[Application of three dimensional printed personalized guide plate assisted arthroscopic ankle arthrodesis in the treatment of ankle arthritis].

Objective: To compare the efficacy of conventional open ankle fusion and three dimensional(3D) printed guide plate assisted arthroscopic ankle fusion. Methods: A retrospective cohort study was performed on 256 patients with advanced traumatic ankle arthritis, who were admitted to the Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2018 to February 2023 and underwent ankle fusion procedures. The study cohort comprised 119 males and 137 females, with an age of (59.6±9.5) years (range: 37 to 83 years). Among them, 175 cases underwent internal fixation with plates and screws (58 cases through the combined medial and lateral approach, and 117 cases through the simple lateral approach), 48 cases underwent internal fixation with screws through the anterior approach (conventional open group), and 33 cases underwent minimally invasive arthroscopic ankle fusion assisted by 3D printed guide plate (3D printed guide plate arthroscopy group). Propensity score matching was employed to achieve a 1∶1 match(caliper value=0.02) between the baseline characteristics of patients in the 3D printed guide plate arthroscopy group and the conventional open group. Perioperative and follow-up data between the two groups were compared using the t-test, Mann-Whitney U test, Wilcoxon signed rank test, χ² test or corrected χ² test as appropriate. Results: Matching was successfully achieved with 20 cases in both the 3D printed guide plate arthroscopy group and the conventional open group, and there were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The operation time in the 3D printed guide plate arthroscopy group was significantly longer than that in the conventional open group ((88.9±5.6) minutes vs. (77.9±11.7) minutes;t=-2.392, P=0.022), while the frequency of intraoperative fluoroscopies ((1.7±0.8) times vs. (5.2±1.2) times; t=10.604, P<0.01) and length of hospitalization ((5.5±0.9) days vs. (6.4±1.5) days;t=2.480, P=0.018) were significantly lower in the 3D printed guide plate arthroscopy group compared to the conventional open group. The fusion rate was 95.0% (19/20) in the 3D printed guide plate arthroscopy group and 85.0% (17/20) in the conventional open group, with no statistically significant difference between the two groups (χ²=0.278,P=0.598). The fusion time was (12.1±2.0) weeks in the conventional open group and (11.1±1.7) weeks in the 3D printed guide plate arthroscopy group, with no statistically significant difference between the two groups (t=1.607, P=0.116). At the final follow-up, the American Orthopedic Foot and Ankle Society ankle hindfoot scale was (72.6±5.5)points in the 3D printed guide plate arthroscopy group and (70.5±5.8)points in the conventional open group, with no statistically significant difference between the two groups (t=-1.003, P=0.322). The pain visual analogue score of the 3D printed guide plate arthroscopy group was (M(IQR)) 1.50 (1.00) points, lower than that of the conventional open group by 3.00 (1.00) points, with statistically significant differences (Z=-3.937, P<0.01). There was no significant difference in complication rate between the conventional open group and the 3D printed guide plate arthroscopy group (25.0%(5/20) vs. 5.0%(1/20), χ²=1.765，P=0.184). Conclusion: 3D printed guide plate assisted arthroscopic ankle fusion exhibited several advantages, including reduced frequency of fluoroscopies, alleviation of postoperative pain, and decreased complications and length of hospitalization.

[Clinical study on the classification of renal artery involvement and comparison of renal function and prognosis of Stanford type B aortic dissection after thoracic aortic endovascular repair].

Objective: To investigate the different types of renal artery involvement in Stanford type B aortic dissection (TBAD) and the comparison of clinical effecacy after thoracic endovascular aortic repair (TEVAR). Methods: This is a retrospective cohort study included 330 patients with TBAD and renal artery involvement treated with TEVAR from June 2002 to September 2021 in General Hospital of Northern Theater Command of the PLA. According to aortic CTA image, unilateral renal artery involvement conditions were divided into 5 types: the true lumen type (renal artery opening completely from the true lumen), false lumen type (renal artery opening completely from the false lumen), double lumen type (renal artery opening from the true and false double lumen), compression type (renal artery opening connected with the true lumen, but the renal artery opening was extremely squeezed by the inner membrane), open type (renal artery opening with intimal tear). There were seven types of bilateral renal artery involvement: true-true type (true lumen-true lumen type), true and false type (true lumen-false lumen type), true-double type (true lumen-double lumen type), true-opening type (true lumen-opening type), false-false type (false lumen-false lumen type), false-compression type (false lumen-compression type), double-double type (double lumen-double lumen type). The primary observation index of this study was the comparison of postoperative renal function and the incidence of clinical adverse events of different types of renal artery involvement. One-way ANOVA test, Kruskal-Wallis H test and paired sample rank sum test were used to compare postoperative renal function between different types of bilateral renal artery involvement. The Chi-square test or Fisher's exact probability test were used to compare the near and long term adverse events between different types of bilateral renal artery involvement. Kaplan-Meier method was used to compare the all-cause mortality of patients with severe renal functional injury and non-severe renal functional injury before surgery. Results: The average age of the patients included in this study was (53±11) years, including 276 males (83.6%) and 54 females (16.4%). There were statistical difference in the level of serum creatinine (preoperative:H=18.686, P=0.005, postoperative:H=18.101, P=0.006) and cystatin C (preoperative:H=17.566, P=0.007, postoperative:H=10.433, P=0.016), pre-and post-operative, between the seven groups of TBAD patients with different renal artery involvement types (P<0.05), and the false-false type group shown the worst kidney function. However, no statistically significant differences were shown when comparing their pre- and post-operative change values (P>0.05). The 30-day follow-up result showed that there were statistically significant differences in the incidence of postoperative acute kidney injury (χ2=15.623, P=0.007), aorta-related adverse events (χ2=15.523, P=0.010), and intraoperative endoleak (χ2=17.935, P=0.004) among the seven groups, and the false-false group was the highest (2/9, 5/9 and 5/9, respectively). In terms of long-term follow-up results, there were statistically significant differences in all-cause death (χ2=14.772, P=0.011) and non-aortic death (χ2=15.589,P=0.008) among the seven groups. Kaplan-Meier survival analysis showed that patients with worse pre-operative renal function showed higher long-term all cause death (17.7% vs. 4.8%, P=0.009). Conclusions: For TBAD patients with renal artery involvement, there were differences in renal function among different types, and TEVAR showed no significant effect on renal function in TBAD patients. The long-term all cause death was higher in patients with worse renal function pre-operative.

Relationship between Coffee Consumption and Osteoporosis Risk Determined by the ESR1 Polymorphism rs2982573.

BACKGROUND: The development of osteoporosis is partly explained by interactions between genetic and lifestyle or environmental factors. OBJECTIVES: In the current study, we determined the relationship between coffee consumption and the risk of osteoporosis among individuals with ESR1 rs2982573 in Taiwan. DESIGN, PARTICIPANTS AND SETTING: In this population-based cross-sectional study, we used genetic, demographic, and lifestyle data from participants recruited in Taiwan Biobank (TWB) between 2016 and 2019. We used multiple logistic regression analyses to determine the relationship between osteoporosis and variant rs2982573 genotypes (TT, TC, and CC). MAIN OUTCOME: The primary outcome was osteoporosis. RESULTS: Individuals with osteoporosis (n = 515) were older than those without the disease (mean age ±SE (year); 61.324±0.361 versus 53.068 ±0.130, p<0.001). There was no significant association between rs2982573 and osteoporosis (OR, 0.904; 95% CI, 0.706-1.157; p=0.422 for TC+CC when compared with the TT genotype). Coffee consumption was associated with a lower risk of osteoporosis (OR, 0.737; 95% CI, 0.592-0.918; p=0.006). The p-value for interaction between rs2982573 and coffee consumption was 0.0393. In our subgroup analyses, the adjusted ORs (95% CI) were 0.635 (0.410-0.985) in coffee drinking TC+CC individuals and 1.095 (0.809-1.482) in non-coffee drinking TC+CC individuals, respectively when compared with their TT genotype counterparts. CONCLUSION: According to our study, participants in the TWB with the TC+CC genotype of ESR1 rs2982573 who consumed at least three cups of coffee per week were less likely to have osteoporosis.

[Clinical effect of endoscopic transnasal sphenoidal approach with simple muscle packing for intrasellar arachnoid cyst].

Objective: To examine the clinical effect of simple muscle packing through transnasal sphenoid approach in the treatment of intrasellar arachnoid cyst. Methods: The clinical data of 11 patients with intrasellar arachnoid cyst treated by transnasal sphenoidal approach with simple muscle packing at the Neurosurgery Department of the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020 were retrospectively analyzed. There were 5 males and 6 females, with a median age of 48 years (range: 23 to 75 years). The clinical manifestations included headache in 6 cases, dizziness in 4 cases, hypo-libido in 1 case, disturbance of consciousness in 1 case, visual impairment in 7 cases and mixed pituitary dysfunction in 5 cases. The enlargement of the sellar fossa was seen in the preoperative MRI images. The enhanced MRI images showed that the cyst wall of the intrasellar arachnoid cyst was not enhanced, and the compression and thinning of the sellar base was seen in the CT images. In 9 cases, the cyst extended suprasellar and the sellar septum was "arched". In 7 cases, the cyst compressed the optic chiasm upward. The cyst walls of all patients were incised through the nasal sphenoid approach under the endoscope, and the muscle was packed after sufficient drainage. The postoperative symptoms, pituitary endocrine function and recurrence of patients were followed up. Results: MRI images of the sellar region in all patients showed significant reduction or disappearance of cysts. Intracranial infection occurred in 1 case and electrolyte disorder in 2 cases, which were relieved after symptomatic treatment. No cerebrospinal fluid rhinorrhea occurred. Postoperative clinical symptoms were completely relieved in 6 cases and partially relieved in 5 cases. Pituitary endocrine function recovered completely in 2 cases and improved significantly in 4 cases. All patients were followed up for 10 to 40 months. One patient found to have a partial recurrence of the cyst 3 months after surgery. Because there were no new symptoms appeared, the follow-up was continued without second operation. Conclusion: Transnasal sphenoidal approach is a feasible method for the treatment of intrasellar arachnoid cyst.

[Efficacy analysis of retroperitoneal laparoscopic selective renal artery branch occlusion and nephron sparing surgery for ≥ T1b stage renal carcinoma].

Objective: To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b. Methods: From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery. Results: Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m2. The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),both P<0.05]. Conclusion: Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

[Open hepatectomy versus laparoscopic in the treatment of primary left-sided hepatolithiasis: a propensity, long-term follow-up analysis at a single center].

To compare short-term and long-term efficacy after laparoscopic left hepatectomy(LLR) to open left hepatectomy(OLH) for primary left-sided hepatolithiasis. Methods: Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ(2) test or Fisher test. Results: No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ(2)=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ(2)=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ(2)=4.029, P=0.045). OLH (95% CI: 1.55 to 10.75, P=0.004) and postoperative complications (95% CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95% CI: 1.428 to 44.080, P=0.018) and residual stones (95% CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95% CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion: Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

[Paraganglioma of urinary bladder: a clinicopathological features analysis of 23 cases].

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis and immunohistochemical (IHC) characteristics of paraganglioma of urinary bladder (PUB). Methods: The clinical and pathological data of 23 cases of PUB were collected at the Second Affiliated Hospital of Fujian Medical University (7 cases); Fujian Provincial Hospital (8 cases); Fujian Medical University Union Hospital (6 cases); and First Affiliated Hospital of Fujian Medical University (2 cases) from May 2010 to November 2018. IHC staining for CK, GATA3, CD56, Syn, CgA, S-100 protein, HMB45, SDHB, OCT3/4 and Ki-67 was done using EliVision method; and the relevant literature was reviewed. Results: There were 14 women and 9 men, aged ranged from 21 to 73 years (median 51 years). Clinically, patients presented with headache, vertigo, palpitation, hypertensive crisis during micturition, hypertension, blurred vision, gross hematuria and paroxysmal pallor. The tumor sizes ranged from 0.9 to 6 cm (mean2.5 cm). Macroscopically, most tumors were exophytic and well delineated within the lamina propria or muscularis propria. The tumors were firm and nodular and showed grayish-tan cut surface. Histologically,the tumor growth pattern was expansive or showed interpenetrating infiltrative growth within the lamina propria or muscularis propria; the tumor cells were typically arranged in distinctive nests (Zellballen) with organoid arrangement; pseudo-rosette were seen in some cases. The cells were rounded or polygonal and had rich, acidophilic or amphophilic cytoplasm and may contain pigmented granules and vacuoles; the nuclei were central or eccentric, with small nucleoli, although occasionally some nuclei were pleomorphic and hyperchromatic. Spindled sustentacular cells could be seen around the nests of tumor cells in some cases. There were abundant vessels that were fissure-like, hemangioma-like or dilated. By IHC, the tumor cells were positive for GATA3 (2/23), OCT3/4 (2/23), CD56 (22/23), Syn (23/23), CgA (22/23), S-100 (sustentacular cell, 23/23) and SDHB (23/23); and negative for CK and HMB45; Ki-67 index was 1%-5%. At follow-up, there was no recurrence or metastasis in 18 cases. Conclusions: The diagnosis of PUB relies on the morphologic and IHC features; but there may be histomorphologic heterogeneity. The most important differential diagnosis is invasive urothelial carcinoma. The tumor cells may show aberrant cytoplasmic expression of OCT3/4; there is no clear correlation between SDHB and OCT3/4 expression in the group.

Meta-analysis of prophylactic cranial irradiation or not in treatment of extensive-stage small-cell lung cancer: The dilemma remains.

PURPOSE: The role of prophylactic cranial irradiation (PCI) in treatment of extensive-stage small-cell lung cancer (SCLC) is controversial. The aim of this study was to systematically evaluate the efficacy and safety of using PCI in the treatment of extensive-stage SCLC. In the present study, we examined whether PCI was essential for the optimal treatment of extensive-disease small-cell lung cancer. MATERIAL AND METHODS: We searched the PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify articles that assessed the efficacy of PCI in treating extensive-stage small-cell lung cancer patients. RESULTS: We identified 8 studies that involved a total of 982 patients who received PCI (PCI group) and a total of 4509 patients who did not receive PCI (control group). The results showed that PCI significantly improved the 1-year overall survival rate (HR=1.50; 95% CI: 1.23-1.82; I2=67%; P<0.0001) and reduced the incidence of brain metastasis (HR=0.46; 95% CI: 0.37-0.58; I2=6%; P<0.00001). CONCLUSION: PCI improves the 1-year overall survival rate and reduces the risk of brain metastasis in patients with extensive-stage SCLC.

Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee.

OBJECTIVE: Acute synovial inflammation following joint trauma is associated with posttraumatic arthritis. Synovial macrophages have been implicated in degenerative changes. In this study, we sought to elucidate the role of intra-articular macrophages in the acute inflammatory response to fracture in the mouse knee. METHOD: A closed articular fracture was induced in two models of synovial macrophage depletion: genetically-modified MaFIA mice administered AP20187 to induce programmed macrophage apoptosis, and wild-type C57BL/6 mice administered clodronate liposomes, both via intra-articular injection. Synovial inflammation, bone morphology, and levels of F4/80+ macrophages, NOS2+ M1 macrophages, and CD206+ M2 macrophages were quantified 7 days after fracture using histology and micro-computed tomography. RESULTS: Intra-articular macrophage depletion with joint injury did not reduce acute synovitis or the number of synovial macrophages 7 days after fracture in either macrophage-depleted MaFIA mice or in clodronate-treated C57BL/6 mice. In macrophage-depleted MaFIA mice, macrophage polarity shifted to a dominance of M1 macrophages and a reduction of M2 macrophages in the synovial stroma, indicating a shift in M1/M2 macrophage ratio in the joint following injury. Interestingly, MaFIA mice depleted 2 days prior to fracture demonstrated increased synovitis (P = 0.003), reduced bone mineral density (P = 0.0004), higher levels of M1 macrophages (P = 0.013), and lower levels of M2 macrophages (not statistically significant, P=0.084) compared to control-treated MaFIA mice. CONCLUSION: Our findings indicate that macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury and suggest that inhibition of macrophage function can have prominent effects on joint inflammation and bone homeostasis after joint trauma.

[The association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age among neonatal twins in Shaanxi Province].

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion: Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

The role of macrophages in osteoarthritis and cartilage repair.

Osteoarthritis (OA) is a family of degenerative diseases affecting multiple joint tissues. Despite the diverse etiology and pathogenesis of OA, increasing evidence suggests that macrophages can play a significant role in modulating joint inflammation, and thus OA severity, via various secreted mediators. Recent advances in next-generation sequencing technologies coupled with proteomic and epigenetic tools have greatly facilitated research to elucidate the embryonic origin of macrophages in various tissues including joint synovium. Furthermore, scientists have now begun to appreciate that macrophage polarization can span beyond the conventionally recognized binary states (i.e., pro-inflammatory M1-like vs anti-inflammatory M2-like) and may encompass a broad spectrum of phenotypes. Although the presence of these cells has been shown in multiple joint tissues, additional mechanistic studies are required to provide a comprehensive understanding of the precise role of these diverse macrophage populations in OA onset and progression. New approaches that can modulate macrophages into desired functional phenotypes may provide novel therapeutic strategies for preventing OA or enhancing cartilage repair and regeneration.

What drives depression in empty nose syndrome? A Sinonasal Outcome Test-25 subdomain analysis.

BACKGROUND: Empty nose syndrome (ENS) is a debilitating disorder characterised by paradoxical nasal obstruction after excessive surgical excision of nasal tissues. ENS negatively impacts the quality of life (QOL) and psychological status of patients. This study aimed to determine the associations among disease-specific QOL impairments and the severity of anxiety and depression before and after surgery in ENS patients. METHODS: A total of 68 ENS patients were prospectively recruited and underwent submucosal Medpor implantation. QOL impairments and the severity of anxiety and depression were evaluated using the Sinonasal Outcome Test-25 (SNOT-25), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) 1 day before and 6 months after surgery. RESULTS: The BDI-II and BAI scores were significantly associated with the total score and ear/facial symptoms, psychological dysfunction, sleep dysfunction, and empty nose symptoms domains of the SNOT-25. Surgery improved disease-specific and psychological symptoms. Post-operative changes in the BDI-II score were correlated with changes in the total score and sleep dysfunction and empty nose symptoms domains of the SNOT-25. A SNOT-25 total score of greater than 60, sleep dysfunction domain score of greater than 18, and empty nose symptoms domain score of greater than 14 were good predictors of moderate-to-severe depression. CONCLUSIONS: ENS symptoms are associated with psychological burden and could be good predictors of moderate-to-severe depression. Targeted symptom improvement could reduce the psychological burden.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.

BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.

The association between LncRNA HOTAIR and cancer lymph node metastasis and distant metastasis: a meta-analysis.

HOTAIR has been reported to be associated with development and metastasis in different types of cancer. This meta- analysis collected all relevant articles and explored the correlation of HOTAIR with lymph node metastasis (LNM) and distant metastasis (DM). A literature collection was conducted by searching PubMed, Web of Science, Google Scholar and Cochrane Library (up to Sep 11, 2016). The odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the association with strength. Nineteen studies were included in this study, with a total of 1874 patients. The study objects were all Asians. We found high HOTAIR expression in tumor tissues was significantly correlated with LNM and DM, and analysis showed a pooled OR of 3.18 (95% CI: 2.10-4.81, p<0.00001) and 3.93 (95% CI: 2.39-6.47, p<0.00001), respectively. HOTAIR may serve as a novel diagnostic biomarker for cancer metastasis.

Serum Cyr61 as a potential biomarker for diagnosis of colorectal cancer.

PURPOSE: To determine the sensitivity and specificity of serum Cyr61 as a potential biomarker for the diagnosis of colorectal cancer (CRC) and to assess the association between serum Cyr61 level and CRC clinicopathological status. METHODS: We used an enzyme-linked immunosorbent assay to measure serum Cyr61 in patients with CRC, patients with colorectal adenomas, and healthy controls. We also analyzed the relationship between serum Cyr61 and clinicopathological features of CRC patients. The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were quantified using the Roche Cobas 6000 Analyzer. The sensitivity and specificity of Cyr61, CEA, CA19-9 and CEA + CA19-9 were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The serum level of Cyr61 was significantly increased in CRC patients compared with colorectal adenoma patients and healthy controls (p < 0.001). Furthermore, the area under the ROC curve for Cyr61 was 0.935 (95 % confidence interval 0.902-0.968), higher than that for CEA + CA19-9 (0.827, 95 % confidence interval: 0.783-0.871). Use of a Cyr61 cutoff value of 92.0 pg/mL allowed distinguishing CRC patients and healthy controls with a sensitivity of 83 % and a specificity of 97 %. Among CRC patients, an elevated level of serum Cyr61 was significantly associated with more advanced TNM stage (p < 0.0042), lymph node metastasis (p < 0.0088), and vascular invasion (p = 0.0027). CONCLUSION: Cyr61 has potential as a serum biomarker for the diagnosis of CRC and for assessment of the clinicopathological status of CRC.

Hyperactivated FRS2α-mediated signaling in prostate cancer cells promotes tumor angiogenesis and predicts poor clinical outcome of patients.

Metastasis of tumors requires angiogenesis, which is comprised of multiple biological processes that are regulated by angiogenic factors. The fibroblast growth factor (FGF) is a potent angiogenic factor and aberrant FGF signaling is a common property of tumors. Yet, how the aberration in cancer cells contributes to angiogenesis in the tumor is not well understood. Most studies of its angiogenic signaling mechanisms have been in endothelial cells. FGF receptor substrate 2α (FRS2α) is an FGF receptor-associated protein required for activation of downstream signaling molecules that include those in the mitogen-activated protein and AKT kinase pathways. Herein, we demonstrated that overactivation and hyperactivity of FRS2α, as well as overexpression of cJUN and HIF1α, were positively correlated with vessel density and progression of human prostate cancer (PCa) toward malignancy. We also demonstrate that FGF upregulated the production of vascular endothelial growth factor A mainly by increasing expression of cJUN and HIF1α. This then promoted recruitment of endothelial cells and vessel formation for the tumor. Tumor angiogenesis in mouse PCa tissues was compromised by tissue-specific ablation of Frs2α in prostate epithelial cells. Depletion of Frs2α expression in human PCa cells and in a preclinical xenograft model, MDA PCa 118b, also significantly suppressed tumor angiogenesis accompanied with decreased tumor growth in the bone. The results underscore the angiogenic role of FRS2α-mediated signaling in tumor epithelial cells in angiogenesis. They provide a rationale for treating PCa with inhibitors of FGF signaling. They also demonstrate the potential of overexpressed FRS2α as a biomarker for PCa diagnosis, prognosis and response to therapies.

Amelioration of experimental arthritis by intra-articular injection of an epidermal growth factor receptor tyrosine kinase inhibitor.

OBJECTIVES: Selectively targeting signalling pathways represents a promising pharmacological approach in rheumatoid arthritis (RA). Abundant levels of epidermal growth factor receptor (EGFR) are expressed in the synovial lining layers, and the anti-arthritis effect of erlotinib and lapatinib, small-molecule EGFR tyrosine kinase inhibitors (TKIs), has been demonstrated through the systemic administration on experimental arthritis models. Nevertheless, their therapeutic responses by the intra-articular (i.a.) route remain to be explored in rheumatoid joint. METHODS: The administration of an EGFR TKI (a gefitinib analogue) was explored in two in vivo models of collagen-induced arthritis (CIA) and in vitro experiments by using synovial fibroblasts (SF) from RA patients and CIA rats. RESULTS: There was a significant reduction of arthritis scores in CIA mice receiving the daily intraperitoneal injection. After the onset of arthritis in CIA rats, ankle joints receiving a single i.a. injection had significant lower articular indexes with reduced synovial inflammation, pannus formation and erosion on cartilage and bone as well as total histological scores by histopathological analyses. In CIASF or RASF, upon in vitro human EGF stimulation, there was a dose-dependent increase in cell proliferation and Akt activation with suppressed responses under the EGFR TKI treatment. CONCLUSIONS: These findings demonstrate the effect of i.a. injection of an EGFR TKI on amelioration of rheumatoid joint through the suppression of synovial inflammation, pannus formation and erosion on cartilage and bone in experimental arthritis, implicating targeting the i.a. EGFR signalling transduction as a pharmacological strategy.

Potent antitumor activity of Oct4 and hypoxia dual-regulated oncolytic adenovirus against bladder cancer.

Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor-selective replication of oncolytic adenoviruses may be hindered by oxygen deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus, retaining its antitumor activity even in a hypoxic environment. We have previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven by nine copies of the Oct4 response element (ORE) for specifically killing Oct4-overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual-regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2α and Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF-2α was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells, while sparing normal cells. AdLCY exerted potent antitumor effects in mice bearing human bladder tumor xenografts and syngeneic bladder tumors. It could target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4 is expressed in various cancers, AdLCY may be further explored as a broad-spectrum anticancer agent.

Combination of vinblastine and oncolytic herpes simplex virus vector expressing IL-12 therapy increases antitumor and antiangiogenic effects in prostate cancer models.

Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in tumor cells causing direct killing, that is, oncolysis, while sparing normal cells. The oHSVs are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We hypothesized that combining the direct oncolytic and antiangiogenic activities of the interleukin (IL)-12-secreting NV1042 oHSV with microtubule disrupting agents (MDAs) would be an effective means to enhance antitumor efficacy. Vinblastine (VB) was identified among several MDAs screened, which displayed consistent and potent cytotoxic killing of both prostate cancer and endothelial cell lines. In matrigel tube-forming assays, VB was found to be highly effective at inhibiting tube formation of human umbilical vein endothelial cells. The combination of VB with NV1023 (the parental virus lacking IL-12) or NV1042 showed additive or synergistic activity against prostate cancer cell lines, and was not due to increased oHSV replication by VB. In athymic mice bearing CWR22 prostate tumors, VB in combination with NV1042 was superior to the combination of VB plus NV1023 in reducing tumor burden, appeared to be nontoxic and resulted in a statistically significant diminution in the number of CD31(+) cells as compared with other treatment groups. In human organotypic cultures using surgical samples from radical prostatectomies, both NV1023 and NV1042 were localized specifically to the epithelial cells of prostatic glands but not to the surrounding stroma. These data highlight the therapeutic advantage of combining the dual-acting antitumor and antiangiogenic activities of oHSVs and MDAs.