Predicting the efficacy of immune checkpoint inhibitors monotherapy in advanced non-small cell lung cancer: a machine learning method based on multidimensional data.

Immunotherapy has improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC), but only a small subset of patients achieved clinical benefit. The purpose of our study was to integrate multidimensional data using a machine learning method to predict the therapeutic efficacy of immune checkpoint inhibitors (ICIs) monotherapy in patients with advanced NSCLC. We retrospectively enrolled 112 patients with stage IIIB-IV NSCLC receiving ICIs monotherapy. The random forest (RF) algorithm was used to establish efficacy prediction models based on five different input datasets, including precontrast computed tomography (CT) radiomic data, postcontrast CT radiomic data, a combination of the two CT radiomic data, clinical data, and a combination of radiomic and clinical data. The 5-fold cross-validation was used to train and test the random forest classifier. The performance of the models was assessed according to the area under the curve (AUC) in the receiver operating characteristic curve. Survival analysis was performed to determine the difference in progression-free survival (PFS) between the two groups with the prediction label generated by the combined model. The radiomic model based on the combination of precontrast and postcontrast CT radiomic features and the clinical model produced an AUC of 0.92±0.04 and 0.89±0.03, respectively. By integrating radiomic and clinical features together, the combined model had the best performance with an AUC of 0.94±0.02. The survival analysis showed that the two groups had significantly different PFS times (p<0.0001). The baseline multidimensional data including CT radiomic and multiple clinical features were valuable in predicting the efficacy of ICIs monotherapy in patients with advanced NSCLC.

How do Paraspinal Muscles Contract during the Schroth Exercise Treatment in Patients with Adolescent Idiopathic Scoliosis (AIS)?

The Schroth exercise can train the paraspinal muscles of patients with adolescent idiopathic scoliosis (AIS), however, muscle performance during the training remains unknown. This study applied surface electromyography (sEMG) to investigate the paraspinal muscle activities before, during and after Schroth exercise in nine AIS patients. This study found that after the Schroth exercise, the paraspinal muscle symmetry index (PMSI) was significantly reduced (PMSI = 1.3), while symmetry exercise significantly lowered the PMSI (PMSI = 0.93 and 0.75), and asymmetric exercise significantly increased the PMSI (PMSI = 2.56 and 1.52) compared to relax standing (PMSI = 1.36) in participants (p < 0.05). Among the four exercises, the PMSI of on all fours (exercise 1) and kneeling on one side (exercise 3) was the most and the least close to 1, respectively. The highest root mean square (RMS) of sEMG at the concave and convex side was observed in squatting on the bar (exercise 2) and sitting with side bending (exercise 4), respectively. This study observed that the asymmetric and symmetric exercise induced more sEMG activity on the convex and concave side, respectively, and weight bearing exercise activated more paraspinal muscle contractions on both sides of the scoliotic curve in the included AIS patients. A larger patient sample size needs to be investigated in the future to validate the current observations.

Endometriosis of the sciatic nerve masquerading as lumbar spondylosis in a 40-year-old Chinese woman.

A 40-year-old Chinese woman presented with a 4-year history of lower back pain and left lower leg sciatica. The patient had previously tried different modalities of treatments, including massage, acupuncture, ultrasound, alternative Bowen therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), all of which only provided temporary relief. On presentation to a tertiary hospital, careful and comprehensive history taking found that the sciatica pattern of pain always coincided with menstruation. An MRI identified a thickened left sciatic nerve, with surgery confirming sciatic nerve endometriosis. The case highlights the importance of comprehensive history taking in accurately diagnosing a rare aetiology of sciatica with subsequent prompt surgical intervention to avoid severe disability as well as follow-up treatment to prevent recurrence.

Safe level for harvesting for ulnar and median nerve transfers: a microanatomical and histological study.

In selective ulnar and median nerve transfers, donor nerve fascicles should be harvested in an area where motor and sensory fascicles are intermingled to minimize motor or sensory deficits. We aimed to define such an area for ulnar and median nerve harvesting through microanatomical dissection and histology in 12 fresh adult cadaveric upper extremities. Anatomically, we studied the arrangement, localization, and histological features of fascicle groups in two nerves at eight segments of the upper arms. Histological sections were examined to confirm the findings of the anatomical dissections. We found that sensory and motor fascicles were mixed proximally to the third most distal segment of the ulnar nerve and to the fourth most distal segment of the median nerve. We conclude that harvesting a part of the ulnar or median nerve proximal to these levels minimizes donor nerve deficits.

Comparison between direct repair and human acellular nerve allografting during contralateral C7 transfer to the upper trunk for restoration of shoulder abduction and elbow flexion.

Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system; meaningful recovery was defined as M3-M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restoration of shoulder abduction and elbow flexion. Thus, if direct coaptation is not possible, use of acellular nerve allografts is a suitable option. This study was approved by the Medical Ethical Committee of the First Affiliated Hospital of Sun Yat-sen University, China (Application ID: [2017] 290) on November 14, 2017.

Contralateral C7 transfer combined with acellular nerve allografts seeded with differentiated adipose stem cells for repairing upper brachial plexus injury in rats.

Nerve grafting has always been necessary when the contralateral C7 nerve root is transferred to treat brachial plexus injury. Acellular nerve allograft is a promising alternative for the treatment of nerve defects, and results were improved by grafts laden with differentiated adipose stem cells. However, use of these tissue-engineered nerve grafts has not been reported for the treatment of brachial plexus injury. The aim of the present study was to evaluate the outcome of acellular nerve allografts seeded with differentiated adipose stem cells to improve nerve regeneration in a rat model in which the contralateral C7 nerve was transferred to repair an upper brachial plexus injury. Differentiated adipose stem cells were obtained from Sprague-Dawley rats and transdifferentiated into a Schwann cell-like phenotype. Acellular nerve allografts were prepared from 15-mm bilateral sections of rat sciatic nerves. Rats were randomly divided into three groups: acellular nerve allograft, acellular nerve allograft + differentiated adipose stem cells, and autograft. The upper brachial plexus injury model was established by traction applied away from the intervertebral foramen with micro-hemostat forceps. Acellular nerve allografts with or without seeded cells were used to bridge the gap between the contralateral C7 nerve root and C5-6 nerve. Histological staining, electrophysiology, and neurological function tests were used to evaluate the effect of nerve repair 16 weeks after surgery. Results showed that the onset of discernible functional recovery occurred earlier in the autograft group first, followed by the acellular nerve allograft + differentiated adipose stem cells group, and then the acellular nerve allograft group; moreover, there was a significant difference between autograft and acellular nerve allograft groups. Compared with the acellular nerve allograft group, compound muscle action potential, motor conduction velocity, positivity for neurofilament and S100, diameter of regenerating axons, myelin sheath thickness, and density of myelinated fibers were remarkably increased in autograft and acellular nerve allograft + differentiated adipose stem cells groups. These findings confirm that acellular nerve allografts seeded with differentiated adipose stem cells effectively promoted nerve repair after brachial plexus injuries, and the effect was better than that of acellular nerve repair alone. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University of China (approval No. 2016-150) in June 2016.

Construction of tissue-engineered lymphatic vessel using human adipose derived stem cells differentiated lymphatic endothelial like cells and decellularized arterial scaffold: A preliminary study.

We have previously demonstrated that human adipose-derived stem cells (hADSCs) can be differentiated into lymphatic endothelial like cells. The purpose of this study was to investigate the feasibility of utilizing the induced lymphatic endothelial like cells and decellularized arterial scaffold to construct the tissue-engineered lymphatic vessel. The hADSCs were isolated from adipose tissue in healthy adults and were characterized the multilineage differentiation potential. Decellularized arterial scaffold was prepared using the Triton x-100 method. ADSCs were differentiated into lymphatic-like endothelial cells, and the induced cells were then seeded onto the decellularized arterial scaffold to engineer the lymphatic vessel. The histological analyses were performed to examine the endothelialized construct. The decellularized arterial scaffold was successfully obtained and was able to maintain its vessel morphology. The isolated ADSCs can be differentiated into osteocytes and adipocytes. After seeding onto the scaffold, the seeded cells attached and grew well on the decellularized arterial scaffold. Our preliminary results demonstrated that the induced lymphatic endothelial like cells combined with decellularized arterial scaffold could be utilized to successfully engineer the lymphatic vessel. Our findings may be helpful for the development of tissue-engineering of the lymphatic graft.

Clinical significance of expression of proliferating cell nuclear antigen and E-cadherin in gastric carcinoma.

AIM: to investigate the expression of proliferating cell nuclear antigen (PCNA) and E-cadherin in gastric carcinoma and to analyze their clinical significance. METHODS: A total of 146 patients were selected for this study, including 38 patients with intestinal metaplasia, 42 with dysplasia, and 66 with primary gastric cancer. In addition, 40 patients with normal gastric tissues were selected as controls. The expression of PCNA and E-cadherin was detected by immunohistochemistry. Differences in PCNA and the E-cadherin labeling indexes among normal gastric mucosa, intestinal metaplasia, dysplasia, and gastric carcinoma were compared. Subjects with normal gastric tissues were assigned to a normal group, while gastric cancer patients were assigned to a gastric cancer group. The difference in PCNA and E-cadherin expression between these two groups was compared. The relationship between expression of PCNA and E-cadherin and clinicopathological features was also explored in gastric cancer patients. Furthermore, prognosis-related factors, as well as the expression of PCNA and E-cadherin, were analyzed in patients with gastric cancer to determine the 3-year survival of these patients. RESULTS: The difference in PCNA and the E-cadherin labeling indexes among normal gastric mucosa, intestinal metaplasia, dysplasia, and gastric carcinoma was statistically significant (P < 0.05). During the transition of normal gastric mucosa to gastric cancer, the PCNA labeling index gradually increased, while the E-cadherin labeling index gradually decreased (P < 0.05). The PCNA labeling index was significantly higher and the E-cadherin labeling index was significantly lower in gastric cancer than in dysplasia (P < 0.05). The expression of PCNA was significantly higher in the gastric cancer group than in the normal group, but E-cadherin was weaker (P < 0.05). There was a negative correlation between the expression of PCNA and E-cadherin in gastric carcinoma (r = -0.741, P = 0.000). PCNA expression differed significantly between gastric cancer patients with and without lymph node metastasis and between patients at different T stages. E-cadherin expression also differed significantly between gastric cancer patients with and without lymph node metastasis (P < 0.05). High T stage and positive PCNA expression were risk factors for the prognosis of patients with gastric cancer (RR > 1), while the positive expression of E-cadherin was a protective factor (RR < 1). The sensitivity, specificity, and accuracy of PCNA positivity in predicting the 3-year survival of patients with gastric cancer were 93.33%, 38.89%, and 0.64, respectively; while these values for E-cadherin negativity were 80.0%, 41.67%, and 0.59, respectively. When PCNA positivity and E-cadherin negativity were combined, the sensitivity, specificity, and accuracy were 66.67%, 66.67%, and 0.67, respectively. CONCLUSION: Combined detection of PCNA and E-cadherin can improve the accuracy of assessing the prognosis of patients with gastric cancer.

Diagnostic Value and Surgical Implications of the 3D DW-SSFP MRI On the Management of Patients with Brachial Plexus Injuries.

Three-dimensional diffusion-weighted steady-state free precession (3D DW-SSFP) of high-resolution magnetic resonance has emerged as a promising method to visualize the peripheral nerves. In this study, the application value of 3D DW-SSFP brachial plexus imaging in the diagnosis of brachial plexus injury (BPI) was investigated. 33 patients with BPI were prospectively examined using 3D DW-SSFP MR neurography (MRN) of brachial plexus. Results of 3D DW-SSFP MRN were compared with intraoperative findings and measurements of electromyogram (EMG) or somatosensory evoked potentials (SEP) for each injured nerve root. 3D DW-SSFP MRN of brachial plexus has enabled good visualization of the small components of the brachial plexus. The postganglionic section of the brachial plexus was clearly visible in 26 patients, while the preganglionic section of the brachial plexus was clearly visible in 22 patients. Pseudomeningoceles were commonly observed in 23 patients. Others finding of MRN of brachial plexus included spinal cord offset (in 16 patients) and spinal cord deformation (in 6 patients). As for the 3D DW-SSFP MRN diagnosis of preganglionic BPI, the sensitivity, the specificity and the accuracy were respectively 96.8%, 90.29%, and 94.18%. 3D DW-SSFP MRN of brachial plexus improve visualization of brachial plexus and benefit to determine the extent of injury.

A High-Density Genetic Linkage Map for Cucumber (Cucumis sativus L.): Based on Specific Length Amplified Fragment (SLAF) Sequencing and QTL Analysis of Fruit Traits in Cucumber.

High-density genetic linkage map plays an important role in genome assembly and quantitative trait loci (QTL) fine mapping. Since the coming of next-generation sequencing, makes the structure of high-density linkage maps much more convenient and practical, which simplifies SNP discovery and high-throughput genotyping. In this research, a high-density linkage map of cucumber was structured using specific length amplified fragment sequencing, using 153 F2 populations of S1000 × S1002. The high-density genetic map composed 3,057 SLAFs, including 4,475 SNP markers on seven chromosomes, and spanned 1061.19 cM. The average genetic distance is 0.35 cM. Based on this high-density genome map, QTL analysis was performed on two cucumber fruit traits, fruit length and fruit diameter. There are 15 QTLs for the two fruit traits were detected.

Neurotization of free gracilis transfer with the brachialis branch of the musculocutaneous nerve to restore finger and thumb flexion in lower trunk brachial plexus injury: an anatomical study and case report.

OBJECTIVE: To investigate the feasibility of using free gracilis muscle transfer along with the brachialis muscle branch of the musculocutaneous nerve to restore finger and thumb flexion in lower trunk brachial plexus injury according to an anatomical study and a case report. METHODS: Thirty formalin-fixed upper extremities from 15 adult cadavers were used in this study. The distance from the point at which the brachialis muscle branch of the musculocutaneous nerve originates to the midpoint of the humeral condylar was measured, as well as the length, diameter, course and branch type of the brachialis muscle branch of the musculocutaneous nerve. An 18-year-old male who sustained an injury to the left brachial plexus underwent free gracilis transfer using the brachialis muscle branch of the musculocutaneous nerve as the donor nerve to restore finger and thumb flexion. Elbow flexion power and hand grip strength were recorded according to British Medical Research Council standards. Postoperative measures of the total active motion of the fingers were obtained monthly. RESULTS: The mean length and diameter of the brachialis muscle branch of the musculocutaneous nerve were 52.66±6.45 and 1.39±0.09 mm, respectively, and three branching types were observed. For the patient, the first gracilis contraction occurred during the 4th month. A noticeable improvement was observed in digit flexion one year later; the muscle power was M4, and the total active motion of the fingers was 209°. CONCLUSIONS: Repairing injury to the lower trunk of the brachial plexus by transferring the brachialis muscle branch of the musculocutaneous nerve to the anterior branch of the obturator nerve using a tension-free direct suture is technically feasible, and the clinical outcome was satisfactory in a single surgical patient.

Neurotization of free gracilis transfer with the brachialis branch of the musculocutaneous nerve to restore finger and thumb flexion in lower trunk brachial plexus injury: an anatomical study and case report

OBJECTIVE: To investigate the feasibility of using free gracilis muscle transfer along with the brachialis muscle branch of the musculocutaneous nerve to restore finger and thumb flexion in lower trunk brachial plexus injury according to an anatomical study and a case report. METHODS: Thirty formalin-fixed upper extremities from 15 adult cadavers were used in this study. The distance from the point at which the brachialis muscle branch of the musculocutaneous nerve originates to the midpoint of the humeral condylar was measured, as well as the length, diameter, course and branch type of the brachialis muscle branch of the musculocutaneous nerve. An 18-year-old male who sustained an injury to the left brachial plexus underwent free gracilis transfer using the brachialis muscle branch of the musculocutaneous nerve as the donor nerve to restore finger and thumb flexion. Elbow flexion power and hand grip strength were recorded according to British Medical Research Council standards. Postoperative measures of the total active motion of the fingers were obtained monthly. RESULTS: The mean length and diameter of the brachialis muscle branch of the musculocutaneous nerve were 52.66±6.45 and 1.39±0.09 mm, respectively, and three branching types were observed. For the patient, the first gracilis contraction occurred during the 4th month. A noticeable improvement was observed in digit flexion one year later; the muscle power was M4, and the total active motion of the fingers was 209°. CONCLUSIONS: Repairing injury to the lower trunk of the brachial plexus by transferring the brachialis muscle branch of the musculocutaneous nerve to the anterior branch of the obturator nerve using a tension-free direct suture is technically feasible, and the clinical outcome was satisfactory in a single surgical patient.

Functioning free gracilis transfer to reconstruct elbow flexion and quality of life in global brachial plexus injured patients.

In the study, the functional recovery and relative comprehensive quality of life of cases of global brachial plexus treated with free functioning muscle transfers were investigated. Patients who received functioning gracilis muscle transfer between August 1999 and October 2014 to reconstruct elbow flexion, wrist and fingers extension were recruited. The mean age of the patients was 26.36 (range, 16-42) years. The mean period of time from gracilis transfer to the last follow-up was 54.5 months (range, 12-185 months). Muscle power, active range of motion of the elbow flexion, wrist extension, and total active fingers extension were recorded. SDS, SAS and DASH questionnaires were given to estimate patients' quality of life. 35.71% reported good elbow flexion and 50.00% reported excellent elbow flexion. The average ROM of the elbow flexion was 106.5° (range, 0-142°) and was 17.00° (range, 0-72°) for wrist extension. The average DASH score was 51.14 (range, 17.5-90.8). The prevalence of anxiety and depression were 42.86% and 45.24%. Thrombosis and bowstringing were the most common short and long-term complications. Based on these findings, free gracilis transfer using accessory nerve as donor nerve is a satisfactory treatment to reconstruct the elbow flexion and wrist extension in global-brachial-plexus-injured patients.

Donor-side morbidity after contralateral C-7 nerve transfer: results at a minimum of 6 months after surgery.

OBJECT Donor-side morbidity associated with contralateral C-7 (CC7) nerve transfer remains controversial. The purpose of this study was to evaluate functional deficits in the donor limb resulting from prespinal route CC7 nerve transfer. METHODS A total of 63 patients were included. Forty-one patients had undergone CC7 nerve transfer surgery at least 6 months previously and were assigned to one of 2 groups based on the duration of postoperative follow-up. Group 1 (n = 21) consisted of patients who had undergone surgery between 6 months and 2 years previously, and Group 2 (n = 20) consisted of patients who had undergone surgery more than 2 years previously. An additional 22 patients who underwent CC7 nerve transfer surgery later than those in Groups 1 and 2 were included as a control group (Group 3). Results of preoperative testing in these patients and postoperative testing in Groups 1 and 2 were compared. Testing included subjective assessments and objective examinations. An additional 3 patients had undergone surgery more than 6 months previously but had severe motor weakness and were therefore evaluated separately; these 3 patients were not included in any of the study groups. RESULTS The revised Short-Form McGill Pain Questionnaire (SF-MPQ-2) was the only subjective test that showed a significant difference between Group 3 and the other 2 groups, while no significant differences were found in objective sensory, motor, or dexterity outcomes. The interval from injury to surgery for patients with a normal SF-MPQ-2 score in Groups 1 and 2 was significantly less than for those with abnormal SF-MFQ-2 scores (2.4 ± 1.1 months vs 4.6 ± 2.9 months, p = 0.002). The 3 patients with obvious motor weakness showed a tendency to gradually recover. CONCLUSIONS Although some patients suffered from long-term sensory disturbances, resection of the C-7 nerve had little effect on the function of the donor limb. Shortening preoperative delay time can improve sensory recovery of the donor limb.

Microanatomy of the Separable Length of the C7.

OBJECTIVE: The objective of this study was to provide anatomical data on modified contralateral C7 (cC7) nerve root transfers by dissecting and measuring the separable lengths of the C7 root, trunk, and divisions. MATERIALS AND METHODS: Fifteen adult cervicothoracic specimens were dissected and measured using Vernier calipers after exposing the brachial plexus. Measurements included the length of the C7 from the root to the trunk, the lengths of the C7 root-trunk-anterior division (and posterior division). The epineuria at the C7 root-division-cord junctions were opened until the internal nerve bundles fused together and could not be separated by microdissection. The lengths of the C7 root-trunk-anterior (and posterior) division were measured again after microdissection. The lengths of cC7 nerve of 20 patients with bracial plexus avulsion were measured using the former technique. RESULTS: The length of the C7 root-trunk was 45.87 SD 10.43 mm. Before separation, the lengths of the C7 root-trunk-anterior division and the root-trunk-posterior division were 61.14 SD 13.44 and 54.63 SD 11.35 mm, respectively; after separation, the lengths were 74.67 SD 12.86 and 68.73 SD 11.86 mm, respectively. The prolonged lengths were 13.15 SD 4.26 and 14.21 SD 6.98 mm, respectively. The prolonged lengths were significantly greater (p < 0.05). The prolonged length of C7 nerve clinically was anterior division, 15.30 SD 3.76 mm and posterior division, 11.10 SD 3.01 mm. CONCLUSION: The C7 division lengths can be prolonged by dissecting the epineuria at the division-cord junction of the C7 nerve root.

Diagnostic accuracy of three sensory tests for diagnosis of sensory disturbances.

BACKGROUND: Clinical diagnosis of sensory disturbances is extremely challenging, partly because the utility of sensory tests is questionable. Transection of C7 nerve root provides an objective assessment model to determine the diagnostic accuracy of sensory tests. The purpose of this study was to investigate the diagnostic accuracy of Semmes-Weinstein Monofilaments (SWM; Sammons Preston, Bolingbrook, IL), static two-point discrimination (s2PD), and current perception threshold (CPT) tests in patients with contralateral C7 nerve root transfer. METHODS: The contralateral index finger of patients was tested preoperatively and 6 weeks postoperatively, including the Revised Short-Form McGill Pain Questionnaire (SF-MPQ-2), SWM, s2PD, and CPT tests. The SF-MPQ-2 was used as a gold standard for sensory disturbances. RESULTS: A total of 38 patients were included in the study. The likelihood probability ratio of SWM and CPT tests generated small shifts in probability, whereas the s2PD test did not show any capacity to detect sensory disturbances. The areas under the curves (AUC) for SWM and CPT tests were 0.724 and 0.697, respectively. Based on different positive test standards, the AUCs for s2PD (≥ 6 mm) and s2PD (≥ 7 mm) tests were 0.632 and 0.658, respectively. When CPT and SWM tests were combined as a measure, the AUC increased to 0.763. CONCLUSION: The SWM and CPT tests show a small capacity to detect sensory disturbances, whereas the s2PD test does not show any diagnostic capacity. To better understand sensory disturbances, a comprehensive testing protocol including valid measures of physical impairment and symptom-specific measurement tools should be adopted.