World Jewish Congress. Celebration of the twenti-fifth anniversary of the work of 1936-1961

Svjetski jevrejski kongres (SJK) je najobuhvatnija organizacija te vrste među Jevrejima. On povezuje blizu 70 teritorijalnih jedinica putem lokalnih i autonomnih organizacija u tim područjima, i uspostavlja vezu između njih ili njih sa njegovim centrima (SJK podržava deset centralnih ureda - u Njujorku, Londonu, Ženevi, Parizu, Jerušalajimu, Tel-Avivu, Buenos-Airesu, Rimu, Rio de Žaneiru i Montevideu), te njih sa međunarodnim organizacijama, napose Ujedinjenim nacijama, UNESCO-m itd...The World Jewish Congress (WJC) is the most comprehensive organization of its kind among Jews. It connects close to 70 territorial units through local and autonomous organizations in these areas, and establishes links between them or their centers (WJC supports ten central offices - in New York, London, Geneva, Paris, Jerusalem, Tel-Aviv, Buenos Aires, Rome, Rio de Janeiro, and Montevideo), and with international organizations, in particular the United Nations, UNESCO, etc ..

Simultaneous determination of the kinetics of cardiac output, systemic O2 delivery and lung O2 uptake at exercise onset in men.

We tested whether the kinetics of systemic O2 delivery (Q'aO2) at exercise start was faster than that of lung O2 uptake (V' O2), being dictated by that of cardiac output (Q'), and whether changes in Q' would explain the postulated rapid phase of the V'O2 increase. Simultaneous determinations of beat-by-beat (BBB) Q' and Q' aO2, and breath-by-breath V'O2 at the onset of constant load exercises at 50 and 100 W were obtained on six men (age 24.2 +/-3.2 years, maximal aerobic power 333 +/- 61 W). V'O2 was determined using Grønlund’s algorithm. Q' was computed from BBB stroke volume (Qst, from arterial pulse pressure profiles) and heart rate (fH, electrocardiograpy) and calibrated against a steadystate method. This, along with the time course of hemoglobin concentration and arterial O2 saturation (infrared oximetry) allowed computation of BBB Q'aO2. The Q', Q'aO2 and V'O2 kinetics were analyzed with single and double exponential models. fH, Qst, Q', and V'O2 increased upon exercise onset to reach a new steady state. The kinetics of Q'aO2 had the same time constants as that of Q'. The latter was twofold faster than that of V'O2. The V'O2 kinetics were faster than previously reported for muscle phosphocreatine decrease. Within a two-phase model, because of the Fick equation, the amplitude of phase I Q' changes fully explained the phase I of V'O2 increase. We suggest that in unsteady states, lung V' O2 is dissociated from muscle O2 consumption. The two components of Q' and Q'aO2 kinetics may reflect vagal withdrawal and sympathetic activation

Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation

The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift and sustained response, underscoring the potential role of belzutifan as a viable option in second or subsequent lines of therapy for individuals with somatic VHL mutations. Despite both patients experiencing a pulmonary crisis with respiratory compromise, their rapid response to belzutifan further emphasizes its potential utility in cases involving pulmonary or visceral crises. This report contributes valuable insights into the treatment landscape for advanced ccRCC with somatic VHL mutations

Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation

The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift and sustained response, underscoring the potential role of belzutifan as a viable option in second or subsequent lines of therapy for individuals with somatic VHL mutations. Despite both patients experiencing a pulmonary crisis with respiratory compromise, their rapid response to belzutifan further emphasizes its potential utility in cases involving pulmonary or visceral crises. This report contributes valuable insights into the treatment landscape for advanced ccRCC with somatic VHL mutations

Phase I dynamics of cardiac output, systemic O2 delivery and lung O2 uptake at exercise onset in men in acute normobaric hypoxia.

We tested the hypothesis that vagal withdrawal plays a role in the rapid (phase I) cardiopulmonary response to exercise. To this aim, in five men (24.6+/-3.4 yr, 82.1+/-13.7 kg, maximal aerobic power 330+/-67 W), we determined beat-by-beat cardiac output (Q), oxygen delivery (QaO2), and breath-by-breath lung oxygen uptake (VO2) at light exercise (50 and 100 W) in normoxia and acute hypoxia (fraction of inspired O2=0.11), because the latter reduces resting vagal activity. We computed Q from stroke volume (Qst, by model flow) and heart rate (fH, electrocardiography), and QaO2 from Q and arterial O2 concentration. Double exponentials were fitted to the data. In hypoxia compared with normoxia, steady-state fH and Q were higher, and Qst and VO2 were unchanged. QaO2 was unchanged at rest and lower at exercise. During transients, amplitude of phase I (A1) for VO2 was unchanged. For fH, Q and QaO2, A1 was lower. Phase I time constant (tau1) for QaO2 and VO2 was unchanged. The same was the case for Q at 100 W and for fH at 50 W. Qst kinetics were unaffected. In conclusion, the results do not fully support the hypothesis that vagal withdrawal determines phase I, because it was not completely suppressed. Although we can attribute the decrease in A1 of fH to a diminished degree of vagal withdrawal in hypoxia, this is not so for Qst. Thus the dual origin of the phase I of Q and QaO2, neural (vagal) and mechanical (venous return increase by muscle pump action), would rather be confirmed

Cardiac output by model flow method from intra-arterial and finger tip pulse pressure profiles

Modelflow®, when applied to non-invasive fingertip pulse pressure recordings, is a poor predictor of cardiac output (Q’ litre· min-1). The use of constants established from the aortic elastic characteristics, which differ from those of finger arteries, may introduce signal distortions, leading to errors in computing Q’. We therefore hypothesized that peripheral recording of pulse pressure profiles undermines the measurement of Q’ withModelflow®, so we compared Modelflow® beat-by-beat Q’ values obtained simultaneously non-invasively from the finger and invasively from the radial artery at rest and during exercise. Seven subjects (age, 24.0 + - 2.9 years; weight, 81.2 + - 12.6 kg) rested, then exercised at 50 and 100 W, carrying a catheter with a pressure head in the left radial artery and the photoplethysmographic cuff of a finger pressure device on the third and fourth fingers of the contralateral hand. Pulse pressure from both devices was recorded simultaneously and stored on a PC for subsequent Q’ computation. The mean values of systolic, diastolic and mean arterial pressure at rest and exercise steady state were significantly (P < 0.05) lower from the finger than the intra-arterial catheter. The corresponding mean steady-state Q’ obtained from the finger (Q’porta) was significantly (P < 0.05) higher than that computed from the intra-arterial recordings (Q’pia). The line relating beat-by-beat Q’porta and Q’pia was y = 1.55x - 3.02 (r2 = 0.640). The bias was 1.44 litre · min-1 and the precision was 2.84 litre · min-1.The slope of this line was significantly higher than 1, implying a systematic overestimate of Q’ by Q’porta with respect to Q’pia. Consistent with the tested hypothesis, these results demonstrate that pulse pressure profiles from the finger provide inaccurate absolute Q’ values with respect to the radial artery, and therefore cannot be used without correction with a calibration factor calculated previously by measuring Q’ with an independent method

Prolonged head down bed rest-induced inactivity impairs tonic autonomic regulation while sparing oscillatory cardiovascular rhythms in healthy humans.

Background. Physical inactivity represents a major risk for cardiovascular disorders, such as hypertension, myocardial infarction or sudden death; however, underlying mechanisms are not clearly elucidated. Clinical and epidemiological investigations suggest, beyond molecular changes, the possibility of an induced impairment in autonomic cardiovascular regulation. However, this hypothesis has not been tested directly. Methods. Accordingly, we planned a study with noninvasive, minimally intrusive, techniques on healthy volunteers. Participants were maintained for 90 days strictly in bed, 24 h a day, in head-down (S6-) position (HDBR). Physical activity was thus virtually abolished for the entire period of HDBR. We examined efferent muscle sympathetic nerve activity, as a measure of vascular sympathetic control, baroreceptor reflex sensitivity, heart rate variability (assessing cardiovagal regulation), RR and systolic arterial pressure and low-frequency and high-frequency normalized components (as a window on central oscillatory regulation). Measures. were obtained at rest and during simple maneuvers (moderate handgrip, lower body negative pressure and active standing) to assess potential changes in autonomic cardiovascular responsiveness to standard stimuli and the related oscillatory profiles. Results HDBR transiently reduced muscle sympathetic nerve activity,RR,heart ratevariabilityandbaroreceptor reflex sensitivity late during HDBR or early during the recovery phase. Conversely, oscillatory profiles of RR and systolic arterial pressure variability were maintained throughout. Responsiveness to test stimuli was also largely maintained

The effect of lower body negative pressure on phase 1 cardiovascular responses at exercise onset in healthy humans

We tested the hypothesis that vagal withdrawal and increased venous return interact in determining the rapid cardiac output response (Phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood dislocation to the heart by muscle pump action and simultaneously reduce resting vagal activity. At exercise start, we expected larger response amplitude for stroke volume and smaller for heart rate at progressively stronger LBNP levels, so that the cardiac output response would remain unchanged. Ten subjects performed 50 W exercise supine in Control condition and during -45 mmHg LBNP exposure. On single beat basis, we measured heart rate (HR), stroke volume (SV), and we calculated cardiac output (CO). We computed Phase I response amplitudes (A1) using an exponential model. SV A1 was higher under LBNP than in Control (p &lt; 0.05). Conversely, the A1 of HR, was 23 ± 56 % lower under LBNP than in Control (although NS). Since these changes tended to compensate each other, the A1 for CO was unaffected by LBNP. The rapid SV kinetics at exercise onset is compatible with an effect of increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR kinetics. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, as hypothesized, one acting on SV, the other on H

Disease characteristics and clinical outcome over two decades from the Swiss pulmonary hypertension registry

Pulmonary hypertension (PH), especially pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH), are rare and progressive conditions. Despite recent advances in treatment and prognosis, PH is still associated with impaired quality of life and survival. Long-term PH-registry data provide information on the changing PH-epidemiology and may help to direct resources to patient's needs. This retrospective analysis of the Swiss Pulmonary Hypertension Registry includes patients newly diagnosed with PH (mainly PAH/CTEPH) registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient characteristics (age, body mass index, gender, diagnosis), hemodynamics at baseline, treatment, days of follow-up, and events (death, transplantation, pulmonary endarterectomy, or loss to follow-up) at last visit were analyzed. Patients were stratified into four time periods according to their date of diagnosis. Survival was analyzed overall and separately for PAH/CTEPH and time periods. 1427 PH patients were included (thereof 560 PAH, 383 CTEPH). Over the years, age at baseline (mean ± SD) significantly increased from 59 ± 14 years in 2001–2005 to 66 ± 14 years in 2016–2019 (p < 0.001) while the gender distribution tended toward equality. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased over time (from 46 ± 15 to 41 ± 11 mmHg, respectively, 9 ± 5 to 7 ± 4 WU, p < 0.001). Three-year survival substantially increased over consecutive periods from 69% to 91% (for PAH 63%–95%, for CTEPH 86%–93%) and was poorer in PAH than CTEPH independently of time period (p < 0.001). Most patients were treated with mono- or combination therapy and an increasing number of CTEPH underwent pulmonary endarterectomy (40% 2016–2019 vs. 15% 2001–2005). This long-term PH registry reveals that over two decades of observation, newly diagnosed patients are older, less predominantly female, have less impaired hemodynamics and a better survival

Disease characteristics and clinical outcome over two decades from the Swiss pulmonary hypertension registry.

Pulmonary hypertension (PH), especially pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH), are rare and progressive conditions. Despite recent advances in treatment and prognosis, PH is still associated with impaired quality of life and survival. Long-term PH-registry data provide information on the changing PH-epidemiology and may help to direct resources to patient's needs. This retrospective analysis of the Swiss Pulmonary Hypertension Registry includes patients newly diagnosed with PH (mainly PAH/CTEPH) registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient characteristics (age, body mass index, gender, diagnosis), hemodynamics at baseline, treatment, days of follow-up, and events (death, transplantation, pulmonary endarterectomy, or loss to follow-up) at last visit were analyzed. Patients were stratified into four time periods according to their date of diagnosis. Survival was analyzed overall and separately for PAH/CTEPH and time periods. 1427 PH patients were included (thereof 560 PAH, 383 CTEPH). Over the years, age at baseline (mean ± SD) significantly increased from 59 ± 14 years in 2001-2005 to 66 ± 14 years in 2016-2019 (p < 0.001) while the gender distribution tended toward equality. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased over time (from 46 ± 15 to 41 ± 11 mmHg, respectively, 9 ± 5 to 7 ± 4 WU, p < 0.001). Three-year survival substantially increased over consecutive periods from 69% to 91% (for PAH 63%-95%, for CTEPH 86%-93%) and was poorer in PAH than CTEPH independently of time period (p < 0.001). Most patients were treated with mono- or combination therapy and an increasing number of CTEPH underwent pulmonary endarterectomy (40% 2016-2019 vs. 15% 2001-2005). This long-term PH registry reveals that over two decades of observation, newly diagnosed patients are older, less predominantly female, have less impaired hemodynamics and a better survival