Metabolic syndrome predicts new damage in systemic lupus erythematosus patients: Data from the Almenara Lupus Cohort

Objectives This study aims to determine whether the MetS predicts damage accrual in SLE patients. Methods This longitudinal study was conducted in a cohort of consecutive SLE patients seen since 2012 at one single Peruvian institution. Patients had a baseline visit and then follow-up visits every 6 months. Patients with ≥ 2 visits were included. Evaluations included interview, medical records review, physical examination, and laboratory tests. Damage accrual was ascertained with the SLICC/ACR damage index (SDI) and disease activity with the SLEDAI-2K. Univariable and multivariable Cox-regression survival models were carried out to determine the risk of developing new damage. The multivariable model was adjusted for age at diagnosis; disease duration; socioeconomic status; SLEDAI; baseline SDI; the Charlson Comorbidity Index; daily dose; and time of exposure of prednisone (PDN), antimalarials, and immunosuppressive drugs. Results Two hundred and forty-nine patients were evaluated; 232 of them were women (93.2%). Their mean (SD) age at diagnosis was 35.8 (13.1) years; nearly all patients were Mestizo. Disease duration was 7.4 (6.6) years. The SLEDAI-2K was 5.2 (4.3) and the SDI, 0.9 (1.3). One hundred and eight patients (43.4%) had MetS at baseline. During follow-up, 116 (46.6%) patients accrued at least one new point in the SDI damage index. In multivariable analyses, the presence of MetS was a predictor of the development of new damage (HR: 1.54 (1.05–2.26); p < 0.029). Conclusions The presence of MetS predicts the development of new damage in SLE patients, despite other well-known risk factors for such occurrence.

Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy

Genotyping divides transthyretin cardiac amyloidosis (ATTR-CA) in hereditary (ATTRv) and wild type (ATTRwt) forms. This study investigated the prevalence and clinical presentation of ATTRv in a contemporary cohort of consecutive ATTR-CA patients diagnosed at a tertiary Danish amyloidosis center. Age at diagnosis, clinical- and echocardiographic data, and transthyretin (TTR) genotype were recorded. Relatives of ATTRv patients underwent clinical phenotyping and predictive gene testing. Genetic testing in 102 patients identified four TTR variant carriers: p.Pro63Ser, p.Ala65Ser (n = 2) and p.Val142Ile. The mean age of ATTRv index patients was significantly lower compared to ATTRwt patients: 70.2 ± 1.2 versus 80.0 ± 6.2, p-value: 0.005. Evaluation of ATTRv families identified seven TTR variant carriers with a median age of 65 years (range 48–76) and three were diagnosed with ATTR-CA by DPD-scintigraphy. Family members with ATTR-CA were all asymptomatic and had normal levels of cardiac biomarkers. In conclusion, the prevalence of ATTRv in a contemporary Danish ATTR-CA cohort is 4%. ATTRv index patients were significantly younger age at diagnosis than ATTRwt patients. Non-p.Leu131Met TTR variants have reduced penetrance at the age of 65 years in which approximately half of variant carriers have asymptomatic ATTR-CA with normal LV systolic function and cardiac biomarker analyses.

Mitochondrial DNA copy number as a prognostic marker is age-dependent in adult glioblastoma

Background Glioblastoma (GBM) is the most common and aggressive form of glioma. GBM frequently displays chromosome (chr) 7 gain, chr 10 loss and/or EGFR amplification (chr7+/chr10-/EGFRamp). Overall survival (OS) is 15 months after treatment. In young adults, IDH1/2 mutations are associated with longer survival. In children, histone H3 mutations portend a dismal prognosis. Novel reliable prognostic markers are needed in GBM. We assessed the prognostic value of mitochondrial DNA (mtDNA) copy number in adult GBM. Methods mtDNA copy number was assessed using real-time quantitative PCR in 232 primary GBM. Methylation of POLG and TFAM genes, involved in mtDNA replication, was assessed by bisulfite-pyrosequencing in 44 and 51 cases, respectively. Results Median age at diagnosis was 56.6 years-old and median OS, 13.3 months. 153/232 GBM (66 %) displayed chr7+/chr10-/EGFRamp, 23 (9.9 %) IDH1/2 mutation, 3 (1.3 %) H3 mutation and 53 (22.8 %) no key genetic alterations. GBM were divided into two groups, “Low” (n = 116) and “High” (n = 116), according to the median mtDNA/nuclear DNA ratio (237.7). There was no significant difference in OS between the two groups. By dividing the whole cohort according to the median age at diagnosis, OS was longer in the “High” vs “Low” subgroup (27.3 vs 15 months, p = 0.0203) in young adult GBM (n = 117) and longer in the “Low” vs “High” subgroup (14.5 vs 10.2 months, p = 0.0116) in older adult GBM (n = 115). POLG was highly methylated, whereas TFAM remained unmethylated. Conclusion mtDNA copy number may be a novel prognostic biomarker in GBM, its impact depending on age.

Factors Associated with Surgery Among South Asian American and Non-Hispanic White Women with Breast Cancer

South Asian American (SA) women are diagnosed with more aggressive breast cancer than non-Hispanic White (NHW) women. Understanding the factors associated with the types of surgery received by these women sheds light on disease management in these culturally distinct populations. We used data on age at diagnosis, stage, grade, estrogen and progesterone receptors, and surgery from 4,590 SA and 429,030 NHW breast cancer cases in the Surveillance, Epidemiology and End Results (SEER) program. We used logistic regression with surgery as the binary outcome (subcutaneous, total, or radical mastectomy (STRM) versus partial mastectomy, no, unknown or other (PNUM)) and included additive effects of all the variables and interactions of age, stage, grade, and estrogen and progesterone receptors with race/ethnicity. Type I error of 5% was used to assess statistical significance of the effects. SA were significantly more likely than NHW cases to receive STRM relative to PNUM surgery among women diagnosed at or after age 50 years and having localized stage disease (Odds Ratio (OR) = 1.27, 95% Confidence Interval (CI) = 1.06 – 1.52). Further, SA were significantly less likely than NHW cases to receive STRM relative to PNUM surgery among those diagnosed before age 50 years and having regional or distant stage disease (OR = 0.75, 95% CI = 0.59 – 0.95 for age at diagnosis < 40 years; OR = 0.77, 95% CI = 0.62 – 0.95 for age at diagnosis 40-49 years). The type of surgery received by SA and NHW women differ according to age at diagnosis and disease stage. KEYWORDS: Breast Cancer; Surgery; Cancer Health Equity; Disease Characteristics; South Asian American; Non-Hispanic White; Logistic Regression; Interaction

Hydrocortisone Suspension Provides Similar Growth Outcomes as Hydrocortisone Tablets in Young Children with CAH

Background Young children with CAH require small doses (0.1-1.25 mg) of hydrocortisone (HC) to control excess androgen production and avoid the negative effects of overtreatment. The smallest commercially available HC formulation, before the recent FDA approval of HC granules, was a scored 5 mg tablet. The options to achieve small doses were limited to using a pharmacy-compounded suspension, which the CAH Clinical Practice Guidelines recommended against, or splitting tablets into quarters or eighths, or dissolving tablets into water. Methods Cross sectional chart review of 130 children with classic CAH treated with tablets versus a pharmacy-compounded alcohol-free hydrocortisone suspension to compare growth, weight, skeletal maturation, total daily HC dose and exposure over the first four years of life. Results No significant differences were found in height, weight, or BMI z-scores at 4 years, and in predicted adult height, before or after adjusting for age at diagnosis and sex. Bone age z-scores averaged 2.8 SDs lower for patients on HC suspension compared to HC tablets (p&lt;0.001) after adjusting for age at diagnosis and sex. The suspension group received 30.4% lower (p&gt;0.001) average cumulative HC doses by their 4th birthday. Conclusions Our data indicates that treatment with alcohol-free HC suspension decreased androgen exposure as shown by lower bone age z-scores, allowed lower average and cumulative daily HC dose compared to HC tablets, and generated no significant differences in SDS in growth parameters in children with CAH at 4 years of age. Longitudinal studies of treating with smaller HC doses during childhood are needed.

Patient Age Is Significantly Related to Distant Metastasis of Papillary Thyroid Microcarcinoma

ObjectiveDistant metastasis in papillary thyroid microcarcinoma (PTMC) is rare but fatal, and its relationship with patient age remains unclear. The objective of this study was to examine the association between age at diagnosis and metachronous distant metastasis in PTMC.MethodsConsecutive patients who underwent thyroidectomy for PTC measuring 10 mm or less at a tertiary hospital from January 2000 to December 2016 were enrolled. Patients who had evidence of distant metastasis at diagnosis or underwent postoperative radioiodine (RAI) ablation were excluded. A Cox proportional hazards model with restricted cubic splines (RCS) was applied to examine the association between age at diagnosis and distant metastasis.ResultsA total of 4,749 patients were evaluated. The median age was 44 years (range, 8–78 years), and 3,700 (78%) were female. After a median follow-up of 65 months, 21 distant metastases (20 lung, 1 liver) were recognized. A univariate Cox proportional model using a 5-knot RCS revealed a significant overall (p = 0.01) and a potential nonlinear association (p = 0.08) between distant metastasis and age at diagnosis. In multivariate analysis, age at diagnosis, extrathyroidal extension (ETE), and lymph node metastasis (pN+) were independent risk factors for distant metastasis. Compared with the middle-aged group (30–45 years old), younger and older patients had a higher risk of distant metastasis [HR, 95% CI, p-value, age ≤ 30, 4.54 (0.91–22.60), 0.06, age &gt; 45, 6.36 (1.83–22.13), &lt;0.01].ConclusionAge at diagnosis is associated with metachronous distant metastasis of PTMC, and patients with younger or older age have a higher risk of distant metastasis than middle-aged patients.

Long durations from symptom onset to diagnosis and from diagnosis to treatment in obsessive-compulsive disorder: A retrospective self-report study

Background Although obsessive-compulsive disorder (OCD) is one of the most common mental disorders, it takes up to 17 years for patients with OCD to receive adequate therapy. According to existing outdated literature, this study aimed to investigate the current duration between symptom onset and diagnosis and between diagnosis and the beginning of therapy separately. Methods In a cross-sectional study, N = 100 patients diagnosed with OCD undergoing treatment in a psychiatric outpatient department were assessed, using self-report questionnaires on sociodemographic and clinical variables. Based on self-reported information, the durations between age at symptom onset and age at diagnosis, and between age at diagnosis and beginning of therapy were calculated. To investigate associated factors, two subgroups of patients, one with a short duration between symptom onset and diagnosis < 7 years, and another with a long duration between symptom onset and diagnosis ≥ 7 years, respectively, were compared. Results and conclusion Patients reported first symptoms of OCD at a mean age of 18.72 years. The mean duration between age at symptom onset and age at diagnosis was 12.78 years and the mean duration between age at diagnosis and the beginning of therapy was 1.45 years. Subgroup comparison indicated that patients with a short duration between symptom onset and diagnosis were significantly younger than patients with a long duration. However, patients with a short duration between symptom onset and diagnosis were at an older age when they reported first symptoms of OCD. Further, they showed less severe symptoms of OCD, higher functioning levels, and less self-stigmatization than patients with a long duration. It can be concluded that the duration until patients with OCD are diagnosed correctly and receive adequate treatment is still very long. Therefore, the duration between symptom onset and diagnosis should be shortened. Further, the duration between diagnosis and the beginning of therapy could be a good additional approach to reduce the overall duration of untreated disorder.

Macular Hemorrhage Due to Age-Related Macular Degeneration or Retinal Arterial Macroaneurysm: Predictive Factors of Surgical Outcome

Objective: The study aimed to determine the outcomes and prognostic factors of vitrectomy, subretinal injection of tissue-plasminogen activator and gas tamponade in macular hemorrhage (MaH) due to age-related macular degeneration (AMD) or retinal arterial macroaneurysm (RAM). Methods: The study design utilized a multicentric retrospective case series design of consecutive patients undergoing surgery between 2014 and 2019. Results: A total of 65 eyes from 65 patients were included in the study. Surgery was performed after a mean period of 7.1 days. Displacement of MaH was achieved in 82% of the eyes. Mean best-corrected visual acuity (BCVA) improved from 20/500 to 20/125 at month(M)1 and M6 (p < 0.05). At M6, BCVA worsening was associated with an older age at diagnosis (p = 0.0002) and higher subretinal OCT elevation of MaH (p = 0.03). The use of treat and extend (TE) (OR = 16.7, p = 0.001) and small MaH fundus size (OR = 0.64 and 0.74 for horizontal and vertical fundus size, p < 0.05) were predictive of a higher likelihood of obtaining a countable BCVA at M1. Baseline BCVA was predictive of postoperative BCVA (p < 0.05). Retinal detachment and MaH recurrence occurred in 3% and 9.3% of cases at M6. Conclusion: MaH surgery stabilizes or improves BCVA in 85% of cases. Younger age at diagnosis, better baseline BCVA figures, smaller subretinal MaH height and use of TE regime were predictive of the best postoperative outcomes.

Characterization of patients that can continue conservative treatment for adenomyosis

Background Historically, hysterectomy has been the radical treatment for adenomyosis. Although, some patients may not want to have their uterus removed, patients often have to no choice but to request hysterectomy during conservative treatment. The factors necessitating these hysterectomies remain unknown. The purpose of this study was to determine which patients can continue conservative treatment for adenomyosis. Methods We selected women diagnosed with adenomyosis and provided with conservative treatment at the Kindai University Hospital and Osaka Red Cross Hospital in Osaka Japan from 2008 to 2017. Age at diagnosis, parity, uterine size, subtype of adenomyosis, type of conservative treatment, and timing of hysterectomy for cases with difficulty continuing conservative treatment were examined retrospectively. Results A total of 885 patients were diagnosed with adenomyosis, and 124 started conservative treatment. Conservative treatment was continued in 96 patients (77.4%) and hysterectomy was required in 28 patients (22.6%). The cumulative hysterectomy rate was 32.4%, and all women had hysterectomy within 63 months. In the classification tree, 82% (23/28) of women aged 46 years or younger were able to continue conservative treatment when parity was zero or one. In those with parity two and over, 95% (20/21) of those aged 39 years and older had hysterectomy. Conclusions Patients who continue conservative treatment for approximately 5 years are more likely to have successful preservation of the uterus. Multiparity and higher age at diagnosis are factors that contribute to hysterectomy after conservative treatment. Parity and age at diagnosis may be stratifying factors in future clinical trials of hormone therapy.