Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

<b>Purposeb>As protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.<b>Methodsb>A prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6&nbsp;months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.<b>Resultsb>Among 110 participants,&nbsp;56 (51%) were women. Mean age was 61.7&nbsp;±&nbsp;1.9&nbsp;years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95&nbsp;%CI 5.25–11.67) folds and 2.40 (95&nbsp;%CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95&nbsp;%CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95&nbsp;%CI 19.1–34.7) fold in and immunocompetent group, was observed.<b>Conclusionb>A third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

股骨转子间骨折的稳定性重建概念演化与研究进展

<b>目的b>؃b;结近年来股骨转b50;间骨折在稳b9a;性重建eb9;面的概念演化与研究ࣽb;展。<b>eb9;法b>查阅国内外相关文献并结合自࣪b;经验，从股骨转b50;间骨折的解剖特pb9;、稳b9a;ոb;骨折与不稳b9a;ոb;骨折分߇b;、稳b9a;性复位与不稳b9a;性复位、术中加Ըb;初֜b;稳b9a;与术后滑动二b21;稳b9a;、内固b9a;术后稳b9a;性bc4;估、早期Ӡb;地站ެb;负重b49;eb9;面ࣽb;行؃b;结分析。<b>结果b>股骨转b50;间骨折发生于股骨颈干šba;端转换区，具有天然的内߿b;不稳b9a;倾向。骨折复位质量是影响后续内固b9a;物b89;放的最重要前提因素。判断骨折复位质量有bf9;~bf;和bf9;位两eb9;面，bf9;~bf;采用 Garden 指数࿱b;在bf9;位eb9;面，随着皮质bf9;位理念（b63;性、中性、负性）的提出，特Ԣb;强调前内侧皮质的相互砥住支撑（解剖、b63;性），是ƒb7;得骨折稳b9a;性复位的关键，而不再强调后内侧小转b50;骨块的作用。术后影像b66;的稳b9a;性bc4;分为早期Ӡb;地站ެb;负重提ӹb;了量化指标。但术中的前内侧皮质支撑复位，在术后头颈骨块滑动ƒb7;得二b21;稳b9a;的过ޠb;中，仍有皮质bf9;位丢失sb0;象，需研究其危险因素和防范措ebd;。<b>结bba;b>股骨转b50;间骨折在取得良好bf9;~bf;的基础上，只要ƒb7;得了前内侧皮质的相互砥住和支撑，并用内固b9a;器hb0;维持住，就ƒb7;得了术后稳b9a;性。术后稳b9a;性bc4;分优良者，可以b89;全地早期Ӡb;地负重、站ެb;行走ۓb;动。     

改良内固定融合术治疗成人Ⅱ型痛性足副舟骨

<b>目的b>探ba8;改良内固b9a;融合术lbb;疗成Nba;Ⅱոb;ݝb;性b3;副舟骨（painful accessory navicular，PAN）的疗效。<b>eb9;法b>2016 年 1 月—2017 年 12 月，采用改良内固b9a;融合术lbb;疗 29 Ӹb;（37 b3;）Ⅱոb; PAN。其中男 12 Ӹb;，女 17 Ӹb;࿱b;年龄 18～50 岁，平均 41.4 岁。扭伤 24 Ӹb;，无明显bf1;因 5 Ӹb;。患者均行 6 个月以上保b88;lbb;疗，症rb6;无明显改善。术前及ٲb;b21;随bbf;时采用美国ݾb;形b3;踝协会（AOFAS）中b3;bc4;分bc4;估临床疗效࿱b;X ~bf;片۔b;量跟骨倾斜角、距骨b2c; 1 跖骨角、距舟关节包bb9;角、距骨b2c; 2 跖骨角。<b>结果b>术后 1 Ӹb;出sb0;切口浅表感染，经加强换药后愈合࿱b;其余患者切口均Ⅰ期愈合，无深部感染或骨髓炎发生。29 Ӹb;均ƒb7;随bbf;，随bbf;时间 12～33 个月，平均 25.1 个月。X ~bf;片示关节面均于术后 2～5 个月愈合，平均 3.4 个月。随bbf;期间未见内固b9a;物松动或断裂。ٲb;b21;随bbf;时，AOFAS ubc;ݝb;、功能、ԩb;~bf;bc4;分及؃b;分以及距舟关节包bb9;角、距骨b2c; 1 跖骨角和距骨b2c; 2 跖骨角均较术前显著改善，差异有统ba1;b66;意义（P<0.05）࿱b;跟骨倾斜角ؤb;术前后差异无统ba1;b66;意义（t=1.097，P=0.276）。 <b>结bba;b>采用改良内固b9a;融合术lbb;疗成Nba;Ⅱոb; PAN 可有效缓解症rb6;，患b3;功能恢复良好，并发症少。     

单纯 Ilizarov 环形外固定技术治疗合并骨筋膜室综合征的胫骨平台骨折

<b>目的b>探ba8;单纯 Ilizarov 环形外固b9a;技术lbb;疗合并骨b4b;膜ba4;综合征的ࠎb;骨平台骨折的疗效。<b>eb9;法b>2013 年 9 月—2017 年 3 月，收lbb; 30 Ӹb;合并骨b4b;膜ba4;综合征的ࠎb;骨平台骨折患者，采用单纯 Ilizarov 环形外固b9a;技术lbb;疗。男 23 Ӹb;，女 7 Ӹb;࿱b;年龄 23～43 岁，平均 34.4 岁。致伤原因：交通Өb;故伤 12 Ӹb;，高处坠落伤 4 Ӹb;，摔伤 8 Ӹb;，重物砸伤 6 Ӹb;。受伤至入院时间 1～12 h，平均 4.8 h。骨折 Schatzker 分ոb;：Ⅱոb; 1 Ӹb;、Ⅲոb; 3 Ӹb;、Ⅳոb; 10 Ӹb;、Ⅴոb; 7 Ӹb;、Ⅵոb; 9 Ӹb;。30 Ӹb;均因骨b4b;膜ba4;综合征行切开减Ըb;࿱b;切开减Ըb;至ؤb;术时间为 10～15 d，平均 12.5 d。lbb;疗后采用膝关节b66;会bc4;分ߏb;统（KSS）及 Ilizarov eb9;法研究与应用协会（ASAMI）协bae;bc4;价膝关节功能。<b>结果b>ؤb;术时间 110～155 min，平均 123.1 min࿱b;术中出血量 100～500 mL，平均 245 mL࿱b;术后住院时间 3～5 d，平均 3.8 d。患者均ƒb7;随bbf;，随bbf;时间 20～24 周，平均 22.7 周。除 2 Ӹb;患者出sb0;针道感染征象外，无其他并发症发生。X ~bf;片复查显示骨折均愈合，愈合时间 10～20 周，平均 14.6 周。ٲb;b21;随bbf;时，膝关节 KSS 临床bc4;分؃b;分为 70～95 分，平均 87.5 分࿱b;功能bc4;分؃b;分为 70～90 分，平均 79.0 分。参照 ASAMI 协bae;bc4;价ƒb7;优 24 Ӹb;、良 3 Ӹb;、可 2 Ӹb;、差 1 Ӹb;。<b>结bba;b>bf9;于合并骨b4b;膜ba4;综合征的ࠎb;骨平台骨折，单纯 Ilizarov 环形外固b9a;技术lbb;疗后患者关节功能可以基本恢复且并发症少，是一项相bf9;b89;全、有效的lbb;疗eb9;法。     

TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFb2; signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFb2;/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐ba;B

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFb2;

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

CO2点阵激光早期控制唇裂二期整复术后瘢痕的疗效观察

<b>目的b>观bdf;bd4;较COb>2b>pb9;阵激光早期控制唇裂术后二期整复术术区瘢痕的临床疗效。<b>eb9;法b>lbb;疗组为43Ӹb;接受唇裂术后৳b;唇畸形二期整复术的患者，早期采用COb>2b>pb9;阵激光lbb;疗，bf9;照组为70Ӹb;曾接受一期唇裂ؤb;术的患者，bf9;两组6个月后的瘢痕恢复情Qb5;ࣽb;行bd4;较࿱b;分析术后距ybb;激光开֜b;lbb;疗时间的长短，性Ԣb;两因素bf9;激光lbb;疗瘢痕疗效的差异。<b>结果b>1）lbb;疗组的疗效优于bf9;照组（P<0.000 1），lbb;疗组中显效和有效所组成的؃b;有效率be;90.7%࿱b;2）男女疗效差异无统ba1;b66;意义（P=0.487），ؤb;术后1年内的患者，ؤb;术后距ybb;开֜b;瘢痕lbb;疗的时间<3个月与≥3个月Ӥb;间，疗效无明显统ba1;b66;差异（P=0.055）。<b>结bba;b>COb>2b>pb9;阵激光在唇裂二期整复术术后瘢痕的lbb;疗中具有较为确切的疗效。且与患者的性Ԣb;无明显相关性。ؤb;术后1年内的患者，术后距ybb;开֜b;瘢痕lbb;疗的时间<3个月和≥3个月疗效无差异，因b64;在唇裂二期ؤb;术后的1年内早期bf9;瘢痕ࣽb;行干预可ƒb7;得良好的效果。     

PD-L1高表达晚期非小细胞肺癌患者单纯免疫治疗与免疫联合化疗疗效比较

<b>背景与目的b>以免ݚb;检查pb9;抑制剂（immune checkpoint inhibitors, ICIs）为代表的免ݚb;lbb;疗越来越广ۍb;地应用于€ba;癌lbb;疗。然而，bf9;于ޠb;序性b7b;亡受体配体1（programmed cell death-ligand 1, PD-L1）高表be;，即€bf;瘤bd4;Ӹb;bc4;分（tumor proportion score, TPS）≥50%的晚期非小细胞€ba;癌（non-small cell lung cancer, NSCLC）患者，采用单纯免ݚb;lbb;疗还是免ݚb;联合化疗在临床上仍b58;争bae;。本研究旨在bc4;估PD-L1高表be;的晚期NSCLC患者接受单纯免ݚb;lbb;疗与免ݚb;联合化疗的疗效。<b>eb9;法b>本研究回顾性分析了49Ӹb;PD-L1高表be;晚期NSCLC患者的临床资料。PD-L1表be;采用22C3抗体行免ݚb;组化染色，按TPS判bfb;PD-L1表be;水平。bd4;较不同临床特征分组患者的ba2;观缓解率（objective response rate，ORR）和无ࣽb;展生b58;时间（progression free survival, PFS）。<b>结果b>免ݚb;单药与免ݚb;联合化疗组的ORR分Ԣb;为47.1%（8/17）和43.8%（14/32），差异无统ba1;b66;意义（P=0.825）。免ݚb;单药与免ݚb;联合化疗组的中位PFS分Ԣb;为8.0个月和6.8个月，差异无统ba1;b66;意义（P=0.502）。并bf9;本组PD-L1高表be;患者免ݚb;lbb;疗的预۔b;因素ࣽb;行了分析，结果显示，一~bf;免ݚb;lbb;疗ORR（12/19, 63.2%）显著优于二~bf;及以上免ݚb;lbb;疗（10/30, 33.3%），差异有统ba1;b66;意义（P=0.041），二者间PFS无差异。年龄、性Ԣb;、吸烟史、功能rb6;态bc4;分（performance status, PS）、病理߇b;ոb;、€bf;瘤大小、€bf;瘤ۜb;巴结转ޟb;（tumor node metastasis, TNM）分期与ORR和PFS不相关。<b>结bba;b>PD-L1高表be;的晚期NSCLC患者接受免ݚb;单药和免ݚb;联合化疗的疗效相近。PD-L1高表be;患者一~bf;免ݚb;lbb;疗的ORR更佳。bf9;b64;߇b;Nba;群的最佳lbb;疗eb9;案有待于前wbb;性临床研究ࣽb;一b65;探索。     

骨填充网袋椎体成形术与经皮椎体后凸成形术治疗Kümmell病的疗效比较

<b>目的b>bd4;较骨ֆb;充网࢈b;椎体成形术（Vesselplasty）与经皮椎体后凸成形术（percutaneous kyphoplasty，PKP）lbb;疗 Kümmell 病的临床疗效。<b>eb9;法b>2015 年 1 月—2018 年 12 月收lbb; 63 Ӹb; Kümmell 病患者，其中 28 Ӹb;采用 Vesselplasty lbb;疗（Vesselplasty 组），35 Ӹb;采用 PKP lbb;疗（PKP 组）。两组患者性Ԣb;、年龄、病ޠb;、骨bc6;度 T 值、骨折节bb5;及术前ubc;ݝb;视觉模拟bc4;分（VAS）、Oswestry 功能障碍指数（ODI）、伤椎前缘高度、后凸 Cobb 角b49;一般资料bd4;较，差异均无统ba1;b66;意义（P>0.05），具有可bd4;性。bb0;录两组ؤb;术时间、术中透视时间、骨水泥注射量、骨水泥渗漏率、骨水泥弥散面积率和随bbf;期间并发症发生情Qb5;，以及术前、术后 1 d、ٲb;b21;随bbf;时 VAS bc4;分、ODI、伤椎前缘高度、后凸 Cobb 角。 <b>结果b>两组患者均ƒb7;随bbf;，随bbf;时间 12～36 个月，平均 24.2 个月。Vesselplasty 组ؤb;术时间、术中透视时间、骨水泥注射量、骨水泥弥散面积率均明显小于 PKP 组（P<0.05）。Vesselplasty 组骨水泥渗漏率（7.14%）明显低于 PKP 组（34.29%）（χ²=5.153，P=0.023）。两组患者术后 1 d 及ٲb;b21;随bbf;时 VAS bc4;分、ODI、伤椎前缘高度、后凸 Cobb 角均较术前显著改善（P<0.05），术后两组间bd4;较差异均无统ba1;b66;意义（P>0.05）。随bbf;期间两组均未见术椎再塌陷，Vesselplasty 组bb;椎骨折发生率（7.14%）与 PKP 组（14.29%）bd4;较，差异无统ba1;b66;意义（χ²=0.243，P=0.622）。 <b>结bba;b>Vesselplasty 和 PKP lbb;疗 Kümmell 病疗效相似，均能有效缓解患者ubc;ݝb;症rb6;，改善生ۓb;质量，部分恢复伤椎高度，ݾb;b63;椎体后凸。但前者具有ؤb;术时间短、术中透视时间少、骨水泥渗漏少b49;优Rbf;。