Transitory ischemic attack associated with a rare fenestration of the cervical segment of the internal carotid artery: a case report

Background Fenestration of the cervical segment of the internal carotid artery is a very rare finding, and its origin is still not fully understood. Explanations of its genesis range from dissections leading to the fenestration to the more common interpretation as a developmental vascular variant. However, most reported cases were symptomatic and presented with dissections, where even endovascular treatment of the fenestration of the cervical segment of the internal carotid artery became necessary. Here we report a case of a fenestration of the cervical segment of the internal carotid artery suffering a transitory ischemic attack and local pain in absence of any sign of dissection. Case presentation A 62-year-old Caucasian male patient was admitted to our institution because of an episode of amaurosis fugax, initially accompanied with headache. Magnetic resonance imaging revealed an intact fenestration of the cervical segment of the internal carotid artery on the symptomatic side. With antiplatelet therapy, all symptoms vanished within 2 months of the initial event. Conclusions Our findings support the interpretation of a fenestration of the cervical segment of the internal carotid artery as a developmental vascular variant, but also suggest a substantial risk for dissection and ischemic stroke. Even in case of an accidental finding, clinicians should be aware of this. At least in this case, antiplatelet therapy seemed beneficial.

Impact of Condensation on the System Performance of a Fuel Cell Turbocharger

A mobile fuel cell systems power output can be increased by pressure amplification using an electric turbocharger. These devices are subject to frequent transient manoeuvres due to a multitude of load changes during the mission in automotive applications. In this paper, the authors describe a simulation approach for an electric turbocharger, considering the impact of moist air and condensation within the cathode gas supply system. Therefore, two simulation approaches are used: an iterative simulation method and one based on a set of ordinary differential equations. Additional information is included from turbine performance maps taking into account condensation using Euler–Lagrange CFD simulations, which are presented. The iterative calculation approach is well suited to show the impact of condensation and moist air on the steady state thermodynamic cycle and yields a significant shift of the steady state operating line towards the surge line. It is shown that a substantial risk of surge occurs during transient deceleration manoeuvres triggered by a load step.

Choosing Startups as Suppliers: A Supplier Selection Archetypes Typology

Recent research demonstrates the value of examining collaborations between established organizations and startups via the lens of the buyer–supplier relationship. However, enterprises must first find, analyze, and select potential startups as suppliers before they can exploit startups' resources and talents in a buyer–supplier relationship. Due to the fact that earlier research has focused exclusively on how purchasing firms select established firms as suppliers, it is unknown which processes, tools, or organizational approaches purchasing organizations employ when selecting startup firms as suppliers. These suppliers are qualitatively distinct in that they lack organizational structure, financial resources, and operational competencies, offering a substantial risk to purchasing organizations. This inductive, qualitative case study research elicits data from twenty established purchasing firms and examines how they choose startup suppliers. We begin by identifying five design motifs that differentiate purchasing firms' selection procedures. We create a typology of three supplier selection paradigms based on these themes. The findings suggest that enterprises who are ready and able to adjust their selection technique to startups should exhibit a higher level of selection performance, implying a greater likelihood of selecting acceptable startups as suppliers. The findings contribute to the literature on supplier selection and shed light on the burgeoning sector of new venture suppliers.

TYMS 3′-UTR Polymorphism: A Novel Association with FOLFIRINOX-Induced Neurotoxicity in Pancreatic Cancer Patients

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy that has the worst 5-year survival rate of all of the common malignant tumors. Surgery, chemotherapy, and/or chemoradiation remain the main tactics for PDAC treatment. The efficacy of chemotherapy is often compromised because of the substantial risk of severe toxicities. In our study, we focused on identification of polymorphisms in the genes involved in drug metabolism, DNA repair and replication that are associated with inter-individual differences in drug-induced toxicities. Using the microarray, we genotyped 12 polymorphisms in the DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, and TYMS genes in 78 PDAC patients treated with FOLFIRINOX. It was found that the TYMS rs11280056 polymorphism (6 bp-deletion in TYMS 3′-UTR) predicted grade 1–2 neurotoxicity (p = 0.0072 and p = 0.0019, according to co-dominant (CDM) and recessive model (RM), respectively). It is the first report on the association between TYMS rs11280056 and peripheral neuropathy. We also found that PDAC patients carrying the GSTP1 rs1695 GG genotype had a decreased risk for grade 3–4 hematological toxicity as compared to those with the AA or AG genotypes (p = 0.032 and p = 0.014, CDM and RM, respectively). Due to relatively high p-values, we consider that the impact of GSTP1 rs1695 requires further investigation in a larger sample size.

Study of maternal deaths with COVID-19 infection in a tertiary care centre

Background: COVID-19 has been a major speed braker not only for world economy and development but also for health sector. The susceptible population including elderly, co-morbid adults and pregnant females were likewise affected in both major COVID-19 waves in India. Association between COVID-19 cases and pregnancy has been studied throughout the world.COVID-19 is associated with substantial risk of morbidity and mortality in postpartum patients and their infants world-wide, compared with their not-infected pregnant counter-parts, especially if these individuals were symptomatic or have comorbidities.Methods: This single-centre prospective observational study, included all consecutive maternal mortalities with COVID-19 infection admitted to Lokmanya Tilak municipal medical college and general hospital (Mumbai, India), a tertiary referral hospital, from 1 April 2020, to June 2021.In this study, a total of 390 patients were included who were found COVID-19 positive during the study period and 17 patients who died during their admission in hospital. The relation of risk factors and demographics were studied for all the patients.Results: The COVID-19 related maternal mortality was more in women of age group 20-30 years (89%). Most women presented to our centre with complaints of fever, cough, cold or breathlessness (55.5%). Patients who succumbed to COVID-19 were mostly primiparous patients (52.9%) and died within 5 days of delivery (46%). 64% of patients died following 5 days of diagnosis of COVID-19.The co-morbidity present in most patients with COVID-19 associated maternal mortality was pre-eclampsia (31.5%). Most patients were referred with only 17% patients registered at our centre and the type of delay involved in management was mostly Type 1 and 2 (82.2%)Conclusions: Multi-centre retrospective analysis with larger population size is required in order for this to be statistically significant.

An Unprecedented Challenge: The North Italian Gastroenterologist Response to COVID-19

Background: COVID-19 pandemic has profoundly changed the activities and daily clinical scenarios, subverting organizational requirements of our Gastroenterology Units. AIM: to evaluate the clinical needs and outcomes of the gastroenterological ward metamorphosis during the COVID-19 outbreaks in a high incidence scenario. Methods: we compared the pertinence of gastroenterological hospitalization, modality of access, mortality rate, days of hospitalization, diagnostic and interventional procedures, age, Charlson comorbidity index, and frequency of SARS-CoV-2 infections in patients and healthcare personnel across the first and the second COVID-19 outbreaks in a COVID-free gastroenterological ward in the metropolitan area of Milan, that was hit first and hardest during the first COVID-19 outbreak since March 2020. Results: pertinence of gastroenterological hospitalization decreased both during the first and, to a lesser degree, the second SARS-CoV2 waves as compared to the pre-COVID era (43.6, 85.4, and 96.2%, respectively), as occurred to the admissions from domicile, while age, comorbidities, length of stay and mortality increased. Endoscopic and interventional radiology procedures declined only during the first wave. Hospitalized patients resulted positive to a SARS-CoV-2 nasopharyngeal swab in 10.2% of cases during the first COVID-19 outbreak after a median of 7 days since admission (range 1–15 days) and only 1 out of 318 patients during the second wave (6 days after admission). During the first wave, 19.5% of healthcare workers tested positive for SARS-CoV-2. Conclusions: a sudden metamorphosis of the gastroenterological ward was observed during the first COVID-19 outbreak with a marked reduction in the gastroenterological pertinence at the admission, together with an increase in patients’ age and multidisciplinary complexity, hospital stays, and mortality, and a substantial risk of developing a SARS-CoV-2 test positivity. This lesson paved the way for the efficiency of hospital safety protocols and admission management, which contributed to the improved outcomes recorded during the second COVID-19 wave.

Late Recurrence of Hepatocellular Carcinoma in a Patient 10 Years after Liver Transplantation Unrelated to Transplanted Organ

Liver transplantation (LTx) is an accepted method of hepatocellular carcinoma (HCC) treatment in cirrhotic patients; however, it has many limitations, and there is a substantial risk of recurrence. Most relapses occur within the first 2 posttransplant years. We aimed to present a late extrahepatic recurrence of HCC 10 years after LTx, and we discuss the possible risk factors and ways to improve transplantation results. A 68-year-old patient with liver cirrhosis and HCC on the background of chronic HCV and past HBV infection was transplanted urgently due to the rapid decompensation. Anti-HCV treatment before surgery was unsuccessful. Pretransplant computed tomography showed 1 focal 4.5 cm lesion consistent with HCC. Histopathology of the explanted organ showed 2 nodules outside the Milan criteria. Angioinvasion was not found. The patient achieved a sustained viral response to pegylated interferon and ribavirin 2 years post-LTx. Eight years were uneventful. CT of the abdomen performed occasionally was normal. Ten years after LTx, the patient unexpectedly presented with shortness of breath, fatigue, and weight loss. Two metastatic nodules of HCC in the lungs and pelvis were found. Although late HCC recurrence post-LTx is rare, it should be always considered, especially when risk factors such as viral infections and underestimation of tumor advancement were identified. We advocate that oncological surveillance of HCC relapse has to be continued during the whole posttransplant period. High AFP levels, the unfavorable neutrophil to lymphocyte ratio, and better estimation of primary tumor size seem to be useful in the identification of good candidates for transplantation.

Relapsed disease: off-the-shelf immunotherapies vs customized engineered products

Innovations in immuno-oncology for lymphomas have outpaced therapeutic developments in any other cancer histology. In the 1990s, rituximab, a CD20 monoclonal antibody, drastically changed treatment paradigms for B-cell non-Hodgkin lymphomas (B-NHLs). In parallel, the concept that T cells could be genetically reprogrammed and regulated to address tumor cell evasion was developed. Twenty years later, this concept has materialized—3 customized engineered CD19 chimeric antigen receptor T-cell (CART) constructs have been embraced as third-line therapies and beyond for aggressive B-NHL. Responses with CARTs are durable in 30% to 40% of patients, with consistent results in older patients, primary refractory disease, high-grade B-cell lymphoma, and patients with concurrent secondary central nervous system disease, all features historically associated with poorer outcomes. Challenges associated with the administration of CARTs include cumbersome and time-consuming manufacturing processes, toxicities, and cost, not to mention a substantial risk of relapse. Fortunately, as our understanding of how to manipulate the immune system to achieve full antitumor potential has grown, so has the rapid development of off-the-shelf immunotherapies, with CD20/CD3 bispecific antibodies standing out above all others. These agents have shown promising activity in aggressive B-NHL and have the potential to circumvent some of the challenges encountered with customized engineered products. However, toxicities remain substantial, dosing schedules intensive, and experience limited with these agents. Novel customized and off-the-shelf therapeutics as well as rational combinations of these agents are underway. Ultimately, growing experience with both customized engineered and off-the-shelf immunotherapies will provide guidance on optimal methods of delivery and sequencing.

A Case for Thalamic Mechanisms of Schizophrenia: Perspective From Modeling 22q11.2 Deletion Syndrome

Schizophrenia is a severe, chronic psychiatric disorder that devastates the lives of millions of people worldwide. The disease is characterized by a constellation of symptoms, ranging from cognitive deficits, to social withdrawal, to hallucinations. Despite decades of research, our understanding of the neurobiology of the disease, specifically the neural circuits underlying schizophrenia symptoms, is still in the early stages. Consequently, the development of therapies continues to be stagnant, and overall prognosis is poor. The main obstacle to improving the treatment of schizophrenia is its multicausal, polygenic etiology, which is difficult to model. Clinical observations and the emergence of preclinical models of rare but well-defined genomic lesions that confer substantial risk of schizophrenia (e.g., 22q11.2 microdeletion) have highlighted the role of the thalamus in the disease. Here we review the literature on the molecular, cellular, and circuitry findings in schizophrenia and discuss the leading theories in the field, which point to abnormalities within the thalamus as potential pathogenic mechanisms of schizophrenia. We posit that synaptic dysfunction and oscillatory abnormalities in neural circuits involving projections from and within the thalamus, with a focus on the thalamocortical circuits, may underlie the psychotic (and possibly other) symptoms of schizophrenia.

Clinical features of UK Biobank subjects carrying protein truncating variants in genes implicated in schizophrenia pathogenesis

The SCHEMA consortium has identified ten genes in which protein truncating variants (PTVs) confer substantial risk of schizophrenia. Exome-sequenced participants in the UK Biobank who carried PTVs in these genes were studied to determine to what extent they demonstrated features of schizophrenia or had neuropsychiatric impairment. Following automated quality control and visual inspection of reads, 251 subjects were identified as having well-supported PTVs in one of these genes. The frequency of PTVs in CACNA1G was higher than had been observed in SCHEMA cases, casting doubt on its role in schizophrenia pathogenesis, but otherwise rates were similar to those observed in SCHEMA controls. Numbers were too small to allow formal statistical analysis but in general carriers of PTVs did not appear to have high rates of psychiatric illness or reduced educational or occupational functioning. One subject with a PTV in SETD1A had a diagnosis of schizophrenia. one with a PTV in HERC1 had psychotic depression and two subjects seemed to have developmental disorders, one with a PTV in GRIN2A and one with a PTV in RBCC1. There seemed to be somewhat increased rates of affective disorders among carriers of PTVs in HERC1 and RB1CC1. Carriers of PTVs did not appear to have subclinical manifestations of schizophrenia. Although PTVs in these genes can substantially increase schizophrenia risk, their effect seems to be dichotomous and most carriers appear psychiatrically well.This research has been conducted using the UK Biobank Resource.