Ibrutinib Treatment in Early Stage CLL Prolongs Time to Active Disease

Clinical and biochemical studies of 40 children with lipoid nephrosis are evaluated. Twenty-six (65 %) are alive; 19 have been entirely well for 1 to 16 years, including three who had minimal hematuria on various occasions. Three have been well for less than a year, one still has proteinuria only, and three still have active disease. Of 22 children who had received sulfonamides for infections, only three have died. Necropsy was done on 10 of the 14 children who died. Minor glomerular changes were seen in the kidneys of four children not known to have had hematuria. Pronounced glomerular changes occurred in two children who had minimal hematuria. Of the four children who did not show any glomerular changes, two had minimal hematuria on several occasions. Pathologic changes in the liver were minimal unless acacia had been given. Laboratory determinations revealed no significant alteration of the prothrombin time. Most of the increase in the plasma fats was in the cholesterol fraction. The precentage of cholesterol esters was not decreased. In case of recovery, the cholesterol seemed to return to normal values at a slower rate than the serum albumin. Plasma fat reached values exceeding 5 gm./100 ml. in some instances. No "critical edema level" for albumin was found. The erythrocyte sedimentation test was a reliable guide in determining the course of the disease. Choline citrate (0.8 gm. each day), given to seven children for prolonged periods, failed to produce essential changes in the plasma fats or definite clinical improvement. Periods of sudden change in edema were found to be critical times for the nephrotic child. Two children developed cardiac failure after injection of large volumes of sucrose. Early diagnosis is important, for treatment is most effective in the early stage. The prognosis is good since the advent of chemo- and antibiotic therapy, and is not impaired by prolonged duration of the disease. Growth of the children who recover is good.

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Illness Understanding of Oncology Patients in a Community-Based Cancer Institute

Journal of Oncology Practice ◽

10.1200/jop.2017.020982 ◽

2017 ◽

Vol 13 (9) ◽

pp. e800-e808 ◽

Cited By ~ 4

Author(s):

Shanthi Sivendran ◽

Sarah Jenkins ◽

Sarah Svetec ◽

Michael Horst ◽

Kristina Newport ◽

...

Keyword(s):

Advanced Cancer ◽

Early Stage ◽

Stage I ◽

Cancer Stage ◽

Stage At Diagnosis ◽

Community Based ◽

Oncology Patients ◽

Number Of Patients ◽

Knowledge Of Cancer ◽

Active Disease

Purpose: Several studies have demonstrated that patients have a poor understanding of prognosis, survival, and effectiveness of chemotherapy, particularly in the setting of advanced cancer. This study examines oncology patients’ understanding of their illness based on accurate reporting of stage at diagnosis and knowledge of cancer status (ie, free of cancer or in remission v active disease). Materials and Methods: Two hundred eight patients with cancer previously treated at our large community-based cancer institute participated in the Consumer-Based Cancer Care Value Index field survey. Electronic medical record documentation of stage at diagnosis and cancer status was compared with patients’ self-reported responses. Concordance of responses and variables influencing discordance were evaluated. Results: In 51.0% of patients, self-reported cancer stage matched the abstracted stage, with the highest concordance in patients with advanced cancer (72%) versus patients with stage I to III disease (36.4% to 61.5%). Unexpectedly, discordance was lower among patients with advanced cancer compared with patients with stage I to III cancer ( P = .0528). Patients who were concordant for cancer stage at diagnosis were significantly more likely to be female ( P = .001), be younger than age 65 years ( P = .01), have an income > $60,000 ( P = .03), and have more education ( P = .02). In 64.4% of patients, self-reported cancer status (ie, free of cancer or in remission v active disease) matched the abstracted status. Nearly 30% of patients were not sure about their status, even when they were free of cancer or in remission. Conclusion: Our findings confirm that more than one quarter of patients with advanced cancer have poor illness understanding and highlight that an even greater number of patients with early stage I to III cancer have poor illness understanding. These observations highlight the need to improve illness understanding for patients across the entire cancer continuum.

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Overall Survival In Early Stage Chronic Lymphocytic Leukemia Patients With Treatment Indication Due To Disease Progression: Follow-Up Data Of The CLL1 Trial Of The German CLL Study Group (GCLLSG)

Blood ◽

10.1182/blood.v122.21.4127.4127 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4127-4127 ◽

Cited By ~ 3

Author(s):

Manuela A. Bergmann ◽

Raymonde Busch ◽

Barbara Eichhorst ◽

Andreas Buehler ◽

Norbert Fischer ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Risk Stratification ◽

Disease Progression ◽

Early Stage ◽

Lymphocytic Leukemia ◽

Free Survival ◽

Treatment Indication ◽

Active Disease

Abstract Introduction Chronic lymphocytic leukemia (CLL) is typically diagnosed at an early stage and a watch & wait (W&W) strategy is applied. Only when the disease progresses to a more active, symptomatic form, treatment is indicated. The prospective CLL1 trial was designed to evaluate the benefit of early risk-adapted therapy with fludarabine (F) monotherapy, and to document the natural course of the disease from diagnosis. Here we present follow-up data to assess overall survival from the time point of treatment indication. Methods At enrolment, risk stratification was performed based on bone marrow (BM) infiltration pattern, lymphocyte doubling time (LDT), serum beta2-microglobulin (ß2-MG), and serum thymidine kinase (TK). Pts were “high-risk” (HR) if they had diffuse BM infiltration pattern and/or LDT<12 months (mo) combined with TK >7.0 U/L and/or ß2-MG >3.5 mg/L at enrolment. HR pts were randomized in a 1:1 ratio to early F (HR-F), or to W&W until classical treatment indication (HR-W&W), which was also applied to all low-risk (LR) pts. Results Between 1997 and 2004, 710 pts with Binet A stage CLL were enrolled and underwent risk stratification (RS) per protocol. Median time from diagnosis to enrolment was 3.2 mo (range 0-33.7) and median follow-up time was 8.5 years (yrs) (range 0-13.9). 521 pts (73%) were stratified to LR and 189 pts (27%) to HR, of whom 93 pts (49%) were randomized to HR-F and 96 pts (51%) to HR-W&W. Median age was 60 (range 32-75) yrs, 61% were male, 34% had unmutated IGHV status; high-risk cytogenetic features (17p- and 11q-) had 3% and 8% of pts, respectively. Early intervention with F among HR pts significantly prolonged progression-free survival (PFS) (30 vs. 13 mo; p<.001) and treatment-free survival (TFS) (74 vs. 41 mo; p=0.036) but did not significantly impact overall survival (OS) (127 mo vs. not reached; p=0.75). 303 patients had received treatment due to disease progression. 23% of patients received combination chemotherapy, 22% chemoimmunotherapy, 18% monotherapy with chlorambucil, and 15% monotherapy with purine analogues. Median OS for all pts was 91 mo (95% CI, 86 to 101 mo) from start of first treatment due to active disease. Patients with high risk (HR) for disease progression according to risk stratification had a significant shorter OS from start of first treatment than patients with low risk (LR) (71 mo vs. not reached; p=0.001). Early treatment with F did not show a significant impact on survival, when patients progressed after risk-adapted F, but showed a trend to a more favorable outcome for the watch and wait arm receiving their first therapy only when they had progressed to active disease (HR-F: median OS 51 mo versus HR-W&W not reached; p=0.055). Multivariate analyses on 237 pts identified 17p-, 11q-, unmutated IGHV, ß2-MG >3.5 mg/L, and age >60 yrs as independent prognostic factors for OS for patients with progressive, active disease and treatment indication. Conclusions Monotherapy with fludarabine is not superior to the W&W approach for the management of early stage CLL pts, since early F did not improve OS or outcome following subsequent therapies. Disclosures: No relevant conflicts of interest to declare.

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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Automated high-resolution microscopy: the approaches so far

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100125312 ◽

1987 ◽

Vol 45 ◽

pp. 58-61

Author(s):

W. O. Saxton

Keyword(s):

High Resolution ◽

Early Stage ◽

Automatic Recording ◽

Microprocessor Control ◽

Alternative Systems ◽

Electron Image ◽

Complete Automation ◽

Analysis System ◽

High Resolution Microscopy

Recent commercial microscopes with internal microprocessor control of all major functions have already demonstrated some of the benefits anticipated from such systems, such as continuous magnification, rotation-free diffraction and magnification, automatic recording of mutually registered focal series, and fewer control knobs. Complete automation of the focusing, stigmating and alignment of a high resolution microscope, allowing focal series to be recorded at preselected focus values as well, is still imminent rather than accomplished, however; some kind of image pick-up and analysis system, fed with the electron image via a TV camera, is clearly essential for this, but several alternative systems and algorithms are still being explored. This paper reviews the options critically in turn, and stresses the need to consider alignment and focusing at an early stage, and not merely as an optional extension to a basic proposal.

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Direct observation of Fe-Al-Zn ternary intermetallic compound and its transformation during the early stage of hot-dip galvanizing

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100151416 ◽

1993 ◽

Vol 51 ◽

pp. 1116-1117

Author(s):

C. S. Lin ◽

W. A. Chiou ◽

M. Meshii

Keyword(s):

Intermetallic Compound ◽

Reaction Rate ◽

Diffusion Rate ◽

Early Stage ◽

Zinc Bath ◽

Steel Sheets ◽

Direct Observations ◽

Solid Iron ◽

Iron And Zinc ◽

Ternary Intermetallic Compound

The galvannealed steel sheets have received ever increased attention because of their excellent post-painting corrosion resistance and good weldability. However, its powdering and flaking tendency during press forming processes strongly impairs its performance. In order to optimize the properties of galvanneal coatings, it is critical to control the reaction rate between solid iron and molten zinc.In commercial galvannealing line, aluminum is added to zinc bath to retard the diffusion rate between iron and zinc by the formation of a thin layer of Al intermetallic compound on the surface of steel at initial hot-dip galvanizing. However, the form of this compound and its transformation are still speculated. In this paper, we report the direct observations of this compound and its transformation.The specimens were prepared in a hot-dip simulator in which the steel was galvanized in the zinc bath containing 0.14 wt% of Al at a temperature of 480 °C for 5 seconds and was quenched by liquid nitrogen.

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Anisotropy of interfacial defects in the initial stage of MOVPE GaAs growth On Si

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100176095 ◽

1990 ◽

Vol 48 (4) ◽

pp. 592-593

Author(s):

C. Vannuffel ◽

C. Schiller ◽

J. P. Chevalier

Keyword(s):

Early Stage ◽

Threading Dislocations ◽

Mbe Growth ◽

Detailed Mechanism ◽

Si Substrates ◽

Initial Stage ◽

Interfacial Defects ◽

Interfacial Dislocations ◽

Step Growth ◽

Essential Problem

Recently, interest has focused on the epitaxy of GaAs on Si as a promising material for electronic applications, potentially for integration of optoelectronic devices on silicon wafers. The essential problem concerns the 4% misfit between the two materials, and this must be accommodated by a network of interfacial dislocations with the lowest number of threading dislocations. It is thus important to understand the detailed mechanism of the formation of this network, in order to eventually reduce the dislocation density at the top of the layers.MOVPE growth is carried out on slightly misoriented, (3.5°) from (001) towards , Si substrates. Here we report on the effect of this misorientation on the interfacial defects, at a very early stage of growth. Only the first stage, of the well-known two step growth process, is thus considered. Previously, we showed that full substrate coverage occured for GaAs thicknesses of 5 nm in contrast to MBE growth, where substantially greater thicknesses are required.

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