This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRAS^G12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFR^L858R and EGFR^Δ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFR^T790M showed no difference compared to classical activating mutations without EGFR^T790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRAS^G12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFR^T790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Extracellular Matrix Proteins/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Treatment Outcome

Objective:To explore the clinical efficacy and feasibility of applying a medial plantar vein flap to repair the great toenail flap donor site.Methods:A retrospective analysis was performed on the clinical data of patients who underwent great toenail flap or partial great toenail flap transplantation for finger reconstruction from January 2020 to June 2021 in Longgang Orthopedic Hospital of Shenzhen. During the operation, the donor site of the great toenail flap was repaired with medial plantar venous flaps, and the donor site of the medial plantar venous flaps was repaired with a free full-thickness skin graft. The survival of the flap was observed and the appearance, sensation, and complications of the flap were followed up. The foot function was evaluated by the Maryland foot function evaluation standard.Results:A total of 6 cases were enrolled, including 5 males and 1 female with an average of 22 years, ranged from 14-28 years old. The wound area of the great toenail flap was 2.2 cm×3.7 cm-5.5 cm×7.0 cm, and the skin flap was 2.5 cm×3.8 cm-5.5 cm×7.1 cm. All flaps survived. 2 cases developed tension blisters. All patients were followed up for 3-18 months, with an average of 9 months. And all flaps had no swollen appearance, good color, texture, and no ulcers or pain. Two-point discrimination was 7-10 mm, and the second/third donor area was concealed. According to the Maryland foot function evaluation standard, all 6 cases were rated as excellent.Conclusion:The application of the medial plantar vein flap to repair the donor area of the great toenail flap is an effective repair method. The donor area is concealed, the flap is not bloated, the texture is good, the survival rate is high, and the sensation recovered satisfactory.

Objective:To explore the clinical efficacy and feasibility of applying a medial plantar vein flap to repair the great toenail flap donor site.Methods:A retrospective analysis was performed on the clinical data of patients who underwent great toenail flap or partial great toenail flap transplantation for finger reconstruction from January 2020 to June 2021 in Longgang Orthopedic Hospital of Shenzhen. During the operation, the donor site of the great toenail flap was repaired with medial plantar venous flaps, and the donor site of the medial plantar venous flaps was repaired with a free full-thickness skin graft. The survival of the flap was observed and the appearance, sensation, and complications of the flap were followed up. The foot function was evaluated by the Maryland foot function evaluation standard.Results:A total of 6 cases were enrolled, including 5 males and 1 female with an average of 22 years, ranged from 14-28 years old. The wound area of the great toenail flap was 2.2 cm×3.7 cm-5.5 cm×7.0 cm, and the skin flap was 2.5 cm×3.8 cm-5.5 cm×7.1 cm. All flaps survived. 2 cases developed tension blisters. All patients were followed up for 3-18 months, with an average of 9 months. And all flaps had no swollen appearance, good color, texture, and no ulcers or pain. Two-point discrimination was 7-10 mm, and the second/third donor area was concealed. According to the Maryland foot function evaluation standard, all 6 cases were rated as excellent.Conclusion:The application of the medial plantar vein flap to repair the donor area of the great toenail flap is an effective repair method. The donor area is concealed, the flap is not bloated, the texture is good, the survival rate is high, and the sensation recovered satisfactory.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95％ confidence interval (CI), 1.01?1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95％ CI, 1.49?2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95％ CI, 0.48?1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95％ CI, 0.39?1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A (USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95％ CI, 0.32?0.82; P=0.0077), PFS (adjusted HR, 0.51; 95％ CI, 0.38?0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95％ CI, 2.75?8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95％ CI, 1.88?6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12C mutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.

Objective:To explore the clinical effect of medial plantar venous flow-through flap combined with vein transplantation to repair incomplete finger amputation with circularity soft tissue defect.Methods:A retrospective analysis was performed on the clinical data of patients with incomplete finger amputation injury with circularity soft tissue defect treated by medial plantar venous flow-through flap combined with vein transplantation from January 2016 to October 2020 in Longgang Orthopedic Hospital of Shenzhen. According to the length of the arterial and venous defects of the injured finger and the area of the circular wound, a venous flap (including 2-3 veins )was designed and harvested in the medial plantar. And then two superficial veins were harvested from the donor site to repair the dominant digital artery and distal digital vein of the severed finger. One vein in the flap was bridged to repair the non-dominant digital artery of the severed finger, and the other 1-2 veins were anastomosed with the subcutaneous vein of the proximal wound. The recipient site was closed. The donor site was repaired with full-thickness skin grafting. The appearance, two-point discrimination of the flap, as well as the shape, two-point discrimination, and the extension and flexion of the finger were followed up after the operation. The evaluation was performed by the trial standard for the replantation function of amputated fingers of the Chinese Medical Association Hand Surgery Branch.Results:In this study, a total of 11 patients with thermal crush injury were enrolled, including 7 males and 4 females, aged 16-46 years old. Cyclic skin and soft tissue defect was 1.4 cm×4.5 cm - 3.2 cm×5.4 cm in size after debridement, the arterial defect was 1.6-3.5 cm in length, and the venous defect was 1.7-3.3 cm in length. The flap was 1.6 cm×4.6 cm-3.3 cm×5.5 cm in size, and the harvested vein was 1.7-3.5 cm in length. All severed fingers and flaps survived. Eleven cases were followed up 11-18 months. The appearance of flap was not swollen, and the color and texture were close to the surrounding skin. The two-point discrimination was 7-11 mm. The shape of the finger was good, the two-point discrimination was 5-8 mm, and the extension and flexion activity of the finger was good. Ultimately, the hand function of 10 cases could be rated as excellent, and 1 case could be rated as good. There was slight pigmentation in the donor area, but no ulceration or pain, and no obvious abnormality in wearing shoes, walking, or running.Conclusions:The medial plantar venous flow-through flap combined with vascular transplantation is an ideal repair method to repair incomplete finger amputation with circularity soft tissue defect. It can not only reliably rebuild the blood supply of the distal finger, but also repair the annular defect of the proximal finger. The impact on the donor site is slight.

Objective:To explore the clinical effect of medial plantar venous flow-through flap combined with vein transplantation to repair incomplete finger amputation with circularity soft tissue defect.Methods:A retrospective analysis was performed on the clinical data of patients with incomplete finger amputation injury with circularity soft tissue defect treated by medial plantar venous flow-through flap combined with vein transplantation from January 2016 to October 2020 in Longgang Orthopedic Hospital of Shenzhen. According to the length of the arterial and venous defects of the injured finger and the area of the circular wound, a venous flap (including 2-3 veins )was designed and harvested in the medial plantar. And then two superficial veins were harvested from the donor site to repair the dominant digital artery and distal digital vein of the severed finger. One vein in the flap was bridged to repair the non-dominant digital artery of the severed finger, and the other 1-2 veins were anastomosed with the subcutaneous vein of the proximal wound. The recipient site was closed. The donor site was repaired with full-thickness skin grafting. The appearance, two-point discrimination of the flap, as well as the shape, two-point discrimination, and the extension and flexion of the finger were followed up after the operation. The evaluation was performed by the trial standard for the replantation function of amputated fingers of the Chinese Medical Association Hand Surgery Branch.Results:In this study, a total of 11 patients with thermal crush injury were enrolled, including 7 males and 4 females, aged 16-46 years old. Cyclic skin and soft tissue defect was 1.4 cm×4.5 cm - 3.2 cm×5.4 cm in size after debridement, the arterial defect was 1.6-3.5 cm in length, and the venous defect was 1.7-3.3 cm in length. The flap was 1.6 cm×4.6 cm-3.3 cm×5.5 cm in size, and the harvested vein was 1.7-3.5 cm in length. All severed fingers and flaps survived. Eleven cases were followed up 11-18 months. The appearance of flap was not swollen, and the color and texture were close to the surrounding skin. The two-point discrimination was 7-11 mm. The shape of the finger was good, the two-point discrimination was 5-8 mm, and the extension and flexion activity of the finger was good. Ultimately, the hand function of 10 cases could be rated as excellent, and 1 case could be rated as good. There was slight pigmentation in the donor area, but no ulceration or pain, and no obvious abnormality in wearing shoes, walking, or running.Conclusions:The medial plantar venous flow-through flap combined with vascular transplantation is an ideal repair method to repair incomplete finger amputation with circularity soft tissue defect. It can not only reliably rebuild the blood supply of the distal finger, but also repair the annular defect of the proximal finger. The impact on the donor site is slight.

Objective:To investigate the clinical efficacy and feasibility of anterolateral thigh perforator flap with fascia lata in repairing hand and foot wounds complicated with extensor tendon defect.Methods:The clinical data of patients with hand and foot wounds complicated with extensor tendon defect who were repaired with anterolateral thigh perforator flap with fascia lata in Long Gang District Orthopedic Hospital of Shenzhen from May 2014 to December 2019 were analyzed retrospectively. During the operation, fascia lata was used to repair the defect of extensor tendon.The proximal and distal endof fascia lata were anastomosis with defect extensor tendon by figure 8 sutures.The soft tissue defects of hand and foot were repaired with anterolateral thigh (ALT)perforator flap. The donor site was closed primarily or covered by free skin graft. After operation, the sensory recovery of the flap was evaluated according to the evaluation standard of sensory function after peripheral nerve injury formulated by British Medical Research Association. According to the total active range of movement (TAM) of fingers recommended by the evaluation standard of hand tendon repair of Hand Surgery Society of Chinese Medical Association, the hand motor function was evaluated systematically. Foot motor function was evaluated according to the ankle-hind foot scoring system developed and recommended by the American Association of Foot and Ankle Surgeons.Results:A total of 23 patients were enrolled, including 19 males and 4 females, aged from 9 to 61 years old, with an average age of 26 years old. Causes of injury: there were 11 cases of crushinjury associated with machine, 4 cases of road traffic injury, 6 cases of injury by falling heavy object, 2 cases of saw injury. The area of wound defect ranged from 2 cm × 6 cm to 7 cm × 25 cm, and the length of tendon defect ranged from 1.0 cm to 10.0 cm. All cases were complicated with partial or complete defect of extensor tendon. There were 19 cases with fracture and nerve injury. All the injuries were successfully repaired. All the flaps survived well. The rande of flap harvest was 3 cm × 5 cm to 9 cm × 23 cm, and the fascia lata was 1.0 cm × 1. 5 cm to 4.5 cm × 11. 0 cm. There were no complications such as arteriovenous crisis, infection, fat liquefaction, etc. Andall the wounds were closed primarily. Follow-up period ranged from 3 to 36 months (average 14 months) showed that all flaps had aestheticappearance, good color, and texture. Sensory recovery: excellent in 19 cases and good in 4 cases. TAM system evaluation method and ankle-hind foot scoring system were used to evaluate the function of hand and foot: 21 cases were excellent and 2 cases were good.Conclusions:The application of anterolateral thigh perforator flap with fascia lata to repair the hand and foot wound with extensor tendon defect can restore the motor and sensory function of the injured limb while covering the wound surface.This method has less damage to the donor site and less postoperative complications, and can significantly improve the quality of life of patients. It is an effective method to repair the wounds of hand and footcombined with extensor tendon defect.

Objective:To investigate the clinical efficacy and feasibility of anterolateral thigh perforator flap with fascia lata in repairing hand and foot wounds complicated with extensor tendon defect.Methods:The clinical data of patients with hand and foot wounds complicated with extensor tendon defect who were repaired with anterolateral thigh perforator flap with fascia lata in Long Gang District Orthopedic Hospital of Shenzhen from May 2014 to December 2019 were analyzed retrospectively. During the operation, fascia lata was used to repair the defect of extensor tendon.The proximal and distal endof fascia lata were anastomosis with defect extensor tendon by figure 8 sutures.The soft tissue defects of hand and foot were repaired with anterolateral thigh (ALT)perforator flap. The donor site was closed primarily or covered by free skin graft. After operation, the sensory recovery of the flap was evaluated according to the evaluation standard of sensory function after peripheral nerve injury formulated by British Medical Research Association. According to the total active range of movement (TAM) of fingers recommended by the evaluation standard of hand tendon repair of Hand Surgery Society of Chinese Medical Association, the hand motor function was evaluated systematically. Foot motor function was evaluated according to the ankle-hind foot scoring system developed and recommended by the American Association of Foot and Ankle Surgeons.Results:A total of 23 patients were enrolled, including 19 males and 4 females, aged from 9 to 61 years old, with an average age of 26 years old. Causes of injury: there were 11 cases of crushinjury associated with machine, 4 cases of road traffic injury, 6 cases of injury by falling heavy object, 2 cases of saw injury. The area of wound defect ranged from 2 cm × 6 cm to 7 cm × 25 cm, and the length of tendon defect ranged from 1.0 cm to 10.0 cm. All cases were complicated with partial or complete defect of extensor tendon. There were 19 cases with fracture and nerve injury. All the injuries were successfully repaired. All the flaps survived well. The rande of flap harvest was 3 cm × 5 cm to 9 cm × 23 cm, and the fascia lata was 1.0 cm × 1. 5 cm to 4.5 cm × 11. 0 cm. There were no complications such as arteriovenous crisis, infection, fat liquefaction, etc. Andall the wounds were closed primarily. Follow-up period ranged from 3 to 36 months (average 14 months) showed that all flaps had aestheticappearance, good color, and texture. Sensory recovery: excellent in 19 cases and good in 4 cases. TAM system evaluation method and ankle-hind foot scoring system were used to evaluate the function of hand and foot: 21 cases were excellent and 2 cases were good.Conclusions:The application of anterolateral thigh perforator flap with fascia lata to repair the hand and foot wound with extensor tendon defect can restore the motor and sensory function of the injured limb while covering the wound surface.This method has less damage to the donor site and less postoperative complications, and can significantly improve the quality of life of patients. It is an effective method to repair the wounds of hand and footcombined with extensor tendon defect.

Objective:The defects of thumbs and fingers are common and devastating in hand injuries, which make both physical and mental affecets to the patients. With deeper understanding in anatomy and faster development in micro-surgical techniques, the reconstruction of thumbs and fingers from toes with vascular anastomosis became a mainstream in the hand surgeons. These procedures were acclaimed as methods with desired outcome in function, sensation and aesthetics. However, a multitude of modification is responsible for the lack of normalization. We expects this review would provide a reference in fulfilling the surgical strategies.

Objective To investigate the hallux nail flap with the tibia lateral diamond shaped flap of the second phalange,joints,tendon combined tissue combination reengineering the surgical methods and clinical effects of thumb.Methods From May,2010 to February,2015,thcrc had fifteen cases of the thumb defect on Ⅱ-Ⅳ degree of the patients in our hospital,and we took anastomosis vascular pedicle of the hallux nail flap and thumb reconstruction with a second phalange with the tibia lateral diamond shaped flap,joint,and tendon composite tissue combination to reconstruct the thumb.The provided district of the second metatarsal was amputated to repair the ligaments between metatarsal bones.And we took the second toe bone nail flap covering the hallux toe area wound in anterograde shift.Results 15 cases of thumb reconstruction survived.The patients were followed-up for 6 to 30 months,the shape of the reconstructed thumb was closed to the contralateral thumb.The thumb to the finger and the palm function was good,two-point discrimination of the finger pulp were 0.6-1.0 cm.According to the upper limb function of the Chinese Medical Association Hand Surgery Society,the upper limb partial function of the evaluation trial standard:excellent in 11 cases,good in 4 cases.The district was recovered well,normal walking and running function were not restricted.Long term follow-up showed no blisters formation and skin ulceration.No nail deformity,good growth.Conclusion The hallux nail flap with the tibia lateral diamond shaped flap of the second phalange,joints,tendon combined tissue combination to reconstruct the thumb of the defect on Ⅱ-Ⅳ degree can restore good function and feeling,but also to have beautiful appearance.It is an effective method for reconstruction of thumb defect on Ⅱ-Ⅳ degree.