Outcomes Following Cytoreductive Surgery and Hyperthermic Intraoperative Thoraco-Abdominal Chemotherapy with Diaphragm Resection for Peritoneal Carcinomatosis: A Retrospective Cohort Study.

PURPOSE: We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. METHODS: PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. RESULTS: Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60 years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. CONCLUSIONS: HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.

Intraoperative urinary tract resection and construction in CRS + HIPEC procedures: a single center retrospective analysis.

INTRODUCTION: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction. METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison. RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively). CONCLUSION: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.

Clinical outcomes following direct anterior approach during total hip arthroplasty without hip extension: a retrospective comparative study.

BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.

Diterpenoid Alkaloids from Delphinium liangshanense.

Two new C19-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.

Effect of standardized fluid management on cardiac function after CRS + HIPEC in patients with PMP: a single-center case-control study.

OBJECTIVE: To investigate the effects of standardized fluid management (SFM) on cardiac function in patients with pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: Patients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. The patients were divided into control and study groups according to whether SFM was applied after CRS + HIPEC. We compared the preoperative and postoperative cardiac and renal function parameters, daily fluid volume three days after CRS, and cardiovascular-related adverse events. Univariate and multivariate analyses were performed to identify the indicators affecting clinical prognosis. RESULT: Among the 104 patients, 42 (40.4%) were in the control group and 62 (59.6%) in the study group. There were no statistically significant differences between the two groups in the main clinicopathological characteristics, preoperative cardiac and renal function parameters, and CRS + HIPEC-related indicators. The incidences of cardiac troponin I (CTNI) > upper limit of normal (ULN), >2 × ULN, >3 × ULN, serum creatinine > ULN, and blood urea nitrogen > ULN were higher in the control group than in the study group (p < 0.05). The median daily fluid volume of the control group was higher than that of the study group 3 days after CRS (p < 0.05). Postoperative CTNI > 2 × ULN was an independent risk factor for serious circulatory adverse events. Survival analysis revealed pathological grading, completeness of cytoreduction score, and postoperative CTNI > ULN as independent prognostic factors. CONCLUSIONS: SFM after CRS + HIPEC in patients with PMP may reduce cardiovascular adverse events risk and improve clinical outcomes.

Standardized Tip-Apex Distance (STAD): a modified individualized measurement of cephalic fixator position based on its own femoral head diameter in geriatric intertrochanteric fractures with internal fixation.

OBJECTIVE: To design a standardized Tip-Apex Distance (STAD) and analyze the clinical significance of STAD in predicting cut-out in geriatric intertrochanteric fractures with internal fixation. METHODS: Firstly, we designed STAD according to the rule of TAD. We measured the STAD individually based on its own femoral head diameter (iFHD) instead of the known diameter of the lag screw in calculating TAD, resulting in that the STAD is simply the relative quantitation relationship of iFHD (the times of iFHD). In this study, we assumed that all the iFHD was 6D (1iFHD = 6D, or 1D = 1/6 of iFHD) in order for complete match of the Cleveland zone system, easy comparison of the STAD, and convenient identification for artificial intelligence. Secondly, we calculated and recorded all the STAD of cephalic fixator in 123 eligible ITF patients. Thirdly, we grouped all the ITF patients into the Failure and Non-failure groups according to whether cut-out or not, and analyzed the correlation between the cut-out and the STAD. RESULTS: Cleveland zone, Parker's ratio (AP), TAD, and STAD were associated with the cut-out in univariate analysis. However, only STAD was the independent predictor of the cut-out by multivariate analysis. No cut-out was observed when STAD ≤ 2D (1/3 of iFHD). The Receiver Operating Characteristic (ROC) curve indicated that STAD was a reliable predictor of cut-out, and the best cut-off value of STAD was 2.92D. Cut-out rate increased dramatically when STAD increased, especially when STAD > 3D (1/2 of iFHD). CONCLUSION: Essentially, the STAD is a relative quantitation relationship of iFHD. The STAD is a reliable measurement of cephalic fixator position in predicting cut-out in geriatric ITF patients with single-screw cephalomedullary nail fixations. For avoiding cut-out, the STAD should be no more than a half of iFHD. LEVEL OF EVIDENCE: Level III, Prognostic Study.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial.

Importance: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective: To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results: Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03661411.

Clinicopathological features of desmoplastic small round cell tumors: clinical series and literature review.

BACKGROUND AND PURPOSE: Desmoplastic small round cell tumor (DSRCT) is a highly malignant sarcoma that occurs in the abdominopelvic cavities of adolescents. The accurate diagnosis of DSRCT is challenging owing to limited literatures. Our study aimed to investigate the relationship between clinicopathological features and prognosis in patients with DSRCTs. METHODS: Data of 8 patients with DSRCT originating from the abdominal cavity were retrospectively reviewed. The clinical manifestations, pathological characteristics, treatment approaches, and prognosis were analyzed. The histopathological (identified using hematoxylin-eosin staining), immunohistochemical, and molecular diagnostic (using fluorescence in situ hybridization) features were also reviewed. RESULTS: All patients were male aged between 24 and 45 years (median age, 30 years). The main clinical symptoms included abdominal distension, abdominal pain, and constipation. Seven of the 8 patients developed metastases to either distant organs or lymph nodes. Multiple gray nodules with diameters of 1-10 cm and poorly defined boundaries were scattered throughout the omentum and mesentery. Histopathological examination demonstrated well-defined nests composed of small round blue cells separated by markedly desmoplastic stroma. Immunohistochemical analysis revealed positive expressions of desmin, vimentin and C-terminal of Wilm's tumor suppressor (WT-1). The Ewing sarcoma breakpoint region 1 gene fused with WT1 (EWSR1-WT1) gene fusion was detected in all patients. Cytoreductive surgery (CRS) was performed in 6 patients. Follow-up period ranged from 7.5 to 28.5 months with a median of 17.2 months. Three patients died during follow-up. CONCLUSION: DSRCT is highly aggressive and presents distinctive morphological features. CRS is the essential therapy for DSRCT. A test for the combined expression of desmin, cytokeratins, and C-terminal of WT-1, as well as the analysis of morphologic features, might be helpful during DSRCT diagnosis, and the EWSR1-WT1 gene fusion is the gold standard for definitive diagnosis. Our work will provide new insights into the diagnosis and treatment of DSRCTs.

Joint Salvage and Biological Repair of Massive-Cavity Bone Defects After Extensive Curettage of Campanacci Grade II or III Giant Cell Tumor Around the Knee With Vascularized Fibular Autograft and Cancellous Allograft.

OBJECTIVE: The aim of the study was to report the clinical outcomes of repair of massive-cavity bone defects after extensive curettage of Campanacci grade II or III giant cell tumor (GCT) around knee with vascularized fibular autograft and cancellous allograft. METHODS: There were 12 consecutive patients with Campanacci grade II or III GCT around knee treated in our department between 2004 and 2016. All the patients underwent clinical evaluation, plain radiography, and/or magnetic resonance imaging of the knee right after admission. To preserve their knee function, we repaired the massive-cavity bone defects after extensive curettage of GCT by vascularized fibular autografts and cancellous allograft. All the patients were evaluated through clinical examinations, plain radiography of the knee and chest, and Musculoskeletal Tumor Society (MSTS) scores of the lower extremity in the follow-ups. RESULTS: The follow-up ranged from 1.5 to 12.0 years (mean, 4.2 years). There were no local recurrences or lung metastasis in any of the 12 patients at the last follow-up. Ten patients had no pain or experienced occasional pain, and 9 were able to resume their previous work. The mean range of motion of knee flexion was 117 degrees, and the extension was -6 degrees. The mean MSTS score was 24.7, and a total of 10 patients had excellent or good MSTS scores. CONCLUSIONS: It is reliable to achieve knee joint salvage and repair massive-cavity bone defects after extensive curettage with vascularized fibular autograft and cancellous allograft in patients with Campanacci grade II or III GCT around the knee.

Repair of Small-Size Wound With Achilles Tendon Exposure With Proximal Pedicled Cutaneous Neurovascular Flap.

OBJECTIVE: To investigate the clinical outcomes associated with repairing of small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap in the dorsolateral foot. METHODS: After thorough debridement, 16 cases with small-sized wounds of Achilles tendon exposure were repaired by proximal pedicled cutaneous neurovascular flap of the dorsolateral foot, and their clinical outcomes were observed. RESULTS: All the flaps in the 16 cases survived completely, excluding the marginal part necrosis in 1 case, and all the wounds were healed. The 2-point discrimination of the flaps was 14.53 ± 1.55 mm (range, 12-17 mm) in patients without sural nerve injury after 3 to 18 months follow-up. No discomfort was felt in wearing normal shoes by all the 16 patients. CONCLUSIONS: It is reasonable to repair the small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap of dorsolateral foot due to its effective repair of the wound, relatively uncomplicated surgery, and had satisfactory healing recovery.

RNF123 has an E3 ligase-independent function in RIG-I-like receptor-mediated antiviral signaling.

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytoplasmic sensors crucial for recognizing different species of viral RNAs, which triggers the production of type I interferons (IFNs) and inflammatory cytokines. Here, we identify RING finger protein 123 (RNF123) as a negative regulator of RIG-I and MDA5. Overexpression of RNF123 inhibits IFN-ß production triggered by Sendai virus (SeV) and encephalomyocarditis picornavirus (EMCV). Knockdown or knockout of endogenous RNF123 potentiates IFN-ß production triggered by SeV and EMCV, but not by the sensor of DNA viruses cGAS RNF123 associates with RIG-I and MDA5 in both endogenous and exogenous cases in a viral infection-inducible manner. The SPRY and coiled-coil, but not the RING, domains of RNF123 are required for the inhibitory function. RNF123 interacts with the N-terminal CARD domains of RIG-I/MDA5 and competes with the downstream adaptor VISA/MAVS/IPS-1/Cardif for RIG-I/MDA5 CARD binding. These findings suggest that RNF123 functions as a novel inhibitor of innate antiviral signaling mediated by RIG-I and MDA5, a function that does not depend on its E3 ligase activity.

Current status and future prospects of clinical trials on CRS + HIPEC for gastric cancer peritoneal metastases.

PURPOSE: There is no standard treatment for peritoneal metastases (PM) from gastric cancer (GC). The aim of this review is to evaluate the clinical trials on cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for GC PM. MATERIALS AND METHODS: The published clinical trials on CRS + HIPEC for GC PM are critically evaluated, and survival and safety are the primary endpoints. In addition, the registered ongoing clinical trials are summarised. RESULTS: The natural course of GC PM is <5 months. CRS + HIPEC could improve the overall survival (OS). In prospective studies, the median OS was 11.0 months in the CRS + HIPEC group vs. 5.4 months in the CRS alone group. In case-control studies, the median OS was 13.3 months in the CRS + HIPEC group vs. 7.9 months in the CRS alone group. In cohort studies, the median OS after CRS + HIPEC was 13.3. The median 1-, 2- and 5-year survival rates after CRS + HIPEC were 50.0%, 35.8% and 13.0%, respectively. There is no statistically significant increase in serious adverse events that are directly attributed to CRS + HIPEC. CONCLUSIONS: The combination of CRS and HIPEC is a promising integrated treatment strategy for GC PM that has encouraging initial results, calling for urgent further evaluation of this strategy in randomised control trials (RCTs).

Identification of cytokines for early prediction of malignant middle cerebral artery infarction.

PURPOSE: We aimed to profile cytokines in patients with malignant middle cerebral artery infarction (MMI) and non-acute cerebral infarction (NACI), and identify potential cytokines for early prediction of MMI. MATERIALS AND METHODS: A total of 16 subjects were recruited, including 8 patients with MMI and 8 patients with NACI. Cytokine profiles and levels in serums were analyzed by Quantibody® Human Cytokine Antibody Array700. The two-tailed Student t-test and Fisher's Exact Test were respectively conducted for continuous variables and categorical variables to evaluate their differences between patients with MMI and those with NACI. Binary logistic regression was further conducted to verify the association of differentially expressed cytokines with MMI. RESULTS: The concentrations of 320 unique inflammatory cytokines in serums were measured. Ten cytokines were discovered to be differentially expressed between patients with MMI and patients with NACI, including transforming growth factor beta-1 (TGFB1), matrix metallopeptidase 10 (MMP10), neural cell adhesion molecule 1 (NCAM1), interleukin-27 (IL27), epidermal growth factor (EGF), insulin-like growth factor-binding protein 6 (IGFBP6), platelet-derived growth factor subunit A (PDGFA), C-C motif chemokine 2 (C-C CCL2), neutrophil gelatinase-associated lipocalin (Lipocalin 2) and lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1). Among these cytokines, the concentrations of NCAM1, IGFBP6, Lipocalin2 and LYVE1 were significantly higher while the concentrations of the other six cytokines were significantly lower in patients with MMI compared with those in patients with NACI. Multivariate logistic regression analysis verified the association of these 10 cytokines with MMI except for IL-27 (p = 0.5422). CONCLUSIONS: Nine cytokines, including NCAM1, IGFBP6, Lipocalin2, LYVE1, TGFB1, MMP10, EGF, PDGFA and CCL2, might act as potential markers for early prediction of MMI and involve in the progression from NACI to MMI. Further studies with a better control group are still needed.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for the treatment of primary peritoneal serous carcinoma: Results of a Chinese retrospective study.

Purpose Primary peritoneal serous carcinoma (PPSC) is a rare condition with a poor survival rate, even after treatment with debulking surgery followed by systemic chemotherapy. This study evaluated the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PPSC. Patients and methods This retrospective study included 22 female patients with primary advanced PPSC (group A, n = 12) or recurrent PPSC (group B, n = 10) treated with 25 CRS + HIPEC procedures. The primary end point was overall survival (OS), and the secondary end points were safety profiles. Results A total of 25 CRS + HIPEC procedures were performed in these 22 patients. The median OS was 31.0 months (95% confidence interval (CI) 22.3-39.7), and the 1-, 3-, and 5-year survival rates were 100%, 45.5%, and 27.3%, respectively. Subgroup analyses revealed that the median OS was 31.0 months (95% CI 19.8-42.2) for group A vs. 38.5 months (95% CI 9.6-67.4) for group B (P = 0.832, log rank test); 51.5 months (95% CI 34.9-68.1) for peritoneal cancer index (PCI) ≤ 15 vs. 20.3 months (95% CI 12.6-28.0) for PCI > 15 (P = 0.000, log rank test); and 38.5 months (95% CI 22.5-54.5) for completeness of cytoreduction (CC) of 0-1 vs. 23.5 months (95% CI 15.3-31.7) for CC of 2-3 (P = 0.178, log rank test). There were no perioperative deaths. Serious adverse events (SAEs) occurred in two patients (9.1%). A univariate analysis identified PCI ≤ 15 as the only prognostic predicator (hazard ratio (HR) 13.1, 95% CI 2.7-63.4, P = 0.001). Conclusions CRS + HIPEC could contribute to favourable outcomes for select PPSC patients with acceptable safety profiles.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel improves survival for patients with peritoneal carcinomatosis from abdominal and pelvic malignancies.

BACKGROUND: This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. METHODS: Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. RESULTS: One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. CONCLUSIONS: CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00454519.

Distal radius reconstruction with vascularized proximal fibular autograft after en-bloc resection of recurrent giant cell tumor.

BACKGROUND: Giant cell tumors (GCTs) located in the distal radius are likely to recur, and the treatment of such recurrent tumors is very difficult. Here, we report our clinical experience in distal radius reconstruction with vascularized proximal fibular autografts after en-bloc excision of the entire distal radius in 17 patients with recurrent GCT (RGCT) of the distal radius. METHODS: All 17 patients with RGCT in distal radius underwent plain radiography and/or magnetic resonance imaging (MRI) of the distal radius as the initial evaluation after hospitalization. Then the distal radius were replaced by vascularized proximal fibular autografts after en-bloc RGCT resection. We assessed all patients by using clinical examinations, plain radiography of the wrist and chest, and Mayo wrist scores in the follow-ups. RESULTS: After an average follow-up of 4.3 years (range: 1.5-10.0 years), no lung metastasis or local recurrence was detected in any of the 17 patients. In total, 14 patients had excellent or good functional wrist scores, 16 were pain free or had occasional pain, and 15 patients returned to work. The mean range of motion of the wrist was 101° (flexion-extension), and the mean grip strength was 77.2 % of the contralateral normal hand. CONCLUSION: En-bloc excision of the entire distal radius and distal radius reconstruction with a vascularized proximal fibular autograft can effectively achieve local tumor control and preserve wrist function in patients with RGCT of the distal radius.

Negative regulation of RIG-I-mediated innate antiviral signaling by SEC14L1.

Retinoic acid-inducible gene I (RIG-I) is a key sensor for recognizing nucleic acids derived from RNA viruses and triggers beta interferon (IFN-ß) production. Because of its important role in antiviral innate immunity, the activity of RIG-I must be tightly controlled. Here, we used yeast two-hybrid screening to identify a SEC14 family member, SEC14L1, as a RIG-I-associated negative regulator. Transfected SEC14L1 interacted with RIG-I, and endogenous SEC14L1 associated with RIG-I in a viral infection-inducible manner. Overexpression of SEC14L1 inhibited transcriptional activity of the IFN-ß promoter induced by RIG-I but not TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3). Knockdown of endogenous SEC14L1 in both HEK293T cells and HT1080 cells potentiated RIG-I and Sendai virus-triggered IFN-ß production as well as attenuated the replication of Newcastle disease virus. SEC14L1 interacted with the N-terminal domain of RIG-I (RIG-I caspase activation and recruitment domain [RIG-I-CARD]) and competed with VISA/MAVS/IPS-1/Cardif for RIG-I-CARD binding. Domain mapping further indicated that the PRELI-MSF1 and CRAL-TRIO domains but not the GOLD domain of SEC14L1 are required for interaction and inhibitory function. These findings suggest that SEC14L1 functions as a novel negative regulator of RIG-I-mediated antiviral signaling by preventing RIG-I interaction with the downstream effector.

Baseline neurological deficit and argatroban plus alteplase in acute ischemic stroke: A post hoc analysis of ARAIS trial.

BACKGROUND: The ARAIS trial didn't demonstrate argatroban significantly improve functional outcome at 90 days in acute ischemic stroke. We conducted post hoc analysis of ARAIS to investigate whether baseline neurological deficit was associated with outcomes. METHODS: Patients without endovascular therapy who met screening criteria as protocol and completed argatroban treatment were enrolled and classified into two subgroups according to NIHSS score at admission. Primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0 to 1. Early neurological deterioration (END), defined as an increase of ≥4 in the NIHSS score from baseline within 48 hours, was investigated as secondary outcome. Compared with alteplase alone, we investigated treatment effect of argatroban plus alteplase on outcomes in subgroups and interaction with subgroups. RESULTS: A total of 675 patients from full analysis set were included: 390 were assigned into NIHSS score <10 subgroup and 285 into NIHSS score ≥10 subgroup. For primary outcome, there was similar treatment effect between argatroban plus alteplase and alteplase alone in NIHSS score ≥10 subgroup (adjusted RD, 5.8%; 95% CI, -6.0% to 17.5%; P = 0.33) and in NIHSS score <10 subgroup (adjusted RD, -1.4%; 95% CI, -9.9% to 7.1%; P = 0.75), and no significant interaction (P = 0.43). Occurrence of early neurological deterioration within 48 hours were significantly lower in NIHSS score ≥10 subgroup, compared with NIHSS score <10 subgroup (P = 0.006). CONCLUSION: Among patients with NIHSS score ≥10, argatroban plus alteplase could safely reduce END within 48 hours.

Gene and stem cell therapy for inherited cardiac arrhythmias.

Inherited cardiac arrhythmias are a group of genetic diseases predisposing to sudden cardiac arrest, mainly resulting from variants in genes encoding cardiac ion channels or proteins involved in their regulation. Currently available therapeutic options (pharmacotherapy, ablative therapy and device-based therapy) can not preclude the occurrence of arrhythmia events and/or provide complete protection. With growing understanding of the genetic background and molecular mechanisms of inherited cardiac arrhythmias, advancing insight of stem cell technology, and development of vectors and delivery strategies, gene therapy and stem cell therapy may be promising approaches for treatment of inherited cardiac arrhythmias. Recent years have witnessed impressive progress in the basic science aspects and there is a clear and urgent need to be translated into the clinical management of arrhythmic events. In this review, we present a succinct overview of gene and cell therapy strategies, and summarize the current status of gene and cell therapy. Finally, we discuss future directions for implementation of gene and cell therapy in the therapy of inherited cardiac arrhythmias.