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Background Coronavirus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus that is affecting the entire world population. The objective of this study was to analyze the repercussion of the disease in a group of patients at risk such as heart transplant recipients. Methods From February 2020 to February 2021, heart transplant recipients diagnosed with COVID-19 were consecutively included. The total number of transplant recipients in outpatient follow-up at that time was 381. Three levels of infection were determined: group A: asymptomatic patients or with trivial symptoms without the need for hospital admission (6 patients); group B: patients admitted to the hospital for respiratory symptoms (12 patients); and group C: patients with severe symptoms and need for admission to the critical care unit (2 patients). At each risk level, medical performance was different: group A: close control, no therapeutic modification; group B: reduction of calcineurin inhibitor and substitution of mycophenolate mofetil for everolimus; group C: reduction of calcineurin inhibitor and withdrawal of mycophenolate mofetil. Results The prevalence of infection in the series was 5.2%. Most patients admitted had a pathologic chest x-ray with fever, cough, dyspnea, or vomiting. The change in immunosuppression performed in patients in group 2 was well tolerated and there was no graft rejection. Antiviral treatment was little used. However, boluses of steroids and some antibiotics were used frequently. The need for supplemental oxygen was 50% in group 2 and 100% in group 3. Conclusions A significant number of transplant recipients will be affected by COVID-19 (5.3%). Management of the infection will depend on the severity of the infection and must be based on a balance between reduction and adjustment of immunosuppression, strict control of the cardiologic situation, and treatment of the infection.

Background: Over the last two decades, humanity has observed the extraordinary anomaly caused by novel, weird coronavirus strains, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). As the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has made its entry into the world, it has dramatically affected life in every domain by continuously producing new variants. The vaccine development is an ongoing process, although some vaccines got marketed. The big challenge is now whether the vaccine candidates can provide long-lasting protection or prevention against mutant variants. Methods: The information was gathered from various journals, electronic searches via Internet-based information such as PubMed, Google Scholar, Science Direct, online electronic journals, WHO landscape, world meters, WHO website, and News. Results: This review will present and discuss some coronavirus disease 19 (COVID-19) related aspects including: the pathophysiology, epidemiology, mutant variants vaccine candidates, vaccine efficacy, and management strategies. Due to the high death rate, continuous spread, an inadequate workforce, lack of required therapeutics, and incomplete understanding of the viral strain, it becomes crucial to build the knowledge of its biological characteristics and make available the rapid diagnostic and vital therapeutic machinery for the combat and management of an infection. Conclusion: The data summarizes current research on the COVID 19 infection and therapeutic interventions, which will direct future decision-making on the effort-worthy phases of the COVID 19 and the development of critical therapeutics. The only possible solution is the vaccine development targeting against all variant strains to halt its progress; the identified theoretical and practical knowledge can eliminate the gaps to improve a better understanding of the novel coronavirus structure and its design of a vaccine. In addition, to that the long-lasting protection is another challenging objective that need to be looked into.

Objective COVID-19 patients may develop coagulopathy which is associated with poor prognosis and high risk of thrombosis. The objective of this work was to evaluate the prevalence of deep venous thrombosis of lower limbs (DVT) through ultrasonography in patients infected with COVID-19 admitted to hospital in conventional units with 5 days monitoring. The secondary objective was to determine if D-dimer levels body mass index (BMI) and C-reactive ; protein (CRP) were associated with DVT. Materials and Methods 72 patients with a mean age of 65±12.3 years infected with COVID-19 were admitted to three conventional units at our institution ,28 patients were women. A COVID-19 diagnosis was made by transcriptase polymerase chain reaction by means of nasopharyngeal swab or by chest computer tomography (CT) without iodine contrast media. Demographics ,co-morbidities characteristics and laboratory parameters were collected . A preventive anticoagulation treatment was established on admission with low molecular weight heparin (LMWH) . A complete venous duplex ultrasound (DU) test of lower limbs was performed on Day (D) 0 and D5 .A pulmonary CT angiograms with iodine contrast media (CTPA) was required when was ; suspected pulmonary embolism (PE). Results On D0 the DU showed acute DVT in seven patients (9.75%).A CTPA was performed in 12 patients (16.65%) ,3 of whom with an acute PE (25 %). On D0 acute DVT was not significantly associated with CRP (mean 101±98.6 in the group without DVT versus 67.6±58.4 mg/l p=0.43) or BMI ( 27.7 ±5.04 versus 28.1 ± 2.65 Kg/m2 p=0.54 ).However we found a significant association between acute DVT and D-dimer levels (1536±2347 versus 9652 ±10205 ng/ml p, In 72 patients admitted to standard hospital wards with COVID-19 pneumonia screening duplex ultrasound (DU) found 9.7% had DVT on admission and 15.6% without DVT on admission had and examined with DU on day 5 had developed DVT despite preventative anticoagulation justifying DU screening in non-ICU hospitalized patients with COVID-19 pneumonia.

Tumor immunity represents a new avenue for cancer therapy. Immune checkpoint inhibitors have successfully improved outcomes in several tumor types. In addition, currently, immune cell-based therapy is also attracting significant attention. However, the clinical efficacy of these treatments requires further improvement. The mechanisms through which cancer cells escape the immune response must be identified and clarified. Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. CSCs can initiate tumors in partially immunocompromised mice, whereas non-CSCs fail to form tumors, suggesting that tumor initiation is a definitive function of CSCs. However, the fact that non-CSCs also initiate tumors in more highly immunocompromised mice suggests that the immune evasion property may be a more fundamental feature of CSCs rather than a tumor-initiating property. In this review, we summarize studies that have elucidated how CSCs evade tumor immunity and create an immunosuppressive milieu with a focus on CSC-specific characteristics and functions. These profound mechanisms provide important clues for the development of novel tumor immunotherapies., Highlights • Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. • Immune evasion is a fundamental feature of CSCs. • Immune evasion mechanisms must be precisely clarified to improve tumor immunotherapy. • CSCs are promising targets for tumor immunotherapy.

A 56-year-old man underwent cardiac transplantation in April 2018. His post-operative course was uncomplicated and he had normal allograft function. On December 2019 he was admitted for fever and diarrhea and was found to have cytomegalovirus infection. A few weeks later, he presented with Guillain-Barré Syndrome. (Level of Difficulty: Advanced.), Graphical abstract

The novel betacoronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread across the globe at an unprecedented rate since its first emergence in Wuhan City, China in December 2019. Scientific communities around the world have been rigorously working to develop a potent vaccine to combat COVID-19 (coronavirus disease 2019), employing conventional and novel vaccine strategies. Gene-based vaccine platforms based on viral vectors, DNA, and RNA, have shown promising results encompassing both humoral and cell-mediated immune responses in previous studies, supporting their implementation for COVID-19 vaccine development. In fact, the U.S. Food and Drug Administration (FDA) recently authorized the emergency use of two RNA-based COVID-19 vaccines. We review current gene-based vaccine candidates proceeding through clinical trials, including their antigenic targets, delivery vehicles, and route of administration. Important features of previous gene-based vaccine developments against other infectious diseases are discussed in guiding the design and development of effective vaccines against COVID-19 and future derivatives., Graphical abstract Unlabelled Image

We report the case of a 10-year-old boy with acute-onset diplopia and ptosis in the right eye. CR was positive for SARS-CoV-2. The patient was managed successfully with corticosteroids. We highlight the need for heightened suspicion of occult COVID-19 infection among children presenting with unusual III nerve palsy.

We report a case of giant cell myocarditis in a 76-year-old patient managed with combined immunosuppression and biventricular intravascular microaxial blood pumps. This case highlights a feasible approach for managing such patients who are not candidates for transplantation or durable ventricular assist devices. (Level of Difficulty: Intermediate.), Graphical abstract, We report a case of giant cell myocarditis in a 76-year-old patient managed with combined immunosuppression and biventricular intravascular m…

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:39 issue:11 pages:1171-1190 ispartof: location:United States status: published

We present the case of an acute onset ANCA positive vasculitis in an asymptomatic COVID-19 infected teenager, resulting in significant colonic damage. The patient was initially diagnosed with Henoch-Schönlein purpura and presented with worsening symptoms with significant necrosis of her perineum and rectum requiring surgical debridement and diverting colostomy. As a part of her work-up, she tested positive for COVID-19 total IgG/IgM antibodies and ANCA antibodies. This case complements previously reported cases of COVID-19 induced autoimmune disease in children but is novel in describing extensive intestinal disease as a result of an autoimmune vasculitis in a child.

The introduction of Cystic Fibrosis Trans Regulatory modulator (CFTRm) drugs has seen a transformation in Cystic Fibrosis (CF) treatment. This has led to a significant improvement in lung function and quality of life with the potential for a real impact on life expectancy. Transient mild to moderate hepatic transaminitis is a well-known side effect of CFTRm drugs, which often improves on cessation and may not recur following the re-institution of the drug. We describe a case of transaminitis developing nine months after the initiation of Kaftrio, which progressed to liver necrosis despite stopping Kaftrio and took many months to resolve. The patient had experienced significant improvement in lung function and overall health while on Kaftrio and deteriorated when it was stopped. He was keen to restart; however, Kaftrio was not reinstated due to the potential risk of acute liver failure.

The coronavirus disease 2019 (COVID-19) has swept the world, posing a serious threat to people's lives and health. Several cases of COVID-19 infection in renal transplant recipients (RTRs) have been reported, but the treatment and prognosis have not been fully elucidated. We followed-up with RTRs infected with SARS-CoV2 in our center and classified them as five clinical types-asymptomatic, mild, moderate, severe, and critical. The immunosuppressive agents were not adjusted in asymptomatic carriers and mild patients, the former was mainly treated by isolation, and the latter was treated by low-dose intravenous immunoglobulin (IVIG) to enhance immunity. For moderate or severe patients, the immunosuppressive agents were largely reduced or even interrupted, low-dose IVIG was adopted, and low-dose methylprednisolone (MP) was used to inhibit inflammation and rejection. Immunosuppressants were discontinued early in critical patients; IVIG, high-dose MP, and antibiotics were used. Meanwhile, all patients received at least one antiviral drugs. After aggressive treatment, three patients developed acute kidney injury, and two showed reversal, while the remaining one lost the allograft kidney; one patient died, while other patients were discharged. For different clinical types of RTRs infected with COVID-19, personalized therapies were essential, Meanwhile, patients with COVID-19 infection may have different outcomes due to their different clinical manifestations.

Visual Abstract, Highlights • rAAV vectors increase cardiac-specific expression of RNR and elevate cardiomyocyte 2-dATP levels. • Elevated myocardial RNR and subsequent increase in 2-dATP rescues the performance of failing myocardium, an effect that persists long term. • We show the ability to increase both cardiac baseline function and high workload contractile performance in aged (22- to 24-month old) mdx4cv mice, by high-level muscle-specific expression of either microdystrophin or RNR. • Five months post-treatment, mice systemically injected with rAAV6 vector carrying a striated muscle-specific regulatory cassette driving expression of microdystrophin in both skeletal and cardiac muscle, exhibited the greatest effect on systolic function. In comparison, mice treated with rAAV6 vector carrying RNR that expresses exclusively in cardiac muscle not only exhibited greatly improved baseline systolic function but also improved diastolic function. • Importantly, vector-directed overexpression of RNR did not impair cardiac reserve during increased physiological demand in aged mdx4cv hearts., Summary Mutations in the gene encoding for dystrophin leads to structural and functional deterioration of cardiomyocytes and is a hallmark of cardiomyopathy in Duchenne muscular dystrophy (DMD) patients. Administration of recombinant adeno-associated viral vectors delivering microdystrophin or ribonucleotide reductase (RNR), under muscle-specific regulatory control, rescues both baseline and high workload-challenged hearts in an aged, DMD mouse model. However, only RNR treatments improved both systolic and diastolic function under those conditions. Cardiac-specific recombinant adeno-associated viral treatment of RNR holds therapeutic promise for improvement of cardiomyopathy in DMD patients.

Objective: The prognosis of adrenoleukodystrophy (ALD)with neurological involvement is generally dismal; however, allogeneic stem cell transplantation (SCT) is recognized as effective to stabilize or improve the clinical symptoms of ALD. Herein, we report the clinical outcomes of patients with ALD who consecutively underwent allogeneic stem cell transplantation with reduced intensity conditioning at our institution. Patients: Sixteen patients with ALD, who were symptomatic (n = 14) or presymptomatic (n = 2), received SCT from 2010 to 2016. The stem cell source was cord blood (n = 14), or bone marrow from a human leukocyte antigen identical sibling (n = 2). The conditioning regimen prior to transplantation was reduced intensity and consisted of fludarabine (125 mg/m2), melphalan (140 mg/m2) and low dose total body irradiation (TBI) of 4Gy (n = 15) or 3Gy (n = 1). Results: Primary engraftment was obtained in 11 patients, and 4 of the 5 patients who lost the primary graft received a second cord blood transplantation and were engrafted. Five years overall and event-free survival were 90.9% and 61.1% respectively, with a median of 45 months (range 16–91). Loes score stabilized or improved by 18 months after transplantation except for patients with internal capsule involvement. Conclusion: Allogeneic SCT with reduced intensity conditioning for patients with ALD was safely performed without major transplant-related complications even in symptomatic patients and neurological symptoms were stabilized after SCT in patients without internal capsule involvement. Keywords: Adrenoleukodystrophy, Allogeneic stem cell transplantation, Loes score, Very long chain fatty acid

Highlights • In the patients with DPD deficiency, advert events appear more rapidly than usual and can be lethal. • Cytomegalovirus enterocolitis is likely to occur in the state of immunosuppression and lethal because of massive bleeding or perforation. • Screening for DPD deficiency should be done, and genetic study can be effective screening for DPD deficiency., Introduction 5-Fluorouracil (5-FU) is widely used for cancer treatment. The reduced activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme in 5-FU inactivation, increases a patient’s risk of developing severe 5-FU related toxicity. However, screening for DPD deficiency is rarely performed before 5-FU administration. Presentation of case Our patient was a 69-year-old man with rectal cancer (T2N1bM0 stage IIIA) who underwent laparoscopic low anterior resection. He developed severe neutropenia and diarrhea 15 days after the administration of capecitabine for adjuvant chemotherapy, and was admitted to our hospital. Four days after admission, he was transferred to the intensive care unit for sepsis. DPD protein screening revealed DPD deficiency. On day 27, massive melena suddenly appeared. He died of continual bleeding 41 days after admission. Pathological autopsy revealed cytomegalovirus enterocolitis. Discussion The administration of 5-FU to patients with DPD deficiency is lethal. Genotypic and phenotypic assessments are reliable tests for DPD deficiency. A genetic study can effectively screen for DPD deficiency; however, its use has not been established in the national insurance system. Patients with DPD deficiency tend to develop severe neutropenia, so clinicians should pay attention to opportunistic infections such as cytomegalovirus enterocolitis. Conclusion Screening for DPD deficiency is necessary prior to 5-FU administration.

COVID-19 infection can cause inflammatory reactions that could involve several organs. In the pediatric population, Multi-System Inflammatory Syndrome in Children (MIS-C) has been reported as one of the consequences of COVID-19. We report a unique pediatric COVID-19 patient with MIS-C, associated with paralysis of the extremities. MRI showed abnormal signal in the cervical spinal cord compatible with transverse myelitis. Methylprednisolone and IVIG were administered, without significant symptom improvement. As a next step, Infliximab was tried for her, and she responded remarkably well to this treatment. Infliximab may be considered as a treatment option in COVID-19 patients with transverse myelitis.

The outbreak of coronavirus disease 2019 (COVID-19) has disproportionately affected patients with comorbidities, including recipients of solid organ and hematopoietic stem cell transplants (SCT). Upon recovery from COVID-19, the degree of the immunological protection from reinfection remains unclear. Here we describe a 33-year-old patient with erythropoietic protoporphyria (EPP) who had undergone liver transplantation with splenectomy followed by allogeneic SCT in 2013 after an initial failed liver and umbilical cord transplant. The patient developed mild upper respiratory symptoms in the spring of 2020 and was found to have anti-SARS-CoV2 antibodies suggesting past infection. A comprehensive analysis of T cell functionality in peripheral blood from this patient revealed robust in vitro responses against SARS CoV2 antigens Spike (S) 1 and 2, membrane (M) and nucleoprotein (NP), comparable to the reactivity against common antigens from CMV, EBV, Ad and BK viruses, while only low reactivity was seen in healthy donors without documented history of COVID-19. Moreover, the patient displayed a marked recognition of counterpart antigens from related human coronaviruses (hCoVs) 229E, OC43, NL63 and HKU1. Thus, despite lifelong immunosuppression, this survivor of COVID-19 retained a remarkable degree of immunocompetence and showed broad-spectrum T cell memory specific for SARS-CoV2 and related hCoVs including less studied hCoV M and NP antigens. The study highlights the role of cellular immunity after natural COVID-19 infection, suggesting broader use of T cell assays as a tool for risk stratification, measurement of immunocompetence and/or post-infection or post-vaccination protection, and possible T cell-based adoptive immunotherapy strategies in high-risk patients.

A 73-year-old woman who visited our hospital complaining of dry cough for three months was refractory to antimicrobial therapy. Chest computed tomography revealed subpleural consolidation. Specimens obtained from surgical lung biopsy revealed subpleural perilobular airspace organization and fibrosis. After the biopsy, mechanic's hand and Gottron's papules appeared, and anti-melanoma differentiation-associated gene 5 (MDA5) antibody was found to be positive. Subsequently, anti-MDA5 antibody measured in cryopreserved serum from her first admission proved to be positive. It is difficult to suspect the presence of anti-MDA-5 antibody in patients with interstitial lung disease without typical dermatomyositis symptoms or slow disease progression.

Neonates and prematures are among the most transfused categories of patients. Adverse reactions due to transfusions, such as transfusion-transmitted infections, can affect the rest of their lives. In this systematic review, we revised the literature concerning transfusion-transmitted infection in neonates. We reported case-reports and case-series previously published and we integrated these data with our experience at local neonatal intensive care unit. Moreover, we illustrated strategies for mitigating transfusion-transmitted infections, including donor selection and testing, pathogen inactivation technologies and combined approaches, as for Cytomegalovirus infection, integrating leukoreduction and identification of seronegative donors.

Disseminated histoplasmosis is a rare opportunistic infection in non-endemic areas, where the disease is often diagnosed late. The spectrum of clinical manifestations is broad and life-threatening complications occur. We present a detailed case of a kidney liver transplant patient with disseminated histoplasmosis in a non-endemic area. Our case highlights the wide range of pathogens to consider in the immunocompromised patient, the delayed diagnosis of Histoplasmosis Capsulatum in non-endemic areas and the possibility of severe gastrointestinal disease. We also briefly review diagnostic tests and treatment options. ispartof: IDCASES vol:22 ispartof: location:Netherlands status: published

Purpose Takayasu arteritis (TA) is a systemic granulomatous large vessel vasculitis that involves mainly the aorta and its primary branches, and occurs most commonly in young females. Ocular manifestations of TA include small vessels dilation, microaneurysm, arteriovenous anastomosis, retinal ischemia and retinopathy. However, no specific and effective treatments for Takayasu retinopathy is applied. This case aimed to demonstrate the role of anti-VEGF (vascular endothelial growth factor) therapy in treating Takayasu retinopathy. Observations We herein reported an 18-year-old Asian woman who presented with typical wreath-like arteriovenous anastomosis around the disc in the right eye and vitreous hemorrhage in the left eye. The stenosis and occlusion of bilateral subclavian arteries, carotid arteries and other proximal arteries on angiography confirmed the diagnosis of TA. Meanwhile, elevated ESR and CRP revealed that TA was in the active stage. We applied anti-VEGF therapy in treating Takayasu retinopathy specially to inhibit neovascularization. Additionally, vitreous extraction was conducted in the left eye after the treatment of anti-VEGF therapy. Conclusions and importance This is the first report of effective application of anti-VEGF therapy in inhibiting wreath-like arteriovenous anastomosis and improving vitrectomy in TA.

IKBKB immune deficiency is a rare but life-threatening primary immunodeficiency disorder, involving activation defects in adaptive and innate immunity. We present sixteen cases of a homozygous IKBKB mutation (c.1292dupG) in infants characterized by early-onset bacterial, viral, fungal and Mycobacterial infections. In most cases, T- and B-cells were quantitatively normal, but phenotypically naive, with severe hypogammaglobulinemia. T-cell receptor excision circles were normal, meaning newborn screening by TREC analysis would miss IKBKB cases. Although IKBKB immune deficiency does not meet traditional laboratory based definitions for SCID, this combined immune deficiency appears to be at least as profound. Urgent HSCT, performed in eight patients, remains the only known curative therapy, although only three patients are survivors. Ongoing infections after transplant remain a concern, and may be due to combinations of poor social determinants of health, secondary graft failure, and failure of HSCT to replace non-hematopoietic cells important in immune function and dependent upon IKK/NF-κB pathways.

Summary Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the “single-patient” investigational new drug [IND] application). Additionally, recent state and federal laws—so-called “right to try legislation”—allow patients to approach drug companies directly for access prior to FDA approval. While these pathways provide potential access for individual patients to investigational drugs, different EA pathways permit entire groups of certain patients to access investigational drugs prior to FDA approval. This review focuses on special categories of EA INDs intended for multiple patients—the intermediate-group IND and the widespread-treatment IND—as well as emergency authorization for use of investigational drugs and biological products (e.g., vaccines) in public health emergencies.

Background The impact of viral infections on acute exacerbations in idiopathic pulmonary fibrosis (IPF) and/or non-IPF interstitial lung disease (ILDs) has been scarcely described. Objectives To elucidate the frequency of virus infections in patients with IPF or non-IPF ILDs including idiopathic interstitial pneumonia (IIP) or connective tissue disease (CTD)-associated pneumonia, and its influence on their short-term mortality. Methods We prospectively enrolled adult patients with acute exacerbation of IPF and non-IPF ILDs who were admitted to the hospital during the last 3 years, and examined the respiratory samples obtained from nasopharyngeal, sputum, and bronchoalveolar lavage fluid. Results A total of 78 patients were identified, consisting of 27 patients with acute exacerbation of IPF and 51 patients with non-IPF ILDs (IIP: n = 27, CTD-associated IP: n = 24). Of all patients, 15 (19.2%) had viruses detected in their respiratory samples including the human herpesvirus 7 (HHV7; n = 4) and cytomegalovirus (CMV) plus HHV7 (n = 3). The proportion of virus infections in the IPF and non-IPF ILDs groups was comparable. The Kaplan-Meier survival curves over 60 days revealed a lower survival probability in the virus positive group (n = 15, 60%) than in the virus negative group (n = 60, 83.3%, p

PURPOSE: To examine the performance of radiologists in differentiating COVID-19 from non-COVID-19 atypical pneumonia and to perform an analysis of CT patterns in a study cohort including viral, fungal and atypical bacterial pathogens. METHODS: Patients with positive RT-PCR tests for COVID-19 pneumonia (n = 90) and non-COVID-19 atypical pneumonia (n = 294) were retrospectively included. Five radiologists, blinded to the pathogen test results, assessed the CT scans and classified them as COVID-19 or non-COVID-19 pneumonia. For both groups specific CT features were recorded and a multivariate logistic regression model was used to calculate their ability to predict COVID-19 pneumonia. RESULTS: The radiologists differentiated between COVID-19 and non-COVID-19 pneumonia with an overall accuracy, sensitivity, and specificity of 88% ± 4 (SD), 79% ± 6 (SD), and 90% ± 6 (SD), respectively. The percentage of correct ratings was lower in the early and late stage of COVID-19 pneumonia compared to the progressive and peak stage (68 and 71% vs 85 and 89%). The variables associated with the most increased risk of COVID-19 pneumonia were band like subpleural opacities (OR 5.55, p

Made available in DSpace on 2022-04-28T19:45:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Agencia Nacional de Investigación e Innovación Comisión Sectorial de Investigación Científica Rijksuniversiteit Groningen Universidad de la República Uruguay Fondo Nacional de Desarrollo Científico y Tecnológico During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (

Progress in life-supporting kidney transplantation in the genetically-engineered pig-to-nonhuman primate model has been encouraging, with pig kidneys sometimes supporting life for > 1 year. What steps need to be taken by (i) the laboratory team, and (ii) the clinical team to prepare for the first clinical trial? The major topics include (i) what currently-available genetic modifications are optimal to reduce the possibility of graft rejection, (ii) what immunosuppressive therapeutic regimen is optimal, and (iii) what steps need to be taken to minimize the risk of transfer of an infectious microorganism with the graft. We suggest that patients who are unlikely to live long enough to receive a kidney from a deceased human donor would benefit from the opportunity of a period of dialysis-free support by a pig kidney, and the experience gained would enable xenotransplantation to progress much more rapidly than if we remain in the laboratory.

Interstitial lung disease (ILD) comprises an array of heterogeneous parenchymal lung diseases that are associated with a spectrum of pathologic, radiologic, and clinical manifestations. There are ILDs with known causes and those that are idiopathic, making treatment strategies challenging. Prognosis can vary according to the type of ILD, but many exhibit gradual progression with an unpredictable clinical course in individual patients, as seen in idiopathic pulmonary fibrosis and the phenomenon of “acute exacerbation”(AE). Given the often poor prognosis of these patients, the search for a reversible cause of respiratory worsening remains paramount. Infections have been theorized to play a role in ILDs, both in the pathogenesis of ILD and as potential triggers of AE. Research efforts thus far have shown the highest association with viral pathogens; however, fungal and bacterial organisms have also been implicated. This review aims to summarize the current knowledge on the role of infections in the setting of ILD.

Temsirolimus is an inhibitor of mammalian target of rapamycin and interstitial lung disease (ILD) is known to be one of the adverse events associated with temsirolimus, which usually improves rapidly after discontinuation of the drug and rarely worsens thereafter. Herein, we report a case of delayed exacerbation of ILD after discontinuation of temsirolimus for metastatic renal cell carcinoma in an 86-year-old male with chronic ILD. The patient developed gradually worsening dyspnea five weeks after an initiation of temsirolimus and was admitted to our facility. On his admission, although a pulmonary function test revealed a decreased diffusion capacity, there was no obvious progression of ILD on HRCT scan. His dyspnea once improved after discontinuation of temsirolimus, but it recurred and acute exacerbation of ILD was diagnosed 40 days after his last administration of temsirolimus. He received high-dose steroid therapy, however, he deteriorated and died. Histopathological examination of the lungs at autopsy revealed overlapping diffuse alveolar damage with chronic interstitial changes. In the present case, since there were no specific factors that could have caused acute exacerbation of ILD except for temsirolimus, it was considered to contribute to the exacerbation of underlying ILD. In conclusion, physicians should be aware of the possibility of temsirolimus-induced ILD not only while the medication is administered, but also even after it is discontinued. It is important to carefully interview the patient and to recognize the value of physiological tests, such as respiratory function tests and blood gas analysis, as well as imaging findings on HRCT.

A 67-year-old female with rheumatoid arthritis and asthma-chronic obstructive pulmonary disease overlap syndrome was admitted for drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine. Human herpes virus 6 (HHV-6) variant B was strongly positive on peripheral blood. Multiple cavities with ground grass opacities rapidly emerged predominantly in the upper and middle lobes. She was diagnosed with invasive pulmonary aspergillosis (IPA), and was treated successfully with antifungal agents. Therapeutic systemic corticosteroids, emphysematous change in the lungs, and the worsening of the patient's general condition due to DIHS were considered major contributing factor leading to IPA. HHV-6 reactivation could have an effect on clinical course of IPA. Cavities with halo sign would provide an early clue to IPA in non-neutropenic and immunosuppressive patients.

Author(s): Chiang, Audris; Shiu, Jessica; Elsensohn, Ashley N; Chapman, Lance W; de Feraudy, Sebastien; Smith, Janellen

Purpose While most influenza patients have a self-limited respiratory illness, 5–10% of hospitalized patients develop severe disease requiring ICU admission. The aim of this study was to identify influenza-specific factors associated with ICU admission and mortality. Furthermore, influenza-specific pulmonary bacterial, fungal and viral co-infections were investigated. Methods 199 influenza patients, admitted to two academic hospitals in the Netherlands between 01-10-2015 and 01-04-2016 were investigated of which 45/199 were admitted to the ICU. Results A history of Obstructive/Central Sleep Apnea Syndrome, myocardial infarction, dyspnea, influenza type A, BMI > 30, the development of renal failure and bacterial and fungal co-infections, were observed more frequently in patients who were admitted to the ICU, compared with patients at the normal ward. Co-infections were evident in 55.6% of ICU-admitted patients, compared with 20.1% of patients at the normal ward, mainly caused by Staphylococcus aureus, Streptococcus pneumoniae, and Aspergillus fumigatus. Non-survivors suffered from diabetes mellitus and (pre-existent) renal failure more often. Conclusions The current study indicates that a history of OSAS/CSAS, myocardial infarction and BMI > 30 might be related to ICU admission in influenza patients. Second, ICU patients develop more pulmonary co-infections. Last, (pre-existent) renal failure and diabetes mellitus are more often observed in non-survivors., Highlights • A history of OSAS/CSAS, myocardial infarction and BMI > 30 are risk factors for ICU admission. • Non-survivors suffer more often from diabetes mellitus and (pre-existent) renal failure. • ICU patients develop renal failure and bacterial/fungal co-infections more often.

Infectious bronchitis virus, otherwise known as coronavirus, can cause mild upper respiratory tract illnesses in children and adults. Rarely has coronavirus been linked, either by serology or nasal wash, to pneumonia. We report a case of a young woman who, following treatment for stage IIIA breast cancer using a high-dose chemotherapy regimen followed by autologous bone marrow and stem cell transplantation, developed respiratory failure and was found to have coronavirus pneumonia as diagnosed by electron microscopy from BAL fluid. We propose that coronavirus should be considered in the differential diagnosis of acute respiratory failure in cancer patients who have undergone high-dose chemotherapy and autologous hematopoietic support.

Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory condition with tissue destruction due to abnormal immune activation. We present a series of 2 cases of cytomegalovirus-induced HLH in children during maintenance chemotherapy for acute lymphoblastic leukemia. These cases emphasize the importance of considering secondary HLH in this high-risk subset of pediatric patients.

The global pandemic of severe acute respiratory coronavirus 2 (SARS-CoV-2), which causes the novel beta coronavirus 2019 disease (COVID-19), has become an unprecedented medical, economic, and psychosocial crisis. The pandemic and its management strategies have resulted in immense challenges for health systems, not only in caring for those with COVID-19 but also in the ongoing management of chronic medical conditions. Kidney transplant recipients present a unique challenge given their need for ongoing monitoring and management as well as their higher risk of COVID-19 infection. In the absence of clear guidelines, it is unclear how to best provide routine care to this unique patient population during the pandemic. Rigorous medical and psychosocial patient-centered risk stratification strategies are needed to avoid adverse outcomes in stable solid organ transplant recipients. This review will focus on the challenges faced by kidney transplant recipients and health care providers and provides strategies to address these issues., Highlights • Kidney transplant recipients present unique characteristics, including disease vintage, immunosuppression, and a single kidney. • The current COVID-19 pandemic has resulted in immense challenges to the management of patients with a kidney transplant. • In the absence of clear guidelines, it is unclear how to provide the best routine care for this particular group of patients. • This review article is focused on the challenges faced by kidney transplant recipients and health care providers during the current pandemic.

A 29-year old male with recurrent respiratory and skin infections, anaemia and neutropaenia during childhood required immunoglobulin replacement for antibody deficiency from age 16. He remained relatively well until age 28 when he presented with a two-week history of fatigue, sore throat, fever and productive cough. He was found to have EBV viraemia and splenomegaly and a diagnosis of EBV-driven lymphoproliferative disease was made following bone marrow trephine. Family history was notable with three siblings: a healthy sister and two brothers with anaemia and neutropaenia; one who succumbed to septicaemia secondary to neutropaenic enterocolitis age 5 and another who developed intestinal vasculitis and antibody deficiency and had a successful haemopoetic stem cell transplant. The proband's DNA underwent targeted sequencing of 279 genes associated with immunodeficiency (GRID panel). The best candidates were two ADA2 variants, p.Arg169Gln (R169Q) and p.Asn370Lys (N370K). Sanger sequencing and co-segregation of variants in the parents, unaffected sister and all three affected brothers was fully consistent with compound heterozygous inheritance. Subsequent whole genome sequencing of the proband identified no other potential causal variants. ADA2 activity was consistent with a diagnosis of ADA2 deficiency in affected family members. This is the first description of EBV-driven lymphoproliferative disease in ADA2 deficiency. ADA2 deficiency may cause susceptibility to severe EBV-induced disease and we would recommend that EBV status and viral load is monitored in patients with this diagnosis and allogeneic SCT is considered at an early stage for patients whose ADA2 deficiency is associated with significant complications., Highlights • We report a patient with ADA2 deficiency and EBV-driven lymphoproliferative disease. • ADA2 deficiency may predispose to severe EBV-induced disease. • We would recommend that EBV status and viral load is monitored in patients with ADA2 deficiency.

Although acute HIV-induced HLH is rare in literature, HIV is an important differential diagnosis in patients with HLH. In our study, a 33-year-old previously healthy male patient was admitted with fever of unknown origin, lymphadenopathy, generalized edema, transaminitis, acute renal failure, oliguria, myalgias, night sweats, unintentional weight loss, and leukopenia. Disease course was indicative of a viral-like prodrome of roughly 2-month duration. At an outside hospital, full viral work-up (including EBV, CMV, HIV antibodies, hepatitis panel) was negative. HIV p24 antigen assay was not available at the outside facility. Outside liver chemistry and lymph node biopsy were suggestive of HLH. HLH was confirmed via serum ferritin, white cell receptor, and cytokine studies. Repeat viral and rheumatologic studies revealed a positive p24 antigen with indeterminant HIV antibody. We demonstrate efficacy of a specific treatment plan as well as importance of p24 antigen studies in patients with HLH and/or the HIV window-period, adding to available literature/documentation of a rare disease process.

Cytomegalovirus (CMV) is a double-stranded DNA virus, which infects a large portion of the adult population. In immunocompetent patients, it typically is asymptomatic or manifests as mild and self-limiting flu-like illness symptoms, whereas in immunocompromised patients, CMV can cause significant disease. Herein we report an unusual case of CMV pancreatitis in an immunocompetent 75-year-old female. Patient developed severe significant pancreatic necrosis that failed non-operative management, and ultimately underwent pancreatic necrosectomy. Later on, she developed three spontaneous gastric perforations. The first two perforations were managed operatively, but after the third perforation family decided not to undergo another operation. The CMV pancreatitis diagnosis was based on pancreatic histopathology and confirms by a prompt response to ganciclovir. Patient was promptly started on intravenous (IV) ganciclovir which resulted in clinical recovery and she remained asymptomatic more than one-year post op. This is a rare case of CMV pancreatitis with gastric perforations in an immunocompetent patient. High degree of suspicion and appropriate treatment are important for such clinical scenarios.

Introduction: Antifungal agents are routinely used in the post-transplant setting for both prophylaxis and treatment of presumed and proven fungal infections. Micafungin is an echinocandin-class antifungal with broad antifungal cover and favorable side effect profile but, notably, it has no activity against molds of the order Mucorales. Presentation of case: A 47-year-old woman underwent multivisceral transplantation for intestinal failure-associated liver disease. She had a prolonged post-operative recovery complicated by invasive candidiasis and developed an intolerance to liposomal amphotericin B. In view of her immunosuppression, she was commenced on micafungin as prophylaxis to prevent invasive fungal infection. However, she developed acute graft versus host disease with bone marrow failure complicated by disseminated mucormycosis which was only diagnosed post mortem. Discussion: Non-Aspergillus breakthrough mold infections with micafungin therapy are rare with only eight other cases having been described in the literature. Breakthrough infections have occurred within one week of starting micafungin. Diagnosis is problematic and requires a high degree of clinical suspicion and microscopic/histological examination of an involved site. The management of these aggressive infections involves extensive debridement and appropriate antifungal cover. Conclusion: A high level of suspicion of invasive fungal infection is required at all times in immunosuppressed patients, even those receiving antifungal prophylaxis. Early biopsy is required. Even with early recognition and aggressive treatment of these infections, prognosis is poor. Keywords: Antifungal therapy, Micafungin, Mucormycosis, Multivisceral transplantation, Immunosuppression, Fungal infection

Highlights • Amylmetacresol/2,4-dichlorobenzyl alcohol lozenge showed virucidal effects against parainfluenza virus and cytomegalovirus. • Hexylresorcinol lozenge showed virucidal effects against parainfluenza virus. • Mean reductions in viral titre were significantly greater compared with their respective placebo lozenge. • Peak virucidal effects were observed following 1 min of incubation in vitro., Most respiratory tract infections are self-limiting and caused by viruses, and do not warrant antibiotic treatment. Despite this, patients with respiratory tract infections often receive antibiotics, fuelling the rise of antibiotic resistance. Therefore, there is a need to encourage patients to try alternative non-antibiotic therapies, which ideally treat the symptoms and the cause. Lozenges containing amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA lozenges) as well as lozenges containing hexylresorcinol have been shown to provide effective symptomatic relief for sore throat. In this study, we investigated whether these lozenges also have virucidal effects in vitro against two viruses associated with respiratory tract infections, parainfluenza virus type 3 and cytomegalovirus. Both viruses were incubated with AMC/DCBA lozenge, placebo lozenge or the active ingredients (AMC/DCBA) as free substances, and parainfluenza virus type 3 was incubated with hexylresorcinol lozenge, placebo lozenge or hexylresorcinol as a free substance. Virucidal effects were observed with the active lozenges and the active ingredients as free substances against both parainfluenza virus type 3 and cytomegalovirus. Mean reductions in viral titre were significantly greater compared with placebo lozenge and peak effects were observed for the shortest incubation time, 1 min. These findings suggest that AMC/DCBA lozenge and hexylresorcinol lozenge have the potential to have local antiviral effects in patients with sore throat due to viral respiratory tract infections. Use of such over-the-counter treatments for self-limiting respiratory tract infections may satisfy patients’ desire for an anti-infective medication and reduce the demand for antibiotics.

Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse systemic reaction.1 DIHS is characterized by its limited number of causative drugs, late onset, clinical similarity to infectious mononucleosislike syndrome, and prolonged clinical course owing to relapse.2 Subjects with DIHS are known to show reactivation of human herpesvirus (HHV)-6, cytomegalovirus (CMV), Epstein-Barr virus, and HHV-7.3 This report describes the case of DIHS with a dramatic reactivation of CMV and a development of gastric ulcers, in which CMV was immunohistochemically detected.

Panniculitides are a group of conditions characterized by inflammation of subcutaneous fat.1 Pancreatic panniculitis is a rare lobular panniculitis that appears in roughly 2% to 3% of patients with pancreatic diseases, such as pancreatitis and pancreatic carcinoma. Less commonly, pancreatic panniculitis has been reported in transplant patients in association with acute kidney or pancreas allograft rejection.2, 3, 4, 5 Patients often present with tender erythematous nodules, which may drain an oily substance, on the distal lower extremities. Associated symptoms may include acute arthritis, necrosis of abdominal or bone marrow fat, pleural effusions, mesenteric thrombosis, leukemoid reaction, and eosinophilia. The pathogenesis is hypothesized to involve release of pancreatic enzymes, such as lipase, from the inflamed pancreas into the portal and lymphatic circulation and subsequently deposited in distant sites where they hydrolyze subcutaneous fat.

Visceral leishmaniasis is an infection with an insidious and disabling course caused by parasites of the genus Leishmania. In Europe, it is mostly associated with HIV infection. Systemic lupus erythematosus and its treatment are associated with increased risk of infection, neoplastic and concomitant autoimmune disorders. The association of these diseases may go unnoticed.A 60 year-old Caucasian woman with lupus presented with a one-year history of fever, malaise, weakness and weight loss. The highlights on physical examination were pallor, palpable hepatosplenomegaly and low-grade fever. Blood tests showed pancytopenia, hyperproteinemia with hypoalbuminemia and hypergammaglobulinemia; electrophoresis showed a polyclonal gamma curve. Full-body CT scan revealed massive hepatosplenomegaly. Microbiology investigation was negative for the most common pathogens, including tuberculosis. There were no signs of hematologic malignancy in the bone marrow smear. PCR for Leishmania infantum was positive both in blood and bone marrow. The patient was treated with liposomal amphotericin B, and immunosuppression was adjusted. She showed rapid clinical improvement and 6 months later had no signs of disease.The differential diagnosis in a patient with lupus presenting with fever and multisystemic manifestations includes infectious or neoplastic disorders. The patient lived in an endemic area of Leishmania, and typical clinical and analytical changes were all present, making this case highly educational. The case highlights the importance of a patient's epidemiological background and how it can lead to the diagnosis and timely treatment of a rare disease.

Human cytomegalovirus (CMV) serology is positive in nearly two-thirds of individuals in the United States, but cutaneous manifestations of infection are exceedingly rare.1, 2, 3, 4 To our knowledge, few cases of CMV-induced cutaneous manifestations have been reported and most commonly occur in immunocompromised populations. Here we report a case of localized sclerodermoid skin changes in an immunocompetent patient with CMV infection.

Highlights • NVAC activities improved the U.S. immunization enterprise over the past 30 years. • NVAC focused on the implementation of immunization across the lifespan and system. • Tracking the implementation of NVAC recommendations remains difficult. • Standards for practicesacross the lifespan continue to help practitioners immunize., Thirty years after passage of legislation that created the National Vaccine Advisory Committee (NVAC) “to achieve optimal prevention of human infectious diseases through immunization and to achieve optimal prevention against adverse reactions to vaccines,” this review reflects NVAC’s role and impact on the U.S. vaccine and immunization enterprise as an external advisor to the Department of Health and Human Services. We reviewed the history of NVAC in the context of the principles of its establishment, with a focus on its reports and recommendations. We performed a systematic literature review to identify NVAC reports published in widely-accessible public health journals, and we reviewed the available archives to identify other reports and resolutions approved by the committee not published in journals. We characterized key issues considered by NVAC according to the five goals of the 2010 National Vaccine Plan. The predominance of NVAC activities to date related to the implementation of immunization across the lifespan and the many aspects of the system needed to foster the goal of full immunization. Reflecting on the impacts of NVAC to date, this review identified 30 NVAC approved reports published in journals, 22 stand-alone resolutions, and 26 unique unpublished reports. The development of new and improved vaccines continues to represent a significant priority for NVAC, and we identified several challenges related to future vaccine innovation. Given the many factors that impact on policy changes in the vaccine and immunization enterprise, we encountered challenges associated with demonstrating attribution of specific policy changes to NVAC recommendations. Although difficult to quantify, this review suggests that NVAC played an important role in the improvements in the U.S. immunization enterprise over the past 30 years and that NVAC can and will continue to play an important role supporting U.S. immunization going forward.

Highlights • Gastrointestinal Mucormycosis after penetrating abdominal trauma. • Presented post-operatively as a gastropleural fistula. • Disease progresses rapidly and potentially fatal. • Treatment involves early diagnosis, surgical debridement, and anti-fungal therapy.