Building on the backbone of CD47-based therapy in cancer: Combination strategies, mechanisms, and future perspectives

Described as a "don't eat me" signal, CD47 becomes a vital immune checkpoint in cancer. Its interaction with signal regulatory protein alpha (SIRPα) prevents macrophage phagocytosis. In recent years, a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect. Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies, indicating the combination strategy as a general trend of the future. In this review, clinical and preclinical cases about the current combination strategies targeting CD47 are collected, their underlying mechanisms of action are discussed, and ideas from future perspectives are shared.

CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer / 医学前沿

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.

Masquerade of Falls and Depression, and Transitions of Care

Falls in an elderly require a comprehensive bio-psycho-social approach to evaluate for the root causes. These may be multi-factorial, and we need to deal with most of them, if not all, in order to effectively reduce the risk for falls. Frailty is a marker of poor functional outcomes. Sarcopenia is a major modifiable risk factor for frailty. There are various community programmes providing a comprehensive range of services to keep the elderly physically, mentally, and socially active. Communication with primary care physicians is important to ensure smooth transition back into the community, optimal management of chronic diseases and minimal re-admission.

Clinical application of fast-track surgery with Chinese medicine treatment in the devascularization operation for cirrhotic portal hypertension / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of fast-track surgery combined with Chinese medicine treatment in devascularization operation for cirrhotic esophageal varices.</p><p><b>METHODS</b>Seventy-two patients with cirrhotic esophageal varices were selected from January 2009 to June 2013, and randomly assigned to a conventional group and a fast-track group (fast-track surgery combined with Chinese medicine treatment) using a randomized digital table, 36 cases in each group. Operation and anesthesia recovery time, postoperative hospitalization and quality of life were recorded and compared between groups during the perioperative period.</p><p><b>RESULTS</b>Compared with the conventional group, the fast-track group had longer operation time (253.6±46.4 min vs. 220.6±51.0 min) and anesthesia recovery time (50.5±15.9 min vs. 23.5±9.6 min; P<0.01); less bleeding (311.3±46.8 mL vs. 356.2±57.5 mL; P<0.01) and less transfusion (1932.3±106.9 mL vs. 2045.6±115.4 mL; P<0.01); as well as faster recovery of gastrointestinal function, shorter postoperative hospitalization and higher quality of life. There were no serious postoperative complications and no further bleeding occurred.</p><p><b>CONCLUSION</b>Fast-track surgery combined with Chinese medicine treatment is a safe and feasible approach to accelerate the recovery of patients with cirrhotic portal hypertension in perioperative period of devascularization operation.</p>

Clinical application of blood purification (artificial liver) in treatment of acute liver failure in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical application, indication, timing and prognosis of blood purification (artificial liver, BP) in treatment of acute liver failure in children.</p><p><b>METHOD</b>Artificial liver was used to treat 30 cases of pediatric acute liver failure (PALF), who were hospitalized in pediatric intensive care unit of Bayi Children's Hospital Affiliated to Beijing Military Command General Hospital, during March 2010 to July 2013. Simple plasma exchange (PE) mode was used for PALF without complications, while PE combined with continuous veno-venous hemodiafiltration (CVVHDF) mode was used for PALF with cerebral edema and/or hepatorenal syndrome and/or serious abnormality of electrolyte and acid-base balance.</p><p><b>RESULT</b>Sixteen cases survived and restored hepatic function, with a survival rate of 53.3%. Single PE therapy could significantly decrease total bilirubin (TBIL) from (293.96 ± 214.52) µmol/L to (155.64 ± 140.97) µmol/L (P = 0.033), increase prothrombin time activity (PTA) from (34.50 ± 18.34) % to (60.50 ± 33.97) % (P = 0.013), while it did not significantly influence ammonia from (156.43 ± 67.23) µmol/L to (124.03 ± 62.58) µmol/L (P = 0.156) and alanine transarninase (ALT) from (752.53 ± 1 291.84) U/L to (132.00 ± 98.57) U/L (P = 0.066). PE + CVVHDF therapy could significantly ameliorate TBIL from (326.90 ± 233.85) µmol/L to (157.53 ± 125.31) µmol/L (P = 0.033), ALT from (1 476.64 ± 1 728.18) U/L to (169.38 ± 207.18) U/L (P = 0.019), ammonia from (215.83 ± 83.92) µmol/L to (141.25 ± 63.09) µmol/L (P = 0.022) and PTA from (36.68 ± 23.13)% to (71.75 ± 50.50) % (P = 0.044). Prothrombin time (PT) from (29.71 ± 17.75)s to (16.27 ± 6.38)s (P = 0.008) , ALT from (1 574.11 ± 1 775.96) U/L to (145.81 ± 113.89 ) U/L (P = 0.003) , TBIL from (233.16 ± 219.70) µmol/L to (75.19 ± 86.07) µmol/L (P = 0.012) , ammonia from (182.75 ± 90.07) µmol/L to (101.81 ± 37.14) µmol/L (P = 0.002) and PTA from (38.38 ± 20.39)% to (83.13 ± 41.68)% (P = 0.001) in survived cases significantly ameliorated after BP therapy. TBIL from (394.04 ± 192.80) µmol/L to (249.34 ± 113.97) µmol/L (P = 0.023) in died cases declined significantly after BP therapy, while alteration of PT, ALT, ammonia , and PTA had no statistical significance (P > 0.10) after BP therapy.</p><p><b>CONCLUSION</b>PE + CVVHDF therapy could significantly ameliorate not only TBIL and PTA but also ammonia and ALT compared with single PE therapy. The decline of only an index like TBIL or ALT after BP therapy could not improve the prognosis. The inconsistency between serum bilirubin and ALT levels was an important factor that suggested poor prognosis of ALF, and it might increase survival rate to use BP therapy before that inconsistency emerged.</p>

Analysis of the effect of laparoscopic hepatectomy on 61 cases of primary liver cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility and the effect of laparoscopic hepatectomy for primary liver cancer(PLC).</p><p><b>METHODS</b>A retrospective study on 61 cases of laparoscopic hepatectomy for PLC was made between November 2002 and June 2007, among which there were 49 male and 12 female, aged from 14 to 71 years. All patients were diagnosed as PLC by type-B ultrasonic, CT or MRI, and APF.</p><p><b>RESULTS</b>Fifty-six patients were completed laparoscopically successfully. Five cases underwent conversion to open operation because of hemorrhage. The mean operative time was 60 min (30-150 min). The mean blood loss was 450 ml (100-2000 ml). The mean hepatic portal block time was 20 min (15-30 min). All the patients had excellent recovery without any postoperative surgical complications. The patients were mobilized out of the bed in 24 hours. Oral intake of food started in 1 to 3 days. The average postoperative hospital stay was 6.6 d (5-10 d).</p><p><b>CONCLUSION</b>Laparoscopic hepatectomy for PLC is safe and feasible by using hepatic portal block instrument.</p>

The application of laparoscopy in biliary reconstruction and rehabilitation after transection injury of biliary duct / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the feasibility of biliary reconstruction and rehabilitation after transection injury of biliary duct by laparoscopy.</p><p><b>METHODS</b>The clinical data of 24 cases receiving biliary reconstruction after transection injury of biliary duct by laparoscopy were analyzed retrospectively from August 2002 to April 2008, including operation indications, contraindications, related operation skills and so on. In these 24 cases, the reasons of transection of biliary duct as followed: 15 cases were pancreaticoduodenectomy, 6 cases were resection of the choledochal cyst, 1 case was resection of high cholangiocarcinoma, 1 case was cholecystectomy and 1 case was resection of gastric cancer.</p><p><b>RESULTS</b>Biliary reconstruction and rehabilitation was successfully completed in 24 cases by laparoscopy. There was 1 case of bile leakage and no duct stenosis complications.</p><p><b>CONCLUSIONS</b>Biliary reconstruction and rehabilitation by laparoscopy was feasible and safe procedure, has a high successful rate, and deserves further clinical trials in hospitals.</p>

Laparoscope hepatectomy for hepatic hemangioma: a report of 18 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and practicality of laparoscopic hepatectomy for hepatic hemangioma.</p><p><b>METHODS</b>Candidate for laparoscopic liver resection were 18 cases of hepatic hemangioma from January 2002 to October 2006. The portal bloods stream was blocked by the laparoscope portal blood blocker. The Electric-cautery and ultracision were used for liver transection. Operative procedures included anatomical left hepatectomy in 2 cases, non-anatomical left hepatectomy 1 case, left lobectomy 5 cases, local liver resection 10 cases. Two cases of hepatic hemangioma associated with gallbladder stone were performed cholecystectomy synchronously, 1 case associated with chronic appendicitis were performed appendectomy synchronously.</p><p><b>RESULTS</b>Laparoscopic left liver resection was successfully performed in all 18 cases. The operative duration was (185.4 +/- 55.7) min. The quantity of blood lost during the operation was (416.2 +/- 128.8) ml. The postoperative recovery was smooth and good. No critical complications occurred. The duration for hospitalization was (6.2 +/- 1.0) d.</p><p><b>CONCLUSION</b>Laparoscope hepatectomy for hepatic hemangioma is safe and feasible.</p>