Introduction Vitamin B12 (VitB12) deficiency rarely manifests with visual symptoms. Optic nerve damage in VitB12 deficiency is thought to be via degeneration. However, optic neuritis, though infrequent, has been reported secondary to VitB12 deficiency. Material and methods We conducted a systematic review of all the reported cases of VitB12 deficiency with optic nerve involvement in Pubmed, Cochrane, and Google Scholar any date up to September 6, 2020. We have discussed the findings and compiled the available information on ophthalmological manifestations of VitB12 deficiency. We aim to provide a unified knowledge about the evidence related to types of optic neuropathies reported to date secondary to VitB12 deficiency. We also present a case of bilateral optic neuritis secondary to VitB12 deficiency. Presentation of case We present a 29-year-old previously healthy male with progressive, painful, bilateral, but asymmetric visual deterioration for forty-five days. A detailed history, examination, and laboratory workup were carried out. He was diagnosed as having optic neuritis secondary to VitB12 deficiency. He showed partial improvement with the replacement of VitB12. Conclusion We suggest promptly identifying and replacing VitB12 in patients with optic neuritis with proven VitB12 deficiency to prevent permanent damage to the optic nerve. Patients with VitB12 deficiency should have a baseline fundoscopic exam to rule out subclinical optic nerve damage. Moreover, patients who present with visual disturbances should be screened for VitB12 deficiency, especially the vegan population.

<p></p><p>The ongoing pandemic of Coronavirus Disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a serious threat to global public health. Currently no approved drug or vaccine exists against SARS-CoV-2. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, is a time efficient approach to find effective drugs against SARS-CoV-2 in this emergency situation. Both experimental and computational approaches are being employed in drug repurposing with computational approaches becoming increasingly popular and efficient. In this study, we present a robust experimental design combining deep learning with molecular docking experiments to identify most promising candidates from the list of FDA approved drugs that can be repurposed to treat COVID-19. We have employed a deep learning based Drug Target Interaction (DTI) model, called DeepDTA, with few improvements to predict drug-protein binding affinities, represented as KIBA scores, for 2,440 FDA approved and 8,168 investigational drugs against 24 SARS-CoV-2 viral proteins. FDA approved drugs with the highest KIBA scores were selected for molecular docking simulations. We ran docking simulations for 168 selected drugs against 285 total predicted and/or experimentally proven active sites of all 24 SARS-CoV-2 viral proteins. We used a recently published open source AutoDock based high throughput screening platform virtualflow to reduce the time required to run around 50,000 docking simulations. A list of 49 most promising FDA approved drugs with best consensus KIBA scores and AutoDock vina binding affinity values against selected SARS-CoV-2 viral proteins is generated. Most importantly, anidulafungin, velpatasvir, glecaprevir, rifabutin, procaine penicillin G, tadalafil, riboflavin 5’-monophosphate, flavin adenine dinucleotide, terlipressin, desmopressin, elbasvir, oxatomide, enasidenib, edoxaban and selinexor demonstrate highest predicted inhibitory potential against key SARS-CoV-2 viral proteins.</p><p></p>

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Rationale: BRASH syndrome is a relatively unknown medical entity in which there is a combination of bradycardia, renal injury, hypoperfusion, and hyperkalemia. It is clinically essential to take these manifestations as a syndrome rather than isolated findings because they are interrelated and have synergistic effects. Bradycardia can result in hypoperfusion, which can cause renal injury. The resultant renal injury causes hyperkalemia (which can also be the initial trigger), which potentiates the bradycardia. Deteriorating patients with the syndrome usually do not respond to regular Advanced Cardiac Life Support resuscitation protocols. Treatment focused on the timely replacement of fluids and electrolytes gives better outcomes. It is vital to keep BRASH syndrome in diagnostic possibilities while seeing patients with refractory bradycardia, hyperkalemia, and renal injury, especially when other diagnoses are ruled out. Patient concerns: In this report, we present a 64-years-old gentleman who came with generalized fatigue, non-bloody diarrhea, vomiting, and low oral intake for the past 5 days. Diagnoses: The patient was diagnosed with BRASH syndrome. Interventions: The patient received intravenous fluids, 2 doses of atropine 0.5 mg and received dextrose 50 percent with insulin regular 10 units, and salbutamol 5 mg for hyperkalemia. He was intubated due to a low Glasgow Coma Scale and received dialysis for resistant hyperkalemia. A transvenous pacemaker was inserted due to bradycardia. Outcomes: The patient had 2 cardiac arrests and could not survive the second. Lessons: BRASH is a life-threatening yet largely underdiagnosed condition. Physicians should keep a high index of suspicion for BRASH while seeing patients with resistant and self-potentiating bradycardia, hyperkalemia, and renal failure, as a timely diagnosis is crucial in the management. Variable clinical presentations and limited literature create a diagnostic challenge. Further studies are warranted to understand the pathophysiology and develop better and accurate management algorithms. Patients’ risk of developing BRASH syndrome should be considered while prescribing causative medications (Atrioventricular nodal blocking drugs such as beta-blockers) in hospitals and outpatient settings.

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a well-known cause of hemolysis. It has a notable prevalence in African, Asian, and Mediterranean countries. Favism is a common trigger of oxidative stress in G6PD deficient people, which can lead to hemolysis. Additionally, fava bean ingestion can cause methemoglobinemia (MethHgb), an abnormal variation in the Hgb in which the ferrous (Fe2+) iron in heme is oxidized to the ferric (Fe3+) state. It is rare to have both G6PD deficiency and MethHgb secondary to favism at the same time. The first-line treatment for MethHgb is methylene blue. However, in G6PD deficient patients, it can potentiate hemolysis. Methods: We reviewed the literature using PubMed and Google scholar and found 6 cases of MethHgb secondary to favism in patients with G6PD deficiency. We also analyzed two cases which are still unpublished, making a total of 8 cases. Results: All 8 cases were male with median age of 18 years (1 - 56). 1 patient had a prior diagnosis of G6PD deficiency while 7 were newly diagnosed. Median Hgb was 8.3gm/dL (4.6 - 12.5) and median MetHgb was 7.8 % (3.5 - 35). 1 patient received methylene blue, and 4 received Vitamin C. All of the patients recovered and were discharged [Table 1]. Unpublished case 1: A 56-year-old male presented with MethHgb and hemolytic anemia, secondary to fava bean ingestion. Hgb on admission and lowest recorded were 9.9 and 6.5 gm/dL, respectively. He had an SPO2 of 70% on room air and 101.2 % on ABG. Methylene blue administration worsened the hemolysis as he was G6PD deficient but not diagnosed before. He got better with discontinuation of methylene blue and Vitamin C and was discharged on day 5. Unpublished case 2: A 43-year-old male, known case of G6PD deficiency presented with MethHgb and hemolytic anemia, secondary to fava bean ingestion. Hgb on admission and lowest recorded were 12.5 and 7.4 gm/dL, respectively. He had an SPO2 of 82% on room air and 100 % on ABG. He received IV vitamin C and recovered and was discharged on day 4. Discussion: Methemoglobinemia is usually acquired, secondary to oxidative stress in the body, but can rarely be congenital. Enzyme systems such as NADH methemoglobin reductase, NADPH methemoglobin reductase, ascorbic acid, and glutathione reductase systems keep a check on the accumulation of methemoglobin in the blood. However, these mechanisms can be insufficient to counter the conversion of Hgb to MethHgb, consequently promoting an oxidative state in the body. It can be due to the overproduction of methemoglobin (secondary to exposure to certain drugs, chemicals, or food items, but can sometimes be hereditary) or under conversion to Hgb due to unavailable enzyme mechanisms. One of the causes of the inability to counteract methemoglobin can be secondary to G6PD deficiency. Patients with MetHgb have a low oxygen saturation (SPO2) on pulse oximeters but a falsely high SPO2 on arterial blood gasses (ABG). The treatment depends on symptoms and the level of MethHgb. The first step is to remove any possible precipitator if present. Symptomatic patients (and asymptomatic with a level of methemoglobin &gt;30 %) are treated with methylene blue (1-2mg/kg), which is reduced to leuko-methylene blue via NADPH dependent methemoglobin reductase. This, in turn, reduces methemoglobin back to Hgb, correcting the abnormality [Figure 1]. Rarely, patients can present with co-occurrence of MethHgb and G6PD deficiency. In such cases, caution is required while giving methylene blue as they do not have sufficient levels of NADPH to reduce it. Otherwise, a cascade of oxidative hemolysis ensues secondary to underlying G6PD deficiency, resulting in a vicious cycle of further methemoglobinemia. The most frequent cause of this co-occurrence is the ingestion of fava beans, which can simultaneously induce MethHgb and potentiate G6PD deficiency. One of our patients had a history of favism without developing any symptoms. Only this time, he ate fava beans in a larger amount, leading to hemolysis and MethHgb. Conclusion: Favism is a rare cause of the co-occurrence of methemoglobinemia and hemolysis in G6PD deficient individuals. It is vital to identify G6PD deficiency in patients presenting with MethHgb, as the initiation of methylene blue in such individuals can result in a cascade of oxidative hemolysis. A history of fava beans ingestion without any symptoms does not rule out G6PD deficiency, as it is proportional to the number of beans ingested. Disclosures No relevant conflicts of interest to declare.

The co‐occurrence of acute hemolysis and methemoglobinemia secondary to favism in G6PD deficient individuals is rare. Identifying it promptly is of high clinical significance as treating methemoglobinemia (with methylene blue) can worsen hemolysis.

Background: Post-transplant lymphoproliferative disease (PTLD), is one of the major complications after organ transplantation. The aim of this study is to study the incidence, various risk factors especially EBV status, histopathological types, management, and outcomes of PTLD following kidney transplantation in the pediatric groups. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. The initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found five retrospectives observational, one retrospective questionnaire survey, one prospective observational, and one prospective trial study. We extracted the data for baseline characteristics, the reason for transplantation, recipient & donor EBV status, immunosuppression used, type & stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We included eight studies with a total (n) number of 1713 post-kidney transplant pediatric patients, out of which 148 (8.63%) patients who developed PTLD as a complication of transplantation were studied(table 1). Among the 148 patients diagnosed with PTLD, 96 (64.86%) were males, 49 (33.1%) female participants and 3 (2.2%) were unknown. 34/148 (22.97%) PTLD recipients were EBV (+), 86 (58.1%) EBV (-) and 28 (18.9%) unknown at the time of transplant. EBV status for donors was known in only 2 studies, showing 7/99 (7.1%) to be EBV (+) at the time of transplant. Höcker et al. have shown that antiviral prophylaxis with ganciclovir/valganciclovir in the first year post-renal transplant reduces the risk of EBV viremia. Post-transplant immunosuppressive drugs included tacrolimus, mycophenolate mofetil, azathioprine, sirolimus, cyclosporine, IL-2R antagonist, methylprednisolone, basiliximab, daclizumab, anti-thymocyte globulin/anti-lymphocyte globulin, OKT3. In some cohorts, rituximab and antiviral prophylaxis with ganciclovir or valganciclovir were also used in some patients. The median time from transplant to the diagnosis of PTLD from five studies with 125 patients was 16 months (0.9m-186m). Longmore et al. reported a bimodal distribution curve, with 50% presenting with early PTLD, i.e. after a median duration of 313 days and 50% presenting late after a median duration of 8 years. The histopathological types of PTLD were diagnosed via biopsy samples, showing predominance with polymorphic type 48 (32.4%), followed by monomorphic type 45 (30.4%), early lesion 4 (2.7%), Kaposi like PTLD 1 (0.67%) and Hodgkin lymphoma 1 (0.67%). The histological testing results from two of the studies also showed that 18/19 (94.7%) of diagnosed PTLD samples were EBV positive. PTLD was managed with reduction or cessation of the immunosuppressive drugs, anti-CD20 antibodies, chemotherapy for lymphoma, and in some cases mTOR inhibitors, intravenous immunoglobulins, and surgical resection. Data from 5 studies show the mortality rate of 12/51 (23.5%) among PTLD groups. The survival rate from 2 studies was 100% among 17 PTLD patients and 1 study showed a 5-year survival rate of 85% among 92 PTLD patients. Cleper et al. in their study concluded that the type of PTLD might have a significant effect on the outcome, as ¾ (75%) deaths in the PTLD group were attributed to anaplastic T-cell type. Conclusions: Our analysis shows the EBV infection is closely associated with a higher risk of PTLD development. Recipients' EBV seronegativity and positive EBV status of the donor have been shown to increase post-transplant EBV infection risk which is associated with a higher risk of PTLD development. Furthermore, our study shows that PTLD may occur in less than a month to more than 15 years of renal transplant. The polymorphic type was the most common and Hodgkin lymphoma-type, the least commonly reported PTLD type. The main therapeutic approach is the reduction or cessation of immunosuppression. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Background: Post-transplant lymphoproliferative disease (PTLD), a group of lymphoid disorders ranging from indolent polyclonal proliferation to aggressive lymphomas is a known complication following solid organ transplantation. The aim is to study the characteristics, predictive factors, management, and outcomes of PTLD among pediatric groups after liver transplantation in particular. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. Initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found five retrospectives observational, one observational cohort study, and one multicenter cohort in the pediatric population. We extracted the data for baseline characteristics, the reason for transplantation, recipient & donor EBV status, immunosuppression used, type & stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We included seven retrospective observational studies with a total (n) number of 3116 post-liver transplant pediatric patients, out of which 135 (4.33%) patients who developed PTLD as a complication of transplantation were studied. The male to female ratio was 41: 55 with the gender of 6 patients unknown. In five studies, with 118 PTLD patients, 34 recipients and 24 donors were positive for EBV at the time of liver transplantation. In addition to EBV, CMV status of patients in 5 studies showed 11/25 (44%) PTLD patients positive for CMV at the time of transplant. Post-transplant immunosuppression was achieved among these seven cohorts with cyclosporine, tacrolimus, OKT3, mycophenolate mofetil, prednisone, and basiliximab. The diagnosis was made via biopsy, showing all histopathological types including early lesions 14/46 (30.4%), polymorphic 13/46 (28.3%), monomorphic 18/46 (39.1%), and classic Hodgkin's lymphoma PTLD 1/46 (2.1%). Diffuse large B-cell lymphoma was the most common subtype in 6/18 (33.3%) of samples with monomorphic PTLD. Hsu, et al. in their study showed a five-year survival rate of 33.3% for St. Jude's classification stage IV lymphoma compared to 88.9% for stage I-III. The median age for 36 patients from three studies at the diagnosis of PTLD was 39.6 months (range 24-48 months). The median duration from transplantation to the diagnosis of PTLD was 13.48 months (range 8-24 months) in 54 patients from four studies. PTLD treatment was achieved with a combination of reduction or withdrawal of the immunosuppressive drugs with antiviral prophylaxis, chemotherapy, irradiation & the use of monoclonal antibodies in a total of 57 PTLD patients for which post-transplant immunosuppression data was available. Study by Hsu, et al. reported that 5/16 (31.3%) patients had acute graft rejection and 2 had a chronic rejection in a group of 16 PTLD patients undergoing treatment for PTLD with a reduction in immunosuppressive therapy. The overall mortality in patients who developed PTLD was 15/54 (27.8%) in four of the studies. Conclusions: Pre-transplant EBV-naive status in patients was associated with a higher incidence of PTLD. Advanced stage (Stage IV) lymphoma was associated with poor survival outcomes. Monomorphic histopathology may be most commonly associated with PTLD post-liver transplant. The main approach for the treatment of PTLD is the reduction or complete withdrawal of immunosuppressive drugs, administration of antiviral drugs (ganciclovir/valganciclovir),and lymphoma treatment with chemotherapy or irradiation, and monoclonal antibody therapy such as rituximab. Management of PTLD with reduction or withdrawal of post-transplant immunosuppressive drugs in one cohort was associated with an increased risk of graft rejection. Thus immunosuppressive therapy maintaining a fine balance between the risk of graft rejection and risk of developing PTLD may be associated with better patient outcomes post-liver transplant. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.