The role of rapid diagnostic point of care IgG/IgM antibody tests in the diagnosis of SARS-CoV-2 infection

Background: Current testing of symptomatic patients for SARS-CoV-2 involves the use of nucleic acid amplification tests, also known as genetic, RNA or PCR to detect viral RNA. The initial use of point-of-care (POC) antibody tests, also known as serological tests in the management of SARS-CoV-2 infection was limited. In this review, we determine the significance of POC antibody serological tests and explore their possible role in the diagnosis and management of patients infected with SARS-CoV-2 virus. Methods: A literature search was conducted in Google Scholar, PubMed, and Embase, and supplemented by searching the Center for Disease Control (CDC), and the Infectious Diseases Society of America (IDSA) websites. We identified 7 articles published in the last 6 months pertaining to the keywords. The sensitivity and specificity of the IgG/IgM antibody tests obtained from these studies were compared and used to determine the clinical importance of the rapid diagnostic antibody test in SARS-CoV-2 infection. Results: Through the literature review, it was found that POC diagnostic antibody tests can be used as an adjuvant with the nucleic acid amplification tests in determining both active and post-exposure antibodies. These rapid antibody IgG/IgM tests had high sensitivity, the ability of a test to correctly identify those with the disease, and high specificity, the ability of the test to correctly identify those without the disease. Conclusion: Emerging studies indicate the importance of POC antibody serological testing as an important diagnostic tool in the current SARS-CoV-2 pandemic. Considering the limitations of the molecular methods of testing, POC antibody tests can help reduce dependency on the molecular assays of testing when used in conjunction with them

Streptococcus anginosus lung infection and empyema: A case report and review of the literature

Streptococcus milleri group (SMG) also referred to as the Streptococcus anginosus group. These are Gram-positive, variable hemolysis, catalase negative, microaerophilic, non-motile facultative anaerobes which have been known to cause abscesses in humans. We report a case of empyema caused by Streptococcus anginosus in a patient with an unresolved pneumonia for over a month. In early October 2018, the patient presented to an emergency room with the complaints of shortness of air, productive cough, chills, subjective fever and weight loss for 4 weeks. A chest X-ray revealed a left lower lobe pneumonia. He was treated with 250 mg of azithromycin for 4 days. During a follow-up visit in November 2018, he reported having persistent symptoms. The chest CT revealed a localized pleural fluid collection at the left lower chest highly suggestive of empyema. He was prescribed 100mg of doxycycline for a month. However, he was admitted to the hospital a week later due to worsening symptoms. The microbiological cultures for sputum and blood were negative; however, pleural fluid cultures grew Streptococcus anginosus resistant to clindamycin and erythromycin. The patient was treated with broad spectrum antimicrobial regimen in conjunction with surgical management. Initially, the patient underwent CT guided placement of chest tube with instillation of Tissue Plasminogen Activator (TPA) for the drainage of pleural fluid followed Video-assisted Thoracoscopy with lateral decortication and drainage of empyema of the left lung due to persistence of complicated effusion. There was remarkable improvement in his symptoms, and he recovered subsequently. Our case highlights the infections caused by the Streptococcus milleri group (SMG) in individuals with an unresolved pneumonia. Such patients should be diagnosed accurately and treated aggressively with rapid and effective interventions

Potassium Profiling in Hemodialysis

Cardiac dysrhythmia and sudden death account for a large proportion of cardiac mortality in dialysis patients. Risk factors for sudden death that are specific to dialysis patients include fluid and electrolyte imbalances during hemodialysis, particularly those of potassium. The risk of arrhythmia may be related to changes in serum K+ concentration during dialysis, and thus close attention should be paid to the dialysate K+ concentration and the serum–dialysate concentration gradient. Potassium profiling is a technique where the dialysate K+ concentration is gradually reduced to keep the gradient between blood and dialysate at a non-fluctuating low level. We provide a review of studies that compare constant potassium concentration in dialysate to gradual reduction in dialysate potassium concentration. These studies illustrate that adequate and more gradual potassium removal can be achieved with potassium profiling techniques, while having lower cardiac irritability

Outcomes of Patients Hospitalized with Community-Acquired Pneumonia with Liver Disease or Cirrhosis.

Introduction: Liver disease and cirrhosis are common causes of mortality worldwide. Community-acquired pneumonia is recognized as a significant cause of morbidity and mortality in this population of adults. There is a lack of data regarding outcomes or prognosis in patients with liver dysfunction who develop CAP. The objective of this study was to evaluate the clinical characteristics, incidence, and outcomes of hospitalized patients with CAP and liver disease. Methods: This was a secondary analysis of the University of Louisville Pneumonia Study, which was a prospective population-based cohort study of adults hospitalized with community-acquired pneumonia. All patients were divided into three groups: 1) patients without liver disease, 2) patients with liver disease, and 3) patients with cirrhosis. Short and long-term outcomes were analyzed. Results: Among 9,201 patients, 8,566 patients did not have liver disease, 515 patients had liver disease, and 120 patients had cirrhosis. The median age of patients with liver disease or cirrhosis was approximately 10 years younger than the median age of overall population, and a higher proportion was admitted directly to the ICU. Compared to patients without liver disease, we found no significant difference in time to clinical stability for patients with liver diseases (adjusted hazard ratio [aHR] 1.01 [95% CI 0.92–1.12]; P=0.790) or cirrhosis (aHR 0.85 [95% CI 0.69–1.05]; P=0.127). There were also no differences in median length of stay (LOS) between any two groups. Patients with cirrhosis had a 35% higher risk of death at any time compared to patients with no liver disease (aHR 1.35 [95% CI 1.00–1.82]; P=0.049) but did not have significantly increased risk compared to patients with liver disease (aHR 1.37 [95% CI 0.97–1.93], P=0.070). Conclusion: In this study of hospitalized adults with CAP, patients with cirrhosis had a significantly higher risk of death compared to patients without liver disease

Detection of BRCA1, and BRCA2 Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting

Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious BRCA1 and/or 2 mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of BRCA mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting. Methods: Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect. Results: The presence or absence of mutations in the BRCA gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0–232) months. BRCA mutation was present in the patient’s original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% [95% CI, 95.3–99.1%]. The adjusted concordance between metastatic samples and cfDNA was 93.5% [95% CI, 86.4–97.3%]. Of the patients who had a BRCA mutation detected in their prostate tissue, there was a 70% probability of detecting a BRCA mutation in the patient’s cfDNA as well. For patients who did not have a detectable BRCA mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%. Conclusion: There is a high level of concordance between tissue and blood for BRCA mutations. Testing cfDNA can provide reliable information on BRCA mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new BRCA mutation later in the disease course is a rare event

Response and Outcomes of Maintenance Avelumab After Platinum-Based Chemotherapy (PBC) in Patients With Advanced Urothelial Carcinoma (aUC): "Real World" Experience

Background: Platinum-based chemotherapy (PBC) followed by avelumab switch maintenance in nonprogressors is standard first line (1L) treatment for advanced urothelial carcinoma (aUC). We describe clinical features and outcomes in a "real-world' cohort treated with avelumab maintenance for aUC. Materials and methods: This was a retrospective cohort study of patients (pts) who received 1L switch maintenance avelumab after no progression on PBC for aUC. We calculated progression-free survival (PFS) and overall survival (OS) from initiation of maintenance avelumab. We also described OS and PFS for specific subsets using Cox regression and observed response rate (ORR). Results: A total of 108 pts with aUC from 14 sites treated with maintenance avelumab were included. There was a median of 6 weeks1-30 from end of PBC to avelumab initiation; median follow-up time from avelumab initiation was 8.8 months (1-42.7). Median [m]PFS was 9.6 months (95%CI 7.5-12.1) and estimated 1-year OS was 72.5%. CR/PR (vs. SD) to 1L PBC (HR = 0.33, 95% CI 0.13-0.87) and ECOG PS 0 (vs. ≥1), (HR = 0.15, 95% CI 0.05-0.47) were associated with longer OS. The presence of liver metastases was associated with shorter PFS (HR = 2.32, 95% CI 1.17-4.59). ORR with avelumab maintenance was 28.7% (complete response 17.6%, partial response 11.1%), 29.6% stable disease, 26.9% progressive disease as best response (14.8% best response unknown). Conclusions: Results seem relatively consistent with findings from JAVELIN Bladder100 trial and recent "real world" studies. Prior response to platinum-based chemotherapy, ECOG PS 0, and absence of liver metastases were favorable prognostic factors. Limitations include the retrospective design, lack of randomization and central scan review, and possible selection/confounding biases

Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

BackgroundSites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI.MethodsWe identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line.ResultsWe identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant.ConclusionBone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses

Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma

BackgroundEarly progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.Patients and methodsWe performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors.ResultsWe included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months.ConclusionAmong patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy