Cutaneous squamous cell carcinoma and mortality in end-stage renal disease.

BACKGROUND: In the general population, cutaneous squamous cell carcinoma (cSCC) is associated with increased all-cause mortality. Transplant patients have been shown to have an increased risk of developing cSCC, and their cSCC is associated with an increased risk for mortality. In end-stage renal disease (ESRD) patients, there is extensive mortality and immune dysfunction. Because of this immune system dysfunction, we examined whether cSCC is associated with increased risk of all-cause mortality among ESRD patients, as well as the risk factors for cSCC. METHODS: We analyzed ESRD patients in the United States Renal Data System from 2004-2014, excluding organ transplant recipients. We assessed mortality using a Cox Proportional Hazards (CPH) model to control for various demographic and clinical parameters, identified using international classification of diseases (ICD)-9 codes. RESULTS: Of the 1,035,193 patients included, 624 (0.1%) were diagnosed with cSCC. The median survival time for those with cSCC was 3.91 years [95% confidence interval (CI) = 3.67-4.15], versus 2.92 years [95%CI = 2.92-2.93] for patients without cSCC. ESRD patients with cSCC were at lower risk of death [adjusted hazard ratio = 0.75; 95%CI = 0.69-0.82] compared to those without. Decreased risk of death was also associated with parameters such as black race, Hispanic ethnicity, tobacco dependence and actinic keratosis. Increased mortality risk was associated with increasing age, male sex, hemodialysis (versus peritoneal dialysis) and alcohol dependence. CONCLUSIONS: Contrary to expectations, ESRD patients with a cSCC diagnosis showed reduced all-cause mortality risk relative to those without. The reason for this discrepancy remains unclear, suggesting the need for further study.

Association of psoriasis with myocardial infarction in end-stage renal disease patients.

BACKGROUND: Previous research in non-dialysis patients suggests that the inflammatory skin disease psoriasis is associated with an increased risk of severe vascular events like myocardial infarction (MI). Thus, we determined whether psoriasis represents a significant risk factor for MI in end-stage renal disease (ESRD) patients. METHODS: We queried the United States Renal Data System for ESRD patients starting dialysis between 2004 and 2015. ICD-9 and ICD-10 codes were used to identify those with at least two diagnoses of psoriasis, a diagnosis of MI, and other clinical risk factors. Logistic regression was used to examine the association of psoriasis and various risk factors with MI. RESULTS: Of a cohort of 1,062,693, we identified 6823 (0.6%) subjects with psoriasis and 181,960 (17.1%) with MI. Of the 6823 patients with psoriasis, 1671 (24%) developed an MI. Psoriasis was associated with an increased risk of MI in an unadjusted model [odds ratio (OR) = 1.34; confidence interval (CI) = 1.26-1.42]. However, after controlling for demographics, dialysis modality, access type, and various conditions related to the Charlson Comorbidity Index, psoriasis was not associated with MI (OR = 0.95, CI = 0.89-1.01). Confounders of the association of psoriasis with MI included congestive heart failure (OR = 5.26, CI = 5.17-5.36), pulmonary disease (OR = 1.25, CI = 1.23-1.26), and diabetes with complications (OR = 1.82, CI = 1.79-1.85). CONCLUSIONS: Contrary to prior research in the general population, in the ESRD population psoriasis was not associated with an increased risk of MI after controlling for various demographic and clinical parameters. These data emphasize the importance of an integrated approach since comorbidities may influence the choice of therapy for psoriasis and outcomes.

Non-tuberculous mycobacterial infections in patients with end-stage renal disease: Prevalence, risk factors, and mortality.

Non-tuberculous mycobacterial (NTM) disease has increased in prevalence in the USA, however, little is known on NTM in the population with end-stage renal disease (ESRD). Thus, we investigated patients with ESRD to determine risk factors for NTM disease and mortality. We queried the United States Renal Data System from 2005 to 2015 using International Classification of Diseases (ICD)-9/ICD-10 codes to identify NTM and risk factors. Logistic regression was used to examine the association of risk factors with NTM and Cox proportional hazards modeling was used to assess the association of NTM with mortality. Of 1,068,634 included subjects, 3232 (0.3%) individuals were identified with any NTM diagnosis. Hemodialysis versus peritoneal dialysis (OR=0.10, 95% CI=0.08 to 0.13) was protective for NTM, whereas black (OR=1.27, 95% CI=1.18 to 1.37) or other race compared with white race (OR=1.39, 95% CI=1.21 to 1.59) increased the risk of NTM. HIV (OR=15.71, 95% CI=14.24 to 17.33), history of any transplant (OR=4.25, 95% CI=3.93 to 4.60), kidney transplant (OR=3.00, 95% CI=2.75 to 3.27), diabetes (OR=1.32, 95% CI=1.23 to 1.43), rheumatologic disease (OR=1.92, 95% CI=1.77 to 2.08), and liver disease (OR=2.09, 95% CI=1.91 to 2.30) were associated with increased risk for NTM diagnosis. In multivariable analysis, there was a significant increase in mortality with any NTM diagnosis (HR=1.83, 95% CI=1.76 to 1.91, p≤0.0001). Controlling for relevant demographic and clinical risk factors, there was an increased risk of mortality associated with any diagnosis of NTM. Early diagnosis and treatment of NTM infection may improve survival in patients with ESRD.

Identification of circulating microvesicle-encapsulated miR-223 as a potential novel biomarker for ARDS.

Acute respiratory distress syndrome (ARDS) is a lethal disease with severe forms conferring a mortality rate approaching 40%. The initial phase of ARDS results in acute lung injury (ALI) characterized by a severe inflammatory response and exudative alveolar flooding due to pulmonary capillary leak. Timely therapies to reduce ARDS mortality are limited by the lack of laboratory-guided diagnostic biomarkers for ARDS. The purpose of this study was to evaluate the prognostic role of circulating microvesicles (MVs)-containing miR-223 (MV-miR-223) if indicate more severe lung injury and worse outcomes in ARDS patients. Human plasma samples from one hundred ARDS patients enrolled in Albuterol to Treat Acute Lung Injury (ALTA) trial were compared to a control group of twenty normal human plasma specimens. The amount of MV-miR-223 was measured using absolute real-time polymerase chain reaction (PCR) with a standard curve. Mann-Whitney-Wilcoxon, Spearman correlation, Chi-squared tests, and Kaplan-Meier curves were computed to assess different variables and survival. Plasma levels of MV-miR-223 were significantly higher in ARDS patients compared to normal control subjects. Upon receiver operator characteristic (ROC) analysis of MV-miR-223 in relation to 30-day mortality, MV-miR-223 had an area under the curve (AUC) of 0.7021 with an optimal cut-off value of 2.413 pg/ml. Patients with high MV-miR-223 had higher 30-day mortality than subjects with low MV-miR-223 levels. MV-miR-223 was negatively correlated with ICU-free days, ventilator-free days, and organ failure-free days. Patients with high MV-miR-223 levels had higher 30 and 90-day mortality. MV-miR-223 was associated with 28-day clinical outcomes of ALTA trial including ICU-free days, ventilator-free days, and organ failure-free days. Thus, circulating MV-miR-223 may be a potential biomarker in prognosticating patient-centered outcomes and predicting mortality in ARDS.

Association of intermittent versus continuous hemodialysis modalities with mortality in the setting of acute stroke among patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) are 8-10 times more likely to suffer from a stroke compared with the general public. Despite this risk, there are minimal data elucidating which hemodialysis modality is best for patients with ESRD following a stroke, and guidelines for their management are lacking. We retrospectively queried the US Renal Data System administrative database for all-cause mortality in ESRD stroke patients who received either intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). Acute ischemic stroke and hemorrhagic stroke were identified using the International Classification of Diseases 9th Revision (ICD-9)/ICD-10 codes, and hemodialysis modality was determined using Healthcare Common Procedure Coding System (HCPCS) codes. Time to death from the first stroke diagnosis was the outcome of interest. Cox proportional hazards modeling was used, and associations were expressed as adjusted HRs. From the inclusion cohort of 87,910 patients, 92.9% of patients received IHD while 7.1% of patients received CRRT. After controlling for age, race, sex, ethnicity, and common stroke risk factors such as hypertension, diabetes, tobacco use, atrial fibrillation, and hyperlipidemia, those who were placed on CRRT within 7 days of a stroke had an increased risk of death compared with those placed on IHD (HR=1.28, 95% CI 1.25 to 1.32). It is possible that ESRD stroke patients who received CRRT are more critically ill. However, even when the cohort was limited to only those patients in the intensive care unit and additional risk factors for mortality were controlled for, CRRT was still associated with an increased risk of death (HR=1.32, 95% CI 1.27 to 1.37). Therefore, further prospective clinical trials are warranted to address these findings.

Psoriasis and pneumonia in the end-stage renal disease population.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease associated with an increased risk for acute infections. Because chronic kidney disease is a risk factor for pneumonia, end-stage renal disease (ESRD) patients with psoriasis may have an increased risk for acquiring pneumonia. MATERIAL AND METHODS: A retrospective cohort analysis was performed using the United States Renal Data System, a medical claims database of all ESRD patients undergoing dialysis in the US. Logistic regression analysis was used to investigate the association of psoriasis with pneumonia in ESRD patients. RESULTS: A total of 6841 (0.7%) ESRD patients were diagnosed with psoriasis; 385,976 (36%) ESRD patients had pneumonia. Although simple models showed that psoriasis was associated with an increased risk of pneumonia in the ESRD population (odds ratio (OR) = 1.14), the final multivariable model found that psoriasis was protective for pneumonia (OR = 0.56) when controlling for age, race, sex, ethnicity, dialysis modality, Charlson Comorbidity Index (CCI), multiple sclerosis, tobacco use and alcohol use. This is due to both the CCI and tobacco use being strong confounders of the association of psoriasis and pneumonia. Black, other race and Hispanic ethnicity were also protective for pneumonia, while increasing age and CCI, female sex, hemodialysis, multiple sclerosis and tobacco and alcohol use were associated with increased risk. CONCLUSIONS: When controlling for multiple factors, psoriasis does not increase the risk for pneumonia in ESRD patients. In this cohort, other factors, such as the CCI and tobacco use, were more strongly associated with increased risk for pneumonia than psoriasis.

Varicella Zoster Aseptic Meningitis Presenting as an Atypical Mucocutaneous Eruption Involving All Three Divisions of the Trigeminal Nerve.

Herpes zoster involving all three divisions of the trigeminal nerve is extremely rare and may pose a diagnostic challenge, especially in young and immunocompetent patients. We present a unique case of herpes zoster involving all three divisions of the trigeminal nerve and illustrate that this uncommon eruption can be a presenting sign of varicella zoster aseptic meningitis. This case emphasizes the importance of fundamental morphology recognition, particularly its ability to aid in clinical diagnosis and its potential to decrease patient morbidity and mortality by expediting the initiation of appropriate treatment.

Septic arthritis in the end-stage renal disease population.

Septic arthritis is important to consider in any patient who presents with joint pain because it is a medical emergency with an 11% fatality rate. Diagnosis and treatment may improve prognosis; however, many patients do not regain full joint function. In patients with end-stage renal disease (ESRD), immune dysfunction due to uremia and chronic vascular access leads to increased risk of infection. We examined the incidence, risk factors and sequelae of septic arthritis in a cohort of hemodialysis patients. The US Renal Data System was queried for diagnoses of septic arthritis and selected sequelae using International Statistical Classification of Diseases and Related Health Problems-9 and Current Procedural Terminology-4 codes in patients who initiated hemodialysis between 2005 and 2010. Multivariable logistic regression was used to determine potential risk factors for septic arthritis and its sequelae. 7009 cases of septic arthritis were identified, an incidence of 514.8 per 100,000 persons per year. Of these patients, 2179 were diagnosed with a documented organism within 30 days prior to or 14 days after the septic arthritis diagnosis, with methicillin-resistant Staphylococcus aureus infections (57.4%) being the most common. Significant risk factors for septic arthritis included history of joint disease, immune compromise (diabetes, HIV, cirrhosis), bacteremia and urinary tract infection. One of the four sequelae examined (joint replacement, amputation, osteomyelitis, Clostridioides difficile infection) occurred in 25% of septic arthritis cases. The high incidence of septic arthritis and the potential for serious sequelae in patients with ESRD suggest that physicians treating individuals with ESRD and joint pain/inflammation should maintain a high clinical suspicion for septic arthritis.

CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection.

Gram-negative (G-) bacteria are the leading cause of hospital-acquired pneumonia in the United States. The devastating damage caused by G- bacteria results from the imbalance of bactericidal effects and overwhelming inflammation. Despite decades of research, the underlying mechanisms by which runaway inflammation is developed remain incompletely understood. Clara Cell Protein 16 (CC16), also known as uteroglobin, is the major protein secreted by Clara cells and the most abundant protein in bronchoalveolar lavage fluid (BALF). However, the regulation and functions of CC16 during G- bacterial infection are unknown. In this study, we aimed to assess the regulation of CC16 in response to Klebsiella pneumoniae (K. pneu) and to investigate the role of CC16 in bronchial epithelial cells. After K. pneu infection, we found that CC16 mRNA expression was significantly decreased in bronchial epithelial cells. Our data also showed that K. pneu infection upregulated cytokine and chemokine genes, including IL-1ß, IL-6, and IL-8 in BEAS-2B cells. Endogenously overexpressed CC16 in BEAS-2B cells provided an anti-inflammatory effect by reducing these markers. We also observed that endogenous CC16 can repress NF-κB reporter activity. In contrast, the recombinant CC16 (rCC16) did not show an anti-inflammatory effect in K. pneu-infected cells or suppression of NF-κB promoter activity. Moreover, the overexpression of CC16 reduced reactive oxygen species (ROS) levels and protected BEAS-2B cells from K. pneu-induced apoptosis.

The Potential of Lung Epithelium Specific Proteins as Biomarkers for COVID-19-Associated Lung Injury.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was first reported in Wuhan, China, and was declared a pandemic by the World Health Organization (WHO) on 20 March 2020. The respiratory system is the major organ system affected by COVID-19. Numerous studies have found lung abnormalities in patients with COVID-19, including shortness of breath, respiratory failure, and acute respiratory distress syndrome. The identification of lung-specific biomarkers that are easily measurable in serum would be valuable for both clinicians and patients with such conditions. This review is focused on the pneumoproteins and their potential to serve as biomarkers for COVID-19-associated lung injury, including Krebs von den Lungen-6 (KL-6), surfactant proteins (SP-A, SP-B, SP-C, SP-D), and Clara cell secretory protein (CC16). The current findings indicate the aforementioned pneumoproteins may reflect the severity of pulmonary manifestations and could serve as potential biomarkers in COVID-19-related lung injury.

Campylobacter jejuni prosthetic joint infection in an ulcerative colitis patient in the absence of gastrointestinal symptoms.

73-year-old man with ulcerative colitis was diagnosed with Campylobacter jejuni prosthetic knee infection. No preceding gastrointestinal illness was reported. Joint aspirate and operative cultures were negative; however, blood cultures were positive for Campylobacter jejuni. The role of ulcerative colitis in inducing bacteremia and subsequent prosthetic joint infection is discussed.