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Objective: To analyze the clinical manifestations, diagnostic methods and treatment process of the patients with non-Hodgkin's lymphoma complicated with human coronavirus(HCoV)-HKU1 pneumonia and improve the clinical medical staff's awareness of the disease, and to reduce the occurrence of clinical adverse events. Method(s): The clinical data of a patient with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia with hot flashes and night sweats, dry cough and dry throat as the main clinical features who were hospitalized in the hospital in January 2021 were analyzed, and the relevant literatures were reviewed and the clinical manifestations and diagnosis of HCoV-HKU1 were analyzed. Result(s): The female patient was admitted to the hospital due to diagnosed non-Hodgkin's lymphoma for more than 2 months. The physical examination results showed Karnofsky score was 90 points;there was no palpable enlargement of systemic superfical lymph nodes;mild tenderness in the right lower abdomen, no rebound tenderness, and slightly thicker breath sounds in both lungs were found, and a few moist rales were heard in both lower lungs. The chest CT results showed diffuse exudative foci in both lungs, and the number of white blood cells in the urine analysis was 158 muL-1;next generation sequencing technique(NGS) was used the detect the bronchoalveolar lavage fluid, and HCoV-HKU1 pneumonia was diagnosed. At admission, the patient had symptoms such as dull pain in the right lower abdomen, nighttime cough, and night sweats;antiviral treatment with oseltamivir was ineffective. After treatment with Compound Sulfamethoxazole Tablets and Lianhua Qingwen Granules, the respiratory symptoms of the patient disappeared. The re-examination chest CT results showed the exudation was absorbed. Conclusion(s): The clinical symptoms of the patients with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia are non-specific. When the diffuse shadow changes in the lungs are found in clinic, and the new coronavirus nucleic acid test is negative, attention should still be paid to the possibility of other HCoV infections. The NGS can efficiently screen the infectious pathogens, which is beneficial to guide the diagnosis and treatment of pulmonary infectious diseases more accurately.Copyright © 2023 Jilin University Press. All rights reserved.
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This study examines clinical outcomes in patients with cytomegalovirus (CMV) and SARS-CoV-2 coinfection. Between June and November 2020, previously immunocompetent patients with SARS-CoV-2 and CMV coinfection were identified at Houston Methodist Hospital as part of routine clinical correlation by a molecular pathologist. SARS-CoV-2 nasopharyngeal specimens were analyzed by real time reverse-transcriptase polymerase chain reaction (RT-PCR). All CMV tests were performed on plasma or bronchoalveolar lavage (BAL) specimens and analyzed by competitive polymerase chain reaction. 65 previously immunocompetent patients with CMV and SARS-CoV-2 coinfection were identified. Patient demographics include 41 male patients (63%) and 24 female patients (37%) ranging in age from 34 to 86 years (mean: 66.04, median 68). Documented pre-existing conditions include 27 patients with hypertension 41.5%), 19 patients with diabetes mellitus (29.2%), 9 patients with coronary artery disease (13.8%), and 3 patients with asthma (4.6%). Eight patients (12.3%) had no documented pre-existing conditions. The plasma CMV viral load ranged from <300 to 21,566 IU/mL. The CMV PCR results from bronchoalveolar lavage and bronchial wash specimens ranged from <300 to 59,127 IU/mL. CMV PCR was initially negative in 10 patients then positive on serial testing. 60 patients were critically ill requiring ventilator support (92.3%). 47 patients (72.3%) expired, 7 patients (10.8%) were transferred to a long term acute care facility, 3 patients (4.6%) were discharged to a rehabilitation facility, 3 patients (4.6%) were discharged home, and 1 patient (1.5%) remained in-patient at the time of analysis. The prevalence of CMV seropositivity and medical comorbidities increases with age. Reactivation of latent CMV is a known occurrence in critically ill patients that is associated with poor outcomes. The majority of the patients in our cohort were 50 years old, and all were severely to critically ill with a mortality rate of 72.3% These findings suggest CMV portends a worse prognosis in patients with COVID-19. These findings also demonstrate the importance of clinical correlation in molecular testing.
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Case: Wiskott-Aldrich Syndrome (WAS) is a rare X-linked inborn error of immunity caused by mutations in the WAS gene. It is classically characterized by immunodeficiency, eczema, and micro-thrombocytopenia. It has been known since the 1960s that patients with WAS have an increased risk of lymphoproliferative disease though the exact incidence remains unknown in the American population. Limited case reports have discussed EBV-related lymphoproliferative disease in patients with WAS. We present a case of a 9-year-old boy with known WAS complicated by eczematous rash, thrombocytopenia, recurrent ear infections, and monoclonal gammopathy who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. Family had been offered treatment with hematopoietic stem cell transplant but declined multiple times in the past. Earlier in the year, he presented with possible MIS-C with negative SARS-CoV-2 PCR. He presented to our hospital with mastoiditis and lymphadenopathy. Physical examination showed severe eczema on hands and tender right mastoid. Laboratory evaluation showed thrombocytopenia, elevated IgG of 6290, IgA of 744, IgE of 827, low IgM of 41, and 14% response to pneumococcal titers. He was empirically treated with intravenous antibiotics. ENT performed right postauricular incision and drainage and the culture grew Hemophilus influenza. Throughout his hospital stay, his submandibular lymphadenopathy became more prominent despite treatment. Core needle biopsy of right submandibular lymph node was suggestive of EBV-associated lymphoid hyperplasia. EBV PCR and antibodies were both positive. CT chest, abdomen, and pelvis revealed multifocal pulmonary lymphadenopathy and a diffuse, bilateral nodularity as well as retroperitoneal and mesenteric lymphadenopathy. He was given four doses of weekly Rituximab, which successfully decreased EBV viremia below linear detectability. Immunoglobulin replacement therapy (IgRT) was initiated. Bronchoalveolar lavage and lung biopsy were performed and are results are currently pending. Discussion(s): We present a case of a 9-year-old boy with known WAS awaiting transplant who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. While lymphoproliferative disease is a known complication of WAS, EBV-related lymphoproliferative disease in WAS patients has only been reported as case reports and remains a rare but known complication of patient with WAS.Copyright © 2023 Elsevier Inc.
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Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.
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Introduction: Most modern healthcare systems are striving to improve patient outcomes in an evidence-based manner. Increasingly, performance metrics are seen as key tools for accurately measuring and improving patient outcomes and healthcare value.1 However, in order to achieve better outcomes, process measures need to be identified. Process measures are evidence-based, best practices metrics that can be measured and thus, used to identify if outcomes are being met. Good process measures can improve patient outcomes by reducing the amount of variation in care delivery. During the Covid-19 pandemic, vast quantities of data were generated while managing ARDS (Acute Respiratory Distress Syndrome) on the ICU. Furthermore, there was as a concomitant evolution of treatment strategies, which made it exceedingly difficult to identify processes that were actually improving patient outcomes. Objective(s): The aim of our quality improvement project was to promote standardised high quality care for intubated Covid-19 patients by identifying potential quality indicators and trends in their management. It is our intention to expand on this work to report metrics on all severe acute respiratory failure patients. Method(s): 15 process metrics surrounding the early care of intubated of Covid-19 patients were selected via a consultant led review process and a literature review in an effort to identify markers of quality surrounding intubation on our ITU. The variables selected included: - P/F ratio 24 hours pre-intubation, CPAP (continuous positive airway pressure) duration prior to intubation, Recording intubation location, Enhanced thromboprophylaxis prescribed, Permissive hypercapnia, Driving pressure documented, prone position and paralysis initiated if P/F ratio was less than 20 kPa, Echo post intubation. Result(s): Data surrounding the intubation of Covid-19 patients was collected over an 11 week period between September and November 2021. The data was collected in a standardised fashion from patient notes and nursing notes, then stored in an excel file. Our data showed more than half the patients admitted were either intubated on the ward or immediately following arrival onto our ICU, possible indicating a delay in admitting Covid-19 patients. Our data also demonstrated heterogeneity of duration in CPAP prior to intubation which may also indicate delayed intubation for these patients.2 Conclusion(s): Our data demonstrated a reasonable degree of heterogeneity in our approach to the early care of intubated Covid-19 Patients. Areas of concern highlighted were the number of patients intubated on the ward or immediately upon arrival to ITU, rather than admitting prior to deterioration (most likely due to bed pressure) and variation in post intubation respiratory sampling between invasive and non-invasive broncheoalveolar lavage. Ongoing PDSA (plan-do-study-act) cycling are in progress to refine the data collection processes and reporting for all severe acute respiratory failure patients.
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Background & Aim: Ricin is one of the most lethal toxins, particularly if inhaled, and is considered a biological threat agent due to its wide availability and ease of production. Pulmonary ricin intoxication manifests in ARDS, cytokine storm, immune infiltration, and severe edema. Passive immunization is the preferred measure against pulmonary ricinosis, but only if administered shortly after exposure. Despite their potential to remedy pulmonary injury and inflammation, mesenchymal cell (MSC) therapies were never investigated in ricinosis. Here, we report the potential for treating pulmonary ricinosis with MesenCure, a professionalized allogeneic MSC therapy shown to reduce the mortality of patients suffering from severe pulmonary manifestations of COVID by 68%. Methods, Results & Conclusion(s): Preliminary studies demonstrated positive MesenCure effects in a sub-lethal pulmonary ricinosis model in CD1 mice. This model is regarded as highly translational due to the broad heterogeneity of these outbred mice. Positive effects included a reduction in excess protein content of the bronchoalveolar lavage fluid (BALF) by 45% when MesenCure was injected intravenously (IV) at 125k cells/animal, 48h post-exposure (PE) and evaluated one day later (p<0.05, Fig. 1A). Moreover, we found up to 52% reduction in the excess BALF leukocytes, when MesenCure was injected IV, 24h PE using the same dose (p<0.05, Fig. 1B) or 6h PE using a double dose (p<0.01, Fig. 1C), and evaluated two days PE. Optimizing the dose and administration route further improved the therapeutic outcome of MesenCure applied 6h PE as assessed by weight loss. As shown in Fig. 1D-E, IV injection of 250k-500k MesenCure cells/animal slightly protected the intoxicated animals against weight loss (p for treatment x time interaction <0.01 or <0.05 for 250k and 500k cells/animal, respectively). Interestingly, one million cells IV resulted in a lesser effect (not shown), however when injected subcutaneously (SC), 1M cells were very effective (p<0.001, Fig. 1F), seemingly even more effective than 2M cells/animal SC (Fig. 1G). Surprisingly, 2M thawed cells/animal injected SC protected the animals against weight loss almost completely (p<0.0001, Fig. H). In conclusion, we provide evidence for the potential of SC MSCs, specifically MesenCure, for treating pulmonary ricinosis and possibly other forms of ARDS. In agreement with Giri and Galipeau (2020), we provide further evidence for the dependency of MSC outcomes on their specific state and administration route. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease characterized by macrophage dysfunction leading to the accumulation of surfactant in the alveoli and bronchiolar spaces, leading to impaired gas exchange and severe hypoxemia. The underlying mechanisms of PAP are not fully understood, but it is believed to involve impaired clearance of surfactant and abnormal immune responses. Diagnosis of PAP typically involves imaging studies and bronchoscopy, and treatment options include whole-lung lavage, pharmacotherapy, and lung transplantation. We report PAP in a 56-year-old female who worked in a dental office and had no prior diagnosis of lung disease.
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Introduction Reports are rare on the usefulness of the FilmArray Respiratory Panel 2.1 (FARP) using lower respiratory tract specimens. This retrospective study assessed its use, as part of a comprehensive infectious disease panel, to detect the viral causes of pneumonia using bronchoalveolar lavage samples from immunosuppressed patients. Methods This study included immunocompromised patients who underwent bronchoalveolar lavage or bronchial washing by bronchoscopy between April 1, 2021, and April 30, 2022. The collected samples were submitted for comprehensive testing, including FARP test; reverse transcription polymerase chain reaction (RT-PCR) for cytomegalovirus, varicella-zoster virus DNA, and herpes simplex virus; PCR for Pneumocystis jirovecii DNA; antigen testing for Aspergillus and Cryptococcus neoformans; and loop-mediated isothermal amplification method for Legionella. Results Out of 23 patients, 16 (70%) showed bilateral infiltrative shadows on computed tomography and three (13%) were intubated. The most common causes of immunosuppression were anticancer drug use (n=12, 52%) and hematologic tumors (n=11, 48%). Only two (9%) patients tested positive for severe acute respiratory syndrome coronavirus 2 and adenovirus by FARP. Four patients (17%) tested positive for cytomegalovirus by RT-PCR, but no inclusion bodies were identified cytologically. Nine (39%) patients tested positive for Pneumocystis jirovecii by PCR, but cytology confirmed the organism in only one case. Conclusions Comprehensive infectious disease testing, performed using bronchoalveolar lavage samples collected from lung lesions in immunosuppressed patients, showed low positive detection by FARP. The viruses currently detectable by FARP may be less involved in viral pneumonia diagnosed in immunocompromised patients.
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Objectives Immunocompromised patients, specifically those with solid organ transplants or cancer on chemotherapy, are at particularly high risk of severe pneumonia and opportunistic infections. In select patients, bronchoalveolar lavage (BAL) is performed to provide high-quality samples for analysis. We compare BioFire® FilmArray® Pneumonia Panel (BioFire Diagnostics, Salt Lake City, Utah, United States), a multiplex polymerase chain reaction (PCR) assay, with standard of care diagnostics in BAL samples from immunocompromised patients to identify opportunities for this test to affect clinical decision making. Methods Patients hospitalized with pneumonia based on clinical and radiographic findings who underwent evaluation with bronchoscopy between May 2019 to January 2020 were reviewed. Among those patients undergoing bronchoscopy, those who were immunocompromised were selected for inclusion in the study. BAL specimens submitted to the microbiology laboratory were chosen based on as part of the internal validation of the panel in comparison with sputum culture at our hospitals. We compared the outcomes of the multiplex PCR assay with traditional culture methods and evaluated the role of PCR assay in de-escalating antimicrobial therapy. Results Twenty-four patients were identified for testing with the multiplex PCR assay. Of the 24 patients, 16 were immunocompromised, all with solid or hematological malignancy or a history of organ transplant. Seventeen individual BAL samples from the 16 patients were reviewed. BAL culture results and the multiplex PCR assay were in agreement in 13 samples (76.5%). In four cases, the multiplex PCR assay identified a possible causative pathogen not detected by standard workup. The median time to de-escalation of antimicrobials was three days (interquartile range (IQR) 2-4) from the day of collection of the BAL samples. Conclusions Studies have established the additive role of multiplex PCR testing in addition to traditional diagnostic tools like sputum culture in diagnosing the etiology of pneumonia. Limited data exist specifically looking at immunocompromised patients, in whom a timely and accurate diagnosis is particularly important. There is a potential benefit for performing multiplex PCR assays as an additive diagnostic tool in BAL samples for these patients.
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COVID-19-related acute respiratory distress syndrome (CARDS) is associated with high mortality rates. We still have limited knowledge of the complex alterations developing in the lung microenvironment. The goal of the present study was to comprehensively analyze the cellular components, inflammatory signature, and respiratory pathogens in bronchoalveolar lavage (BAL) of CARDS patients (16) in comparison to those of other invasively mechanically ventilated patients (24). In CARDS patients, BAL analysis revealed: SARS-CoV-2 infection frequently associated with other respiratory pathogens, significantly higher neutrophil granulocyte percentage, remarkably low interferon-gamma expression, and high levels of interleukins (IL)-1ß and IL-9. The most important predictive variables for worse outcomes were age, IL-18 expression, and BAL neutrophilia. To the best of our knowledge, this is the first study that was able to identify, through a comprehensive analysis of BAL, several aspects relevant to the complex pathophysiology of CARDS.
Subject(s)
COVID-19 , Pneumonia , Respiratory Distress Syndrome , Humans , Prospective Studies , Bronchoalveolar Lavage Fluid , COVID-19/diagnosis , SARS-CoV-2 , Bronchoalveolar Lavage , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/metabolismABSTRACT
Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.
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AIM: to estimate the features of pseudomembranous colitis in patients with COVID-19, diagnostics, conservative treatment and surgery for complications. PATIENTS AND METHODS: a retrospective analysis of 396 patients with pseudomembranous colitis (PMC) in patients with new coronavirus infection was carried out for the period from March 2020 to November 2021. Among them there were 156 (39.3%) males, females - 240 (60.6%), moderate and severe forms of COVID-19 occurred in 97.48%. The diagnosis of PMC was established due to clinical picture, laboratory, instrumental methods (feces on Cl. difficile, colonoscopy, CT, US, laparoscopy). RESULT(S): the PMC rate in COVID-19 was 1.17%. All patients received antibiotics, 2 or 3 antibiotics - 44.6%, glu-cocorticoids were received by all patients. At 82.8%, PMC developed during the peak of COVID-19. To clarify the PMC, CT was performed in 33.8% of patients, colonoscopy - 33.08%, laparoscopy - in 37.1% (to exclude bowel perforation, peritonitis). Conservative treatment was effective in 88.8%, 76 (19.1%) patients had indications for surgery (perforation, peritonitis, toxic megacolon). Most often, with peritonitis without clear intraoperative confir-mation of perforation, laparoscopic lavage of the abdominal cavity was performed (60 patients - 78.9%, mortality - 15.0%), colon resection (n = 6 (7.9%), mortality - 66.6%), ileo-or colostomy (n = 8 (10.5%), mortality - 37.5%), colectomy (n = 2 (2.6%), mortality - 50.0%). The overall postoperative mortality rate was 22.4%, the incidence of surgical complications was 43.4%. In addition, in the postoperative period, pneumonia was in 76.3%, thrombosis and pulmonary embolism in 22.3% of patients. In general, the overall mortality in our patients with PMC was 11.4%, with conservative treatment - 8.8%. CONCLUSION(S): pseudomembranous colitis is a severe, life-threatening complication of COVID-19. In the overwhelm-ing majority of patients, conservative therapy was effective, but almost 1/5 of patients developed indications for surgery, the latter being accompanied by high mortality and a high morbidity rate. Progress in the treatment of PMC, apparently, is associated with early diagnosis, intensive conservative therapy, and in the case of indications for surgery, their implementation before decompensation of the patient's condition and the development of severe intra-abdominal complications and sepsis.Copyright © 2022, Association of Coloproctologists of Russia. All rights reserved.
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BACKGROUND: SARS-CoV-2 was reported to induce cell fusions to form multinuclear syncytia that might facilitate viral replication, dissemination, immune evasion, and inflammatory responses. In this study, we have reported the types of cells involved in syncytia formation at different stages of COVID-19 disease through electron microscopy. METHODS: Bronchoalveolar fluids from the mild (n = 8, SpO2 > 95%, no hypoxia, within 2-8 days of infection), moderate (n = 8, SpO2 90% to ≤ 93% on room air, respiratory rate ≥ 24/min, breathlessness, within 9-16 days of infection), and severe (n = 8, SpO2 < 90%, respiratory rate > 30/min, external oxygen support, after 17th days of infection) COVID-19 patients were examined by PAP (cell type identification), immunofluorescence (for the level of viral infection), scanning (SEM), and transmission (TEM) electron microscopy to identify the syncytia. RESULTS: Immunofluorescence studies (S protein-specific antibodies) from each syncytium indicate a very high infection level. We could not find any syncytial cells in mildly infected patients. However, identical (neutrophils or type 2 pneumocytes) and heterotypic (neutrophils-monocytes) plasma membrane initial fusion (indicating initiation of fusion) was observed under TEM in moderately infected patients. Fully matured large-size (20-100 µm) syncytial cells were found in severe acute respiratory distress syndrome (ARDS-like) patients of neutrophils, monocytes, and macrophage origin under SEM. CONCLUSIONS: This ultrastructural study on the syncytial cells from COVID-19 patients sheds light on the disease's stages and types of cells involved in the syncytia formations. Syncytia formation was first induced in type II pneumocytes by homotypic fusion and later with haematopoetic cells (monocyte and neutrophils) by heterotypic fusion in the moderate stage (9-16 days) of the disease. Matured syncytia were reported in the late phase of the disease and formed large giant cells of 20 to 100 µm.
Subject(s)
COVID-19 , Humans , COVID-19/metabolism , SARS-CoV-2 , Microscopy, Electron , Alveolar Epithelial Cells , Macrophages , Giant CellsABSTRACT
Purpose of Study Non-diabetic COVID-19 patients with elevated admission fasting blood glucose levels ('hyperglycemia') inexplicably have an increased 28 day mortality and higher inhospital complications including the Acute Respiratory Distress Syndrome (ARDS) but potentially contributing blood glucose changes during ARDS development were not reported (Wang S et al: Diabetologia 2020). Our goal was to determine blood glucose alterations before and during acute lung injury development in a rat model used to study ARDS. Methods Used We sequentially evaluated blood glucose levels for 24 hours and lung lavage protein levels (lung permeability) and lung lavage neutrophil numbers (lung inflammation) at 24 hours to assess acute lung injury ('ARDS') in young (~3 month) and old (~12 month) control and a novel strain of hyperoxia surviving 'resistant' rats before and after administering high and low insulin doses and before and after interleukin- 1/lipopolysaccharide (IL-1/LPS) insufflation. Summary of Results Glucose levels increase rapidly and sequentially in young control, but not young resistant, rats peaking ~2 hours after insufflation. Glucose levels also increase in old control and old resistant rats after insufflation compared to young control and young resistant rats after insufflation. The pattern of glucose levels at 2 hours after insufflation resembles lung lavage proteins and neutrophils at 24 h after insufflation (table 1). Administering high insulin (High In) doses decreases glucose levels ('hypoglycemia') and worsens ARDS while administering low insulin (Low In) doses correct glucose levels and improve ARDS. Conclusions Hyperglycemia develops in both young and old rats developing ARDS and high or low glucose levels parallel worse acute lung inflammation and acute lung injury ('ARDS'). Controlling glucose judiciously with insulin may be beneficial in combatting ARDS caused by SARS-CoV-2 infection and other insults.
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The COVID-19 outbreak has fashioned to severe threat to each and every individual in social and economic aspects in the country. This required improved wisdom to know how it is different and dominant, to diagnose and determine effective vaccines to avoid the transmission of these deadly causative agents. From this review, the probable property of these deadly transmissible viruses is related to that of SARS-CoV-2 as a fright zone of viruses. It also provides some sparks about effective and accurate diagnosis and treatment strategies. The effective management and control of panic zone of virus (PZV) and SARS-CoV-2 are more important to reduce the pandemic situation.Copyright © 2023 Inderscience Enterprises Ltd.
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Introduction: Diagnosis of ventilator-associated pneumonia (VAP) in COVID-19 patients remains challenging. Also, the lack of gold standard for microbiological sampling undermines clinical judgement and management. We studied incidences of microbiologically-confirmed VAP comparing endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) in COVID-19 patients. Etiological agreement between ETA and BAL was then assessed. Method(s): Single-center prospective cohort study (NCT04766983). Patients were enrolled within 48 h from intubation;surveillance ETA ( ETASURV) was performed twice weekly. ETA ( ETACX) and BAL ( BALCX) samples were collected upon VAP suspicion (Johanson's criteria). CDC definitions were used for microbiological confirmation. ETA-BAL agreement (interrater reliability and Cohen's kappa) and clinical/microbiological data were assessed for the first episodes of suspected VAP per patients. Result(s): Ninety intensive care (ICU) patients enrolled from 01/2021 to 05 06/2022, of which 26 females (28.9%);median age was 60 [52-66] years. In-ICU mortality was 30/90 (33.3%), median length of stay in survivors 19 (10-32) days. Fifty-three patients (58.9%) had >= 1 episode of suspected VAP after 6 [5;10] days from ICU admission. ETASURV were available in 52 cases, 2 [1;3] days before VAP suspect, and tested positive in 28 (53.8%). ETACX and BALCX resulted positive in 35 (66.0%) and 29 (54.7%) of episodes. Main microbiological results are displayed in Fig. 1, panel A. Etiological agreement between techniques is shown in Fig. 1, panel B. Incidence rate of VAP suspicions per 1000 ventilator-days was 60.2 (95% CI 43.9-76.4), while incidence rates of microbiologically-confirmed VAP were 27.4 (18.3-36.5) with ETACXand 18.9 (95% CI 12.0-25.8) with BALCX, respectively. Conclusion(s): We observed different incidence of VAP in COVID-19 ICU patients depending on sampling method. Etiological agreement between techniques yielded limited interrater reliability. The potential clinical impact needs further studies.
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Towards the end of 2019 a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) caused the ongoing global pandemic. The virus surface consists of spike proteins that mediate SARS-CoV-2 entry into cells through its receptor-binding domain (RBD) that attaches to the human receptor Angiotensin- Converting Enzyme 2 (ACE2). Upon infection with foreign material, like viruses and bacteria, the human immune system responds by producing a humoral response specific to the viral antigen. Cells from the innate immune system and antibodies generated in the humoral response work to destroy and block infectious antigens from causing damage to the human cells. The S protein of SARSCoV- 2 is the key protein that stimulates the immune system to generate neutralizing antibodies. To safely test and investigate SARS-CoV-2 in BSL-2 lab setting, we propagated a surrogate pseudo typed virus to evaluate the ability of antibodies to reduce viral cell entry and replication in SARS-CoV-2 infected mice model. Quantifying the functional ability of neutralizing antibodies would help us understand how they influence reinfection in recovered individuals. We hypothesize that antibodies generated in SARS-CoV-2 infected mice models will induce a protective immune response against the SARSCoV- 2 infection. To detect and quantify the protective immune response generated in mice, we performed two different serological assays and identified antibodies endpoint titers. Mice were infected with Delta and Beta at time points Day 3 and Day 4. We performed a SARS-CoV-2 Spike pseudo virus neutralization assay and measured luminescence to determine the percentage neutralization of functional antibodies induced in mice serum samples upon infection. Utilizing indirect ELISAs,' we measured absorbance for IgA antibodies in Bronchoalveolar lavage fluid (BALF) serum and total IgG antibodies in cardiac bleeds. Our results showed we did not obtain neutralizing activity of antibodies in mice serum samples taken at early time points, 24 hrs and 4 days, after infection with the Delta variant of SARS CoV2 virus using both the pseudo viruses Omicron andWA spike.We obtained 100% neutralizing activity in mice serum samples taken at day 21 and infected with Beta variant of SARS CoV2 virus using both the pseudo viruses Omicron and WA spike demonstrating that there is cross-neutralization against various variants of concern. Antibodies (IgA, IgM, IgG) generated in mice 3 weeks post infection with SARS CoV2 (Beta) virus are capable of neutralizing and inhibiting the entry of WA spike and Omicron pseudo viruses in human HEK293 T Ace2 cells. Moving forward utilizing samples with timepoints surpassing 3 weeks could possibly yield higher concentrations of IgA and IgM antibodies that can neutralize the SARS-CoV-2 pseudo virus. Thank you to Dr. Rhea Coler, the entire Coler lab, National Institutes of Health (NIH), and Seattle Children's Research Institute.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Purpose of Study Surgical site infections (SSI) burden U.S. hospitals with around $1.5 billion annually. To reduce SSI, irrigating the incision with an antimicrobial solution before closure is recommended. Hence, we evaluate the impact of Irrisept, a form of diluted chlorohexidine 0.05%, on reducing the prevalence of SSI in a high-risk breast cosmetic surgery population. Methods Used We conducted a retrospective cohort study using data in the electronic medical record for breast implant exchange patients in one practice and analyzed infection rates between 42 patients from July 2018-June 2019 that did not receive Irrisept irrigation (control group) with 16 patients from July 2019-July2020 that received Irrisept irrigation (experimental group;significantly less due to Covid-19). We executed descriptive analyses, independent T test, ANOVA (for 3 types of incision location), and Chi-squared to assess comorbidities and intraoperative factors. Summary of Results Among the control group (n=42), 4 patients had a postoperative infection;in the experimental group (n=16), 0 had an infection (9.52% vs. 0%;p=0.04) suggesting the use of Irrisept significantly decreases SSI. The p values from the T test and ANOVA (p<0.05=significant) showed no significant differences in breast cancer (0.84), previous radiation (0.32), history of chemotherapy (0.57), obesity (0.40), renal failure (0.32), smoker/previous smoker (0.41), type of implant (0.32), incision location (0.68), acellular dermal matrix use (0.32), or drain use (0.58) between two groups. The only significant comorbidity was diabetes (p=0.04) with 9.52% (control) vs. 0% (experimental). However, greater percentage of experimental group were obese (25% vs.14.29%) and had a history of smoking (25% vs. 9.52%). Conclusions A concern regarding the implementation of Irrisept irrigation is associated costs. However, the results show the use of Irrisept decreases the infection rates, ultimately relieving the financial burden of postoperative infections. Therefore, we recommend irrigating the incisions of breast surgery patients with Irrisept as both a preventative and economic measure.
ABSTRACT
Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.