Ischemic cerebrovascular complications with initial presentation of genetic atypical hemolytic uremic syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease, with scarce reports of neurologic manifestations in the acute setting. Ischemic cortical infarcts concurrently with aHUS presentation have not been described in adult patients. CASE DESCRIPTION: A 46-year-old male presented with acutely declining mental status and progressive weakness, in the setting of longstanding hypertension and known type B aortic dissection. Urgent neuroimaging showed bilateral multifocal multiterritorial ischemic infarcts, concerning for an embolic source or hypercoagulable state. Systemic workup was notable for microangiopathic hemolytic anemia and acute kidney injury. Empiric plasmapheresis was initiated for presumed thrombotic thrombocytopenic purpura. Broad workup did not support such a diagnosis, and kidney biopsy showed findings compatible with aHUS. Additional blood testing showed increased complement pathway activity. Shiga toxin was negative, and overall clinical picture fit with aHUS as diagnosis. Treatment with complement inhibitor was started and patient gradually recovered. Genetic testing confirmed a pertinent pathogenic mutation, CFHR1 homozygous deletion. CONCLUSION: Acute multifocal multiterritorial ischemic infarcts and systemic thrombotic microangiopathy may be a manifestation of aHUS, and with associated genetic mutation, even in adult population.

Cutaneous iontophoresis of vasoactive medications in patients with scleroderma-associated pulmonary arterial hypertension.

BACKGROUND: It remains unknown whether the cutaneous microvascular responses are different between patients with scleroderma-associated pulmonary arterial hypertension (SSc-PAH) and SSc without pulmonary hypertension (PH). METHODS: We included 59 patients with SSc between March 2013 and September 2019. We divided patients into 4 groups: (a) no PH by right heart catheterization (RHC) (n = 8), (b) no PH by noninvasive screening tests (n = 16), (c) treatment naïve PAH (n = 16), and (d) PAH under treatment (n = 19). Microvascular studies using laser Doppler flowmetry (LDF) were done immediately after RHC or at the time of an outpatient clinic visit (group b). RESULTS: The median (IQR) age was 59 (54-68) years, and 90% were females. The responses to local thermal stimulation and postocclusive reactive hyperemia, acetylcholine, and sodium nitroprusside iontophoresis were similar among groups. The microvascular response to treprostinil was more pronounced in SSc patients without PH by screening tests (% change: 340 (214-781)) compared with SSc-PAH (naïve + treatment) (Perfusion Units (PU) % change: 153 (94-255) % [p = .01]). The response to A-350619 (a soluble guanylate cyclase (sGC) activator) was significantly higher in patients with SSc without PH by screening tests (PU % change: 168 (46-1,296)) than those with SSc-PAH (PU % change: 22 (15-57) % [p = .006]). The % change in PU with A350619 was directly associated with cardiac index and stroke volume index (R: 0.36, p = .03 and 0.39, p = .02, respectively). CONCLUSIONS: Patients with SSc-PAH have a lower cutaneous microvascular response to a prostacyclin analog treprostinil and the sGC activator A-350619 when compared with patients with SSc and no evidence of PH on screening tests, presumably due to a peripheral reduction in prostacyclin receptor expression and nitric oxide bioavailability.

Platelet glycolytic metabolism correlates with hemodynamic severity in pulmonary arterial hypertension.

Group 1 pulmonary hypertension (PH), i.e., pulmonary arterial hypertension (PAH), is associated with a metabolic shift favoring glycolysis in cells comprising the lung vasculature as well as skeletal muscle and right heart. We sought to determine whether this metabolic switch is also detectable in circulating platelets from PAH patients. We used Seahorse Extracellular Flux to measure bioenergetics in platelets isolated from group 1 PH (PAH), group 2 PH, patients with dyspnea and normal pulmonary artery pressures, and healthy controls. We show that platelets from group 1 PH patients exhibit enhanced basal glycolysis and lower glycolytic reserve compared with platelets from healthy controls but do not differ from platelets of group 2 PH or dyspnea patients without PH. Although we were unable to identify a glycolytic phenotype unique to platelets from PAH patients, we found that platelet glycolytic metabolism correlated with hemodynamic severity only in group 1 PH patients, supporting the known link between PAH pathology and altered glycolytic metabolism and extending this association to ex vivo platelets. Pulmonary artery pressure and pulmonary vascular resistance in patients with group 1 PH were directly associated with basal platelet glycolysis and inversely associated with maximal and reserve glycolysis, suggesting that PAH progression reduces the capacity for glycolysis even while demanding an increase in glycolytic metabolism. Therefore, platelets may provide an easy-to-harvest, real-time window into the metabolic shift occurring in the lung vasculature and represent a useful surrogate for interrogating the glycolytic shift central to PAH pathology.

Is There Value in Repeating Inhaled Nitric Oxide Vasoreactivity Tests in Patients with Pulmonary Arterial Hypertension?

BACKGROUND: In patients with pulmonary arterial hypertension (PAH), it remains unknown if the response to the acute pulmonary vasoreactivity test changes over time and determines prognosis. METHODS: We included PAH patients who underwent two right heart catheterizations (RHC) with acute vasoreactivity challenge using inhaled nitric oxide (NO). The hemodynamic response was assessed by absolute or percentage change in mean pulmonary artery pressure (mPAP) or pulmonary vascular resistance (PVR). RESULTS: We included 54 patients, age 51 ± 17 years, and 44 (82%) female. The median (IQR) time between the two RHC was 24.5 months (14.8-42 months). The percentage drop in mPAP was less pronounced in the second RHC (- 8.6 ± 8.1 versus - 12.3 ± 13.8 mmHg, p = 0.02). A total of 8 (14%) patients met criteria for a positive vasodilatory test during the first RHC but only 1 during the second. Patients with increased vasoreactivity at second RHC were more likely to receive (a) treatment with phosphodiesterase-5 inhibitors (PDE5-inh) at first RHC (56% versus 27%, p = 0.04) and (b) more PAH-specific medications by second RHC (2.3 ± 0.8 versus 1.8 ± 0.9, p = 0.03). Cox survival analysis showed that change in mPAP or PVR during vasodilatory challenge at or between the first and second RHC had no impact on survival. CONCLUSIONS: Pulmonary vascular reactivity to inhaled NO might decrease over time; however, there is great variability among patients. The use of PDE5-inh at first RHC and number of PAH-specific treatments by the second RHC were associated with an improvement in pulmonary vasoreactivity over time.

Treatment and practical considerations of diabetic kidney disease.

Diabetic kidney disease (DKD) is a complication of diabetes that can lead to kidney failure. Over the years, several drugs have been developed to combat this disease. In the early 90s, angiotensin blockade (ACEi and ARBs) was introduced, which revolutionized the treatment of DKD. In recent years, newer drugs such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin antagonists, and mineralocorticoid receptor antagonists (MRA) have shown great promise in reducing albuminuria and protecting the kidneys. These drugs are being used in combination with lifestyle modifications, patient education, and risk factor modification to effectively manage DKD. In this review, we will explore the latest pharmacological options, their efficacy, and their potential to revolutionize the management of this debilitating disease.

Fluid loading during the hemodynamic evaluation of pulmonary hypertension: a cross-sectional study.

Background: Compensated pulmonary hypertension due to left heart disease (PH-LHD) may be difficult to identify based on resting hemodynamics. Fluid challenge is commonly used to unmask occult PH-LHD. We sought to determine the hemodynamic effect of fluid loading and its association with the clinical pretest probability of PH-LHD. Methods: We included consecutive patients evaluated for PH who underwent right heart catheterization (RHC) with fluid challenge at Cleveland Clinic between April 2013 and January 2019. We obtained hemodynamic measurements at rest and after intravenous rapid fluid challenge (500 mL of normal saline). We calculated the pretest probability of PH-LHD based on the 6th World Symposium on PH proceedings. For statistical analyses we used t-test, analysis of variance (ANOVA), Chi-square, paired t-test, Wilcoxon signed-rank test and linear regression as indicated. Results: We included 174 patients with mean ± standard deviation (SD) age of 63.7±13.0 years and 123 (71%) of female sex. Baseline pulmonary artery wedge pressure (PAWP) was 11±5 mmHg, with a PAWP/cardiac output (CO) ratio of 2.1±1.1 Wood units (WU). The absolute increase in PAWP and PAWP/CO was 6.9±3.6 mmHg and 1.06±0.91 WU, respectively. The change in PAWP was inversely associated with baseline PAWP (P<0.001). The PAWP with fluids was >18 mmHg in 81% of the patients with baseline PAWP 13-15 mmHg. We found no strong associations between the change in PAWP, PAWP/CO or right atrial pressure to pulmonary arterial wedge pressure ratio (RAP/PAWP) and the pretest probability of PH-LHD. Conclusions: The absolute change in PAWP, PAWP/CO, or achieving a PAWP >18 mmHg with rapid fluid loading was not robustly associated with the pretest probability of PH-LHD. Patients with PAWP between 13-15 mmHg commonly had a positive fluid challenge, questioning the utility of this intervention in these patients.

Telehealth Perceptions Among US Immigrant Patients at an Academic Internal Medicine Practice: Cross-sectional Study.

BACKGROUND: The use of telemedicine has increased dramatically through the COVID-19 pandemic. Although data are available about patient satisfaction with telemedicine, little is known about immigrant patients' experience. OBJECTIVE: We sought to investigate patients' experiences with telehealth compared to in- person visits between immigrants and nonimmigrants. We wanted to identify and describe next visit preferences within the Farmington University of Connecticut Internal Medicine practice to ultimately guide suggestions for more equitable use and accessibility of visit options. METHODS: A total of 270 patients including 122 immigrants and 148 nonimmigrants were seen by 4 Internal Medicine providers in an in-person (n=132) or telemedicine (n=138) university practice setting. Patients were queried between February and April 2021, using an adaptation of a previously validated patient satisfaction survey that contained standard questions developed by the Consumer Assessment of Healthcare Providers and Systems Program. Patients seen via in-person visits completed a paper copy of the survey. The same survey was administered by a follow-up phone call for telemedicine visits. Patients surveyed spoke English, Spanish, or Arabic and were surveyed in their preferred language. For televisits, the same survey was read to the patient by a certified translator. The survey consisted of 10 questions on a Likert scale of 1-5. Of them, 9 questions assessed patient satisfaction under the categories of access to care, interpersonal interaction, and quality of care. An additional question asked patients to describe and explain the reasons behind next visit preferences. Survey question responses were compared by paired t tests. RESULTS: Across both immigrant and nonimmigrant patient populations, satisfaction with perceived quality of care was high, regardless of visit type (P=.80, P=.60 for televisits and P=.76, P=.37 for in-person visits). During televisits, immigrants were more likely to feel providers spent sufficient time with them (P<.001). Different perceptions were noted among nonimmigrant patients. Nonimmigrants tended to perceive more provider time during in-person visits (P=.006). When asked to comment on reasons behind next televisit preference, nonimmigrant patients prioritized convenience, whereas immigrants noted not having to navigate office logistics. For those who chose in-person visits, both groups prioritized the need for a physical exam. CONCLUSIONS: Although satisfaction was high for both telemedicine and in-person visits across immigrant and nonimmigrant populations, significant differences in patient priorities were identified. Immigrants found televisits desirable because they felt they spent more time with providers and were able to avoid additional office logistics that are often challenging barriers for non-English speakers. This suggests opportunities to use information technology to provide cultural and language-appropriate information throughout immigrants' in-person and telemedicine visit experience. A focus on diminishing these barriers will help reduce health care inequities among immigrant patients.

Mixed Venous Oxygen Saturation Is a Better Prognosticator Than Cardiac Index in Pulmonary Arterial Hypertension.

BACKGROUND: European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines include thermodilution cardiac index (TDCI) and mixed venous oxygen saturation (SvO2) as two of the three hemodynamic determinations used in risk assessment of patients with pulmonary arterial hypertension (PAH). SvO2 may be a better measurement than TDCI to assess prognosis in patients with either idiopathic or heritable PAH. RESEARCH QUESTION: What is the concordance between TDCI and SvO2 ESC/ERS risk group allocation and their prognostic value in patients with PAH? STUDY DESIGN AND METHODS: In this retrospective study, we assessed the correlation between SvO2 and TDCI in patients with idiopathic and heritable PAH. We determined concordance in the ESC/ERS risk group allocation and association with survival, both at baseline and follow-up. RESULTS: A total of 158 patients (mean age, 58 ± 17 years; 72% women) with idiopathic (91%) and heritable (9%) PAH were included. There was moderate association between TDCI and SvO2 (r = 0.50; 95% CI, 0.37-0.62). Weighted kappa revealed a fair agreement between TDCI and SvO2 (κ = 0.30; 95% CI, 0.18-0.42), with concordance in risk group allocation in 49% of patients. During a median follow-up of 45 months (interquartile range, 23-105), 62 patients (39%) died. Using Kaplan-Meier analysis, survival was impacted by the SvO2 (log rank = 0.002) but not by the TDCI risk group allocation (log-rank = 0.51). Using the Cox proportional hazard model, adjusted for age and sex, SvO2 (but not TDCI) was associated with mortality (hazard ratio per 1% change, 0.94; 95% CI, 0.91-0.97; P < .001). INTERPRETATION: When using the cutoffs proposed by the ESC/ERS guidelines, we noted poor concordance in risk score allocation between TDCI and SvO2. In patients with idiopathic or heritable PAH, SvO2 measurements are superior to TDCI in predicting long-term mortality.