Search

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Acute promyelocytic leukemia (APL) is a unique, highly curable subtype of acute myeloid leukemia, owing to the therapeutic advances of the last decades which led to high complete remission rates and excellent long-term survival. Nevertheless, it remains associated with high early mortality rates. Early death is the major cause of treatment failure in APL and is mainly attributed to coagulopathy, differentiation syndrome, and less commonly, infectious events. Timely recognition of each complication plays a crucial role in the management of patients diagnosed with APL. Coronavirus Infectious Disease 2019 (COVID-19) has shown great heterogeneity in patient presentation. Clinical manifestations range from asymptomatic disease to severe forms, mainly characterized by a hyperinflammatory syndrome leading to acute respiratory distress and multiorgan failure. Patients with acute leukemia and concomitant COVID-19-related hyperinflammatory syndrome have particularly poor outcomes. We hereby report the case of a 28-year-old male patient who was diagnosed with high-risk APL, with severe associated coagulopathy at presentation. He was treated with chemotherapy according to the AIDA regimen. The first week of induction therapy was complicated by a differentiation syndrome manifesting as fever not attributable to infection and respiratory distress with pulmonary infiltrates, resolved after ATRA discontinuation and corticotherapy. On the fourth week of treatment, he tested positive for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with minor pulmonary involvement. Clinical manifestations over the following days included tachycardia and hypotension, associated with elevated inflammatory markers and cardiac biomarkers (troponin I x58 upper NV). Cardiovascular magnetic resonance imaging was consistent with myocarditis. COVID-19-associated myocarditis was successfully treated with methylprednisolone, intravenous immunoglobulins and Anakinra. Differentiation syndrome and COVID-19-associated myocarditis are two life-threatening complications that adversely impact survival. However, early recognition and prompt treatment initiation can improve clinical outcomes, as was the case of our patient.

Background: Peri‐implant mucositis (PIM) is a pathological precursor of peri‐implantitis, but its pattern of conversion to peri‐implantitis is unclear and complicated to diagnose clinically, while none of the available protocols yield complete disease resolution. The aim of this study was the evaluation of PIM responsiveness to standard anti‐infective mechanical treatment (AIMT) at clinical and biomarker levels, and estimation of the diagnostic capacity of bone markers as surrogate endpoints and predictors. Methods: Systemically healthy outpatients presenting one implant exhibiting clinical signs of inflammation confined within the soft tissue (PIM) and one healthy control (HC) implant at a non‐adjacent position were included. Clinical parameters and peri‐implant crevicular fluid samples were collected baseline and 6 months following mechanical therapy, to assess the levels of RANKL, OPG, and IGFBP2. PIM clustering was performed using machine learning algorithms. Results: Overall, 38 patients met the inclusion criteria. Therapy resulted in the reduction of all clinical and biological indicators, but respective values remained significantly higher compared to HC. Clinical examination noted 30% disease resolution at the 6‐month follow‐up, while 43% showed no active bone resorption. OPG showed positive prognostic value for treatment outcome, while the clustering based on active bone resorption did not differ in terms of therapeutic effectiveness. Conclusion: AIMT is effective in reducing the clinical and biological indicators of PIM, but complete clinical resolution was achieved in only 30% of the cases. Around one third of PIM patients exhibited active bone resorption bellow clinical detectability that was not associated with disease progression and poor treatment responsiveness. [ABSTRACT FROM AUTHOR]

Summary: The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs). The ASC/NLRP3 specks were significantly elevated in MDS patients compared to healthy controls (p < 0.001) and these levels were comparable to those found in patients with AIDs. The distribution of protein specks positive only for ASC was different to ASC/NLRP3 ones suggesting that other ASC‐containing inflammasome complexes might be important in the pathogenesis of MDS. Patients with MDS‐SLD had the lowest levels of interleukin (IL)‐1β, tumour necrosis factor (TNF), IL‐23, IL‐33, interferon (IFN) γ and IFN‐α2, compared to other diagnostic categories. We also found that inflammatory cytokine TNF was positively associated with MDS progression to a more aggressive form of disease and IL‐6 and IL‐1β with time to first red blood cell transfusion. Our study shows that there is value in analysing inflammatory biomarkers in MDS, but their diagnostic and prognostic utility is yet to be fully validated. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by an excessive production of functionally mature and terminally differentiated myeloid cells. MPNs can transform into secondary acute myeloid leukemia (sAML/blast phase MPN) and are linked to alterations in the redox balance, i.e., elevated concentrations of reactive oxygen species and markers of oxidative stress (OS), and changes in antioxidant systems. We evaluated OS in 117 chronic phase MPNs and 21 sAML cases versus controls by measuring total antioxidant capacity (TAC) and 8-hydroxy-2′-deoxy-guanosine (8-OHdG) concentrations. TAC was higher in MPNs than controls (p = 0.03), particularly in ET (p = 0.04) and PMF (p = 0.01). MPL W515L-positive MPNs had higher TAC than controls (p = 0.002) and triple-negative MPNs (p = 0.01). PMF patients who had treatment expressed lower TAC than therapy-free subjects (p = 0.03). 8-OHdG concentrations were similar between controls and MPNs, controls and sAML, and MPNs and sAML. We noted associations between TAC and MPNs (OR = 1.82; p = 0.05), i.e., ET (OR = 2.36; p = 0.03) and PMF (OR = 2.11; p = 0.03), but not sAML. 8-OHdG concentrations were not associated with MPNs (OR = 1.73; p = 0.62) or sAML (OR = 1.89; p = 0.49). In conclusion, we detected redox imbalances in MPNs based on disease subtype, driver mutations, and treatment history. [ABSTRACT FROM AUTHOR]

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential. [ABSTRACT FROM AUTHOR]

Introduction Papillary thyroid carcinoma (PTC) and colloid goiter (CG) represent the most common thyroid malignant and benign diseases, respectively. Oxidative stress is considered to have an important role in the pathogenesis of both diseases, but without sufficient and comprehensive data. The aim was to evaluate the redox profile, its influence on cell survival of PTC, comparing it with CG as a control and its relation with demographic, pathological and clinical parameters. Material and methods We evaluated for the first time the PTC and CG tissue profile of advanced oxidation protein products (AOPP) and total thiols as parameters of redox metabolism and deoxyribonuclease I (DNase I) and deoxyribonuclease II (DNase II) activity as biomarkers of cell turnover and apoptosis. Tissue levels of biochemical parameters were quantified in PTC and CG tissue using spectrophotometric methods. Study parameters were evaluated in light of different demographic, clinical and pathological features of PTC and CG. Results Papillary thyroid carcinoma tissue is characterized by increased antioxidant activity and a normal prooxidation level. Biochemical parameters show numerous correlations with demographic and clinical characteristics of PTC and CG patients. DNase I and II activities are dependent upon the AOPP concentration in PTC tissue. The size of CG can be predicted with combined use of AOPP, DNase I and DNase II. AOPP is the most powerful predictor of PTC capsular invasion, multicentric intrathyroid dissemination and lymph node metastasis phenotype. Conclusions Evaluated parameters can be used for assessment of tumor redox and survival status and the clinical course of PTC and CG.

Studies aimed at neurological drug discovery have been carried out both in vitro and in vivo. In vitro cell culture models have showed potential as drug testing platforms characterized by high throughput, low cost, good reproducibility and ease of handling and observation. However, in vitro neuronal culture models are facing challenges in replicating in vivo-like activity patterns. This work reports an in vitro culture technique that is capable of producing micro three-dimensional (μ3D) cultures of only a few tens of neurons. The μ3D cultures generated by this method were uniform in size and density of neurons. These μ3D cultures had complex spontaneous synchronized neuronal activity patterns which were similar to those observed in the developing cortex and in much larger 3D cultures, but not in 2D cultures. Bursts could be reliably evoked by stimulation of single neurons. Synchronized bursts in μ3D cultures were abolished by inhibitors of glutamate receptors, while inhibitors of GABAA receptors had a more complex effect. This pharmacological profile is similar to bursts in neonatal cortex. Since large numbers of reproducible μ3D cultures can be created and observed in parallel, this model of the developing cortex may find applications in high-throughput drug discovery experiments.

Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.

Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk MDS/acute myeloid leukemia as events. Of the 1,267 patients included in the analyses, 317 died without progression; in 162 patients the disease had progressed. PFS was significantly associated with age, EQ-5D index, baseline World Health Organization classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with PFS (P

Abstract: Prognosis of lower-risk (International Prognostic Scoring System [IPSS] low/intermediate-1) myelodysplastic syndrome (MDS) is heterogeneous and relies on steady-state assessment of cytopenias. We analyzed relative drops in neutrophil and platelet counts during the first 6 months of follow-up of lower-risk MDS patients. We performed a landmark analysis of overall survival (OS) of lower-risk MDS patients prospectively included in the European LeukaemiaNet MDS registry having a visit at 6 ± 1 month from inclusion to assess the prognostic relevance of relative drops in neutrophils and platelets, defined as (count at landmark − count at inclusion)/count at inclusion. Of 2102 patients, 807 were eligible for the stringent 6-month landmark analysis. Median age was 73 years. Revised IPSS was very low, low, and intermediate/higher in 26%, 43%, and 31% of patients, respectively. A relative drop in platelets >25% at landmark predicted shorter OS (5-year OS, 21.9% vs 48.6% with platelet drop ≤25%, P < 10−4), regardless of baseline IPSS-revised or absolute platelet counts. Relative neutrophil drop >25% had no significant impact on OS. We built a classifier based on red blood cell transfusion dependence (RBC-TD) and relative platelet drop >25% at landmark. Patients with none (62%), either (27%), or both criteria (11%) had 5-year OS of 53.3%, 32.7%, and 9.0%, respectively (P < 10−4). This classifier was validated in an independent cohort of 335 patients. Combining relative platelet drop >25% and RBC-TD at 6 months from diagnosis provides an inexpensive and noninvasive way to predict outcome in lower-risk MDS. This study was registered at www.clinicaltrials.gov as #NCT00600860.

OBJECTIVE: Caudal block is a type of regional anesthesia suitable for inguinal hernia surgery in children. Our goal was to determine the effectiveness of caudal block combined with general anesthesia in providing intraand postoperative analgesia and its effect on hemodynamic stability and drug consumption. PATIENTS AND METHODS: Prospective, randomized controlled study included 78 boys, 3-5 years, with an indication for inguinal herniorrhaphy, divided into groups G (general anesthesia, n=39) and G+C (general anesthesia + caudal block, n=39). We monitored hemodynamic parameters intraoperatively, postoperative pain, and total consumption of all medicaments in the perioperative period. The monitoring of complications and side effects of drugs was also carried out. RESULTS: Boys in group G had statistically significantly higher values of heart rate in the 5th minute (p<0.01), in the 25th minute (p<0.01), and after awakening from anesthesia (p<0.01). We obtained similar results with systolic and diastolic pressure values in the 5th minute (p<0.01), 15th minute (p<0.01), 25th minute (p<0.01), before awakening from anesthesia (p<0.01) and after awakening (p<0.01). They also had significantly statistically higher total consumption of propofol, fentanyl, and acetaminophen (p<0.01). Boys in group G+C had significantly lower postoperative pain scores: initially (p<0.01), after 2 hours (p<0.01), and after 5 hours (p<0.01). No complications occurred in this group. CONCLUSIONS: In children, the combination of general anesthesia with caudal block, compared to general anesthesia only, is more effi- cient in suppressing visceral pain, leading to better hemodynamic stability, and reducing the consumption of medicines in the perioperative period. [ABSTRACT FROM AUTHOR]

Introduction: Etopic pancreas is a rare developmental anomaly. It is presence of pancreatic tissue without anatomic or vascular continuity with the normally developed pancreas. The most common heterotopic site is the stomach commonly involving antrum and prepyloric region on the greater curvature or posterior wall. Ectopic pancreas is diagnosed by endoscopic ultrasound, gastroscopy and biopsy, CT scan and MRI of the abdomen, a definitive diagnosis is verified by histopathological examination. Treatment is surgical. Case report: A 56-year-old woman presented with epigastric pain, nausea and fatigue. Esophagogastroduodenoscopy showed submucosal mass in the prepyloric region, biopsy was performed. Histopatological findings described normal gastric mucosa. Endoscopic ultrasonogpraphy and CT of the abdomen showed submucosal tumor, 18 mm in diameter, located in the prepyloric region. Surgical treatment was indicated. Gastrotomy with total extraction of tumor was performed. Histopathology findings showed ectopic pancreatic tissue in the submucosal and muscular layer of the stomach. Postoperatively patient fully recovered, and in the 2 year folow-up did not develop any symptoms related to gastrointestinal tract. Conclusion: Although presentation of ectopic pancreatic tissue in stomach is very rare condition, it should be considered during gastroitestinal diagnostic in patients with nonspecific gastrointestinal symptomatology. In most of cases, for this patients, surgery is curative and definitive solution.

Introduction. The most common functional complications after the treatment of breast cancer are reduction of range of motion in the shoulder joint (incidence of 10 to 73%), lymphedema of the arm (10-30%) and nerve damage of the arm or damage of brachial plexus (1.8-4.9%). Multiple complications rarely occur and they are usually of mild to moderate forms. Case report. VV (woman), born in 1965 was exposed to quadrantectomy of the left breast with axillary dissection in 2003 (pathohystology: ductal carcinoma; 4 removed lymph nodes, 1 of which with a secondary deposit). After the surgical intervention, the patient underwent chemotherapy (CMF protocol VI cycles) and radiation therapy (50 Gy/12 cycles). Four months after the therapy completion, lymphedema of the left arm was developed, and few months later brachial plexus injury as well. First visit to physiatrist was five years later, with a significant reduction of range of motion in the left arm and severe lymphedema (maximum difference to 7.5 cm). EMNG trial indicated a moderate lesion of left median nerve and ulnar nerve and mild to moderate lesion of left radial nerve injury; DASH score was 107. After repeated physical treatments (since 2009), the last control in October 2016 showed that the functional status was significantly improved: reduction of range of motion was present in flexion and abduction only, lymphedema was reduced (maximum difference of 5.5 cm); DASH score was 48, while EMNG indicated a lesion of the median nerve and ulnar nerve in lower level, with signs of recovery. Conclusion. The implementation of an early rehabilitation program for the patients who were surgically treated for breast cancer is necessary in order to prevent functional complications and to enable continuous monitoring of the patients, while in the case with already developed complications, physical therapy should be initiated regardless of the period in which the functional limitations occured.

In this study, a hedonic pricing model with a stochastic frontier is applied to a sample of 183,717 observations of product sales of sausages in Germany to determine the valuation of attributes in the market. The average price of sausages is 1.14€/100 g, with meat substitutes valued at 1.53€/100 g and meat sausages at 1.01€/100 g. Our results show that credence attributes can induce a price premium, but that the effect strongly depends on the type of attribute. This may be important for deriving marketing strategies, as uniform measures may not be effective for both markets. [ABSTRACT FROM AUTHOR]