Pregnancy health in a multi-state U.S. population of systemically underserved patients and their children: PROMISE cohort design and baseline characteristics.

BACKGROUND: Gestational weight gain (GWG) is a routinely monitored aspect of pregnancy health, yet critical gaps remain about optimal GWG in pregnant people from socially marginalized groups, or with pre-pregnancy body mass index (BMI) in the lower or upper extremes. The PROMISE study aims to determine overall and trimester-specific GWG associated with the lowest risk of adverse birth outcomes and detrimental infant and child growth in these underrepresented subgroups. This paper presents methods used to construct the PROMISE cohort using electronic health record data from a network of community-based healthcare organizations and characterize the cohort with respect to baseline characteristics, longitudinal data availability, and GWG. METHODS: We developed an algorithm to identify and date pregnancies based on outpatient clinical data for patients 15 years or older. The cohort included pregnancies delivered in 2005-2020 with gestational age between 20 weeks, 0 days and 42 weeks, 6 days; and with known height and adequate weight measures needed to examine GWG patterns. We linked offspring data from birth records and clinical records. We defined study variables with attention to timing relative to pregnancy and clinical data collection processes. Descriptive analyses characterize the sociodemographic, baseline, and longitudinal data characteristics of the cohort, overall and within BMI categories. RESULTS: The cohort includes 77,599 pregnancies: 53% had incomes below the federal poverty level, 82% had public insurance, and the largest race and ethnicity groups were Hispanic (56%), non-Hispanic White (23%) and non-Hispanic Black (12%). Pre-pregnancy BMI groups included 2% underweight, 34% normal weight, 31% overweight, and 19%, 8%, and 5% Class I, II, and III obesity. Longitudinal data enable the calculation of trimester-specific GWG; e.g., a median of 2, 4, and 6 valid weight measures were available in the first, second, and third trimesters, respectively. Weekly rate of GWG was 0.00, 0.46, and 0.51 kg per week in the first, second, and third trimesters; differences in GWG between BMI groups were greatest in the second trimester. CONCLUSIONS: The PROMISE cohort enables characterization of GWG patterns and estimation of effects on child growth in underrepresented subgroups, ultimately improving the representativeness of GWG evidence and corresponding guidelines.

Offline memory replay in recurrent neuronal networks emerges from constraints on online dynamics.

During spatial exploration, neural circuits in the hippocampus store memories of sequences of sensory events encountered in the environment. When sensory information is absent during 'offline' resting periods, brief neuronal population bursts can 'replay' sequences of activity that resemble bouts of sensory experience. These sequences can occur in either forward or reverse order, and can even include spatial trajectories that have not been experienced, but are consistent with the topology of the environment. The neural circuit mechanisms underlying this variable and flexible sequence generation are unknown. Here we demonstrate in a recurrent spiking network model of hippocampal area CA3 that experimental constraints on network dynamics such as population sparsity, stimulus selectivity, rhythmicity and spike rate adaptation, as well as associative synaptic connectivity, enable additional emergent properties, including variable offline memory replay. In an online stimulus-driven state, we observed the emergence of neuronal sequences that swept from representations of past to future stimuli on the timescale of the theta rhythm. In an offline state driven only by noise, the network generated both forward and reverse neuronal sequences, and recapitulated the experimental observation that offline memory replay events tend to include salient locations like the site of a reward. These results demonstrate that biological constraints on the dynamics of recurrent neural circuits are sufficient to enable memories of sensory events stored in the strengths of synaptic connections to be flexibly read out during rest and sleep, which is thought to be important for memory consolidation and planning of future behaviour. KEY POINTS: A recurrent spiking network model of hippocampal area CA3 was optimized to recapitulate experimentally observed network dynamics during simulated spatial exploration. During simulated offline rest, the network exhibited the emergent property of generating flexible forward, reverse and mixed direction memory replay events. Network perturbations and analysis of model diversity and degeneracy identified associative synaptic connectivity and key features of network dynamics as important for offline sequence generation. Network simulations demonstrate that population over-representation of salient positions like the site of reward results in biased memory replay.

Atopic Dermatitis and the Risk of Infection in End-Stage Renal Disease.

Background and Objectives: Atopic dermatitis (AD), also known as eczema, is a common chronic inflammatory skin condition affecting 16.5 million adults in the United States. AD is characterized by an impaired epidermal barrier that can predispose individuals to infection. End-stage renal disease (ESRD) is also commonly complicated by infections due to chronic vascular access and immune-system dysfunction, possibly related to uremia. Multiple studies have reported that renal disease is a common comorbidity in adults with atopic dermatitis. The aim of this study was to determine whether AD is a risk factor for certain infections in patients with ESRD. Materials and Methods: Using the United States Renal Data System, a retrospective cohort analysis was conducted on adult ESRD patients initiating dialysis between 2004 and 2019 to investigate associations between infections and AD in this population. Results: Of 1,526,266 patients, 2290 were identified with AD (0.2%). Infectious outcomes of interest were bacteremia, septicemia, cellulitis, herpes zoster, and conjunctivitis. In all infectious outcomes except for conjunctivitis, patients with the infectious outcomes were more likely to carry a diagnosis of AD. After controlling for demographic and clinical covariates, AD was associated with an increased risk of cellulitis (adjusted relative risk (aRR) = 1.39, 95% confidence interval (CI) = 1.31-1.47) and herpes zoster (aRR = 1.67, CI = 1.44-1.94), but not with bacteremia (aRR = 0.96, CI = 0.89-1.05), septicemia (aRR = 1.02, CI = 0.98-1.08), or conjunctivitis (aRR = 0.97, CI = 0.740-1.34). Conclusions: Overall, after controlling for demographic and clinical covariates and adjusting for person-years-at-risk, AD was associated with an increased risk for some, but not all, infections within the population of patients with ESRD.

Modes of failure of hip hemiarthroplasty for femoral neck fracture.

BACKGROUND: Hemiarthroplasty is a common treatment for displaced femoral neck fractures, but limited Canadian data are available about hemiarthroplasty failure. We evaluated the frequency and predictors of hemiarthroplasty failure in Manitoba. METHODS: In this retrospective multicentre province-wide study, billing and joint registry databases showed 4693 patients who had hemiarthroplasty for treatment of femoral neck fracture in Manitoba over an 11-year period (2005-2015), including 155 hips with subsequent reoperations (open or closed) for treatment of hemiarthroplasty failure. Hospital records were reviewed to identify modes of hemiarthroplasty failure, comorbidities and reoperations. Data were analyzed using χ2 test and Poisson and γ regression models. RESULTS: During our study period, 155 hips (154 patients [3%]) underwent 230 reoperations. Of these, 131 hips (85%) initially had an uncemented unipolar modular implant. Indications for first-time reoperation included periprosthetic femur fracture (49 hips [32%]), dislocation (45 hips [29%]), acetabular wear (28 hips [18%]) and infection (26 hips [17%]). There were 46 hips (30%) that had 2 or more reoperations. Reoperation for dislocation was associated with presence of dementia; acetabular wear was associated with absence of dementia. Time from hemiarthroplasty to reoperation was associated inversely with age at hemiarthroplasty, dislocation and dementia and was directly associated with acetabular wear. The risk of having 2 or more reoperations was associated independently with dislocation, infection, and alcohol abuse. CONCLUSION: Hemiarthroplasty for femoral neck fracture in Manitoba had a low frequency of failure. Risk factors for multiple reoperations included dislocation, infection and alcohol abuse.

Spectrochemical Probing of MicroRNA Duplex Using Spontaneous Raman Spectroscopy for Biosensing Applications.

MicroRNAs are emerging as both diagnostic and therapeutic targets in different human pathologies. An accurate understanding of the structural dependency of microRNAs for their biological functions is essential for designing synthetic oligos with various base and linkage modifications that can transform into highly sensitive diagnostic devices and therapeutic molecules. In this proof-of-principle study, we have utilized label-free spontaneous Raman spectroscopy to understand the structural differences in sense and antisense microRNA-21 by hybridizing them with complementary RNA and DNA oligos. Overall, the results suggest that the changes in the Raman band at 785 cm-1 originating from the phosphodiester bond of the nucleic acid backbone, linking 5' phosphate of the nucleic acid with 3' OH of the other nucleotide, can serve as a marker to identify these structural variations. Our results support the application of Raman spectroscopy in discerning intramolecular (ssRNA and ssDNA) and intermolecular (RNA-RNA, RNA-DNA, and DNA-DNA hybrids) interactions of nucleic acids. This is potentially useful for developing biosensors to quantify microRNAs in clinical samples and to design therapeutic microRNAs with robust functionality.

Cognitive-communication and psychosocial functioning 12 months after severe traumatic brain injury.

OBJECTIVE: Cognitive-communication deficits after severe Traumatic Brain Injury (TBI) may contribute to poor psychosocial functioning, however, the possible nature of this relationship remains unclear and warrants investigation. The current study explored the variance and correlations of a measure of cognitive-communication with a measure of psychosocial outcome in adults 12 months following TBI. METHOD: 36 adults with severe TBI evaluated at 12 months post-injury. Cognitive-communication skills were evaluated with the Functional Assessment of Verbal Reasoning and Executive Strategies (FAVRES), Sydney Psychosocial Reintegration Scale-2 (SPRS-2) Form A - Informant version assessed psychosocial functioning. Multiple regression analyses were used to investigate association between cognitive-communication and psychosocial outcomes. RESULTS: Two measures of cognitive-communication assessment (Accuracy and Rationale of the FAVRES) contributed significantly to total psychosocial outcome (SPRS-2). Multiple regression analyses revealed these variables accounted for 29.1% of the variance. Cognitive-communication variables accounted for 24.0% and 28.6% of the Work/Leisure and Relationship domains of the SPRS-2. CONCLUSION: Cognitive-communication ability was significantly related to psychosocial functioning at 12 months post-TBI. Findings suggested continued speech pathology involvement in the post-acute stages of recovery may improve social, vocational and overall psychosocial functioning. The FAVRES is a promising cognitive-communication assessment for identification of treatable factors impacting psychosocial outcomes.

The Assessment of Infection Risk in Patients with Vitiligo Undergoing Dialysis for End-Stage Renal Disease: A Retrospective Cohort Study.

Vitiligo is an autoimmune condition that causes patchy skin depigmentation. Although the mechanism by which vitiligo induces immunocompromise is unclear, other related autoimmune diseases are known to predispose those affected to infection. Individuals with vitiligo exhibit epidermal barrier disruption, which could potentially increase their susceptibility to systemic infections; patients with renal disease also show a predisposition to infection. Nevertheless, there is little research addressing the risk of infection in dialysis patients with vitiligo in comparison to those without it. A retrospective analysis was performed on patients with end-stage renal disease (ESRD) in the United States Renal Data System who started dialysis between 2004 and 2019 to determine if ESRD patients with vitiligo are at an increased risk of bacteremia, cellulitis, conjunctivitis, herpes zoster, or septicemia. Multivariable logistic regression modeling indicated that female sex, black compared to white race, Hispanic ethnicity, hepatitis C infection, and tobacco use were associated with an enhanced risk of vitiligo, whereas increasing age and catheter, versus arteriovenous fistula, and access type were associated with a decreased risk. After controlling for demographics and clinical covariates, vitiligo was found to be significantly associated with an increased risk of bacteremia, cellulitis, and herpes zoster but not with conjunctivitis and septicemia.

Deep neck space infections in end-stage renal disease patients: Prevalence and mortality.

Deep neck space infections (DNSI) are severe infections within the layers of neck fascia that are known to be associated with underlying immunocompromised states. Although uremia associated with kidney disease is known to cause immune system dysfunction, DNSI in patients with kidney disease has been poorly studied. This study investigated the prevalence of DNSI and the associated risk of mortality within the United States end-stage renal disease (ESRD) population, using a retrospective cohort study design and the United States Renal Data System database of patients (ages 18-100) who initiated dialysis therapy between 2005 and 2019. International Classification of Disease-9 and -10 codes were used to identify the diagnosis of DNSI and comorbid conditions. Of the 705,891 included patients, 2.2% had a diagnosis of DNSI. Variables associated with increased risk of DNSI were female sex, black compared to white race, catheter, or graft compared to arteriovenous fistula (AVF) access, autoimmune disease, chronic tonsillitis, diagnoses in the Charlson Comorbidity Index (CCI), tobacco use, and alcohol dependence. DNSI diagnosis was an independent risk factor for mortality, which was also associated with other comorbidity factors such as older age, catheter or graft compared to AVF access, comorbidities in the CCI, tobacco use, and alcohol dependence. Because of the increased mortality risk of DSNI in the ESRD population, health professionals should encourage good oral hygiene practices and smoking cessation, and they should closely monitor these patients to reduce poor outcomes.

Trimester-specific rate of gestational weight loss or gain and birth size: differences by prepregnancy BMI.

OBJECTIVE: The objective of this study was to estimate the effects of trimester-specific gestational weight gain (GWG) on small and large (compared with appropriate) for gestational age (i.e., SGA, LGA, and AGA) by prepregnancy BMI classifications. METHODS: We conducted a cohort study of pregnancies in a national network of community health care organizations, stratifying by prepregnancy BMI (n = 20,676 with normal weight; 19,156 with overweight; 11,647 with obesity class I; 5124 with obesity class II; and 3197 with obesity class III). SGA and LGA (vs. AGA) were modeled as a function of trimester 1, 2, or 3 GWG rate, previous trimester(s) GWG rate, and maternal characteristics using modified Poisson regression. RESULTS: GWG rates ranged from weight loss to substantial gains. GWG-LGA associations were strongest in trimester 1 (risk ratio [RR] range for 10th vs. 50th percentile GWG, across BMI categories: 0.60-0.73). GWG-SGA associations were strongest in lower BMI categories and in trimester 2; RRs were 1.62, 1.40, and 1.17 for prepregnancy normal weight, obesity class I, and obesity class III, respectively, with curvilinear associations for class II and III. CONCLUSIONS: Among people with prepregnancy obesity class II or III, GWG rate is associated with higher LGA risk in a dose-dependent manner, including understudied ranges of weight loss, but with weak associations with SGA.

Spatial-dependent suppressive aftereffect produced by a sound in the rat's inferior colliculus is partially dependent on local inhibition.

In a natural acoustic environment, a preceding sound can suppress the perception of a succeeding sound which can lead to auditory phenomena such as forward masking and the precedence effect. The degree of suppression is dependent on the relationship between the sounds in sound quality, timing, and location. Correlates of such phenomena exist in sound-elicited activities of neurons in hearing-related brain structures. The present study recorded responses to pairs of leading-trailing sounds from ensembles of neurons in the rat's inferior colliculus. Results indicated that a leading sound produced a suppressive aftereffect on the response to a trailing sound when the two sounds were colocalized at the ear contralateral to the site of recording (i.e., the ear that drives excitatory inputs to the inferior colliculus). The degree of suppression was reduced when the time gap between the two sounds was increased or when the leading sound was relocated to an azimuth at or close to the ipsilateral ear. Local blockage of the type-A γ-aminobutyric acid receptor partially reduced the suppressive aftereffect when a leading sound was at the contralateral ear but not at the ipsilateral ear. Local blockage of the glycine receptor partially reduced the suppressive aftereffect regardless of the location of the leading sound. Results suggest that a sound-elicited suppressive aftereffect in the inferior colliculus is partly dependent on local interaction between excitatory and inhibitory inputs which likely involves those from brainstem structures such as the superior paraolivary nucleus. These results are important for understanding neural mechanisms underlying hearing in a multiple-sound environment.

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.

Risk factors and mortality in patients with listeriosis and end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) is a known immunocompromising status that predisposes patients to developing infections. Disease from Listeria monocytogenes may affect any host but tends to be more severe in the immunocompromised. METHODS: We used a large population of patients with ESRD to identify risk factors for listeriosis and mortality. Patients with a diagnosis of Listeria and other risk factors for listeriosis were identified using claims data from the United States Renal Data System database from 2004-2015. Demographic parameters and risk factors associated with Listeria were modeled using logistic regression while association with mortality was assessed with Cox Proportional Hazards modeling. RESULTS: A diagnosis of Listeria was identified in 291 (0.01%) of a total 1,071,712 patients with ESRD. Cardiovascular disease, connective tissue disease, upper gastrointestinal ulcerative disease, liver disease, diabetes, cancer, and human immunodeficiency virus were all associated with an increased risk of Listeria. Patients with Listeria had an increased risk of death relative to patients without Listeria (adjusted hazard ratio=1.79; 95% confidence interval 1.52-2.10). CONCLUSIONS: Incidence of listeriosis in our study population was over 7 times higher than what has been reported for the general population. The independent association of a Listeria diagnosis with increased mortality is also consistent with the disease's high mortality in the general population. Due to limitations with diagnosis, providers should maintain high clinical suspicion for listeriosis when patients with ESRD present with a compatible clinical syndrome. Further prospective study may help precisely quantify the increased risk of listeriosis in patients with ESRD.

Association of psoriasis and stroke in end-stage renal disease patients.

BACKGROUND: Previous research in the general population suggests that the inflammatory skin disease psoriasis is associated with an increased risk of vascular events, such as stroke. Thus, psoriasis may also represent a risk factor for stroke in end-stage renal disease (ESRD) patients. METHODS: We queried the United States Renal Data System for incident dialysis patients between 2004 and 2015. Psoriasis was defined as having at least two international classification of disease (ICD)-9 or ICD-10 diagnosis codes. ICD codes were also used to query the outcome of interest, stroke, as well as other clinical risk factors. Logistic regression was used to examine the association of psoriasis and other risk factors with stroke. RESULTS: Of 966,399 ESRD patients, we identified 89,700 (9.3%) subjects with stroke and 6,286 (0.7%) with psoriasis. Of these psoriasis patients, 796 (0.9%) also had a stroke. Psoriasis was associated with an increased risk of stroke in an unadjusted model [odds ratio (OR)=1.16; 95% confidence interval (CI)=1.08-1.25]. However, after controlling for demographic and clinical risk factors, the final adjusted model showed that psoriasis was not associated with stroke (OR=0.96, CI=0.88-1.04). Congestive heart failure [adjusted OR of 1.79 (CI=1.75-1.83)] was a confounder of the association of psoriasis with stroke. CONCLUSIONS: Contrary to prior research in the general population, psoriasis in ESRD patients was not associated with the risk of stroke after controlling for various demographic and clinical parameters. Our finding emphasizes the importance of controlling for a variety of factors in population studies examining associations of diseases and risk factors.

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.

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.

Sex-Dependent Hepatoprotective Role of IL-22 Receptor Signaling in Non-Alcoholic Fatty Liver Disease-Related Fibrosis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex differences in NAFLD pathogenesis have been reported, the mechanisms underlying such differences remain understudied. Interleukin (IL)22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL22 was shown to be hepatoprotective in NAFLD-related liver injury. However, these studies relied primarily on exogenous administration of IL22 and did not examine the sex-dependent effect of IL22. Here, we sought to characterize the role of endogenous IL22-receptor signaling during NAFLD-induced liver injury in males and females. METHODS: We used immunofluorescence, flow cytometry, histopathologic assessment, and gene expression analysis to examine IL22 production and characterize the intrahepatic immune landscape in human subjects with NAFLD (n = 20; 11 men and 9 women) and in an in vivo Western high-fat diet-induced NAFLD model in IL22RA knock out mice and their wild-type littermates. RESULTS: Examination of publicly available data sets from 2 cohorts with NAFLD showed increased hepatic IL22 gene expression in females compared with males. Furthermore, our immunofluorescence analysis of liver sections from NAFLD subjects (n = 20) showed increased infiltration of IL22-producing cells in females. Similarly, IL22-producing cells were increased in wild-type female mice with NAFLD and the hepatic IL22/IL22 binding protein messenger RNA ratio correlated with expression of anti-apoptosis genes. The lack of endogenous IL22-receptor signaling (IL22RA knockout) led to exacerbated liver damage, inflammation, apoptosis, and liver fibrosis in female, but not male, mice with NAFLD. CONCLUSIONS: Our data suggest a sex-dependent hepatoprotective antiapoptotic effect of IL22-receptor signaling during NAFLD-related liver injury in females.

A Care Step Pathway for the Diagnosis and Treatment of COVID-19-Associated Invasive Fungal Infections in the Intensive Care Unit.

BACKGROUND: In March 2020, the World Health Organization declared COVID-19, caused by the SARS-CoV-2 virus, a pandemic. Patients with severe cases resulting in hospitalization and mechanical ventilation are at risk for COVID-19-associated pulmonary aspergillosis, an invasive fungal infection, and should be screened for aspergillosis if they have persistent hemodynamic instability and fever. Early detection and treatment of this fungal infection can significantly reduce morbidity and mortality in this population. OBJECTIVE: To develop an evidence-based care step pathway tool to help intensive care unit clinicians assess, diagnose, and treat COVID-19-associated pulmonary aspergillosis. METHODS: A panel of 18 infectious disease experts, advanced practice registered nurses, pharmacists, and clinical researchers convened in a series of meetings to develop the Care Step Pathway tool, which was modeled on a tool developed by advanced practice nurses to evaluate and manage side effects of therapies for melanoma. The Care Step Pathway tool addresses various aspects of disease management, including assessment, screening, diagnosis, antifungal treatment, pharmacological considerations, and exclusion of other invasive fungal coinfections. RESULTS: The Care Step Pathway tool was applied in the care of a patient with COVID-19-associated aspergillosis. The patient was successfully treated. CONCLUSION: The Care Step Pathway is an effective educational tool to help intensive care unit clinicians consider fungal infection when caring for COVID-19 patients receiving mechanical ventilation in the intensive care unit, especially when the clinical course is deteriorating and antibiotics are ineffective.

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.