Early Outcome of Multisystem Inflammatory Syndrome in Neonates Diagnosed following Prenatal Maternal COVID-19 Infection: A Three-Case Series.

BACKGROUND: The aim of this case series report is to evaluate the characteristics of multisystem inflammatory syndrome (MIS) in neonates following prenatal maternal COVID-19 infection. METHODS: We present a case series of three newborns (≤28 days of age) diagnosed with MIS due to the vertical transmission of SARS-CoV2 infection and admitted from 1 January 2021 to 1 June 2023. The inclusion criteria were negative RT-PCR-SARS-CoV-2 test in infants, initial negative IgM-SARS-CoV-2 in infants followed by the emergence of positive IgG-SARS-CoV-2 antibodies in infants and maternal COVID-19 infection in the third trimester of pregnancy. Patients enrolled in this case series were admitted due to acute febrile illnesses. RESULTS: All three cases occurred in patients born at a mean gestational age of 39 weeks and who were appropriate for gestational age. The mean age at admission was 18.3 days. Fibrinogen (>400 mg/dL) and ferritin (>120 mg/dL) were elevated above the upper normal limit. Elevated levels of myocardial biomarkers (D-dimers, N-terminal pro b-type natriuretic peptide troponin T and creatine phosphokinase myocardial band) were recorded, with normal heart function evaluated using echocardiography. All three patients were treated with antibiotics; one received intravenous immunoglobulin. A 4-week follow-up was completed in two patients when their myocardial biomarkers and ferritin were still elevated but lower compared with previous examinations. D-dimers levels were normalized in 2/3 patients. CONCLUSIONS: Subclinical myocarditis was diagnosed as an early outcome in infants with MIS diagnosed postnatally due to the vertical transmission of SARS-CoV2 infection and may represent a new challenge for pediatricians in the pandemic era.

Bevacizumab Treatment for Metastatic Colorectal Cancer in Real-World Clinical Practice.

Background and Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality and morbidity worldwide. Bevacizumab was approved for the treatment of metastatic colorectal cancer (mCRC) based on favorable benefit-risk assessments from randomized controlled trials, but evidence on its use in the real-world setting is limited. The aim of the current study is to evaluate the outcomes and safety profile of bevacizumab in mCRC in a real-world setting in Romania. Patients and Methods: This was an observational, retrospective, multicentric, cohort study conducted in Romania that included patients with mCRC treated with bevacizumab as part of routine clinical practice. Study endpoints were progression-free survival, overall survival, adverse events, and patterns of bevacizumab use. Results: A total of 554 patients were included in the study between January 2008 and December 2018. A total of 392 patients (71%) received bevacizumab in the first line and 162 patients (29%) in the second line. Bevacizumab was mostly combined with a capecitabine/oxaliplatin chemotherapy regimen (31.6%). The median PFS for patients treated with bevacizumab was 8.4 months (interquartile range [IQR], 4.7-15.1 months) in the first line and 6.6 months (IQR, 3.8-12.3 months) in the second line. The median OS was 17.7 months (IQR, 9.3-30.6 months) in the first line and 13.5 months (IQR, 6.7-25.2 months) in the second line. Primary tumor resection was associated with a longer PFS and OS. The safety profile of bevacizumab combined with chemotherapy was similar to other observational studies in mCRC. Conclusions: The safety profile of bevacizumab was generally as expected. Although the PFS was generally similar to that reported in other studies, the OS was shorter, probably due to the less frequent use of bevacizumab after disease progression and the baseline patient characteristics. Patients with mCRC treated with bevacizumab who underwent resection of the primary tumor had a higher OS compared to patients with an unresected primary tumor.

Effective Connectivity in Spinal Cord Injury-Induced Neuropathic Pain.

AIM: The aim of this study was to differentiate the effects of spinal cord injury (SCI) and central neuropathic pain (CNP) on effective connectivity during motor imagery of legs, where CNP is typically experienced. METHODS: Multichannel EEG was recorded during motor imagery of the legs in 3 groups of people: able-bodied (N = 10), SCI with existing CNP (N = 10), and SCI with no CNP (N = 20). The last group was followed up for 6 months to check for the onset of CNP. Source reconstruction was performed to obtain cortical activity in 17 areas spanning sensorimotor regions and pain matrix. Effective connectivity was calculated using the directed transfer function in 4 frequency bands and compared between groups. RESULTS: A total of 50% of the SCI group with no CNP developed CNP later. Statistically significant differences in effective connectivity were found between all groups. The differences between groups were not dependent on the frequency band. Outflows from the supplementary motor area were greater for the able-bodied group while the outflows from the secondary somatosensory cortex were greater for the SCI groups. The group with existing CNP showed the least differences from the able-bodied group, appearing to reverse the effects of SCI. The connectivities involving the pain matrix were different between able-bodied and SCI groups irrespective of CNP status, indicating their involvement in motor networks generally. SIGNIFICANCE: The study findings might help guide therapeutic interventions targeted at the brain for CNP alleviation as well as motor recovery post SCI.

Winners and losers in brain computer interface competitive gaming: directional connectivity analysis.

Objective. To characterize the direction within and between brain connectivity in winning and losing players in a competitive brain-computer interface game.Approach. Ten dyads (26.9 ± 4.7 yr old, eight females and 12 males) participated in the study. In a competitive game based on neurofeedback, they used their relative alpha (RA) band power from the electrode location Pz, to control a virtual seesaw. The players in each pair were separated into winners (W) and losers (L) based on their scores. Intrabrain connectivity was analyzed using multivariate Granger causality (GC) and directed transfer function, while interbrain connectivity was analyzed using bivariate GC.Main results. Linear regression analysis revealed a significant relationship (p< 0.05) between RA and individual scores. During the game, W players maintained a higher RA than L players, although it was not higher than their baseline RA. The analysis of intrabrain GC indicated that both groups engaged in general social interactions, but only the W group succeeded in controlling their brain activity at Pz. Group L applied an inappropriate metal strategy, characterized by strong activity in the left frontal cortex, indicative of collaborative gaming. Interbrain GC showed a larger flow of information from the L to the W group, suggesting a higher capability of the W group to monitor the activity of their opponent.Significance. Both innate neurological indices and gaming mental strategies contribute to game outcomes. Future studies should investigate whether there is a causal relationship between these two factors.

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review.

In CRC, screening compliance is decreased due to the experienced discomfort associated with colonoscopy, although this method is the gold standard in terms of sensitivity and specificity. Promoter DNA methylation (hypomethylation or hypermethylation) has been linked to all CRC stages. Study objectives: to systematically review the current knowledge on approved biomarkers, reveal new potential ones, and inspect tactics that can improve performance. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; the risk of bias was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). The Web of Science® Core Collection, MEDLINE® and Scopus® databases were searched for original articles published in peer-reviewed journals with the specific keywords "colorectal cancer", "early detection", "early-stage colorectal cancer", "epigenetics", "biomarkers", "DNA methylation biomarkers", "stool or blood or tissue or biopsy", "NDRG4", "BMP3", "SEPT9", and "SDC2". Based on eligibility criteria, 74 articles were accepted for analysis. mSDC2 and mSEPT9 were frequently assessed in studies, alone or together as part of the ColoDefense panel test-the latter with the greatest performance. mBMP3 may not be an appropriate marker for detecting CRC. A panel of five methylated binding sites of the CTCF gene holds the promise for early-stage specific detection of CRC. CRC screening compliance and accuracy can be enhanced by employing a stool mt-DNA methylation test.

Brain Synchrony in Competition and Collaboration During Multiuser Neurofeedback-Based Gaming.

EEG hyperscanning during multiuser gaming offers opportunities to study brain characteristics of social interaction under various paradigms. In this study, we aimed to characterize neural signatures and phase-based functional connectivity patterns of gaming strategies during collaborative and competitive alpha neurofeedback games. Twenty pairs of participants with no close relationship took part in three sessions of collaborative or competitive multiuser neurofeedback (NF), with identical graphical user interface, using Relative Alpha (RA) power as a control signal. Collaborating dyads had to keep their RA within 5% of each other for the team to be awarded a point, while members of competitive dyads scored points if their RA was 10% above their opponent's. Interbrain synchrony existed only during gaming but not during baseline in either collaborative or competitive gaming. Spectral analysis and interbrain connectivity showed that in collaborative gaming, players with higher resting state alpha content were more active in regulating their RA to match those of their partner. Moreover, interconnectivity was the strongest between homologous brain structures of the dyad in theta and alpha bands, indicating a similar degree of planning and social exchange. Competitive gaming emphasized the difference between participants who were able to relax and, in this way, maintain RA, and those who had an unsuccessful approach. Analysis of interbrain connections shows engagement of frontal areas in losers, but not in winners, indicating the formers' attempt to mentalise and apply strategies that might be suitable for conventional gaming, but inappropriate for the alpha neurofeedback-based game. We show that in gaming based on multiplayer non-verbalized NF, the winning strategy is dependent on the rules of the game and on the behavior of the opponent. Mental strategies that characterize successful gaming in the physical world might not be adequate for NF-based gaming.

The Role of Histopathology and Immunohistochemistry in the Diagnosis of Neuroendocrine Biliary Duct Tumor.

Neuroendocrine tumors of the biliary tract are rare entities developed form Kulchitsky cells which undergo a process of malignant transformation. However, the differential diagnostic between neuroendocrine tumors of the biliary tract and hilar cholangiocarcinoma is very difficult to be established during the preoperative workup; therefore, most patients are submitted to surgery with radical intent and the final diagnostic remains to be confirmed through histopathological and immunohistochemistry studies of the specimen of resection. We present the case of a 60 year old patient who was submitted to en bloc extended right hepatectomy (including segment IV and caudate lobe) with extra hepatic biliary tree resection and left hepatic duct preservation, left cholangiojejunostomy (Roux-En-Y technique), celiac and common hepatic arteries lymphadenectomy and segmental portal vein resection with end-to-end anastomosis for a tumor of the biliary carrefour extended to the right biliary duct and invading the portal vein. The histopathological and immunohistochemistry studies confirmed the presence of a grade 1 neuroendocrine tumor, the staining being positive for Chromogranin A, Neuron-Specific Enolase (NSE) and Ki-67 (1% nuclear positive). At 24 months follow-up the patient is free of recurrent disease.

The macroscopic examination of the placental vasculature with a corrosive agent.

The placental development is a complex process, in which any disturbance can induce changes with grave consequences for the offspring. Villi and villous vascularization development is in, and underdevelopment can lead to villous placental insufficiency. This paper aims to analyze the arterial and venous vasculature of the placenta, both macroscopic and morphologically, by different injection techniques of contrast agents (plastic substances type AGO II) in 50 human placentas with different ages of gestation.

Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study.

AIM: This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. METHODS: We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. RESULTS: Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. CONCLUSION: Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.