Social isolation, loneliness, and inflammation: A multi-cohort investigation in early and mid-adulthood.

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N = 6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N = 881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N = 1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers.

Changes of Exercise, Screen Time, Fast Food Consumption, Alcohol, and Cigarette Smoking during the COVID-19 Pandemic among Adults in the United States.

OBJECTIVE: To investigate the impact of the COVID-19 pandemic on multiple lifestyle changes among adults in the United States (USA). METHODS: We conducted a survey, the Health, Ethnicity, and Pandemic (HEAP) Study, in October 2020 among USA adults. Participants were selected from the United States using 48 sampling strata, including age, race, ethnicity, education, and gender, and were asked to report five lifestyle behaviors (i.e., exercise time, screen time, fast-food meal consumption, alcohol drinking, and cigarette smoking) before and during the COVID-19 pandemic. The associations of sociodemographic factors with each lifestyle change were estimated using weighted multivariable logistic regression models. RESULTS: All 2709 HEAP participants were included in this study. Compared to pre-pandemic, the time spent on exercise decreased (32.06 vs. 38.65 min/day; p < 0.001) and screen time increased (6.79 vs. 5.06 h/day; p < 0.001) during the pandemic. The percentage of individuals who reported consuming fast-food meals ≥3 times/week decreased from 37.7% before the pandemic to 33.3% during the pandemic. The percentage of heavy drinkers (≥5 times/week) increased from 20.9% before the pandemic to 25.7% during the pandemic. Among smokers, heavy smoking (≥11 cigarettes/day) increased from 5.8% before the pandemic to 7.9% during the pandemic. We also identified subgroups who were more vulnerable to adverse influences from the pandemic, including racial/ethnic minority groups and young adults. CONCLUSIONS: The COVID-19 pandemic had negative impacts on multiple lifestyle behaviors among Americans. Mitigating such negative impacts of COVID-19 requires effective interventions, particularly for some vulnerable subgroups.

Population vs Individual Prediction of Poor Health From Results of Adverse Childhood Experiences Screening.

Importance: Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems. Objective: To test the predictive accuracy of ACE screening for later health problems. Design, Setting, and Participants: This study comprised 2 birth cohorts: the Environmental Risk (E-Risk) Longitudinal Twin Study observed 2232 participants born during the period from 1994 to 1995 until they were aged 18 years (2012-2014); the Dunedin Multidisciplinary Health and Development Study observed 1037 participants born during the period from 1972 to 1973 until they were aged 45 years (2017-2019). Statistical analysis was performed from May 28, 2018, to July 29, 2020. Exposures: ACEs were measured prospectively in childhood through repeated interviews and observations in both cohorts. ACEs were also measured retrospectively in the Dunedin cohort through interviews at 38 years. Main Outcomes and Measures: Health outcomes were assessed at 18 years in E-Risk and at 45 years in the Dunedin cohort. Mental health problems were assessed through clinical interviews using the Diagnostic Interview Schedule. Physical health problems were assessed through interviews, anthropometric measurements, and blood collection. Results: Of 2232 E-Risk participants, 2009 (1051 girls [52%]) were included in the analysis. Of 1037 Dunedin cohort participants, 918 (460 boys [50%]) were included in the analysis. In E-Risk, children with higher ACE scores had greater risk of later health problems (any mental health problem: relative risk, 1.14 [95% CI, 1.10-1.18] per each additional ACE; any physical health problem: relative risk, 1.09 [95% CI, 1.07-1.12] per each additional ACE). ACE scores were associated with health problems independent of other information typically available to clinicians (ie, sex, socioeconomic disadvantage, and history of health problems). However, ACE scores had poor accuracy in predicting an individual's risk of later health problems (any mental health problem: area under the receiver operating characteristic curve, 0.58 [95% CI, 0.56-0.61]; any physical health problem: area under the receiver operating characteristic curve, 0.60 [95% CI, 0.58-0.63]; chance prediction: area under the receiver operating characteristic curve, 0.50). Findings were consistent in the Dunedin cohort using both prospective and retrospective ACE measures. Conclusions and Relevance: This study suggests that, although ACE scores can forecast mean group differences in health, they have poor accuracy in predicting an individual's risk of later health problems. Therefore, targeting interventions based on ACE screening is likely to be ineffective in preventing poor health outcomes.

Optical coherence tomography: current and future clinical applications in otology.

PURPOSE OF REVIEW: This article reviews literature on the use of optical coherence tomography (OCT) in otology and provides the reader with a timely update on its current clinical and research applications. The discussion focuses on the principles of OCT, the use of the technology for the diagnosis of middle ear disease and for the delineation of in-vivo cochlear microarchitecture and function. RECENT FINDINGS: Recent advances in OCT include the measurement of structural and vibratory properties of the tympanic membrane, ossicles and inner ear in healthy and diseased states. Accurate, noninvasive diagnosis of middle ear disease, such as otosclerosis and acute otitis media using OCT, has been validated in clinical studies, whereas inner ear OCT imaging remains at the preclinical stage. The development of recent microscopic, otoscopic and endoscopic systems to address clinical and research problems is reviewed. SUMMARY: OCT is a real-time, noninvasive, nonionizing, point-of-care imaging modality capable of imaging ear structures in vivo. Although current clinical systems are mainly focused on middle ear imaging, OCT has also been shown to have the ability to identify inner ear disease, an exciting possibility that will become increasingly relevant with the advent of targeted inner ear therapies.

Platinum-Induced Ubiquitination of Phosphorylated H2AX by RING1A Is Mediated by Replication Protein A in Ovarian Cancer.

Platinum resistance is a common occurrence in high-grade serous ovarian cancer and a major cause of ovarian cancer deaths. Platinum agents form DNA cross-links, which activate nucleotide excision repair (NER), Fanconi anemia, and homologous recombination repair (HRR) pathways. Chromatin modifications occur in the vicinity of DNA damage and play an integral role in the DNA damage response (DDR). Chromatin modifiers, including polycomb repressive complex 1 (PRC1) members, and chromatin structure are frequently dysregulated in ovarian cancer and can potentially contribute to platinum resistance. However, the role of chromatin modifiers in the repair of platinum DNA damage in ovarian cancer is not well understood. We demonstrate that the PRC1 complex member RING1A mediates monoubiquitination of lysine 119 of phosphorylated H2AX (γH2AXub1) at sites of platinum DNA damage in ovarian cancer cells. After platinum treatment, our results reveal that NER and HRR both contribute to RING1A localization and γH2AX monoubiquitination. Importantly, replication protein A, involved in both NER and HRR, mediates RING1A localization to sites of damage. Furthermore, RING1A deficiency impairs the activation of the G2-M DNA damage checkpoint, reduces the ability of ovarian cancer cells to repair platinum DNA damage, and increases sensitivity to platinum. IMPLICATIONS: Elucidating the role of RING1A in the DDR to platinum agents will allow for the identification of therapeutic targets to improve the response of ovarian cancer to standard chemotherapy regimens.

Association of Adverse Experiences and Exposure to Violence in Childhood and Adolescence With Inflammatory Burden in Young People.

Importance: Childhood stress exposure is associated with inflammation as measured by C-reactive protein (CRP) and interleukin 6 (IL-6). However, findings are inconsistent and effect sizes are small. The addition of soluble urokinase plasminogen activator receptor (suPAR), a new biomarker of chronic inflammation, may improve measurement of stress-related inflammatory burden. Objectives: To assess whether exposure to adverse experiences, stress, and violence is associated with an increase in suPAR levels in young people and to test the hypothesis that measuring suPAR in addition to CRP or IL-6 levels improves the assessment of the inflammatory burden associated with early-life stress. Design, Setting, and Participants: This cohort study included 1391 participants from a 1994 to 1995 birth cohort of twins from the nationally representative Environmental Risk Longitudinal Twin Study in the United Kingdom. Participants were followed up until 18 years of age (93% retention). Plasma samples were analyzed in July 2018, and statistical analysis was performed from October 1, 2018, to May 31, 2019. Exposures: Adverse childhood experiences and childhood and adolescent experience of stress and violence exposure. Main Outcomes and Measures: Plasma CRP, IL-6, and suPAR levels at 18 years of age. Results: Among 1391 young people (mean [SD] age, 18.4 [0.36] years; 733 [52.7%] female), those who had been exposed to stressful experiences had elevated suPAR levels by 18 years of age after controlling for sex, body mass index, and smoking: 0.03-ng/mL (95% CI, 0.01-0.05 ng/mL) increase in suPAR per each additional adverse childhood experience, 0.09-ng/mL (95% CI, 0.01-0.17 ng/mL) increase in suPAR per each additional severe childhood experience of stress or violence, and 0.04-ng/mL (95% CI, -0.02 to 0.10 ng/mL) increase in suPAR per each additional severe adolescent experience of stress or violence. Individuals exposed to multiple types of violence in both childhood and adolescence had 0.26-ng/mL (95% CI, 0.07-0.45 ng/mL) higher suPAR levels compared with children who did not experience stress or violence. These stress-exposed young people were significantly more likely to have elevated suPAR levels at 18 years of age even if they did not have elevated CRP or IL-6 levels. Measuring suPAR in addition to CRP or IL-6 increased the association between stress exposure and inflammatory burden. For example, after adjusting for CRP and IL-6 levels, each additional adverse childhood experience was associated with a 0.05-mL (95% CI, 0.03-0.07 ng/mL) increase in suPAR, each additional severe childhood experience of stress or violence was associated with a 0.14-ng/mL (95% CI, 0.06-0.22 ng/mL) increase in suPAR, and each additional severe adolescent experience of stress or violence was associated with a 0.10-ng/mL (95% CI, 0.04-0.16 ng/mL) increase in suPAR. Conclusions and Relevance: The results suggest that adult inflammation is associated with childhood exposure to stress. Adding information about suPAR to traditional biomarkers of inflammation may improve the measurement of inflammatory burden associated with exposure to stress and violence.

Trauma or tumour: giant cell tumour of distal biceps tendon sheath, an unusual cause of elbow pain.

We report the case of a middle-age lady who presented following minor trauma, with dominant-sided anterior elbow pain and swelling of 6 months in duration. She was assessed clinically, and underwent investigations, which confirmed features consistent with giant cell tumour (GCT) of distal biceps tendon sheath. She underwent uneventful en-bloc excisional surgery. She did not have radiotherapy. She is now 5 years postoperatively asymptomatic, with full function, and with no signs of recurrence.

The incidence of flare reaction and short-term outcome following steroid injection in the shoulder.

BACKGROUND: To determine the short-term effects following corticosteroid injection into the shoulder. METHODS: Type-specific shoulder injection was administered, followed by physiotherapy 7 days to 10 days later. One hundred and sixteen adult patients were prospectively followed-up. The primary outcome was a visual analogue score (VAS) for pain. Scores were recorded immediately before injection, 30 minutes after, daily until day 7 and then at 6 weeks. Post injection pain was defined as an increase of 2 or more points in the VAS score after the injection. The secondary outcome was determined at 6 months as successful discharge or progression onto surgery. RESULTS: The VAS showed a significant reduction from the pre-injection score for all patients at day 1 and was maintained until week 6. Forty-one (35.3%) patients experienced post-injection pain. The mean duration of symptoms was 3.9 days. At 6 months, 81 (69.8%) patients were discharged successfully and, at a mean of 23.2 months, did not require re-referral; 29 (25%) had surgery; and six (5.2%) were referred for a spinal opinion. CONCLUSIONS: One in three patients developed delayed post-injection pain. Flare phenomenon had no determinate effect on outcome. Patients' pain response by 6 weeks is predictive of final outcome at 6 months and may help clinicians plan further treatment without delay.

Optic neuropathy secondary to eosinophilic angiocentric fibrosis.

Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory disorder with a predilection for upper respiratory tract submucosa. We report a 45-year-old man with progressive unilateral visual loss secondary to a retroorbital soft tissue mass with histological features consistent with EAF. The patient experienced marked improvement in vision after endoscopic optic nerve decompression through sphenoethmoidectomy.

Factors influencing K-wire migration in tension-band wiring of olecranon fractures.

BACKGROUND: Tension-band wiring is a popular method of internal fixation for simple olecranon fractures. Although fracture union rates and clinical outcomes are good, up to 80% of patients require removal because of prominent/symptomatic metalwork. The current literature remains unclear as to the best orientation of the longitudinal wires to minimize hardware failure. The aim of this study was to determine the surgically modifiable factors related to spontaneous wire pullout. METHODS: A retrospective review of hospital theater records over a period of 6 years was performed to identify all olecranon tension-band wire procedures. Preoperative radiographs were used to confirm and classify the fracture. Intraoperative and postoperative radiographs were analyzed for a number of wire-associated variables: wire length within the ulna, medullary/cortical position, parallelism of wires, proximal wire prominence, wire angle relative to the ulna, distance from the articular surface, fracture gap, and subsequent pullout. RESULTS: A total of 182 wires were analyzed. The mean age was 52.5 years, and the mean radiographic follow-up period was 7.3 months. Intramedullary wires had a mean pullout of 5.5 mm compared with 2.4 mm for transcortical wires (P < .0001). A multiple regression model noted 7 independent variables affecting wire pullout: age, bent wires, medullary/transcortical wire positioning, proximal prominence, ulnar shaft angle, distance from the articular surface, and articular step. CONCLUSION: To minimize postoperative pullout of wires, we suggest anatomic reduction and transcortical wire orientation, without bending, in the subchondral bone close to the articular surface.

Rating papilloedema: an evaluation of the Frisén classification in idiopathic intracranial hypertension.

The appearance of the optic disc is a key measure of disease status in idiopathic intracranial hypertension (IIH). The Frisén classification describes stages of optic disc swelling (grades 0-5). It is the only classification of papilloedema, and is used internationally in clinical and research practice. Despite this, there has been very limited evaluation of the scale. We assessed the inter-rater reproducibility and ability to discriminate optic disc changes over time using the Frisén classification compared with a system of ranking papilloedema severity in patients with IIH. Paired disc photographs (before and after treatment) were obtained from 47 patients with IIH (25 acute and 22 chronic). Six neuro-ophthalmologists blinded to patient identity, clinical information and chronology of the photographs reviewed the discs and allocated a Frisén grade and ranked the paired discs in order of papilloedema severity (disc ranking). A total of 188 optic disc photographs were reviewed. All six reviewers agreed in only three comparisons (1.6%) when using the Frisén classification, compared with 42 comparisons (45.2%) when using disc ranking. The probability of agreement between any two reviewers was 36.1% for Frisén grade and 70.0% for disc ranking. Disc ranking had significantly greater sensitivity for finding differences in degree of disc oedema, identifying a difference in 75.3% of paired photographs compared to 53.2% detected using the Frisén classification (p < 0.001). This study demonstrated the limited reproducibility and discriminative ability of the Frisén classification in identifying changes in serial optic disc photographs in IIH. Simple optic disc ranking appears to be a more sensitive and reliable tool to monitor changes in optic disc appearance. The use of disc ranking in clinical practice and research studies is recommended to monitor alterations in optic disc appearance until alternative schemes, specific to IIH, have been developed.

A randomised controlled trial of treatment for idiopathic intracranial hypertension.

The cause of idiopathic intracranial hypertension (IIH) remains unknown, and no consensus exists on how patients should be monitored and treated. Acetazolamide is a common treatment but has never been examined in a randomised controlled trial. The objectives of this pilot trial are to prospectively evaluate the use of acetazolamide, to explore various outcome measures and to inform the design of a definitive trial in IIH. Fifty patients were recruited from six centres over 23 months and randomised to receive acetazolamide (n = 25) or no acetazolamide (n = 25). Symptoms, body weight, visual function and health-related quality-of-life measures were recorded over a 12-month period. Recruited patients had typical features of mild IIH and most showed improvement, with 44% judged to have IIH in remission at the end of the trial. Difficulties with recruitment were highlighted as well as poor compliance with acetazolamide therapy (12 patients). A composite measure of IIH status was tested, and the strongest concordance with final disease status was seen with perimetry (Somers' D = 0.66) and optic disc appearance (D = 0.59). Based on the study data, a sample size of 320 would be required to demonstrate a 20% treatment effect in a substantive trial. Clinical trials in IIH require pragmatic design to involve sufficiently large numbers of patients. Future studies should incorporate weighted composite scores to reflect the relative importance of common outcome measures in IIH.

Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study.

OBJECTIVE: To observe intracranial pressure in women with idiopathic intracranial hypertension who follow a low energy diet. DESIGN: Prospective cohort study. SETTING: Outpatient department and the clinical research facility based at two separate hospitals within the United Kingdom. PARTICIPANTS: 25 women with body mass index (BMI) >25, with active (papilloedema and intracranial pressure >25 cm H(2)O), chronic (over three months) idiopathic intracranial hypertension. Women who had undergone surgery to treat idiopathic intracranial hypertension were excluded. INTERVENTION: Stage 1: no new intervention; stage 2: nutritionally complete low energy (calorie) diet (1777 kJ/day (425 kcal/day)); stage 3: follow-up period after the diet. Each stage lasted three months. MAIN OUTCOME MEASURE: The primary outcome was reduction in intracranial pressure after the diet. Secondary measures included score on headache impact test-6, papilloedema (as measured by ultrasonography of the elevation of the optic disc and diameter of the nerve sheath, together with thickness of the peripapillary retina measured by optical coherence tomography), mean deviation of Humphrey visual field, LogMAR visual acuity, and symptoms. Outcome measures were assessed at baseline and three, six, and nine months. Lumbar puncture, to quantify intracranial pressure, was measured at baseline and three and six months. RESULTS: All variables remained stable over stage 1. During stage 2, there were significant reductions in weight (mean 15.7 (SD 8.0) kg, P<0.001), intracranial pressure (mean 8.0 (SD 4.2) cm H(2)O, P<0.001), score on headache impact test (7.6 (SD 10.1), P=0.004), and papilloedema (optic disc elevation (mean 0.15 (SD 0.23) mm, P=0.002), diameter of the nerve sheath (mean 0.7 (SD 0.8) mm, P=0.004), and thickness of the peripapillary retina (mean 25.7 (SD 36.1) micro, P=0.001)). Mean deviation of the Humphrey visual field remained stable, and in only five patients, the LogMAR visual acuity improved by one line. Fewer women reported symptoms including tinnitus, diplopia, and obscurations (10 v 4, P=0.004; 7 v 0, P=0.008; and 4 v 0, P=0.025, respectively). Re-evaluation at three months after the diet showed no significant change in weight (0.21 (SD 6.8) kg), and all outcome measures were maintained. CONCLUSION: Women with idiopathic intracranial hypertension who followed a low energy diet for three months had significantly reduced intracranial pressure compared with pressure measured in the three months before the diet, as well as improved symptoms and reduced papilloedema. These reductions persisted for three months after they stopped the diet.

The "purse-string" technique: an arthroscopic technique for stabilization of anteroinferior instability of the shoulder with early and medium-term results.

PURPOSE: We report the early and midterm results of the "purse-string" technique, a simple, new arthroscopic technique for stabilization of anteroinferior instability of the glenohumeral joint that addresses both the Bankart lesion and capsular stretching. METHODS: The patients comprised 36 individuals (37 shoulders), with a mean age of 26 years, who had recurrent anteroinferior post-traumatic instability as a result of a traumatic Bankart lesion. They had sustained a mean of 5 dislocations per shoulder (range, 1 to 11). The cohort included 5 professional and 6 semiprofessional athletes, all of whom were involved in collision or overhead sports. A purse-string suture anchor at the 4-o'clock position was used to ensure a purse-string effect in tightening the capsule in the inferior-superior plane and creation of anterior glenoid bumper. All of the patients were assessed by an independent investigator (T.M.) at a mean of 36 months (range, 27 to 87 months) after surgery. RESULTS: Postoperatively, the mean Rowe score was 93 (range, 55 to 100), the mean Walch-Duplay score was 93 (range, 70 to 100), and the mean Constant score was 97 (range, 77 to 100). Of the patients, 97% returned to the same sport that they had played before injury. Furthermore, 66% of patients returned to their preinjury level of sports, and all of the professional athletes resumed full activities. One patient continued to have symptoms of instability, and one patient had a further dislocation after a new traumatic event. CONCLUSIONS: The early and medium-term results obtained are very encouraging, with a rate of failure of only 5.4%, a high level of return to preinjury sporting activities (with 97% of patients returning to the same sport and 66% returning to their preinjury level of sports), and a high patient satisfaction rate (with excellent or good results in 94% of patients). LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Solitary intracranial extra-osseous plasmacytoma presenting with ophthalmic signs.

Solitary plasmacytomas rarely develop in the skull, meninges, or brain. Ophthalmic signs as the initial manifestations of solitary intracranial plasmacytoma have rarely been described. We report the neuro-ophthalmologic, imaging, and pathologic findings for two patients. One patient presented with optic neuropathy, the second with bilateral sixth nerve palsies. Plasmacytoma is a treatable intracranial tumor that should be considered in the differential diagnosis of patients who present with optic neuropathy or sixth nerve palsy.