Candidates to salvage therapy after external-beam radiotherapy of prostate cancer: Predictors of local recurrence volume and metastasis-free survival

PurposeThe purpose of this study was to assess the predictors of metastasis-free survival (MFS) and of the volume of the local recurrence in patients with rising prostate-specific antigen (PSA) serum level after radiotherapy for prostate cancer and referred for prostate magnetic resonance imaging (MRI) and biopsy in view of salvage treatment.Materials and methodsA total of 132 consecutive men (median age, 70 years; IQR, 66–77 years) with rising PSA after prostate radiotherapy who underwent prostate MRI and biopsy in view of salvage treatment between January 2010 and July 2017 were retrospectively evaluated at a single center. MFS predictors were assessed with Cox models. Predictors of the volume of the local recurrence (number of invaded prostate sectors at biopsy) were assessed using Poisson regression among variables available at PSA relapse.ResultsAt multivariate analysis, an initial Gleason score ≥ 8 (OR = 7 [95% confidence interval (CI): 1.2–40]; P = 0.03), a recent radiotherapy (OR = 17 [95% CI: 3.9–72]; P < 0.0001), the use of androgen deprivation therapy at PSA relapse (OR = 12.5 [95% CI: 2.8–57]; P = 0.001) and the number of invaded prostate sectors (OR = 1.5 [95% CI: 1.1–2]; P = 0.007) and maximum cancer core length (OR = 0.7 [95%CI: 0.6–0.9]; P = 0.002) at biopsy performed at PSA relapse were significant MFS predictors. The PSA level at relapse was significant independent predictor of the volume of local recurrence only when used as a continuous variable (P = 0.0002) but not when dichotomized using the nadir + 2 threshold (P = 0.41).ConclusionPathological and clinical factors can help predict MFS in patients with rising PSA after prostate radiotherapy and candidates to salvage treatment. The PSA level at relapse has strong influence on the local recurrence volume when used as a continuous variable.     

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population

IntroductionCytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility.Material and methodsA case–control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk.ResultsWe observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01–0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01–0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01–0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01–0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13–2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15–2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09–1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (A_rs11207535C_rs10889159T_rs1155002 and A_rs11207535C_rs10889159C_rs1155002) significantly decreased COPD risk.ConclusionIt suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.     

The impact of serum albumin and serum protein levels on POSSUM score of patients with proximal femur fractures

BackgroundPOSSUM was developed to predict risk-adjusted mortality and morbidity rates for surgical procedures. We evaluated the impact of serum albumin and serum protein levels on POSSUM scores.MethodsMedical files of 2269 patients operated for proximal femur fractures were reviewed. Preoperative serum albumin levels were available for 387 patients (mean 35.1 g/l, range 22–49) and serum protein levels for 279 patients (mean 61.6 g/l, range 40–86).ResultsSerum albumin and protein levels were inversely associated with mortality in multivariate models (albumin, OR = 0.89, p = 0.009; protein, OR = 0.92, p = 0.009) and in composite outcome models as well (albumin, OR = 0.955, p = 0.219, protein, OR = 0.94, p = 0.014). The area under the curve (AUC) for POSSUM prediction of mortality (n = 1770) was 0.632 (95% CI: 0.580–0.684, p < 0.001). The AUC for a model including serum protein levels was 0.742 (95% CI: 0.649–0.834, p < 0.001). Hospitalisation time was longer for patients with lower serum proteins levels (p = 0.045), with an inverse correlation (Pearson correlation −0.164, p = 0.011).ConclusionsLower preoperative serum albumin and serum protein levels were associated with increased risk for mortality, increased hospitalisation time and poorer outcomes in patients operated for proximal femoral fractures. Including those values to POSSUM scores would increase their predictive power.     

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis

BackgroundThe role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.ObjectiveTo assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT + BT).Design, setting, and participantsWe identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT + BT).Outcome measurements and statistical analysisBiochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.Results and limitationsA total of 299 EBRT patients (41%) and 320 EBRT + BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT + BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT + BT groups were 58% and 78%, respectively. The median follow-up was 5.6 yr. WPRT was associated with improved bRFS among patients treated with EBRT + BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2–0.9, p = 0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6–1.2, p = 0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7–1.7, p = 0.8 for DMFS and HR 0.7, 95% CI 0.4–1.1, p = 0.1 for PCSS), or in the EBRT + BT group (HR 0.6, 95% CI 0.3–1.4, p = 0.2 for DMFS and HR 0.5 95% CI 0.2–1.2, p = 0.1 for PCSS).ConclusionsWPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT + BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT + BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.Patient summaryWhen men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.     

La obesidad,la hipertensión y la diabetes mellitus afectan la tasa de complicaciones de las diferentes técnicas de nefrectomía

IntroductionTo investigate whether obesity, hypertension, and diabetes mellitus (DM) would increase post-nephrectomy complication rates using standardized classification method.MethodsWe retrospectively included 843 patients from March 2006 to November 2012, of whom 613 underwent radical nephrectomy (RN) and 229 had partial nephrectomy (PN). Modified Clavien classification system was applied to quantify complication severity of nephrectomy. Fisher's exact or chi-square test was used to assess the relationship between complication rates and obesity, hypertension, as well as DM.ResultsThe prevalence of obesity, hypertension, and DM was 11.51%, 30.84%, 8.78%, respectively. The overall complication rate was 19.31%, 30.04%, 35.71% and 36.36% for laparoscopic radical nephrectomy (LRN), open-RN, LPN and open-PN respectively. An increasing trend of low grade complication rate as BMI increased was observed in LRN (P = .027) and open-RN (P < .001). Obese patients had greater chance to have low grade complications in LRN (OR = 4.471; 95% CI: 1.290-17.422; P = 0.031) and open-RN (OR = 2.448; 95% CI: 1.703-3.518; P < .001). Patients with hypertension were more likely to have low grade complications, especially grade ii complications in open-RN (OR = 1.526; 95% CI: 1.055-2.206; P = .026) and open PN (OR = 2.032; 95% CI: 1.199-3.443; P = .009). DM was also associated with higher grade i complication rate in open-RN (OR = 2.490; 95% CI: 331-4.657; P = .016) and open-PN (OR = 4.425; 95% CI: 1.815-10.791; P = .013). High grade complication rates were similar in comparison.ConclusionsObesity, hypertension, and DM were closely associated with increased post-nephrectomy complication rates, mainly low grade complications.     

Association between common risk factors and molecular subtypes in breast cancer patients

BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer.MethodsThis cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis.ResultsThousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15–1.74; p = 0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01–2.25; p = 0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03–2.13; p = 0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83–1.88; p = 0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47–0.97; p = 0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53–1.04; p = 0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93–5.17; p = 0.04) and luminal A (OR 1.87, 95% CI 0.93–3.90, p = 0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06–3.37; p = 0.04 and OR 1.90 95% CI 1.00–3.61; p = 0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43–0.95; p = 0.02 and OR 0.50 95% CI 0.32–0.76; p = 0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands.ConclusionsReproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.     

Long-term follow-up of trauma patients before and after implementation of a physician-staffed helicopter: A prospective observational study

IntroductionThe first Danish Helicopter Emergency Medical Service (HEMS) was introduced May 1st 2010. The implementation was associated with lower 30-day mortality in severely injured patients. The aim of this study was to assess the long-term effects of HEMS on labour market affiliation and mortality of trauma patients.MethodsProspective, observational study with a maximum follow-up time of 4.5 years. Trauma patients from a 5-month period prior to the implementation of HEMS (pre-HEMS) were compared with patients from the first 12 months after implementation (post-HEMS). All analyses were adjusted for sex, age and Injury Severity Score.ResultsOf the total 1994 patients, 1790 were eligible for mortality analyses and 1172 (n = 297 pre-HEMS and n = 875 post-HEMS) for labour market analyses. Incidence rates of involuntary early retirement or death were 2.40 per 100 person-years pre-HEMS and 2.00 post-HEMS; corresponding to a hazard ratio (HR) of 0.72 (95% confidence interval (CI) 0.44–1.17; p = 0.18). The HR of involuntary early retirement was 0.79 (95% CI 0.44–1.43; p = 0.43). The prevalence of reduced work ability after three years were 21.4% vs. 17.7%, odds ratio (OR) = 0.78 (CI 0.53–1.14; p = 0.20). The proportions of patients on social transfer payments at least half the time during the three-year period were 30.5% vs. 23.4%, OR = 0.68 (CI 0.49–0.96; p = 0.03). HR for mortality was 0.92 (CI 0.62–1.35; p = 0.66).ConclusionsThe implementation of HEMS was associated with a significant reduction in time on social transfer payments. No significant differences were found in involuntary early retirement rate, long-term mortality, or work ability.     

Nephron-sparing management (distal ureterectomy with reimplantation of ureter) for carcinoma of distal ureter: A single-center experience

ObjectiveRadical nephroureterectomy with bladder-cuff excision has been the traditional treatment for upper tract urothelial carcinoma because of its high rate of recurrence. However, given the morbidity of nephrectomy and the risk of developing chronic kidney disease or dialysis-dependent renal failure, the nephron-sparing approach may be preferable in selected patients.Materials and methodsA total of 118 patients who received unilateral distal ureterectomy with reimplantation at a single center in Taiwan were included, using surgical code numbers, from March 2006 to December 2014. A total of 82 patients were excluded due to nonmalignancy and 17 due to concomitant bladder cancer. Finally, 19 patients with primary, solitary, unilateral ureter lesions and confirmed to have ureter malignancy (urothelial carcinoma, n = 18; squamous cell carcinoma, n = 1) were included.ResultsOf the 19 patients (13 males and 6 females) included, the mean age was 69.3 ± 10.7 years. Tumor pathological staging was Tis (n = 1), Ta (n = 3), T1 (n = 2), T2 (n = 6), and T3 (n = 5). Histopathology grading was low grade (n = 3) and high grade (n = 13). No local recurrence was noted; nine patients had bladder recurrence (47.4%), three had distant metastasis (15.8%), and two had progression and finally underwent radical nephroureterectomy (10.5%). The mean time to bladder recurrence was 12.4 months (3–24 months); the mean follow-up time was 28.1 months (1–90 months). The 5-year overall survival rate was 73.7% (14/19); four patients were lost to follow-up, and one patient expired. The mean 5-year progression-free survival was 67.74%. The mean preoperative creatinine level was 1.61 mg/dL, and at 12 months after operation it was 1.56 mg/dL (p = 0.95).ConclusionIn selected patients, distal ureterectomy with reimplantation, in our experience, is a feasible option for distal ureter tumor. Favorable postoperative outcomes with a low local recurrence rate, a low rate of progression to nephroureterectomy, and renal function preservation may prove the value of this modality and should be taken into consideration in suitable patients.     

Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis

ObjectiveMany clinical studies have been carried out to investigate the relationship between periodontitis and rheumatoid arthritis (RA). Owing to limited evidence and inconsistent findings among these studies, it is unclear whether periodontitis would increase the risk for RA. This meta-analysis was performed to evaluate whether periodontitis represents a risk factor for RA.MethodsPubMed, Cochrane Library, Embase, Web of Science, and Wanfang were searched for eligible studies that compared periodontitis patients with controls. A pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between periodontitis and RA.ResultsThirteen studies including a total of 706611 periodontitis patients and 349983 control subjects were included. The pooled OR of RA risk between periodontitis and controls was (OR: 1.69; 95% CI: 1.31–2.17; P < 0.0001), indicating that the patients in periodontitis group had a 69% greater risk for RA than people in control group. When stratified by disease type, the pooled results showed periodontitis represents a risk factor for incident RA (OR = 1.70, 95%CI: 0.75–3.85, P < 0.001) and mixed RA (OR = 1.61, 95%CI: 1.26–2.06; P < 0.001). When stratified by disease duration, the pooled results showed periodontitis represents a risk factor for RA disease duration > 5 years (OR = 2.88, 95%CI: 0.66–12.62, P = 0.018), disease duration < 5 years (OR = 2.59, 95%CI: 0.83–8.11, P < 0.001), mixed disease duration (OR = 1.53; 95%CI: 1.05–2.22, P < 0.001).ConclusionOur meta-analysis revealed an increased risk of RA in patients with periodontitis compared to healthy controls. Moreover, when stratified by disease type, there was a higher risk between incident RA and periodontitis. When stratified by disease duration, the patients with periodontitis might be more closely associated with the RA patients with disease duration >5 years.     

Risk factors for failed conversion of labor epidural analgesia to cesarean delivery anesthesia: a systematic review and meta-analysis of observational trials

BackgroundThis systematic review and meta-analysis evaluates evidence for seven risk factors associated with failed conversion of labor epidural analgesia to cesarean delivery anesthesia.MethodsOnline scientific literature databases were searched using a strategy which identified observational trials, published between January 1979 and May 2011, which evaluated risk factors for failed conversion of epidural analgesia to anesthesia or documented a failure rate resulting in general anesthesia.Results1450 trials were screened, and 13 trials were included for review (n = 8628). Three factors increase the risk for failed conversion: an increasing number of clinician-administered boluses during labor (OR = 3.2, 95% CI 1.8–5.5), greater urgency for cesarean delivery (OR = 40.4, 95% CI 8.8–186), and a non-obstetric anesthesiologist providing care (OR = 4.6, 95% CI 1.8–11.5). Insufficient evidence is available to support combined spinal–epidural versus standard epidural techniques, duration of epidural analgesia, cervical dilation at the time of epidural placement, and body mass index or weight as risk factors for failed epidural conversion.ConclusionThe risk of failed conversion of labor epidural analgesia to anesthesia is increased with an increasing number of boluses administered during labor, an enhanced urgency for cesarean delivery, and care being provided by a non-obstetric anesthesiologist. Further high-quality studies are needed to evaluate the many potential risk factors associated with failed conversion of labor epidural analgesia to anesthesia for cesarean delivery.     

Diagnosis of postoperative recurrence of Crohn disease with MR-enterography: Value of diffusion-weighted imaging

PurposeTo compare the diagnostic capabilities of MR enterography (MRE) using contrast-enhanced (CE) sequences with those of MRE using diffusion-weighted (DW) imaging for the diagnosis of postoperative recurrence at the neo-terminal ileum and/or anastomosis after ileocolonic resection in patients with Crohn disease (CD), and to clarify the role of additional DW imaging to CE-MRE in this context.Material and methodsForty patients who underwent ileal resection for CD, and both endoscopy and MRE within the first year after surgery were included. There were 21 men and 19 women, with a mean age of 38 years ± 12 (SD) years (range: 18–67 years). MRE examinations were blindly analyzed independently by one senior (R1) and one junior (R2) radiologist for the presence of small bowel postoperative recurrence at the anastomotic site. During a first reading session, T2-, steady-state- and DW-MRE were reviewed (DW-MRE or set 1). During a separate distant session, T2-, steady-state- and CE-MRE were reviewed (CE-MRE or set 2). Lastly, all sequences were analyzed altogether (set 3). Performances of each reader for the diagnosis of postoperative recurrence were evaluated using endoscopic findings as the standard of reference (Rutgeerts score ≥ i2b).ResultsFifteen patients out of 40 (37.5%) had endoscopic postoperative recurrence at the anastomotic site. Sensitivity for the diagnosis of postoperative recurrence was 73% (95% CI: 51–96%) for R1 and 67% (95% CI: 43–91%) for R2 using set 1, and 80% (95% CI: 60–100%) for both readers using set 2. There was no significant differences in sensitivity between reading set 1 and reading set 2, for either R1 or R2 (R1, P  > 0.99; R2, P = 0.48). Specificity was 96% (95% CI: 88–100%) for both readers using set 1 or using set 2. Reading set 3 yielded an area under the ROC curve (AUC) of 0.93 (95% CI: 0.84–1) versus 0.89 (95% CI: 0.75–1) with set 1 (P = 0.18) and versus 0.89 (95% CI: 0.78–1) with set 2 (P = 0.21). No significant differences in AUC were found between set 1 or 2 and set 3 (P = 0.18), nor between set 1 and 2 (P = 0.76). Accuracies were 88% (95% CI: 74–95%) and 85% (95% CI: 71–93%) for DW-MRE for R1 and R2, respectively; 90% (95% CI: 77–96%) for CE-MRE for both readers; and 93% (95% CI: 80–97%) and 88% (95% CI: 74–95%) for R1 and R2 with set 3, respectively.ConclusionDW-MRE has diagnostic capabilities similar to those of CE-MRE for the diagnosis of postoperative recurrence of CD at the anastomotic site.     

Survey of nulliparous parturients' attitudes regarding timing of epidural analgesia initiation

Study objectiveAt our hospital, although > 90% of nulliparous parturients eventually choose epidural analgesia for labor, many delay its initiation, experiencing considerable pain in the interim. This survey probed parturients' views about the timing of initiation of epidural labor analgesia.DesignSingle-center, nonrandomized quantitative survey.SettingLabor and delivery suite in a large tertiary academic medical center.PatientsTwo hundred laboring nulliparous women admitted to the labor and delivery suite.Interventions: After their pain was relieved, parturients completed a questionnaire regarding their decision to request labor epidural analgesia.MeasurementsA variety of factors regarding epidural use were assessed including the influence of painful contractions and of childbirth education class attendance on the decision to request epidural analgesia, and parturients' perception of the timing of epidural initiation on the progress and outcome of labor.Main resultsAnalysis revealed that the desire of parturients to use epidural analgesia was increased from 27.9% before the onset of painful contractions to 48.2% after (p < 0.01). Two-thirds of participants attended a non-physician taught childbirth education class. An antepartum plan to definitely forgo an epidural was 1.8 times more likely among women who attended a childbirth class when compared to those who did not attend. (OR = 1.8; 95%CI:1.1–3.1; p = 0.04). The most common views affecting decision-making were that epidural analgesia should not be administered “too early” (67.5%), and that it would slow labor (68.5%). Both of these views were more likely to be held if the parturient had attended a childbirth class, OR = 2.0 (95%CI:1.1–3.8; p = 0.03) and OR = 2.0 (95% CI: 1.1 to 3.7; p = 0.03), respectively.ConclusionsWe found that nulliparous parturients have misconceptions about epidurals, which are not supported by evidence-based medicine. Moreover, we found that attendance at childbirth education classes was associated with believing these misconceptions.     

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome*

ObjectivesTo assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients.MethodsIn this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected.ResultsA total of 253 patients (245 females) with confirmed pSS, aged 56.6 ± 13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio–OR– = 1.25 per OSS unit increase; confidence interval–CI–95% = 1.05–1.49; P = 0.01; OR = 1.31 per OSS unit increase; CI95% = 1.09–1.58, P = 0.002, and OR = 1.34 per OSS unit increase; CI95% = 1.12–1.59; P = 0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR = 2.03; CI95% = 1.03–4.00; P < 0.05 and OR = 2.52, CI95% = 1.31–4.90; P < 0.01, respectively).ConclusionAssociation between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.     

Prediction of overall survival in patients with hepatocellular carcinoma treated with Y-90 radioembolization by imaging response criteria

PurposeTo evaluate the potential of imaging criteria in predicting overall survival of patients with hepatocellular carcinoma (HCC) after a first transcatheter arterial yttrium-90 radioembolization (TARE)Materials and methodsFrom October 2013 to July 2017, 37 patients with HCC were retrospectively included. There were 34 men and 3 women with a mean age of 60.5 ± 10.2 (SD) years (range: 32.7–78.9 years). Twenty-five patients (68%) were Barcelona Clinic Liver Cancer (BCLC) C and 12 (32%) were BCLC B. Twenty-four primary index tumors (65%) were > 5 cm. Three radiologists evaluated tumor response on pre- and 4–7 months post-TARE magnetic resonance imaging or computed tomography examinations, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified RECIST (mRECIST), European Association for Study of the Liver (EASL), volumetric RECIST (vRECIST), quantitative EASL (qEASL) and the Liver Imaging Reporting and Data System treatment response algorithm. Kaplan–Meier survival curves were used to compare responders and non-responders for each criterion. Univariate and multivariate Cox proportional hazard ratio (HR) analysis were used to identify covariates associated with overall survival. Fleiss kappa test was used to assess interobserver agreement.ResultsAt multivariate analysis, RECIST 1.1 (HR: 0.26; 95% confidence interval [95% CI]: 0.09–0.75; P = 0.01), mRECIST (HR: 0.22; 95% CI: 0.08–0.59; P = 0.003), EASL (HR: 0.22; 95% CI: 0.07–0.63; P = 0.005), and qEASL (HR: 0.30; 95% CI: 0.12–0.80; P = 0.02) showed a significant difference in overall survival between responders and nonresponders. RECIST 1.1 had the highest interobserver reproducibility.ConclusionRECIST and mRECIST seem to be the best compromise between reproducibility and ability to predict overall survival in patients with HCC treated with TARE.     

Higher prevalence of morphometric vertebral fractures in patients with recent coronary events independently of BMD measurements

Cardiovascular disease and osteoporosis are important causes of morbi-mortality in the elderly and may be mutually related. Low bone mineral density (BMD) may be associated with increased risk of cardiovascular events. We investigated the prevalence of low bone mass and fractures in metabolic syndrome patients with acute coronary events. A case–control study was conducted with 150 individuals (30–80 years-old) with metabolic syndrome. Seventy-one patients had had an acute coronary syndrome episode in the last 6 months (cases) and the remaining 79 had no coronary event (controls). Cases and controls were matched for gender, BMI and age. DXA measurements and body composition were performed while spine radiographs surveyed for vertebral fractures and vascular calcification. Biochemical bone and metabolic parameters were measured in all patients. No statistically significant difference in BMD and the prevalence of osteopenia, osteoporosis and non-vertebral fractures was observed between cases and controls. The prevalence of vertebral fractures and all fractures was higher in the cases (14.1 versus 1.3%, p = 0.003 and 22.5versus7.6%, p = 0.010, respectively). Male gender (OR = 0.22 95% CI 0.58 to 0.83, p = 0.026) and daily intake of more than 3 portions of dairy products (OR = 0.19 95% CI 0.49 to 0.75, p = 0.017) were associated with lower prevalence of fractures. Cases had higher risk for fractures (OR = 4.97, 95% CI 1.17 to 30.30, p = 0.031). Bone mass and body composition parameters were not associated with cardiovascular risk factors or bone mineral metabolism. Patients with fragility fractures had higher OPG serum levels than those without fractures (p < 0.001). Our findings demonstrated that patients with recent coronary events have a higher prevalence of vertebral fractures independently of BMD.     

Prognostic Role of Overt Hypercortisolism in Completely Operated Patients with Adrenocortical Cancer

BackgroundAlthough prognostic parameters are important to guide adjuvant treatment, very few have been identified in patients with completely resected adrenocortical carcinoma (ACC).ObjectiveTo assess the prognostic role of clinical symptoms of hypercortisolism in a large series of patients with completely resected ACC.Design, setting, and participantsA total of 524 patients followed at referral centers for ACC in Europe and the United States entered the study. Inclusion criteria were ≥18 yr of age, a histologic diagnosis of ACC, and complete surgery (R0). Exclusion criteria were a history of other malignancies and adjuvant systemic therapies other than mitotane.InterventionAll ACC patients were completely resected, and adjuvant mitotane therapy was prescribed at the discretion of the investigators.Outcome measurements and statistical analysisThe primary end point was overall survival (OS). The secondary end points were recurrence-free survival (RFS) and the efficacy of adjuvant mitotane therapy according to cortisol secretion.Results and limitationsOvert hypercortisolism was observed in 197 patients (37.6%). Patients with cortisol excess were younger (p = 0.002); no difference according to sex and tumor stage was observed. The median follow-up of the series was 50 mo. After adjustment for sex, age, tumor stage, and mitotane treatment, the prognostic significance of cortisol excess was highly significant for both RFS (hazard ratio [HR]: 1.30; 95% confidence interval [CI], 1.04–2.62; p = 0.02) and OS (HR: 1.55; 95% CI, 1.15–2.09; p = 0.004). Mitotane administration was associated with a reduction of disease progression (adjusted HR: 0.65; 95% CI, 0.49–0.86; p = 0.003) that did not differ according to the patient's secretory status. A major limitation is that only symptomatic patients were considered as having hypercortisolism, thus excluding information on the prognostic role of elevated cortisol levels in the absence of a clinical syndrome.ConclusionsClinically relevant hypercortisolism is a new prognostic factor in patients with completely resected ACC. The efficacy of adjuvant mitotane does not seem to be influenced by overt hypercortisolism.     

Age- and sex-specific effects of obesity,metabolic syndrome and its components on back pain: The English Longitudinal Study of Ageing

ObjectivesWe aimed to investigate age- and sex-specific effects of obesity, metabolic syndrome (MetS) and its components on back pain in middle-aged and older English individuals.MethodsWe used data from the English Longitudinal Study of Ageing, wave 2 (2004–2005). Body mass index (BMI) expressed the obesity, while MetS was defined according to revised Adult Treatment Panel (ATP) III criteria. We assessed associations between obesity, MetS and its components with presence and severity of back pain and provided estimates per strata, middle-aged (50–64 years) and older (65–79 years), women and men.ResultsThe study sample included 3328 participants, 1021 and 835 middle-aged women and men and 773 and 699 older women and men, respectively. We found that BMI (OR = 1.07, 95% CI 1.05–1.09), MetS (OR = 1.47, 95% CI 1.22–1.77), high waist circumference (WC), high triglycerides (TG), and high fasting blood glucose were associated with the presence of back pain. Effects of BMI were consistent across the strata. However, MetS was associated with back pain only in women, middle-aged (OR = 1.59, 95% CI 1.14–2.21) and older (OR = 1.43, 95% CI 1.01–2.05). The MetS component driving this association was high WC, supported by high TG in older women. Higher BMI, presence of MetS, high blood pressure and TG were associated with back pain severity.ConclusionsWe found that obesity was associated with the presence and severity of back pain, irrespective of age and sex. However, we found women-specific effects of MetS driven by high WC, indicating that metabolic dysregulation contributes to back pain pathophysiology in women.     

Veterans Affairs Cooperative Studies Program Study #553: Chemotherapy After Prostatectomy for High-risk Prostate Carcinoma: A Phase III Randomized Study

BackgroundThe Veterans Affairs Cooperative Studies Program study #553 was designed to evaluate the efficacy of adjuvant chemotherapy added to the standard of care (SOC) for patients who are at high risk for relapse after prostatectomy.ObjectiveTo test whether addition of chemotherapy to surgery for high-risk prostate cancer improves progression-free survival (PFS).Design, setting, and participantsEligible patients after prostatectomy were randomized to the SOC group with observation or to the chemotherapy group with docetaxel and prednisone administered every 3 wk for six cycles. Randomization was stratified for prostate-specific antigen, Gleason, tumor stage, and surgical margin status.Outcome measurements and statistical analysisThe primary endpoint was PFS. Secondary endpoints included overall, prostate cancer–specific, and metastasis-free survival, and time to androgen deprivation therapy.Results and limitationsA total of 298 of the planned 636 patients were randomized. The median follow-up was 59.1 mo (0.2–103.7 mo). For the primary endpoint, the two groups did not statistically differ in PFS (median 55.5 mo in the chemotherapy group and 42.2 mo in the SOC group; test adjusted for site via gamma frailty p = 0.21; adjusted hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.58–1.11; p = 0.18). Prespecified subgroup analyses showed benefit in PFS for patients with tumor stage ≥T3b (HR 0.54, 95% CI 0.32–0.92; p = 0.022) and patients with Gleason score ≤7 (HR 0.65, 95% CI 0.43–0.99; p = 0.046). Secondary endpoint analyses are hampered by low event rates. The most common adverse events (≥grade 3 related or possibly related to chemotherapy) included neutropenia (43%), hyperglycemia (20%), and fatigue (5%), with febrile neutropenia in 2%.ConclusionsAdjuvant chemotherapy in high-risk prostate cancer using docetaxel and prednisone did not lead to statistically significant improvement in PFS for the intention-to-treat population as a whole. The analysis was challenged by lower power due to accrual limitation. Subgroup analyses suggest potential benefit for patients with Gleason grade ≤7 and stage ≥ pT3b (ClinicalTrials.gov number NCT00132301).Patient summaryIn this randomized trial, we tested whether addition of chemotherapy to surgery for high-risk prostate cancer decreased the risk of prostate-specific antigen rise after surgery. We found no benefit from docetaxel given after radical prostatectomy, although some subgroups of patients may benefit.     

Impacto de la expresión de p53, MIB-1 y PECAM-1 en el pronóstico del carcinoma urotelial de la pelvis renal

ObjectiveDetermine whether the overexpression p53, MIB-1 and PECAM-1 of protein levels is of interest in predicting the prognosis of transitional cell carcinoma of the upper urinary tract (TCC-UUT) with the primary seat in the renal pelvis.Material and methodA univariate and multivariate analysis was conducted for prognosis prediction in a series of 82 patients with TCC-UUT of the renal pelvis who had no metastases at diagnosis (N0/Nx M0) and were treated exclusively with nephroureterectomy. We assessed clinicopathological parameters (age, gender, tumor grade and extent, histological variety, growth pattern, vascular invasion, infiltration of the renal parenchyma, tumor necrosis) and the immunohistochemical expression of p53, MIB-1 (ki-67) and PECAM-1 (CD31) in sections performed with tissue microarray (TMA).ResultsA total of 47.6% of the patients had high-grade lesions according to the USIP-WHO classification. The growth pattern was flat in 15.85%. The distribution by T category was: 3.7% pTa, 51.2% pT1, 11% pT2, 29.3% pT3 and 4.9% pT4. The mean follow-up was 46.8+38.5 (range, 4-172) months. The median survival was reached at 57 (95% CI 44-63) months. The univariate analysis revealed that survival in these patients is associated with tumor size (P = .028), histological variety (P < .0001), growth pattern (P < .0001), grade (P < .0001), pT (P = .01), vascular invasion (P = .025), necrosis (P = .004) and overexpression of p53 (P = .0006), PECAM-1 (P = .0036) and MIB-1 (P = .0038). The Cox regression model showed that high-grade (HR, 4.2; 95% CI 1.28-13.79; P = .018), flat growth pattern (HR, 2.52; 95% CI 1.05-6.03; P = .038) and p53 overexpression (HR, 2.8; 95% CI 1.22-6.44; P = .015) were independent predictors.ConclusionHistological grade, tumor growth pattern and p53 overexpression were established as the primary predictors of prognosis for primary TCC-UUT of the renal pelvis. The independent value of MIB-1 observed in other studies was not reproduced in this study.     

Comparison of prognostic models for burn patients: A retrospective nationwide registry study

BackgroundPrognostic burn index (PBI) is a unique model utilized to predict mortality of burn patients in Japan. In contrast, other prediction models are rarely used in Japan, and their accuracy and predictive value are unknown. The present study aimed to compare commonly used burn prediction models and determine the appropriate model for mortality prediction in Japanese burn patients.MethodsJapanese burn patients registered in the nationwide burn registry of Japanese Society for Burn Injury between April 1, 2011 and March 31, 2019 were reviewed retrospectively. The prognostic performance of PBI was compared with Baux score, revised Baux score, abbreviated burn severity index (ABSI), Ryan score and Belgian outcome in burn injury score (BOBI). The primary outcome was in-hospital mortality.ResultsThe study included 7911 acute burn patients. The overall mortality rate was 10.7%, the median age was 52 (interquartile range, 26–72) years, and the median % total body surface area was 7% (interquartile range, 3%–17%). The areas under the receiver operating characteristic curve for PBI, Baux score, ABSI, revised Baux score, Ryan score, and BOBI were 0.940 (95% confidence interval [CI]: 0.931–0.948), 0.943 (95% CI: 0.934–0.951; p = 0.002), 0.945 (95% CI: 0.937–0.953; p = 0.058), 0.946 (95% CI: 0.937–0.953; p = 0.002), 0.859 (95% CI: 0.846–0.870; p < 0.001), and 0.896 (95% CI: 0.885–0.905; p < 0.001), respectively.ConclusionAlthough the performance of PBI was good, it was not superior to the Baux score, revised Baux score, and ABSI. These three scores have a high prognostic accuracy. Hence, they are considered as alternative burn prognostic scores in Japan. The Baux score was an optimal prognostic model for patients with burns in Japan.