Significant Risk Factor For Progression Research Articles

Hip Displacement After Triradiate Closure in Ambulatory Cerebral Palsy: Who Needs Continued Surveillance?

Hip surveillance in cerebral palsy (CP) is an accepted practice with evidence-based guidelines implemented. For the skeletally immature with open triradiate cartilage (TRC), recommendations for radiographic surveillance stemmed from population-based studies. For nonambulatory CP, progression of hip displacement after skeletal maturity has been reported; less is known for ambulatory CP. We aimed to determine the prevalence and risk factors associated with progressive hip displacement after TRC closure, a proxy for skeletal maturity, for ambulatory CP. This is a retrospective cohort study of patients with ambulatory CP (Gross Motor Function Classification System I-III), with unilateral or bilateral involvement, hypertonic motor type, regular hip surveillance (≥3 radiographs after age 10 yr, 1 before TRC closure, ≥1 after age 16 yr), and 2-year follow-up post-TRC closure. The primary outcome was migration percentage (MP). Other variables included previous preventative/reconstructive surgery, topographic pattern, sex, scoliosis, epilepsy, and ventriculoperitoneal shunt. An "unsuccessful hip" was defined by MP ≥30%, MP progression ≥10%, and/or requiring reconstructive surgery after TRC closure. Statistical analyses included chi-square and multivariate Cox regression. Kaplan-Meier survivorship curves were also determined. Receiver operating characteristic analysis was used to determine the MP threshold for progression to an "unsuccessful hip" after TRC closure. Seventy-six patients (39.5% female) met the inclusion criteria, mean follow-up 4.7±2.1 years after TRC closure. Sixteen (21.1%) patients had an unsuccessful hip outcome. By chi-square analysis, diplegia (P=0.002) and epilepsy (P=0.04) were risk factors for an unsuccessful hip. By multivariate analysis, only first MP after TRC closure (P<0.001) was a significant risk factor for progression to an unsuccessful hip; MP ≥28% being the determined threshold (receiver operating characteristic curve analysis, area under curve: 0.845, P<0.02). The risk of MP progression after skeletal maturity is relatively high (21%), similar to nonambulatory CP. Annual hip surveillance radiographs after TRC closure should continue for Gross Motor Function Classification System I-III with an MP ≥28% after TRC closure, especially for bilateral CP and epilepsy. III.

Malignant Transformation of Benign Meningiomas with or without Radiotherapy

Most meningiomas are benign, slow growing tumors, which rarely progress to a higher grade. The incidence rate of malignant progression is estimated to be 2.98/1000 patient-year. However, non-skull base location is a significant risk factor for progression. The median time to malignant progression is 4.3 years; however, the cumulative rate of progression approaches a plateau after 10 years. Although radiosurgery does not appear to increase the incidence rate(0.5/1000 patient-year), exact comparisons have been difficult because of differences in study populations. The median time to progression is 7.0 years from initial diagnosis and 5.0 years from radiosurgery. The cumulative rate appears to increase even after 10 years. The risk of malignant transformation after radiotherapy may increase in patients with tumor-prone syndromes, with some controversies regarding patients with neurofibromatosis type 2. Although short term follow-up in patients with meningioma suggests that radiosurgery is safe, there is uncertainty regarding its use in pediatric patients, and those with tumor-prone syndromes.

Active Rheumatoid Arthritis and Scoliosis: A Mid-Term Cohort Study.

Retrospective cohort study. To elucidate the factors related to progression of scoliosis in patients with rheumatoid arthritis (RA) using longitudinal cohort data. Thirty percent of patients with RA have lumbar scoliosis. However, the effectiveness of current treatment methods in preventing the progression of scoliosis is not well-understood due to a lack of longitudinal studies. We enrolled 180 patients with RA who were followed up for over two years, all of whom underwent standing spinal X-rays. These patients were categorized based on their disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR) into two groups: those in remission (n=76) and those in non-remission (n=104). We evaluated various radiographic measures, including C7 center sacral vertical line (C7-CSVL), pelvic obliquity, major Cobb angle, and curve location. Fifty-three (29.4%) patients presented progression of scoliosis during a mean follow-up period of 4.8 years. Patients in the non-remission showed larger Cobb angle at baseline and final follow-up, compared to those in remission. The annual progression rate of the curve was also greater in the non-remission group (1.04 degree /year), than in the remission group (0.59 degree /year, P=0.001). There was no difference in the incidence of new vertebral fractures. The presence of a baseline cobb angle of 10 degree or more (OR: 3.14; 95% CI: 1.38-7.13; P=0.006), glucocorticoid use (OR: 2.88; 95% CI: 1.18-7.06; P=0.021), and non-remission at baseline (OR: 2.83; 95% CI: 1.25-6.41; P=0.012) were significant risk factors for progression of scoliosis. RA disease activity is linked to progression of scoliosis in patients with RA. Patients with RA who present with an initial scoliosis of 10 degrees or greater, require glucocorticoids for treatment and are in non-remission at baseline may be at high risk for scoliosis progression.

Risk factors for severe COVID-19 among patients with systemic lupus erythematosus: a real-world analysis of a large representative US administrative claims database, 2020–2021

ObjectivesTo identify risk factors for progression to severe COVID-19 and estimate the odds of severe COVID-19 associated with vaccination among patients with systemic lupus erythematosus (SLE).MethodsThis retrospective cohort study identified...

Impact of pregnancy in women with desmoid fibromatosis: An international retrospective observational study.

11513 Background: Desmoid fibromatosis (DF) often occurs during pregnancy/peripartum. Guidance for planning new pregnancies during active surveillance or following DF resection has been limited. Thus, we sought to evaluate outcomes and decision making in the peripartum. Methods: Women of child-bearing age with DF diagnosed between 2000 and 2020 were interviewed about procreation decisions, in a multicenter retrospective observational study (NCT05284305). Pregnancies simultaneous or after diagnosis were analyzed. Primary outcome was DF progression/recurrence within 1 yr postpartum. Secondary outcomes were spontaneous regression, switch to active treatment, and obstetric risks. To estimate probability of progression, a random intercept logistic model was fit to account for correlation of progression in multiple pregnancies in the same patient. Results: Of 483 pts interviewed, 120 (24.8%) postponed, 32 (6.6%) interrupted, and/or 232 (48%) avoided pregnancy (in 93.3%, 50%, and 72.9% of cases because of DF), respectively. 147 pregnancies in 131 pts were concurrent with or after diagnosis: 26 (17.7%, Group A) concurrent with diagnosis, 48 (32.7%, B) after DF resection, and 73 (49.7%, C) with DF on surveillance. Estimated probability of progression was 12.0% (CI 2.0 – 48.4) during pregnancy and 15.8% (5.6 – 37.5) postpartum; for pregnancies after diagnosis (Groups B and C), these rates were 5.1% (0.4 – 40.0) and 9.0% (1.8 – 35.0). On multivariate analysis, age at pregnancy and size of primary DF were significant risk factors for progression (Table). Estimated probability of spontaneous regression was 3.6% (CI 0.2-40.7) during pregnancy and 7.1% (CI 0.3 – 67.2) postpartum. 7/38 (18.4%) spontaneously regressed after pregnancy-related PD, 4/23 (17.4%) in Groups B and C. Treatment for progression was needed in 9/79 (11.4%) postpartum, in 4/63 (6.3%) in Groups B and C. Obstetric complications were comparable to population data in developed countries. Conclusions: After DF diagnosis, pregnancy is safe with a risk of progression of 5% during pregnancy and 9% postpartum. Treatment is needed in only 6%. Spontaneous regression is less common but occurs even after initial progression. Patients decision making about procreation appeared to be influenced by their DF diagnosis. This study supports counseling that fertility options should be fully explored with expert guidance as intervention rates are low. [Table: see text]

Significance of dorsal bladder neck involvement in predicting the progression of non-muscle-invasive bladder cancer.

Accurately predicting of progression is important for patients with non-muscle-invasive bladder cancer (NMIBC). We previously reported that bladder neck involvement (BNI) was significantly associated with progression of NMIBC. In this study, we evaluated the prognostic significance of the detailed BNI location in NMIBC patients. We retrospectively reviewed 651 patients diagnosed with primary NMIBC at a single center between 2000 and 2018. Using the detailed BNI location, patients were divided into the following three groups: dorsal BNI (BNId; 4 to 8 o'clock position), ventral BNI (BNIv; 8 to 4 o'clock but not 4 to 8 o'clock position), and non-BNI group. Both time to progression to muscle-invasive disease and distant metastasis was compared among the three groups. A prognostic model was developed and its discriminative ability was evaluated. Dorsal bladder neck involvement and BNIv were observed in 43 (6.6%) and 36 (5.5%) patients, respectively. During a median follow-up of 61months, 35 (5.4%) patients progressed. The cumulative incidence at 5 years was 12%, 0%, and 5.0% in BNId, BNIv, and non-BNI groups, respectively. On multivariate analysis, BNId was a significant and independent risk factor for progression, tumor stage pT1, and histologic grade G3. One point was assigned to each factor, and patients were classified into four well-stratified prognostic groups based on the total score. Dorsal bladder neck involvement was an independent and significant risk factor for progression in primary NMIBC. Our simple and practical prognostic model including BNId is easy to use and may help selecting the optimal treatment and its timing.

A high number of co-occurring genomic alterations detected by NGS is associated with worse clinical outcomes in advanced EGFR-mutant lung adenocarcinoma: Data from LATAM population

BackgroundCo-occurring genomic alterations identified downstream main oncogenic drivers have become more evident since the introduction of next-generation sequencing (NGS) analyses at diagnosis and progression. Emerging evidence has stated that co-occurring genomic alterations at diagnosis might represent de novo and primary resistance mechanisms to tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant (EGFRm) non-small lung cancer (NSCLC). In this study, we assessed the prognostic role of co-occurring genomic alterations in advanced EGFRm NSCLC. MethodsA cohort of 111 patients with advanced NSCLC harboring EGFR-sensitive mutations detected by PCR was analyzed in 5 Latin American oncological centers from January 2019 to December 2020. All eligible patients received upfront therapy with EGFR-TKI. Co-occurring genomic alterations were determined at diagnosis in every patient by the NGS (FoundationOneCDx) comprehensive platform, which evaluates 324 known cancer-related genes. ResultsEGFR exon19 deletion was the most frequent oncogenic driver mutation (60.4 %) detected by NGS. According to the NGS assay, 31 % and 68.3 % of patients had 1–2 and ≥ 3 co-occurring genomic alterations, respectively. The most frequent co-occurring genomic alterations were TP53 mutations (64.9 %) followed by CDKN2AB alterations (13.6 %), BRCA2 (13.6 %), and PTEN (12.7 %) mutations. Baseline central nervous system disease was present in 42.7 % of patients. First- or second-generation EGFR TKIs (gefitinib, afatinib, or erlotinib) were the most common treatment in 67.5 % of patients, while osimertinib was administered in 27.9 % of cases. The median PFS in all evaluated patients was 13.63 months (95 %CI: 11.79–15.52). Using ≥ 3 co-occurring alterations as the cut-off point, patients with ≥ 3 co-occurring genomic alterations showed a median PFS, of 12.7 months (95 %CI: 9.92–15.5) vs 21.3 months (95 %CI: 13.93-NR) in patients with 2 or less co-occurring genomic alterations [HR 3.06, (95 %CI: 1.55–5.48) p = 0.0001]. Also, patients with a TP53 mutation had a shorter PFS, 13.6 (95 %CI: 10.7–15.5) vs 19.2 months (95 %CI: 12.8-NR); in wild type TP53 [HR 2.01 (95 %CI: 1.18–3.74) p = 0.12]. In the multivariate analysis, the number (≥3) of concurrent genomic alterations and ECOG PS of 2 or more were related to a significant risk factor for progression [HR 2.79 (95 %CI: 1.49–5.23) p = 0.001 and HR 2.42 (95 %CI: 1.22–4.80) p = 0.011 respectively]. ConclusionEGFR-mutant NSCLC is not a single oncogene-driven disease in the majority of cases, harboring a higher number of co-occurring genomic alterations. This study finds the number of co-occurring genomic alterations and the presence of TP53 mutations as negative prognostic biomarkers, which confers potentially earlier resistance mechanisms to target therapy.

Prognostic significance of neutrophil to lymphocyte ratio in patients with metastatic breast cancer on the background of eribulin therapy

Background. The neutrophil to lymphocyte ratio (NLR) is a prognostic marker in various carcinomas, including breast cancer. The NLR reflects the balance of systemic immunity and is associated with survival in patients with solid tumors.Aim. This study retrospectively evaluated the significance of the NLR and the absolute lymphocyte count in patients with breast cancer who received eribulin therapy.Materials and methods. The prognostic significance of the NLR and the absolute lymphocyte count in 33 patients with metastatic breast cancer treated with eribulin in 2020–2021 was analyzed.Results. The median follow-up time for patients was 9 [6; 15] months. Twenty-six of 33 (78.8 %) patients progressed. Seven of 33 (21.2 %) patients were censored due to therapy discontinuation, complete discontinuation after 1 course was required in 3 (9.1 %) patients and was associated with the development of hematological toxicity: 1 (3 %) case of a combination of grade 3 leucopenia and grade 3 thrombocytopenia, 2 (6 %) cases of grade 3 neutropenia. According to the analysis results, the NLR was a statistically significant risk factor for progression in patients on eribulin therapy, both without taking into account the influence of other factors (univariate model) and with the underlying influence of the absolute neutrophil count and the absolute lymphocyte count: hazard ratio (95 % confidence interval) was 1.21 [1.04; 1.41], p = 0.015 and 1.30 [1.07; 1.57], p = 0.008, respectively. There was no statistically significant effect of the absolute neutrophil count and the absolute lymphocyte count in both univariate and multivariate models. To illustrate the impact of SNL on the onset of progression, patients were divided into two subgroups based on median SNL: SNL˂ 2.46 and SNL ≥2.46. The median survival in patients with SNL ≥2.46 was 9 months, and in patients with SNL˂ 2.46 it was 15 months.Conclusion. The results of the pilot study state the NLR is a potential prognostic marker of long-term treatment with eribulin for patients with metastatic breast cancer, and can be used in clinical practice.

Risk Factors for Progression of Age-Related Macular Degeneration: Population-Based Amish Eye Study.

Objective: To evaluate the optical coherence tomography (OCT)-based risk factors for progression to late age-related macular degeneration (AMD) in a population-based study of elderly Amish. Methods: A total of 1332 eyes of 666 consecutive subjects who completed a 2-year follow-up visit were included in this multicenter, prospective, longitudinal, observational study. Imaging features were correlated with 2-year incidence of late AMD development. Odds ratios for imaging features were estimated from logistic regression. Baseline OCT images were reviewed for the presence of drusen volume ≥0.03 mm3 in the central 3 mm ring, intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDD), and drusenoid pigment epithelium detachment (PED). Subfoveal choroidal thickness, drusen area, and drusen volume within 3 and 5 mm circles centered on the fovea were also assessed. Results: Twenty-one (1.5%) of 1332 eyes progressed to late AMD by 2 years. The mean age of the study subjects was 65 ± 10.17 (±SD) years and 410 subjects were female. Univariate logistic regression showed that drusen area and volume in both 3 mm and 5 mm circles, subfoveal choroidal thickness, drusen volume ≥ 0.03 mm3 in the 3 mm ring, SDD, IHRF, and hDC were all associated with an increased risk for development of late AMD. The multivariate regression model identified that drusen volume in the 3 mm ring (OR: 2.59, p = 0.049) and presence of IHRF (OR: 57.06, p < 0.001) remained as independent and significant risk factors for progression to late AMD. Conclusions: This population-based study confirms previous findings from clinic-based studies that high central drusen volume and IHRF are associated with an increased risk of progression to late AMD. These findings may be of value in risk-stratifying patients in clinical practice or identifying subjects for early intervention clinical trials.

Diabetic retinopathy: long-term follow-up of Ecuadorian patients with type 2 diabetes in primary care

ObjectivesThe aim of this study is to evaluate the prevalence, associated factors, and time for diabetic retinopathy (DR) development in Ecuadorian patients with type 2 diabetes (DM2) followed for 10 years.MethodsA retrospective cohort study between 2007 and 2017 included 487 patients with DM2 who had at least one dilated fundus eye examination in Diabetes Center in a primary-health-care level followed up for ten years. Data was collected from clinical records. Sociodemographic and laboratory variables were analysed, determining their association (mean difference and bivariate logistic regression) with DR. Survival time was calculated through life tables and Kaplan-Meier analysis.ResultsThe prevalence of DR was 19.95% during the 10-year follow-up period. The median time for developing DR was 28.53 (95% CI: 26.89–27.05), showing that 50% of patients have the risk (HR: 4.57) to develop DR in the third decade of DM disease diagnosis. The significant risk factors for progression of DR were duration of DM2, high glycosylated hemoglobin level > 7% (HbA1c Expβ: 1.709, 95% CI: 1.00–2.89), systemic hypertension (HNT Expβ: 2.348 Expβ: 2.348 95% CI: 1.17–4.70%) 95% CI: 1.17–4.70%), low glomerular filtration rate (Expβ: 1.805, GFR, < 60 ml/min/sc1.73) (95% CI: 1.10–2.94) and albuminuria (Expβ: 2.48 Expβ: 2.48 95% CI: 1.49–4.13).ConclusionsHalf of the patients with DM2 treated in a primary level of care will develop DR in the third decade of the disease. There are risk factors related to development of DR, such as low GFR, high HbA1c, albuminuria and HTN. Low GFR, high HbA1c, albuminuria and high blood pressure are related with the presence of retinopathy in diabetes patients.

Pigmentary abnormality without significant drusen as a risk factor for late age-related macular degeneration

We investigated the incidence and risk factors of late age-related macular degeneration (AMD) in the fellow eye (FE) without significant drusen of patients with unilateral exudative macular neovascularization (MNV). In this retrospective study, 241 eligible patients who were followed-up for more than 3 years were enrolled. We analyzed the incidence and hazard ratios (HRs) of late AMD in the FE according to demographic and ophthalmologic variables. Hypopigmentation on color fundus photography (CFP) corresponds to shallow irregular RPE elevation (SIRE), so-called “double-layer sign” and/or “attenuation or disruption of RPE and/or ellipsoid zone” on OCT. The 5-year incidence of FE exudative MNV conversion was 8.6%. The 5-year incidence of FE exudative MNV of large hypopigmentation (≥ 0.5 disc area; DA) and small hypopigmentation (< 0.5 DA) on CFP, and SIRE (≥ 1000 µm) and small RPE elevation (< 1000 µm) on OCT were 36.2%, 14.2%, 55.0%, and 15.6%, respectively. The multivariate Cox proportional hazard model revealed that large hypopigmentation, small hypopigmentation, SIRE, and small RPE elevation showed HRs of 23.230, 8.037, 132.589, and 41.823 for FE exudative MNV occurrence, respectively. Hypopigmentation on CFP and SIRE on OCT could represent the same lesion. Even small hypopigmentation and small RPE elevation were significant risk factors for progression to exudative MNV.

The natural history of low-grade dysplasia in Barrett's esophagus and risk factors for progression.

Background and AimBarrett's esophagus is associated with increased risk of esophageal adenocarcinoma. The optimal management of low‐grade dysplasia arising in Barrett's esophagus remains controversial. We performed a retrospective study from a tertiary referral center for Barrett's esophagus neoplasia, to estimate time to progression to high‐grade dysplasia/esophageal adenocarcinoma in patients with confirmed low‐grade dysplasia compared with those with downstaged low‐grade dysplasia from index presentation and referral. We analyzed risk factors for progression.MethodsWe analyzed consecutive patients with low‐grade dysplasia in Barrett's esophagus referred to a single tertiary center (July 2006–October 2018). Biopsies were reviewed by at least two expert pathologists.ResultsOne hundred and forty‐seven patients referred with suspected low‐grade dysplasia were included. Forty‐two of 133 (32%) of all external referrals had confirmed low‐grade dysplasia after expert histopathology review. Multivariable analysis showed nodularity at index endoscopy (P < 0.05), location of dysplasia (P = 0.05), and endoscopic therapy after referral (P = 0.09) were associated with progression risk. At 5 years, 59% of patients with confirmed low‐grade dysplasia had not progressed versus 74% of patients in the cohort downstaged to non‐dysplastic Barrett's esophagus.ConclusionOur data show variability in the diagnosis of low‐grade dysplasia. The cumulative incidence of progression and time to progression varied across subgroups. Confirmed low‐grade dysplasia had a shorter progression time compared with the downstaged group. Nodularity at index endoscopy and multifocal low‐grade dysplasia were significant risk factors for progression. It is important to differentiate these high‐risk subgroups so that decisions on surveillance/endotherapy can be personalized.

Latency, Anti-Bacterial Resistance Pattern, and Bacterial Infection-Related Glomerulonephritis.

Bacterial infection-related GN occurs concurrent to or after known or unknown infections. It is important to understand the clinical implications of the bacterial isolates, antimicrobial resistance patterns, and effect of latency-based classification on kidney and patient outcomes. In total, 501 consecutive adults diagnosed with bacterial infection-related GN between 2005 and 2017 were included from a biopsy registry of 15,545 patients at a single center in South India, and follow-up data were collected from electronic medical records until December 2019. Latency was defined as time between resolution of infection and onset of GN, which was classified as parainfectious, peri-infectious, or postinfectious GN. Longitudinal kidney and patient outcomes were studied. The mean age of the cohort was 40 (± 15) years, 6% were above 65 years, and 330 (66%) were men. Diabetes was present in 93 (19%) patients. Seventy percent (353 of 501) of patients had known infections, with the median latent period for parainfectious (115 of 353, 33%), peri-infectious (97 of 353, 27%), and postinfectious (141 of 353, 40%) GN being 0, 5 (4-7), and 15 (10-31) days, respectively. The most common predisposing organism was Streptococcus pyogenes (137 of 353, 39%). Drug-resistant nonstreptococcal bacteria were methicillin-resistant Staphylococcus aureus (25%, four of 16), extended-spectrum β-lactamases (20%, 12 of 59), and carbapenem-resistant organisms (10%, six of 59). Twenty of 22 (91%) of the drug-resistant organisms were isolated from the parainfectious group. The most common site of infection was skin in peri- (23 of 97, 24%) and postinfectious GN (61 of 141, 43%), and urinary tract in parainfectious GN (35 of 115, 30%). Of 321 patients with >3 months of follow-up, 48 (15%) developed kidney failure over a median period of 10 (2-37) months and 14 (4%) died. Parainfectious GN, eGFR<30 ml/min per 1.73 m2, moderate-to-severe interstitial fibrosis and tubular atrophy, and nontreatment with renin-angiotensin system blockers were significant risk factors for progression to kidney failure by a Cox proportional-hazards model. Along with clinical and histologic predictors, parainfectious GN caused predominantly by nonstreptococcal and drug-resistant bacterial infections was associated with poor kidney prognosis.

Renin-angiotensin system inhibition reverses the altered triacylglycerol metabolic network in diabetic kidney disease.

Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). Determining the changes in individual lipids and lipid networks across a spectrum of DKD severity may identify lipids that are pathogenic to DKD progression. We performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.

Elevated glucose level leads to rapid COVID-19 progression and high fatality

ObjectivesWe aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients.MethodsWe enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality.ResultsThe median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8–5.5), 3.0 (1.0–7.0), 3.0 (1.0–8.0), and 6.5 (4.0–16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19.ConclusionsOlder age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.

Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS)

Monoclonal gammopathy of undetermined significance (MGUS) is rare in young patients (age <40 years at diagnosis), with a prevalence of <0.3%, representing ~2% of all patients with MGUS. We hypothesized that MGUS detected in young patients may be associated with a higher risk of progression. We examined 249 patients with MGUS < 40 years old. Among these, 135 patients had immune-related conditions, including infections, autoimmune and inflammatory disorders at the time of diagnosis of MGUS. The risk of progression to multiple myeloma or a related disorder at 5 years and 10 years was 6.0% and 13.8%, respectively. The size of M protein was a significant risk factor for progression (HR 4.2, 95% CI 2.2–7.9). There was a trend that the risk of progression was higher in patients without immune-related conditions (HR 2.36, 95% CI 0.85–6.52, p = 0.088). The M protein resolved in 36 (14%) patients, with a greater likelihood of resolution in patients with immune-related conditions (RR 1.9, 95% CI 1.02–3.6). Young patients with MGUS have a similar risk of progression as older patients, 1.4% per year. Over 50% are diagnosed in the setting of immune-related disorders. Patients with immune-related disorders may have a lower risk of progression.

Severity of foot process effacement is associated with proteinuria in patients with IgA nephropathy.

BackgroundProteinuria is a significant risk factor for progression of IgA nephropathy (IgAN) and has a positive correlation with severity of foot process effacement (FPE). We evaluated the relationship of FPE with proteinuria and histologic characteristics, including the Oxford classification.MethodsPatients who underwent renal biopsy and were diagnosed with IgAN at a single center were retrospectively reviewed. Patients aged less than 18 years and those with the possibility of secondary causes were excluded from the study. Subsequently, we evaluated the association between degree of proteinuria, severity of FPE, and histologic characteristics, including the Oxford classification and other immunofluorescence stains.ResultsA total of 805 cases of renal biopsy was performed at our institution, and 327 patients were diagnosed with IgAN. Among them, 82 patients were excluded. Severity of FPE had an impact on the degree of proteinuria. Notably, the group with diffuse FPE had more than about 1.3 g/day of urine protein compared to those with rare FPE. Among the histologic characteristics, M1 score and immune deposition of IgG affected severity of FPE (hazard ratios [95% confidence interval], 1.90 [1.10 to 3.26], and 3.77 [1.66 to 8.54], respectively).ConclusionSeverity of FPE had an impact on the degree of proteinuria and may be associated with the pathogenesis of IgAN.

Long-term outcome of postmenopausal women with proliferative endometrium on endometrial sampling

Proliferative endometrium has been reported in 15% of endometrial biopsies of women aged 50 years and older. Contrary to endometrial hyperplasia, proliferative endometrium has not been associated with the risk of endometrial cancer. This study aimed to report on the long-term outcome of postmenopausal women who received a diagnosis of proliferative endometrium. This is a retrospective cohort study of 1808 women aged 55 years and older who underwent endometrial sampling between January 1997 and December 2008. Outcome data were available through February 2018. Women with a proliferative endometrium were compared with those with an atrophic endometrium for future development of endometrial hyperplasia or cancer. A subanalysis was performed for those who presented with postmenopausal bleeding. Uni- and multivariable logistic regression analyses were used to assess for confounders. In this study, 297 women (16.4%) received a diagnosis of proliferative endometrium. Furthermore, 962 women met the inclusion criteria. Among those women, 278 had a proliferative endometrium, and 684 had an atrophic endometrium. Women with a proliferative endometrium were younger (61.2 vs 64.5 years; P<.0001) and had a higher body mass index (33.9 vs 30.6 kg/m2; P<.0001). More African American women had a proliferative endometrium. Both groups had a similar length of surveillance (11.9 vs 11.5 years; P=.27). Women with a proliferative endometrium had a higher risk of developing endometrial hyperplasia or cancer (11.9% vs 2.9%; P<.0001), any endometrial cancer (5.8% vs 1.8%; P=.002), atypical endometrial hyperplasia (2.2% vs 0.4%; P=.02), and nonatypical endometrial hyperplasia (2.0% vs 0.7%; P=.001). The risk of developing endometrial cancer and endometrial hyperplasia remained similar after excluding cases on hormonal replacement therapy (12.2% vs 3%; P=.001). On logistic regression analysis, proliferative endometrium histology (odds ratio, 3.89; 95% confidence interval, 2.03-7.49; P<.0001), age >60 years (odds ratio, 1.98; 95% confidence interval, 1.03-3.82; P=.04), and body mass index >35 kg/m2 (odds ratio, 2.3; 95% confidence interval, 1.09-4.83; P<.0001) remained significant risk factors for progression to cancer. One of the 6 postmenopausal women who underwent endometrial sampling had a proliferative endometrium. Furthermore, 11.9% of women developed endometrial hyperplasia or cancer, a 4-fold greater incidence than women with an atrophic endometrium. The findings of this study suggest that long-term monitoring is warranted for women with postmenopausal bleeding and a proliferative endometrium histology. Further studies are needed to examine if a treatment is required to negate the risk of unopposed estrogen.

Prospective Clinical Study of Keratoconus Progression in Patients Awaiting Corneal Cross-linking.

Keratoconus progression should be treated with corneal cross-linking (CXL) in a timely manner. This study aimed to investigate patient factors associated with keratoconus progression between time of listing and at time of CXL. Prospective observational study at a tertiary center. Ninety-six eyes of 96 patients with keratoconus. Demographic, clinical, and tomographic parameters were analyzed to determine the risk factors for keratoconus progression. Analyzed tomographic indices included steepest keratometry, average keratometry, cornea thinnest point, index of surface variance, index of vertical asymmetry, keratoconus index, center keratoconus index, index of height asymmetry, and index of height decentration. A total of 38 eyes (39.6%) were found to have keratoconus progression during an average waiting time of 153 ± 101 days. There were significant differences in preoperative tomographic parameters such as index of surface variance (111.3 ± 36.6 vs. 88.3 ± 31.8; P = 0.002), index of vertical asymmetry (1.1 ± 0.4 vs. 0.9 ± 0.4; P = 0.005), keratoconus index (1.31 ± 0.12 vs. 1.22 ± 0.11; P < 0.001), and index of height decentration (0.16 ± 0.07 vs. 0.11 ± 0.06; P = 0.015) between eyes that progressed and those that remained stable. There were no significant differences in steepest keratometry, average keratometry, cornea thinnest point, and center keratoconus index. Multivariate analysis did not reveal age, presence of atopy/atopic keratoconjunctivitis, eye rubbing, or waiting time to be a significant risk factor for progression; however, Maori ethnicity was a risk factor (odds ratio = 3.89; P = 0.02). A significant proportion of eyes were found to be progressing while waiting for CXL. A risk stratification score for patients awaiting CXL may reduce the risk of progression.

Long-term outcome of postmenopausal women with non-atypical endometrial hyperplasia on endometrial sampling.

To assess the long-term outcome of postmenopausal women diagnosed with non-atypical endometrial hyperplasia (NEH). This was a retrospective study of women aged 55 or older who underwent endometrial sampling in our academic medical center between 1997 and 2008. Women who had a current or recent (< 2 years) histological diagnosis of NEH were included in the study group and were compared with those diagnosed with atrophic endometrium (AE). Outcome data were obtained until February 2018. The main outcomes were risk of progression to endometrial carcinoma and risk of persistence, recurrence or new development of endometrial hyperplasia (EH) ('persistent EH'). Logistic regression analysis was used to identify covariates that were independent risk factors for progression to endometrial cancer or persistent EH. During the study period, 1808 women aged 55 or older underwent endometrial sampling. The median surveillance time was 10.0 years. Seventy-two women were found to have a current or recent diagnosis of NEH and were compared with 722 women with AE. When compared to women with AE, women with NEH had significantly higher body mass index (33.9 kg/m2 vs 30.6 kg/m2 ; P = 0.01), greater endometrial thickness (10.00 mm vs 6.00 mm; P = 0.01) and higher rates of progression to type-1 endometrial cancer (8.3% vs 0.8%; P = 0.0003) and persistent NEH (22.2% vs 0.7%; P < 0.0001). They also had a higher rate of progression to any type of uterine cancer or persistent EH (33.3% vs 3.5%; P < 0.0001). Women with NEH had a significantly higher rate of future surgical intervention (51.4% vs 15.8%; P < 0.0001), including future hysterectomy (34.7% vs 9.8%; P < 0.0001). On multivariable logistic regression analysis, only NEH remained a significant risk factor for progression to endometrial cancer or persistence of EH. Postmenopausal women with NEH are at significant risk for persistent EH and progression to endometrial cancer, at rates higher than those reported previously. Guidelines for the appropriate management of postmenopausal women with NEH are needed in order to decrease the rate of persistent disease or progression to cancer. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.