微整形: 隆鼻/額頭/蘋果肌---生物相容性材料成關鍵 !

鼻形立體顏值新焦點 晉升「側顏殺」美女行列 記者陳鴻謙／台北報導 2018年7月6日近年來，大陸IP劇正夯，全民瘋狂追劇，高顏質女星幾乎是近年陸劇的熱門嬌點。提起新一代人氣女星，如楊冪、迪麗熱巴、劉亦菲等，他們都擁有像西方女性一般的翹鼻，立體分明的鼻形儼然已經成為大陸女星的必備標誌。談到翹鼻，由於基因的緣故，東方人極少天生擁有這種鼻形，但在西方人及東西方混血兒身上卻很常見，如一線美劇女演員Maggie Q，父親是美國人、母親是越南人，完全遺傳到父親挺直的鼻樑，五官顯得更加精緻。耳鼻喉科診所醫師陳建業指出，鼻形是高顏質的決定性因素，東方人臉部較為扁平，鼻形不佳，先天條件上相對弱勢。在面相學上來說，鼻形會改變臉形整體樣貌，也能改變一個人的氣質、氣場，也就是說，鼻整形不再只是增高的物理變化，更是改變整體氣質化學變化。所謂「鼻美則容顏美」，陳建業進一步解釋，鼻美不在鼻高，而在於鼻下1／3的形狀。所謂鼻下1／3的形狀，關鍵在於鼻尖投射角、鼻小柱突出度以及鼻唇角。臨床上，部份女性，會選擇較長的鼻形，但看起來較為男性化，大多數女性，仍會選擇翹鼻。事實上，無論是熟女或輕熟女，只要改成恰到好處的小翹鼻，都會有年輕10歲的效果。現今鼻整形的最新概念是同時也微整側臉，以期達到完美的「側顏殺」。陳建業說明，側面可以從額頭開始做，一直到下巴，讓側面輪廓更加立體分明。而使用的材質，無論是自體肋軟骨或異體肋軟骨，都可以壓成碎片，像魷魚絲一般軟Q，用來填補額頭、夫妻宮、蘋果肌、下巴。這種材質是永久性，可以取代玻尿酸這類1至2年會消失的材料。最後，陳建業提醒，由於臉部的神經血管豐富，進行顏面整形前，最好尋求耳鼻喉科醫師的專業意見。此外，與醫師做術前討論時，也要將皮膚類型、體質、年齡、身體疾病等列入手術考慮的重要因素，並慎選有醫療許可的填充物，如此才能得到預期的手術結果，擠身「側顏殺」美女行列。

肺癌 免疫治療如何精準治療: PD-L1 高低不重要？！癌突變壓力(Tumor mutation burden) 成關鍵？

CheckMate 227 trial in advanced lung cancer by Dr. Borghaei.

Tumor mutation burden matters than PD-L1: 

1, regardless of the level of PD-L1 expression or histology, patients who had this biomarker of a high tumor mutational burden above a certain threshold had a better outcome compared to patients with a relatively low tumor mutational burden, in terms of PFS and response rate, with the combination of ipilimumab plus nivolumab compared to chemotherapy alone.

2, even in this population of PD-L1–negative patients, a high tumor mutational burden was associated with better PFS and better duration of response with ipilimumab plus nivolumab than either chemotherapy alone or nivolumab plus chemotherapy.

3, patients have PD-L1–negative tumors and a low tumor mutational burden, the addition of nivolumab to chemo or ipilimumab to nivolumab didn’t really provide additional benefit over chemotherapy alone.

Side effects: add nivolumab to chemotherapy there are more side effects compared to chemotherapy alone. But interestingly, in this analysis, the group of patients that got ipilimumab plus nivolumab had a lower percentage of the grade 3 and 4 severe side effects. In the chemotherapy-plus-nivolumab group, the grade 3 and 4 toxicities were close to 50%—but only 25% and 35% of patients in the ipilimumab-plus-nivolumab group and chemotherapy-alone group experienced these toxicities.

*Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

* Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity. 

(塩野義製薬 & Purdue): Re-acquisition of all rights relating to Symproic(R) for opioid-induced constipation treatment in the United States

( エーブィエ バイオファーム )米国におけるオピオイド誘発性便秘症治療薬 Symproic®に関する 全権利の再取得について塩野義製薬株式会社2018 年7月6日（本社：大阪市中央区、代表取締役社長：手代木 功、以下「塩野義製薬」）は、当社が創製したオピオイド誘発性便秘症治療薬 Symproic®（一般名：ナルデメジン錠、0.2 mg） について、米国における戦略的提携先のPurdue Pharma 社（以下、Purdue 社）から全ての権利 を再取得したことを、お知らせいたします。 本件は、Purdue 社が事業環境変化に対応するために米国内のビジネスモデルを変革し多様化さ せることを受けたものであり、塩野義製薬とPurdue 社は Symproic®の米国における共同販売活 動に関するアライアンス活動を終了することで合意しております。この件に関し、塩野義製薬には、Purdue 社に対するいかなる金銭的およびその他の義務も発生いたしません。塩野義製薬は、Symproic®の自社販売と流通を既に開始し、販売促進のための新たなパートナ ー企業を選定中です。米国におけるオピオイド誘発性便秘症（OIC）患者数は数百万人にも上る ことから、Symproic®は OIC でお困りの患者さまに対する重要な治療選択肢の一つであると確信 しております。塩野義製薬は、中期経営計画『SGS2020』で経営資源を集中するコア疾患領域のひとつに疼痛領域を選択し、疼痛治療に関する諸課題を解決する革新的新薬の創製に注力しております。引き 続き疼痛領域に対する取り組みを強化し、さまざまな痛みや疼痛治療薬による副作用でお困りの 患者さまの QOL（quality of life）向上に貢献してまいります。

Fifty-Two Week Safety Study on Symproic® (naldemedine) for Opioid-induced Constipation (OIC) in Adults with Chronic Non-cancer Pain Published in PAIN First 52-Week Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of a Peripherally-acting Mu-opioid Receptor Antagonist (PAMORA)  March 06, 2018 08:30 AM Eastern Standard Time OSAKA, Japan & FLORHAM PARK, N.J. & STAMFORD, Conn.--(BUSINESS WIRE)--Shionogi Inc. and Purdue Pharma L.P. today announced the publication of a study known as COMPOSE-3. The study is the first to investigate a peripherally-acting mu-opioid receptor antagonist (PAMORA) over the course of 52 weeks in a randomized, placebo-controlled and double-blind manner. The study was published online ahead of print in PAIN, the journal of the International Association for the Study of Pain. "We are pleased to share with the scientific community the publication of the first 52-week double-blind study evaluating the safety of a PAMORA in adult patients with OIC and chronic non-cancer pain""The publication of the results of COMPOSE-3 in PAIN is significant as the study provides additional important information regarding the safety and tolerability of Symproic over the course of 52 weeks for adults with OIC and chronic non-cancer pain," said Dr. Tsutae "Den" Nagata, Chief Medical Officer, Shionogi.

Study Design and Results This randomized, double-blind, placebo-controlled, parallel-group, Phase 3 clinical trial (COMPOSE-3) evaluated the long-term safety and tolerability of once-daily oral Symproic 0.2 mg for 52 weeks in patients with chronic non-cancer pain, on a stable opioid therapy, and who could be on a routine laxative regimen but still had OIC. In the study, 2,414 patients were screened. Patients had to be aged 18 to 80, have had chronic non-cancer pain for at least 3 months, were receiving a stable daily dose of opioids (greater than or equal to 30 mg oral morphine equivalents) for at least one month prior to screening, and had self-reported OIC. From the patients screened, 1,246 eligible patients with confirmed OIC were randomized 1:1 to receive once-daily oral Symproic 0.2 mg (n=623) or placebo (n=623) for 52 weeks.  The primary endpoint was summary measures of treatment-emergent adverse events (TEAEs). Similar proportions of patients taking Symproic and placebo experienced TEAEs (Symproic, 68.4% (n=425) vs placebo 72.1% (n=446); difference: −3.6% [95% CI: −8.7-1.5]) and TEAEs leading to study discontinuation (Symproic 6.3% vs placebo 5.8%; difference: 0.5% [95% CI: –2.2-3.1]). Diarrhea was the most common TEAE in the Symproic group (11%) and was reported more frequently vs placebo (5.3%; difference: 5.6% [95% CI: 2.6-8.6]). A greater proportion of patients treated with Symproic vs placebo reported other gastrointestinal-related treatment-emergent adverse events, including abdominal pain (8.2% vs 3.1%) and vomiting (6.0% vs 3.1%). The incidences of treatment-related serious adverse events (Symproic, 0.5% vs placebo, 1.0%; difference: −0.5% [95% CI: −1.4-0.5]) and serious TEAEs leading to study discontinuation (Symproic, 1.1% vs placebo, 1.9%; difference: −0.8% [95% CI: −2.2-0.6]) were consistent between treatment groups. The 52-week safety study included efficacy endpoints as well, which were secondary. One of these endpoints, frequency of bowel movements, was also assessed in the primary endpoint of the two 12-week pivotal studies, and the results were consistent. "We are pleased to share with the scientific community the publication of the first 52-week double-blind study evaluating the safety of a PAMORA in adult patients with OIC and chronic non-cancer pain," said Monica Kwarcinski, PharmD, Head of Medical Affairs, Purdue Pharma L.P. "In collaboration with our partners at Shionogi, we are committed to supporting adult patients who live with OIC and chronic non-cancer pain and the physicians who treat them." 

Symproic, a once-daily oral PAMORA medication approved by the U.S. Food and Drug Administration (FDA) in March 2017, is indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Symproic is available as a 0.2 mg once-daily oral tablet and may be taken at any time of day, with or without food, and with or without laxatives. Alteration of analgesic dosing regimen prior to initiating Symproic is not required. Patients receiving opioids for less than 4 weeks may be less responsive to Symproic. Treatment with Symproic should be discontinued if treatment with the opioid medicine is also discontinued. 

INDICATION Symproic® (naldemedine) is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

晟德 出售 蘇州東曜 股份 貢獻14.91 億元

晟德子公司增資成功 Q3認列15億處分利益 每股純益貢獻4.65元 鉅亨網 鉅亨網記者黃雅娟 台北 2018年7月6日 晟德 (4123-TW) 今 (6) 日董事會決議，通過子公司蘇州東曜募資案，晟德持有股份將由現在的 46.55％ 降低為 34.58%，處分利益約為 14.91 億元，每股純益將貢獻 4.65 元，預計將於第 3 季入帳。晟德表示，同意通過子公司蘇州東曜募資，將成功引進策略夥伴，並幫助東曜專注於高端抗腫瘤藥物開發。此次現金增資案通過後，晟德持有股份將由 46.55% 降為約 34.58%，處分利益約 14.91 億元新台幣，貢獻每股純益約 4.65元。晟德預估，該筆利益將於今年第 3季入帳。晟德 2017 年每股純益為0.79 元，今年第 1 季每股純益為 1.41 元。

Fda顧問利益衝突可能性浮上檯面

Report details possible conflict of interest issues for FDA advisors July 6, 2018 by Bob Yirka, Medical Xpress Charles Piller, a contributing correspondent for the journal Science, has published a Feature piece in the journal detailing what he describes as possible conflicts of interest issues by people who serve as advisors to the FDA. In his report, he offers examples of what he describes as possible conflicts of interest. He also suggests the FDA might want to review its rules regarding what advisors can and cannot do after they have served in an advisory role for the agency. The Food and Drug Agency is tasked with providing a safeguard for the public. Food and drugs proposed by business entities are reviewed by teams at the agency and must win a seal of approval before they are allowed to sell a product to the public. As part of this process, the FDA calls in expert advisors to offer testimony or advice on given products, such as new drugs. In his report, Piller focuses on people who worked as advisors for the FDA who later received what could be perceived as compensation from those they have reviewed, for their efforts. He and associate Jia You looked at publicly available data concerning 107 doctor advisors and found that 40 of them received benefits such as payment for hotels or research grants. More than half of them, he notes, received over $100,000 in such "gifts," and seven of them got more than $1 million worth. And none of the payments were reported by the FDA. One doctor in particular, he notes, received $1.9 million from a pharmaceutical company after one of its drugs was approved by a panel on which that doctor had been an advisor. In a related segment, Piller notes that it is not just advisors who might be engaging in questionable activities. He notes that one former director for the agency who was once involved in reviewing drugs now operates a consulting business that offers advice to pharmaceutical companies on how to get their drugs approved.Piller sums up his paper by suggesting that it might be time for the FDA to shore up its non-compete contracts for both advisors and employees—doing so, he notes would eliminate the possibility of such people making decisions that are in their own best interests rather than those of the public.

More information: Charles Piller. Hidden conflicts?, Science (2018). DOI: 10.1126/science.361.6397.16 Summary An investigative report uncovers little recognized and unpoliced potential conflicts of interest among those who serve on FDA advisory panels that review drugs. Some members of such panels are later receiving significant payments from either the makers of drugs they previously reviewed, or from competitors. This is happening despite the FDA's established system to identify possible financial conflicts of interest among those recruited for the drug advisory panels. The investigation analyzed records on the federal Open Payments website between 2013 and 2016. Of 107 physician advisors who voted on FDA advisory committees during this time, 26 later took more than $100,000 from the makers of drugs, or from competing firms. in post-hoc earnings or research support. Even though these payments might not be truly "quid-pro-quo," according to Vinay Prasad, an oncologist who also studies financial conflicts that exist in drug approvals, those asked to weigh in stand to gain tremendously in their further professional careers. "It's in their best interest to play nice with the companies." FDA may also have missed or judged insignificant financial ties physicians had before their service on the drug approval advisory panels.