Evaluation of chromatin condensation in human spermatozoa: a flow cytometric assay using acridine orange staining

The quality of sperm chromatin is an important factor in fertilization and is especially critical where one spermatozoon is artificially selected for fertilizing an egg (as in intracytoplasmic sperm injection). In this study, flow cytometry after staining of human spermatozoa with Acridine Orange was used to study chromatin structure. A method is described for estimating the percentage of cells in a human sperm sample that have completed epididymal maturation in regard to chromatin condensation. Of the 121 samples of the semen that were examined, nine contained a higher percentage of hypocondensed spermatozoa and six samples contained elevated amounts of hypercondensed spermatozoa. In addition to aberrancies in chromatin condensation other defects showed up as satellite populations of spermatozoa with higher than normal ratios of red/green fluorescence after Acridine Orange staining. Such defects were found in 15 semen samples. The use of swim-up and Percoll gradient centrifugation methods was shown to improve the percentage of spermatozoa with normal chromatin structure in some samples with poor initial quality.      

Utility of PET-CT for Evaluation of Patients With Peripheral T-cell Lymphoma

Background

Fluorine-18 fluorodeoxyglucose (FDG) avidity varies in peripheral T-cell lymphoma (PTCL). We evaluated FDG avidity of pretreatment positron emission tomography/computed tomography (P-PET/CT), to appraise the prognostic significance of interim PET/CT (I-PET/CT) and end of treatment PET/CT (E-PET/CT) in PTCL.

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.     

Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the MEK Inhibitor RO4987655 (CH4987655) in Patients with Advanced Solid Tumors

PURPOSE: This phase I study of the mitogen-activated protein/extracellular signal-regulated kinase inhibitor RO4987655 (CH4987655) assessed its maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetic/pharmacodynamic profile, and antitumor activity in patients with advanced solid tumors. Patients and Methods: An initial dose escalation was conducted using a once-daily dosing schedule, with oral RO4987655 administered at doses of 1.0 to 2.5 mg once daily over 28 consecutive days in 4-week cycles. Doses were then escalated from 3.0 to 21.0 mg [total daily dose (TDD)] using a twice-daily dosing schedule. RESULTS: Forty-nine patients were enrolled. DLTs were blurred vision (n = 1) and elevated creatine phosphokinase (n = 3). The MTD was 8.5 mg twice daily (TDD, 17.0 mg). Rash-related toxicity (91.8%) and gastrointestinal disorders (69.4%) were the most frequent adverse events. The pharmacokinetic profile of RO4987655 showed dose linearity and a half-life of approximately 4 hours. At the MTD, target inhibition, assessed by suppression of extracellular signal-regulated kinase phosphorylation in peripheral blood mononuclear cells, was high (mean 75%) and sustained (90% of time >IC(50)). Of the patients evaluable for response, clinical benefit was seen in 21.1%, including two partial responses (one confirmed and one unconfirmed). 79.4% of patients showed a reduction in fluorodeoxyglucose uptake by positron emission tomography between baseline and day 15. CONCLUSION: In this population of heavily pretreated patients, oral RO4987655 showed manageable toxicity, a favorable pharmacokinetics/pharmacodynamics profile, and promising preliminary antitumor activity, which has been further investigated in specific populations of patients with RAS and/or RAF mutation driven tumors. Clin Cancer Res; 18(17); 4794-805. ?2012 AACR.     

Comparison of outcome of recurrent versus first ST-segment elevation myocardial infarction (from national Israel surveys 1998 to 2006)

Patients with recurrent acute myocardial infarction (AMI), who represent ≤35% of hospitalized patients with AMI, are at an increased risk of complications and death. Our study purpose was to compare the treatment and outcome of patients hospitalized with recurrent acute ST-segment elevation myocardial infarction (STEMI) from 1998 to 2006 with those of patients with a first STEMI. We performed 5 biennial nationwide 2-month surveys during 1998 to 2006, collecting data prospectively from all patients hospitalized for AMI or acute coronary syndrome in all 25 coronary care units in Israel. The present cohort included 4,543 patients with STEMI, 3,679 (76%) with first and 864 (24%) with recurrent STEMI. The patients with recurrent STEMI were older (66 ± 13 vs 62 ± 13 years), had greater rates of diabetes, hypertension, and previous angina, had a worse Killip class on admission, and experienced more in-hospital complications. The all-cause hospital crude mortality rate was 8.1% in patients with recurrent STEMI versus 5.5% in those with a first STEMI (adjusted odds ratio 1.71 95% confidence interval 1.19 to 2.44), and the 1-year mortality rate was 18.9% versus 10.9%, respectively (hazard ratio 1.85, 95% confidence interval 1.41 to 2.43). From 1998 to 2006, an insignificant trend toward a 1-year mortality reduction among patients with recurrent STEMI was seen and those with a first STEMI had a significant mortality decrease. In conclusion, patients admitted for recurrent STEMI have worse in-hospital and 1-year outcomes that did not improve during the study period. An improved therapeutic approach is needed for these high-risk patients.     

The role of neoadjuvant chemotherapy in children with malignant solid tumors

Pediatric surgeons play a critical role in diagnosing, staging, and treating malignant solid tumors in children. Over the years, the surgical management of the primary tumor site has evolved from an aggressive en-bloc resection at diagnosis to a more tailored surgical approach, often affecting definitive local control after the delivery of neoadjuvant therapy, as currently directed by many solid tumor protocols. In fact, inappropriate upfront resection can lead to unnecessary short- and long-term morbidity, an incomplete resection, and may be associated with a delay in the initiation of the systemic chemotherapy that is critical to the treatment of gross or occult metastatic disease. Therefore, it is important for the pediatric surgeon, as a member of the multidisciplinary team involved in the care of these children, to understand the indications for and implications of neoadjuvant therapy in the treatment of pediatric solid tumors. Here we review the current management of childhood solid tumors focusing on the role of neoadjuvant therapy.     

Contribution of Routine to Sleep Quality in Community Elderly

Introduction:

Among the common problems related to aging is sleep quality; over half of older adults suffer from symptoms of insomnia. Age-related changes in circadian sleep/wake regulation constitute a major underlying factor. Constant and organized lifestyle may moderate the effects of circadian rhythm changes on sleep. Preliminary findings have linked daily regularity to sleep quality among healthy adults and in patients with Parkinson disease. The current study investigated the relationships between daily routines and sleep quality among community dwelling elderly.

Methods:

Ninety-six Israeli Russian-speaking elderly living in a retirement community (mean age 75 ±13.88, 72% women, 82% living alone) participated. Routines were assessed with the Scale of Older Adults Routine (SOAR) by a trained interviewer at 3 time points 2 weeks apart. A subsample (n = 33) completed the Social Rhythm Metric (SRM) 2-week diary. Sleep quality was evaluated using the Pittsburg Sleep Quality Index (PSQI). Daily Functional status was assessed with the Lawton Instrumental Activities of Daily Living (IADL).

Results:

Mean sleep efficiency was 78%, functional status was fairly good (mean IADL 45 of 50 [SD = 6.12]). Regression analyses indicated that increased stability in daily routine, as measured by the SOAR for the entire sample, predicted shorter sleep latency, higher sleep efficiency and improved sleep quality, beyond functional status, comorbidities, and age. Similar associations were found for the subsample using the SRM.

Conclusion:

Maintenance of daily routines is associated with a reduced rate of insomnia in the elderly. Further studies should examine these relations in broader populations with regard to health, functional status, and cultural background.

Citation:

Zisberg A; Gur-Yaish N; Shochat T. Contribution of routine to sleep quality in community elderly. SLEEP 2010;33(4):509-514.     

Undisclosed Financial Conflicts of Interest of Authors of Clinical Drug Trials Published in Influential Medical Journals: A Cohort Study

The International Committee of Medical Journal Editors requires authors to disclose all financial conflicts of interest (COI) that can be perceived as influencing the related trials. Undisclosed financial COI may influence the perception of the authors' scientific impartiality and erode the public trust in the reported results. Data regarding completeness of COI disclosure in high-impact–factor general medicine journals are limited. We compared payments disclosed by US-based physicians who were first or last authors of clinical drug trials published between August 2016 and August 2018 in the New England Journal of Medicine, JAMA, and Lancet, to payments reported by industry to the Centers for Medicare & Medicaid Services Open Payments Database. Of 247 included authors, 198 (80%) have not disclosed some or all received payments. The median undisclosed sum was $8409 (US Dollars) (interquartile range [IQR] $123 to $44,890). Most authors (n=170, 69%) have received more than $10,000 per year (median $120,403, IQR $58,905 to $242,014). The median undisclosed sum for these authors was $26,530 (IQR $7462 to $71,562). Median undisclosed sums for authors of papers from studies performed with and without industry funding were $20,899 (IQR $4191 to $59,883) and $149 (IQR $0 to $3276), respectively. In 10 (8%) of 125 industry-funded trials, the first or last author had not disclosed personal payments from the study sponsor (median $9741, IQR $4508 to $101,484). These findings could raise concerns about the authors' equipoise toward the trial results and influence the public perception of the credibility of reported data. Health care professionals, reviewers, and journal editors should demand more transparent reporting of financial COI.     

Usefulness of lung impedance-guided pre-emptive therapy to prevent pulmonary edema during ST-elevation myocardial infarction and to improve long-term outcomes

Patients sustaining an ST-segment elevation myocardial infarction (STEMI) frequently develop pulmonary congestion or pulmonary edema (PED). We previously showed that lung impedance (LI) threshold decrease of 12% to 14% from baseline during admission for STEMI marks the onset of the transition zone from interstitial to alveolar edema and predicts evolution to PED with 98% probability. The aim of this study was to prove that pre-emptive LI-guided treatment may prevent PED and improve clinical outcomes. Five hundred sixty patients with STEMI and no signs of heart failure underwent LI monitoring for 84 ± 36 hours. Maximal LI decrease throughout monitoring did not exceed 12% in 347 patients who did not develop PED (group 1). In 213 patients LI reached the threshold level and, although still asymptomatic (Killip class I), these patients were then randomized to conventional (group 2, n = 142) or LI-guided (group 3, n = 71) pre-emptive therapy. In group 3, treatment was initiated at randomization (LI = -13.8 ± 0.6%). In contrast, conventionally treated patients (group 2) were treated only at onset of dyspnea occurring 4.1 ± 3.1 hours after randomization (LI = -25.8 ± 4.3%, p <0.001). All patients in group 2 but only 8 patients in group 3 (11%) developed Killip class II to IV PED (p <0.001). Unadjusted hospital mortality, length of stay, 1-year readmission rate, 6-year mortality, and new-onset heart failure occurred less in group 3 (p <0.001). Multivariate analysis adjusted for age, left ventricular ejection fraction, risk factors, peak creatine kinase, and admission creatinine and hemoglobin levels showed improved clinical outcome in group 3 (p <0.001). In conclusion, LI-guided pre-emptive therapy in patients with STEMI decreases the incidence of in-hospital PED and results in better short- and long-term outcomes.