Major neurological syndromes with COVID-19: lessons to learn

Objective: Covid-19 is a highly infectious viral disease, and our understanding of the impact of this virus on the nervous system is limited. Therefore, we aimed to do a systematic analysis of the neurological manifestations. Methods: We retrospectively studied the clinical, laboratory, and radiological findings of patients with major neurological syndromes (MNS) in Covid-19 over 6 months. Results: We had 39 patients with major neurological syndromes (MNS). The most common MNS was cerebrovascular disease (CVD) (61.53%), in which ischemic stroke (83.33%), cortical sinus thrombosis (12.50%), and haemorrhagic stroke (4.16%) were seen. Among ischemic stroke patients, 50% had a large vessel occlusion, and 66.66% of patients with CVD had a significant residual disability. Cranial neuropathy (15.38%), GBS (10.26%), encephalitis (7.26%), and myelitis (5.12%) were the other MNS. Among the three encephalitis cases, two had CSF-Covid-19 PCR positivity and had severe manifestations and a poor outcome. Associated comorbidities included hypertension (30.76%), diabetes mellitus (12.82%), chronic kidney diseases (7.69%), and polycythaemia vera (2.56%). Lung involvement was seen in 64.1% of patients. Mortality was 17.94% in MNS with Covid-19. Conclusions: The most common major neurological syndrome associated with Covid-19 is CVD with increased frequency of large vessel occlusion causing significant morbidity and mortality. Simultaneous lung and other systemic involvement in MNS results in a deleterious outcome.

Clinical profile and outcome of neonates born to COVID positive mothers

Background: A new type of Corona virus that is SARS-COV-2 called COVID-19 had a huge pandemic worldwide. On January 30, 2020 the World Health Organization (WHO) declared the outbreak of COVID19 as a public health emergency of international concern. Method(s): Descriptive and retrospective study carried out at general hospital, Sapthagiri institute of medical science and research centre from September 2020 to September 2021. Result(s): Among 153 tested neonates, 91 were SARS-COV-2 positive. Out of 91 (59%), most common symptom reported is respiratory distress in the form of TTNB (43%) and require respiratory support for longer period compared to COVID negative group. Conclusion(s): 55% of neonates were symptomatic and reported higher incidence of NICU admission rates in SARS-COV-2 positive neonates born to SARS-COV-2 infected mothers which is comparable to our study.Copyright © 2022 Scientific Publishers of India. All rights reserved.

Ruxolitinib treatment in myelofibrosis and polycythemia vera causes suboptimal humoral immune response following standard and booster vaccination with BNT162b2 mRNA COVID-19 vaccine.

Patients affected by myelofibrosis (MF) or polycythemia vera (PV) and treated with ruxolitinib are at high risk for severe coronavirus disease 2019. Now a vaccine against the virus SARS-CoV-2, which is responsible for this disease, is available. However, sensitivity to vaccines is usually lower in these patients. Moreover, fragile patients were not included in large trials investigating the efficacy of vaccines. Thus, little is known about the efficacy of this approach in this group of patients. In this prospective single-center study, we evaluated 43 patients (30 MF patients and 13 with PV) receiving ruxolitinib as a treatment for their myeloproliferative disease. We measured anti-spike and anti-nucleocapsid IgG against SARS-CoV2 15-30 days after the second and the third BNT162b2 mRNA vaccine booster dose. Patients receiving ruxolitinib showed an impaired antibody response to complete vaccination (2 doses), as 32.5% of patients did not develop any response. After the third booster dose with Comirnaty, results slightly improved, as 80% of these patients produced antibodies above the threshold positivity. However, the quantity of produced antibodies was well below that reached than those reported for healthy individuals. PV patients elicited a better response than patients affected by MF. Thus, different strategies should be considered for this high-risk group of patients.

Outcomes of SARS-CoV-2 infection in Ph-neg chronic myeloproliferative neoplasms: results from the EPICOVIDEHA registry.

Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19-197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58-77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357-3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363-3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363-3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary: EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease.The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN.To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020.The database provided clinical data of 398 patients with MPN incurring COVID-19:Patients were mostly elderly (median age was 69 years);Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN;Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19.Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted byOlder age;Comorbidities;Exposure to immunosuppressive therapies.Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold byOlder age;Comorbidities;Exposure to immunosuppressive therapies before the infection.In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.

Polycythemia in a Pediatric Patient with Chronic Kidney Disease: Overuse of Erythropoetin During COVID-19 Isolation

We describe a case of a patient with Chronic Kidney Disease who developed polycythemia due to Erythropoiesis Stimulating Agents overuse during COVID-19 isolation. A 12-year-old male had not been able to attend routine controls since had been in isolation for 4 months after the COVID-19 outbreak. He had continued to take Erythropoiesis-Stimulating Agents during that period at the starting dose of 150 U/kg/week. He had been on peritoneal dialysis in the last year because of end-stage renal failure. Laboratory investigation revealed a hemoglobin (Hb) level of 20.8 g/dl, hematocrit level of 66%, creatinine level of 6.5 mgr/dl. He underwent daily phlebotomy sessions (10cc/kg/session). During this period aspirin was also started (5mg/kg). After 5 sessions his Hb level decreased to 14 gr/dl and hematocrit to 40%. Pediatric nephrologist should be aware that there is a potential risk of polycythemia with Erythropoiesis Stimulating Agents when Hb level is not appropriately followed on a routine basis. Copyright © 2021 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

Face masks and polycythemia is the standard hemoglobin cutoff valid in the pandemic?

BACKGROUND: Polycythemia is a common reason for patients' admissions. With the introduction of COVID-19, face masks reached very common usage in the population. Masks may cause some degree of hypoxia that may result in high hemoglobin in healthy individuals. Here, we aimed to investigate the frequency of patients applying for high hemoglobin and tested for possible polycythemia vera (PV) in the pandemic era. MATERIALS AND METHODS: We collected patients who applied to the hematology outpatient clinic between March 2019 and April 2021 for the study. The research was carried out at a single center at Ankara Oncology Training and Research Hospital. We collected demographic data such as age and sex, laboratory parameters such as complete blood count and erythropoietin level, concomitant diseases, smoking history, and spleen size. RESULTS: The median age of the cohort was 41 (16-83). Groups were different regarding age (P = 0.04). Groups were similar regarding gender (P = 0.350). Comorbidities were similar in both groups. Smoking was more frequent in the pre-COVID era group (P = 0.046). The frequency of the Janus kinase 2 (JAK2) test order was 102 examinations out of 7920 for the pre-COVID era and 152 examinations out of 6087 for the COVID era;this was statistically significant (P < 0.001). CONCLUSION: Clinicians may need to re-evaluate the threshold of hemoglobin levels to order JAK2 tests in the pandemic era, and the significance of mildly elevated hemoglobin may be neglected while testing for potential PV.

Particular evolutive modalities in SARS-CoV-2 infection

The COVID-19 pandemic has challenged the medical world in many ways regarding diagnosis troubles and therapeutic options. In this paper, we will present three cases of patients from different age groups, in which we identified specific ways of evolution, from both clinically and laboratory data point of view. We used a critical evolution risk estimation calculator at admission and compared the results with the subsequent evolution of patients. From the analysis of the presented cases, we found persistent organic damage that will require their long-term follow-up. © 2020, Amaltea Medical Publishing House. All rights reserved.

"BUT I AM TOO YOUNG FOR THIS": EARLY PRESENTATION OF USUAL INTERSTITIAL PNEUMONIA

SESSION TITLE: Diagnosis of Lung Disease through Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Usual interstitial pneumonia (UIP) is a histological term used to describe a pattern of interstitial fibrosis with alternating areas of the normal lung with temporal fibrosis and architectural alteration due to chronic scarring or honeycomb change. It is a subset of idiopathic interstitial pneumonias (IPF) that usually presents in the sixth and seventh decades of life with progressive dyspnea on exertion and productive cough. CASE PRESENTATION: We present a 46 y/o man with a history of thyroid disease, hypertension and a former smoker of 20 pack-year smoking. Presented to ED complaining of low oxygen saturation with pulse oximetry at home with readings between 60-80%. Accompanied with progressive dyspnea on exertion and unintentional weight loss of 80 pounds in the last year. Also referred productive cough of white sputum that was worse in the morning. Home nebulized Albuterol therapy did not provide improvement. Denied recent viral respiratory infections, night sweats, environmental exposures nor family history of lung disease. DISCUSSION: Physical exam demonstrated bilateral expiratory dry crackles and pulse oximetry oxygen saturation at room air of 78%. RBBB evidenced on EKG. Bloodwork showed polycythemia with hemoglobin of 17.8;ABG's with pH: 7.40, Pco2: 42.2, PO2: 59.8, HCO3: 26, O2 sat: 90.8 and ideal PO2: 85.6 consistent with metabolic alkalosis with BMP CO2 of 30, A/a gradient: 43.0. Mycoplasma IgM, Influenza A & B and COVID-19 antigen test were negative. CXR with increased vascular markings, chest CT demonstrated small pericardial effusion, bilateral coarse interstitial pulmonary markings and bronchiectasis suggestive of chronic interstitial lung disease with no specific pattern. Left heart catheterization revealed right ventricular hypertrophy, normal EF >55%, and no evidence of coronary disease. Alpha-1 antitrypsin: 158, EPO: 6.5, HIV, and hepatitis panel were all negative. Rheumatology work up with only an ANA antibody positive, with titer 1:160. Patient underwent VATS procedure with wedge biopsy of the right upper and middle lobe that revealed usual interstitial pneumonia pattern. Patient improved and was discharged on home oxygen 3L. At follow-up, treatment was started with Nintedanib and Sildenafil Citrate. He had clinical improvement and oxygen requirements decreased to intermittent oxygen. CONCLUSIONS: Patients with interstitial pulmonary fibrosis experience slow progressive decline with typical clinical presentation over 60 years of age. This case remarks the importance of the need for stratification of interstitial lung disease classification, when pattern and history are non specific, with the use of VATS procedure for early start of treatment. Our patient with no environmental exposure or connective tissue disease had an uncommon early presentation of usual interstitial pneumonia. Reference #1: Tibana, R.C.C., Soares, M.R., Storrer, K.M. et al. Clinical diagnosis of patients subjected to surgical lung biopsy with a probable usual interstitial pneumonia pattern on high-resolution computed tomography. BMC Pulm Med 20, 299 (2020). https://doi.org/10.1186/s12890-020-01339-9 DISCLOSURES: No relevant relationships by Jesse Aleman No relevant relationships by Carlos Martinez Crespí no disclosure submitted for Jean Ramos;No relevant relationships by Alexandra Rodriguez Perez No relevant relationships by Paola Vazquez No relevant relationships by Nahomie Veguilla Rivera

A PATIENT WITH COVID-19 PNEUMONIA, PULMONARY EMBOLISM, AND OSA

SESSION TITLE: Global Case Reports in Critical Care SESSION TYPE: Global Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Thrombotic complications in patients diagnosed with COVID-19 pneumonia are emerging as an important and significant morbidity and mortality burden, with overwhelming inflammation, hypoxia, immobilization, and diffuse intravascular coagulation among possible causes of a procoagulant state (1). Obstructive sleep apnea (OSA), with intermittent arterial oxygen desaturation, may in its turn contribute to a procoagulant state, causing hemodynamic alterations as polycythemia and sluggish blood flow (2). Here we report on a case of sudden and massive non-lethal pulmonary thromboembolism (PTE) in a patient with COVID-19 severe pneumonia, for whom OSA was suspected and documented as a possible concurrent mechanism of thromboembolic complication during follow-up. CASE PRESENTATION: A 55-year-old male non-smoker obese (BMI 33 Kg/m2) was admitted to our hospital after 9 days of fever. In the Emergency Room, a chest HRCT scan showed bilateral diffuse ground glass opacities. He was treated with subcutaneous Tocilizumab (324 mg) single shot, Remdesivir (200 mg/day for first day and 100/daily for further 4 days), methyl-prednisolone 40 mg/daily, Enoxaparin 6000 UI/twice daily, azithromycin 500 mg/daily, high flow nasal cannula oxygen (50 L/min, TC 34°C, FiO2 35%) for moderate acute respiratory failure due to COVID-19 pneumonia (pO2: 58 mmHg, PCO2 34 mmHg pH 7.50, P/F 275). After 10 days, patient's clinical conditions worsened, needing non-invasive respiratory support;D-dimer increased abruptly, rising to 10 ng/mL, with findings consistent with PTE at a computed tomographic angiography (CTA, Fig 1). The patient was successfully treated with 10 mg/daily subcutaneous fondaparinux for 12 days, while assisted in the Intensive Care Unit, being discharged home in room air shortly later with oral anticoagulants. At the 3-month follow-up visit, OSA was suspected due to reported excessive daytime sleepiness and weakness, snoring, disturbed night sleep, morning headache in the last 4 years. The patient underwent a home sleep apnea test (HSAT) overnight. Test results revealed an AHI of 50 events/h, with several prolonged episodes of obstructive sleep apnea (307 apnea and hypopnea (A+H) events, 70 obstructive apnea and 233 hypopnea events, with a mean duration of 10% and an average arterial saturation of 93% (Fig. 2). He was adapted to CPAP therapy, with benefit and good correction of polygraphic indexes. DISCUSSION: The pathogenetic mechanisms of COVID 19 and OSA could have played a synergistic effect on endothelial damage, thus increasing the risk of thromboembolism. CONCLUSIONS: The presence of underdiagnosed comorbidities may well worsen the clinical course and complication of COVID-19;an earlier diagnosis of OSA is a prerequisite for timely treatment and, potentially, improved long-term clinical outcomes. Reference #1: Suh YJ, et al. Pulmonary embolism and deep vein thrombosis in COVID 19: a systematic review and meta-analysis. Radiology 2021;298 (2): E70-E80. Reference #2: Alfonso-Fernandez A., Garcia Surquia A., de la Pena M. OSA is a risk factor for recurrent VTE Chest. 2016;150 (6): 1291-1301. DISCLOSURES: no disclosure on file for Antonietta Esposito;no disclosure on file for Antonella Frattari;no disclosure on file for Giustino Parruti;no disclosure on file for Giorgia Patrizio;no disclosure on file for Pierpaolo Prosperi;no disclosure on file for Giorgia Rapacchiale;No relevant relationships by ANTONELLA SPACONE no disclosure on file for Giacomo Zuccarini;

The Prevalence of Anemia and Hematological Findings in COVID-19 Patients in Saudi Arabia

Objectives: The aim of this study was to estimate the prevalence of anemia among COVID-19 patients in Saudi Arabia and evaluate their hematological parameters. Materials and Methods: A descriptive, cross-sectional, hospital-based study was conducted between February 2021 to March 2021, data collection covered the period between September 2020 to March 2021. All the patients were hospitalized for confirmed COVID-19. Results: A total of 6048 COVID-19 patients included in our study, 2358 (48.9%) were anemic, 3666 (60.61%) were normal HGB level, and only 24 (0.49%) were having polycythemia. Hemoglobin level ranged from 5 g/dL to 18 g/dL with a median (interquartile range) of 11.8 g/dL (8.9 to 13.1) g/dL. The median for male (interquartile range) was for anemic patient’s 9.8 g/dL (8.5 to 11.4) g/dL, normal 14 g/dL (13.5 to 14.8) g/dL, and polycythemia 17.4 g/dL (17.2 to 17.7) g/dL. The median for female (interquartile range) was for anemic patient’s 9.1 g/dL (8.2 to 10.2) g/dL, normal 13.5 g/ dL (12.5 to 14.5) g/dL, and polycythemia 17 g/dL (16.82 to 17.2) g/dL. Hematological parameters detected are indicative of severe complications in anemic patients compared to non-anemic patients. Conclusion: Our findings were consistent with other studies that reported poor outcomes of anemia in COVID-19 patients. © 2022, Association of Pharmaceutical Teachers of India. All rights reserved.

SIGNIFICANT INCREASE IN NEWLY DIAGNOSED HEMATOLOGICAL MALIGNANCIES FOLLOWING LOCKDOWN EASE IN CROATIA

Background: Special epidemiological measures aimed at suppressing SARS-CoV-2 outbreak were introduced in Croatia in March 2020, thus reducing regular work capacity in hematological outpatient and inpatient care. In our hospital, this included relocating the entire Hematology Department to a remote location, reduction of hospital beds in the Hematology Inpatient Unit by approximately 60%, Day Clinic operating at a reduced capacity, and a complete suspension of Hematology Polyclinic during first lockdown. Aims: Herein we report our observation of unusually high incidence of newly diagnosed malignant hematological diseases following first lockdown ease in May/June 2020. Methods: We collected data of patients hospitalized in Hematology Department for 4 periods: May 1 - June 15, 2020 for the test arm, and the same calendar period during previous 3 years (May 1 - June 15 of each of the calendar years 2017, 2018 and 2019), for the control arm. The rationale for such design was that a phenomenon of re-establishing regular work capacity, following temporary restriction, was only observed in the test arm. The study included patients of both sexes older than 18 who were diagnosed with either: Hodgkin lymphoma (C81.0 -C81.9 according to the 10th ICD Revision), different types of non-Hodgkin lymphoma (subsections C82.0 - C83.9 and C85.1-C85), as well as multiple myeloma and malignant plasma cell neoplasms (C90.0 - C90.3). Excluded from our study were diagnoses of T/NK cell lymphoma (C84.0- C84.9;C86.0 - C86.6), malignant immunoproliferative diseases (C88.0 - C88.9), leukemias and other specified malignant neoplasms of lymphatic, hematopoietic and related tissues (C91.0 - C96.9) as well as polycythemia vera and non-malignant hematological diseases (D45 and D50 - D89 in ICD-10). Results: In years 2017-2019, similar numbers of patients were diagnosed with a hematological malignancy in our Department (n=4 for 2017, n=8 for 2018, n=4 for 2019) whereas in 2020, a total of 28 patients were diagnosed during the same calendar period (Hodgkin lymphoma: n=5, NHL n=12, multiple myeloma n=7, CLL/SLL n=4). Statistical analysis revealed a significant increase (p ≤0.05) of newly diagnosed hematological malignancies in May and first half of June 2020, when compared to the same calendar periods during previous three years. Further statistical analysis has not established significant differences in outcome (difference in EFS statistically insignificant, p=0.86), as we had expected in the short follow-up period. (Table Presented) Summary/Conclusion: Facilitating treatment of patients affected by the novel coronavirus represented a welcome change in healthcare system in early 2020, in our country and abroad. At the same time, however, the reduction of tertiary health care capacity aimed at population with hematological diseases presented serious risks for successful diagnosis and treatment outcome, a subject that gained wide attention in literature. It has been reported that, also due to psychological reasons, a fraction of patients delayed seeking medical attention after noticing symptoms. In our study we aimed at analyzing the effects of lockdown ease on the number of newly diagnosed hematological malignancies. We were able to demonstrate the effect of pandemic-related measures on detecting new disease cases. It remains to be clarified if a sudden surge in new diagnoses was due to delayed first physician's appointments/hospitalizations, as is suggested by available literature. The results of our study suggest that longer follow-up period will be required in order to clarify the effects of possible late diagnoses on the treatment outcome.

Treatment of Focal and Segmental Glomerulosclerosis Secondary to High Altitude Polycythemia with Acetazolamide.

Vizcarra-Vizcarra, Cristhian A., Eduardo Chávez-Velázquez, Carmen Asato-Higa, and Abdías Hurtado-Aréstegui. Treatment of focal and segmental glomerulosclerosis secondary to high altitude polycythemia with acetazolamide. High Alt Med Biol. 23:286-290, 2022.-Focal segmental glomerulosclerosis (FSGS) is a morphological pattern, caused by glomerular injury and is the leading cause of nephrotic syndrome in adults. We present the case of a 59-year-old female patient, resident of a high-altitude city (3,824 m), who had polycythemia and nephrotic syndrome. A renal biopsy was performed, and the findings were compatible with FSGS. The patient received phlebotomy 500 ml three times, which reduced, partially, the hemoglobin concentration. However, she had refractory proteinuria, despite the use of enalapril and spironolactone. We observed that proteinuria worsened with the increase in hemoglobin levels. So, she was treated with acetazolamide 250 mg bid for 4 months, which reduced proteinuria and hemoglobin. During the coronavirus disease 2019 (COVID-19) pandemic, the patient did not take acetazolamide and again, she had an increase in hemoglobin and proteinuria levels. We conclude that acetazolamide may be an effective treatment in FSGS due to high altitude polycythemia.

High rates of neonatal polycythemia and hyperbilirubinemia during the first phase of COVID-19 pandemic in Italy: a single-center experience.

In our third-level Neonatal Unit in Northern Italy, we recorded a high rate of neonatal hyperbilirubinemia requiring phototherapy in March-November 2020, during the first phase of COVID-19 pandemic, compared to the previous year (198/1348, 14.2%, vs 141/1432, 9.8%, p = 0.0004). Supposing it could be the result of neonatal polycythemia, we evaluated capillary hematocrit (Hct) and the rate of hyperbilirubinemia in all newborns ≥36 weeks gestational age born in December 2020. Out of 73 neonates, 37 had Hct ≥65% (50.7%). However, as capillary blood samples may overestimate Hct by 5-15%, even downsizing all values by 15%, Hct was still ≥65% in 9/73 neonates (12.3%), much higher than 0.4-5% prevalence of polycythemia reported in healthy newborns. All those newborns were singleton and healthy, with no clinical signs of hyperviscosity and no underlying factors predisposing to polycythemia. Out of 73 newborns, 13 (17.8%) developed hyperbilirubinemia requiring phototherapy. Their mean Hct value was 66.3 ± 8.2%. Since hyperbilirubinemia is common in the offspring of women with SARS-CoV-2 infection and we recorded increased rates of neonatal hyperbilirubinemia in the first phase of COVID-19 pandemic, it could be hypothesized that even asymptomatic Sars-CoV2 infection during pregnancy might cause placental vascular malperfusion, eliciting polycythemia in the fetus as a compensatory response, that could be the link between COVID-19 in the mothers and hyperbilirubinemia in the newborns.

Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant in Patients with Philadelphia-Negative Myeloproliferative Neoplasm: A Single Center Experience.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral agent responsible for the coronavirus disease of 2019. The disease is primarily a respiratory illness; however, multisystem involvement is not uncommon. The infection is reported to be more severe in patients with multiple comorbidities and immunocompromised patients. Patients with hematological malignancies are immunocompromised and prone to develop severe SARS-CoV-2 infection. The SARS-CoV-2 had developed several mutations that resulted in different strains with different virulence and different degree of protection by vaccination or prior infection. The Omicron variant is reported to cause mild illness; however, the effect on patients with hematological malignancies like myeloproliferative neoplasms (MPNs) is not clear. We present patients with MPNs who had infection with the Omicron variant of the SARS-CoV-2 and their outcomes. METHODS: Retrospective data from the National Center for Cancer Care and Research records from December 20, 2021, to January 30, 2022. Participants were adults over the age of 18 years with Omicron infection who had been diagnosed with Philadelphia-negative MPNs, essential thrombocythemia, polycythemia vera (PV), and primary myelofibrosis according to the 2008/2016 WHO classification for MPN. RESULTS: Twenty-two patients with Philadelphia-negative MPN had Omicron infection. All patients had a mild disease according to the WHO classification of COVID-19 severity. Most of the patients had medical comorbidities, with hypertension being the most common comorbidity. However, only one patient with PV required hospitalization. DISCUSSION/CONCLUSIONS: In patients with Philadelphia-negative MPN, the Omicron variant of SARS-CoV-2 usually results in mild infection.

Janus kinase (JAK) inhibitors in the treatment of neoplastic and inflammatory disorders.

The Janus kinase (JAK) family of nonreceptor protein-tyrosine kinases consists of JAK1, JAK2, JAK3, and TYK2 (Tyrosine Kinase 2). Each of these proteins contains a JAK homology pseudokinase (JH2) domain that interacts with and regulates the activity of the adjacent protein kinase domain (JH1). The Janus kinase family is regulated by numerous cytokines including interferons, interleukins, and hormones such as erythropoietin and thrombopoietin. Ligand binding to cytokine receptors leads to the activation of associated Janus kinases, which then catalyze the phosphorylation of the receptors. The SH2 domain of signal transducers and activators of transcription (STAT) binds to the cytokine receptor phosphotyrosines thereby promoting STAT phosphorylation and activation by the Janus kinases. STAT dimers are then translocated into the nucleus where they participate in the regulation and expression of dozens of proteins. JAK1/3 signaling participates in the pathogenesis of inflammatory disorders while JAK1/2 signaling contributes to the development of myeloproliferative neoplasms as well as several malignancies including leukemias and lymphomas. An activating JAK2 V617F mutation occurs in 95% of people with polycythemia vera and about 50% of cases of myelofibrosis and essential thrombocythemia. Abrocitinib, ruxolitinib, and upadacitinib are JAK inhibitors that are FDA-approved for the treatment of atopic dermatitis. Baricitinib is used for the treatment of rheumatoid arthritis and covid 19. Tofacitinib and upadacitinib are JAK antagonists that are used for the treatment of rheumatoid arthritis and ulcerative colitis. Additionally, ruxolitinib is approved for the treatment of polycythemia vera while fedratinib, pacritinib, and ruxolitinib are approved for the treatment of myelofibrosis.

First-Time Submassive Pulmonary Embolism Likely Caused by Testosterone-Enhancing Supplement.

Pulmonary embolism (PE) is a potentially fatal occurrence with a broad spectrum of risk factors. A 75-year-old male presented to the emergency room with five days of shortness of breath, back pain, and hemoptysis. A CT angiogram demonstrated bilateral pulmonary emboli with a larger thrombus on the right, as well as signs of right heart strain. The patient was started on IV heparin and ultimately underwent a successful embolectomy. Evaluation to determine the underlying etiology of this patient's first-time PE was performed to further stratify his risk of recurrence and the length of anticoagulation required. The provoking factor for his PE was initially unclear as he lacked any risk factors such as recent surgeries, periods of immobility, or previous diagnosis of malignancy. The patient was noted to be on an erectile dysfunction supplement called "Eroxin," and he had been taking it for the past six months. Eroxin contains an ingredient called fenugreek, which is believed to enhance testosterone levels by inhibiting aromatase and 5-alpha-reductase activity. Fenugreek has previously been associated with the formation of PEs, and likely contributed to the PE in this patient. This is likely due to testosterone-induced polycythemia and increased platelet aggregation. This case highlights the concern around supplements as their ingredients are poorly regulated and occasionally found to be tainted with unlisted ingredients. This also highlights the importance of gathering a complete supplement history from patients as their use can lead to serious illness. Lastly, it encourages considering testosterone use as a potential thrombogenic risk factor.

Single centre, real-world retrospective analysis of the use of azacitadine and venetoclax as firstline treatment in patients with AML in the COVID era

To manage the complexities of treating acute myeloid leukaemia (AML) during the COVID pandemic, NICE have recommended the use of venetoclax and azacitadine as first-line treatment in patients with in patients would otherwise be eligible for standard intensive induction chemotherapy, with the hope that this will reduce inpatient stay, and reduce the risk of neutropenia . This combination has been shown to have favourable outcomes in high-risk patients which is defined as;the elderly, those with unfavourable cytogenetics and secondary AML. Here were discuss the 11 patients diagnosed with AML in the two-year period between 1 January 2020 and 31 December 2021 at Northwick Park Hospital, London, that were eligible to initiate azacitadine and venetoclax as first-line therapy, and evaluate how these new treatment recommendations have affected patient outcomes. One patient was removed due to insufficient written records, leaving a total of 10 patients;seven male, and three female with an average age of 78.2 years, at the time of diagnosis. All but one had secondary AML. Fifty per cent of cases were secondary to MDS, two secondary to CML, one to polycythaemia and one with CML/MDS overlap. Four (36%) received only one cycle of treatment. Ninety per cent of patients had treatment complications, with seven (70%) having cytopenia, three (30%) having cardiovascular complications and nine (90%) having infection related complications. Other serious complications included, transient ischaemic attack and pyoderma gangrenosum. Each patient had an average of 2.3 admissions with one patient having six hospital admissions since initiating treatment. The average length of hospital admission is 11.65 days per visit. Prolonged and frequent hospital admissions during critical times of the pandemic, counteract the intention of wanting to use these oral treatment agents to minimise their exposure to infections. Six (60%) obtained complete morphological remission after the first cycle of treatment. The maximum number of cycles received is 15 and counting. Three (30%) of patients only tolerated one cycle of treatment due to prolonged neutropenia, and/or infective complications. Although all patient developed neutropenia during, and after the completion of the first cycle of treatment, the 40% that are still alive, did not develop concurrent thrombocytopenia after cycle 1 of treatment. Sixty per cent of the patients have died since initiating treatment, making an average of 19.95 weeks from the initiation of treatment to death. Fifty per cent of these patients died from sepsis related causes. The remainder, had unclearly documented cause of death. While being mindful of the small sample size, these realworld data show that although most patients will achieve a good response to the combination of azacytidine and venetoclax after the first cycle, cytopenias, and in particular neutropenia, remains a difficult challenge to tackle leading to recurrent and prolonged hospital admissions, treatment delays and discontinuation of therapy. Although this treatment combination remains a safer option during the pandemic compared to intensive chemotherapy, the data compel us to reflect on the intentions of treatment, and encourage us to have more transparent conversations with patients about the likelihood of recurrent hospital admissions at a time where hospitals are deemed more dangerous than self-isolating, and the possibility of contracting an infection stronger than their body's ability to cope.

Pegylated Interferon is an effective and well-tolerated cytroreductive agent in patients with myeloproliferative neoplasms aged over 60 years

Pegylated Interferon (PegIFN) is the recommended first-line cytoreductive therapy in patients aged <40 years with essential thrombocythaemia (ET) or polycythaemia vera (PV). However, its use in patients >60 years is often limited due to concerns about tolerability. In this study, we evaluate the efficacy and tolerability of PegIFN in patients >60 years at University College London Hospitals (UCLH). Using electronic medical records, we identified patients with ET, PV or myelofibrosis at UCLH who commenced treatment with PegIFN between 2010 and 2020 and were aged >60 years on starting therapy. Data were collected until April 2021 to allow a minimum of 1-year follow-up. Complete Haematological responses were defined as per standard European Leukaemia Net criteria. Adverse events (AE) were graded 1-5 according to Common Terminology Criteria for Adverse Events (CTCAE). Thrombosis risk was graded according to IPSET criteria for ET patients. Patients with PV were classed as high risk if they were aged >65 or had a previous history of thrombosis. Eighteen patients were included in the study. The median age was 75.1 years (range 63-91), 61% were female. Ten out of 18 (56%) had a diagnosis of ET, seven out of 18 (39%) of PV and 1/18 (6%) of post-ET myelofibrosis. Fifteen out of 18 (83%) were positive for JAK2 V617F, and two out of 18 (17%) were positive for CALR mutation. Ten out of 18 (56%) had significant cardiovascular co-morbidities at diagnosis. Five out of 18 (28%) had arterial or venous thromboembolic disease at diagnosis. Sixteen out of 18 (89%) were high-risk for thromboembolic events at diagnosis. Seventeen (94%) patients had PegIFN as a second-or thirdline agent. Of these, 15 out of 17 had received hydroxycarbamide (HU) as first-line therapy;two out of 17 had interferon alpha. PegIFN was started at a median age of 70 years (range 50-86) and continued for 5.7 years (range 2-13). Twelve out of 18 (67%) patients achieved complete remission (CR) on PegIFN monotherapy;1 out of 18 (6%) achieved CR on PegIFN and HU combination therapy, and the remaining 5 out of 18 (28%) achieved a partial remission (PR). The median time to CR was 5 months (range 1-40 months). Ten out of 18 (56%) had grade 1-2 AEs including skin rashes, cytopenia and fatigue. Three out of 18 (17%) developed a major thromboembolic event while on treatment (brachial artery embolism, transient ischaemic attack and a non-ST elevation myocardial infarction). Of these, two out of three failed to achieve a CR on PegIFN and required ongoing venesection. The third had suboptimal response due to dose escalation limited by grade 3 neutropenia. Thirteen patients (72%) remained on pegIFN at the end of the study period. Of those who discontinued, three out of five stopped due to cytopenias, one out of five died during the study period of Covid-19 infection and one out of five transformed to myelodysplastic syndrome. In this study, we present a group of patients who were at high risk for thrombosis due to their age and cardiovascular risk factors. The majority of AEs documented were grade 1-2, with only three out of 18 (17%) patients discontinuing due to AEs. The rate of CR 72% similar to that quoted in imminent studies including MPN-RC (Knudsen et al, 2018) and DALIAH trials (Mascarenhas et al, 2018), which recruited larger numbers of youngers ET and PV patients on PegIFN. Over 20% of MPN patients develop resistance or intolerance to HU (Sever et al, 2014);therefore, there is a need for alternative cytoreductive agents. Our study demonstrates PegIFN to be effective and well-tolerated for use in patients >60 years and is an excellent cytoreductive option in this cohort.

Patient experience of MPN/CML clinic communication during the covid pandemic

One hundred and sixty-five questionnaires were posted to patients who were regularly seen in the nurse-led haematology out-patient clinic. This is an established service that has been operating for approximately 14 years. These patients had all been seen prior to the Covid pandemic, and then during this period. The questionnaire was sent out in August 2021. These patients are treated for either chronic myeloid leukaemia (CML), myeloproliferative neoplasms (MPN) or non-primary polycythaemia/thrombocythaemia. The MPN patients were diagnosed with either essential thrombocythaemia, polycythaemia vera or myelofibrosis. One hundred and thirty-three questionnaires were returned by patients. This is an 81% response. Before the pandemic, patients were mainly seen face to face, with a small number by telephone or email. Patients were happy with this at the time. From March 2020, at the start of the Covid pandemic appointments were suddenly changed to telephone (96%), with a small number by email (2%) or face to face (2%). 96% of the telephone follow-up patients were happy with this method, as were all of the email follow-ups. Patients were asked how they would prefer to be communicated with in the future. The majority of patients would prefer a face to face or telephone appointment. Text, email and video consultations were generally unpopular. People found it easier to communicate face to face, and preferred seeing a healthcare professional this way. A recurring theme was that telephone appointments were acceptable, on the understanding that if there was a change in their condition, a face-to-face appointment could be booked. Patients who worked were very supportive of telephone appointments. People generally felt 'safer' having their appointments remotely, and their blood tests carried out nearer to where they live, instead of at the hospital. Very few patients wanted to have text, video calls or email in the future-they preferred the personal contact, and many did not have the necessary equipment. Issues of long waits in the Pathology department and the difficulty of car-parking at the hospital prepandemic were mentioned by patients. Patients were very happy with the nurse-led haematology clinics. They liked the continuity, and having a point of contact. Over the time of the pandemic, processes were changed, with more use of electronic prescribing, different ways of documenting discussions, and non-paper requesting of blood tests. Together with increased use of email and the telephone, this has meant that services have been continued despite staff being isolated at home. There are increasing numbers of nurse-led clinics in Haematology, and these have been shown to be cost-effective and safe, providing holistic care and continuity (Thompson et al 2012). As services are redesigned, it is important to consider the views of the patients who are users of the clinics. The Covid pandemic has forced changes to healthcare services, and there may be long-term effects on the way that services are delivered in Haematology for patients with chronic conditions. Resilience needs to be built into the way that patients are monitored in the future, to ensure that they can continue without interruption, both during and post pandemic.

Cerebral venous thrombosis and myeloproliferative neoplasms: A three-center study of 74 consecutive cases

Background The recent association of cerebral venous thrombosis (CVT) with COVID-19 vaccinations (JAMA;2021;325, N Engl J Med 2021;384) motivated the current review of CVT and MPN. Our objectives were, i) provide an estimation of the incidence of CVT in the context of MPN, followed by a description of clinical phenotype and therapeutic strategies, ii) determine long term outlook in terms of recurrent thromboses, hemorrhage, and survival, iii) identify salient features which distinguish MPN associated from COVID vaccine- related CVT. Methods 74 consecutive MPN patients with CVT that underwent evaluation at the Mayo Clinic, Rochester MN, USA (n=36), Catholic University, Rome, Italy, (n=23), and University of Florence, Italy (n=15) between 1991 and 2021 were included. The cohort from a previously published multi-center study that included 42 MPN cases with CVT, which were not included in the current study, was used for comparison of observations. Diagnosis of CVT was established with computed tomography or magnetic resonance imaging with venography. Results Patient characteristics at time of CVT Among 74 patients with CVT and MPN (median age 44 years, range 15-85;61% females);disease-specific frequencies were 1.3% (39/2,893), 1.2% (21/1,811) and 0.2% (3/1,888) for essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF), respectively. CVT occurred prior to (n=20, 27%, median time to MPN diagnosis 16.5 months), at (n=32, 44%) or after (n=21, 29%, median time to CVT 26 months) MPN diagnosis. 72% of patients presented with headaches, 22% visual changes, 12% nausea/vomiting, 8% neurological deficits, and 6% seizures. Transverse (51%), sagittal (43%) and sigmoid (35%) sinuses were involved with central nervous system hemorrhage in 10 (14%) patients. MPN phenotype included ET (n=39, 53%), PV (n=21, 28%), pre-fibrotic MF (n=6, 8%), MPN-unclassified (n=4, 5%), PMF (n=3, 4%) and post-PV MF (n=1, 1%). Driver mutation testing was performed in 65 patients: 91% harbored JAK2V617F, 3% CALR type 1, 2% MPL, 5% triple negative;moreover, JAK2V617F was mutated in 27/33 (82%) ET patients. An underlying thrombophilia was identified in 19 (31%) cases. No patient had thrombocytopenia. (Table 1). Notably, one patient received the Ad26.COV2.S vaccine, five days prior to presenting with CVT, not associated with thrombosis in other sites, thrombocytopenia or platelet factor 4 antibodies. A history of thrombosis was documented in 10 (14%) patients with three splanchnic venous events. These observations were similar to those noted in our comparative group from a previously published report that included 42 cases;(ET (n=25, 60%), PV (n=11, 26%), PMF (n=5, 12%);median age 51 years, range 16-84;55% females;81% JAK2V617F mutated). Prior thrombosis occurred in 8(19%) patients with four splanchnic venous events. Treatment for CVT included systemic anticoagulation alone in 27 (36%) patients or in conjunction with aspirin (n=24, 32%), cytoreductive therapy (n=14, 19%), or both aspirin and cytoreduction (n=9, 12%). 5/21 (24%) patients with CVT post MPN diagnosis, were on anticoagulation at the time of CVT. 1. Outcome following CVT At a median follow-up of 5.1 years (range;0.1-28.6), recurrent CVT was documented in 3 (4%) patients;incidence rates for other arterial and venous thromboses and hemorrhage were 11% (2 per 100 patient-years), 9% (1.9 per 100 patient-years) and 14% (3 per 100 patient-years), respectively. 3 of 7 (43%) venous thromboses were splanchnic events. Antithrombotic therapy was ongoing in 53% and 80% of patients with thrombotic recurrences and hemorrhage, respectively. A higher incidence of venous thrombosis was noted in the aforementioned previously published cohort (12 (29%) vs 7 (9%), p=0.01);with 5/12 (42%) splanchnic events. Incidence rates for arterial thrombosis and major hemorrhage were similar. Fibrotic and leukemic transformation occurred in 5 (8%) and 1(1%) patient, respectively, with five (7%) deaths unrelated to CVT. Conclusions The current study highlights close association of CVT w th JAK2V617F, younger age, and female gender. Clinical features distinguishing COVID vaccine-related from MPN-associated CVT include lower likelihood of concomitant non-CVT venous thromboses with the latter;moreover, the absence of thrombocytopenia resulted in a lower rate of intracerebral hemorrhage in MPN cases;as a result, MPN-CVT was not fatal. (Figure Presented).