Background: Although combination therapy with immune checkpoint inhibitors (ICIs) provides a promising efficacy in multiple cancers, their use is facing challenges for a high incidence of adverse effects. This meta-analysis was conducted to compare the risks of organ-specific immune-related adverse events (IRAEs) associated with ICI monotherapy versus combination therapy among cancer patients.Methods: Electronic databases were systematically searched to include eligible randomized controlled trials (RCTs). Any-grade and 3-5 grade IRAEs (colitis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism, and hypophysitis) were extracted for meta-analysis. Two reviewers independently assessed the methodological quality. The RevMan 5.3.5 software was used for meta-analysis.Results: A total of 10 studies involving 8 RCTs with 2716 patients were included in this study. The most common any-grade adverse event was colitis (14.5%), followed by hypothyroidism (13.8%), hepatitis (10.4%), hypophysitis (10.0%), hyperthyroidism (9.3%), and pneumonitis (4.6%). Meta-analysis showed that ICI combination therapy significantly increased the risks of any-grade IRAEs in colitis [relative risk (RR), 3.56; 95% confidence interval (CI), 1.56-8.12; p < 0.05], pneumonitis (RR, 2.31; 95% CI, 1.54-3.45; p < 0.05), hepatitis (RR, 2.54; 95% CI, 1.65-3.91; p < 0.05), hypothyroidism (RR, 2.17; 95% CI, 1.71-2.76; p < 0.05), hyperthyroidism (RR, 3.13; 95% CI, 2.08-4.70; p < 0.05), and hypophysitis (RR, 3.54; 95% CI, 2.07-6.07; p < 0.05) compared with ICI monotherapy, as well as 3-5 grade IRAEs in colitis (RR, 2.50; 95% CI, 1.62-3.86; p < 0.05), pneumonitis (RR, 1.99; 95% CI, 1.00-3.93; p = 0.05), and hepatitis (RR, 2.70; 95% CI, 1.29-5.63; p < 0.05). Conclusions:This meta-analysis demonstrated that, compared with ICI monotherapy, patients receiving ICI combination therapy significantly increased organ-specific IRAEs in colitis, hypothyroidism, hepatitis, hypophysitis, hyperthyroidism, and pneumonitis. The incidence and severity of organ-specific IRAEs were drug and dose independent.

Background To minimize the killer turn caused by the sharp margin of the tibial tunnel exit in transtibial PCL reconstruction, surgeons tend to maximize the angle of the tibial tunnel in relation to the tibial plateau. However, to date, no consensus has been reached regarding the maximum angle for the PCL tibial tunnel. Questions/purposes In this study we sought (1) to determine the maximum tibial tunnel angle for the anteromedial and anterolateral approaches in transtibial PCL reconstruction; (2) to compare the differences in the maximum angle based on three measurement methods: virtual radiographs, CT images, and three-dimensional (3D) knee models; and (3) to conduct a correlation analysis to determine whether patient anthropomorphic factors (age, sex, height, and BMI) are associated with the maximum tibial tunnel angle. Methods Between January 2018 and December 2020, 625 patients who underwent CT scanning for knee injuries were retrospectively reviewed in our institution. Inclusion criteria were patients 18 to 60 years of age with a Kellgren-Lawrence grade of knee osteoarthritis less than 1 and CT images that clearly showed the PCL tibial attachment.

Epithelial-mesenchymal transition (EMT) is the process by which epithelial cells depolarize and acquire a mesenchymal phenotype, and is a common early step in the process of metastasis. Patients with lung cancer frequently already have distant metastases when they are diagnosed, highlighting the requirement for early and effective interventions to control metastatic disease. Transforming growth factor-β1 (TGF-β1) is able to induce EMT, however the molecular mechanism of this remains unclear. In the current study, TGF-β1 was reported to induce EMT and promote the migration of non-small cell lung cancer (NSCLC) cells. A notable observation was that EMT induction was accompanied by the upregulation of human glioma-associated oncogene homolog 1 (Gli1) mRNA and protein levels. Furthermore, Gli1 levels were depleted by small interfering RNA, and the Gli1 inhibitor GANT 61 attenuated the TGF-β1-mediated induction of EMT and cell migration. The results of the current study suggest that Gli1 regulates TGF-β1-induced EMT, which may provide a novel therapeutic target to inhibit metastasis in patients with NSCLC.

Objective To determine the permissive safe angle (PSA) of the tibial tunnel in transtibial posterior cruciate ligament (PCL) reconstruction based on a three‐dimensional (3D) simulation study. Methods This was a computer simulation study of transtibial PCL reconstruction using 3D knee models. CT images of 90 normal knee joints from 2017 to 2020 were collected in this study, and 3D knee models were established based on CT data. The tunnel approaches were subdivided into the anterior 1/3 of the anteromedial tibia (T1), middle 1/2 of the anteromedial tibia (T2), the tibial crest (T3), anterior 1/3 of the anterolateral tibia (T4), middle 1/2 of the anterolateral tibia (T5). Five tibial tunnels (T1–T5) were simulated on the 3D knee models. The PSAs, in different tibial tunnel approaches were measured, and subgroup analyses of sex, age and height were also carried out. Results The mean PSAs of the tibial tunnels with 5 different approaches (T1–T5) were 58.49° ± 6.82°, 61.14° ± 6.69°, 56.12° ± 7.53°, 52.01° ± 8.89° and 49.90° ± 10.53°, respectively. The differences of the mean PSAs between the anteromedial and anterolateral approaches were significant (P < 0.05). However, there was no significant difference of the mean PSA value between the two anteromedial tibial tunnel approaches (T1–T2) (P > 0.05), as well as between the two anterolateral tibial tunnel approaches (T4–T5). The patient's anthropomorphic characteristics of sex, age, and height were not associated with the PSAs. Conclusions The PSA varied with the anteromedial, tibial crest and anterolateral approaches for transtibial PCL reconstruction, and surgeons should limit the PCL drill guide by referring to the specific PSA for different surgical approaches.

Background Interference screw is commonly used for graft fixation in anterior cruciate ligament (ACL) reconstruction. However, previous studies had reported that the insertion of interference screws significantly caused graft laceration. The purposes of this study were to (1) quantitatively evaluate the graft laceration from one single insertion of PEEK interference screws; and (2) determine whether different types of sutures reduced the graft laceration after one single insertion of interference screws in ACL reconstruction. Methods The in-vitro ACL reconstruction model was created using porcine tibias and bovine extensor digitorum tendons of bovine hind limbs. The ends of grafts were sutured using three different sutures, including the bioabsorbable, Ethibond and ultra-high molecular weight polyethylene (UHMWPE) sutures. Poly-ether-ether-ketone (PEEK) interference screws were used for tibial fixation. This study was divided into five groups (n = 10 in each group): the non-fixed group, the non-sutured group, the absorbable suture group, the Ethibond suture group and the UHMWPE suture group. Biomechanical tests were performed using the mode of pull-to-failure loading tests at 10 mm/min. Tensile stiffness (newtons per millimeter), energy absorbed to failure (in joules) and ultimate load (newtons) were recorded for analysis. Results All prepared tendons and bone specimens showed similar characteristics (length, weight, and pre-tension of the tendons, tibial bone mineral density) among all groups (P > 0.05). The biomechanical tests demonstrated that PEEK interference screws significantly caused the graft laceration (P < 0.05). However, all sutures (the bioabsorbable, Ethibond and UHMWPE sutures) did not reduce the graft laceration in ACL reconstruction (P > 0.05). Conclusions Our biomechanical study suggested that the ultimate failure load of grafts was reduced of approximately 25 % after one single insertion of a PEEK interference screw in ACL reconstruction. Suturing the ends of the grafts using different sutures (absorbable, Ethibond and UHMWPE sutures) did not decrease the graft laceration caused by interference screws.

Objective During the transtibial posterior cruciate ligament (PCL) reconstruction, surgeons commonly pay more attention to the graft turning angle in the sagittal plane (GASP), but the graft turning angle in the coronal plane (GACP) is always neglected. This study hypothesized that the three‐dimensional (3D) killer turn angle was determined by both the GASP and GACP, and aimed to quantitively analyze the effects of the GASP and GACP on the 3D killer turn angle. Methods This was an in‐vitro computer simulation study of transtibial PCL reconstruction using 3D knee models. Patients with knee injuries who were CT scanned were selected from the CT database (April 2019 to January 2021) at a local hospital for reviewing. A total of 60 3D knees were simulated based on the knees' CT data. The femoral and tibial PCL attachment were located on the 3D knee model using the Rhinoceros software. The tibial tunnels were simulated based on different GASP and GACP. The effects of the GASP and GACP on the 3D killer turn angle were quantitatively analyzed. One‐way analysis of variance was used to compare the outcomes in different groups. The regression analysis was performed to identify variables of the GASP and GACP which significantly affected 3D killer turn angle. Results The 3D killer turn angle showed a significant proportional relationship not only with the GASP (r2 > 0.868, P < 0.001), but also with the GACP (r2 > 0.467, P < 0.001). Every 10° change of the GACP caused 2.8° to 4.4° change of the 3D killer turn angle, whereas every 10° change of the GASP caused 6.4° to 9.2° change of the 3D killer turn angle. Conclusions The 3D killer turn angle was significantly affected by both the GASP and GACP. During the transtibial PCL reconstruction, the proximal anterolateral tibial tunnel approach could increase the 3D killer turn angle more obviously compared with the most distal anteromedial tibial tunnel approach. To minimize the killer turn effect, both the GASP and GACP were required to be considered to increase.

Germ cell tumor is the most common malignant tumor of the gonads, sometimes they are found in locations other than the gonads, called Extra-gonadal Germ cell tumours (EGCTs). Primary mediastinal germ cell tumors (PMGCTs) are a kind of rare neoplasm in the anterior mediastinum, including seminoma and non-seminomatous, or appear as a mixture. Primary mediastinal seminoma mixed with sarcoma is an extremely rare clinicopathologic entity. Previous studies have revealed that primary pure mediastinal seminomas are commonly sensitive to chemoradiotherapy and possibly to palliative excision. The treatment options for mixed germ cell tumor composed of seminoma and sarcoma remain unknown. Only one case of primary mediastinal seminoma with rhabdosarcoma has been reported in the literature up to date and the patient benefited from chemotherapy as the neoadjuvant therapy. However, cases of primary mediastinal seminoma with leiomyosarcoma have not been documented. Herein, we report a case of an 18-year-old patient, who presented with dyspnea, orthopnea, and chest pain, the CECT scan of the chest showed a large mass in the anterior mediastinum, which turned out to be seminoma mixed with leiomyosarcoma after partial excision. We investigate the treatment strategy and potential molecular mechanism of this disease. Finally, our study demonstrated that the patient benefited from the treatment of chemotherapy alone, or combined with target therapy after the operation. Meanwhile, the BRAF p.G466V, TP53 mutations, MTOR p.T1977I and exons 2-5 deletion of FLCN may be potential molecular mechanisms and oncogenic drivers of this disease.

No consensus has been reached on the optimal position of PCL tibial tunnel. The purpose of this study was to compare the biomechanical properties of proximal, distal and anatomic tibial tunnel in transtibial posterior cruciate ligament reconstruction. An in-vitro model of transtibial posterior cruciate ligament reconstruction was simulated using porcine tibias and bovine extensor tendons. Two models of biomechanical testing, load-to-failure loading, and cyclic loading, were performed in this study. The load-to-failure loading found that distal tibial tunnel resulted in greater ultimate load and yield load than the anatomic and proximal tunnel group ( p < 0.05), whereas there were no significant differences in mean tensile stiffness among three groups ( p > 0.05). The cyclic loading found no differences in the graft displacement at 250, 500, and 1000 cycles among three groups ( p > 0.05). It was found that distal tibial tunnel showed superior ultimate load and yield load in load-to-failure loading testing compared with proximal and anatomic tibial tunnels, whereas no significant difference was found in terms of the mean displacement of the survived grafts in cyclic loading testing among three groups.