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.     

Association between reactogenicity and SARS-CoV-2 antibodies after the second dose of the BNT162b2 COVID-19 vaccine

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of&nbsp;≥38℃ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

<b>Backgroundb>In order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.<b>Methodsb>We retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n&nbsp;=&nbsp;225, January 2018–December 2020).<b>Resultsb>In this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p&nbsp;=&nbsp;0.065); Bethesda IV, Bethesda V, Bethesda VI (P&nbsp;< 0.0001); BRAF^V600E mutation (P&nbsp;< 0.0001); Calcitonin>5&nbsp;pg/ml (p&nbsp;=&nbsp;0.0037); and FNA-Tg>30&nbsp;ng/ml (p&nbsp;=&nbsp;0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.<b>Conclusionb>A simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

免疫检查点抑制剂治疗少见突变非小细胞肺癌疗效的研究进展

驱动基因的发sb0;及针bf9;驱动基因的靶向lbb;疗已显著提高了€ba;癌患者的生b58;质量和时间，但目前bf9;于BRAF、HER2、MET、RETb49;少见驱动基因改变€ba;癌患者的靶向药物的选择仍然较少。近年来免ݚb;检查pb9;抑制剂在€ba;癌lbb;疗中取得了一b9a;的疗效，但因为少见驱动基因突变的€ba;癌患者本࣪b;样本量少，开展大规模临床随机bf9;照bd5;验尚b58;在一b9a;的困–be;，目前b64;߇b;患者接受免ݚb;检查pb9;抑制剂lbb;疗的疗效情Qb5;仍不明确。本文将bf9;目前已掌握的免ݚb;检查pb9;抑制剂lbb;疗BRAF、HER2、MET、RETb49;少见驱动基因改变€ba;癌患者的临床研究结果ࣽb;行综述，以期在一b9a;ޠb;度上为临床工作提ӹb;一өb;依据和参考。     

粪便SEPT-9和miRNA-34b/c基因甲基化检测在大肠肿瘤筛查中的临床应用

目的 评估检测大肠肿瘤患者粪便中SEPT-9和微RNA（miRNA）-34b/c基因甲基化对大肠肿瘤筛查的临床性能。方法 采用病例对照研究方法,使用甲基化敏感性高分辨率熔解曲线法检测大肠肿瘤患者（大肠癌组35例、大肠腺瘤组47例）和正常对照人群（正常对照组52名）粪便中SEPT-9和miRNA-34b/c基因是否存在甲基化,来评估其筛查大肠肿瘤的性能。结果 大肠癌组SEPT-9和miRNA-34b/c基因的甲基化阳性率分别为68.6%、71.4%,大肠腺瘤组分别为57.4%、63.8%,正常对照组分别为9.6%、11.5%。3组的SEPT-9、miRNA-34b/c基因甲基化阳性率比较差异均有统计学意义（²b>SEPT-9b> = 37.185,²b>miRNA-34b/cb> = 40.040,P均< 0.001）,利用Bonferroni法进行两两比较,大肠癌组和大肠腺瘤组的甲基化阳性率比较差异无统计学意义,两者与正常对照组比较差异均有统计学意义（P均< 0.001）。3组联合检测SEPT-9和miRNA-34b/c基因的甲基化阳性率为88.6%、76.6%、13.5%,大肠癌组和大肠腺瘤组联合检测的甲基化阳性率均高于SEPT-9单基因检测和miRNA-34b/c单基因检测（P均< 0.05）。结论 检测粪便中SEPT-9和miRNA-34b/c基因甲基化具有效好的大肠肿瘤筛查性能,或许可作为大规模人群筛查大肠肿瘤新的生物标志物组合;多基因甲基化联合检测筛查的性能优于单基因。     

小分子抗血管生成药物在非小细胞肺癌中的研究进展

€ba;癌是世界上发病率最高的癌症Ӥb;一，且尚无二~bf;ࣽb;展后的标准lbb;疗eb9;案，而€bf;瘤血ba1;生成目前已ࢊb;确b9a;为恶性€bf;瘤的重要lbb;疗靶pb9;，小分b50;多靶pb9;血ba1;激酶抑制剂可通过抑制血ba1;生成相关信号通路，抑制€bf;瘤血ba1;的生成。目前已开展多项小分b50;抗血ba1;生成药物lbb;疗非小细胞€ba;癌的临床bd5;验，且已有部分血ba1;内皮生长因b50;受体酪氨酸激酶抑制剂（vascular endothelial growth factor receptor-tyrosine kinase inhibitors, VEGFR-TKIs）ƒb7;批lbb;疗晚期非小细胞€ba;癌，本文基于国内外多项小分b50;抗血ba1;生成药物lbb;疗非小细胞€ba;癌的发展sb0;rb6;，归~b3;了多个VEGFR-TKIs及成纤维细胞生长因b50;受体（fibroblast growth factor receptor, FGFR）-TKI单药或联合[包括分Ԣb;与化疗、表皮生长因b50;受体（epidermal growth factor receptor, EGFR）-TKIs、免ݚb;lbb;疗、放疗b49;联合）]lbb;疗非小细胞€ba;癌的疗效与b89;全性研究，同时探ba8;了VEGFR-TKIs可能b58;在的耐药机制及疗效预۔b;指标b49;，并bf9;未来抗血ba1;lbb;疗非小细胞€ba;癌的发展ࣘb;Rbf;以及b58;在的潜在问题ࣽb;行展ٱb;，同时为€ba;癌后续的|be;准lbb;疗及个体化lbb;疗提ӹb;eb0;的思路。     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6&nbsp;years). All patients with a relapse-free survival of ≥9&nbsp;months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3&nbsp;months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n&nbsp;=&nbsp;75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n&nbsp;=&nbsp;9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p&nbsp;<&nbsp;0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p&nbsp;=&nbsp;0.026; mean IgG of responders 816&nbsp;mg/dl vs. 475&nbsp;mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p&nbsp;=&nbsp;0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

Oropharyngeal shedding of herpesviruses before and after BNT162b2 mRNA vaccination against COVID-19

<b>Introductionb>Concerns were raised over an increase in Bell's palsy, herpes simplex and herpes zoster after BNT162b2 vaccination, all are manifestations of herpesviruses reactivation. As herpesviruses commonly reactivate in the oropharynx, we have hypothesized that oropharyngeal shedding of herpesviruses will increase after vaccination.<b>Methodsb>Immune-competent Adults, excluding those using topical steroids or manifesting symptomatic herpesvirus infection, were sampled before BNT162b2 vaccination and one week after. Herpesviruses 1–7 shedding was tested with a multiplexed PCR.<b>Resultsb>In 103 paired samples the prevalence of herpesviruses was similar before and after vaccination: HSV1, 3.9% vs. 5.8% (p&nbsp;=&nbsp;0.75); HSV2, 0% vs. 1% (p&nbsp;=&nbsp;not applicable, NA); VZV, 0% vs. 0% (p&nbsp;=&nbsp;NA); EBV, 14.6% vs. 17.5% (p&nbsp;=&nbsp;0.63); CMV, 0% vs. 0% (p&nbsp;=&nbsp;NA); HHV6, 4.9% vs. 7.8% (p&nbsp;=&nbsp;0.55); HHV7, 71.8% vs. 72.8% (p&nbsp;=&nbsp;1); any herpesvirus, 73.8% vs. 74.8% (p&nbsp;=&nbsp;1).<b>Discussionb>We did not find evidence for increased oropharyngeal reactivation of herpesviruses one week after BNT162b2.     

Platelets are important for the development of immune tolerance: Possible involvement of TGF‐β in the mechanism

Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti‐platelet antibody or control antibody during the tolerance induction phase every 3&nbsp;days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24&nbsp;hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti‐platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3⁺ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low‐dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)‐β1. Interestingly, platelet depletion reduced plasma TGF‐β1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF‐β1 during platelet depletion in mice with LZT. Administration of anti‐TGF‐β antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF‐β1.