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74 [63-83] mm, p=0.001). In addition, the RSB group had significantly lower VAS-R and VAS-C scores, and postoperative opioid requirement, up to 6h after surgery compared to the non-RSB group. Moreover, the VAS-R was significantly lower in the RSB group than in the non-RSB group 24h after surgery.

Preoperative RSB significantly improved analgesia during the early period after RALP. The long-term analgesic efficacy of RSB needs further study.

Preoperative RSB significantly improved analgesia during the early period after RALP. The long-term analgesic efficacy of RSB needs further study.

Several studies have shown that there are no significant differences in anastomotic leakage associated with Transanal total mesorectal excision (taTME) versus laparoscopic TME (lapTME) for rectal cancer; however, little is known about late anastomotic leakage, such as that primarily found in the chronic presacral sinus. We aimed to compare the occurrence of anastomotic leakage and chronic presacral sinus in rectal cancer for taTME and lapTME.

In this retrospective cohort study, data were collected for patients with rectal cancer who underwent surgery between January 2009 and September 2019. Of the 220 patients included in this study, 182 were in the lapTME group and 38 in the taTME group. We compared factors associated with anastomotic leakage and chronic presacral sinus formation between the two groups. A binary-logistic model was used to determine the risk factors for chronic presacral sinus.

Anastomotic leakage occurred in six patients (15.8%) in the taTME group and 36 patients (19.7%) in the lapTME group. Chronic presacral sinus occurred in three patients (7.9%) in the taTME group and 15 patients (8.2%) in the lapTME group. There was no significant difference in anastomotic leakage or chronic presacral sinus between groups (P=0.569 and P=1.000, respectively). Pathologic stage III or higher was significantly associated with chronic presacral sinus formation (P=0.006).

There were no significant differences between taTME and lapTME regarding the incidence of anastomotic leakage or chronic presacral sinus. Almost one-third of anastomotic leakages developed into chronic presacral sinus.

There were no significant differences between taTME and lapTME regarding the incidence of anastomotic leakage or chronic presacral sinus. Almost one-third of anastomotic leakages developed into chronic presacral sinus.

The use of prosthetic meshes in abdominal wall reconstruction is a well-established approach; however, in certain cases where a bowel resection coexists its application is disputed. Any underlying inflammatory process may augment adhesion formation which is a major postoperative complication. In this animal study, our aim was to investigate the effect of N-acetyl-l-cysteine (NAC) on adhesion formation and the expression of inflammatory markers when a mesh was used in a clean or a potentially contaminated environment.

Sixty male Wistar rats were randomly and equally allocated in 3 groups A, B and C. Animals in all groups underwent laparotomy, a prosthetic mesh was placed and chemoprophylaxis with ciprofloxacin was administered. In groups B and C an enterectomy was also performed. NAC was injected intraperitoneally in group C. Adhesion formation, IL-1a, IL-6, TNF-a and histological data including fibrosis, neutrophils' infiltration and neovascularization were assessed. Mesh samples were sent for cultivation.

Adhesion formation was significantly less and inflammation markers were also lower in group C compared to group B (p<0.05). Histological findings were significant for greater fibrosis, neutrophils' infiltration and neovascularization in group B compared to both group A and C. Regarding mesh cultures, more specimens were tested positive in group B (p <0.05). Outcomes between group A and C did not differ.

NAC effectively ameliorated adhesion formation and inflammation in a potentially septic environment where a prosthetic mesh was placed.

NAC effectively ameliorated adhesion formation and inflammation in a potentially septic environment where a prosthetic mesh was placed.

Efficacy of Anthracycline derivative Doxorubicin (Dox) has been proven in several malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphoma, acute leukemia, lung, thyroid and ovarian cancer. However its clinical usefulness is restricted due to its cardiotoxicity and nephrotoxicity. Rosa centifolia belongs to family Rosaceae and in Ayurveda it is claimed for use in renal disorders. The main phyto-constituents of the plant are terpenoids, glycosides, flavonoids, tannins, phenolic compounds, pro-antroocyanides, pectin and riboflavin.

To investigate the ameliorative role of ethanolic extract of petals of R.centifolia in doxorubicin induced nephrotoxicity in rats.

Nephrotoxicity was produced by administration of doxorubicin (2.5mg/kg b.w., i.p. alternate day) in six equal injections for two weeks to achieve a cumulative concentration of 15mg/kg. Low (LERC - 100mg/kg p.o.) and high (HERC - 200mg/kg p.o.) dosees of ethanolic extract of petals of R.centifolia was administered as a pretreatment prior dant property.

The biochemical and histopathological data from the present study clearly support the nephroprotective effect of ethanolic extract of petals of R. centifolia, which might be credited to its anti-oxidant property.

Parts 4 and 5 of the phase 1/2 KEYNOTE-022 study investigated the maximum tolerated dose (MTD), safety,and efficacy of pembrolizumab plus trametinib in solid tumours and BRAF wild-type melanoma.

Patients received intermittent or concurrent dosing of pembrolizumab plus trametinib. Concurrent dosing was 2 or 4 weeks of trametinib run-in followed by concurrent pembrolizumab every 3 weeks (Q3W) plus trametinib once daily (QD). Intermittent dosing was 2 weeks of trametinib run-in followed by pembrolizumab plus intermittent trametinib (1 week off/2 weeks on). A 3+3 dose escalation was used, followed by dose confirmation.

Forty-two patients were enrolled. No dose-limiting toxicities (DLTs) occurred at initial dose levels (DL). At subsequent DLs, 10 of 38 evaluable patients had DLTs. For concurrent dosing, MTD was pembrolizumab 200mg Q3W plus trametinib 1.5mg QD, with a 2-week trametinib 1.5mg QD run-in (concurrent DL2a); in concurrent DL2a group, five (31%) patients had grade 3/4 treatment-related adverse events (TRAEs); the objective response rate (ORR) was 0%. ORR was 40% in concurrent DL1 and 0% in concurrent DL2b. For intermittent dosing, MTD was pembrolizumab 200mg Q3W plus trametinib 2mg QD with a 2-week trametinib 2mg QD run-in (intermittent DL2); in the intermittent DL2 group, seven (47%) patients had grade 3/4 TRAEs; ORR was 27%. ORR in intermittent DL1 was 33%.

MTDs for concurrent and intermittent dosing of pembrolizumab with trametinib were identified. The combination had limited antitumour activity, numerically higher ORR with intermittent versus concurrent dosing, and manageable safety. CLINICALTRIALS.

NCT02130466.

NCT02130466.

GeparOcto demonstrated that pathological complete response (pCR) of intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddEPC) was comparable to weekly paclitaxel/non-pegylated liposomal doxorubicin (plus carboplatin (PM(Cb) in triple-negative breast cancer [TNBC]) in high-risk early breast cancer (BC). Here, we report time-to-event secondary end-points.

Patients were randomised to receive 18 weeks of E (150mg/m

) followed by P (225mg/m

) followed by C (2000mg/m

), each q2w or weekly P (80mg/m

) plus M (20mg/m

) plus, in TNBC, Cb (AUC 1.5). Patients with human epidermal growth factor receptor 2-positive (HER2+)BC received trastuzumab (6[loading dose 8]mg/kg q3w) and pertuzumab (420[840]mg q3w) with P and C cycles.

945 patients started treatment (iddEPC n=470; PM(Cb) n=475). After a median follow-up of 47.0 (range 1.6-61.5) months, 162 (75 in iddEPC; 87 in PM(Cb)) invasive disease-free survival (iDFS) events and 79 (41 in iddEPC; 38 in PM(Cb)) deaths were reported. No significant difference was observed in 4-year iDFS (81.9% iddEPC versus 79.7% PM(Cb), HR=1.16 [95%CI 0.85-1.59], log-rank p=0.334) or 4-year overall survival (OS) (90.3% iddEPC versus 90.6% PM(Cb), HR=0.90 [95%CI 0.58-1.40], log-rank p=0.637) overall and in HER2+ and TNBC subgroups. HR+/HER2- BC patients, however, had significantly better 4-year iDFS (77.9% iddEPC versus 62.5% PM, HR=2.11 [95%CI 1.08-4.10], log-rank p=0.025) and 4-year OS with iddEPC (94.7% iddEPC versus 80.1% PM, HR=3.26 [95%CI 1.06-10.00], log-rank p=0.029).

While there was no difference in survival for the entire cohort, the HR+/HER2-subgroup significantly benefits from iddEPC. This supports the concept of an additional effect of NACT beyond pCR in patients with HR+/HER2- BC. CLINICALTRIALS.

NCT02125344.

NCT02125344.

Osteolytic diseases share symptoms such as bone loss, fracture and pain, which are caused by over-activated osteoclasts. Targeting osteoclast differentiation has emerged as a therapeutic strategy clinically. Dendrobine is an alkaloid isolated from Chinese herb Dendrobium nobile, with knowing effects of analgesia and anti-inflammation. NSC-330507 The roles of dendrobine on osteoclasts and osteolysis remain unclear.

Herein, the possible roles of dendrobine in osteoclastogenesis, inflammatory osteolysis and the underlying mechanism were explored.

Bone marrow-derived macrophages (BMMs) and RAW264.7 cells were employed to evaluate the roles of dendrobine on osteoclastogenesis, bone absorption and the underlying mechanism in vitro. LPS injection was used to cause inflammatory osteolysis in vivo.

Dendrobine repressed osteoclastogenesis, bone resorption induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro. Mechanistically, dendrobine inhibited RANKL-upregulated intracellular (ROS), p-p38, c-Fos expression and nuclear factor of activated T cells (NFATc1) nucleartranslocation. Osteoclastic genes were reduced, and among them matrix metalloproteinase 9 (MMP9) mRNA was dramatically blocked by dendrobine. Moreover, it substantially suppressed MMP9 protein expression during osteoclastogenesis in vitro. Accordingly, oral 20mg/kg/day dendrobine was capableof preventing LPS-induced osteolysis with decreased osteoclasts in vivo.

Taken together, dendrobine suppresses osteoclastogenesis through restraining ROS, p38-c-Fos and NFATc1-MMP9 in vitro, thus attenuates inflammatory osteolysis in vivo. This finding supports the discover of dendrobine as a novel osteoclast inhibitor for impeding bone erosion in the future.

Taken together, dendrobine suppresses osteoclastogenesis through restraining ROS, p38-c-Fos and NFATc1-MMP9 in vitro, thus attenuates inflammatory osteolysis in vivo. This finding supports the discover of dendrobine as a novel osteoclast inhibitor for impeding bone erosion in the future.

This study aimed to evaluate the validity and reliability of the Turkish version of the Pressure Injury Prevention Knowledge Questionnaire (PIPK).

A methodological study design was used. The instrument was translated into Turkish and back-translated into English. After evaluating the language equivalence and content validity of the scale, test-retest reliability, internal consistency and construct validity were examined. The research was conducted with a total of 324 nurses working in a state hospital and two private hospitals who volunteered to participate in the research. Number, percentage distributions, intraclass correlation coefficient (ICC), Kappa coefficient test, Man Whitney U test and Rasch analysis were used to evaluate the data.

Content validity was evaluated by 11 experts in wound care and the CVI(content validity index was found 0.90. The correlation coefficient between the groups was found to be ICC 0.979 in the Kappa coefficient test performed for the reliability analysis. When the in- and out-of-fit difficulty index values of the scale were examined, it was found that the averages of these values varied between "0.

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