SUMMARY The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states.The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.Thyroid hormone deficiency is known to affect the heart.`13 Although exercise intolerance is a classic feature of hypothyroidism, most studies have focused on the contractile function of the heart at rest' and little attention has been paid to the performance of the left ventricle during exercise.Some radionuclide studies assessed the response of the ejection fraction to stress in hypothyroid patients.7' The ejection fraction is widely accepted as a useful measure of ventricular performance'0 but it has limitations. Because it is the ratio of two physiological variables the size of the left ventricular chamber can change considerably without causing a significant change in ejection fraction. So the Requests for reprints to Dr Siegfried Wieshammer, Cardiology Section, Department of Internal Medicine, University of Ulm, Steinhovelstraf3e 9, D-7900 Ulm, Federal Republic of Germany.Accepted for publication 9 November 1987 haemodynamic consequences of hypothyroidism are only incompletely evaluated by the response of the ejection fraction to stress, and for a more comprehensive assessment left ventricular volumes and pressures must be measured. More importantly, the ejection fraction is dependent not only on the intrinsic contractile state of the heart but also on the preload and afterload." Changes in loading conditions seem to be especially important when thyroid function is abnormal'2 and, therefore, it is u...

Introduction: FIRE-3 compared 1st-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type (wt) mCRC patients ( pts). Retrospective analyses in pts with RAS wt tumors considered 342 pts. An independent radiological review evaluated tumor response according to RECIST 1.1 as well as early tumor shrinkage (ETS) and depth of response (DpR).Methods: Radiological data were centrally collected and evaluated independently with reviewers blinded to patient data. ETS was defined as a reduction in tumor diameters by at least 20% at first tumor assessment after baseline (week 6). DpR was defined as the maximal tumor %-shrinkage observed in a patient. ORR and ETS rates in the two treatment arms were compared using Fisher's exact test and DpR using the Wilcoxon test. Association of ETS with PFS and OS in each treatment group was examined using log rank tests and association of DpR with post-progression survival (PPS) time using the correlation coefficient of Bravais Pearson. Results: At the time of this analysis, 441 pts (74.5%) had complete independent reviews within the KRAS wt ITT population. In the RAS wt population 257 pts (75.1%) had complete assessments. In both populations ORR, ETS and DpR significantly favored the FOLFIRI plus cetuximab arm (Table). In KRAS wt pts in both treatment arms ETS was significantly associated with PFS ( p = 0.0002 and p = 0.0013) and OS ( p < 0.0001 and p < 0.0001). In RAS wt pts associations seemed less strong for PFS ( p = 0.05 and p = 0.19), but were of similar strength for OS ( p = 0.0007 and p = 0.0017). DpR was associated with PPS ( p = 0.003 in KRAS wt and p = 0.02 in RAS wt). Updated results will be presented at the meeting. Conclusion: Based on an independent radiological review, FOLFIRI plus cetuximab induced a significantly higher ORR, a greater rate of ETS, and an increased DpR compared to FOLFIRI plus bevacizumab. These response-related outcomes may in part explain the significant OS advantage of FOLFIRI plus cetuximab observed in FIRE-3.

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This study evaluated strain reactions in young athletes (mean age: 17.6 years). Of 35 male rowers, 21 were selected by rowing ergometer tests to take part in a 26-day training camp before the World Championships in 1989. Blood samples were obtained in the morning of the day after rowing ergometer tests and on the 16th and 26th day. Cortisol (C), testosterone (T), sexual-hormone-binding globulin (SHBG), urea and creatine kinase (CK) were determined in serum and free testosterone (FT) was calculated. In the nonselected rowers C was 10% higher, FT 20% lower, and CK 42% higher compared to the selected rowers. During training, C was related to the intensity of training. It remained constant in phase 1 (12 days, increased volume of training) and increased in phase 2 (10 days, decreased volume and higher intensity). FT decreased in phase 1 and increased in phase 2. Urea showed a close relationship to training volume. CK levels decreased during the training volume. CK levels decreased during the training period as an adaptation to the training. Despite a high training load, there were no indications of overstrain reactions in these young athletes.

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