骨転移を有しない前立腺がん患者へのアンドロゲン除去療法による骨粗鬆症に対する経口ビスフォスフォネート製剤の予防効果について

We studied the short-term efficacy of alendronate, an oral bisphosphonates, on bone mineral density (BMD) during androgen deprivation therapy (ADT) in 45 nonmetastatic prostate cancer patients at the beginning of ADT (treatment group). All received alendronate five mg daily from the initiation of ADT. Lumber BMD was evaluated by dual energy X-ray absorptiometry, at baseline and after six months of treatment. Historical data on 24 patients with prostate cancer who received ADT without bisphosphonate administration were studied as controls (control group). BMD decreased in 13.9 and 45.8% of the patients in the treatment and control groups, respectively. Mean BMD changes in the lumber spine were +1.6 +/- 3.0% in the treatment group and -1.1 +/- 2.7% in the control group (p = 0.006). No pathological fractures occurred during the study period. No severe adverse effects were observed, but three patients could not continue alendronate treatment because of adverse events. Despite the short-term of this evaluation, our results showed that oral alendronate is an effective and safe treatment for preventing bone loss and increasing BMD in patients receiving ADT for prostate cancer.目的:アンドロゲン除去療法は骨塩減少とそれに伴う病的骨折の潜在的な危険因子である。点滴ビスフォスフォネート製剤はアンドロゲン除去療法を受けている前立腺がん患者に対する骨塩量の減少を予防することが示されているが経口ビスフォスフォネート製剤については評価されていない。今回, われわれは経口ビスフォスフォネート製剤の1つであるアレンドン酸を骨転移を有しない前立腺がん患者に投与して骨塩量を測定し短期間での効果を検討した。対象と方法:治療群として45人の骨転移を有しない前立腺がん患者について検討した。アレンドロン酸を1日5mg経口投与し治療前, 治療半年後に腰椎の骨塩量を測定し比較検討した。対照群として24人の骨転移を有しない前立腺がん患者についても同様に検討を行った。結果:骨塩量の減少は治療群で13.9%, 対照群で45.8%に見られた。腰椎における骨塩量の変化は治療群で平均1.6%, 対照群で-1.1%であった(p=0.006)。治療期間内において病的骨折は認められず, 有害事象として重篤なものは認めなかったが副作用のため3例が内服継続困難であった。結語:短期間の検討であるにもかかわらず経口ビスフォスフォネート製剤であるアレンドロン酸は前立腺がん患者に対するアンドロゲン除去療法による骨塩量減少を予防するのに有効で安全な治療法であることが示唆された。(著者抄録

Application of Direct Renin Inhibition to Chronic Kidney Disease

Chronic kidney disease has serious implications with a high risk for progressive loss of renal function, increased cardiovascular events as well as a substantial financial burden. The renin-angiotensin-aldosterone system (RAAS) is activated in chronic kidney disease, especially in diabetes and hypertension, which are the leading causes of chronic kidney disease. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease the rate of progression of diabetic and non-diabetic nephropathy and are recommended therapy for chronic kidney disease. Key clinical trials supporting the use of ACE inhibitors and ARBs in chronic kidney disease are discussed. Recent developments in our understanding of RAAS biology and the use of direct renin inhibition are reviewed in the context of their potential impact on the prevention and management of chronic kidney disease. Despite the clinical success of ACE inhibitors and ARBs the rates of mortality and progression to renal failure remain high in these patient populations. ACE inhibitor or ARB monotherapy, in doses commonly used in clinical practice does not result in complete suppression of the RAAS. Aliskiren, a direct renin inhibitor, offers a novel approach to inhibit the RAAS in chronic kidney disease. High dose ARB therapy or combination therapies with ACE inhibitors and ARBs have shown beneficial effects on surrogate markers of chronic kidney disease. Early data based on urinary protein excretion rates as a surrogate marker for renal function suggest a possibly novel role for aliskiren alone or in combination with ARBs in chronic kidney disease

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腹腔鏡手術の経験が異なる術者での腹腔鏡下仙骨膣固定術の手術成績の比較

We retrospectively analyzed the safety and surgical outcomes of laparoscopic sacrocolpopexy (LSC) by the novice surgeon (performed ＜5 laparoscopic surgery). Between November 2017 and December 2020, there were 15 cases in which the novice surgeon performed part of LSC, 8 cases in which the novice performed all of LSC, and 50 cases in which the experienced surgeon (performed ＞100 laparoscopic surgery) performed all of LSC. We compared surgical outcome of the 50 cases operated by the experienced surgeon and 23 cases operated by the novice. The laparoscopic time was longer when performed by the novice than by the experienced surgeon (median 208 minutes vs 189 minutes, p＝0.039). Cases of pelvic organ prolapse quantification system (POP-Q) stage 4 were operated more often by the experienced surgeon than by the novice (28% vs 4.8%, p＝0.027). There were no significant differences in the complications and recurrence of pelvic organ prolapse (POP-Q≧2). The LSC process was divided into five steps. The laparoscopic time of all steps was longer when performed by the novice than by the experienced surgeon except the step of lifting up the sigmoid colon and hysterectomy. As the number of cases performed by the novice increased, the laparoscopic time of all steps decreased. The short-term surgical outcomes for cases operated by the novice and experienced surgeon were comparable when the novice avoided cases of POP-Q stage 4. LSC has been said to be difficult, but in this study, even novice surgeons in laparoscopic surgery may be able to perform LSC by accumulating cases. Although this study is not generalizable due to limitations, we believe it will inspire many young doctors to perform LSC

Singlet fission as a polarized spin generator for biological nuclear hyperpolarization

Singlet fission (SF), converting a singlet excited state into a spin-correlated triplet-pair state, is the sole way to generate a spin quintet state in organic materials. Although its application to photovoltaics as an exciton multiplier has been extensively studied, use of its unique spin degree of freedom is largely unexplored. Here, we demonstrate that the spin polarization of the quintet multiexcitons generated by SF improves the sensitivity of biological magnetic resonance through dynamic nuclear polarization (DNP). We form supramolecular assemblies of a few pentacene chromophores and use SF-born quintet spins to achieve DNP of water-glycerol, the most basic biological matrix, at lower microwave intensities than for conventional triplet-based DNP. Our demonstration opens a new use of SF as a “polarized spin generator” in bio-quantum technology