scholarly journals 1700. A Rare Case of Candida glabrata Hemorrhagic Cystitis with Empagliflozin Use

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S622-S623
Author(s):  
Ly Tran ◽  
Mathew Thomas ◽  
Jeremy Harvey ◽  
Rahul Sampath ◽  
Richard Rose
Keyword(s):  
Candida Glabrata ◽  
Viral Infections ◽  
Hemorrhagic Cystitis ◽  
Bladder Wall ◽  
Sglt2 Inhibitor ◽  
Symptomatic Improvement ◽  
Immunocompetent Host ◽  
Predisposing Factor ◽  
Increased Risk ◽  
Urinary Glucose

Abstract Background Hemorrhagic cystitis is an inflammatory condition of the bladder, infrequently seen after cancer chemotherapy, pelvic radiation, and viral infections in immunocompromised hosts. Methods We report a case of biopsy-proven Candida glabrata hemorrhagic cystitis in an immunocompetent host associated with empagliflozin use. Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, that increases urinary glucose excretion, and is associated with an increased risk of urogenital mycotic infections Results A 71-year-old man with a history type 2 diabetes, neurogenic bladder status post transurethral resection of the prostate, developed symptoms of pelvic pain and gross hematuria 3 months after the initiation of empagliflozin. The patient received multiple courses of empirical antibiotic therapy without any relief. Six months into the illness, the patient had significant weight loss, fatigue, progressive renal failure, and continued hematuria. Empagliflozin was self-discontinued by the patient secondary to a perceived relation between symptom onset and medication use. Urine cultures were negative. A CT scan showed mucosal thickening of the bladder wall with hydronephrosis. Cystoscopy was consistent with hemorrhagic cystitis. A bladder biopsy was negative for malignancy, stain and PCR negative for fungi, but culture positive for C. glabrata susceptible to Fluconazole. Mycobacterial stains, cultures, and PCR were negative. The patient was treated with Fluconazole for 4 weeks and experienced symptomatic improvement and resolution of hematuria one week into the therapy. Conclusion This is the first reported case of C. glabrata hemorrhagic cystitis in an immunocompetent host associated with empagliflozin. Invasive candida infections in the genitourinary system are rare in immunocompetent patients. We believe that empagliflozin-induced glycosuria may have been a predisposing factor. Disclosures All authors: No reported disclosures.

scholarly journals Immunological Aspects Related to Viral Infections in Severe Asthma and the Role of Omalizumab

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 348
Author(s):  
Francesco Menzella ◽  
Giulia Ghidoni ◽  
Carla Galeone ◽  
Silvia Capobelli ◽  
Chiara Scelfo ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Severe Asthma ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Antiviral Effect ◽  
Point Of View ◽  
Type I ◽  
Effector Cells ◽  
Viral Spread ◽  
Increased Risk

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.

scholarly journals Poliovirus excretion among children with primary immune deficiency in Pakistan: a pilot surveillance study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e045904
Author(s):  
Asma Sadruddin Pethani ◽  
Zaubina Kazi ◽  
Ujala Nayyar ◽  
Muhammad Shafiq-ur-Rehman ◽  
Muhammad Tahir Yousafzai ◽  
...  
Keyword(s):  
Viral Infections ◽  
Scientific Journal ◽  
Polio Eradication ◽  
Warning Signs ◽  
Paralytic Poliomyelitis ◽  
Primary Immune Deficiency ◽  
Increased Risk ◽  
Group Members ◽  
Poster Presentations ◽  
Study Context

IntroductionChildren with primary immunodeficiency disorders (PID) are more susceptible to developing viral infections and are at a substantially increased risk of developing paralytic poliomyelitis. Such children, if given oral polio vaccines tend to excrete poliovirus chronically that may lead to the propagation of highly divergent vaccine-derived poliovirus (VDPV). Consequently, they may act as a reservoir for the community by introducing an altered virus potentially imposing a risk to global polio eradication. However, the risks of chronic and prolonged excretion are not well characterised in the study context. This study seeks to establish a pilot surveillance system for successful identification and monitoring of VDPV excretion among children with PID. It will assess whether the Jeffrey Modell warning signs of PID can be used as an appropriate screening tool for PID in Pakistan.Methods and analysisIn this pilot surveillance, recruitment of PID cases is currently done at participating hospitals in Pakistan. Potential children are screened and tested against the Jeffrey Modell Foundation (JMF) warning signs for immunodeficiency and their stool is collected to test for poliovirus excretion. Cases excreting poliovirus are followed until the two consecutive negative stool samples are obtained over a period of 6 months. The data will be analysed to calculate hospital-based proportions of total Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases over a 2-year period and to determine the sensitivity and specificity of the JMF signs.Ethics and disseminationThis protocol was reviewed and approved by the WHO (WHO Reference-2018/811124-0), Aga Khan University (AKU ERC-2018-0380-1029) and National Bioethics Committee (Ref No. 4-87 NBC-308-Y2). The results will be published in an open access peer-reviewed scientific journal and presented to the iVDPV Working Group members, policy-makers, paediatric consultants and fellow researchers with the same domain interest. It may be presented in scientific conferences and seminars in the form of oral or poster presentations.

scholarly journals Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caroline Bartolo ◽  
Victoria Hall ◽  
N. Deborah Friedman ◽  
Chloe Lanyon ◽  
Andrew Fuller ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fungal Infections ◽  
Case Reports ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Urogenital Tract ◽  
Hypoglycemic Agents ◽  
Drug Induced ◽  
First Case ◽  
Increased Risk

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. Case presentations Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. Conclusions Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

scholarly journals Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1004
Author(s):  
Elena Gangitano ◽  
Rossella Tozzi ◽  
Orietta Gandini ◽  
Mikiko Watanabe ◽  
Sabrina Basciani ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Systemic Inflammation ◽  
Viral Infections ◽  
Invasive Mechanical Ventilation ◽  
Preventive Measure ◽  
Respiratory Compromise ◽  
Obese People ◽  
Increased Risk ◽  
Severely Obese ◽  
Respiratory Conditions

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.

scholarly journals Immunometabolic Status of COVID-19 Cancer Patients

2020 ◽  
Vol 100 (4) ◽  
pp. 1839-1850
Author(s):  
A. Sica ◽  
M. P. Colombo ◽  
A. Trama ◽  
L. Horn ◽  
M. C. Garassino ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Macrophage Activation ◽  
Viral Infections ◽  
Immune Cell ◽  
Case Series ◽  
The United States ◽  
Alternative Activation ◽  
Nad Metabolism ◽  
Increased Risk

Cancer patients appear to be more likely to be diagnosed with coronavirus disease 2019 (COVID-19). This is supported by the understanding of immunometabolic pathways that intersect patients with infection and cancer. However, data derived by case series and retrospective studies do not offer a coherent interpretation, since data from China suggest an increased risk of COVID-19, while data from the United States and Italy show a prevalence of COVID-19 in cancer patients comparable with the general population. Noteworthy, cancer and COVID-19 exploit distinct patterns of macrophage activation that promote disease progression in the most severe forms. In particular, the alternative activation of M2-polarized macrophages plays a crucial role in cancer progression. In contrast, the macrophage-activation syndrome appears as the source of M1-related cytokine storm in severe COVID-19 disease, thus indicating macrophages as a source of distinct inflammatory states in the two diseases, nonetheless as a common therapeutic target. New evidence indicates that NAMPT/NAD metabolism can direct both innate immune cell effector functions and the homeostatic robustness, in both cancer and infection. Moreover, a bidirectional relationship exists between the metabolism of NAD and the protective role that angiotensin converting enzyme 2, the COVID-19 receptor, can play against hyperinflammation. Within this immunometabolic framework, the review considers possible interference mechanisms that viral infections and tumors elicit on therapies and provides an overview for the management of patients with cancer affected by COVID-19, particularly for the balance of risk and benefit when planning normally routine cancer treatments and follow-up appointments.

scholarly journals Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia

2014 ◽  
Vol 306 (2) ◽  
pp. F188-F193 ◽  
Author(s):  
Timo Rieg ◽  
Takahiro Masuda ◽  
Maria Gerasimova ◽  
Eric Mayoux ◽  
Kenneth Platt ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Plasma Concentrations ◽  
Sglt2 Inhibitor ◽  
Double Knockout ◽  
Glucose Reabsorption ◽  
Urinary Glucose ◽  
Sglt2 Inhibition ◽  
Renal Glucose Reabsorption ◽  
Glucose Excretion ◽  
Free Plasma

In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1−/−) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1−/− vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1−/− vs. WT after 24 h (−33 vs. −11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1−/−. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to −1 ± 3% in Sglt1−/−. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50–60% of filtered glucose is excreted.

scholarly journals Harnessing basic and clinic tools to evaluate SGLT2 inhibitor nephrotoxicity

2017 ◽  
Vol 313 (4) ◽  
pp. F951-F954 ◽  
Author(s):  
Danielle L. Saly ◽  
Mark A. Perazella
Keyword(s):  
Early Stage ◽  
Functional Decline ◽  
Healthcare Providers ◽  
Sglt2 Inhibitor ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Chip Technology ◽  
Urinary Glucose

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of medications that target the transporter that reabsorbs ~90% of glucose in the S1 segment of the proximal convoluted tubule. As a result, SGLT2 inhibition increases urinary glucose excretion, effectively lowering plasma glucose levels. In addition to reducing hemoglobin A1c levels, these drugs also lower body weight, blood pressure, and uric acid levels in Type 2 diabetes mellitus (T2DM) patients. Importantly, empagliflozin has been observed to slow progression of kidney disease and reduce dialysis requirements in T2DM patients. However, the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) has collected over 100 cases of acute kidney injury (AKI) for canagloflozin and dapagliflozin since their approval. Of the 101 patients, 96 required hospitalization, 22 required intensive care unit admission, and 15 underwent hemodialysis. The FDA now requires that AKI be listed as a potential side effect of the SGLT2 inhibitors along with cautious prescription of these drugs with other medications, such as renin-angiotensin-system antagonists, diuretics, and NSAIDs. It is unclear, however, whether this FAERS reported “AKI” actually represents structural kidney injury, as randomized, controlled trials of these drugs do not describe AKI as an adverse event despite coprescription with RAS blockers and diuretics. As a result of this FDA warning, diabetic patients with early-stage CKD may not be prescribed an SGLT2 inhibitor for fear of AKI. Thus, it is imperative to ascertain whether the reported AKI represents true structural kidney injury or a functional decline in glomerular filtration rate. We propose using readily available clinical tools with experimental biomarkers of kidney injury and kidney-on-a-chip technology to resolve this question and provide solid evidence about the AKI risk of these drugs for healthcare providers.

scholarly journals Mannan-Binding Lectin Levels and Activity Are Not Altered in Atopic Dermatitis Patients with a History of Eczema Herpeticum

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Kemp W. Bundy ◽  
Laura Y. McGirt ◽  
Lora G. Bankova ◽  
Andreas Wollenberg ◽  
Lisa A. Beck ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Functional Activity ◽  
Viral Infections ◽  
Serum Levels ◽  
Small Samples ◽  
Eczema Herpeticum ◽  
Increased Risk ◽  
History Of ◽  
Mannan Binding Lectin ◽  
Binding Lectin

Background. Eczema herpeticum (EH) is a potentially serious, systemic complication in subjects with atopic dermatitis (AD) caused by herpes simplex virus (HSV). The innate immune dysregulation that predisposes these subjects to cutaneous viral infections is not well understood. We tested the hypothesis that defects in mannan-binding lectin (MBL) may be associated with an increased risk of EH.Methods. We evaluated serum MBL levels and functional activity in 13 AD subjects with a history of EH (EH+) and 21 AD subjects with no history of EH (EH−). MBL levels were detected by enzyme immunoassay. MBL pathway functional activity was evaluated by determining MBL C4b deposition capacity.Results. We found no statistical difference in MBL serum levels or function between EH+ and EH− groups.Conclusion. Considering the limitations of this study (e.g., small samples size) our findings suggest that MBL defects do not play a role in EH.

scholarly journals COVID-19 Mortality is Associated with Impaired Innate Immunity in Pre-existing Health Conditions

2021 ◽  
Author(s):  
Matthew E Lee ◽  
Yung Chang ◽  
Navid Ahmadinejad ◽  
Crista E Johnson-Agbakwu ◽  
Celeste Bailey ◽  
...  
Keyword(s):  
Risk Factors ◽  
Innate Immunity ◽  
Viral Infections ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Therapeutic Interventions ◽  
Health Conditions ◽  
Molecular Abnormalities ◽  
Hazard Ratios ◽  
Increased Risk

Background: COVID-19 poses a life-threatening endangerment to individuals with chronic diseases. However, not all comorbidities affect COVID-19 prognosis equally. Some increase the risk of COVID-19 related death by more than six folds while others show little to no impact. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities in common health conditions that predispose patients to poor prognoses. In this study, we aim to discover some of these molecular risk factors by associating gene expression dysregulations in common health conditions with COVID-19 mortality rates in different cohorts. Methods: We focused on fourteen pre-existing health conditions, for which age-and-sex-adjusted hazard ratios of COVID-19 mortality have been documented. For each health condition, we analyzed existing transcriptomics data to identify differentially expressed genes (DEGs) between affected individuals and unaffected individuals. We then tested if fold changes of any DEG in these pre-existing conditions were correlated with hazard ratios of COVID-19 mortality to discover molecular risk factors. We performed gene set enrichment analysis to identify functional groups overrepresented in these risk factor genes and examined their relationships with the COVID-19 disease pathway. Results: We found that upregulated expression of 70 genes and downregulated expression of 181 genes in pre-existing health conditions were correlated with increased risk of COVID-19 related death. These genes were significantly enriched with endoplasmic reticulum (ER) function, proinflammatory reaction, and interferon production that participate in viral transcription and immune responses to viral infections. Conclusions: Impaired innate immunity in pre-existing health conditions are associated with increased hazard of COVID-19 mortality. The discovered molecular risk factors are potential prognostic biomarkers and targets for therapeutic interventions.

scholarly journals Airway Management in the Emergency Department During Coronavirus Disease (COVID-19)

2020 ◽  
Vol 28 (2) ◽  
pp. 5-11
Author(s):  
Sohil Pothiawala
Keyword(s):  
Emergency Department ◽  
Airway Management ◽  
Viral Infections ◽  
Transmission Risk ◽  
National Guidelines ◽  
Hospital Policy ◽  
Resource Limited ◽  
Increased Risk ◽  
Emerging Viral Diseases ◽  
Evidence Based Guidelines

Front-line health-care workers in the Emergency Department (ED) are at an increased risk of infection during the airway management of patients with known or suspected Emerging Viral Diseases (EVD) like Coronavirus Disease 2019 (COVID-19). The primary route for transmission of the virus from an infected patient to the ED staff is due to aerosolized droplets, and the transmission risk is high despite wearing adequate Personal Protective Equipment (PPE). There are limited evidence-based guidelines for airway management during these viral infections, especially with a focus on the principles of airway management in a busy, fast-paced ED. This article provides an overview of the principles of airway management in suspected or confirmed EVD patients, including COVID-19, particularly in the context of ED, and also considering strategies in resource limited setting. These principles should be adapted to suit your local department and hospital policy on airway management as well as national guidelines.

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