Defining the short-term and long-term skin manifestations of COVID-19: insights after more than three years of the pandemic.

AIM: This review aimed to assess the impact of coronavirus disease 2019 (COVID-19) on skin health to establish a classification of the skin lesions that occur most frequently during the disease and whether a particular category of skin damage is more likely to occur both in the short term and in the long term. METHODS: We conducted a literature search of the PubMed database. Ultimately, 109 articles were included in this review. The exact phrases∕syntax and connectors used for the database search∕query were as follows: "Coronavirus and skin", "COVID-19 and skin", "SARS-CoV-2 and skin", "Coronavirus cutaneous manifestations", "COVID-19 cutaneous manifestations", "SARS-CoV-2 cutaneous manifestations", "Coronavirus dermatology", "SARS-CoV-2 and dermatology", "COVID-19 and dermatology", "COVID-19 and skin eruption", "Coronavirus and skin rash", "COVID-19 and hair", "Coronavirus and hair", "Coronavirus and nails", "SARS-CoV-2 and hair", and "SARS-CoV-2 and nails". Only articles with abstracts referring strictly to cutaneous manifestations of COVID-19 were chosen. Articles without abstracts were not considered. RESULTS: We established six of the most frequently reported clinical patterns associated with COVID-19 and their probability of occurring during COVID-19 disease evolution based on the current literature reports. We did not identify the particular types of skin lesions that are most prone to long-term persistence; most such cases are rare, and no conclusion can be drawn based on them. CONCLUSIONS: Apart from classified COVID-19-related skin disorders, this pandemic has been a challenge for dermatologists and a wide range of cutaneous side effects related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treatments have been reported. We are aware of other polymorphic clinical presentations, with novel data being reported periodically, but the pathophysiological mechanisms and evolution are largely unknown.

The correlation between insulin-like growth factor with glycemic control, glomerular filtration rate, blood pressure, hematological changes or body mass index in patients with type 2 diabetes mellitus.

Insulin-like growth factor (IGF) family is made up of two polypeptides, IGF-I and IGF-II, six specific binding proteins (IGFBPs 1-6) and specific receptors. IGF-I is involved in the regulation of growth and cellular proliferation and has a similar structure to insulin. The major IGF transport function is attributed to IGFBP-3. Some studies have highlighted the association between IGF and diabetes. The aims of this study were to analyze the correlation between IGF with glycemic control, glomerular filtration rate (GFR), blood pressure, hematological changes or body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM). Thirty patients with T2DM and thirty non-diabetic control patients were included in this study. Clinical, anthropometric, biochemical parameters and morphology of blood smear were recorded. Blood pressure was determined by mercury sphygmomanometer. The anthropometric measurement included BMI. The biochemical parameters included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), GFR, serum IGF-I, IGFBP-3 levels. The IGF-I÷IGFBP-3 ratio was evaluated. The plasma glucose was determined enzymatically, HbA1c was determined by high-performance liquid chromatography (HPLC) and GFR was calculated automatically. IGF-I was measured by immunoradiometric assay (ELISA - enzyme-linked immunosorbent assay) and IGFBP-3 by sensitivity immunoassay. For the analysis of the morphology of blood smear, May-Grünwald-Giemsa (MGG) was used as staining technique. The microscopic examination was performed initially with the objectives of 10×÷20× and subsequently with an immersion objective of 100×. Image acquisition was done after the examination of the preparations obtained with a 40× objective, using Image Pro Plus 6.0 software. In the present study, we observed that T2DM leads to an increase in the IGF-I and IGFBP-3 levels. No relationship was obtain between IGF-I, IGFBP-3 levels and IGF-I÷IGFBP-3 ratio with neither parameters studied. The difference of serum IGF-I and IGFBP-3 levels between patients with T2DM and subjects without diabetes showed that IGF-I may be a useful marker for diabetes mellitus and IGFBP-3 for possible complications of this affection.

Comparative evaluation of short-term toxicity of inorganic arsenic compounds on Artemia salina.

The study aimed to assess the short-term effects exerted by two inorganic arsenic species (arsenite and arsenate) on Artemia salina after 24, 48 and 72 h. The dose-lethality curves obtained indicate that the lethality induced by arsenite was higher than by arsenate. The lowest observed effect concentration for arsenite (0.5 µg/mL) is similar with the no observed effect concentration for arsenate, thus indicating that the toxicity of arsenite is higher compared with arsenate. Also, the lethal concentration 50 values confirm that arsenite induced about 1.24-fold higher toxicity than arsenate at 24 h and about three-fold higher toxicity at 48 h and 72 h of exposure. Both LC50 (lethal concentration 50) values are indicating negligible effects exhibited by arsenic at this trophic level after short-term exposure. The predicted no effect concentration in the surface aquatic compartment corresponds to 10.38 µg/L, similar to the limit imposed by Directive 98/83/EC.

Studies regarding the protective effects exhibited by antidepressants on cell models.

The study aimed to assess in vitro the short-term effects exerted by fluoxetine, sertraline and venlafaxine on certain physiological properties in two different study models: U937 monocytes and erythrocytes isolated from patients treated with the above-mentioned molecules. Results on U937 cell suspensions revealed the depolarization of the cell membrane induced by the three antidepressants. The maximal depolarization effect was registered after 15 minutes of cell exposure and was concentration-dependent, in a non-monotonic manner. The effect was also dependent on the tested compound, fluoxetine presenting the strongest depolarizing effect compared to sertraline and venlafaxine. The erythrocyte susceptibility to lipid peroxidation and glucose-6-phosphate dehydrogenase activity were assessed on red blood cells isolated from patients with depressive disorder. Our results revealed that antidepressant treatment induced the antioxidant defense, by decreasing erythrocyte susceptibility to lipid peroxidation and increasing glucose-6-phosphate dehydrogenase activity. The effect is more intense in the case of severe pathology and less evident in the case of moderate or minor disorder, as expressed by MADRS (Montgomery-Åsberg Depression Rating Scale) score. Our results could indicate that selected antidepressants at therapeutic concentrations, besides their known pharmacological effects, exhibit a protective effect against oxidative stress and also influence cells with immune properties.

Papillary thyroid carcinoma with anaplastic dedifferentiation in the lymph node metastasis - a rare form of presentation even for a tall cell variant.

Papillary thyroid carcinoma (PTC) is well known as a differentiated thyroid carcinoma with an established treatment protocol and high survival rates. Nevertheless, its tall cell variant (TCV) is more frequent diagnosed with larger tumor size, advanced age and metastasis comparing to other PTC cases, resembling an increased level of aggressiveness attributable to the histological subtype according to recent studies. We present the case of a 60-year-old woman who came for a recently increase of the thyroid and a left laterocervical mass associated with pain and alteration of general status. Thyroidectomy revealed a TCV of PTC with infiltration of the extrathyroid tissue. The laterocervical mass posed difficulties to surgical excision but in a second attempt proved to be an undifferentiated carcinoma. The findings were associated to a rapid deterioration of the patient's general condition finalized with death within less than three months from the initial presentation.

The prevalence of the red cell morphology changes in patients with type 2 diabetes mellitus.

Previous studies have shown that hematological alterations are a common finding in patients with diabetes. The aim of our study was to estimate the prevalence of the red cell morphology changes in diabetic patients and their correlation with markers of glycemic control. Thirty patients with type 2 diabetes mellitus were recruited for this study. Patient demographics, relevant concomitant illnesses and medical history were recorded. Anthropometric, biochemical parameters (fasting plasma glucose - FPG, glycated hemoglobin - HbA1c, glomerular filtration rate - GFR) and morphology of blood smear were assessed. Results were compared with the same measurements in 30 subjects without diabetes mellitus. The groups were similar in terms of age and gender but there were statistically significant differences for the recorded parameters in patients of study group and control subjects. Regarding the assessment of FPG, in the study group were recorded averages of 217.70±73.20 mg÷dL compared with controls that compared with controls that had a blood glucose value of 90.03±6.59 mg÷dL. In the study group, mean HbA1c was 7.95±1.99%. For the control group, the mean value of HbA1c was 5.65±0.32%. In the study group, GFR ranged between 47.70 and 118.90 mL÷min.÷1.73 m². For the control group, GFR values were between 88.00 and 130.00 mL÷min.÷1.73 m². In the analysis of blood cytology for the study group, there were changes in the smear type hypochromia, anisocytosis and poikilocyosis (20 patients - 66.66%). In terms of red cell morphology, changes were recorded anulocytes type, red cells in "mark to the target fired" (codocytes), bream (leptocytes), schizocytes, and red cells in "drop" (dacryocytes). We observed a high prevalence of the red cell morphology changes in diabetic patients compared with non-diabetic subjects. Our findings suggest the need of screening for routine hematological tests in type 2 diabetes mellitus.

Inhibin alpha-subunit, Melan A and MNF116 in pheochromocytomas.

AIM: The aim of this study was to make immunohistochemical analyses with Inhibin alpha-subunit, Melan A and MNF116 (pan-Cytokeratin antibody) in pheochromocytomas, because immunohistochemistry is useful for the distinction between adrenal tumors. PATIENTS AND METHODS: We used 20 patients with pheochromocytomas submitted to laparoscopic (n=19) or classical (n=1) surgery and we have explored immuno-staining with Inhibin alpha-subunit, Melan A and MNF116 in these tumors. This can be helpful when we cannot make the distinction between adrenal tumors. RESULTS: Pheochromocytomas did not stain with Inhibin alpha-subunit, Melan A and MNF116. CONCLUSIONS: In our study, Inhibin alpha-subunit, Melan A and MNF116 were not sensitive for pheochromocytomas.

The poor prognosis factors in G2 neuroendocrine tumor.

BACKGROUND: The G2 neuroendocrine tumors (NET) or well-differentiated neuroendocrine carcinomas (2010 WHO Classification of Tumours of the Digestive System) embrace different types of evolution despite the fact that they actually are included in the same group of prognosis based on mitotic count and the Ki-67 proliferation index. AIM: We studied the pathological and clinical aspects in patients with G2 NET. MATERIALS AND METHODS: This is a retrospective pilot observational study in patients admitted between January 2008 and January 2013 in "Constantin I. Parhon" National Institute of Endocrinology, Bucharest, Romania. They were evaluated based on the pathological report, imagistic scan, and neuroendocrine markers. RESULTS: Nine patients (female/male ratio: 5/4) with G2 NET were included (mean age at diagnosis 54.11 years). Surgery was performed in 66.66% of cases. 44.44% of tumors had unknown origin. 22.22% of patients had negative immunostain for chromogranin A. Synaptophysin was positive in all cases. Neuronal specific enolase (NSE) was performed in 44.44% of cases and it was positive in all these situations. 88.88% of patients had high neuroendocrine markers. Multiple tumors were found in two cases (follicular thyroid adenoma, and a carcinoma of the port vein, respective bilaterally pheochromocytomas). The youngest patient (39-year-old) had atypical onset with bilateral adrenal tumors (positive for CHROMO, EMA, CK-19, CK-20, negative for SOMATO, CK-7, S-100, glucagon, CD57, and a Ki-67 of 15%). Death was registered in two cases, both with bone metastases. DISCUSSION: Some poor prognosis factors may be taken into account as lack of CHROMO immunostain, young age at diagnosis, genetic background, and lack of therapy options as surgery. Larger databases will provide more information. CONCLUSIONS: It is possible that the G2 NET group of tumors actually includes some different subtypes or in fact, a late diagnosis of the tumor might be associated with a poor diagnosis.

The dedifferentiation of neuroendocrine tumor metastases: myth or reality?

Dedifferentiation is a process that may be found in metastasis from the neuroendocrine tumors. We present the case of a female within the seventh decade of life incidentally diagnosed with a mature teratoma with element of cartilages, bronchia, mucinous glands, and a poorly differentiated neuroendocrine carcinoma (Ki67 of 30%). After six months of chemotherapy and another six months of disease free interval, a metastasis of the great omentum was removed. The dedifferentiation was diagnosed based on much higher Ki67 (of 70%). The loss of estrogen receptor of 40% from the initial site to 3% into metastasis indicates an exclusive neuroendocrine aggressive pattern. The ovarian carcinoid is a rare situation, and metastasis to the great omentum with dedifferentiation is even seldom.

Well-differentiated neuroendocrine tumor and osteoporosis: incidental findings?

The neuroendocrine tumors (NETs) have an increased incidence related to the age. Secondary osteoporosis might be found in patients with bone metastases and in those with NETs associated Cushing's disease or primary hyperparathyroidism. Primary osteoporosis might be found in postmenopausal women, but in case with non-metastatic NET as G1 NET it is difficult to establish the NET contribution to the bone loss. We present the case of a 53-year-old female accidentally diagnosed with G1 lung NET after surgery of the tumor. The immunohistochemistry pointed positive reaction for CHROMO, SYN and negative for CK7 and TTF1, and a Ki67 of 1-2% (well-differentiated neuroendocrine tumor). The central Dual X-Ray Absorptiometry (DXA) showed osteoporosis based on a T-score of -3. The patient had normal neuroendocrine markers and she was asymptomatic. She remained so for one year and the only therapy provided was weekly alendronate with adequate vitamin D and calcium supplements. Based on the pathological and immunohistochemistry profile, the low risk NET was diagnosed. We encourage the skeletal status assessment as central DXA in postmenopausal women with NETs, regardless clinical evidence of bone loss. The future will provide more epidemiological and pathogenic connections between the two dynamic fields of medicine as neuroendocrine tumors and osteoporosis.

The immunohistochemistry aspects in two cases of neurofibromatosis-associated abdominal tumors.

Type 1 neurofibromatosis associates various abdominal tumors as gastrointestinal stromal tumors, duodenal or pancreatic carcinoid, and adrenal tumors like pheochromocytoma. We present the immunohistochemistry report in two cases with different profile regarding the evolution. One case is a 7th decade women diagnosed with unilateral pheochromocytoma and GISTs, with a good prognosis after surgery. The other case is a 41-year-old male diagnosed with duodenal metastatic somatostatinoma after an intestinal occlusive syndrome and later the hormonal profile leaded to the diagnosis of pheochromocytoma. The patient had a fulminate evolution within six months from diagnosis.

The value of the immunohistochemistry in a case of gastric neuroendocrine tumor and thyroid metastasis.

Thyroid metastasis is atypical. We present a 70-year-old female case that was first diagnosed as gastric cancer after surgical approach. Two years later a thyroidectomy was performed and the immunohistochemistry (IHC) profile revealed a neuroendocrine tumor (NET): poorly differentiated neuroendocrine carcinoma (with small cells), with positive reaction for SYN, CROMO, negative for calcitonin, TTF1 and thyreoglobulin. The Ki-67 index was 25%. Considering the unusual metastasis, the IHC exam of the stomach tumor was performed pointing the same features as the thyroid findings. This proved that the thyroid tumor was a metastasis from a primary gastric neoplasia. This is an unusual case of NET because of the thyroid involvement. Nevertheless, the IHC exam played the major role in elucidating the diagnosis and the prognosis of the case.

Contributions to myometrium study in uterine-tubal junction.

Complex coordinated contractions of the tubal musculature are thought to be important for movement of the ovum from the distal end to the proximal end of the tube, while at the same time aiding in the movement of sperm from the proximal end to the distal end of the oviduct. Studies of the anatomy and the physiology of the uterine-tubal junction (UTJ), with a main concern for the muscular pattern and the secretory activity of this part of the tube, in relation with the hormonal and nervous control, can play an important role in understanding and impairment of infertility. Related to these aspects, the purpose of our research is mainly to identify the determining factors in maintaining a morphological and structural balance between contractile items and extracellular matrix items within uterine myometrium, particularly uterine-tubal junction. For this reason, the present study includes analyses of anatomical sections within uterus and uterine tubes extracted from patients during therapeutic surgeries. Thirty anatomical pieces from patients aged 23-37-year-old (uterus and tubes) were used to perform microanatomical sections, 10 pieces for each pathology identified, namely leiomyofibroma, leiomyofibroma with pregnancy, ectopic pregnancies. At the same time, the study proposes a statistic and mathematic analysis of the cases with uterine-tubal junction pathology in Oltenia region within a period of 10 years. The novelty of the study is represented by the identification of certain continuity ratios between myocyte fascicles and average tunica of arteries and arterioles, which explains the existence of "vascular units" determined by myometrial structures. Moreover, the stereo-distribution of "vascular myometrial units" explains the existence of a plexiform cavernous network, which enables many authors to describe numerous barely individualized myometrial tunicas. These units are rich in orthosympathetic vegetative innervations that might be responsible for the unfavorable evolution of circulatory myometrial system in postpartum. Considering all these observations, it is highly necessary to reconsider the structure of the uterine wall and, particularly of uterine-tubal junction.

New approaches to cancellous bone bio-modeling.

The purpose of our research is to develop a model of cancellous bone that would allow us to forecast the changes in this structure under various mechanical forces and to simulate the dynamics of the cancellous bone behavior under these circumstances. At the same time, the suggested model will allow the measurement of the tension/forces applied onto the bone structure, with the purpose of comparing these with the in vitro values, identification of the areas with increased trauma risk, and simulation of the behavior of cancellous substance under different mechanical stimuli, which affect the growth and aging of the bone, as well as to study the materials used in endoprostheses. Two groups of methods have been used for this purpose: micro-anatomical methods - for the visualization of bone structures, and bio-mathematical methods (finite element method) - for the modeling of these structures. The micro-anatomical studies were performed on a group of six bone items, from which 12 samples were harvested from the femoral head and neck, from corpses of both sexes and of varying ages, whose death was not due to specific pathological states or which could regard the bone itself. The obtained results have allowed us in identification of dependency relationships between the microscopic structure of the trabecular bone and its mechanical properties, as well as for the elaboration of bidimensional reconstructive and analytic models of the cancellous bone, which would further allow detailed representation of samples of cancellous bone that are big enough to supply macroscopic information. The conclusions of the present research have illustrated the usefulness of using the finite element method in the study of the mechanical behavior of spongy tissue, thus opening large perspectives in approaching the issue of the behavior of this tissue.

Neuromuscular investigation in diabetic polyneuropathy.

The aim of this paper is to present to new method for assessment diabetic polyneuropathy, before the moment of first clinical sign. Our working presents the method of tensiomyography (TMG) for assess the muscle composition rapports with muscle fibers types I and II. This composition can help to have an image regards the neuromuscular potential of muscle during diabetic process. Tensiomyographic parameters included time contraction Tc, time delay Td, sustain time Ts, displacement Dm, and relax time Tr. All these parameters give information regards muscle fatigue in correlation with muscle composition. Muscle composition regards fibers type I or II is in relation with Tc, increase of these parameters means decrease of muscle fibers type I that means muscle fatigue. Also, values of Dm help us to assess the muscle tonus, elasticity and response to electrostimulus. We consider that this method helps the clinicians to have a prediction of a future polyneuropathy at diabetic patients.