11†Convergence insufficiency: are we making a difference in patients' lives or is it a waste of time!

Convergence insufficiency (CI) is a common condition that can impair visual performance and comfort during close visual work. This prospective study evaluated the effectiveness of interventions on clinical outcomes and quality-of-life using the adult strabismus quality-of-life questionnaire (AS20) in patients with CI.Data was extracted from a database collected at first consultation from 2015 to 2022. Demographics, interventions and outcomes of 84 patients with CI (mean age 47.0±24.9 years) were analysed.Orthoptic exercises were prescribed to 56% of patients, 32% received prisms, 15% received no treatment, with 3 discharged on the same day. At latest follow-up review, 22.6% were recommended to continue exercises, 28.6% had prisms, 1 underwent bimedial resection and 2 had botox. The median follow-up was 5.5(5.0-55)months, 88.1% were discharged with 29.8% following failure to attend and 9.5% deceased. Near-point of convergence (NPC) improved from a median of 15(6-50)cm to 10(6-30)cm. The median AS20 score at presentation were 100(30-100) and 47.5(0-100), and post-intervention were 100(80-100) and 77.5(12.5-97.5) for psychosocial and functional components, respectively.At the latest follow-up, the attendance failure rate was higher for exercises (36%) than for prisms (15%). Improvement was noted in NPC (33%) and mean AS20 scores was 9% higher psychosocially and 32.8% functionally, highlighting the benefits of intervention on patients' quality-of-life.This cohort provides valuable insights into the clinical management of CI, as evidenced by improvements in NPC and AS20 scores. However, the study also found that long-term compliance with treatment is intrinsically challenging, emphasising the importance of disease education.

A validated preoperative risk prediction tool for extended inpatient length of stay following anatomic or reverse total shoulder arthroplasty.

BACKGROUND: Recent work has shown inpatient length of stay (LOS) following shoulder arthroplasty to hold the second strongest association with overall cost (after implant cost itself). In particular, a preoperative understanding for the patients at risk of extended inpatient stays (≥3 days) can allow for counseling, optimization, and anticipating postoperative adverse events. METHODS: A multicenter retrospective review was performed of 5410 anatomic (52%) and reverse (48%) total shoulder arthroplasties done at 2 large, tertiary referral health systems. The primary outcome was extended inpatient LOS of at least 3 days, and over 40 preoperative sociodemographic and comorbidity factors were tested for their predictive ability in a multivariable logistic regression model based on the patient cohort from institution 1 (derivation, N = 1773). External validation was performed using the patient cohort from institution 2 (validation, N = 3637), including area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: A total of 814 patients, including 318 patients (18%) in the derivation cohort and 496 patients (14%) in the validation cohort, experienced an extended inpatient LOS of at least 3 days. Four hundred forty-five (55%) were discharged to a skilled nursing or rehabilitation facility. Following parameter selection, a multivariable logistic regression model based on the derivation cohort (institution 1) demonstrated excellent preliminary accuracy (AUC: 0.826), with minimal decrease in accuracy under external validation when tested against the patients from institution 2 (AUC: 0.816). The predictive model was composed of only preoperative factors, in descending predictive importance as follows: age, marital status, fracture case, ASA (American Society of Anesthesiologists) score, paralysis, electrolyte disorder, body mass index, gender, neurologic disease, coagulation deficiency, diabetes, chronic pulmonary disease, peripheral vascular disease, alcohol dependence, psychoses, smoking status, and revision case. CONCLUSION: A freely-available, preoperative online clinical decision tool for extended inpatient LOS (≥ 3 days) after shoulder arthroplasty reaches excellent predictive accuracy under external validation. As a result, this tool merits consideration for clinical implementation, as many risk factors are potentially modifiable as part of a preoperative optimization strategy.

Assessment of conditions leading to lost-to-follow-up of head and neck cancer patients.

PURPOSE: Head and neck cancer patients require close clinical follow up to monitor and address sequelae of treatment and for adequate cancer surveillance. The goal of this study is to determine barriers and risk factors for head and neck cancer patients who are lost-to-follow-up. MATERIALS AND METHODS: A chart review of the Head and Neck Cancer Registry was performed to identify patients who were lost-to-follow-up (LTF). LTF was defined as missing two consecutive appointments as recommended by their oncologic surgeon. Those identified as LTF were contacted via email and phone to complete a 16-question survey addressing possible barriers to follow up. RESULTS: Of the 353 patients reviewed, 53 met the criteria for LTF (15%). Forty-eight participants were contacted, and 23 surveys were completed (48%). Of the 23 patients that responded, 22% reported difficulty scheduling an appointment, 30% had transportation barriers, 22% had personal or work obligations that prevented follow up, 17% did not follow up because they "felt better," and 39% were following up with an otolaryngologist or oncologist closer to home. Only three participants (13%) were aware of the recommended 5-year surveillance period. CONCLUSION: Head and neck cancer patients have a variety of reasons they are lost to follow-up. Understanding these barriers is critical to creating a patient-centered model that balances both clinical surveillance needs and reasonable expectations for patients. Improvements can be made to educate patients on the recommended length of follow-up and its importance.

Guided Mindfulness Meditation for Pain Control After Septorhinoplasty: A Randomized-Controlled Pilot Study.

Background: Mindfulness meditation has been shown to alleviate pain and may be an appealing adjunctive pain management option. Objective: To compare measures of pain, mindfulness, and opioid usage, and collect evaluative feedback among patients undergoing septorhinoplasty with and without guided meditation. Methods: Patients undergoing septorhinoplasty were randomized to online-guided meditation postoperative days 0-3 versus standard care; all received the same pain medications. Primary outcome measures included pain intensity, opioid consumption, mindfulness scores, and evaluative feedback. Results: Twenty-one patients received guided meditation and 24 received standard care. No significant difference in opioid consumption or pain scores was seen with the exception of higher opioid use in patients with intranasal splints in the standard care group. Twenty out of 21 patients provided evaluative feedback; all recommended mindfulness meditation to friends undergoing nasal surgery, 90% reported it was beneficial, 85% believed it eased pain/discomfort, and 80% believed it aided with sleep. Conclusion: Although no objective difference was found in opioid consumption or pain scores, most patients reported that guided mindfulness meditation was beneficial to their recovery following septorhinoplasty.

Appropriate patient selection for outpatient shoulder arthroplasty: a risk prediction tool.

BACKGROUND: The transition from inpatient to outpatient shoulder arthroplasty critically depends on appropriate patient selection, both to ensure safety and to counsel patients preoperatively regarding individualized risk. Cost and patient demand for same-day discharge have encouraged this transition, and a validated predictive tool may help decrease surgeon liability for complications and help select patients appropriate for same-day discharge. We hypothesized that an accurate predictive model could be created for short inpatient length of stay (discharge at least by postoperative day 1), potentially serving as a useful proxy for identifying patients appropriate for true outpatient shoulder arthroplasty. METHODS: A multicenter cohort of 5410 shoulder arthroplasties (2805 anatomic and 2605 reverse shoulder arthroplasties) from 2 geographically diverse, high-volume health systems was reviewed. Short inpatient stay was the primary outcome, defined as discharge on either postoperative day 0 or 1, and 49 patient outcomes and factors including the Elixhauser Comorbidity Index, sociodemographic factors, and intraoperative parameters were examined as candidate predictors for a short stay. Factors surviving parameter selection were incorporated into a multivariable logistic regression model, which underwent internal validation using 10,000 bootstrapped samples. RESULTS: In total, 2238 patients (41.4%) were discharged at least by postoperative day 1, with no difference in rates of 90-day readmission (3.5% vs. 3.3%, P = .774) between cohorts with a short length of stay and an extended length of stay (discharge after postoperative day 1). A multivariable logistic regression model demonstrated high accuracy (area under the receiver operator characteristic curve, 0.762) for discharge by postoperative day 1 and was composed of 13 variables: surgery duration, age, sex, electrolyte disorder, marital status, American Society of Anesthesiologists score, paralysis, diabetes, neurologic disease, peripheral vascular disease, pulmonary circulation disease, cardiac arrhythmia, and coagulation deficiency. The percentage cutoff maximizing sensitivity and specificity was calculated to be 47%. Internal validation showed minimal loss of accuracy after bias correction for overfitting, and the predictive model was incorporated into a freely available online tool to facilitate easy clinical use. CONCLUSIONS: A risk prediction tool for short inpatient length of stay after shoulder arthroplasty reaches very good accuracy despite requiring only 13 variables and was derived from an underlying database with broad geographic diversity in the largest institutional shoulder arthroplasty cohort published to date. Short inpatient length of stay may serve as a proxy for identifying patients appropriate for same-day discharge, although perioperative care decisions should always be made on an individualized and holistic basis.

A validated preoperative risk prediction tool for discharge to skilled nursing or rehabilitation facility following anatomic or reverse shoulder arthroplasty.

BACKGROUND: As bundled payment models continue to spread, understanding the primary drivers of cost excess helps providers avoid penalties and ensure equal health care access. Recent work has shown discharge to rehabilitation and skilled nursing facilities (SNFs) to be a primary cost driver in total joint arthroplasty, and an accurate preoperative risk calculator for shoulder arthroplasty would not only help counsel patients in clinic during shared decision-making conversations but also identify high-risk individuals who may benefit from preoperative optimization and discharge planning. METHODS: Anatomic and reverse total shoulder arthroplasty cohorts from 2 geographically diverse, high-volume centers were reviewed, including 1773 cases from institution 1 (56% anatomic) and 3637 from institution 2 (50% anatomic). The predictive ability of a variety of candidate variables for discharge to SNF/rehabilitation was tested, including case type, sociodemographic factors, and the 30 Elixhauser comorbidities. Variables surviving parameter selection were incorporated into a multivariable logistic regression model built from institution 1's cohort, with accuracy then validated using institution 2's cohort. RESULTS: A total of 485 (9%) shoulder arthroplasties overall were discharged to post-acute care (anatomic: 6%, reverse: 14%, P < .0001), and these patients had significantly higher rates of unplanned 90-day readmission (5% vs. 3%, P = .0492). Cases performed for preoperative fracture were more likely to require post-acute care (13% vs. 3%, P < .0001), whereas revision cases were not (10% vs. 10%, P = .8015). A multivariable logistic regression model derived from the institution 1 cohort demonstrated excellent preliminary accuracy (area under the receiver operating characteristic curve [AUC]: 0.87), requiring only 11 preoperative variables (in order of importance): age, marital status, fracture, neurologic disease, paralysis, American Society of Anesthesiologists physical status, gender, electrolyte disorder, chronic pulmonary disease, diabetes, and coagulation deficiency. This model performed exceptionally well during external validation using the institution 2 cohort (AUC: 0.84), and to facilitate convenient use was incorporated into a freely available, online prediction tool. A model built using the combined cohort demonstrated even higher accuracy (AUC: 0.89). CONCLUSIONS: This validated preoperative clinical decision tool reaches excellent predictive accuracy for discharge to SNF/rehabilitation following shoulder arthroplasty, providing a vital tool for both patient counseling and preoperative discharge planning. Further, model parameters should form the basis for reimbursement legislation adjusting for patient comorbidities, ensuring no disparities in access arise for at-risk populations.

Cardiovascular findings on chest computed tomography associated with COVID-19 adverse clinical outcomes.

STUDY OBJECTIVE: Chest computed tomography (chest CT) is routinely obtained to assess disease severity in COVID-19. While pulmonary findings are well-described in COVID-19, the implications of cardiovascular findings are less well understood. We evaluated the impact of cardiovascular findings on chest CT on the adverse composite outcome (ACO) of hospitalized COVID-19 patients. SETTING/PARTICIPANTS: 245 COVID-19 patients who underwent chest CT at Rush University Health System were included. DESIGN: Cardiovascular findings, including coronary artery calcification (CAC), aortic calcification, signs of right ventricular strain [right ventricular to left ventricular diameter ratio, pulmonary artery to aorta diameter ratio, interventricular septal position, and inferior vena cava (IVC) reflux], were measured by trained physicians. INTERVENTIONS/MAIN OUTCOME MEASURES: These findings, along with pulmonary findings, were analyzed using univariable logistic analysis to determine the risk of ACO defined as intensive care admission, need for non-invasive positive pressure ventilation, intubation, in-hospital and 60-day mortality. Secondary endpoints included individual components of the ACO. RESULTS: Aortic calcification was independently associated with an increased risk of the ACO (odds ratio 1.86, 95% confidence interval (1.11-3.17) p < 0.05). Aortic calcification, CAC, abnormal septal position, or IVC reflux of contrast were all significantly associated with 60-day mortality and major adverse cardiovascular events. IVC reflux was associated with in-hospital mortality (p = 0.005). CONCLUSION: Incidental cardiovascular findings on chest CT are clinically important imaging markers in COVID-19. It is important to ascertain and routinely report cardiovascular findings on CT imaging of COVID-19 patients as they have potential to identify high risk patients.

The prognostic value of cardiac troponin for 60 day mortality and major adverse events in COVID-19 patients.

BACKGROUND: The variability of coronavirus disease 2019 (COVID-19) illness severity has puzzled clinicians and has sparked efforts to better predict who would benefit from rapid intervention. One promising biomarker for in-hospital morbidity and mortality is cardiac troponin (cTn). METHODS: A retrospective study of 1331 adult patients with COVID-19 admitted to the Rush University System in Illinois, USA was performed. Patients without cTn measurement during their admission or a history of end stage renal disease or stage 5 chronic kidney disease were excluded. Using logistic regression adjusted for baseline characteristics, pre-existing comorbidities, and other laboratory markers of inflammation, cTn was assessed as a predictor of 60-day mortality and severe COVID-19 infection, consisting of a composite of 60-day mortality, need for intensive care unit, or requiring non-invasive positive pressure ventilation or intubation. RESULTS: A total of 772 patients met inclusion criteria. Of these, 69 (8.9%) had mild cTn elevation (> 1 to < 2x upper limit of normal (ULN)) and 46 (6.0%) had severe cTn elevation (≥ 2x ULN). Regardless of baseline characteristics, comorbidities, and initial c-reactive protein, lactate dehydrogenase, and ferritin, when compared to the normal cTn group, mild cTn elevation and severe cTn elevation were predictors of severe COVID-19 infection (adjusted OR [aOR] aOR 3.00 [CI: 1.51 - 6.29], P < 0.01; aOR 9.96 [CI: 2.75 - 64.23], P < 0.01, respectively); severe cTn elevation was a predictor of in-hospital mortality (aOR 2.42 [CI: 1.10 - 5.21], P < 0.05) and 60-day mortality (aOR 2.45 [CI: 1.13 - 5.25], P < 0.05). CONCLUSION: In our cohort, both mild and severe initial cTn elevation were predictors of severe COVID-19 infection, while only severe cTn elevation was predictive of 60-day mortality. First cTn value on hospitalization is a valuable longitudinal prognosticator for COVID-19 disease severity and mortality.

The ratio of morning cortisol to CRP prospectively predicts first-onset depression in at-risk adolescents.

RATIONALE: Early-onset adolescent depression is related to poor prognosis and a range of psychiatric and medical comorbidities later in life, making the identification of a priori risk factors for depression highly important. Increasingly, dysregulated levels of immune and neuroendocrine markers, such as C-reactive protein (CRP) and cortisol, have been demonstrated as both precursors to and consequences of depression. However, longitudinal research with adolescent populations is limited and demonstrates mixed immuno-endocrine-depression links. OBJECTIVE: This study explored the putative bidirectional relationship between salivary measures of cortisol (Cort) and CRP, including the novel Cort:CRP ratio and depression. METHODS: Participants from the randomized control trial 'Sleep and Education: learning New Skills Early' (SENSE) Study were 122 adolescents at risk for depression (73 females) aged 12-16 years (M = 12.71 years, SD = 1.01 years) assessed at baseline (T1), post-intervention (T2), and a two-year follow-up (T3). RESULTS: Logistic regression results demonstrated that adolescents with higher T1 Cort:CRPmorn ratio levels were two-fold more likely to develop a first-onset depressive disorder from T2 to T3 as compared to adolescents with lower Cort:CRPmorn ratio levels, ß = 0.73, t (36) = 2.15, p = .04, OR = 2.08. This effect was not moderated by treatment condition (ß = -1.38, t (13) = -1.33, p = .20) and did not change when controlling for known risk factors for depression, including sex, age, body-mass index, socio-economic status, T1 anxiety disorder, nor T1 sleep disturbance, anxiety, or depressive symptoms (ß = 0.91, t (31) = 2.14, p = .04). CONCLUSION: Results highlight potential immuno-endocrine dysregulation as an underlying risk factor for adolescent first-onset depression, and may inform the development of targeted, preventative biobehavioral treatment strategies for youth depression.

Impact of pre-existing heart failure on 60-day outcomes in patients hospitalized with COVID-19.

BACKGROUND: In the coronavirus disease 2019 (COVID-19) global pandemic, patients with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. However, the relationship between COVID-19 and heart failure (HF) is unclear, specifically whether HF is an independent risk factor for severe infection or if other accompanying comorbidities are responsible for the increased risk. METHODS: This is a retrospective analysis of 1331 adult patients diagnosed with COVID-19 infection between March and June 2020 admitted at Rush University System for Health (RUSH) in metropolitan Chicago, Illinois, USA. Patients with history of HF were identified by International Classification of Disease, Tenth Revision (ICD-10) code assignments extracted from the electronic medical record. Propensity score matching was utilized to control for the numerous confounders, and univariable logistic regression was performed to assess the relationship between HF and 60-day morbidity and mortality outcomes. RESULTS: The propensity score matched cohort consisted of 188 patients in both the HF and no HF groups. HF patients did not have lower 60-day mortality (OR 0.81; p = 0.43) compared to patients without HF. However, those with HF were more likely to require readmission within 60 days (OR 2.88; p < 0.001) and sustain myocardial injury defined as troponin elevation within 60 days (OR 3.14; p < 0.05). CONCLUSIONS: This study highlights the complex network of confounders present between HF and COVID-19. When balanced for these numerous factors, those with HF appear to be at no higher risk of 60-day mortality from COVID-19 but are at increased risk for morbidity.

Enhancing wound healing dressing development through interdisciplinary collaboration.

The process of wound healing includes four phases: Hemostasis, inflammation, proliferation, and remodeling. Many wound dressings and technologies have been developed to enhance the body's ability to close wounds and restore the function of damaged tissues. Several advancements in wound healing technology have resulted from innovative experiments by individual scientists or physicians working independently. The interplay between the medical and scientific research fields is vital to translating new discoveries in the lab to treatments at the bedside. Tracing the history of wound dressing development reveals that there is an opportunity for deeper collaboration between multiple disciplines to accelerate the advancement of novel wound healing technologies. In this review, we explore the different types of wound dressings and biomaterials used to treat wounds, and we investigate the role of multidisciplinary collaboration in the development of various wound management technologies to illustrate the benefit of direct collaboration between physicians and scientists.

Sex Differences in COVID-19 Hospitalization and Mortality.

Background: To investigate sex differences in coronavirus disease 2019 (COVID-19) outcomes in a large Illinois-based cohort. Methods: A multicenter retrospective cohort study compared males versus females with COVID-19 infections from March 1, 2020, to June 21, 2020, in the Rush University System. We analyzed sex differences in rates of hospitalization, intensive care unit (ICU) admission, vasopressor use, endotracheal intubation, and death in this cohort. A multivariable model correcting for age and sum of comorbidities was used to explore associations between sex and COVID-19-related outcomes. Results: There were 8108 positive COVID-19 patients-4300 (53.0%) females and 3808 (47.0%) males. Males had higher rates of hospitalization (19% vs. 13%; p < 0.001), ICU transfer (8% vs. 4%; p < 0.001), vasopressor support (4% vs. 2%; p < 0.001), and endotracheal intubation (5% vs. 2%; p < 0.001). Of those who died, 92 were males and 64 were females (2% vs. 1%; p = 0.003). A multivariable model correcting for age and sum of comorbidities showed a significant association between male sex and mortality in the total cohort (odds ratio, 1.96; 95% confidence interval, 1.34-2.90; p = 0.001). Conclusion: Male sex was independently associated with death, hospitalization, ICU admissions, and need for vasopressors or endotracheal intubation, after correction for important covariates.

Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function: The Genetic Epidemiology of COPD Study.

BACKGROUND: Pulmonary endothelial damage has been shown to precede the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema. RESEARCH QUESTION: Is intraparenchymal vascular pruning associated with longitudinal progression of emphysema on CT imaging or decline in lung function over 5 years? STUDY DESIGN AND METHODS: The Genetic Epidemiology of COPD Study enrolled ever smokers with and without COPD from 2008 through 2011. The percentage of emphysema-like lung, or "percent emphysema," was assessed at baseline and after 5 years on noncontrast CT imaging as the percentage of lung voxels < -950 Hounsfield units. An automated CT imaging-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are postbronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (< 5 mm2 cross-sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking, and COPD, with emphysema models also adjusting for CT imaging scanner and lung function models adjusting for clinical center and baseline percent emphysema. RESULTS: At baseline, the 4,227 participants were 60 ± 9 years of age, 50% were women, 28% were Black, 47% were current smokers, and 41% had COPD. Median percent emphysema was 2.1 (interquartile range, 0.6-6.3) and progressed 0.24 percentage points/y (95% CI, 0.22-0.26 percentage points/y) over 5.6 years. Mean FEV1 to FVC ratio was 68.5 ± 14.2% and declined 0.26%/y (95% CI, -0.30 to -0.23%/y). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/y per 1-SD increase in arterial pruning; 95% CI, 0.09-0.16 percentage points/y), including after adjusting for baseline percent emphysema and FEV1. Arterial pruning also was associated with a faster decline in FEV1 to FVC ratio (-0.04%/y per 1-SD increase in arterial pruning; 95% CI, -0.008 to -0.001%/y). INTERPRETATION: Pulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV1 to FVC ratio over 5 years in ever smokers, suggesting that pulmonary vascular differences may be relevant in disease progression. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study.

BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. METHODS/DESIGN: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. DISCUSSION: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. TRIAL REGISTRATION: Netherlands Trial Register: NL6281/NTR6455 . Registered 18 May 2017, https://www.trialregister.nl/trial/6281.

Dynamic gut microbiome changes following regional intestinal lymphatic obstruction in primates.

The pathogenesis of inflammatory bowel disease (IBD) has been linked with lymphostasis, but whether and how lymphatic obstruction might disturb the intestinal microbiome in the setting of Crohn's Disease (CD) is currently unknown. We employed a new model of CD in African Green monkeys, termed 'ATLAS' (African green monkey truncation of lymphatics with obstruction and sclerosis), to evaluate how gut lymphatic obstruction alters the intestinal microbiome at 7, 21 and 61 days. Remarkable changes in several microbial sub- groupings within the gut microbiome were observed at 7 days post-ATLAS compared to controls including increased abundance of Prevotellaceae and Bacteroidetes-Prevotella-Porphyromonas (BPP), which may contribute to disease activity in this model of gut injury. To the best of our knowledge, these findings represent the first report linking lymphatic structural/gut functional changes with alterations in the gut microbiome as they may relate to the pathophysiology of CD.

Salivary C-reactive protein among at-risk adolescents: A methods investigation of out of range immunoassay data.

Inflammatory markers including C-Reactive Protein (CRP) are increasingly used within research and clinical settings. Yet, varying methodologies for cleaning immunoassay data with out of range (OOR) samples may alter characteristic levels of CRP, thereby obscuring interpretation and reliability. This study investigated the influence of eight immunoassay OOR data treatment techniques on salivary CRP (sCRP) samples from at-risk adolescents. Participants from the 'Sleep and Education: learning New Skills Early' (SENSE) Study were 86 adolescents at-risk for depression (50 female), aged 14.29 years (SD = 1.04). ANOVA results showed no statistically significant differences in average morning (F(7, 590) = 1.24, p = .28) and evening (F(7, 599)=1.29, p = .25) values produced by each OOR data cleaning technique. However, varying techniques produced differences in the magnitude of Pearson's correlations between consecutive saliva samples (r's between 0.27-0.78), and influenced the significance of a sCRP diurnal pattern; two techniques produced statistically higher morning than evening sCRP levels (t(85) = 2.70, p = .01 and t(85) = 2.67, p = .01), whereas six techniques failed to find statistical differences between morning and evening sCRP levels (p's >.05). Varying techniques also produced statistically divergent associations between sCRP and age and depressive symptoms. Results from this study provide evidence for the temporal stability of sCRP among adolescents, show winsorization as an effective OOR data management technique, and highlight the influence of methodological decisions in cleaning salivary biomarker data and the need for consistency within the field.

Correction to: Neurological Symptoms in Hypophosphatasia.

Due to a typesetting error the title of the article was published wrongly.

Neurological symptoms in Hypophosphatasia.

Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options. INTRODUCTION: Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP. METHODS: A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms. RESULTS: Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%. CONCLUSIONS: The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.

Balancing the benefits and harms of thyroid cancer surveillance in survivors of Childhood, adolescent and young adult cancer: Recommendations from the international Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium.

Radiation exposure to the thyroid gland during treatment of childhood, adolescent and young adult cancer (CAYAC) may cause differentiated thyroid cancer (DTC). Surveillance recommendations for DTC vary considerably, causing uncertainty about optimum screening practices. The International Late Effects of Childhood Cancer Guideline Harmonization Group, in collaboration with the PanCareSurFup Consortium, developed consensus recommendations for thyroid cancer surveillance in CAYAC survivors. These recommendations were developed by an international multidisciplinary panel that included 33 experts in relevant medical specialties who used a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. Of the two available surveillance strategies, thyroid ultrasound and neck palpation, neither was shown to be superior. Consequently, a decision aid was formulated to guide the health care provider in counseling the survivor. The recommendations highlight the need for shared decision making regarding whether to undergo surveillance for DTC and in the choice of surveillance modality.