Jokumsenseverinsen2845
Polatuzumab vedotin (Pola) is an antibody-drug conjugate that targets the B-cell antigen CD79b and delivers monomethyl auristatin E (MMAE). It is approved in combination with bendamustine and rituximab (Rit) for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Understanding the molecular basis of Pola combination therapy with Rit, the key component for the treatment of DLBCL, is important to establish the effective treatment strategies against r/r DLBCL. Here, we examined the rationale for the combination of Pola with Rit using Pola-refractory cells. We found that treatment with Pola increased CD20 expression and sensitivity to Rit-induced complement-dependent cytotoxicity (CDC) in several Pola-refractory cells. Pola treatment increased phosphorylation of AKT and ERK and both AKT- and MEK-specific inhibitors attenuated the Pola-induced increase of CD20 and CDC sensitivity, suggesting that these phosphorylation events were required for this combination efficacy. It was revealed that anti-CD79b antibody increased the phosphorylation of AKT but inhibited the phosphorylation of ERK. In contrast, MMAE potentiated phosphorylation of ERK but slightly attenuated the phosphorylation of AKT. Pola also increased CD20 expression on Pola-refractory xenografted tumours and significantly enhanced antitumour activity in combination with Rit. In conclusion, these results could provide a novel rationale for the combination of Pola plus Rit.
To examine racial disparities in severe maternal morbidity in patients with hypertensive disorder of pregnancy (HDP).
Secondary analysis of an observational study of 115,502 patients who had a live birth at ≥ 20 weeks in 25 hospitals in the US, 2008-2011. Only patients with HDP were included in this analysis. Race and ethnicity were categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB) and Hispanic. Associations were estimated between race and ethnicity and the primary outcome of severe maternal morbidity, defined as any of the following blood transfusion ≥4 units, unexpected surgical procedure, need for a ventilator ≥ 12 hours, intensive care unit (ICU) admission, or failure of ≥ 1 organ system, were estimated by unadjusted logistic and multivariable backward logistic regressions. Multivariable models were run classifying HDP into 3 levels 1) gestational hypertension; 2) preeclampsia (mild, severe or superimposed); and 3) eclampsia or HELLP.
A total of 9,612 individuals with HDP were includigher frequencies of blood transfusions and ICU admissions. However, once severity and other confounding factors were taken into account, the differences did not persist.
This study investigated the treatment pattern and the rate of bleeding complications in real-world practice in cancer-associated venous thromboembolism (CT) patients.
We used the Korean Health Insurance Review and Assessment Service database (2014-2018). Among patients with venous thromboembolism, patients with concomitant malignancy diagnostic codes were categorized as CT, while all others were categorized as non-CT. Treatments were categorized as direct oral anticoagulant (DOAC), parenteral anticoagulant (PAC), warfarin, and mixed anticoagulants.
We identified 27,205 CT and 57,711 non-CT patients. DOACs were the most frequently used anticoagulants. The proportion of patients treated with PAC was higher in CT than in non-CT patients (35.7 vs. 19.5%;
< 0.01). In CT, the cumulative incidence of any/major bleeding was higher with DOAC (8.1%/3.9%) than with PAC (7.5%/3.2%;
= 0.04 and 0.01, respectively). However, there was no difference in major bleeding when compared with warfarin (
= 0.11) or mixed anticoagulants (
= 0.94). Overall, gastrointestinal (GI) cancer patients showed higher risks of bleeding. The cumulative incidence of major GI bleeding was higher with DOAC than with PAC (4.9 vs. 3.0%;
< 0.01), while there was no difference compared with warfarin (
= 0.59) or mixed anticoagulants (
= 0.80). Major bleeding with each DOAC showed no difference among entire CT (
= 0.94), GI cancer (
= 0.27), and genitourinary cancer (
= 0.88) patients.
Five years after their introduction into clinical practice, DOACs have become the most prescribed anticoagulant in Korea. In our patient population, bleeding complications occurred more frequently in CT than in non-CT, especially in patients treated with DOACs.
Five years after their introduction into clinical practice, DOACs have become the most prescribed anticoagulant in Korea. In our patient population, bleeding complications occurred more frequently in CT than in non-CT, especially in patients treated with DOACs.
The aim of this study was to describe a simple and effective method to control severe haemorrhage from intraoperative trauma to the cranial tibial artery (CTA) during tibial plateau levelling osteotomy (TPLO) and to report long-term outcomes.
Cadaveric descriptive study and retrospective case series. A TPLO was performed in eight cadaveric limbs, followed by intentional laceration of the CTA under fluoroscopic guidance. Dissection of the limb was performed and the relationship between the CTA and the surrounding structures was evaluated. A computed tomography angiogram was performed following TPLO in one cadaveric limb. Medical records from cases that had intraoperative arterial bleeding between 2015 and 2019 were reviewed. Cases were included if bleeding was controlled by following the usual steps for TPLO. Radiographic follow-up 6 to 10 weeks postoperatively and long-term follow-up owner's questionnaire were available.
During TPLO, the CTA is tightly compressed between the caudal aspect of the proximal tibia and the popliteal musculature. Rotation and compression of the proximal tibia followed by closure of the pes anserinus successfully controlled arterial bleeding during TPLO in nine clinical cases without the need for direct ligation.
Continuing the usual steps of a TPLO can successfully control intraoperative bleeding from the CTA with no long-term complications. This technique should be considered in cases of arterial bleeding during TPLO before direct ligation.
Continuing the usual steps of a TPLO can successfully control intraoperative bleeding from the CTA with no long-term complications. This technique should be considered in cases of arterial bleeding during TPLO before direct ligation.Various age-related chronic diseases have been linked to oxidative stress. The cellular antioxidant response pathway is regulated by the transcription factor nuclear erythroid factor 2. Therefore, plant-derived nuclear erythroid factor 2 activators might be useful therapeutics to stimulate the body's defense mechanisms. Our study focused on the discovery of potent nuclear erythroid factor 2 activators from medicinal plants. Initially, a variety of medicinal plant extracts were screened for nuclear erythroid factor 2 activity using a nuclear erythroid factor 2 luciferase reporter cell line. Among these, Valerian (Valeriana officinalis) root was identified as a potent candidate. Sequential extraction and bioassay-guided fractionation led to the isolation of four nuclear erythroid factor 2-active compounds, which were structurally identified by NMR and LC/HRMS as the known compounds isovaltrate, valtrate, jatamanvaltrate-P, and valerenic acid. find more These four compounds were then tested in relevant biological assays. nt application as a sleep aid.Colorectal cancer is one of the leading causes of death in the Western world. Half of the patients develop colorectal liver metastases (CRLM), while only less than 30% of the patients have surgically resectable metastasis at the time of diagnosis. In case of resectability, classical anatomical (major) hepatectomy offers a high R0 resection rate, but with simultaneously increased perioperative morbidity and mortality. Over the past two decades, the potential benefits of parenchyma-sparing hepatectomy (PSH) for overall oncological outcomes, survival, and re-resection in case of recurrence ("salvageability") have been demonstrated. This article summarizes the current evidence on PSH as a surgical treatment option, and discusses the current "state of the art" in different therapy scenarios.
Anastomotic insufficiency after oesophagectomy contributes significantly to morbidity and mortality of affected patients. A safe surgical technique can reduce the incidence of such anastomotic insufficiencies.
In the treatment of oesophageal cancer, the German guideline recommends minimally invasive or hybrid surgical procedures. In most cases, Ivor-Lewis oesophagectomy and continuity reconstruction using a gastric sleeve are performed. Circular stapler anastomosis seems to be superior.
The preparation of the anastomosis starts intra-abdominally with mobilisation of the stomach and sparing of the gastroepiploic vessels. After the subsequent intrathoracic mobilisation of the oesophagus, the actual anastomosis construction can take place. Here, the oesophagus is either transected with a stapler closure or openly with scissors. This is followed by a purse-string suture on the open oesophageal stump. Alternatively, partial oesophageal opening with prior purse-string suture may later facilitate insertion of Nevertheless, variations are still possible within this procedure. However, there is no scientific evidence on the advantage for any method in a direct comparison.
In robot-assisted oesophagectomy, the reconstruction of continuity with a circular stapler anastomosis is quite possible and seems comparatively easier to learn. Nevertheless, variations are still possible within this procedure. However, there is no scientific evidence on the advantage for any method in a direct comparison.
Numerous studies from Asian countries, including large collectives, have reported excellent results after laparoscopic resection of choledochal malformation (CM). However, the role of laparoscopic CM resection is still controversial outside Asia. We aimed to analyze the outcome of laparoscopic CM resection in our institution and to compare our outcome with the data reported in the literature.
All patients who underwent laparoscopic CM resection in our pediatric surgical department from 2002 to 2019 were retrospectively analyzed for surgical details and postoperative complications, which were graded according to the Clavien-Dindo classification. A systematic literature search identified all reports on over 10 cases of laparoscopic pediatric CM resection and surgical details, follow-up, and complication rates were extracted.
Fifty-seven patients (72% female) with a mean age of 3.6 + 4.1 years underwent laparoscopic CM resection in our department. Conversion rate was 30%. Total complication rate was 28%fely performed. The learning curve in combination with the low incidence calls for a centralization of patients who undergo laparoscopic CM resection. There seems to be a discrepancy on complications rates reported from Asian and non-Asian countries following laparoscopic CM resection.Chelating agents are an integral part of transition metal complex chemistry with broad biological and industrial relevance. The hexadentate chelating agent ethylenediaminetetraacetic acid (EDTA) has the capability to bind to metal ions at its two nitrogen and four of its carboxylate oxygen sites. We use resonant inelastic X-ray scattering at the 1s absorption edge of the aforementioned elements in EDTA and the iron(III)-EDTA complex to investigate the impact of the metal-ligand bond formation on the electronic structure of EDTA. Frontier orbital distortions, occupation changes, and energy shifts through metal-ligand bond formation are probed through distinct spectroscopic signatures.
