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We sought to examine the relation between sodium bicarbonate prophylaxis for contrast-associated nephropathy (CAN) and mortality. We conducted an individual patient data meta-analysis from multiple randomized controlled trials. We obtained individual patient data sets for 7 of 10 eligible trials (2,292 of 2,764 participants). For the remaining 3 trials, time-to-event data were imputed based on follow-up periods described in their original reports. We included all trials that compared periprocedural intravenous sodium bicarbonate to periprocedural intravenous sodium chloride in patients undergoing coronary angiography or other intra-arterial interventions. Included trials were determined by consensus according to predefined eligibility criteria. The primary outcome was all-cause mortality hazard, defined as time from randomization to death. In 10 trials with a total of 2,764 participants, sodium bicarbonate was associated with lower mortality hazard than sodium chloride at 1 year (hazard ratio 0.61, 95% confidence interval [CI] 0.41 to 0.89, p = 0.011). Although periprocedural sodium bicarbonate was associated with a reduction in the incidence of CAN (relative risk 0.75, 95% CI 0.62 to 0.91, p = 0.003), there exists a statistically significant interaction between the effect on mortality and the occurrence of CAN (hazard ratio 5.65, 95% CI 3.58 to 8.92, p

Background: Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. Methods: Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated. The effect of acidity on mTORC1 activity was determined by Western blot. The anticancer efficacy of rapamycin in combination with sodium bicarbonate to increase the intratumoral pH was tested in two different mouse models and compared to rapamycin treatment alone. Histological analysis was performed on tumor samples to evaluate proliferation, apoptosis and necrosis. Results: Exposing cancer cells to acidic pH in vitro significantly reduced the anti-proliferative effect of rapamycin. At the molecular level, acidity significantly decreased mTORC1 activity, suggesting that cancer cell proliferation is independent of mTORC1 in acidic conditions. In contrast, the activation of mitogen-activated protein kinase (MAPK) or AKT were not affected by acidity, and blocking MAPK or AKT with a chemical inhibitor maintained an anti-proliferative effect at low pH. In tumor mouse models, the use of sodium bicarbonate increased mTORC1 activity in cancer cells and potentiated the anti-cancer efficacy of rapamycin. Combining sodium bicarbonate with rapamycin resulted in increased tumor necrosis, increased cancer cell apoptosis and decreased cancer cell proliferation as compared to single treatment. Conclusions: Taken together, these results emphasize the inefficacy of mTORC1 inhibitors in acidic conditions. They further highlight the potential of combining sodium bicarbonate with mTORC1 inhibitors to improve their anti-tumoral efficacy.

Background: Sodium bicarbonate intake has been shown to improve exercise tolerance, but the effects on high-intensity intermittent exercise are less clear. Thus, the aim of the present study was to determine the effect of sodium bicarbonate intake on Yo-Yo intermittent recovery level 2 test performance in trained young men. Methods: Thirteen men aged 23 ± 1 year (height: 180 ± 2 cm, weight: 78 ± 3 kg; VO2max: 61.3 ± 3.3 mlO2 · kg−1 · min−1; means ± SEM) performed the Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2) on two separate occasions in randomized order with (SBC) and without (CON) prior intake of sodium bicarbonate (0.4 g · kg−1 body weight). Heart rate and rating of perceived exertion (RPE) were measured during the test and venous blood samples were taken frequently. Results: Yo-Yo IR2 performance was 14 % higher (P = 0.04) in SBC than in CON (735 ± 61 vs 646 ± 46 m, respectively). Blood pH and bicarbonate were similar between trials at baseline, but higher (P = 0.003) immediately prior to the Yo-Yo IR2 test in SBC than in CON (7.44 ± 0.01 vs 7.32 ± 0.01 and 33.7 ± 3.2 vs 27.3 ± 0.6 mmol · l−1, respectively). Blood lactate was 0.9 ± 0.1 and 0.8 ± 0.1 mmol · l−1 at baseline and increased to 11.3 ± 1.4 and 9.4 ± 0.8 mmol · l−1 at exhaustion in SBC and CON, respectively, being higher (P = 0.03) in SBC. Additionally, peak blood lactate was higher (P = 0.02) in SBC than in CON (11.7 ± 1.2 vs 10.2 ± 0.7 mmol · l−1). Blood glucose, plasma K+ and Na+ were not different between trials. Peak heart rate reached at exhaustion was 197 ± 3 and 195 ± 3 bpm in SBC and CON, respectively, with no difference between conditions. RPE was 7 % lower (P = 0.003) in SBC than in CON after 440 m, but similar at exhaustion (19.3 ± 0.2 and 19.5 ± 0.2). Conclusion: In conclusion, high-intensity intermittent exercise performance is improved by prior intake of sodium bicarbonate in trained young men, with concomitant elevations in blood alkalosis and peak blood lactate levels, as well as lowered rating of perceived exertion.

70歳男.7年前に膀胱癌, 前立腺癌で膀胱尿道全摘除術及び回腸導管造設術を施行された.術後1年に尿管小腸吻合部狭窄を認め, 順行性に両側ステント留置した.その後ステントの閉塞が頻回となり, 両側に腎瘻を造設したが, 腎盂腎炎を繰り返した.更にカテーテル留置に起因する感染結石が判明し, 両側の経皮的腎結石破砕術後, 腸導管再建術を施行した.尿管は狭窄部付近で蠕動を認めず, 回腸を長く遊離し, 大血管の両側で吻合する方針とした.回腸導管を摘除した後, 回腸を遊離してS状結腸背側に通し, その両側で尿管を吻合した.術後4ヵ月で著明な代謝性アシドーシスを来たし, ナトリウム, クロールの高値, 腎機能低下を認めた.右大腿静脈にダブルルーメンカテーテルを留置して炭酸水素ナトリウムによる補正を開始した.全身状態が良好となった時点で回腸導管造影を行ったが, 尿の流出は良好であった.その後軽度の腎機能低下, クロールの高値は続いているが, 炭酸水素ナトリウム2g/日の投与で酸塩基平衡は正常に保たれている, A 70-year-old man visited our hospital with the complaint of appetite loss. He had undergone an ileal conduit reconstruction due to bilateral ileo-ureteral stenosis 3 months before. Blood gas analysis showed metabolic acidosis (pH 7.091, pO2 120.5 mmHg, pCO2 20.9 mmHg, HCO3 6.1 mmHg), and blood analysis revealed serum chloride 121 mmol/l (normal range: 99-110). Sodium bicarbonate was immediately administered, his condition improved. We concluded that reabsorption of urine from the ileal conduit due to dehydration had caused hyperchloremic metabolic acidosis. He was given sodium bicarbonate 2 g per day, and his blood gas analysis and serum electrolytes remained within normal limits.

A 70-year-old man visited our hospital with the complaint of appetite loss. He had undergone an ileal conduit reconstruction due to bilateral ileo-ureteral stenosis 3 months before. Blood gas analysis showed metabolic acidosis (pH 7.091, pO2 120.5 mmHg, pCO2 20.9 mmHg, HCO3 6.1 mmHg), and blood analysis revealed serum chloride 121 mmol/l (normal range: 99-110). Sodium bicarbonate was immediately administered, his condition improved. We concluded that reabsorption of urine from the ileal conduit due to dehydration had caused hyperchloremic metabolic acidosis. He was given sodium bicarbonate 2 g per day, and his blood gas analysis and serum electrolytes remained within normal limits.