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PURPOSE Intraocular lens (IOL) power calculation in eyes with keratoconus typically results in hyperopic postoperative refractive error. The purpose of this study was to investigate the visual and refractive outcomes in patients with keratoconus having cataract surgery with a toric IOL and compare IOL power calculation accuracy of conventional formulas and keratoconus-specific formulas. SETTING Ein-Tal Eye Center, Tel-Aviv, Israel. DESIGN Retrospective case-series study. METHODS Postoperative visual acuity and manifest refraction were examined. The error in predicted refraction and IOL power calculation accuracy within a range of 0.50 to 2.00 diopters (D) were compared between different IOL calculating formulas. RESULTS 32 eyes with keratoconus were included. Visual acuity improved in all cases, and subjective astigmatism decreased from -2.95 ± 2.10 D to -0.95 ± 0.80 D (P < .001). The mean absolute errors were as follows: Barrett True-K formula for keratoconus with measured or predicted posterior corneal power, 0.34 D; Barrett Universal II formula, 0.64 D; Kane formula, 0.69 D; Kane formula for keratoconus, 0.49 D; SRK/T formula, 0.56 D; Haigis formula, 0.72 D; Holladay 1 formula, 0.71 D, and Hoffer Q formula, 0.87 D. Barrett True-K formula with measured posterior corneal power, SRK/T formula, and Kane formula for keratoconus resulted in a prediction error within ±0.50 D of 87.5%, 59.4%, and 53.1%, respectively. CONCLUSIONS Cataract removal with a toric IOL significantly improves visual acuity and decreases astigmatism in keratoconic eyes with a topographic central relatively regular astigmatic component. Keratoconus-specific formulas resulted in lower mean error in predicted refraction compared with conventional calculating formulas. Using the posterior corneal power within the Barrett True-K formula for keratoconus improved IOL power prediction accuracy.

Introduction Controlling insulin-treated diabetes is challenging in low-resource settings where only Neutral Protamine Hagedorn (NPH), regular (R) and premixed insulin formulations are available, self-monitoring of blood glucose (SMBG) supplies are scarce and food insecurity is common. We examined the impact of a treatment protocol that includes sliding scale-based 70/30 insulin adjustments in Haiti. Methods Thirty young patients aged 11–28 years with diabetes treated with premixed 70/30 insulin twice daily were included in the study. The participants performed one or two daily self-monitoring of blood glucose (SMBG) tests and attended our diabetes clinic monthly. They were randomized to two treatment groups, with one group remaining on the 70/30 insulin formulation (group 70 [G70]) and the other group switching to self-mixed NPH + R (group NR [GNR]). Sliding scales for insulin correction doses and meal insulin doses were designed based on the total daily insulin dose (TDD), carbohydrate ratio and insulin sensitivity factor. SMBG tests and insulin were administered before the morning and evening meals. The frequency of visits to the diabetes clinic was increased to biweekly during a 14-week follow-up. Results Fifteen patients of each group were included in the analysis. Baseline characteristics, increase in total daily dose and number of missed SMBG tests and skipped meals at 14 weeks did not differ between the two groups. Hemoglobin A1c (HbA1c) decreased from 9.5% (interquartile range [IQR] 8.8, 10.5) (80.3 mmol/mol) to 8.0% (IQR 7.1%, 9.0%) (63.9 mmol/mol) in G70 (p = 0.01), and from 10.6% (IQR 8.1,% 13.1)% (92.4 mmol/mol) to 9.0% (IQR 7.6%, 9.6%) (74.9 mmol/mol) in GNR (p = 0.10), with no significant between-group difference in reductions (p = 0.12). No serious acute complications were reported. Stopping the use of sliding scales and resuming monthly visits increased HbA1c to values not significantly different from baseline in both groups after 15 weeks. Conclusion The use of sliding scales adjusted for missed SMBG tests and skipped meals, and frequent clinic visits that focus on patient self-management education significantly improved glycemic control in the patients with youth-onset diabetes in our study treated with premixed 70/30 human insulin in a low-resource setting.

Aims Differentiating exudative from transudative effusions is clinically important and is currently performed via biochemical analysis of invasively obtained samples using Light’s criteria. Diagnostic performance is however limited. Biochemical composition can be measured with T1 mapping using cardiovascular magnetic resonance (CMR) and hence may offer diagnostic utility for assessment of effusions. Methods and results A phantom consisting of serially diluted human albumin solutions (25–200 g/L) was constructed and scanned at 1.5 T to derive the relationship between fluid T1 values and fluid albumin concentration. Native T1 values of pleural and pericardial effusions from 86 patients undergoing clinical CMR studies retrospectively analysed at four tertiary centres. Effusions were classified using Light’s criteria where biochemical data was available (n = 55) or clinically in decompensated heart failure patients with presumed transudative effusions (n = 31). Fluid T1 and protein values were inversely correlated both in the phantom (r = −0.992) and clinical samples (r = −0.663, P Conclusion Native T1 values of effusions measured using CMR correlate well with protein concentrations and may be helpful for discriminating between transudates and exudates. This may help focus the requirement for invasive diagnostic sampling, avoiding unnecessary intervention in patients with unequivocal transudative effusions.

Orthostatic intolerance (OI) following pediatric concussion is not well understood. Assessing the prevalence of concussion-related OI and how it compares to non-concussion-related OI will improve care for patients suffering with these symptoms. OBJECTIVE: We set out to describe concussion-related OI in adolescence, with particular emphasis on time to recovery and differences from non-concussion-related OI (including male vs. female prevalence). Retrospective chart reviews were completed on post-concussion patients endorsing symptoms of OI. The patients' sex, sport history, previous concussions, time since injury, and recovery time were analyzed and compared between males and females as well as against general OI statistics. Thirty-nine pediatric patients, representing 8.7% of all new patients referred to a specialized concussion clinic over a 13-month interval, were included in the chart review. Mean age of onset was 15.0 ± 2.5 years and 18 (46%) were males. The median times from evaluation to symptom resolution were 120 days. Of 18 patients who completed head-up tilt table testing, 17 (94%) had orthostatic tachycardic response (>40 bpm heart rate increment). Post-concussive OI differs from other orthostatic intolerance etiologies, lacking a strong female predominance and exhibiting a shorter time course to recovery compared to other etiologies of OI (but longer recovery time compared to concussion patients in general). Clinical orthostatic vital signs may not be sensitive for diagnosing orthostatic intolerance in athletes, likely due to higher vagal tone and more efficient skeletal muscle pump.

Heart failure (HF) can be considered a disease of older people. It is a leading cause of hospitalisation and is associated with high rates of morbidity and mortality in the over-65s. In 2012, an editorial in this journal detailed the latest HF research and guidelines, calling for greater integration of geriatricians in HF care. This current article reflects upon what has been achieved in this field in recent years, highlighting some future challenges and promising areas. It is written from the perspective of one such integrated team and explores the new role of cardiogeriatrician, working in a multidisciplinary team to deliver and improve care to increasingly complex, older, frail patients with multiple comorbidities who present with primary cardiology problems, especially decompensated HF. Geriatric liaison has improved the care of frail patients in orthopaedics, cancer services, stroke, acute medicine and numerous community settings. We propose that this vital role should now be extended to cardiology teams in general and to HF in particular.

Background and purpose Balance disorders and dizziness are common in people with multiple sclerosis (MS), suggesting dysfunction of the vestibular system. Evaluating how people with MS perform on objective clinical vestibular tools will help broaden understanding of vestibular function in MS. This cross-sectional study's goal was to complete a robust battery of vestibular-ocular reflex (VOR), dynamic visual acuity (DVA), subjective visual vertical (SVV), and cervical and ocular vestibular-evoked myogenic potential (c/oVEMP) tests in people with and without MS. Methods Forty people with relapsing-remitting MS (Expanded Disability Status Scale [EDSS] ≤6.5) and 20 controls completed the vestibular testing battery. Results were compared between groups and correlations with EDSS scores were calculated. Results People with MS were less able to visually cancel their VOR and showed a larger variance in response on SVV. EDSS significantly correlated with VOR cancellation, SVV variance, and DVA lines lost; linear regression showed that VOR cancellation and SVV variance significantly predicted EDSS. Discussion and conclusion Vestibular functions requiring central integration of vestibular information, but not reflexive vestibular functions like VEMP, were impaired in people with MS and correlated with EDSS, suggesting that clinical evaluation of functions requiring central integration best evaluates MS-related vestibular dysfunction. Measures assessing central vestibular integration and not vestibular reflexes may be more sensitive to detecting vestibular deficits in people with mild to moderate MS.Video Abstract available for more insight from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A344).

Aims Despite medical therapy for heart failure (HF) having proven benefits of improving quality of life and survival, many patients remain under‐treated. This may be due to a combination of under‐prescription by medical professionals and poor adherence from patients. In HF, as with many other chronic diseases, adherence to medication can deteriorate over time particularly when symptoms are well controlled. Therefore, detecting and addressing non‐adherence has a crucial role in the management of HF. Significant flaws and inaccuracies exist in the methods currently used to assess adherence such as patient reporting, pill counts, and pharmacy fill records. We aim to use high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS) to detect metabolites of HF medications in the urine samples of chronic HF patients. Methods and results Urine samples were collected from 35 patients in a specialist HF clinic. Patients were included if they had an ejection fraction

Objectives Bangladesh has limited information regarding incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) in young people. The objective of this study was to measure minimum incidence of T1D and T2D, and record other types of new-onset diabetes in children and adolescents Methods Retrospective study using clinical records from Diabetic Association of Bangladesh clinics. Cases were classified by clinical evaluation. Results 725 cases were diagnosed. 482 (66.5%) had T1D, 205 (28.3%) T2D, 14 (1.9%) fibrocalculous pancreatic diabetes, and 24 (3.3%) other types. Male:female ratios for T1D/T2D were 1:1.6 (p Conclusions T1D was most common, but T2D, FCPD and other forms also occur. T2D incidence increased during the study period.

Introduction There are almost a million people with heart failure (HF) in the UK; the incidence increases sharply with age. Older adults receive less evidence-based therapy with few trials specifically examining therapeutic efficacy in older age groups representative of a contemporary UK HF population. Concern that efficacy is less in older adults may underlie under-prescription. With important recent advances in HF therapy, we reviewed the contemporary evidence base for any signal of different efficacy in older adults. Methods We reviewed recent RCTs of medical therapy for heart failure alongside meta-analyses updated with recent therapies including Angiotensin-Neprilysin inhibitors and SGLT2 inhibitors. For those trials in which effect size was presented for age subgroups we compared the effect size. Results Of 68 randomised controlled trials, 10 presented effect sizes for different age groups. The median average cut-off between younger and older age groups was 66 years (IQR 65 to 72.5 years) and the highest cut-off used was 75 years. The median hazard ratio was 0.77 (IQR 0.67 to 0.80) for the younger age group and 0.76 (IQR 0.73 to 0.88) for the older age group. In 8 of the 10 trials, the effect size in the oldest age group was statistically significant on its own including Sacubitril-Valsartan and Dapagliflozin. Conclusion When considering the medical therapeutic armamentarium for heart failure as a totality, there is no evidence it is any less effective in older adults than younger adults. The recent Zannad et al cross-trial analysis supported this showing significant additional life years in the patients over 80 years on HF therapy. Whilst there may be practical and frailty-related reasons for not prescribing life-prolonging therapy, the proportional survival benefits of these medications is similar in older adults. This should be utilised where practically possible and discussed with patients when making an informed choice.

OBJECTIVE The main objective of this study was to assess whether objective vestibular, oculomotor, and balance functions were impaired in children with a current diagnosis of concussion with vestibular and/or ocular symptoms. SETTING Data were collected in a vestibular/ocular clinical laboratory. Patient participants were recruited from a concussion clinic in a children's hospital. PARTICIPANTS Thirty-three children aged 8 to 17 years with a current diagnosis of concussion and vestibular and/or ocular symptoms and 30 children without concussion. DESIGN Cross-sectional single-visit study. MAIN OUTCOME MEASURES Eye-tracking rotary chair oculomotor and vestibular measures, vestibular evoked potentials, and static posturography. RESULTS There were no statistically significant differences on any clinical measure between children with concussion and children without concussion. Younger children without concussion performed significantly worse on several rotary chair and balance measures compared with older children without concussion. CONCLUSIONS No vestibular, oculomotor, or balance measures were significantly different between children with concussion and children without concussion, suggesting these measures may not be useful in the evaluation of a child with concussion and vestibular and/or oculomotor symptoms. Future research should investigate age effects and other vestibular and oculomotor tests to identify objective findings that better relate to vestibular and/or ocular symptoms in children with concussion.

Background Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. Methods and results One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). Conclusions During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Aims Patients with cardiovascular disease appear particularly susceptible to severe COVID‐19 disease, but the impact of COVID‐19 infection on patients with heart failure (HF) is not known. This study aimed to quantify the impact of COVID‐19 infection on mortality in hospitalized patients known to have HF. Methods and results We undertook a retrospective analysis of all patients admitted with a pre‐existing diagnosis of HF between 1 March and 6 May 2020 to our unit. We assessed the impact of concomitant COVID‐19 infection on in‐hospital mortality, incidence of acute kidney injury, and myocardial injury. One hundred and thirty‐four HF patients were hospitalized, 40 (29.9%) with concomitant COVID‐19 infection. Those with COVID‐19 infection had a significantly increased in‐hospital mortality {50.0% vs. 10.6%; relative risk [RR] 4.70 [95% confidence interval (CI) 2.42–9.12], P

To characterize the relationship between objective tympanogram values and patient-reported symptoms and associations with common comorbid conditions.Cross-sectional study with prospective data collection.Tertiary medical center.Patients undergoing routine audiometric evaluation between October 2018 and June 2019 were included. Participants with temporomandibular joint dysfunction, inner ear hydrops, and similar conditions were excluded. Symptoms were assessed with the 7-item Eustachian Tube Dysfunction Questionnaire. Demographics and medical comorbidities were recorded from the medical record. Analysis of tympanometric peak pressure (TPP), demographics, and comorbidities was performed to determine associations with clinically significant eustachian tube dysfunction (ETD) symptoms.A total of 250 patients were included with similar demographics: 101 (40.4%) in the asymptomatic group and 149 (59.6%) in the symptomatic group. The median (interquartile range) TPP was -10 (20) daPa and -25 (100) daPa in the asymptomatic and symptomatic groups, respectively. A diagnosis of rhinitis was more likely to be associated with significant ETD symptoms (adjusted odds ratio, 2.61; 95% CI, 1.23-5.63). A subgroup analysis revealed that symptomatic patients with normal TPP values were negatively skewed as compared with asymptomatic patients. This symptomatic group had a higher prevalence of rhinitis and chronic rhinosinusitis than the asymptomatic group.Patients with symptoms of ETD may have a TPP within a range typically considered normal per conventional standards. This suggests that the currently accepted interpretation of tympanometry findings may be insensitive for the diagnosis of less severe cases of ETD.

Introduction Successfully maintaining (managing) paid employment can be a challenge as people negotiate the cancer care pathway and survivorship. Little research explores the influence of age on this situation. The purpose of this project was to explore the role of age in managing employment for survivors from age 45 to 64 years. Method A qualitative descriptive design was conducted to explore the intersection of age and managing employment for cancer survivors. In-depth semi-structured interviews were conducted with 19 United States cancer survivors (lung, breast, colorectal). Interviews were conducted in person or by phone. Verbatim transcripts were analyzed using thematic analysis. Codes were grouped by categories, incorporated into separate topical files, and then aggregated into broader emergent themes. Findings Survivors are not just “returning” to work after treatment. They are often managing work both during and after treatment. Age may have benefits but can also provide barriers to positive survivorship and employment experiences. Fulfilling the role of employee and maintaining a worker identity was a strong driver for many participants. Again, this was potentially both a support and a barrier. It was discovered that health care providers provided little support to facilitate employment. Conclusion Age is a factor that is poorly understood but influences both health and personal aspects of the experience of managing paid employment during and after cancer treatment. Occupational therapy practitioners should acknowledge this important role in addressing cancer survivorship.

OBJECTIVE To evaluate the effectiveness of neuromodulating agents for the management of atypical facial pain and primary facial neuralgias. METHODS We searched MEDLINE, Embase, CINAHL, and ClinicalTrials.gov databases for original research articles that examine the effectiveness and adverse reactions of pharmacologic therapy for the treatment of trigeminal neuralgia and atypical facial pain. Studies that included surgical interventions for atypical facial pain or facial pain secondary to other causes were excluded. Meta-analysis was conducted for reductions in symptom scores and adverse effects. RESULTS Of 3,409 articles screened, 73 full-text articles were included, consisting of 45 observational studies and 29 randomized controlled trials. Twenty-four different pharmacological agents were assessed; carbamazepine was the most frequently studied while botulinum toxin A demonstrated the highest consistency in reduction of symptom scores. Pooled estimate of three randomized controlled trials revealed that patients with trigeminal neuralgia who received botulinum toxin A had higher odds (odds ratio 7.46; 95% CI 3.53-15.78) of achieving a ≥50% reduction in visual analogue scale scores compared to controls. Pooled estimate of 15 observational studies showed that three-fourths of patients with trigeminal neuralgia who received carbamazepine experienced clinically significant pain reduction (prevalence proportion 0.75; 95% CI 0.66-0.83). CONCLUSIONS Patients receiving botulinum toxin A for trigeminal neuralgia had higher odds of achieving ≥50% reduction in pain scores. A significant proportion of patients with trigeminal neuralgia experienced positive response to carbamazepine. There was moderate evidence for amitriptyline in patients with atypical facial pain. Standardization of outcome reporting would facilitate future quantitative comparisons of therapeutic effectiveness. Laryngoscope, 131:1235-1253, 2021.

Background Young people with type 1 diabetes in low-and-middle income countries face many challenges in accessing care, with various essential supplies needed for survival and long-term health. Aim To study insulin delivery devices and glycated haemoglobin (HbA1c) testing. Methods A survey was conducted in 2019 of leading diabetes centres in 41 countries supported by the Life for a Child Program. The survey covered numerous aspects concerning availability and costs at all levels of the health system, local usage patterns and attitudes, obstacles, and other aspects. Results Thirty-seven countries returned the survey (90.2% response rate). Key findings included: Syringe use was most common (83.1%), followed by insulin pens (16.7%) and pumps (0.2%). 48.6% of public health systems did not provide syringes, even with a co-payment. Use of suboptimal syringe/needle combinations was common. Needles were generally reused in almost all countries (94.3%, n = 35). Aside from donated supplies, there was variable access to HbA1c testing within public health facilities, and, when available, patients often had to cover the cost. Provision was further compromised by numerous problems including stock-outs, and challenges with understanding the test, equipment maintenance, and refrigeration. Conclusion Large gaps exist for adequate access to appropriate insulin delivery devices and HbA1c testing. Public health systems in low-and-middle income countries should increase affordable provision. There are also needs for specific health professional training and diabetes education; elimination of customs duties and taxes; development of inexpensive, robust HbA1c testing methods that do not require refrigeration of testing supplies; differential pricing schemes; and other solutions.

Self-monitoring of blood glucose (SMBG) is an essential component of type 1 diabetes (T1D) management and typically involves several daily tests. However, due to high cost, SMBG supplies are often unavailable in low-resource settings. This study assessed whether the use of two SMBG tests per day improves glycemic control, measured by a change in HbA1c, in youth with T1D followed at the DREAM Trust (DT) in Nagpur, India. Single-site prospective cohort study of youth ≤ 23 years of age with T1D ≥ 1 year followed by DT, who were provided with SMBG meters and two test strips per day. Patients received education regarding SMBG and how to respond to blood glucose values and trends. They were followed every 3 months with HbA1c and questionnaires for a total of 21 months. HbA1c declined significantly from 10.2 ± 2.5% (88 ± 4 mmol/mol) at baseline to 9.5 ± 2.4% (80 ± 3 mmol/mol) at 21 months (p

Objective Data are needed to demonstrate that providing an "intermediate" level of type 1 diabetes (T1D) care is cost-effective compared to "minimal" care in less-resourced countries. We studied these care scenarios in six countries. Methods We modeled the complications/costs/mortality/healthy life years (HLYs) associated with "intermediate" care including two blood glucose tests/day (mean HbA1c 9.0% [75 mmol/mol]) in three lower-gross domestic product (GDP) countries (Mali, Tanzania, Pakistan), or three tests/day (mean HbA1c 8.5% [69 mmol/mol]) in three higher-GDP countries (Bolivia, Sri Lanka, Azerbaijan); and compared findings to "minimal" care (mean HbA1c 12.5% [113 mmol/mol]). A discrete time Markov illness-death model with age and calendar-year-dependent transition probabilities was developed, with inputs of 30 years of complications and Standardized Mortality Rate data from the youth cohort in the Pittsburgh Epidemiology of Diabetes Complications Study, background mortality, and costs determined from international and local prices. Results Cumulative 30 years incidences of complications were much lower for "intermediate care" than "minimal care", for example, for renal failure incidence was 68.1% (HbA1c 12.5%) compared to 3.9% (9%) and 2.4% (8.5%). For Mali, Tanzania, Pakistan, Bolivia, Sri Lanka, and Azerbaijan, 30 years survival was 50.1%/52.7%/76.7%/72.5%/82.8%/89.2% for "intermediate" and 8.5%/10.1%/39.4%/25.8%/45.5%/62.1% for "minimal" care, respectively. The cost of a HLY gained as a % GDP/capita was 141.1%/110.0%/52.3%/41.8%/17.0%/15.6%, respectively. Conclusions Marked reductions in complications rates and mortality are achievable with "intermediate" T1D care achieving mean clinic HbA1c of 8.5% to 9% (69-75 mmol/mol). This is also "very cost-effective" in four of six countries according to the WHO "Fair Choices" approach which costs HLYs gained against GDP/capita.

Background: In the early phases of the 2019 novel coronavirus (COVID-19) pandemic, health system leaders faced the urgent task of translating the unknown into forecasting models for hospital capacity. Our study objective was to demonstrate the application of a practical, locally informed model to estimate the hospital capacity needed even though the community COVID-19 caseload was unknown. Methods: We developed a susceptible-infected-recovered (SIR) model that was adopted from the University of Pennsylvania COVID-19 Hospital Impact Model for Epidemics and employed at 8 hospitals within Ochsner Health, the largest integrated delivery system in Louisiana, between March 16 and April 15, 2020. Intensive care unit (ICU) admissions of cases in the New Orleans area were used to estimate the community case load when testing was delayed. Results: Initially, the observed ICU census trended near R0=2.0, whereas the ventilator census trended between R0=2.0 and 3.0. After implementing social distancing, both the ICU and ventilator capacity trended toward R0=1.3, while non-ICU medical/surgical beds trended toward R0=1.5. The model accurately predicted peak ICU (n=250) and hospital bed (n=487) usage by April 6, 2020. In response to model trends, Ochsner added 130 ICU beds across its hospitals by opening a new ICU and converting operating rooms and parts of emergency departments to ICU beds. Conclusion: When disease testing is limited or results are delayed, ICU admissions data can inform SIR models of the rate of spread of COVID-19 in a community. Our model used various R0 plots to demonstrate an array of scenarios to guide planning for hospital and political leaders.

Background Quantitative cardiovascular magnetic resonance (CMR) T1 and T2 mapping are used to detect diffuse disease such as myocardial fibrosis or edema. However, post gadolinium contrast mapping often lacks visual contrast needed for assessment of focal scar. On the other hand, late gadolinium enhancement (LGE) CMR which nulls the normal myocardium has excellent contrast between focal scar and normal myocardium but has poor ability to detect global disease. The objective of this work is to provide a calculated bright-blood (BB) and dark-blood (DB) LGE based on simultaneous acquisition of T1 and T2 maps, so that both diffuse and focal disease may be assessed within a single multi-parametric acquisition. Methods The prototype saturation recovery-based SASHA T1 mapping may be modified to jointly calculate T1 and T2 maps (known as multi-parametric SASHA) by acquiring additional saturation recovery (SR) images with both SR and T2 preparations. The synthetic BB phase sensitive inversion recovery (PSIR) LGE may be calculated from the post-contrast T1, and the DB PSIR LGE may be calculated from the post-contrast joint T1 and T2 maps. Multi-parametric SASHA maps were acquired free-breathing (45 heartbeats). Protocols were designed to use the same spatial resolution and achieve similar signal-to-noise ratio (SNR) as conventional motion corrected (MOCO) PSIR. The calculated BB and DB LGE were compared with separate free breathing (FB) BB and DB MOCO PSIR acquisitions requiring 16 and 32 heart beats, respectively. One slice with myocardial infarction (MI) was acquired with all protocols within 4 min. Results Multiparametric T1 and T2 maps and calculated BB and DB PSIR LGE images were acquired for patients with subendocardial chronic MI (n = 10), acute MI (n = 3), and myocarditis (n = 1). The contrast-to-noise (CNR) between scar (MI and myocarditis) and remote was 26.6 ± 7.7 and 20.2 ± 7.4 for BB and DB PSIR LGE, and 31.3 ± 10.6 and 21.8 ± 7.6 for calculated BB and DB PSIR LGE, respectively. The CNR between scar and the left ventricualr blood pool was 5.2 ± 6.5 and 29.7 ± 9.4 for conventional BB and DB PSIR LGE, and 6.5 ± 6.0 and 38.6 ± 11.6 for calculated BB and DB PSIR LGE, respectively. Conclusions A single free-breathing acquisition using multi-parametric SASHA provides T1 and T2 maps and calculated BB and DB PSIR LGE images for comprehensive tissue characterization.

Background The Covid-19 pandemic necessitated rapid adoption of remote monitoring across cardiovascular patient cohorts. Most patients with cardiac implantable electronic devices (CIEDs) are now able to be remotely monitored using either scheduled, patient- or threshold-triggered transmissions. The validated “Triage Heart Failure Risk Score” (Triage-HFRS) is a medical algorithm within company-specific CIEDs that can risk-stratify patients as low-, medium- or high-risk of worsening heart failure (WHF) in the next 30 days based on integrated monitoring of physiological parameters. Building on a previous proof-of-concept of the Triage-HF Plus pathway, we integrated remote data with simple 5-question telephone triage within a clinical pathway to identify WHF during the first year of the Covid-19 pandemic. Purpose Prospective evaluation of clinical remote monitoring pathway integrating Triage-HFRS with protocolised telephone triage (Triage-HF Plus pathway). Methods Prospective, real-world evaluation of clinical pathway serving a large urban region over a 12-month period, using data from April 2020 to April 2021 (initiated during the first wave of Covid-19 pandemic in the UK). From a population of 435 patients with CIEDs, 87 “high” Triage-HFRS alerts were received and patients contacted for telephone triage assessment. Screening questions were designed to identify episodes of WHF and non-HF events. Intervention was at discretion of the clinical practitioner and in line with guideline-directed practice. A consecutive sample of 115 “medium” risk scores received the same triage. Results Successful contact was made with 72 (82.8%) high-risk patients. Classification for high scoring patients confirmed on triage included isolated heart failure (18.3%), heart failure concurrent to medical problem (5.7%), alternative medical problem (10.3%), and recent hospital admission (8.0%); triage reassured absence of acute cause of high score in 40.2%. The sensitivity and specificity for detection of WHF was 87.9% (0.77–0.99) and 59.4% (0.50–0.69) respectively. Positive and negative predictive values were 40.3% and 94.0%, respectively. Overall accuracy was 66.2%. Conclusions The Triage-HF Plus pathway served as a useful remote monitoring tool for identifying patients with WHF whose care had been otherwise disrupted by the Covid-19 pandemic, allowing timely intervention and cementing the longer-term role for such models of care delivery. Crucially, in this multimorbid, high-cost population, relevant non-HF issues were also identified. The high negative predictive value further highlights the potential of proactive surveillance over conventional, periodic follow up. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Imperial Health Charity

Purpose: FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high-dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system. Experimental Design: Peripheral blood mononuclear cells (PBMC) were obtained from treatment-naïve (n = 20) and FOLFIRINOX-treated patients (n = 19) with primary PDAC tumors at the time of resection. PBMCs were characterized by 36 markers using mass cytometry by time of flight (CyTOF). Results: Compared with treatment-naïve patients, FOLFIRINOX-treated patients showed distinct immune profiles, including significantly decreased inflammatory monocytes and regulatory T cells (Treg), increased Th1 cells, and decreased Th2 cells. Notably, both monocytes and Treg expressed high levels of immune suppression-associated CD39, and the total CD39+ cell population was significantly lower in FOLFIRINOX-treated patients compared with untreated patients. Cellular alterations observed in responders to FOLFIRINOX included a significantly decreased frequency of Treg, an increased frequency of total CD8 T cells, and an increased frequency of CD27−Tbet+ effector/effector memory subsets of CD4 and CD8 T cells. Conclusions: Our study reveals that neoadjuvant chemotherapy with FOLFIRINOX enhances effector T cells and downregulates suppressor cells. These data indicate that FOLFIRINOX neoadjuvant therapy may improve immune therapy and clinical outcome in patients with PDAC.

Background. Cognitive impairment is common, but poorly managed in people with multiple sclerosis (MS). Balance has been correlated with cognition in people with MS, potentially through shared utilization of central sensory integration pathways. Objective. This study characterized the relationship between central vestibular integration and cognition in people with MS through measurement of several clinical vestibular functions requiring central sensory integration and multiple cognitive domains. Methods. Forty people with MS and 20 controls completed a battery of vestibular and cognitive examinations targeting different central vestibular integration measures and different domains of cognition, respectively. Performance on these measures was compared between people with MS and controls, and then correlational analyses were undertaken between the vestibular and cognitive measures in the MS sample. Results. People with MS performed worse than controls on all vestibular and cognitive measures. There were consistent correlations between vestibular and cognitive measures in the MS sample. Factor analysis of vestibular functions yielded a single factor hypothesized to represent central vestibular integration that demonstrated a significant relationship with a composite cognitive measure in people with MS. Discussion. Our results suggest that vestibular and cognitive dysfunction may both arise from central sensory processing pathways in people with MS. This connection could be targeted through vestibular rehabilitation techniques that improve central sensory processing and both balance and cognition in people with MS.

Supplemental Digital Content is available in the text., Background: Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom end points. Methods: One hundred sixty-four patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment before randomization. Focal disease was defined as a ≥0.03 iFR unit drop within 15 mm, rather than over a longer distance. Analyses were performed using regression modeling. Results: In the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (mean FFR and iFR, focal 0.60±0.15 and 0.65±0.24, diffuse 0.78±0.10 and 0.88±0.08, respectively, P

ObjectiveTo further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents.Research design and methodsDemographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals

Objective Imbalance and fatigue are among the most common and disabling symptoms of multiple sclerosis (MS). Vestibular rehabilitation studies demonstrate not only improvements in balance but fatigue also, suggesting a relationship between central vestibular integration and fatigue. The objective of this study was to determine whether the relationship between balance and fatigue in people with MS is seen between other measures of central vestibular integration and fatigue and to understand how central vestibular integration measures interrelate. Methods This cross-sectional study consisted of 40 people with MS (age = 27–55 years, Expanded Disability Severity Scale score = 1.0–6.5) who completed vestibular ocular reflex testing, subjective visual vertical testing, static posturography, dynamic gait, 2 self-report fatigue surveys, and a 6-Minute Walk Test to assess walking capacity/physical fatigue was completed. Spearman correlations were calculated between variables. Results Measures of central vestibular integration were significantly correlated with measures of fatigue and walking capacity and with each other. The correlations between physical fatigue and central vestibular functions were larger than self-reported fatigue correlations with central vestibular functions. Conclusion The relationship between balance and fatigue extends to other measures requiring central vestibular integration, suggesting a deficit in central vestibular processing in people with MS. These measures may compliment balance assessment as outcome measures for vestibular rehabilitation in people with MS. Fatigue measures should be included in vestibular rehabilitation as secondary outcomes. Impact Correlations between central vestibular integration and fatigue in people with MS suggest that future studies of vestibular rehabilitation should include fatigue, as a secondary outcome measure as vestibular function and fatigue may share similar a similar etiology in people with MS.

The prevalence of diabetes in many South Asian countries is above 10%, but type 1 diabetes (T1D) is not fully characterized due to a lack of widespread access to islet autoantibody (IA) testing. Determining the prevalence of IA positivity in new and recent onset cases of childhood diabetes in these countries will allow for improved classification of diabetes and may impact treatment. We measured IA directed against glutamic acid decarboxylase 65 (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA) and zinc transporter 8 (ZnT8A) using fluid-phase radiobinding assays from dried blood spot eluents in children with diabetes from the Republic of Maldives (n=64), Bangladesh (n=103) and Pakistan (n=54). We compared the results to youth from our large diabetes Center in Colorado (n=132). South Asian children with clinically diagnosed T1D have a lower rate of positivity for each IA when compared to youth with T1D from Colorado (p Disclosure K. Simmons: Other Relationship; Self; Provention Bio, Inc. E. M. Youngkin: None. A. Condie: None. A. Alkanani: None. K. Mcdaniel: None. L. Yu: None. G. D. Ogle: None. A. W. Michels: Stock/Shareholder; Self; IM Therapeutics. Funding National Institutes of Health (K12DK094712-08)

Funding Acknowledgements Type of funding sources: None. Background Cardiovascular magnetic resonance (CMR) is a key diagnostic investigation in acute myocarditis (1) and permits quantification of late gadolinium enhancement (LGE) and myocardial oedema. Follow-up CMR imaging is recommended to check for persistence of scar and oedema (2). Persistent late gadolinium enhancement is associated with a worse prognosis (3). It is not known whether all patients require follow-up scanning or whether the initial scan can provide useful information to identify which patients need convalescent assessment. Purpose In this study we considered whether extent of troponin elevation, extent of T2 elevation and initial late gadolinium enhancement burden predicted long-term late gadolinium enhancement at follow-up. Methods Index and follow-up CMR scans of consecutive patients presenting with a diagnosis of acute myocarditis between 2019 and 2020 across three hospitals were included. Inclusion criteria were: follow-up scan within 9 months of the index scan, CMR with LGE imaging and T2 mapping, and acute myocarditis being the primary diagnosis of the index scan. Myocardial T2 values in the area affected by myocarditis and percentage of LV myocardium showing late enhancement (using a threshold-based full height half width or manual region of interest strategy) were extracted. Results 20 patients were included in the study (80% male; mean age 37 years). Mean interval between the index and follow-up scan was 4.1 months. Peak troponin level during the acute illness was not associated with the proportion of LV myocardium affected by LGE in the index scan (R^2 Conclusions The extent of troponin elevation and initial CMR phenotype was not a good predictor of the burden of long-term late gadolinium enhancement. Although most cases showed improvement in LGE scar burden between index and follow-up imaging, neither peak troponin level during the acute episode, nor T2 values at the first CMR scan were predictive of initial or change in scar burden. Serial CMR assessment is required to identify those patients who have residual long-term scarring.

Funding Acknowledgements Type of funding sources: None. Background Acute myocardial damage is common in hospitalized patients with severe COVID-19, with evidence of myocardial infarction and myocarditis demonstrated on cardiovascular magnetic resonance (CMR). Post-mortem studies have also implicated microvascular thrombosis, which may cause persistent microvascular disease. Purpose To determine the long-term coronary sequelae in recovered COVID-19 using multiparametric CMR including state-of-the-art inline quantitative stress myocardial blood flow (sMBF) mapping to assess global and regional sMBF. Methods Prospective, multicentre observational study of recovered COVID-19 patients scanned at three London CMR units. Results were compared to a propensity-matched, pre-COVID chest pain cohort (104 patients referred for perfusion CMR, with subsequently demonstrated unobstructed coronary arteries) and 27 healthy volunteers (HV). Perfusion image analysis was performed using a novel artificial intelligence approach deriving global and regional stress and rest MBF with a cut-off of >2.25mL/g/min signifying normal sMBF and Results 104 recovered, post-COVID patients (median age 62 years, 76% male; 89[87%] hospitalised, 41/89[46%] requiring ICU) underwent adenosine-stress perfusion CMR at a median 131(IQR 43-179) days from COVID-19 diagnosis. Median LVEF was 67% (IQR 60-71%; 12 (11.5%) with impaired LVEF), 51 patients (49%) had late gadolinium enhancement (LGE); 18% infarct-pattern and 33% non-ischaemic LGE. Global stress MBF in post-COVID patients was no different to age-, sex- and co-morbidities-matched controls (2.57 ± 0.77 vs. 2.40 ± 0.75 ml/g/min, p = 0.11, Figure 1), though lower than HV (3.00 ± 0.76 ml/g/min, p = 0.001). Post-COVID, multivariate predictors of low sMBF were male sex (OR 0.57, 95%CI 0.41-0.80, p = 0.001) and hypertension (OR 0.67, 95%CI 0.51-0.88, p = 0.004), but not COVID-19 disease severity (ICU admission) or presence of scar (ischemic/non-ischemic). 21/42 with reduced sMBF ( Conclusions COVID-19 survivors do not demonstrate evidence of reduced global MBF by CMR compared to risk factor matched controls. Stress perfusion CMR identifies etiology of acute myocardial damage (infarction/myocarditis) and presence of occult coronary ischemia.

Background The objective of this study was to determine the demographic and clinical features of youth supported by member associations of the Federación Mexicana de Diabetes and the Life for a Child Program (LFAC). Methods An analysis of 2017 Annual Clinical Data Sheets of 306 subjects from five Mexican centers was performed. Results Type 1 diabetes (T1D) was diagnosed in 292 subjects; 54.6% were female, with six diagnosed aged 1c (HbA1c) levels for those with duration ≥6 months were 8.7/8.4% (72/68 mmol/mol) and were higher in adolescents vs. children. Elevated body mass index SD, triglycerides (≥150 mg/dL) and non-high-density lipoprotein (HDL)-cholesterol (≥130 mg/dL) were common: 7.6%, 11.0% and 12.7% (n = 288, 218 and 180, respectively). Serum creatinine levels were normal in all tested subjects (n = 194). Conclusions Youth with diabetes in less-resourced families in Mexico are achieving reasonable glycemia. Most T1D patients use a basal bolus insulin regimen and test blood glucose several times daily. Some subjects have adverse vascular risk factor profiles. Further attention is needed to prevent chronic complications. Monogenic diabetes is very likely in some youth, and genetic testing is indicated.

BACKGROUND AND PURPOSE According to the most recent consensus statement on management of sport-related concussion (SRC), athletes with suspected SRC should receive a comprehensive neurological examination. However, which measures to include in such an examination are not defined. Our objectives were to (1) evaluate test-retest reliability and normative data on vestibular and balance tests in athletes without SRC; (2) compare athletes with and without SRC on the subtests; and (3) identify subtests for concussion testing protocols. METHODS Healthy athletes (n = 87, mean age 20.6 years; standard deviation = 1.8 years; 39 female and 48 male) and athletes with SRC (n = 28, mean age 20.7 years; standard deviation = 1.9 years; 11 female and 17 male) were tested using rotary chair, cervical vestibular-evoked myogenic potential (c-VEMP), and the Sensory Organization Test (SOT). A subset (n = 43) were tested twice. We analyzed reliability of the tests, and compared results between athletes with and without SRC. RESULTS Reliability ranged from poor to strong. There was no significant difference between athletes with and without SRC for tests of peripheral vestibular function (ie, rotary chair and c-VEMP). Athletes with SRC had significantly worse scores (P < 0.05) on vestibular-ocular reflex (VOR) cancellation gain, subjective visual vertical and horizontal variance, and all conditions of the SOT. DISCUSSION AND CONCLUSION SRC did not affect medium frequency VOR or saccular function. SRC did affect the ability to use vestibular inputs for perception of vertical and postural control, as well as ability to cancel the VOR.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A274).

Background There is a paucity of literature on contemporary aseptic revision total knee arthroplasty in patients ≤50 years. We sought to determine risk factors for failure in this population, with specific emphasis on survivorship free of (1) all-cause re-revision and (2) re-revision for instability. Methods We retrospectively reviewed 135 nononcologic revision total knee arthroplasties (TKAs) performed from 2000 to 2012 in patients ≤50 years. Mean age was 43 years, and mean body mass index was 31 kg/m2. Mean follow-up was 7 years. There were 99 (73%) first-time revisions, and 36 (27%) with prior revisions. Indications for revision included instability (47%), aseptic loosening (29%), and arthrofibrosis (9%). Multivariate Cox regression analysis was used to identify risk factors. Results Survivorship free of all-cause re-revision was 66% at 10 years, with multiply revised TKAs (hazard ratio [HR] = 2.6, P = .008) having the poorest survivorship. Forty-three (32%) TKAs underwent re-revision including 10 (7%) for periprosthetic joint infection. Survivorship free of re-revision for instability was 88% at 10 years, with revision for instability (HR = 19, P = .03), male gender (HR = 3.0, P = .05), and multiply revised TKAs (HR = 3.5, P = .03) having poorer survival. Of the 64 TKAs revised for instability, 24 (38%) underwent re-revision, including 14 (22%) for recurrent instability. Conclusion Patients ≤50 years undergoing contemporary aseptic revision TKA had a 1 in 3 risk of re-revision. Patients specifically revised for instability or had prior TKA revisions had the highest risk of re-revision at 10 years. Level of Evidence IV.

Background The usage of immunosuppressive medications (ISMs), and specifically disease modifying anti-rheumatic drugs (DMARDs), in a wide range of internal medicine subspecialties has increased the risk of hepatitis B virus re-activation (HBVr). We assessed the understanding of HBVr using a Canada-wide survey. Methods An electronic survey was sent to 521 members of the Canadian Rheumatology Association (CRA). The questions focused on the knowledge of screening, monitoring and management of patients with chronic or past infection with HBV in the setting of starting ISMs.The results were compared to the American Gastroenterology Association (AGA) guidelines. Results A total of142 respondents were included in the analysis (response rate = 27.3%). Over 50% of the respondents would order unnecessary tests such as anti-HBs or anti-HBc for monitoring a HBsAg positive patient on an ISMs. There were 43% of responders who answered incorrectly to starting anti-viral prophylaxis for HBsAg positive patients on synthetic DMARDs (sDMARDs). Conclusion There are some knowledge gaps amongst physicians managing rheumatology patients with chronic or past infection with HBV in the setting of ISMs. The AGA guidelines were summarized and incorporated into a user-friendly guide.

SIGNIFICANCE. Oculomotor tests in concussion commonly show impairment in smooth pursuit and saccadic function. Honing in on the systems likely to be affected by concussion will streamline use of oculomotor function as a supplemental diagnostic and prognostic tool, as well as improve our understanding of the pathophysiology of concussion. PURPOSE. This study investigates oculomotor function between concussed and healthy collegiate athletes, as well as determines measurement test-retest reliability of those tools. METHODS. Eighty-seven healthy athletes were recruited from a US Division 1 sports university and completed a 30-minute vestibular ocular testing battery in an enclosed rotary chair system equipped with 100Hz eye-tracking goggles. Forty-three individuals completed the battery twice. Twenty-eight individuals with a current diagnosis of concussion also completed the battery. All participants were ages 18–24. Bivariate statistical tests examined differences in scores across groups, and intraclass coefficients were computed to test reliability. RESULTS. Concussed individuals had significantly longer saccadic, visual, and dual-task reaction times and reduced saccadic accuracy. There was no difference in optokinetic reflex gain, but few concussed individuals tolerated the task. Reaction time latencies and optokinetic gain show moderate test-retest reliability. Smooth pursuit tasks and saccadic accuracies showed poor test-retest reliability. CONCLUSIONS. Saccadic latency was the most sensitive oculomotor function to change following concussion and was reliable over time. Saccadic accuracy was significantly lower in the concussed group but had poor retest-reliability. Optokinetic gain may warrant more investigation due to its high test-retest reliability and symptom provocation in concussion, despite not showing a significant difference between groups.

Published information on diabetes in Pakistani youth is limited. We aimed to investigate the demographic, clinical, and biochemical features, and HLA-DRB1 alleles in new cases of diabetes affecting children and adolescents

Background: There is a paucity of literature on epidemiology of type 1 diabetes (T1D) in Sri Lanka. This study reviews the characteristics of patients registered in an insulin bank programme in Sri Lanka. Materials and Methods: Data were collected and analysed from records of all 672 patients diagnosed with T1D registered in the insulin bank with dates of the diagnosis ranging from 1971 to 2016. Results: Of the 672 patients, age at the diagnosis ranged from the day of birth to 44 years. The majority of patients, 526 (78.3%) were diagnosed before 15 years of age, with 7 (1.0%) cases diagnosed before 6 months. Females accounted for 56.8% of cases. The ethnic distribution of T1D in the study population was consistent with the overall population. Conclusion: This study gives some insight into the epidemiological features of T1D in young people in Sri Lanka. The peak age at the diagnosis is similar to studies in the western countries. This study also demonstrated a slight female predominance and a small but significant number of cases diagnosed in infancy. Further epidemiological and clinical research would help guide organisation of care and distribution of resources in the management of T1D in Sri Lanka.

ObjectivesThe clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK.MethodsWe retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention.ResultsMean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, pConclusionHypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

BACKGROUND Eritrea has no data on type 1 diabetes incidence in children and youth; therefore, a study was undertaken to determine this in persons aged

Tumor-associated macrophages (TAMs) are among the main contributors to immune suppression in the tumor microenvironment, however, TAM depletion strategies have yielded little clinical benefit. Here, we discuss the concept that TAMs are also key regulators of anti-PD(L)-1-mediated CD8 T cell-dependent immunity. Emerging data suggest that expression of the chemokine CXCL9 by TAMs regulates the recruitment and positioning of CXCR3-expressing stem-like CD8 T (Tstem) cells that underlie clinical responses to anti-PD(L)-1 treatment. We evaluate clinical and mechanistic studies that establish relationships between CXCL9-expressing TAMs, Tstem and antitumor immunity. Therapies that enhance anti-PD(L)-1 response rates must consider TAM CXCL9 expression. In this perspective, we discuss opportunities to enhance the frequency and function of CXCL9 expressing TAMs and draw on comparative analyzes from infectious disease models to highlight potential functions of these cells beyond Tstem recruitment.

Background Coronavirus disease 2019 (COVID-19) myocarditis is emerging as a component of the hyperactive inflammatory response secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Isolated gastrointestinal symptoms are uncommon presenting features in adults with COVID-19 myocarditis. The availability of antibody testing is a valuable addition to the confirmation of COVID-19, when repeated reverse transcriptase–polymerase chain reaction of nasopharyngeal swabs are negative. Case summary A young healthcare worker presented with dizziness and pre-syncope, 4 weeks after his original symptoms that included fever, lethargy, and diarrhoea. Despite 2 weeks of isolation, followed by a quiescent spell, his symptoms had returned. Shortly after, he presented in cardiogenic shock (left ventricular ejection fraction 25%), that required vasopressor support, at the height of the COVID-19 pandemic. Cardiac magnetic resonance imaging suggested florid myocarditis. Three nasopharyngeal swabs (Days 1, 3, and 5) were negative for SARS-CoV-2, but subsequent serology (Day 13) confirmed the presence of SARS-CoV-2 IgG. Treatment with intravenous immunoglobulin and glucocorticoids led to full recovery. Discussion Our case study highlights the significance of the use of the available serological assays for diagnosis of patients presenting late with SARS-CoV-2. Importantly, it supports further research in the use of immunomodulatory drugs for the hyperinflammatory microenvironment induced by COVID-19.

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

High prevalence of non-healing chronic wounds contributes to a huge healthcare burden across the world. Early treatment interventions for non-healing wounds are vital. It was previously shown that accumulation of 15% or more of senescent cells in a chronic wound edge is an indicator that the wound is unlikely to heal. However, determining the presence of senescent cells would require invasive procedures such as tissue biopsies to be taken. In this study, we found a strong correlation between decreased collagen area and presence of senescent cells in human chronic wounds i.e. venous leg ulcer (VLU), diabetic foot ulcer (DFU) and pressure ulcer (PRU). We also report that the lowest collagen levels were found in VLU patients less than 60 years of age, with a persistent wound of > 24 months. Elevated levels of senescent cells were also found in VLU of males. Second harmonic imaging of collagen at the edge of chronic wounds with a handheld multiphoton device could be used to predict the number of senescent cells, indicating if the wound is on a healing trajectory or not. Our data support the use of collagen imaging in cutaneous wound assessment for a faster and non-invasive method to predict cellular senescence and determining wound trajectory of healing. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This research is supported by the Agency for Science, Technology and Research (A*STAR) under its Industry alignment fund—Pre-Positioning Programme (IAF-PP) with grant numbers H17/01/a0/0C9 as part of the Wound Care Innovation for the Tropics (WCIT) programme, sub awards H18/01/a0/019 and H1701a0004. The Skin Research Institute of Singapore, Phase 2: SRIS@Novena. AMP is funded by Singapore’s Agency for Science, Technology & Research (A*STAR) through core funds and under the HBMS IAF-PP Project (H1701a0004) and through the National Research Foundation Singapore under its Shared Infrastructure Support grant for SingaScope—a Singapore-wide microscopy infrastructure network (NRF2017_SISFP10)”.

Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07–1.30, P = 0.11 × 10–2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78–1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

BACKGROUND Standardized diagnostic criteria for Eustachian tube (ET) dysfunction (ETD) have not been established. The purpose of this study was to characterize the relationship between ET inflammation and ETD symptoms and to determine the diagnostic performance of a quantitative score. METHODS Patients were enrolled in a rhinology clinic between October 2018 and June 2019. Patients underwent nasal endoscopy and completed the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7). Nasopharyngeal inflammation identified on endoscopy was quantified using the Endoscopic Evaluation of the Eustachian Tube (3ET) score. Tympanometry was performed as indicated. Comorbid conditions were assigned during the patient encounter. RESULTS A total of 414 patients were included in the study. Patients with clinically significant ETD symptoms (ETDQ-7 ≥2.1) had higher 3ET scores than those without symptoms. A 1-point increase in 3ET score was associated with a 1.7-fold increase in odds of clinically significant ETD symptoms (adjusted OR [aOR], 1.72; 95% CI, 1.46 to 2.05). The 3ET scores were correlated with ETDQ-7 scores (ρ = 0.54) and 22-item Sino-Nasal Outcome Test (SNOT-22) scores (ρ = 0.52). 3ET scores were not associated with tympanometric peak pressures. Patients with ETD symptoms were more likely to have laryngopharyngeal reflux (aOR, 2.71; 95% CI, 1.24 to 6.18). A 3ET score of 4 predicted symptomatic state in 80% of cases with a specificity of 97.8% and positive predictive value of 96.6%. CONCLUSION Inflammatory findings at the nasopharyngeal ET orifice are associated with clinically significant ETD symptoms. The 3ET score is specific for a symptomatic state and has potential clinical utility in the evaluation of suspected ETD. ©2021 ARSAAOA, LLC.

BACKGROUND AND OBJECTIVES:Congenital cytomegalovirus (cCMV) is the leading nongenetic cause of sensorineural hearing loss and developmental disabilities. Because there are limited data from studies of vestibular involvement in select groups of children with cCMV, the true frequency of vestibular disorders in cCMV is likely underestimated. Our objective for this study is to determine the prevalence of vestibular, gaze, and balance disorders in a cohort of children with asymptomatic cCMV.METHODS:Comprehensive vestibular, gaze, and balance assessments were performed in 40 children with asymptomatic cCMV. The function of semicircular canals of the inner ear and vestibulo-visual tract were assessed by measuring vestibulo-ocular reflex in a computer-driven motorized rotary chair; inner ear saccular function was assessed by using cervical vestibular evoked myogenic potential; gaze stability during head movement was assessed by using clinical dynamic visual acuity, and balance was assessed by using the sensory organization test and the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Test results for each variable were compared with those of a control group without cCMV and/or compared to age-matched normative published data.RESULTS:Vestibular disorders were evident in 45% of the cohort on the basis of rotary chair and cervical vestibular evoked myogenic potential testing, suggesting abnormalities in semicircular canals, the utricle and saccule of the inner ear, and vestibulo-visual tracts. Additionally, 46% of the cohort had difficulties maintaining gaze during head movement, and one-third to one-half of the cohort had difficulties maintaining balance.CONCLUSIONS:Vestibular, gaze, and balance disorders are highly prevalent in children with asymptomatic cCMV. Systematic screening for vestibular disorders will be used to determine the full clinical impact for the development of effective interventions.