To evaluate the risk of and risk factors for a second episode (relapse) among patients with remitted primary anterior uveitis.
Retrospective cohort study.
Patients with primary anterior uveitis ...presenting to 1 of 4 academic ocular inflammation subspecialty practices achieving remission of the primary episode within 90 days of initial uveitis diagnosis.
Data were obtained by standardized chart review.
Time to relapse of anterior uveitis and risk factors for relapse.
We included 102 patients with a first episode of anterior uveitis who were seen within 90 days of first-ever uveitis onset and followed for 165 person-years after achieving remission of the initial episode. Most patients were female (60%) and white (78%). Forty patients had a recurrence of anterior uveitis. The incidence of relapse was 24% per person-year (95% confidence interval CI, 17%-33%). At 1.5 years after remission, 61% (95% CI, 48%-71%) were still in remission. Younger adults had significantly higher relapse risk than middle-aged adults (hazard ratio 18- to 35-year-old persons vs. 35- to 55-year-old persons, 2.7; 95% CI, 1.3-6.0).
Our results suggest that many patients with remitted primary anterior uveitis presenting for tertiary uveitis care will relapse. Age in the young adult range was associated with higher risk of relapse. Given the high relapse risk, management of patients with primary anterior uveitis should include an explicit plan for detecting and managing relapses.
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Abstract only
NHPs, with a lifetime on a "healthy" low fat diet, nevertheless, frequently develop obesity, MS and T2DM, fully like those in humans. The aim of the present study was to determine ...whether a high fat/high cholesterol diet (HFHC) vs the standard low fat/low cholesterol diet (LFLC)) would enhance the development of MS in middle‐aged NHPs. The diets were: HFHC 35% kcal CHO, 45% fat, and 20% protein, 0.25% cholesterol by wt (Research Diets, Inc. RD #D07110401); and LFLC: 68%, 13%, 18%, 0.008% ; respectively (LabDiet 5038). 28 NHPs, 50% male, were fed ad libitum either HFHC or LFLC. 7 of the 14 NHP tolerated the HFHC diet for a minimum of 3 months, and showed no changes in total calorie intake, body weight, triglyceride or HDL cholesterol levels, but had significantly increased total and LDL cholesterol compared to baseline (TC: 357 ± 39 vs 166 ± 8.4 mg/dl; p<0.001) and to the LFLC diet (163.7 ± 9.9 mg/dl; p<0.001). However, 7 monkeys fed the HFHC developed intolerance to the diet 2 to 10 days after its initiation. Early lipid changes in the diet intolerant were not different from those of the HFHC tolerant monkeys, and there were no changes in serum chemistry values.
Conclusion
The high fat/high cholesterol diet had no effect to increase calorie intake or to produce weight gain, and altered none of the features of MS, but significantly increased total plasma cholesterol and LDL cholesterol in NHPs.
Supported by NIA HHSN2532008002C and RD, Inc.
Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is ...not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation.
To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2507 African American (AA) and European American (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study. To validate our findings, we assayed an additional 2528 participants from the Cardiovascular Health Study (CHS) (N = 533) and Framingham Heart Study (FHS) (N = 1995). We further assessed the effect of experimental modification of mtDNA-CN through knockout of TFAM, a regulator of mtDNA replication, via CRISPR-Cas9.
Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P < 5 × 10
). Meta-analysis across all cohorts identified six mtDNA-CN-associated CpGs at genome-wide significance (P < 5 × 10
). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including coronary heart disease, cardiovascular disease, and mortality. Experimental modification of mtDNA-CN demonstrated that modulation of mtDNA-CN results in changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the "neuroactive ligand receptor interaction" KEGG pathway was found to be highly overrepresented in the ARIC cohort (P = 5.24 × 10
), as well as the TFAM knockout methylation (P = 4.41 × 10
) and expression (P = 4.30 × 10
) studies.
These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential expression of specific genes that may impact human health and disease via altered cell signaling.
Small studies and anecdotal evidence suggest marked differences in the use of opioids after surgery internationally; however, this has not been evaluated systematically across populations receiving ...similar procedures in different countries.
To determine whether there are differences in the frequency, amount, and type of opioids dispensed after surgery among the United States, Canada, and Sweden.
This cohort study included patients without previous opioid prescriptions aged 16 to 64 years who underwent 4 low-risk surgical procedures (ie, laparoscopic cholecystectomy, laparoscopic appendectomy, arthroscopic knee meniscectomy, and breast excision) between January 2013 and December 2015 in the United States, between July 2013 and March 2016 in Canada, and between January 2013 and December 2014 in Sweden. Data analysis was conducted in all 3 countries from July 2018 to October 2018.
The main outcome was postoperative opioid prescriptions filled within 7 days after discharge; the percentage of patients who filled a prescription, the total morphine milligram equivalent (MME) dose, and type of opioid dispensed were compared.
The study sample consisted of 129 379 patients in the United States, 84 653 in Canada, and 9802 in Sweden. Overall, 52 427 patients (40.5%) in the United States were men, with a mean (SD) age of 45.1 (12.7) years; in Canada, 25 074 patients (29.6%) were men, with a mean (SD) age of 43.5 (13.0) years; and in Sweden, 3314 (33.8%) were men, with a mean (SD) age of 42.5 (13.0). The proportion of patients in Sweden who filled an opioid prescription within the first 7 days after discharge for any procedure was lower than patients treated in the United States and Canada (Sweden, 1086 11.1%; United States, 98 594 76.2%; Canada, 66 544 78.6%; P < .001). For patients who filled a prescription, the mean (SD) MME dispensed within 7 days of discharge was highest in United States (247 145 MME vs 169 93 MME in Canada and 197 191 MME in Sweden). Codeine and tramadol were more commonly dispensed in Canada (codeine, 26 136 patients 39.3%; tramadol, 12 285 patients 18.5%) and Sweden (codeine, 170 patients 15.7%; tramadol, 315 patients 29.0%) than in the United States (codeine, 3210 patients 3.3%; tramadol, 3425 patients 3.5%).
The findings indicate that the United States and Canada have a 7-fold higher rate of opioid prescriptions filled in the immediate postoperative period compared with Sweden. Of the 3 countries examined, the mean dose of opioids for most surgical procedures was highest in the United States.
Abstract Background Physical data are lacking on nutrient transport in human intervertebral discs (IVDs), which supports regeneration. Our objective was to study nutrient transport in porcine IVDs to ...determine the effects of biomechanical and physiological factors. Methods In vitro testing of whole porcine IVDs was performed under different loading conditions. Fifty cervical, thoracic, and lumbar discs with attached end plates were removed from 4 Yorkshire pigs (90-150 pounds). Discs were placed in Safranin O or Fast Green FCF histological stains in diffusion or diurnal compression-tested groups. The end plate was studied by using polyurethane to block it. Traction was studied with a mechanical testing frame. Discs were cut transversely and photographed. Images were analyzed for depth of annulus fibrosus (AF) stained. The nucleus pulposus (NP) was assigned a staining score. Results Results showed no difference in AF staining between the two stains (P=0.60). The depth of AF staining did not increase (P=0.60) due to convection or disc height change via diurnal loading. The NP in all open end plate samples was completely stained by day 3. NP staining was decreased in blocked end plate samples (P=0.07) and AF staining was significantly less in traction samples than in diffusion-only samples (P=0.04). Conclusions This method showed that most small molecule nutrient transport occurs via the end plate. Compressive load was a negligible benefit or hindrance to transport. Traction hindered transport in the short term. This method can be used to study strategies for increasing nutrient transport in IVDs.
Anterior column realignment (ACR) is a powerful but destabilizing minimally invasive technique for sagittal deformity correction. Optimal biomechanical design of the ACR construct is unknown.
...Evaluate the effect of ACR design on radiographic lordosis, range of motion (ROM) stability, and rod strain (RS) in a cadaveric model.
Cadaveric biomechanical study.
Seven fresh-frozen lumbar spine cadaveric specimens (T12–sacrum) underwent ACR at L3–L4 with a 30° implant.
Primary outcome measure of interest was maximum segmental lordosis measured using lateral radiograph. Secondary outcomes were ROM stability and posterior RS at L3/4.
Effect of grade 1 and grade 2 osteotomies with single-screw anterolateral fixation (1XLP) or 2-screw anterolateral fixation (2XLP) on lordosis was determined radiographically. Nondestructive flexibility tests were used to assess ROM and RS at L3–L4 in flexion, extension, lateral bending, and axial rotation. Conditions included (1) intact, (2) pedicle screw fixation and 2 rods (2R), (3) ACR+1XLP with 2R, (4) ACR+2XLP+2R, (5) ACR+1XLP with 4 rods (4R) (+4R), and (6) ACR+2XLP+4R.
Segmental lordosis was similar between ACR+1XLP and ACR+2XLP (p>.28). ACR+1XLP+2R was significantly less stable than all other conditions in flexion, extension, and axial rotation (p<.014); however, adding an extra screw improved stability to levels equal to 4R conditions (p>.36). Adding 4R to ACR+1XLP reduced RS in all directions of loading (p<.048), whereas adding a second screw did not (p>.12). There was no difference in strain between ACR+1XLP+4R and ACR+2XLP+4R (p>.55).
For maximum stability, ACR constructs should contain either fixation into both vertebral bodies (2XLP) or accessory rods (4R). 2XLP can be used without compromising the maximal achievable lordosis but does not provide the same RS reduction as 4R.
ACR is a highly destabilizing technique that is increasingly being used for minimally invasive deformity correction. These biomechanical data will help clinicians optimize ACR construct design.
Background
Inpatient supportive care programs often target patients with advanced solid tumors. To the authors' knowledge, few studies to date have characterized symptom burden in hospitalized ...patients with potentially curable cancers. The objective of the current study was to compare symptom burden, palliative care consultation, and readmission rates in hospitalized patients by cancer type and treatment intent.
Methods
The authors conducted a single‐center study of hospitalized patients with cancer between 2014 and 2017. They assessed physical symptoms using the Edmonton Symptom Assessment System and psychological distress using the Patient Health Questionnaire‐4 and the Primary Care PTSD (Posttraumatic Stress Disorder) Screen. Multivariate linear regression models were used to assess symptom burden, logistic regression was used to assess palliative care use, and competing risk regression was used to compare 90‐day readmission risk.
Results
A total of 1549 patients were enrolled and surveyed. The majority of patients reported moderate to severe fatigue, poor well‐being, and drowsiness with no significant differences noted by cancer type and treatment intent. Compared with other groups, patients with incurable solid cancer reported higher physical symptoms (beta coefficient B, 4.73; P < .01) and symptoms of depression (B, 0.44; P < .01) and anxiety (B, 0.39; P < .01), but no difference in posttraumatic stress disorder. Among patients in the top quartile symptom burden according to the Edmonton Symptom Assessment System, the palliative care service was consulted in 14.7%, 7.9%, 25.0%, and 49.6%, respectively, of patients with potentially curable hematologic, potentially curable solid, incurable hematologic, and incurable solid cancers (P < .001). Compared with patients with potentially curable solid cancer, patients in each group experienced a higher risk of readmission within 90 days.
Conclusions
Hospitalized patients with cancer experience substantial physical and psychological symptoms. Palliative care rarely is consulted for highly symptomatic patients with potentially curable cancers. Supportive care interventions should target the needs of symptomatic patients regardless of treatment intent.
The majority of patients with cancer with an unplanned hospitalization report substantial physical and psychological symptoms. It is interesting to note that patients with hematologic cancers and potentially curable solid cancers receive significantly fewer inpatient palliative care consultations.
Lumbosacral pseudoarthrosis and instrumentation failure is common with long-segment constructs. Optimizing lumbosacral construct biomechanics may help to reduce failure rates. The influence of iliac ...screws and interbody type on range of motion (ROM), rod strain (RS), sacral screw strain (SS) is not well-established.
Investigate the effects of transforaminal lumbar interbody fusion (TLIF), anterior lumbar interbody fusion (ALIF), and iliac screws on long-segment lumbosacral construct biomechanics.
Biomechanical study.
Fourteen human cadaveric spine specimens.
Lumbosacral ROM, RS, and SS.
Specimens were potted at L1 and the ilium. Specimens were equally divided into either an L5–S1 ALIF or TLIF group and underwent testing in the following conditions: (1) intact (2) L2–S1 pedicle screw rod fixation (PSR-S) (3) L2-ilium (PSR-I) (4) PSR-S+ALIF (ALIF-S) or TLIF (TLIF-S) (5) PSR-I + ALIF (ALIF-I) or TLIF (TLIF-I). Pure moment bending (7.5 Nm) in flexion, extension, lateral bending, axial rotation, and compressive loads (400N) were applied and ROM, SS, and RS were measured. Comparisons were performed using a one-way ANOVA (p<.05).
ALIF-S and TLIF-S provided similar decreases in ROM as TLIF-I (p>.05). Compared to PSR-S, PSR-I significantly decreased SS during bending in all directions (p<.02) but increased RS in flexion and extension (p≤.02). Anterior lumbar interbody fusion-S provided similar decreases in SS as TLIF-I in all directions (p>.40) but had significantly less RS than TLIF-I in flexion, extension, compression (p<.01). TLIF-S had more SS than TLIF-I in flexion, extension, axial rotation (p<.02), while TLIF-S had less RS only in flexion (p=.03). Compared to PSR-I, ALIF-I decreased the RS (p<.02) but TLIF-I did not (p>.67).
Iliac screws were protective of SS but increased RS at the lumbosacral junction. Constructs with ALIF and no iliac screws result in comparable SS as constructs with TLIF and iliac screws with significantly reduced RS. If iliac screws are utilized, ALIF but not TLIF reduces the iliac screw-induced RS.
There is a relatively high incidence of lumbosacral instrumentation failure in adult spinal deformity. Optimizing lumbosacral construct biomechanics may help to reduce failure rates. Iliac screws induce lumbosacral rod strain and may be responsible for instrumentation failure. Constructs with lumbosacral ALIF reduce iliac-screw induced rod strain and may obviate the need for fixation to the ilium.
Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, ...and a more severe phenotype in the E815K cohort. We performed mutation analysis and retrospective genotype-phenotype correlations in all eligible patients with AHC enrolled in the US AHC Foundation registry from 1997-2012. Clinical data were abstracted from standardized caregivers' questionnaires and medical records and confirmed by expert clinicians. We identified ATP1A3 mutations by Sanger and whole genome sequencing, and compared phenotypes within and between 4 groups of subjects, those with D801N, E815K, other ATP1A3 or no ATP1A3 mutations. We identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) are missense, and 16 (47%) had not been previously reported. Concordant with prior studies, more than 2/3 of all mutations are clusteredin exons 17 and 18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K(26%) and 11 had G947R (8%) mutations corrected.Patients with an E815K mutation demonstrate an earlier age of onset, more severe motor impairment and a higher prevalence of status epilepticus. This study further expands the number and spectrum of ATP1A3 mutations associated with AHC and confirms a more deleterious effect of the E815K mutation on selected neurologic outcomes. However, the complexity of the disorder and the extensive phenotypic variability among subgroups merits caution and emphasizes the need for further studies.
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