Progressive multifocal leukoencephalopathy in patients with chronic kidney disease.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system infection caused by the human polyomavirus 2, leading to demyelination from oligodendrocyte death and rapid neurologic decline. Most commonly, PML affects patients in immunocompromised states. However, rare reports of PML in an immunocompetent host exist. Here, we report two cases of PML in older individuals with chronic kidney disease (CKD). CKD can ultimately lead to immune system dysfunction and place patients in a relatively immunosuppressed state. Testing for JC virus should remain a consideration for rapid, unexplained neurologic decline even without known immunocompromised status in the appropriate clinical setting.

Is the emergency department used as a substitute or a complement to primary care in Medicaid?

Policies to decrease low-acuity emergency department (ED) use have traditionally assumed that EDs are a substitute for unavailable primary care (PC). However, such policies can exacerbate ED overcrowding, rather than ameliorate it, if patients use EDs to complement, rather than substitute, their PC use. We tested whether Medicaid managed care enrolees visit the ED for nonemergent and PC treatable conditions to substitute for or to complement PC. Based on consumer choice theory, we modelled county-level monthly ED visit rate as a function of PC supply and used 2012-2015 New York Statewide Planning and Research Cooperative System (SPARCS) outpatient data and non-linear least squares method to test substitution vs complementarity. In the post-Medicaid expansion period (2014-2015), ED and PC are substitutes state-wide, but are complements in highly urban and poorer counties during nights and weekends. There is no evidence of complementarity before the expansion (2012-2013). Analyses by PC provider demonstrate that the relationship between ED and PC differs depending on whether PC is provided by physicians or advanced practice providers. Policies to reduce low-acuity ED use via improved PC access in Medicaid are likely to be most effective if they focus on increasing actual appointment availability, ideally by physicians, in areas with low PC provider supply. Different aspects of PC access may be differently related to low-acuity ED use.

Stress Corrosion Cracking of 316L Stainless Steel Additively Manufactured with Sinter-Based Material Extrusion.

This study investigates the stress corrosion cracking (SCC) behavior of type 316L stainless steel (SS316L) produced with sinter-based material extrusion additive manufacturing (AM). Sinter-based material extrusion AM produces SS316L with microstructures and mechanical properties comparable to its wrought counterpart in the annealed condition. However, despite extensive research on SCC of SS316L, little is known about the SCC of sinter-based AM SS316L. This study focuses on the influence of sintered microstructures on SCC initiation and crack-branching susceptibility. Custom-made C-rings were exposed to different stress levels in acidic chloride solutions at various temperatures. Solution-annealed (SA) and cold-drawn (CD) wrought SS316L were also tested to understand the SCC behavior of SS316L better. Results showed that sinter-based AM SS316L was more susceptible to SCC initiation than SA wrought SS316L but more resistant than CD wrought SS316L, as determined by the crack initiation time. Sinter-based AM SS316L showed a noticeably lower tendency for crack-branching than both wrought SS316L counterparts. The investigation was supported by comprehensive pre- and post-test microanalysis using light optical microscopy, scanning electron microscopy, electron backscatter diffraction, and micro-computed tomography.

Impact of Coffee Consumption on Cardiovascular Health.

Background: Coffee is a widely available beverage that is enjoyed by individuals of many cultures. The publication of new studies prompts a review of the clinical updates regarding the association between coffee consumption and cardiovascular disease. Methods: We present a narrative review of the literature related to coffee consumption and cardiovascular disease. Results: Recent (2000-2021) studies have shown that regular coffee consumption is associated with a decreased risk of developing hypertension, heart failure, and atrial fibrillation. However, results are inconsistent with regard to coffee consumption and risk of developing coronary heart disease. Most studies show a J-shaped association, wherein moderate coffee consumption resulted in decreased risk of coronary heart disease and heavy coffee consumption resulted in increased risk. In addition, boiled or unfiltered coffee is more atherogenic than filtered coffee because of its rich diterpene content that inhibits bile acid synthesis and ultimately affects lipid metabolism. On the other hand, filtered coffee, which is essentially devoid of the aforementioned compounds, exerts antiatherogenic properties by increasing high-density lipoprotein-mediated cholesterol efflux from macrophages through the influence of plasma phenolic acid. As such, cholesterol levels are principally influenced by the manner of coffee preparation (boiled vs filtered). Conclusion: Our findings suggest that moderate coffee consumption leads to a decrease in all-cause and cardiovascular-related mortality, hypertension, cholesterol, heart failure, and atrial fibrillation. However, no conclusive relationship between coffee and coronary heart disease risk has been consistently identified.

The associations between exercise and lipid biomarkers.

Cardiovascular diseases (CVD) remain the leading cause of death globally, and further efforts are being undertaken to understand and modify CVD risk factors, such as dyslipidemia (DLD), hypertension, and diabetes. The sedentary lifestyle of most individuals today contributes to the prevalence of these conditions. Uncontrolled dyslipidemia serves as a fertile ground for atherosclerotic plaque formation, while lipoproteins (Lp) act as cofactors for inflammatory processes that cause plaque destabilization leading to subsequent CVD events. As such, many health experts and institutions continue to emphasize the importance of cardiorespiratory fitness (CRF) and muscular strength (MusS) with the intent to reduce atherogenic lipoproteins and proprotein convertase subtilisin kexin type 9 (PCSK-9) expression. Concordantly, the two modes of exercise training (ET), such as aerobic ET (aET) and resistance ET (rET) have both demonstrated to improve CRF and MusS, respectively. Although both modes of ET were shown to independently reduce mortality, participation in both forms resulted in a more pronounced improvement in cholesterol levels and CVD-related mortality. Though reduction of adiposity is not a pre-requisite to achieve better control of DLD through increased CRF and MusS, the beneficial effects of physical activity on the inflammatory processes linked to atherosclerosis are almost always associated with a simultaneous decrease in overall adiposity. It is therefore essential to promote both aET and rET, including weight loss in order to attenuate the risks stemming from atherosclerosis and its proinflammatory components.

Clinical associations between exercise and lipoproteins.

PURPOSE OF REVIEW: One of the major concerns in global health is the deteriorating control of dyslipidemia (DLD), which is a very strong modifiable risk factor for untoward cardiovascular disease (CVD) outcomes. It serves as a foundation for atherosclerotic lesions that can be destabilized by co-inflammatory processes leading to distal clot migration and other related CVD events. There are many misconceptions regarding the management of DLD. Many health sectors advocate for weight loss without a clear-cut target to achieve better CVD outcomes. There is growing evidence that exercise training compliance regardless of weight change is a more reliable indicator of favorable outcomes. This review is intended to understand the relationship between exercise training, lipoprotein readings, and with CVD and all-cause morbidity and mortality. RECENT FINDINGS: Aerobic exercise training (aET) and resistance exercise training (rET) increase cardiorespiratory fitness (CRF) and muscular strength (MusS), respectively. Regardless of weight loss, aET and rET are both known to independently reduce mortality possibly partly through improvement of lipid profiles. Of the two modes of exercise, rET has propensity for enhanced compliance because of its significant lipid and mortality-attenuating effect even with just brief exercise sessions. However, there are several studies showing that participation in both modes of exercise causes more pronounced improvements in DLD and CVD-related mortality compared with either mode of exercise training alone. In addition, Lipoprotein-a [Lp(a)] has been increasingly acknowledged to be atherogenic because of its LDL core. The close proximity of Lp(a) with macrophages triggers the development of atheromas, plaque formation, and growth. This causes a cascade of inflammatory processes that increase the development of ischemic CVD and calcific aortic valve stenosis. Although exercise training is known to reduce plasma LDL-C levels, it has no direct effect on Lp(a) levels as the latter lipoprotein is not influenced by motion nor exercise. Reviews of multiple studies lead us to infer that exercise training may potentially have an indirect impact on Lp(a) attenuation because of the ability of exercise training to inhibit Proprotein Convertase Subtisilin/Kexin type-9 (PCSK-9), as some studies using pharmacologic therapy with PCSK-9 inhibitors were able to show a concomitant decrease in Lp(a) levels. SUMMARY: It is clear that normal-to-overweight populations who are highly active have better CVD outcomes and lipid profiles than their sedentary counterparts, and those who were underweight and unfit fared much worse. This allows us to take a more precise approach in the management of DLD rather than plainly focusing on gross weight in patients. Exercise training certainly has beneficial impact on longevity owing to its advantageous effect on lipoprotein levels and particle size. As such, reputable health societies, such as the ESC, ACC, and AHA have prescribed the ideal exercise training regimen, which have noticeable similarities. Increasing the use of wearable devices may help improve our ability to prescribe, quantify, and precisely track physical activity in our continuing efforts to combat increasing morbidity related to unhealthy lifestyles and inactivity.

Coroner county systems are associated with a higher likelihood of unclassified drug overdoses compared to medical examiner county systems.

Background: There is a striking geographic variation in drug overdose deaths without a specific drug recorded, many of which likely involve opioids. Knowledge of the reasons underlying this variation is limited.Objectives: We sought to understand the role of medicolegal death investigation (MDI) systems in unclassified drug overdose mortality.Methods: This is an observational study of 2014 and 2018 fatal drug overdoses and U.S. county-level MDI system type (coroner vs medical examiner). Mortality data are from the CDC's National Center for Health Statistics. We estimated multivariable logistic regressions to quantify associations between MDI system type and several outcome variables: whether the drug overdose was unclassified and whether involvement of any opioid, synthetic opioid, methadone, and heroin was recorded (vs unclassified), for 2014 (N = 46,996) and 2018 (N = 67,359).Results: In 2018, drug overdose deaths occurring in coroner counties were almost four times more likely to be unclassified (OR 3.87, 95% CI 2.32, 6.46) compared to medical examiner counties. These odds ratios are twice as large as in 2014 (difference statistically significant, P < .001), indicating that medical examiner counties are improving identification of opioids in drug overdoses faster than coroner counties.Conclusions: Accurate reporting of drug overdose deaths depends on MDI systems. When developing state policies and local interventions aimed to decrease opioid overdose mortality, decision-makers should understand the role their MDI system is playing in underestimating the extent of the opioid overdose crisis. Improvements to state and county MDI systems are desirable if accurate reporting and appropriate policy response are to be achieved.

The family physician's role in long COVID management.

A paucity of both data and therapeutics presents obstacles to care and makes your role in symptom management, psychological support, and referral-all described here-essential.

The Effects of Exercise on Lipid Biomarkers.

The World Health Organization has declared obesity to be a global epidemic that increases cardiovascular disease (CVD) mortality risk factors, such as hypertension, diabetes, dyslipidemia, and atherosclerosis. The increasing ratio of time spent in sedentary activities to that spent performing physically demanding tasks increases the trends to obesity and susceptibility to these risk factors. Dyslipidemia is the foundation of atherosclerotic buildup and lipoproteins serve as cofactors to the inflammatory processes that destabilize plaques. Increasing cardiorespiratory fitness and muscular strength helps attenuate concentrations of low-density lipoproteins (LDLs), such as LDL cholesterol, and increase levels of high-density lipoprotein cholesterol, as well as reduce proprotein convertase subtilisin kexin type 9 expression. Effects of physical activity on the inflammatory pathways of atherosclerosis, specifically C-reactive protein, are more closely related to reducing the levels of adiposity in tandem with increasing fitness, than with exercise training alone. The purpose of this review is to describe the physiology of dyslipidemia and relate it to CVD and exercise therapies.

Tailoring the management of hypertension to comorbidities.

PURPOSE OF REVIEW: In this article, we review the most current evidence for initiation and maintenance of various antihypertension (HTN) drug classes, including other misconceptions with respect to common comorbidities in patients with HTN. RECENT FINDINGS: Although the currently available anti-HTN agents have broad applicability in treating HTN, additional agents, such as angiotensin receptor-neprilysin inhibitors and novel nonsteroidal mineralocorticoid antagonists, have recently gained clinical significance. In addition, there have been some anecdotal concerns regarding the adverse effects, indications, and risks of COVID-19 infection/mortality when using certain anti-HTN agents. SUMMARY: Current guidelines currently address the treatment of primary HTN. However, isolated HTN is uncommon and often involves comorbid diseases that require specific regimentation. Several experimental medications are currently in late-stage trials showing potential superiority over current drugs that are available in the market.

Novel Treatment-Refractory Preschool Wheeze Phenotypes Identified by Cluster Analysis of Lung Lavage Constituents.

BACKGROUND: Preschool children with treatment-refractory wheeze often require unscheduled acute care. Current guidelines advise treatment of persistent wheeze with inhaled corticosteroids. Alternative treatments targeting structural abnormalities and specific inflammatory patterns could be more effective. OBJECTIVE: To apply unsupervised analysis of lung lavage (bronchoalveolar lavage [BAL]) variables to identify clusters of preschool children with treatment-refractory wheeze. METHODS: A total of 155 children 6 years or younger underwent bronchoscopy with BAL for evaluation of airway structure, inflammatory markers, and pathogens. Variables were screened with factor analysis and sorted into clusters by Ward's method, and membership was confirmed by discriminant analysis. RESULTS: The model was repeatable in a 48-case validation sample and accurately classified 86% of cases. Cluster 1 (n = 60) had early-onset wheeze, 85% with structural abnormalities, mostly tracheamalacia, with low total IgE and agranulocytic BAL. Cluster 2 (n = 42) had later-onset wheeze, the highest prevalence of gastroesophageal reflux, little atopy, and two-third had increased BAL lipid-laden macrophages. Cluster 3 (n = 46) had mid-onset wheeze, low total IgE, and two-third had BAL viral transcripts, predominately human rhinovirus, with BAL neutrophilia. Cluster 4 (n = 7) was older, with high total IgE, blood eosinophilia, and mixed BAL eosinophils and neutrophils. CONCLUSIONS: Preschool children with recurrent wheeze refractory to inhaled corticosteroid treatment include 4 clusters: airway malacia, gastroesophageal reflux, indolent human rhinovirus bronchoalveolitis, and type-2high inflammation. The results support the risk and cost of invasive bronchoscopy to diagnose causes of treatment-refractory wheeze and develop novel therapies targeting airway malacia, human rhinovirus infection, and BAL neutrophilia in preschool children.

Neurological complications of COVID-19 in hospitalized patients: The registry of a neurology department in the first wave of the pandemic.

OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.

Ultrasonographic and hemodynamic characteristics of patients with symptomatic carotid near-occlusion: results from a multicenter registry study.

PURPOSE: The ultrasonographic and hemodynamic features of patients with carotid near-occlusion (CNO) are still not well known. Our aim was to describe the ultrasonographic and hemodynamic characteristics of a cohort of patients with CNO. METHODS: A prospective, observational, nationwide, and multicenter study was conducted from January/2010 to May/2016. Patients with digital subtraction angiography (DSA)-confirmed CNO were included. We collected information on clinical and demographic characteristics, carotid and transcranial ultrasonography and DSA findings, presence of full-collapse, collateral circulation, and cerebrovascular reactivity (CVR). RESULTS: One hundred thirty-five patients were analyzed. Ultrasonographic and DSA diagnosis of CNO were concordant in only 44%. This disagreement was related to the presence/absence of full-collapse: 45% of patients with CNO with full-collapse were classified as a complete carotid occlusion, and 40% with a CNO without full-collapse were interpreted as severe stenosis (p < 0.001). Mean velocities (mV) and pulsatility indexes (PIs) were significantly lower in the ipsilateral middle cerebral artery compared with the contralateral (43 cm/s vs 58 cm/s, p < 0.001; 0.80 vs 1.00, p < 0.001). Collateral circulation was identified in 92% of patients, with the anterior communicating artery (73%) being the most frequent. CVR was decreased or exhausted in 66% of cases and was more frequent in patients with a poor or absent collateral network compared with patients with ≥ 2 collateral arteries (82% vs 56%, p = 0.051). CONCLUSION: The accuracy of carotid ultrasonography in the diagnosis of CNO seems to be limited, with significant discrepancies with DSA. Decreased ipsilateral mV, PI, and CVR suggest a hemodynamic compromise in patients with CNO.

Interprofessional collaboration and smartphone use as promising strategies to improve prenatal oral health care utilization among US underserved women: results from a qualitative study.

BACKGROUND: Data on barriers and facilitators to prenatal oral health care among low-income US women are lacking. The objective of this study was to understand barriers/facilitators and patient-centered mitigation strategies related to the use of prenatal oral health care among underserved US women. METHODS: We used community-based participatory research to conduct two focus groups with eight pregnant/parenting women; ten individual in-depth interviews with medical providers, dental providers and community/social workers; and one community engagement studio with five representative community stakeholders in 2018-2019. Using an interpretive description research design, we conducted semi-structured interviews and focus groups which were audio-recorded, transcribed, and analyzed for thematic content. RESULTS: We identified individual and systemic barriers/facilitators to the utilization of prenatal oral health care by underserved US women. Strategies reported to improve utilization included healthcare system-wide changes to promote inter-professional collaborations, innovative educational programs to improve dissemination and implementation of prenatal oral health care guidelines, and specialized dental facilities providing prenatal oral health care to underserved women. Moreover, smartphones have the potential to be an innovative entry point to promote utilization of prenatal oral care at the individual level. CONCLUSIONS: Low-income women face multiple, addressable barriers to obtaining oral health care during pregnancy. Inter-professional collaboration holds strong promise for improving prenatal oral health care utilization.

Hypertension in obesity.

PURPOSE OF REVIEW: The obesity epidemic is progressively affecting majority of individuals worldwide leading to many adverse metabolic and cardiovascular outcomes. Increasingly concerning among them is obesity hypertension (HTN). In this review, we delve into the physiology and therapeutic options in obesity HTN as we discuss the implications of obesity HTN on society. RECENT FINDINGS: Obesity is the most common cause of primary HTN and is directly proportional to increases BMI. The significance of adiposity in obesity HTN centers on humoral mechanisms via stimulation of the renal-angiotensin system, leptin activity, sympathetic overdrive, and proinflammatory processes that potentiate vascular remodeling, which results in a higher incidence of the progression of many known serious cardiovascular diseases. Although lifestyle and medical therapies have been recommended for obesity and its sequelae, continued global progression of this disease has driven the development of newer therapies such as carotid baroreflex activation therapy, renal denervation, and selective leptin receptor antagonism. SUMMARY: The pathophysiology of obesity HTN has not yet been fully elucidated despite it being one of the oldest known diseases to mankind. Major efforts to understand obesity HTN endures, paving opportunities for newer and possibly superior therapeutic options.

Plasma exchange in acute attacks of demyelinating diseases of the central nervous system: clinical outcomes and predictors of response.

BACKGROUND: Plasma exchange (PLEX) is a therapeutic option in the treatment of acute attacks of Demyelinating Diseases of the Central Nervous System (DDCNS). Factors related with PLEX response are not well established. METHODS: Descriptive and retrospective study. We included patients treated with PLEX for acute attacks of DDCNS between 2008 and 2017. We recorded demographics, clinical and treatment-related data, and Expanded Disability Status Scale (EDSS) score at admission, at discharge, and at 6 months. RESULTS: We included 64 patients. Forty-eight (75%) were female with a mean age of 48.28 ± 11.5 years. Half of our patients were diagnosed with multiple sclerosis. Clinical improvement was achieved in 51.6% at discharge and 62.5% at 6 months. The logistic regression model showed that EDSS score > 3 at admission (p = 0.04) and early clinical improvement with PLEX (p = 0.00) were predictors of good response to PLEX at discharge and at 6 months, respectively. No serious adverse effects were identified. CONCLUSIONS: PLEX is a safe and effective treatment for acute attacks of DDCNS. EDSS score at admission and early clinical improvement with PLEX were factors associated with good response to PLEX.

Abdominal Pain and Intermittent Fevers in a 16-Year-Old Girl.

A 16-year-old girl presented to the emergency department with intermittent fevers and worsening abdominal pain of 5 weeks duration. She had a history of travel to a less developed country and exposure to possible infectious diseases. Abdominal imaging and blood tests revealed diffuse mesenteric lymphadenopathy, elevated transaminases, and elevation of inflammatory markers. Gastroesophageal and colon endoscopies revealed gastric ulcers, and the patient was discharged with a presumptive diagnosis of systemic juvenile idiopathic arthritis given the lymphadenopathy seen on imaging, serositis, sacroiliac joint stiffness noted on physical examination, and pain relief with celecoxib. She presented again 4 days later with worsening abdominal tenderness, elevated transaminases, and new-onset abdominal distention. Tissue biopsy yielded the diagnosis and directed appropriate treatment.

On the role of composition and processing parameters on the microstructure evolution of Ti-xMo alloys.

Laser Engineered Net Shaping (LENS™) was used to produce a compositionally graded Ti-xMo (0 ≤ x ≤ 12 wt %) specimen and nine Ti-15Mo (fixed composition) specimens at different energy densities to understand the composition-processing-microstructure relationships operating using additive manufacturing. The gradient was used to evaluate the effect of composition on the prior-beta grain size. The specimens deposited using different energy densities were used to assess the processing parameters influence the microstructure evolutions. The gradient specimen did not show beta grain size reduction with the Mo content. The analysis from the perspective of the two grain refinement mechanisms based on a model known as the Easton & St. John, which was originally developed for aluminum and magnesium alloys shows the lower bound in prior-beta grain refinement with the Ti-Mo system. The low growth restriction factor for the Ti-Mo system of Q = 6,5C0 explains the unsuccessful refinement from the solute-based mechanism. The energy density and the grain size are proportional according to the results of the nine fixed composition specimens at different energy densities. More energy absorption from the material represents bigger molten pools, which in turn relates to lower cooling rates.