Haemophagocytic Lymphohistiocytosis Following the anti-PD-1 Nivolumab in a Patient with Gastric Cancer and Ankylosing Spondylitis.

Background: Autoimmune diseases are not contraindications for immune checkpoint inhibitors (ICI) therapy in patients with cancer. However, immune-related adverse events (irAEs) are frequently observed in patients receiving ICIs including dermatitis, thyroiditis, colitis, and pneumonitis. Thrombocytopenic purpura, aplasia, and haemophagocytic lymphohistiocytosis (HLH) are rarely observed during ICIs. Case description: We report the case of a male patient with pre-existing untreated HLA B27 and ankylosing spondylitis with gastric cancer and liver metastases. The 79-year-old man was treated with anti-HER2 trastuzumab and anti-PD-1 nivolumab. Seventeen days after the seventh cycle of treatment, he presented at the emergency department with acute fever, confusion, and hypotension. Laboratory results showed pancytopenia, and elevation of ferritin and triglyceride. No infections were detected. Although not seen in a bone marrow biopsy, clinical presentation, and absence of infection, together with an H-score of 263, indicated HLH. The patient was treated with dexamethasone for four days and discharged on a tapering dose of steroids. At the two-month follow-up, clinical presentation was normal and blood test almost normalised. At 8 months, no liver metastases were observed. Conclusions: In a patient with a pre-existing autoimmune condition, immunotherapy led to the development of HLH, which was controlled by glucocorticoid. Absence of the feature of haemophagocytosis in the bone marrow biopsy did not exclude the diagnosis, as HLH can occur in the spleen or in the liver. Glucocorticoid therapy did not prevent the anti-cancer effect of ICIs, and liver metastases disappeared 8 months post-HLH. This case warrants further research on the interplay between autoimmunity and ICI response, as well as ICI-induced irAEs. LEARNING POINTS: Haemophagocytic lymphohistiocytosis (HLH) post seventh cycle of trastuzumab (anti-HER2) and nivolumab (anti-PD-1) was controlled with glucocorticoid.Breach of tolerance was due to immunotherapy-induced HLH in a patient with pre-existing autoimmune condition (HLA B27- positive ankylosing spondylitis).There was a complete disappearance of liver metastases 8 months post-HLH.

Artificial intelligence in sickle disease.

Artificial intelligence (AI) is rapidly becoming an established arm in medical sciences and clinical practice in numerous medical fields. Its implications have been rising and are being widely used in research, diagnostics, and treatment options for many pathologies, including sickle cell disease (SCD). AI has started new ways to improve risk stratification and diagnosing SCD complications early, allowing rapid intervention and reallocation of resources to high-risk patients. We reviewed the literature for established and new AI applications that may enhance management of SCD through advancements in diagnosing SCD and its complications, risk stratification, and the effect of AI in establishing an individualized approach in managing SCD patients in the future. Aim: to review the benefits and drawbacks of resources utilizing AI in clinical practice for improving the management for SCD cases.

Congenital Methemoglobinemia: First Confirmed Case in the Arab Population with a Novel Variant in the CYB5R Gene in the State of Qatar: A Case Report.

Methemoglobinemia (MetHb) is a rare hematological condition characterized by high methemoglobin levels in the blood. It happens when hemoglobin is oxidized, resulting in hypoxia and cyanosis, which may occur in inherited or acquired forms. Inherited or congenital methemoglobinemia is a rare autosomal recessive condition and has never been reported in the Arab population. Here we report a case of a 22-year-old Arab man with a positive family history who presented with bluish discoloration of the fingers and lips and was found to have methemoglobinemia. Genetic study on the patient and his family revealed compound heterozygous variants in the CYB5R3 Exon 5 c.431G>A p.Gly144Asp likely pathogenic variant and CYB5R3 Exon 9 c.871G>A p.Val291Met variant of unknown significance. We suggest that the novel c.871G>A p.Val291Met variant could be causative for methemoglobinemia.

The effectiveness of tyrosine kinase inhibitor for chronic myeloid leukemia in tuberous sclerosis. A case report and review of literature.

The relationship between chronic myelogenous leukemia (CML) and tuberous sclerosis (TS) is unusual and uncommon. Here, we report a 24-year-old woman diagnosed with TS and later identified with CML, as the second case reported with such coexistence, treated with Nilotinib. This article proposes a hypothesis to explain the association. Therefore, we propose Nilotinib for the treatment of patients with such coexisting diseases. Further studies are warranted to reveal the dynamics between these conditions.

COVID-19 infection presented as Guillain-Barre Syndrome: Report of two new cases and review of 116 reported cases and case series.

BACKGROUND: /Aims: Corona virus disease 2019 (COVID 19) is a pandemic infectious disease of 2020, which often presents with respiratory and gastrointestinal symptoms. The behavior of the virus and its full clinical picture has not been fully studied yet. Many case reports and case series have been running in order to elaborate different presentations and associations. Pulmonary and gastrointestinal features of COVID-19 infection are well outlined; however, neurological manifestations are less defined. CASE PRESENTATION: We report two adult cases of COVID-19 infection presented with acute Guillain-Barre Syndrome (GBS), and a literature review on the causal association between COVID-19 and GBS. CONCLUSION: Our two case reports in addition to literature review of 116 published cases may help offer insight into the clinical course of COVID-19 infection. Our two COVID-19 patients presented with neurological manifestations of GBS which were not preceded with any respiratory, gastrointestinal or other systemic infection. This leads us to raise the possibility of establish direct causal association between COVID-19 infection and GBS. Physicians should have high clinical suspicions when encounter GBS patient during the current COVID-19 pandemic and consider co-existence of COVID-19 infection that may warrant SARS-CoV-2 testing, isolation precautions, and specific treatment for Covid-19 infection.

Rotterdam and Marshall Scores for Prediction of in-hospital Mortality in Patients with Traumatic Brain Injury: An observational study.

Background: We aimed to assess the prognostic value of Rotterdam and Marshall scoring systems to predict in-hospital mortality in patients with traumatic brain injury (TBI).Methods: A retrospective analysis was conducted for patients with TBI who underwent head computerized tomography (CT) scan at a Level I trauma center between 2011 and 2018. Receiver operating characteristic (ROC) curves were used to determine the cutoff values for predicting in-hospital mortality.Results: A total of 1035 patients with TBI were included with a mean age of 30 years. The mean Rotterdam and Marshall scores were higher among non-survivors (p = .001). Patients with higher Rotterdam (>3) or Marshall (>2) CT scores were older, had higher injury severity scores and in-hospital mortality and had lower GCS and blood ethanol levels than those with lower scores. The cutoff point of Rotterdam score was 3.5 (sensitivity, 61.2%; specificity, 85.6%) and Marshall score was 2.5 (74.3% sensitivity and 76.3% specificity). Multivariable logistic regression analyses showed that Marshall and Rotterdam scoring systems were independent predictors of mortality (odds ratio 8.4; 95% confidence interval 4.95-14.17 and odds ratio 4.4; 95% confidence interval 2.36-9.39, respectively).Conclusion: Rotterdam and Marshall CT scores have independent prognostic values in patients with TBI even in alcoholic patients.

Bio-Shock Index: Proposal and Rationale for a New Predictive Tool for In-Hospital Mortality in Patients with Traumatic Brain Injury.

BACKGROUND: We proposed a novel prognostic tool for the prediction of in-hospital mortality based on a combination of hemodynamic parameters and biomarkers in patients with traumatic brain injury (TBI). We hypothesized that a combination of shock index (SI) with high sensitive troponin T (HsTnT), the Bio-Shock Index (Bio-SI), has better prognostic power than its individual components. METHODS: A retrospective chart review was conducted (2011-2018) for patients with TBI. Patients were categorized into 2 groups (low and high Bio-SI) based on the receiver operating characteristic curve. RESULTS: A total of 2619 patients were admitted with TBI, and 1471 fulfilled the inclusion criteria and 73% had high Bio-SI (≥10). High Bio-SI values were associated with more intraventricular hemorrhage (P = 0.001), brain edema (P = 0.001), and had lower mean arterial pressure (P = 0.001), admission Glasgow Coma Scale score (P = 0.001), and higher SI (P = 0.001), serum lactate (P = 0.001), HsTnT values (P = 0.001), and Rotterdam score (P = 0.03). Patients with high Bio-SI had a prolonged hospital (P = 0.003) and intensive care unit stay (P = 0.001); longer ventilatory days (P = 0.001) and had higher rates of pneumonia (P = 0.001), sepsis (P = 0.001), and in-hospital mortality (P = 0.001). The Bio-SI showed high sensitivity and negative predictive value (91.4% and 94.4%, respectively) as compared with elevated SI (50.2% and 87.6%, respectively) and positive troponin (79.7% and 93.7%, respectively). CONCLUSIONS: The Bio-SI is potentially a better tool than its individual components to predict in-hospital mortality among patients with TBI; however, HsTnT alone outperforms SI. Prospective studies and multicenter trials studying troponin levels and SI in all patients with TBI with the inclusion of outcome scores will prove or disprove the predictability of the new index.

A novel approach to the expression and purification of recombinant Xenopus Cdc25C.

The Cdc25 family encodes dual specificity protein phosphatases that play critical roles in cell cycle progression. Activation of the Cdc25C represents a primary driver for meiosis progression in Xenopus oocytes. Given its central role in meiosis the Xenopus Cdc25C has been studied extensively, however purification of the recombinant protein is difficult thus preventing better characterization of its function. Here we describe methods to overcome these difficulties resulting in the production of high purity and yield recombinant Xenopus Cdc25C. We use a synthetic Xenopus Cdc25C gene that was codon optimized for expression in E. coli. We further combine an N-terminal His-tag with a C-terminal Strep-tag II, to isolate extremely pure full-length Cdc25C protein. The recombinant Xenopus Cdc25C is active both in vitro using a phosphatase assay and in vivo when injected into Xenopus oocytes. This new approach should be applicable to the purification of other members of the Cdc25 gene family.