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Acute compartment syndrome: A case report for pre-clinical students’ learning & associated small group worksheet
Full text linkIntroduction:
Acute compartment syndrome is a limb-threatening, orthopedic surgical emergency that is often a result of trauma with associated edema and increased pressure that has limited room for expansion due to the compartments of a limb. During pre-clinical years of medical school, the emphasis on musculoskeletal (MSK) ailments, including acute compartment syndrome, can be limited. It is therefore important to provide case reports that highlight even routine cases of traumatic MSK problems to the learning mind, as repetition is the key to learning. Small group worksheets were utilized during pre-clinical learning sessions, which further play a role in the learning process by forcing students to brainstorm solutions before answers are revealed, and can thus also be utilized to better understand MSK disease.
Case Description:
A male patient in their teens presented to the emergency department following an open fracture of his tibia and fibula after getting his leg stuck between a lawn mower and tree. On the day of injury, surgery was done for intramedullary fixation and distal tibia nailing. Post-op day one, early in the morning, the patient began complaining of mild pain and paresthesia of his toes and plantar foot, however had preserved motor function and brisk capillary refill. Compartments of the lower leg were swollen but not tense. A few hours later, the patient had increased pain with passive stretch, paresthesia up to his knee, and tense anterior compartment. The decision was made to do an emergent fasciotomy. The surgery was uncomplicated, but the post-op course was complicated by incision site infection. The patient has been progressing well and undergoing physical therapy with no gross motor or sensory deficits.
Discussion:
Acute compartment syndrome can be a rapidly progressing injury, and it is therefore vital to keep it high on the differential in patients complaining of pain with passive stretch and paresthesia. Serial physical exams with this patient ensured the fasciotomy was not delayed. While this report is a classic example of acute compartment syndrome, it can aid in the education of preclinical students. Next steps include incorporating this case and worksheet into MSK curriculum to determine if it leads to improved scores on standardized MSK exams
Celiac Disease in Medical Curriculum
No full textIntroduction/Background: Students attending US medical schools are often turning to commercial resources as a primary learning tool during their preclinical years. However, the quality and content of the material presented within these sources has not been widely studied. This study sought to compare sources of preclinical medical education using celiac disease, a common autoimmune illness. Celiac disease has an exceedingly variable range of presentations across many body systems, including subclinical symptoms. Despite accessible testing and treatment, most individuals with celiac have not been diagnosed, imposing significant disease burden.
Study objective/Hypothesis: This study sought to evaluate and compare the IUSM preclinical curriculum and popular commercial resources regarding their presentation of celiac disease.
Methods: After conducting a literature review, an evidence-based rubric was created to evaluate information about celiac disease. The rubric was applied to the IUSM preclinical curriculum and USMLE World, First Aid for the USMLE Step 1, and Boards and Beyond, commercial resources widely used by preclinical medical students.
Results: The IUSM curriculum scored higher overall and higher in all but one category than all the commercial resources. USMLE World had the highest score of the commercial resources. All sources showed deficits in two or more categories.
Conclusions: All sources assessed exhibit opportunities for improvement. However, the IUSM curriculum presented more thorough information regarding celiac disease. Although the commercial resources included within this study are used by students to prepare for standardized exams, they may be more concerned with improving test scores than providing students with the information needed to become effective physicians. Students may gain more complete information regarding celiac disease from the IUSM curriculum
In-utero therapy for cystic fibrosis: Baby Piper's CF journey
No full textA Plainfield mom was the first Riley patient to take Trikafta while pregnant to help her daughter, who was diagnosed with Cystic Fibrosis before birth. Both are doing well today
Who are they talking about and what are they calling us? Hispanic, Latino/a/e/x or something else?
No full textThere has been a push recently to alter the terms used in the Library of Congress Subject headings to better reflect the peoples who are being described by the terms. These terms change over time, and some have been changed in the database, a task that has become far less daunting with the advent of online catalogs in which global updates are possible. Despite this, it is often difficult to demonstrate the need for specific changes. I will explain why I have been having problems with the heading “Hispanic Americans” and why I feel that it needs to be modified. Many Latin American and Indigenous Peoples of the Americas (LAIPA) Funnel Project participants had the same concern, and as we struggled with the possible heading changes, we decided that one of the things we needed to do was to get a better sense as to how the people being included in that term self-identified. We created and disseminated a survey to that effect and are in the process of evaluating it and seeing how the information can have an impact on the suggestions we make to the Library of Congress
Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia
No full textIntroduction: Sex differences are apparent in neurodegenerative diseases but have not been comprehensively characterized in frontotemporal dementia (FTD).
Methods: Participants included 337 adults with autosomal dominant FTD enrolled in the ALLFTD Consortium. Clinical assessments and plasma were collected annually for up to 6 years. Linear mixed-effects models investigated how sex and disease stage are associated with longitudinal trajectories of cognition, function, and neurofilament light chain (NfL).
Results: While sex differences were not apparent at asymptomatic stages, females showed more rapid declines across all outcomes in symptomatic stages compared to males. In asymptomatic participants, the association between baseline NfL and clinical trajectories was weaker in females versus males, a difference that was not present in symptomatic participants.
Discussion: In genetic FTD, females show cognitive resilience in early disease stages followed by steeper clinical declines later in the disease. Baseline NfL may be a less sensitive prognostic tool for clinical progression in females with FTD-causing mutations.
Highlights: Females with genetic FTD exhibit overall steeper increases in plasma neurofilament light chain (NfL) than males. Females with genetic FTD outperform NfL levels in asymptomatic stages compared to males. Once symptomatic, females with genetic FTD decline more rapidly than males. Plasma NfL is a stronger prognostic marker in asymptomatic males than females
Repigmentation by body region in patients with vitiligo treated with ruxolitinib cream over 52 weeks
No full textPerformance of race-neutral eGFR equations in patients with decompensated cirrhosis
No full textThe 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol-measured GFR (mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985 to 2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, Modification of Diet in Renal Disease-4, Modification of Diet in Renal Disease-6, Royal Free Hospital, and GFR Assessment in Liver disease overall and in certain subgroups (ascites, mGFR ≤ 30 mL/min/1.73 m 2 , diagnosis, Model for End-Stage Liver Disease and gender). We examined bias (difference between eGFR and mGFR), accuracy (p30: eGFR within ± 30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the second lowest bias across the entire range of GFR after GFR Assessment in Liver disease (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p < 0.001). The accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30 = 67.8% vs. 67.9%, respectively) which was higher than the other equations ( p < 0.001). It had a similar performance in patients with ascites, by diagnoses, Model for End-Stage Liver Disease subgroups, by gender, and in non-Black patients. However, it had a relatively higher overestimation in mGFR ≤ 30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p < 0.001). Specifically, 64% of patients with mGFR ≤ 30 mL/min/1.73m 2 were incorrectly classified as a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 , which was higher than the alternate equations except for Royal Free Hospital ( p < 0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis, specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis, given implications for organ allocation and dual organ transplant
HapCNV: A Comprehensive Framework for CNV Detection in Low-input DNA Sequencing Data
No full textCopy number variants (CNVs) are prevalent in both diploid and haploid genomes, with the latter containing a single copy of each gene. Studying CNVs in genomes from single or few cells is significantly advancing our knowledge in human disorders and disease susceptibility. Low-input including low-cell and single-cell sequencing data for haploid and diploid organisms generally displays shallow and highly non-uniform read counts resulting from the whole genome amplification steps that introduce amplification biases. In addition, haploid organisms typically possess relatively short genomes and require a higher degree of DNA amplification compared to diploid organisms. However, most CNV detection methods are specifically developed for diploid genomes without specific consideration of effects on haploid genomes. Challenges also reside in reference samples or normal controls which are used to provide baseline signals for defining copy number losses or gains. In traditional methods, references are usually pre-specified from cells that are assumed to be normal or disease-free. However, the use of pre-defined reference cells can bias results if common CNVs are present. Here, we present the development of a comprehensive statistical framework for data normalization and CNV detection in haploid single- or low-cell DNA sequencing data called HapCNV. The prominent advancement is the construction of a novel genomic location specific pseudo-reference that selects unbiased references using a preliminary cell clustering method. This approach effectively preserves common CNVs. Using simulations, we demonstrated that HapCNV outperformed existing methods by generating more accurate CNV detection, especially for short CNVs. Superior performance of HapCNV was also validated in detecting known CNVs in a real P. falciparum parasite dataset. In conclusion, HapCNV provides a novel and useful approach for CNV detection in haploid low-input sequencing datasets, with easy applicability to diploids
Novel rare variant associations with late‐life cognitive performance
No full textBackground:
Despite evidence that Alzheimer’s disease (AD) is highly heritable, there remains substantial “missing” heritability, likely due in part to the effect of rare variants and to the past reliance on case‐control analysis. Here, we leverage powerful endophenotypes of AD (cognitive performance across multiple cognitive domains) in a rare variant analysis to identify novel genetic drivers of cognition in aging and disease.
Method:
We leveraged 8 cohorts of cognitive aging with whole genome sequencing data from the AD Sequencing Project to conduct rare variant analyses of multiple domains of cognition (N = 9,317; mean age = 73; 56% female; 52% cognitively unimpaired). Harmonized scores for memory, executive function, and language were derived using confirmatory factor analysis models. Participants genetically similar to the 1000Genomes EUR reference panel were included in analysis. Variants included in the analysis had a minor allele frequency < 0.01, a minor allele count of ≥ 10, and were annotated as a high or moderate impact SNP using VEP. Associations of baseline scores in each cognitive domain were performed using SKAT‐O, including 92,905 rare variants among 16,243 genes. All tests were adjusted for sex, baseline age, sequencing center and platform, and genetic principal components. Correction for multiple comparisons was completed using the Benjamini‐Hochberg false discovery rate (FDR) procedure.
Result:
APOE was associated with baseline memory, language, and executive function, though only memory survived multiple‐test correction (p.FDR = 0.001). Outside of APOE, ITPKB was associated with baseline executive function (p.FDR = 0.048). AKTIP, SHCBP1L, and CCNF showed nominal associations with multiple domains of cognition that did not survive correction for multiple comparisons (p.FDRs<0.07).
Conclusion:
These results highlight novel rare variants associated with cognition. IPTKB is an AGORA nominated gene target for potential AD treatment. It is important in the regulation of immune cells and displays higher expression in the cortex of AD patients compared to controls. CCNF and AKTIP are brain eQTLs and have differential RNA expression in AD brains. Previously, variants in AKTIP have been associated with educational attainment, intelligence, and memory, while variants in CCNF have been associated with neuritic plaques and neurofibrillary tangles. Future analyses will incorporate longitudinal cognition and expand into additional populations
