developed neoplasia, the patient being free of any other risk factors.