Citations

AbstractBackgroundGoal directed point of care ultrasound (POCUS) is a bedside tool to assist with clinical diagnosis. We examined the impact of POCUS performed by consulting cardiologist (CC) during initial cardiology consult on clinical management and downstream testing.MethodsSixty‐nine study patients (pts) seen in a general cardiology outpatient clinic of a tertiary center by an expert imaging CC were compared to a control group of 65 pts seen by three different CCs without POCUS during the same time‐period, in whom the first standard echo (SE) was performed after the initial visit.ResultsBaseline characteristics were similar between the two groups for age, cardiac risk factors, and referral diagnoses. Echo findings on POCUS and by SE (mean delay of 17.2 days after visit) in the control group were comparable for RV size and function and for valvular heart disease. More patients with lower LVEF, higher LV filling pressures, new regional wall motion abnormalities, and increased aortic root size were present among POCUS group resulting in greater yield of echo abnormalities. There were more cardiovascular medication changes at the first visit (15.3% vs. 5.7%, p < .01), less referral for noninvasive stress testing (10% vs. 29%, p < .01), more advanced cardiac testing and subspecialty referrals (29% vs. 18% pts, p = .06), in the study compared to the control group after cardiology visit.ConclusionPOCUS at time of consultation detects more abnormal echo findings, results in more medication adjustments, less referral for noninvasive stress testing, earlier referral for advanced cardiac diagnostic imaging, and subspecialty cardiac referrals.

Abstract Background Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. Methods Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. Results Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non–MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non–MBL-Ec was 62% (95% CI: 48.2–74.3%). Among infected patients, non–MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. Conclusions Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non–MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.

Background: Blastocystis hominis (B. hominis) is a ubiquitous parasite that has spread worldwide and is commonly present in human stool specimens. It was hypothesized that infection with B. hominis plays a role in the pathogenesis of autoimmune diseases in humans. The aim of this study is to test this hypothesis by investigating patients with autoimmune diseases. Patients with various types of autoimmune diseases with gastrointestinal symptoms were enrolled in this study as cases (n = 72) along with nongastrointestinal symptom patients as controls (n = 58). All participants in this study were subjected to history taking and were investigated for B. hominis infection via wet-mount microscopic stool examinations, staining with trichrome stain, and molecular-based tests applied to their fecal samples. Blood samples were also tested for complete blood counts. B. hominis were identified with specific PCR more in cases (12/72; 16.6%) than in controls (3/58; 5.2%), with a significant difference (p < 0.05). Significant decreases in white blood cell counts were demonstrated in systemic lupus erythematosus (SLE) and ulcerative colitis (UC) patients infected with B. hominis when compared to patients with nongastrointestinal symptoms (p-value < 0.05).

AbstractIgA vasculitis is a small‐vessel vasculitis subtype with increased risk of systemic involvement. We aimed to investigate if any light‐microscopic features can predict the presence of perivascular granular IgA deposits on direct immunofluorescence (DIF) microscopy. We performed a retrospective search of cutaneous pathology reports from our internal and consultation practice (January 1, 2010–October 5, 2021) with a diagnosis of leukocytoclastic vasculitis and accompanying DIF. A blinded dermatopathologist reviewed standard microscopy slides for predetermined histopathological features. Fifty‐six biopsies (48 patients) and 56 biopsies (42 patients) met inclusion criteria for IgA+ and IgA−, respectively. The presence of eosinophils and mid and deep dermal inflammation were statistically more associated with IgA− (41/56 [73.2%] and 31/56 [55.4%], respectively) than IgA+ cases (28/56 [50.0%] and 14/56 [25.0%]; p = 0.049 and 0.006, respectively, chi‐squared test). Other microscopic criteria recorded were not significantly different between the two groups (p > 0.05, chi‐squared and Fisher's exact tests). In this retrospective study of 112 cases, we found that while the absence of eosinophils and absence of mid‐ and deep inflammation were correlated with increased likelihood of IgA perivascular deposition on DIF, no other histopathological features on light microscopy tested could reliably predict the presence of IgA perivascular deposition on DIF. Therefore, DIF remains a necessary component for the accurate diagnosis of cutaneous IgA vasculitis.

Abstract Background and purpose Outcome and rechallenge data on central nervous system (CNS) autoimmunity triggered by immune checkpoint inhibitors (ICIs) are limited. We aim to describe a large series of patients with ICI‐triggered CNS autoimmunity, and to compare these patients with spontaneous paraneoplastic syndromes (PNS). Methods We retrospectively reviewed Mayo Clinic patients with ICI‐triggered CNS autoimmunity (February 2015–June 2021). Clinical characteristics were compared to spontaneous PNS patients (with antineuronal nuclear antibody [ANNA]‐1 or anti‐Hu neurological autoimmunity, and/or neuroendocrine tumors [NET]) evaluated within the same period. Results Thirty‐one patients were included (55% female, median age = 63 years, range = 39–76). Median time from ICI initiation was 3.65 months (range = 0.8–44.5). The most common associated malignancies were melanoma and small cell lung cancer. CNS manifestations included encephalitis ( n = 16), meningoencephalitis ( n = 8), cerebellar ataxia ( n = 4), demyelinating syndrome ( n = 2), and myelopathy ( n = 1). Magnetic resonance imaging was abnormal in 62%. Cerebrospinal fluid was inflammatory in 70%. Neural autoantibodies were identified in 47%, more frequently in patients with NET ( p = 0.046). ICI was discontinued in 97%; 90% received immunosuppressive treatment. After median 6.8 months follow‐up (range = 0.7–46), 39% had unfavorable outcomes (grade ≥ 3). This was associated with higher severity degree at onset, shorter period from ICI to neurological symptom onset, and encephalitis. Four patients were rechallenged with ICI, and one relapsed. Patients with NET and with ANNA‐1 ICI‐triggered CNS autoimmunity had associated peripheral nervous system manifestations more frequently than their spontaneous counterparts ( p = 0.007 and p = 0.028, respectively). Conclusions One third of ICI‐related CNS autoimmunity patients have unfavorable outcomes. Relapses may occur after ICI rechallenge. Neural autoantibodies are often present, more commonly in patients with NET.

AbstractContextPregnant women with mutations in the thyroid hormone receptor beta (THRB) gene expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a normal fetus (NlFe) but not to an affected fetus (AfFe). However, no information is available about differences in placental TH regulators.ObjectiveTo investigate whether there are differences in placentas associated with a NlFe compared with an AfFe, we had the unique opportunity to study placentas from 2 pregnancies of the same woman with THRB mutation G307D. One placenta supported a NlFe while the other an AfFe.MethodsSections of placentas were collected and frozen at −80 °C after term delivery of a NlFe and an AfFe. Two placentas from healthy women of similar gestational age were also obtained. The fetal origin of the placental tissues was established by gDNA quantitation of genes on the X and Y chromosomes and THRB gene. Expression and enzymatic activity of deiodinases 2 and 3 were measured. Expression of following genes was also quantitated: MCT10, MCT8, LAT1, LAT2, THRB, THRA.ResultsThe placenta carrying the AfFe exhibited a significant reduction of deiodinase 2 and 3 activities as well as the expression of the TH transporters MCT10, LAT1 and LAT2, and THRA.ConclusionWe present the first study of the effect of the fetal THRB genotype on the placenta. Though limited by virtue of the rarity of THRB mutations and sample availability, we show that the fetal THRB genotype influences the levels of TH regulators in the placenta.