Silent cerebral infarction during immune TTP remission: prevalence, predictors, and impact on cognition.

Immune thrombotic thrombocytopenic purpura (iTTP) survivors have increased risk of cardiovascular disease, including strokes, and report persistent cognitive difficulties during remission. We conducted this prospective study involving iTTP survivors during clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neurodeficits. We also tested the hypothesis that SCI is associated with cognitive impairment, assessed using the National Institutes of Health ToolBox Cognition Battery. For cognitive assessments, we used fully corrected T scores adjusted for age, sex, race, and education. Based on the diagnostic and statistical manual 5 criteria, we defined mild and major cognitive impairment as T scores with a 1 or 2 standard deviation (SD) and >2 SD below the mean on at least 1 test, respectively. Forty-two patients were enrolled, with 36 completing MRIs. SCI was present in 50% of the patients (18), of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs 27.7%; P = .026), including major cognitive impairment (50% vs 5.6%; P = .010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment (odds ratio [OR] 10.5 [95% confidence interval (95% CI), 1.45-76.63]; P = .020) and major cognitive impairment (OR 7.98 [95% CI, 1.11-57.27]; P = .039) after adjusting for history of stroke and Beck depression inventory scores. MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these silent infarcts are neither silent nor innocuous.

Corrigendum: D-dimer trends elaborate the heterogeneity of risk in hospitalized patients with COVID-19: a multi-national case series from different waves.

[This corrects the article DOI: 10.3389/fmed.2023.1103842.].

D-dimer trends elaborate the heterogeneity of risk in hospitalized patients with COVID-19: A multi-national case series from different waves.

Introduction: Variable D-dimer trends during hospitalization reportedly result in distinct in-hospital mortality. In this multinational case series from the first and second waves, we show the universality of such D-dimer trends. Methods: We reviewed 405 patients with COVID-19 during the first wave admitted to three institutions in the United States, Italy, and Colombia, and 111 patients admitted to the U.S. site during the second wave and 55 patients during the third wave. D-dimer was serially followed during hospitalization. Results: During the first wave, 66 (15%) patients had a persistently-low pattern, 33 (8%) had early-peaking, 70 (16%) had mid-peaking, 94 (22%) had fluctuating, 30 (7%) had late-peaking, and 112 (26%) had a persistently-high pattern. During the second and third waves, similar patterns were observed. D-dimer patterns were significantly different in terms of in-hospital mortality similarly in all waves. Patterns were then classified into low-risk patterns (persistently-low and early-peaking), where no deaths were observed in both waves, high-risk patterns (mid-peaking and fluctuating), and malignant patterns (late-peaking and persistently-high). Overall, D-dimer trends were associated with an increased risk for in-hospital mortality in the first wave (overall: HR: 1.73) and stayed the same during the second (HR: 1.67, p < 0.001) and the third (HR: 4.4, p = 0.001) waves. Conclusion: D-dimer behavior during COVID-19 hospitalization yielded universal categories with distinct mortality risks that persisted throughout all studied waves of infection. Monitoring D-dimer behavior may be useful in the management of these patients.

Novel ALK mutation with durable response to brigatinib-a case report.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors are the preferred initial treatment for ALK rearranged non-small cell lung cancer (NSCLC). While initial responses to next-generation inhibitors are robust, acquired resistance is expected for nearly all patients. Resistance is often mediated by point mutations along the solvent front. Use of the acquired mutational profile to guide therapy is still investigational and largely based on preclinical data demonstrating sensitivity of resistant cell lines to available kinase inhibitors. Here, we describe outcomes after development of an ALK L1196Q mutation. We present a patient with stage IV ALK rearranged lung cancer received who received first line crizotinib at 250 mg twice daily, then at progression, second line alectinib at 600 mg twice daily. When radiographic evidence of progression was noted, a biopsy was performed. Next generation sequencing (NGS) identified an acquired ALK L1196Q mutation. The patient was treated with third line brigatinib, at 90 mg daily and escalating to 180 mg daily, and achieved a partial response that is still ongoing, one year later. We highlight false-negative ALK mutation results when only plasma is used, particularly in early metastatic disease. We also discuss how the use of specific ALK resistance mutations to guide therapy is clinically relevant is being investigated.

Immune Checkpoint Inhibitor-induced Fanconi Syndrome.

Immune checkpoint inhibitors (ICI) have been approved by the Food and Drug Administration (FDA) for use in many solid tumors and hematological malignancies. Immune-related adverse events (irAEs) are potential side effects that can arise during or after treatment with ICI therapy. We describe a case of ICI-induced Fanconi syndrome in a 58-year-old man with extensive-stage small-cell lung cancer (ES-SCLC), who had disease progression after initial chemotherapy and radiation. He was started on nivolumab and ipilimumab as second-line treatment. Three weeks into the therapy, he developed abdominal pain with grade 3 transaminitis and required steroids and mycophenolate for presumed autoimmune hepatitis. Subsequently, he presented with worsening abdominal pain and was found to have an enlarging right adrenal mass. Laboratory work-up revealed a white blood cell (WBC) count of 17 K/µL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 99/210 U/L, direct bilirubin 2.8 mg/dL, blood urea nitrogen (BUN) 43 mg/dL, Cr 2.31 mg/dL (baseline: 1.1 mg/dL), phosphorus 2.3 mg/dL, and glucose 303 mg/dL with metabolic acidosis. There was no evidence of urinary tract obstruction. Urinary findings were notable for glucosuria (>500 mg/dL), fractional excretion of phosphorus and uric acid of 56% (normal range 10%-20%) and 75% (normal range 7%-10%), respectively. He was started on intravenous (IV) bicarbonate and methylprednisolone. Fanconi syndrome with proximal tubular damage secondary to ICI therapy was diagnosed. He was discharged on oral bicarbonate and steroid taper. On follow-up after four weeks, his renal function recovered to baseline.

Efficacy and Safety of Direct-Acting Oral Anticoagulants (DOACs) in the Overweight and Obese.

Obesity plays an essential role in the safety of pharmacologic drugs. There is paucity of data for direct oral anticoagulants (DOACs) in the obese, despite these agents becoming more widely used. The primary and secondary objectives of this study were to assess the safety and efficacy of DOACs in the overweight and obese populations when used for primary prophylaxis in the setting of non-valvular atrial fibrillation (NVAF) and for treatment of venous thromboembolisms (VTE). We conducted a retrospective cohort study in a large tertiary care center and obtained data through review of electronic health records. Among patients with NVAF and VTE on apixaban, there were no differences in rates of major bleeding (MB) and clinically relevant nonmajor bleeding (CRNMB) in the overweight and obese populations when compared to normal weight and underweight individuals. The multivariate adjusted analysis for rivaroxaban found that the odds of CRNMB for patients with BMI <25 was 5.37 (95% CI 1.50-19.32) times higher than that of BMI ≥25. Moreover, patients on medications that had known interactions with DOACs had 6.40 times higher odds of CRNMB than patients without such interactions (95% CI 1.49-27.57), which was not accounted for by the effects of aspirin and plavix alone. Efficacy was similar between all weight groups, for both apixaban and rivaroxaban. These results support previous analyses preformed in the large phase III trials and confirm that apixaban and rivaroxaban are safe in the overweight and obese.

Acute kidney injury in lymphoma: a single centre experience.

Background. Acute kidney injury (AKI) is a common but least studied complication of lymphoma. Objective. To determine the frequency and predictors of AKI in lymphoma and to study the impact of AKI on hospital stay and mortality. Methods. Retrospective review of medical records of hospitalized lymphoma patients aged ≥14 years between January 2008 and December 2011 was done. Results. Out of 365 patients, AKI was present in 31.8% (116/365). Multivariate logistic regression analysis showed that independent predictors for AKI included sepsis (odds ratio (OR) 3.76; 95% CI 1.83-7.72), aminoglycosides (OR 4.75; 95% CI 1.15-19.52), diuretics (OR 2.96; 95% CI 1.31-6.69), tumor lysis syndrome (OR 3.85; 95% CI 1.54-9.59), and R-CVP regimen (OR 4.70; 95% CI 1.20-18.36). AKI stages 2 and 3 was associated with increased hospital stay (OR 2.01; 95% CI 1.19-3.40). Conclusion. AKI was significantly associated with sepsis, aminoglycoside, diuretics, presence of tumor lysis syndrome, and use of R-CVP regimen. Presence of AKIN (Acute Kidney Injury Network) stages 2 and 3 AKI had increased hospital stay. AKI was also associated with increased mortality.

Effects of goal setting on dietary and physical activity changes in the Boy Scout badge projects.

BACKGROUND: This study evaluates the relationship of goal setting to low-fat vegetable (LV) and fruit/100% juice (FJ) consumption and physical activity (PA) change. METHODS: A total of 473 10- to 14-year-old Boy Scouts from Houston took part in a 9-week intervention. A two-group (LV and FJ or PA) intervention design was used with each group serving as the control for the other. Internet-based activities included goal setting at home. Food frequencies measured dietary intake. RESULTS: Goals attained were not related to LV intake or PA. Immediate posttest FJ consumption increased about 0.7 servings as home FJ availability increased, but social desirability of response appeared to confound reports of FJ intake at posttest 6 months assessment. CONCLUSIONS: Goals attained were not related to LV intake or PA but was related to FJ intake, but only when home FJ availability was high and the relationship was confounded by social desirability of response. Further research is needed with higher quality measures of dietary intake to clarify these relationships.