Publications

BACKGROUND: Primary immunodeficiency is common among patients with autoimmune cytopenia.

OBJECTIVE: The purpose of this study is to retrospectively identify key clinical features and biomarkers of primary immunodeficiency (PID) in pediatric patients with autoimmune cytopenias (AIC) so as to facilitate early diagnosis and targeted therapy.

METHODS: Electronic medical records at a pediatric tertiary care center were reviewed. We selected 154 patients with both AIC and PID (n=17), or AIC alone (n=137) for inclusion in two cohorts. Immunoglobulin levels, vaccine titers, lymphocyte subsets (T, B and NK cells), autoantibodies, clinical characteristics, and response to treatment were recorded.

RESULTS: Clinical features associated with AIC-PID included splenomegaly, short stature, and recurrent or chronic infections. PID patients were more likely to have autoimmune hemolytic anemia (AIHA) or Evans syndrome than AIC-only patients. The AIC-PID group was also distinguished by low T cells (CD3 and CD8), low immunoglobulins (IgG and IgA), and higher prevalence of autoantibodies to red blood cells, platelets or neutrophils. AIC diagnosis preceded PID diagnosis by 3 years on average, except among those with partial DiGeorge syndrome. AIC-PID patients were more likely to fail first-line treatment.

CONCLUSIONS: AIC patients, especially those with Evans syndrome or AIHA, should be evaluated for PID. Lymphocyte subsets and immune globulins serve as a rapid screen for underlying PID. Early detection of patients with comorbid PID and AIC may improve treatment outcomes. Prospective studies are needed to confirm the diagnostic clues identified and to guide targeted therapy.

Hinge motions are essential for many protein functions, and their dynamics are important to understand underlying biological mechanisms. The ways that these motions are represented by various computational methods differ significantly. By focusing on a specific class of motion, we have developed a new hinge-domain anisotropic network model (hdANM) that is based on the prior identification of flexible hinges and rigid domains in the protein structure and the subsequent generation of global hinge motions. This yields a set of motions in which the relative translations and rotations of the rigid domains are modulated and controlled by the deformation of the flexible hinges, leading to a more restricted, specific view of these motions. hdANM is the first model, to our knowledge, that combines information about protein hinges and domains to model the characteristic hinge motions of a protein. The motions predicted with this new elastic network model provide important conceptual advantages for understanding the underlying biological mechanisms. As a matter of fact, the generated hinge movements are found to resemble the expected mechanisms required for the biological functions of diverse proteins. Another advantage of this model is that the domain-level coarse graining makes it significantly more computationally efficient, enabling the generation of hinge motions within even the largest molecular assemblies, such as those from cryo-electron microscopy. hdANM is also comprehensive as it can perform in the same way as the well-known protein dynamics models (anisotropic network model, rotations-translations of blocks, and nonlinear rigid block normal mode analysis), depending on the definition of flexible and rigid parts in the protein structure and on whether the motions are extrapolated in a linear or nonlinear fashion. Furthermore, our results indicate that hdANM produces more realistic motions as compared to the anisotropic network model. hdANM is an open-source software, freely available, and hosted on a user-friendly website.

Individuals with neurofibromatosis (NF) experience poorer quality of life (QoL), in part contributed by the clinical manifestations of NF, such as functional disability, chronic pain, and altered physical appearance. Mind-body therapies (MBTs) tailored to NF have been developed, and have demonstrated promising potential to improve QoL in this population. We sought to systematically review current evidence on the effectiveness of MBTs in addressing QoL deficits in NF patients. Databases were reviewed between the date of inception and June 2020, using search terms: neurofibromatosis, schwannomatosis, psychotherapy, mind-body, mindfulness, meditation, resiliency, and behavioral therapy. Quality appraisal was assessed using the Cochrane Risk of Bias Tools and National Institutes of Health Study Quality Assessment Tools. We conducted a meta-analysis of mean differences and reported aggregate effect estimates with 95% confidence intervals. A total of 10 articles, including randomized-controlled trials and pre-post studies, were identified. Meta-analytic results of randomized-controlled trial data from six citations demonstrated MBTs were associated with improved physical (MD = 13.63, 95%CI 6.95-20.30, P < .0001, I2 = 24%), psychological (MD = 14.11, 95%CI 6.44-21.78, P = .0003, I2 = 38%), social (MD = 9.63, 95%CI 2.93-16.33, P = .005, I2 = 0%), and environmental QoL (MD = 14.14, 95%CI 8.28-20.00, P < .00001. I2 = 0%) in NF patients. These associations were maintained at 6-months follow-up for physical, psychological, and environmental QoL (P < .05). Our findings suggest that NF-adapted MBT strategies are associated with improving QoL in diverse NF populations, including NF2 patients experiencing deafness and youth NF patients. Providers and caregivers for NF should be aware of the potential benefits of MBT in chronic NF management.

Achalasia Quality of Life (ASQ) and Eckardt scores are two patient-reported instruments widely used to assess symptom severity in achalasia patients. ASQ is validated and reliable. Although Eckardt is commonly used, it has not been rigorously assessed for validity or reliability. This study aims to evaluate (i) the accuracy of Eckardt and ASQ for assessing improvement post-treatment (predictive validity), (ii) accuracy of Eckardt and ASQ for assessing improvement post-treatment with pneumatic dilatation (PD) versus surgical myotomy (predictive validity), and (iii) convergent validity of Eckardt and ASQ tools. Patients with achalasia treated between 2011 and 2018 were eligible. Both instruments were administered by telephone. Treatment failure was determined by the review of medical records by two clinicians. The predictive ability of ASQ and Eckardt instruments in identifying treatment successes and failures was determined using receiver operating characteristics analysis and summarized as area under the curve (AUC). A total of 106 patients met inclusion criteria with 39 PD, 51 Heller myotomy, and 16 per-oral endoscopic myotomy. A review of medical records and esophageal testing revealed 13 failures (12%). AUC for Eckardt was 0.96 (95% confidence interval [CI] 0.87-0.99] and ASQ 0.97 (95% CI 0.92-0.99). The Eckardt cutoff 4, and ASQ, cutoff 15, were 94% and 87% accurate in identifying treatment successes versus failures, respectively. The correlation coefficient between the two tools was 0.85. In conclusions, (i) ASQ and Eckardt scores are valid and reliable tools to assess symptom severity in achalasia patients, (ii) both instruments accurately classify treatment successes versus failures, and (iii) the choice of tool should be informed by the physicians and patients' values and preferences and repeat physiologic testing may be reserved for treatment failures with either instrument and patients classified, as treatment successes may be spared routine physiologic testing in the long term.

BACKGROUND: Lumboperitoneal shunt is a known procedure for communicating hydrocephalus. Being an extracranial procedure, it can also be utilized in normal-sized ventricles.

OBJECTIVE: To report our experience of lumboperitoneal shunt done with a minimal follow-up of 12 months with an emphasis on patient selection, technique, and complication avoidance.

METHODS: This was a retrospective analysis of patients who underwent LP shunt during October 2014-October 2019 at the authors' institute. Inclusion criteria were patients with communicating hydrocephalus due to tubercular meningitis, normal pressure hydrocephalus, idiopathic intracranial hypertension, and postoperative refractory cerebrospinal fluid leaks. Data were collected for demographics, Glasgow coma scale and Glasgow outcome scale, vision, gait, memory, urinary incontinence, failed attempts, and complications.

RESULTS: A total of 426 patients underwent the LP shunt procedure. The commonest indication was tubercular meningitis followed by idiopathic intracranial hypertension and normal pressure hydrocephalus. Age ranged from 16 to 72 years. There were 255 male and 171 female patients. The mean follow-up was 41 ± 8 months. Overall, 301 patients (70.6%) had neurological improvement. Shunt-related complications occurred in 112 (26.29%) patients, of which shunt block was the commonest. Other complications were infection in 17 (3.9%) patients and extrusion in four (0.9%) patients. Transient postural headache was seen in 46 (10.7%) patients, which gradually improved.

CONCLUSION: Lumboperitoneal shunt was found to be a safe and effective treatment in appropriately selected communicating hydrocephalus patients. A meticulous technique reduces the complication rate.

INTRODUCTION: The physical examination is a core competency in the training of pre-clerkship medical students. It is important to certify proficiency in the physical examination before students start their clinical rotations. Many institutions use home grown assessment tools for this purpose; however, there currently are no validated rubrics designed to assess the performance a head to toe physical examination by a pre-clerkship medical student. The goal of this study is to assess the reliability (inter-rater and intra-rater) of our institutionally developed rubric.

METHODS: Clinical faculty with various levels of teaching experience watched videos of students doing a head to toe physical examination and scored the students using our assessment rubric. These scores were evaluated for intra-rater and inter-rater reliability.

RESULTS: A total of 15 student videos were reviewed by five faculty members with varying levels of teaching experience. The degree of inter-rater agreement (between raters) for single and average measure was excellent and the degree of intra-rater agreement (same rater twice) for single and average measure was excellent.

DISCUSSION: We conclude that our institutionally developed physical examination assessment rubric is a reliable means to certify proficiency in the physical examination before students start their clinical clerkships.

BACKGROUND: Endoscopic third ventriculostomy (ETV) has become a proven modality for treating obstructive and selected cases of communicating hydrocephalus.

OBJECTIVE: This review aims to summarize the indications, preoperative workup, surgical technique, results, postoperative care, complications, advantages, and limitations of an ETV.

MATERIALS AND METHODS: A thorough review of PubMed and Google Scholar was performed. This review is based on the relevant articles and authors' experience.

RESULTS: ETV is indicated in obstructive hydrocephalus and selected cases of communicating hydrocephalus. Studying preoperative imaging is critical, and a detailed assessment of interthalamic adhesions, the thickness of floor, arteries or membranes below the third ventricle floor, and prepontine cistern width is essential. Blunt perforation in a thin floor, while bipolar cautery at low settings and water jet dissection are preferred in a thick floor. The appearance of stoma pulsations and intraoperative ventriculostomography reassure stoma and basal cistern patency. The intraoperative decision for shunt, external ventricular drainage, or Ommaya reservoir can be taken. Magnetic resonance ventriculography and cine phase-contrast magnetic resonance imaging can determine stoma patency. Good postoperative care with repeated cerebrospinal fluid drainage enhances outcomes in selected cases. Though the complications mostly occur in an early postoperative phase, delayed lethal ones may happen. Watching live surgeries, assisting expert surgeons, and practicing on cadavers and models can shorten the learning curve.

CONCLUSION: ETV is an excellent technique for managing obstructive and selected cases of communicating hydrocephalus. Good case selection, methodical technique, and proper training under experts are vital.

OBJECTIVE(S): To determine the association of pharmacist medication counseling with medication adherence, 30-day hospital readmission, and mortality.

METHODS: The initial search identified 21,590 citations. After applying the inclusion and exclusion criteria, 62 randomized controlled trials (RCTs) (49 for the meta-analysis) were included in the final analysis. Data were pooled using a random-effects model.

RESULTS: The participants in most of the studies were older patients with chronic diseases who, therefore, were taking many drugs. The overall methodologic quality of evidence ranged from low to very low. Pharmacist medication counseling versus no such counseling was associated with a statistically significant 30% increase in relative risk (RR) for medication adherence, a 24% RR reduction in 30-day hospital readmission (number needed to treat = 4.2), and a 30% RR reduction in emergency department visits. RR reductions for primary care visits and mortality were not statistically significant.

CONCLUSION: The evidence supports pharmacist medication counseling to increase medication adherence and to reduce 30-day hospital readmissions and emergency department visits. However, higher-quality RCT studies are needed to confirm or refute these findings.

OBJECTIVE: To describe the association between unmet rehabilitation needs and life satisfaction 5 years after traumatic brain injury (TBI).

DESIGN: Prospective observational cohort.

SETTING: Five Veterans Affairs (VA) Polytrauma Rehabilitation Centers.

PARTICIPANTS: VA TBI Model Systems participants (N=301); 95% male; 77% white; average age, 39±14y).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Satisfaction With Life Scale (SWLS).

RESULTS: Average SWLS score was 22±8. Univariable analyses demonstrated several statistically significant predictors of life satisfaction, including employment status, participation, psychiatric symptom severity, past year mental health treatment, and total number of unmet rehabilitation needs (all P<.05). Multivariable analyses revealed that depression and participation were each associated with life satisfaction. An ad hoc mediation model suggested that unmet rehabilitation needs total was indirectly related to life satisfaction. Total unmet rehabilitation needs ranged from 0-21 (mean, 2.0±3.4). Correlational analyses showed that 14 of the 21 unmet rehabilitation needs were associated with life satisfaction.

CONCLUSIONS: Findings support the need for rehabilitation engagement in later stages of TBI recovery. Ongoing assessment of and intervention for unmet rehabilitation needs in the chronic phase of recovery have the potential to mitigate decline in life satisfaction.

BACKGROUND AND AIMS: Procedural standardization in endoscopic ultrasound-guided liver biopsy (EUS-LB) is necessary to obtain core biopsy specimens for accurate diagnosis. The objective of this study was to directly compare the diagnostic yield of 2 EUS-LB fine-needle biopsy (FNB) systems in vivo.

METHODS: In this prospective, single-center study, 108 adult patients undergoing EUS-LB over a 1-year period were included. Each EUS-LB consisted of an EGD, followed by EUS-guided biopsy of the left lobe of the liver sequentially using 2 different 19-gauge needles: the fork-tip (SharkCore) and Franseen (Acquire) FNB systems. Specimens were then reviewed by a GI histopathologist to determine diagnostic adequacy as well as the number of complete portal tracts, specimen length, and degree of fragmentation.

RESULTS: In 79.4% of cases, the fork-tip FNB system yielded a final diagnosis compared with 97.2% of the Franseen FNB specimens (P < .001). The mean number of complete portal tracts in the fork-tip FNB samples was 7.07 compared with 9.59 in the Franseen FNB samples (P < .001). The mean specimen length was 13.86 mm for the fork-tip FNB and 15.81 mm for the Franseen FNB (P = .004). Cores were intact in 47.6% of the fork-tip FNB samples and in 75.2% of the Franseen FNB samples (P = .004).

CONCLUSIONS: In EUS-LB, we found that the 19-gauge Franseen FNB system resulted in a statistically significant increase in diagnostic adequacy compared with biopsy using the fork-tip FNB system.