Characterising the prevalence of overweight and obese status among adults with sickle cell disease.

Individuals with sickle cell disease (SCD) have historically been considered underweight. Despite increasing body mass index (BMI) in the general population, the prevalence of overweight and obese status remains unclear in the adult SCD population. Our primary aim was to determine the prevalence of overweight and obese status and to identify associations between BMI, demographic, and clinical characteristics. We conducted an analysis of abstracted electronic health record data and patient-reported outcomes from the Sickle Cell Disease Implementation Consortium registry; individuals aged 20-45 years were included. The median (interquartile range) BMI for the 1664 adults in this analysis was 23.9 (21.1-28) kg/m2 . In this cohort, 42.9% had a BMI of >25 kg/m2 (Centers for Disease Control and Prevention definition of overweight/obese). In multivariable analysis, higher odds of being overweight or obese were associated with female gender, older age, college education, private insurance, and hypertension diagnosis. Higher odds of a BMI of >25 kg/m2 were observed in individuals with HbSC or HbSß+ thalassaemia regardless of hydroxycarbamide (hydroxyurea) exposure (odds ratio [OR] 3.4, p < 0.0001) and HbSS or HbSß0 thalassaemia exposed to hydroxycarbamide (OR 1.6, p = 0.0003) compared to those with HbSS or HbSß0 thalassaemia with no hydroxycarbamide exposure. These data highlight the importance of early identification, prevention, and intervention for increasing BMI to reduce obesity-related complications that may impact SCD-related complications.

Role of CD4+ T Cells in Parkinson's Disease.

Parkinson's disease (PD) is a progressive condition that affects both the central nervous system and other body parts that are controlled by the nervous system. PD is characterized by brain dopaminergic neurons loss and, at present, there are only symptomatic treatments available to alleviate the effects of the disease. With extensive research, new insights have led to defining PD as a multi-system disorder with immune dysfunction playing a dominant part in the disease pathogenesis as well as its progression. Neuroinflammation in PD leads to neurodegeneration, which is, in turn, regulated by the peripheral adaptive immunity, with CD4+ T cells being a significant player. Patients with PD have diverse CD4+ T cell phenotypes and functional profiles. These phenotypes vary, from being proinflammatory (Th1 and Th17) to anti-inflammatory (Th2 and Tregs). This report focuses on reviewing the expression of CD4+ T cells in PD and its role in the prognosis and treatment of PD.

Antimicrobial resistance is a risk factor for mortality in adults with sickle cell disease.

Not available.

Red blood cell exchange to avoid intubating a COVID-19 positive patient with sickle cell disease?

As the COVID-19 pandemic continues to claim lives across the globe, insufficient data exists regarding the optimal treatment. It is well known that patients 55 years of age or older and patients with certain chronic diseases are at higher risk of severe illness, including acute respiratory distress syndrome and death. A potentially fatal pulmonary complication of sickle cell disease, acute chest syndrome, can be precipitated by acute infections, including respiratory viruses. We report the case of a patient with sickle cell disease (HbSC) who developed COVID-19 pneumonia and acute chest syndrome who was treated with emergent red blood cell exchange in order to avoid endotracheal intubation.

Examining Mental Health, Education, Employment, and Pain in Sickle Cell Disease.

Importance: Pain related to sickle cell disease (SCD) is complex and associated with social determinants of health. Emotional and stress-related effects of SCD impact daily quality of life and the frequency and severity of pain. Objective: To explore the association of educational attainment, employment status, and mental health with pain episode frequency and severity among individuals with SCD. Design, Setting, and Participants: This is a cross-sectional analysis of patient registry data collected at baseline (2017-2018) from patients treated at 8 sites of the US Sickle Cell Disease Implementation Consortium. Data analysis was performed from September 2020 to March 2022. Main Outcomes and Measures: Electronic medical record abstraction and a participant survey provided demographic data, mental health diagnosis, and Adult Sickle Cell Quality of Life Measurement Information System pain scores. Multivariable regression was used to examine the associations of education, employment, and mental health with the main outcomes (pain frequency and pain severity). Results: The study enrolled a total of 2264 participants aged 15 to 45 years (mean [SD] age, 27.9 [7.9] years; 1272 female participants [56.2%]) with SCD. Nearly one-half of the participant sample reported taking daily pain medication (1057 participants [47.0%]) and/or hydroxyurea use (1091 participants [49.2%]), 627 participants (28.0%) received regular blood transfusion, 457 (20.0%) had a depression diagnosis confirmed by medical record abstraction, 1789 (79.8%) reported severe pain (rated most recent pain crises as ≥7 out of 10), and 1078 (47.8%) reported more than 4 pain episodes in the prior 12 months. The mean (SD) pain frequency and severity t scores for the sample were 48.6 (11.4) and 50.3 (10.1), respectively. Educational attainment and income were not associated with increased pain frequency or severity. Unemployment (ß, 2.13; 95% CI, 0.99 to 3.23; P < .001) and female sex (ß, 1.78; 95% CI, 0.80 to 2.76; P < .001) were associated with increased pain frequency. Age younger than 18 years was inversely associated with pain frequency (ß, -5.72; 95% CI, -7.72 to -3.72; P < .001) and pain severity (ß, 5.10; 95% CI, -6.70 to -3.51; P < .001). Depression was associated with increased pain frequency (ß, 2.18; 95% CI, 1.04 to 3.31; P < .001) but not pain severity. Hydroxyurea use was associated with increased pain severity (ß, 1.36; 95% CI, 0.47 to 2.24; P = .003), and daily use of pain medication was associated with both increased pain frequency (ß, 6.29; 95% CI, 5.28 to 7.31; P < .001) and pain severity (ß, 2.87; 95% CI, 1.95 to 3.80; P < .001). Conclusions and Relevance: These findings suggest that employment status, sex, age, and depression are associated with pain frequency among patients with SCD. Depression screening for these patients is warranted, especially among those experiencing higher pain frequency and severity. Comprehensive treatment and pain reduction must consider the full experiences of patients with SCD, including impacts on mental health.

Haptoglobin 1 allele predicts higher serum haptoglobin concentration and lower multiorgan failure risk in sickle cell disease.

Haptoglobin (HP) is an acute-phase protein and the main scavenger of cell-free hemoglobin. When HP is depleted, as observed in hemolytic conditions such as sickle cell disease (SCD), cell-free hemoglobin can lead to acute organ damage. The impact of the HP 1-1, 2-1, and 2-2 isoforms on HP and cell-free hemoglobin concentrations and SCD-related complications is unclear. In a longitudinal cohort of patients with SCD, the HP 1 allele was associated with higher HP and lower cell-free hemoglobin concentrations at a routine clinic visit as well as during hospitalization for a vaso-occlusive episode or acute chest syndrome. With a median follow-up of 6.8 years, acute chest syndrome occurred in 42% (n = 163) and multiorgan failure in 14% (n = 53) of 391 patients with SCD with a minimum follow-up of 6 months. The HP 1 allele was independently associated with lower risk of developing multiorgan failure during acute chest syndrome (additive model hazard ratio, 0.5; P < .001). Future studies assessing the regulation of HP concentrations and ability to bind cell-free hemoglobin according to the HP genotype may help to identify patients with SCD at high risk for multiorgan failure and to guide interventions, such as rapid initiation of exchange transfusion or HP replacement therapy.

Evaluation of point-of-care International Normalized Ratio in sickle cell disease.

BACKGROUND: Point-of-care (POC) International Normalized Ratio (INR) measurement provides efficient monitoring of warfarin therapy; however, its reliability may be affected in patients with anemia, such as those with sickle cell disease (SCD). OBJECTIVES: To evaluate the correlation of POC-INR to clinical laboratory INR (CL-INR) in SCD and use of a correction factor. PATIENT/METHODS: In this retrospective study, the accuracy of POC-INR compared to CL-INR was evaluated in a cohort of patients with SCD and in a non-SCD Black cohort. RESULTS: Despite the difference in anemia, the SCD cohort showed a similar percentage of in-range POC-INR values as observed in the non-SCD cohort (37% vs 42%). The SCD cohort was randomly divided to form discovery and validation cohorts. In the discovery cohort, 86% of POC-INRs were in range when the POC-INRs were ˂4.0, but only 24% were in range if POC-INRs were ≥4.0. A linear regression of CL-INR versus POC-INR for POC-INR values ≥4.0 yielded a coefficient of 0.72 (95% confidence interval, 0.69-0.75); Multiplying POC-INR by this correction factor, rounded to 0.7 for ease of use in clinical practice, improved the proportion of in-range POC-INR values ≥4.0 from 24% to 100% in the SCD discovery cohort and from 19% to 95% in the SCD validation cohort. Similar findings applied to analyses of the non-SCD cohort. CONCLUSIONS: POC-INR and CL-INR in patients with SCD are similar when POC-INR is <4.0, and the accuracy of POC-INR values ≥4.0 can be improved by applying an institution-specific correction factor.

A diagnosis of late-onset Myasthenia gravis unmasked by topical antibiotics.

Myasthenia Gravis (MG) is a disorder of the neuromuscular junction (NMJ) that manifests as fluctuating fatiguable weakness of the muscles. There are many factors that can exacerbate myasthenia symptoms including a variety medications and drugs, systemic illness, and pregnancy. A number of medications have been implicated in exacerbating MG symptoms, including aminoglycosides. We present a case of an elderly female with newly diagnosed MG following the use of tobramycin eye drops for 3 days. There have been limited reports in the literature of topical medications that exacerbate MG symptoms. Clinicians prescribing tobramycin eye drops (or other associated medications) should have a high index of suspicion of MG as early discontinuation and therapy will limit long-term morbidity and mortality in these patients.

Response to BRAF/MEK Inhibition After Progression With BRAF Inhibition in a Patient With Anaplastic Pleomorphic Xanthoastrocytoma.

Pleomorphic xanthoastrocytoma (PXA) is a rare primary central nervous system tumor which frequently harbors mutations in BRAF. Anaplastic PXA follow a more aggressive course than their nonanaplastic counterparts. We present the case of an anaplastic PXA initially treated with the BRAF inhibitor vemurafenib. After progression of disease the MEK inhibitor trametinib was added to the regimen leading to radiographic improvement. The rationale for combined BRAF and MEK inhibition in PXA is reviewed.

An unexpected deterrent in diagnosing refractory celiac disease and enteropathy-associated T-cell lymphoma: a gluten-free diet.

Enteropathy-associated T-cell lymphoma (EATL) is a rare disease found in the small bowel and is seen most commonly in patients with refractory celiac disease (RCD). We present a case of an elderly male with celiac disease (CD) diagnosed in childhood with months of abdominal pain and diarrhea despite attempting to avoid gluten in his diet. After persistent symptoms for months, the patient was admitted for an acute abdomen and was found to have small bowel perforation due to a jejunal mass that was diagnosed as an EATL. In 2-5% of adult onset CD, serious complications such as RCD or malignancy develop. The clinical course for EATL is aggressive and generally has a poor prognosis. This case highlights the importance of early clinical suspicion for a small bowel malignancy in patients with a long-standing history of CD and acute worsening of symptoms. Early workup and diagnosis is vital in improving morbidity and mortality in patients with EATL.

A devastating cardiovascular event in an adult cystic fibrosis patient: An unforeseen outcome of increasing life expectancy.

The improving life expectancy for CF is known to be one of the biggest success stories in medicine. Life expectancy has increased from 6 months during the early 20th century to 42.7 years from in 2012-2016. As the life expectancy of CF patients has increased, it is important to consider other co-morbidities that these patients may encounter, and the impact this may have on their morbidity and mortality. We present a case of a 33-year-old male admitted to the hospital for a CF exacerbation who had an acute neurological decompensation due to an infarction of his right occipital and posterior temporal lobe.

Double-Stranded Biotinylated Donor Enhances Homology-Directed Repair in Combination with Cas9 Monoavidin in Mammalian Cells.

Homology-directed repair (HDR) induced by site specific DNA double-strand breaks with CRISPR-Cas9 is a precision gene editing approach that occurs at low frequency in comparison to indel forming non-homologous end joining (NHEJ). In order to obtain high HDR percentages in mammalian cells, we engineered a Cas9 protein fused to a monoavidin domain to bind biotinylated donor DNA. In addition, we used the cationic polymer, polyethylenimine, to deliver Cas9-donor DNA complexes into cells. Improved HDR percentages of up to 90% in three loci tested (CXCR4, EMX1, and TLR) in standard HEK293T cells were observed. Our results suggest that donor DNA biotinylation and Cas9-donor conjugation in addition to delivery influence HDR efficiency.

Drug-induced dyspnea versus cystic fibrosis exacerbation: a diagnostic dilemma.

Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. Orkambi and mucolytics decrease the viscosity of mucous secretions, leading to an accumulation of hypoviscous fluid in the alveoli, resulting in dyspnea. This presentation can be mistaken for an infective exacerbation. We present a case in which a young female with CF recently started on Orkambi therapy presented to her primary care physician with dyspnea and increased respiratory secretions and was admitted to the hospital for 2 weeks of intravenous and inhaled antibiotic therapy for a presumed CF exacerbation. We highlight this case to bring awareness and educate patients and clinicians of the side-effect profile of Orkambi therapy with an intent to avoid unnecessary hospitalizations, inpatient antibiotics, and other costly medical services.

Solitary parotid metastasis 8 years after a nephrectomy for renal cell carcinoma.

Renal cell carcinoma is a common cancer, known for its aggressive behavior and ability to metastasize nearly every organ system in the body. While the cancer commonly spreads to a select few organs and metastasis usually develops within 5 years of diagnosis, there have been numerous case reports of atypical sites of metastasis and cases of relapse up to decades after treatment. We present a case a 65-year-old male who presented with right preauricular swelling 8 years after the initial diagnosis and right nephrectomy for clear cell renal cell cancer. We take a look at previous case reports with similar presentations.