Citations

SIGNIFICANCE When exploring relationships among clinical measures and patient‐reported outcome measures in adults with convergence insufficiency, worse symptoms (Convergence Insufficiency Symptom Survey [CISS] score) seemed to be correlated with worse reading function domain score (Adult Strabismus‐20 quality‐of‐life questionnaire). After treatment, improved symptoms were associated with improved reading function quality of life. PURPOSE This study aimed to explore relationships between clinical measures and patient‐reported outcome measures in adults undergoing treatment for symptomatic convergence insufficiency. METHODS In a prospective multicenter observational study, we evaluated adults with symptomatic convergence insufficiency (i.e., clinical measures of near exodeviation, receded near point of convergence, reduced near positive fusional vergence; CISS score ≥21). Fifty‐seven participants treated with vision therapy/exercises (n = 35) or base‐in prism (n = 22) were analyzed. Spearman correlation coefficients ( R ) were used to assess associations among the three clinical measures and patient‐reported outcome measures (CISS, Diplopia Questionnaire, four Adult Strabismus‐20 quality‐of‐life domains) before treatment (baseline) and after 10 weeks and 1 year. Associations were interpreted to be present when the lower limit of the 95% confidence interval (CI) was moderate to strong ( R ≥ 0.4). RESULTS Among multiple exploratory analyses, the only moderate to strong baseline correlation was between worse CISS and worse Adult Strabismus‐20 reading function scores ( R = 0.62; 95% CI, 0.43 to 0.76). Regarding change in measures with treatment, the only moderate to strong correlations were between improved CISS and improved Adult Strabismus‐20 reading function scores for prism at 10 weeks ( R = 0.78; 95% CI, 0.52 to 0.91) and 1 year ( R = 0.85; 95% CI, 0.65 to 0.94) and for vision therapy/exercises at 1 year ( R = 0.78; 95% CI, 0.57 to 0.89). CONCLUSIONS In exploratory analyses, we found positive correlations between CISS symptom scores and reading function quality‐of‐life scores. The absence of correlations between symptoms and individual clinical measures is consistent with clinical experience that, in convergence insufficiency, symptoms and clinical findings can be discordant.

Abstract Manganese superoxide dismutase (MnSOD) is an important reactive oxygen species (ROS) scavenger which has largely been studied in pancreatic cancer cell lines, where it contributes to invasion but also decreases proliferation. In pancreatic cancer, it is unknown whether MnSOD contributes to or prevents lesion development. Therefore, we utilize a transgenic mouse model to study precancerous lesion development and progression. We here show that knockout of Sod2 in a p48Cre;LSL-KrasG12D (KC) mouse model accelerates formation of abnormal tissue area, increases abundance of DCLK1+ cancer stem cells (CSCs) and oxidative damage, and promotes formation of atypical flat lesions (AFLs) which are a direct precursor to pancreatic ductal adenocarcinoma (PDA). We further characterize AFLs as having fewer senescent cells and less oxidative damage than low grade PanIN lesions. Thus, MnSOD has a protective effect in early pancreatic lesion development and its deletion drives tumor development. Citation Format: Alicia K. Fleming Martinez, Brandy H. Edenfield, Irene Esposito, Peter Storz. Knockout of Sod2 accelerates formation of pancreatic atypical flat lesions which are a direct precursor to pancreatic ductal adenocarcinoma (PDA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 922.

Currently, there are no internationally accepted consensus guidelines for pathologic evaluation of posttherapy pancreatectomy specimens. The Neoadjuvant Therapy Working Group of Pancreatobiliary Pathology Society was formed in 2018 to review grossing protocols, literature, and major issues and to develop recommendations for pathologic evaluation of posttherapy pancreatectomy specimens. The working group generated the following recommendations: (1) Systematic and standardized grossing and sampling protocols should be adopted for pancreatectomy specimens for treated pancreatic ductal adenocarcinoma (PDAC). (2) Consecutive mapping sections along the largest gross tumor dimension are recommended to validate tumor size by histology as required by the College of American Pathologists (CAP) cancer protocol. (3) Tumor size of treated PDACs should be measured microscopically as the largest dimension of tumor outer limits that is bound by viable tumor cells, including intervening stroma. (4) The MD Anderson grading system for tumor response has a better correlation with prognosis and better interobserver concordance among pathologists than does the CAP system. (5) A case should not be classified as a complete response unless the entire pancreas, peripancreatic tissues, ampulla of Vater, common bile duct, and duodenum adjacent to the pancreas are submitted for microscopic examination. (6) Future studies on tumor response of lymph node metastases, molecular and/or immunohistochemical markers, as well as application of artificial intelligence in grading tumor response of treated PDAC are needed. In summary, systematic, standardized pathologic evaluation, accurate tumor size measurement, and reproducible tumor response grading to neoadjuvant therapy are needed for optimal patient care. The criteria and discussions provided here may provide guidance towards these goals.

Purpose: The purpose of this study was to determine whether session rating of perceived exertion-derived training load (sRPE-TL) correlates with GPS-derived measures of external load in National Collegiate Athletics Association (NCAA) Division I female soccer athletes. Methods: Twenty-one NCAA Division 1 collegiate women’s soccer athletes (11 starters, 10 non-starters; 65.1 ± 7.2 kg, 168.4 ± 7.9 cm, 20.3 ± 1.5 yrs) volunteered to take part in this study. Data for this study were collected over the course of 16 weeks during the 2018 NCAA women’s soccer season. External load and heart rate (HR) data were collected during each training session and match during the season. At least 30 min after the end of an activity (e.g., match or practice), athletes were prompted to complete a questionnaire reporting their perceived exertion for the session. sRPE-TL was calculated at the end of the season by multiplying perceived exertion by the respective session duration. Results: sRPE-TL was very strongly correlated with total distance, distance covered in velocity zones 1–3, the number of accelerations in zones 4 and 5, total PlayerLoad™, and PlayerLoad™. For internal load, sRPE-TL correlated very strongly (0.70 ≤ |r| < 0.90) with Edward’s and Bannister’s TRIMP and strongly (0.50 ≤ |r| < 0.70) with duration spent in in heart rate zones 5 and 6 (80–90% and 90–100% max HR, respectively) while correlations with maximum HR (bpm), mean HR (bpm), and mean HR (%) and sRPE-TL were moderate (0.30 ≤ |r| < 0.50). Conclusions: In NCAA Division I women soccer, sRPE-TL is strongly associated with external measures of workload. These relationships were stronger during match play, with acceleration load and total distance exhibiting the strongest relationship with sRPE-TL.

As passionate readers, occasional writers, reviewers, and editors with different experiences, when we were asked to participate in shaping and proposing a new journal, the first question that we had to deal with was, of course, “do we really need a new nephrology journal [...]

Abstract Context Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Objective Multicenter survey on current clinical approaches in managing AI during pregnancy. Design Retrospective anonymized data collection from 19 international centers from 2013 to 2019. Setting and Patients 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Results Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. Conclusions This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

Abstract Introduction: Recent reviews indicate that transfusional hemosiderosis may be associated with an increased risk of mortality in lower-risk pts with MDS. This trial is designed to evaluate the efficacy and long-term safety of deferasirox (Exjade®, ICL670) in MDS. Deferasirox is an oral iron chelator approved for use in pts with transfusional iron overload. Methods: This is a Phase II, open-label, 3-yr clinical trial in 55 US centers, enrolling 150 pts (aged ≥18 years) with Low- or Int-1-risk MDS (by IPSS criteria) and transfusional iron overload (serum ferritin ≥1000 ng/mL and &gt;20 units RBC transfusions). Deferasirox dosing is 20–30 mg/kg/day. Serum ferritin, iron, transferrin and transferrin saturation are being assessed at screening and monthly in yr 1, then quarterly in yrs 2 and 3, while labile plasma iron (LPI) is assessed quarterly in yr 1. In addition, creatinine, calculated creatinine clearance, echocardiograms and endocrine and hematological status are being assessed. This report describes baseline data in these pts. Results: As of June 2006, 84 pts have enrolled. Demographic data are available from 79 pts: median age 71 years (range 47–87); sex (52 male, 27 female); ethnicity (74 Caucasian, 2 Black, 2 Hispanic, 1 Oriental); and IPSS Risk Group (Low: 22 pts; Int-1: 56 pts). Iron status is summarized in the table: Parameter n Mean ± SD Median Range Normal range n/a, not applicable Serum ferritin,μg/L 84 3779 ± 4070 2951 1160–36280 12–370 Serum iron, μg/dL 84 205 ± 64 201 48–409 37–180 Transferrin, mg/dL 82 153 ± 31 152 83–244 190–375 Transferrin saturation, % 83 85 ± 15 91 20–94 15–50 LPI, μmol/L 38 0.52 ± 0.63 0.25 0–2.9 0 Total transfusions, n 78 63.3 ± 66.3 41.5 14–435 n/a Years of transfusion 75 3.4 ± 1.9 3 1–12 n/a Baseline concurrent therapies: 5-azacytidine (Vidaza): 5 pts; lenalidomide (Revlimid): 1 pt. Calculated creatinine clearance: normal (&gt;80 mL/min): 37 pts; mildly abnormal (51–80 mL/min): 30 pts; moderately abnormal (30–50 mL/min): 9 pts. Hematological parameters: Anemia was present in all pts; other cytopenias included: neutropenia (&lt;1800/μL): 13 pts, thrombocytopenia (&lt;100,000/μL): 15 pts; neutropenia and thrombocytopenia: 12 pts. A total of 53 pts had received chelation prior to enrolling: 51 deferoxamine (Desferal®); and 2 deferasirox. Conclusions: Despite the prior availability of deferoxamine, these baseline data demonstrate significant levels of iron overload among transfused pts with myelodysplasia. Serum iron, ferritin and LPI are all well above the clinically significant thresholds associated with increased complications. Since recent data has suggested that iron overload may be a poor prognostic indicator in MDS, increased attention to maintaining appropriate iron balance is warranted. The recent availability of an oral iron chelator may be more acceptable to MDS pts and their physicians. This ongoing trial is designed to assess the long-term efficacy, safety, and clinical benefits of deferasirox in pts with MDS.

Abstract INTRODUCTION: The majority of patients (pts) with MDS require red blood cell transfusions, which can result in iron overload and its clinical sequelae. The US03 trial is designed to evaluate the long-term efficacy and safety of the once-daily, oral iron chelator, deferasirox (DFX), in pts with lower-risk MDS. In this ongoing study 93/176 pts have now completed 12 months of treatment. METHODS: US03 is a Phase II, open-label, 3-year trial in pts with Low- or Int-1 IPSS-risk MDS and transfusional iron overload (serum ferritin [SF] 1000 μg/L and &gt;20 units RBC transfusions), with serum creatinine (SCr) 2-fold the upper limit of normal (ULN). Initial DFX dose was 20 mg/kg/day and could be increased to 40 mg/kg/day based on tolerability and response. SF was monitored monthly; labile plasma iron (LPI), the reactive species of non-transferrin-bound iron, was assessed quarterly. BASELINE FEATURES: 176 pts were enrolled at 45 centers. Mean age: 70 years (range 21–90); 105 men and 71 women; IPSS Low risk (n=47; 27%); Int-1 (n=126; 72%); other (n=3; 2%). Mean baseline iron status was: SF, 3397 μg/L (863–36,280); LPI, 0.4 μmol/L (0.0–3.6). Forty-one percent of pts had elevated LPI at baseline (≥0.5 μmol/L). Mean number of lifetime prior transfusions: 63; mean duration of transfusions: 3.5 years (0–34). MDS therapy at study entry included azacitidine, hydroxyurea, lenalidomide, thalidomide or decitabine in 25 pts, and growth factors in 48 pts. Calculated creatinine clearance was normal (&gt;80 mL/min) in 77 pts and abnormal (abn) in 99: mildly abn (51– 80 mL/min) in 71; moderately abn (30–50 mL/min) in 25; severely abn (&lt;30 mL/min) in 3. RESULTS: Over 12 months, the mean dose of DFX was 21 mg/kg/day, and the mean transfusion rate was 3.4 units/month. Mean SF±SEM (μg/L) values at baseline, 3, 6, 9 and 12 months were 3397±233 (n=176), 3057±144 (n=143), 2802±128 (n=126), 2635±148 (n=109) and 2501±139 (n=93), respectively. In pts with elevated baseline LPI, sustained suppression of mean LPI to the normal range was achieved after 3 months of treatment. The figures show reductions (±SEM) in SF, and in LPI in pts with baseline LPI ≥0.5 μmol/L. Hematological improvement by IWG 2000 criteria was achieved in 8 pts (5%): erythroid response in 5 (major 3; minor 2); platelet in 1 (major); neutrophil in 1 (major); and combined platelet and neutrophil in 1. SAFETY: Of 173 pts, 18 (10%) discontinued DFX because of suspected adverse events (AEs), and an additional 5 (3%) because of serious AEs (SAEs). The most common AEs were diarrhea (n=9), rash (n=3) and nausea (n=2), while the most common SAEs were rash (n=2) and diarrhea (n=1). Of 147 pts with normal baseline SCr, 26 (18%) increased &gt;ULN on at least two occasions (3.0 mg/dL max SCr). There were 9/172 (5%) and 22/168 (13%) new onset cases of grade 3–4 thrombocytopenia and neutropenia, respectively, none suspected to be related to DFX; 7 and 11 of these pts, respectively, were receiving other MDS treatment therapies, including lenalidomide, decitabine, hydroxyurea and azacitidine. There were 17 deaths (10%), due to sepsis/infection (n=8), disease progression (n=4), intracranial bleed (n=2), cardio-respiratory arrest (n=2) and renal failure (n=1), all thought to be unrelated to DFX. CONCLUSIONS: In these heavily iron-overloaded pts, DFX was generally well tolerated. New onset cytopenias were consistent with the underlying disease. A 2-year extension phase of this study will assess the long-term safety and efficacy of DFX as well as the clinical impact on cardiac, hepatic and endocrine function. Figure Figure