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Introduction: The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high‐volume single center. Methods: Demographic, clinicopathological data on the diagnosis, treatment and follow‐up of all sarcoma patients aged 16–39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late‐treatment effects. Results: We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS). Among STSs, 13% were small round cell tumors (SRCT), 52% intermediate–high‐grade, 24% low‐grade STSs. Among BS, 32% were high‐grade. Median TTD and TTT were 120 (0–8255) and 7 days (0–83), respectively. Surgery was performed in 83%, radiotherapy in 29%, and systemic therapy in 27%. Median follow‐up was 72.9 months(1.6–145), 5‐year and 10‐year OS were 78.5% and 62%, respectively. Kaplan–Meyer analysis showed a significantly better 5‐year OS and PFS for patients with >92 days of TTD (OS 85.7% vs. 66.7%, p = 0.001, PFS 50.2% vs. 24.9%, p = 0.009). According to age (≤25 years vs. > 25 years), 5‐year OS was 69.8% versus 82.2%, respectively (p = 0.047). Conclusion: Our analysis confirmed previous data on sarcoma AYA patients followed in a referral center. Unexpectedly, diagnostic delay was not associated with poor OS and PFS. Patients <25 years showed a poorer prognosis due to the higher incidence of SRCT. [ABSTRACT FROM AUTHOR]

Background: Hospitals may provide less positive patient experiences for older than younger patients. Methods: We used 2019 HCAHPS data from 4358 hospitals to compare patient‐mix adjusted HCAHPS Survey scores for 19 experience of care items for patients ages 75+ versus 55–74 years and tested for interactions of age group with patient and hospital characteristics. We contrasted the age patterns observed for inpatient experiences with those among respondents to the 2019 Medicare CAHPS (MCAHPS) Survey of overall experience. Results: Patients 75+ years (31% of all HCAHPS respondents) reported less‐positive experiences than those 55–74 (46% of respondents) for 18 of 19 substantive HCAHPS items (mean difference −3.3% points). Age differences in HCAHPS top‐box scores were large (>5 points) for 1 of 3 Nurse Communication items, 1 of 3 Doctor Communication, 2 of 2 Communication about Medication items, 1 of 2 Discharge Information items, and 2 of 3 Care Transition items. In contrast, for MCAHPS, those 75+ reported similar experiences to younger adults. The magnitude of age differences varied considerably across hospitals; some hospitals had very large age disparities for older patients (age 75+ vs. ages 55–74), while others had none. These age differences were generally smaller for patients in government and non‐profit than in for‐profit hospitals, and in the Pacific region than in other parts of the United States. This variation in age disparities across hospitals may help to identify best practices. Conclusions: Patients ages 75+ reported less‐positive experiences than patients ages 55–74, especially for measures of communication. These differences may be specific to inpatient care. Further study should investigate the effectiveness of hospital staffs' communication with older patients. Hospital protocols designed for younger patients may need to be adjusted to meet the needs of older patients. There may also be opportunities to learn from outpatient interactions with older patients. See related editorial by Aanand D. Naik in this issue. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis has an important role in thymic epithelial tumors (TETs). Regorafenib inhibits vascular endothelial growth factor receptors (VEGFRs), platelet‐derived growth factor receptor β (PDGFR‐β), and fibroblast growth factor receptors (FGFRs). This study explored the activity of regorafenib as monotherapy in patients with advanced or recurrent B2‐B3 thymoma (T) and thymic carcinoma (TC) previously treated with platinum‐containing chemotherapy. Methods: A Fleming single‐arm, single‐stage, phase 2 trial to evaluate the activity of regorafenib (160 mg once a day by mouth for 3 weeks on/1 week off) was planned. The study was designed to reject the null hypothesis of an 8‐week progression‐free survival (PFS) rate ≤25% with a type I error of 0.10 and a statistical power of 80% at the alternative hypothesis of an 8‐week PFS rate of ≥50% (≥8 of 19 evaluable patients progression‐free at 2 months). Results: From June 2016 to November 2017, 19 patients were enrolled (11T/8TC). We observed partial response (PR) in 1 patient (1T) (5.3%), stable disease (SD) in 14 patients (9T/5TC) (73.7%), and progressive disease in 2 patients (1T/1TC) (10.5%), with a disease control rate of 78.9%. According to Choi‐criteria, 13 patients (68.4%) achieved PR, and 2 patients SD (10.5%). The median PFS was 9.6 months whereas median overall survival was 33.8 months. The 8‐week PFS rate was 78.9% (15 of 19 patients). Grade 3‐4 treatment‐related adverse events were observed in 10 patients (52.6%). Conclusions: The primary end point of this study was reached. The high rate of PR (Choi‐criteria) suggests antitumor activity of regorafenib in TETs. On the basis of survival outcomes, the efficacy of regorafenib should be further evaluated in larger studies. The results of the activity and toxicity profile of regorafenib observed in this small series of thymic epithelial tumors are encouraging and should be better evaluated in subsequent larger and specific study phases. [ABSTRACT FROM AUTHOR]

Background: Significant efforts have been made to investigate the molecular pathways involved in thymic carcinogenesis. However, genetic findings have still not impacted clinical practice. The aim of this exploratory trial was to evaluate the immunoscore and molecular profile of a series of thymic carcinomas (TCs), correlating this data with clinical outcome. Methods: Formalin‐fixed, paraffin‐embedded (FFPE) TC tissues were retrieved from our center archive. The immunoscore was evaluated according to Angell and Gallon. DNA was extracted from FFPE tumor samples and, when available, from adjacent histologically normal tissues. Next‐generation sequencing (NGS) was performed targeting hotspot regions of 50 oncogenes and tumor suppressor genes. Results: A series of 15 TCs were analyzed. After a median follow‐up of 82.4 months, the median overall survival was 104.7 months. The immunoscore was >2 in 5/15 patients (33%). Among the investigated genes, absence of mutations was observed in 5/15 patients (33%), whereas three variants in 1/15 (6%) patient, two variants in 4/15 (26%) patients, and one variant in 5/15 patients (33%) were found. The most recurrently mutated genes were FGFR3 (five mutations) and CDKN2A (three mutations, two of which were nonsense). Patients with CDKN2A loss showed a statistically significantly worse survival (P = 0.0013), whereas patients with FGFR3 mutations showed a statistically significantly better survival (P = 0.048). Conclusions: This study adds data to the few existing reports on the mutational landscape of TCs, providing the first comprehensive analysis to date. Here, we confirm the low rate of mutations in TCs and suggest FGFR3 and CDKN2A mutations as intriguing potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective: To describe differences in patient experiences of hospital care by preferred language within racial/ethnic groups.Data Source: 2014-2015 HCAHPS survey data.Study Design: We compared six composite measures for seven languages (English, Spanish, Russian, Portuguese, Chinese, Vietnamese, and Other) within applicable subsets of five racial/ethnic groups (Hispanics, Asian/Pacific Islanders, American Indian/Alaska Natives, Blacks, and Whites). We measured patient-mix adjusted overall, between- and within-hospital differences in patient experience by language, using linear regression.Data Collection Methods: Surveys from 5 480 308 patients discharged from 4517 hospitals 2014-2015.Principal Findings: Within each racial/ethnic group, mean reported experiences for non-English-preferring patients were almost always worse than their English-preferring counterparts. Language differences were largest and most consistent for Care Coordination. Within-hospital differences by language were often larger than between-hospital differences and were largest for Care Coordination. Where between-hospital differences existed, non-English-preferring patients usually attended hospitals whose average patient experience scores for all patients were lower than the average scores for the hospitals of their English-preferring counterparts.Conclusions: Efforts should be made to increase access to better hospitals for language minorities and improve care coordination and other facets of patient experience in hospitals with high proportions of non-English-preferring patients, focusing on cultural competence and language-appropriate services. [ABSTRACT FROM AUTHOR]

Given its anti-angiogenic activity, lenalidomide may have a role in the treatment of POEMS (Peripheral neuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder and Skin changes) syndrome. This prospective, open-label, pilot study evaluated the combination of lenalidomide + dexamethasone (RD) in 18 POEMS syndrome patients (13 pre-treated, 5 newly-diagnosed but ineligible for high-dose therapy). Treatment consisted of six cycles of lenalidomide (25 mg/day for 21 days followed by 7 days rest) plus dexamethasone (40 mg/once a week). Patients responding after six cycles continued treatment until progression or unbearable toxicity. The primary endpoint was the proportion of patients with either neurological or clinical improvement. The RD combination was considered as deserving further evaluation if 9 of the first 15 patients responded. Ten responses were observed among the first 15 enrolled patients, meeting the primary endpoint. Fifteen of 18 patients (83%) completed six RD cycles: 13 (72%) patients responded and nine had both clinical and neurological improvement. Among the 15 patients who completed the six RD cycles, four were still on treatment after a 25-month follow-up. At 39 months of follow-up, all patients were alive with a 3-year progression-free survival of 59%. No patient discontinued RD for toxicity. Overall, the RD regimen showed a high incidence of prolonged symptoms improvement and was well tolerated in most POEMS patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of metabolic parameters analyzed at baseline and at interim FDG-PET in predicting disease outcome in unresectable MPM patients receiving pemetrexed-based chemotherapy. A consecutive series of MPM patients treated between February 2004 and July 2013 with first-line pemetrexed-based chemotherapy, and evaluated by FDG-PET and CT scan at baseline and after two cycles of chemotherapy, was reviewed. Best CT scan response was assessed according to modified RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were correlated with FDG-PET parameters, such as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and percentage changes in SUVmax (∆SUV) and TLG (∆TLG). Overall, 142 patients were enrolled; 77 (54%) received talc pleurodesis before chemotherapy. Baseline SUVmax and TLG showed a statistically significant correlation with PFS and OS ( P < 0.05) in both group of patients (treated and untreated with pleurodesis). In 65 patients not receiving pleurodesis, SUVmax reduction ≥25% (∆SUV ≥ 25%) and TLG reduction ≥30% (∆TLG ≥ 30%) were significantly associated with longer PFS ( P < 0.05). Patients showing both ∆SUV ≥ 25% and ∆TLG ≥ 30% responses had a significant reduction in the risk of disease progression (HR:0.31, P < 0.001) and death (HR:0.52, P = 0.044). Neither ∆SUV nor ∆TLG showed similar association with survival outcomes in patients treated with pleurodesis. Our study confirmed the prognostic role of baseline FDG-PET in a large series of MPM patients treated with first-line pemetrexed-based chemotherapy. Moreover, use of ∆SUV ≥ 25% and ∆TLG ≥ 30% as cut-off values to define early metabolic response supported the role of FDG-PET in predicting disease outcome and treatment response in patients not receiving pleurodesis. [ABSTRACT FROM AUTHOR]

Objectives To use items from the Medicare Health Outcomes Survey ( HOS) to adapt or validate a simple method for identifying community-dwelling older adults at greater risk of death and to extend the method to identify a very high-risk group. Design Analysis of longitudinal data. Setting National sample of beneficiaries from Medicare Advantage plans with 500 or more enrollees. Participants Medicare beneficiaries aged 65 and older responding to 2009 baseline and 2011 follow-up HOS (N = 238,687). Measurements Bivariate and multivariate analyses of the HOS; adaptation and validation of a previously validated Vulnerable Elders Survey-13 ( VES-13) scoring system that uses age and self-reported function to predict mortality. Results A modified predictive model, that uses substitutes for several items in the previously validated VES-13, predicted 2-year mortality; 10.6% of those scoring 3 or more, and 2.4% of those scoring less than 3 died within 2 years (relative risk of death 4.4, similar to 4.2 for the original VES-13 sample), and 15.5% of those scoring 7 or more died within 2 years (relative risk of death (relative to scores <3) of 6.5). Sixteen percent of HOS beneficiaries were missing some data; 2-year mortality for those with missing items was 9.5%, versus 7.1% for those with no missing items ( P < .001). Imputation of median values for missing VES-13 items results in valid predictions of mortality for those with partially missing data. Conclusion The VES-13 algorithm is robust to substitution of functional items and can be used to identify very high-risk older adults. Multiple imputation of missing items reduces loss-to-follow-up bias and increases sample size. [ABSTRACT FROM AUTHOR]

KRAS mutant colorectal cancer ( CRC) patients develop lung and brain metastases more frequently than KRAS wild-type ( WT) counterpart. We retrospectively investigated the prognostic role of KRAS, BRAF, and PIK3 CA (exon 20) mutations and loss of phosphatase and tensin homolog ( PTEN) in surgically resected lung metastases. Lung specimens from 75 metastatic CRC ( mCRC) patients treated with one or more metastasectomies with curative intent were analyzed. Sixty-four percent of patients had KRAS WT lung metastases. PTEN loss-of-function was found in 75%. BRAF and PIK3 CA exon 20 mutations were not found. Seven patients subsequently developed brain metastases and 43% of them had KRAS mutation. In univariate analysis, median overall survival ( OS) for KRAS WT patients was longer, compared to KRAS mutant patients (median 60.9 vs. 36.6 months, P = 0.035). In addition, both progression-free survival ( PFS) and lung disease-free survival ( LDFS) between lung surgery and relapse were not associated with KRAS and PTEN status. In multivariate analysis, the risk of death was significantly increased by KRAS mutational status ( OS Hazard ratio ( HR) 2.17, 95% IC 1.19-3.96, P = 0.012) and lack of adjuvant chemotherapy ( OS HR 0.10, 95% IC 0.01-0.74, P = 0.024). The proportion of KRAS mutations in lung metastases was similar to the expected proportion in primary tumors. Patients harboring KRAS mutation had a poorer survival rate compared to WT group both in univariate and multivariate analysis. Moreover, administration of adjuvant chemotherapy after lung metastasectomy ( LM) significantly improved both PFS and OS. KRAS mutation is a negative prognostic factor in mCRC patients undergoing LM. Further larger and prospective studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: Measure HCAHPS improvement in hospitals participating in the second and fifth years of HCAHPS public reporting; determine whether change is greater for some hospital types.Data: Surveys from 4,822,960 adult inpatients discharged July 2007-June 2008 or July 2010-June 2011 from 3,541 U.S. hospitals.Study Design: Linear mixed-effect regression models with fixed effects for time, patient mix, and hospital characteristics (bedsize, ownership, Census division, teaching status, Critical Access status); random effects for hospitals and hospital-time interactions; fixed-effect interactions of hospital characteristics and patient characteristics (gender, health, education) with time predicted HCAHPS measures correcting for regression-to-the-mean biases.Data Collection Methods: National probability sample of adult inpatients in any of four approved survey modes.Principal Findings: HCAHPS scores increased by 2.8 percentage points from 2008 to 2011 in the most positive response category. Among the middle 95 percent of hospitals, changes ranged from a 5.1 percent decrease to a 10.2 percent gain overall. The greatest improvement was in for-profit and larger (200 or more beds) hospitals.Conclusions: Five years after HCAHPS public reporting began, meaningful improvement of patients' hospital care experiences continues, especially among initially low-scoring hospitals, reducing some gaps among hospitals. [ABSTRACT FROM AUTHOR]

A high-resolution integrated study has been performed in a super-expanded marine record (sedimentation rate spanning from 11 cm/100 years to 20 cm/100 years) from the continental shelf area of the southeastern Tyrrhenian Sea. Planktonic foraminiferal distribution illustrates 6 major environmental changes during the past 2000 years: (i) the Roman Period-Dark Age transition (from herbivorous-opportunistic to carnivorous species); (ii) the Dark Age-MCA transition (from carnivorous to herbivorous-opportunistic species); (iii) the Medieval Classic Anomaly-Little Ice Age transition (a further and definitive change from carnivorous to herbivorous-opportunistic species); (iv) the period during the Maunder event between approximately 1720 AD and 1740 AD (turnover from the carnivorous planktonic foraminifer Globigerinodes ruber to the herbivorous-opportunistic planktonic foraminifer Turborotalita quinqueloba); (v) the Industrial Period (dominance of herbivorous-opportunistic planktonic foraminifera); and (vi) the Modern Warm Period at approximately 1940 AD (the last turnover in favor of herbivorous-opportunistic planktonic foraminifers, associated with an increase in benthic foraminifera). Our studies lead us to link this latter feature to an anthropogenic impact associated with the damming of Sele River (Salerno Gulf) at 1934 AD, which induced a change in the sediment input with a strong decrease in coarse-grained fraction and a probable alteration in nutrient supply. The δ18O G. ruber record of the past 2000 years shows the alternation of warm/wet and cold/dry events related to the Roman Period, the Dark Age, the Medieval Classic Anomaly, the Little Ice Age, the Industrial Period and the Modern Warm Period. The 5 evident δ18O G. ruber oscillations (between approximately 1325 AD and 1940 AD) coincide with the 5 minima in the solar activity record (Wolf, Spörer, Maunder, Dalton and Damon events). [ABSTRACT FROM AUTHOR]

Objective To examine gender differences in inpatient experiences and how they vary by dimensions of care and other patient characteristics. Data Source A total of 1,971,632 patients (medical and surgical service lines) discharged from 3,830 hospitals, July 2007- June 2008, and completing the HCAHPS survey. Study Design We compare the experiences of male and female inpatients on 10 HCAHPS dimensions using multiple linear regression, adjusting for survey mode and patient mix. Additional models add additional patient characteristics and their interactions with patient gender. Principal Findings We find generally less positive experiences for women than men, especially for Communication about Medicines, Discharge Information, and Cleanliness. Gender differences are similar in magnitude to previously reported HCAHPS differences by race/ethnicity. The gender gap is generally larger for older patients and for patients with worse self-reported health status. Gender disparities are largest in for-profit hospitals. Conclusions Targeting the experiences of women may be a promising means of improving overall patient experience scores (because women comprise a majority of all inpatients); the experiences of older and sicker women, and those in for-profit hospitals, may merit additional examination. [ABSTRACT FROM AUTHOR]

Abstract: Pompe disease (PD) is a metabolic myopathy caused by a deficiency of acid‐alpha glucosidase (GAA), a lysosomal enzyme that cleaves glycogen. The classic infantile‐onset form is characterised by severe hypotonia and cardiomyopathy. Untreated patients usually die within the first year of life due to cardiorespiratory failure. Several studies involving patients with infantile‐onset PD have shown that enzyme replacement therapy (ERT) with alglucosidase alfa, recombinant human GAA (rhGAA), significantly prolongs survival, decreases cardiomegaly, and improves cardiac function and conduction abnormalities. However, the efficacy on motor, cognitive and social milestones appears to be more related to the condition of the patient before the start of treatment. To date, the sample of early diagnosed and treated patients is small and the length of follow‐up is still limited. We report the results of a long‐term follow‐up of one patient presenting severe bradycardia and cardiomyopathy at birth, diagnosed in the third day of life and successfully treated by ERT. Serum muscle enzymes at diagnosis were AST 200 U/L, ALT 99 U/L and CPK 731 U/L (n.v. 0‐295); the molecular study identified the homozygous missense mutation c.1933 G> A p.Asp645Asn (GAA exon 14). Left Ventricular Mass Index (LVMI) at baseline was 171 g/m2 (Z‐score = 4.3) and decreased to normal values since the 3‐month follow‐up. A muscle biopsy performed at 18 months after the start of therapy, showed only a low degree of muscle involvement. To our knowledge, this is the longest ERT treatment follow‐up in a symptomatic neonatal patient with Pompe disease. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated whether early 2-[fluorine-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) after two cycles of salvage chemotherapy (PET2) could predict survival after high-dose chemotherapy (HDC). Twenty-four Hodgkin lymphoma (HL) patients were included. PET2 was negative in 58% and positive in 42% of patients. Ninety per cent of patients (9/10) with positive PET2 relapsed after HDC while all but one patient with negative PET2 maintained a complete remission. The 2-year progression-free survival was 93% vs. 10% for patients with negative and positive PET2, respectively ( P < 0.001). This study shows that interim PET can predict the outcome after high-dose chemotherapy in HL patients. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the need for survey mode adjustments to hospital care evaluations by discharged inpatients and develop the appropriate adjustments. Data Source. A total of 7,555 respondents from a 2006 national random sample of 45 hospitals who completed the CAHPS® Hospital (HCAHPS [Hospital Consumer Assessments of Healthcare Providers and Systems]) Survey. Study Design/Data Collection/Extraction Methods. We estimated mode effects in linear models that predicted each HCAHPS outcome from hospital-fixed effects and patient-mix adjustors. Principal Findings. Patients randomized to the telephone and active interactive voice response (IVR) modes provided more positive evaluations than patients randomized to mail and mixed (mail with telephone follow-up) modes, with some effects equivalent to more than 30 percentile points in hospital rankings. Mode effects are consistent across hospitals and are generally larger than total patient-mix effects. Patient-mix adjustment accounts for any nonresponse bias that could have been addressed through weighting. Conclusions. Valid comparisons of hospital performance require that reported hospital scores be adjusted for survey mode and patient mix. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the need for survey mode adjustments to hospital care evaluations by discharged inpatients and develop the appropriate adjustments.Data Source: A total of 7,555 respondents from a 2006 national random sample of 45 hospitals who completed the CAHPS Hospital (HCAHPS [Hospital Consumer Assessments of Healthcare Providers and Systems]) Survey.Study Design/data Collection/extraction Methods: We estimated mode effects in linear models that predicted each HCAHPS outcome from hospital-fixed effects and patient-mix adjustors.Principal Findings: Patients randomized to the telephone and active interactive voice response (IVR) modes provided more positive evaluations than patients randomized to mail and mixed (mail with telephone follow-up) modes, with some effects equivalent to more than 30 percentile points in hospital rankings. Mode effects are consistent across hospitals and are generally larger than total patient-mix effects. Patient-mix adjustment accounts for any nonresponse bias that could have been addressed through weighting.Conclusions: Valid comparisons of hospital performance require that reported hospital scores be adjusted for survey mode and patient mix. [ABSTRACT FROM AUTHOR]

The article discusses the use of chemo-radiotherapy in patients with Hodgkin lymphoma (HL) wherein some patient with early and advanced stage diseases experience a disease relapse. It examines the activity and efficacy of a single-agent bendamustine in patients with HL through an objective response rate (ORR) including partial remission (PR), overall survival (OS) and progression-free survival (PFS). It mentions the integration of stem cell transplantation (SCT) to treat the diseases.