Volume 102 ·  Issue 13 ·  2022

Osteoporotic fracture is fundamentally different from traumatic fracture. It is a pathological fracture based on the skeletal system in the state of osteoporosis, and the essence of its lesion is the decline of bone strength. Bone strength is influenced by a variety of factors, including the material properties and tissue structure of the bone, as well as muscle load. The pathological changes of osteoporotic fracture both of the damage of bone mass and bone quality. After the occurrence of osteoporotic fracture, even successful surgical treatment cannot prevent the further aggravation of osteoporotic bone damage. In this paper, the material properties and tissue structure damage of osteoporotic fractures are elaborated, and it is emphasized to clarify and pay attention to these bone lesions and their risks. Anti-osteoporosis treatment is of great importance to improve the clinical efficacy of osteoporosis and fracture intervention and prevent the occurrence of re-fractures.

Cortical bone track screw (CBT) is an emerging technology in recent years. Compared with traditional transpedicular screw internal fixation, CBT internal fixation has the advantages of short operation duration, small exposure range of soft tissue, low blood loss, good biomechanical stability and quick recovery of patients, etc. It has been widely used in the treatment of various lumbar degenerative diseases. At present, there are still many controversies about its preoperative evaluation method, key surgical technique, complication prevention and treatment, and postoperative follow-up in clinic, which leads to some doctors' unclear grasp of the indications and contraindications of this technique. In order to standardize the application of CBT technology, the lumbar spine research group of Spinal Cord Professional Committee of Chinese Rehabilitation Medicine Association took the lead and formulated this consensus through the improved Delphi survey method, in order to provide a reference for the standardized development and promotion of CBT technology in clinic.

To explore the effect of F-box and WD-40 domain protein 7 (FBXW7) gene mutation on the prognosis of immunotherapy in patients with non-small cell lung cancer (NSCLC).

(1) The clinical data of 125 patients with advanced NSCLC in the First Affiliated Hospital of Nanjing Medical University from January 2019 to June 2021 were collected. There were 70 males and 55 females, with a median age [M (Q₁, Q₃)] of 64(57, 70) years. The correlation of FBXW7 mutation with immunotherapy efficacy and prognosis was analyzed. (2) The Data set of NSCLC patients treated with immunotherapy from cBioPortal database was downloaded. A total of 261 patients were included as immunotherapy group. There were 120 males and 141 females, with a median age of 66(57, 73) years. The association of FBXW7 mutation with clinical characteristics and prognosis of NSCLC patients was investigated. (3) The data of patients with NSCLC from the cancer genome atlas (TCGA) database were downloaded. A total of 1 030 patients were included as TCGA group. There were 633 males and 397 females, with a median age of 67(60, 73) years. The effect of FBXW7 mutation on the efficacy of immunotherapy was analyzed. The key molecules and their biological functions were also determined

Among the 125 NSCLC patients, the FBXW7 mutation rate was 5.6% (7/125). All FBXW7 mutation types was truncating mutation. In these FBXW7 mutation patients who received immunotherapy, 4 had partial response, 2 had stable disease, and 1 had progressive disease. The objective response rate (ORR) and disease control rate (DCR) were 4/7 and 6/7, respectively. The median progression-free survival (PFS) was 13.0 months (95%CI: 7.0-22.0 months) for patients with FBXW7 mutation and 4.0 months (95%CI: 2.0-11.5 months) for patients with FBXW7 wild type, with a statistically significant difference (P=0.046). The bioinformatics analysis indicated that patients with FBXW7 mutation have higher clinical benefits from immunotherapy. Moreover, patients with FBXW7 mutation in immunotherapy group had higher tumor mutational burden (TMB) [M (Q₁, Q₃): 17.8 (11.5, 29.3)/Mb] than those with FBXW7 wild type [5.7 (3.0, 10.4)/Mb, P=0.001]. The TMB of patients with FBXW7 mutation in TCGA group was 15.9 (4.2, 28.1)/Mb, insertion-deletion (Indel) neoantigen was 192.5 (70.8, 535.0) and single nucleotide variant (SNV) neoantigen was 363.0 (194.8, 534.8), which were significantly higher than those of patients with FBXW7 wild type [5.6 (3.2, 8.9)/Mb, 53.0 (12.0, 131.0), 83.5 (34.0, 178.0), respectively] (P=0.002, P=0.008, P<0.001). The results indicated that FBXW7 mutated tumors had stronger immunogenicity, which might generate anti-tumor immunity. FBXW7 mutation was also related to the activation of T cells (T lymphocyte receptor complexes and signaling). In addition, FBXW7 mutation was correlated with increased infiltration of CD8⁺T cells and M1 macrophages. CD8⁺T cells and M1 macrophages infiltration level was significantly up-regulated in FBXW7 mutation group than wild-type group [10% (8%, 14%) vs 7%(4%, 12%), P=0.049; 8%(4%, 11%) vs 4%(1%, 8%), P=0.046].

NSCLC patients with FBXW7 mutant have higher clinical benefits from immunotherapy. FBXW7 mutation has the potential as a predictive marker for the efficacy of immunotherapy in NSCLC patients.

To explore the efficacy and prognostic factors of immunotherapy in advanced non-small cell lung cancer (NSCLC) patients with different driver gene mutations.

Medical records of advanced NSCLC patients who harbored driver gene mutations (EGFR, KRAS, ALK and etc.) and received PD-1 inhibitors in Henan Cancer Hospital from April 2016 to May 2021 were collected. Treatment patterns, progression free survival (PFS), overall survival (OS) and prognostic factors of patients with driver gene mutations were estimated.

A total of 120 patients were included. There were 70 males and 50 females, with a median age [M(Q₁,Q₃)] of 57 (50, 65) years. Of these, 52 patients harbored KRAS mutations, 42 patients harbored EGFR mutations, 16 patients harbored ERBB2 mutations, 5 patients harbored MET mutations or amplifications, 5 patients harbored ROS-1 mutations, 2 patients harbored BRAF mutations, and the last 2 patients harbored ALK and RET mutations, respectively. The PFS and OS [M (95%CI)] were 6.4 (5.1-7.8) and 31.2 (22.0-40.3) months in 120 participated patients. Patients with KRAS mutations showed the greatest survival benefit from Immune checkpoint inhibitors (ICIs) with the PFS of 9.7 (4.8-14.6) months and OS of 31.2 (19.4-50.6) months. They mostly received the first-line (34.6%, 18/52) and second-line (38.5%, 20/52) ICIs. The PFS and OS of EGFR mutant patients were 3.9 (1.8-6.1) months and 18.0 (12.1-23.8) months, respectively. They tended to receive ICIs after resistance to EGFR-tyrosine kinase inhibitors (TKIs), and the proportion of second-, third-, fourth or further-line drugs was 38.1% (16/42), 11.9% (5/42), and 47.6% (20/42), respectively. PD-L1 expression level (negative vs ≥50% positive: HR=3.710, 95%CI: 1.372-10.031, P=0.010; 1%-49% positive vs ≥50% positive: HR=2.738, 95%CI: 0.841-8.912, P=0.094), age (every additional year: HR=0.957, 95%CI: 0.933-0.982, P=0.001) and different driver mutations status (EGFR vs KRAS: HR=2.676, 95%CI: 1.317-5.436, P=0.006; ERBB2 vs KRAS: HR=3.411, 95%CI: 1.493-7.792, P=0.004; other mutations vs KRAS: HR=0.727, 95%CI: 0.322-1.643, P=0.444) were prognostic factors for PFS. While PD-L1 expression level (negative vs ≥50% positive: HR=2.305, 95%CI: 0.748-7.103, P=0.146; 1%-49% positive vs ≥50% positive: HR=1.286, 95%CI: 0.337-4.913, P=0.713), and treatment lines of ICIs (first-line vs ≥ third-line: HR=0.322, 95%CI: 0.114-0.914, P=0.033; second-line vs ≥ third-line: HR=0.375, 95%CI: 0.178-0.789, P=0.010) were prognostic factors for OS.

KRAS mutant NSCLC patients mostly receive ICIs at the front line, and have best survival benefits from immunotherapy. While EGFR mutant NSCLC patients tend to receive ICIs at the back line, and obtain reasonable survival benefits. PD-L1 expression level, age, and different driver mutations status are prognostic factors for PFS, and PD-L1 expression level and treatment lines of ICIs are prognostic factors for OS.

To investigate the efficacy and safety of anti-vascular drug anlotinib in combination with stereotactic radiosurgery (SRS) for the treatment of brain metastases from non-small cell lung cancer (NSCLC).

A total of 46 patients diagnosed with NSCLC brain metastases and treated with SRS in Peking University Third Hospital were included from October 2017 to June 2019. Of these, 21 patients (33 lesions) received anlotinib combined with SRS (combined treatment group), while 25 patients (35 lesions) only received SRS (SRS-alone group). The data of combined treatment group and SRS-alone group were compared, including remission rate of intracranial hypertension, response rate (RR) of local control of intracranial lesions, incidence of radiation-induced brain necrosis and intracranial progression-free survival (iPFS). The medication and adverse reactions of anlotinib in the combined treatment group were recorded.

The remission rate of intracranial hypertension in the combined treatment group was 71.4% (15/21), which was significantly higher than that in the SRS-alone group [12.0% (3/25), P<0.001). However, the RR of combined treatment group and SRS-alone group was 80.9% (17/21) and 60.0% (15/25), respectively, with no statistically significant difference (P=0.289). The incidence of radiation-induced brain necrosis in the combined treatment group was 3.0% (1/33), which was significantly lower than that in the SRS-alone group [20.0% (7/35), P=0.030]. The iPFS of the combination treatment group was (13.9±2.4) months, which was significantly longer than that in the SRS-alone group [(11.4±1.8) months, P<0.001]. The medication time of anlotinib in the combined treatment group was 6 (6, 18) weeks. One patient developed grade Ⅰ hypertension and one patient developed grade Ⅰ hand-foot syndrome. The incidence of drug-related adverse reactions was 9.5% (2/21).

Anlotinib in combination with SRS may relieve brain edema, reduce the rate of radiation-induced brain necrosis, and the rate of drug-related adverse reactions were low.

To investigate the relationship between the levels of exosomes in bronchoalveolar lavage fluid (BALF) and plasma and the severity of lung injury and its outcome in patients with acute respiratory distress syndrome (ARDS).

Patients who were admitted to the Department of Critical Care Medicine, Zhongda Hospital Affiliated to Southeast University and received invasive mechanical ventilation were selected from August 2020 to April 2021, and they were divided into ARDS group and non-ARDS group. Finally, 33 ARDS patients were included, including 18 males and 15 females, aged (65.5±15.5) years; 10 non-ARDS patients, 8 males and 2 females, aged (57.2±15.3) years. The BALF and plasma of the two groups of patients were collected within 24 hours after enrollment, and the total exosomes of the samples were collected by ultracentrifugation. Nanoparticle tracking analysis (NTA) was used to detect and compare the differences in exosome content between the two groups. Correlation of content with the severity and prognosis of lung injury in ARDS patients.

There was no significant difference in gender and age between ARDS group and non-ARDS group (both P>0.05). The exosome in plasma of ARDS group was significantly higher than that of non-ARDS group [(25.3±1.2)/ml vs (24.2±1.6)/ml, P=0.031], while the exosomes in BALF of ARDS group was also higher than that of non-ARDS group [(26.5±1.6)/ml vs (24.6±1.1)/ml, P=0.001]. The exosomes in BALF of patients with ARDS caused by intrapulmonary causes was higher than that in ARDS group caused by extrapulmonary causes [(26.9±1.5)/ml vs (25.2±0.9)/ml, P=0.01], and the infection caused by bacterial shows that the highest exosome level in BALF. The exosomes in the BALF of the mild ARDS group was significantly lower than that of the severe ARDS group [(25.7±1.3)/ml vs (27.2±1.5)/ml, P=0.038]; the exosomes in BALF of ARDS patients was negatively correlated with P/F ratio (r=-0.38, P=0.03); and it was positively correlated with Murray lung injury score (r=0.47, P=0.01). However, the static compliance levels, length of hospital stay, duration of mechanical ventilation, and 28-day outcome were not associated with the exosomes in BALF.

Compared with non-ARDS patients, ARDS patients have significantly higher levels of exosomes in BALF and plasma, there is a certain correlation between exosomes derived from BALF and the severity of lung injury in ARDS.

To investigate the clinical manifestations, treatment characteristics and outcomes of myasthenia gravis (MG) dually positive for anti-acetylcholine receptor antibody (AChR-Ab) and anti-muscle-specific tyrosine kinase antibody (MuSK-Ab).

MG patients hospitalized in the First Affiliated Hospital of Sun Yat-sen University from August 2017 to November 2020 were retrospectively collected. Thirty-four MuSK-Ab positive MG (MuSK-MG) patients, 11 double-antibodies positive MG (DP-MG) patients, and 80 AChR-Ab positive MG (AChR-MG) patients were included and allocated to three different groups. The clinical data of patients in the three groups were collected, and the differences of demographic characteristics, clinical manifestations and treatment outcomes between DP-MG patients and AChR-MG and MuSK-MG patients were analyzed.

The proportion of female and male patients in DP-MG group was 7/11 and 4/11 respectively, and the onset age of DP-MG was (41±27) years.The difference in gender distribution between DP-MG and AChR-MG groups was statistically significant (P<0.05). The proportion of extraocular muscle involvement in the DP-MG and MuSK-MG groups (8/11 and 52.9%) was lower than that in the AChR-MG group (83.8%), and the difference was statistically significant (P<0.05). The incidence of myasthenia crisis in DP-MG and MuSK-MG groups (54.5% and 61.8%) were higher than that in AChR-MG group (20.0%), with astatistically significant difference(P<0.05). The positive rate of neostigmine test in DP-MG and MuSK-MG groups(8/11 and 74.2%) were lower than that of AChR-MG group (96.8%), and the positive rate of low frequency repetitive nerve stimulation (RNS) in DP-MG group (5/10) was lower than that in AChR-MG group (85.1%), with statistically significant differences (all P<0.05). MuSK-Ab titer was positively correlated with the course of disease (r=0.466, P<0.05), and antibody titer decreased after symptom improvement (P<0.05). The response of patients in DP-MG and MuSK-MG groups to cholinesterase inhibitors (2/11 and 9.1%) was worse than that in the AChR-MG group (66.3%), and the incidence of side effects in the two groups (5/11 and 39.4%) was higher than that in the AChR-MG group (15.0%), with statistically significant differences (all P<0.05). There were 4 DP-MG patients underwent thymectomy, and the pathological results detected two cases of thymoma and two cases of thymic hyperplasia. Subsequent follow-up showed that 5 (5/11) DP-MG patients achieved minimal manifestation status or better status.

The gender distribution, age of onset, pharmacological characteristics and electrophysiological examination of DP-MG patients were similar to those of MuSK-MG patients, but the severity of DP-MG patients was between that of AChR-MG and MuSK-MG patients.

To explore the diagnostic value of third ventricle width (TVW) measured by transcranial ultrasound (TCS) in the clinical diagnosis of Alzheimer′s disease (AD) by analyzing and comparing the image characteristics of TVW in AD patients and healthy controls, and its correlation with cranial magnetic resonance medial temporal lobe atrophy (MTA) visual score and neuropsychological characteristics.

TCS examination, MTA score and neuropsychological tests were performed in 39 confirmed AD and 41 normal controls from the Second Affiliated Hospital of Soochow University between January and July 2021. The correlation of TVW with MTA score and neuropsychological characteristics was analyzed and compared between the two groups.

A total of thirty-nine AD patients were enrolled, with 28 males and 11 females, aged (73±9) years, including 18 mild, 20 moderate, and 1 severe AD patient. Meanwhile, 41 healthy controls were also included, with 24 males and 17 females, aged (69±6) years old. TVW in AD patients was significantly wider than that in normal controls [0.76(0.66, 0.87) cm vs 0.50(0.44, 0.56) cm, P<0.001]. In neuropsychological tests, compared with normal controls, AD patients showed impaired performances in several cognitive functions, and there were statistically significant differences in delayed memory [0(0, 0) vs 4.0(4.0, 5.0), P<0.001], naming [2.0(1.0, 3.0) vs 3.0(2.0, 3.0), P<0.001], executive function [2.0(2.0, 3.0) vs 3.0(2.5, 3.0), P<0.001], language [0.0(0.0, 2.0) vs 3.0(2.0, 3.0), P<0.001] and other aspects between AD patients and normal controls (all P<0.05). TVW was negatively correlated with immediate memory (r=-0.339, P=0.035), delayed recall (r=-0.523, P<0.001), attention and computing power (r=-0.409, P=0.045), visual space and executive function (r=-0.333, P=0.039), but positively correlated with the atrophy of the medial temporal lobe (r= 0.552, P<0.001).

TCS can be used to measure TVW in AD patients. When combined with MTA score and neuropsychological tests, it can provide a reliable objective basis for the clinical diagnosis of AD.

To investigate the feasibility of multi-slice spiral CT(MSCT) imaging features of gastric stromal tumor (GST) in predicting pathological NIH risk classification, providing imaging basis for patients with GST before treatment.

The clinical and CT imaging data of 504 patients(506 GST lesions), 259males and 245 females, aged from 13 to 85(60±11) years, with GST confirmed by surgery and pathology collected in the Zhongshan Hospital Affiliated to Fudan University and the Affiliated TCM Hospital of Southwest Medical University. According to pathological NIH risk classification, 506 lesions were divided into low risk group (very low and low risk degree, 277 lesions) and high risk group (medium and high risk degree, 229 lesions).Clinical data and imaging characteristics were compared between two groups. Multivariate logistic regression analysis was performed to screen out independent risk factors for statistically significant imaging indicators. Receiver operating curve (ROC) was used to evaluate the predictive value of tumor length for risk classification.

Between low risk group and high risk group,there were significant differences in gender(male/female:131/146 vs 129/100), gastrointestinal bleeding(present/absent:39/238 vs 59/170), morphology(regular/Irregular:218/59 vs 95/134), calcification(present/absent:36/241 vs 53/176), degree of necrosis(0°/Ⅰ°/Ⅱ°/Ⅲ°:197/61/16/3 vs 58/98/32/41), ulceration(present/absent:32/245 vs 94/135), growth pattern(endophytic/exophytic/mixed:102/105/70 vs 44/98/87), tumor location(fundus/cardia/body/angle/antrum:98/7/135/12/25 vs 98/6/114/5/6), feeding artery(present/absent:32/245 vs 104/125), vascular enhancement(present/absent:19/258 vs 88/141), effusion of around the disease(present/absent:0/277 vs 13/216), positive sign of fat around the disease(present/absent:0/277 vs 30/199),maximum long diameter[2.82(2.04,3.80) cm vs 5.93(4.06,8.29) cm] and short diameter [2.31(1.60,2.88) cm vs 4.40(3.21,6.37) cm]of tumor(all P<0.05).The maximum long diameter of tumor (OR=2.08,95%CI:1.35-3.20) and ulceration positive(OR=2.01,95%CI:1.03-3.92) were independent risk factors of risk classification(all P<0.05).Gastric antrum was used as the reference for tumor location, gastric fundus(OR=7.77,95%CI:2.00-30.24) and gastric body(OR=3.93,95%CI:1.03-15.01) were independent risk factors of risk classification(all P<0.05).The area under curve(AUC) of the maximum long diameter of tumor for predicting risk classification was 0.87, and the optimal critical value, sensitivity and specificity were 4.98cm, 62.9% and 95.3% respectively.

MSCT image features of GST had certain characteristics. MSCT has certain predictive value for pathological NIH risk classification of GST, which can provide certain imaging basis for patients before treatment.

This paper analyzed the imaging data of intravascular papillary endothelial hyperplasia (IPEH) in 5 cases, with 1 male, 4 females, aged 28-61 years. MRI of IPEH revealed well-demarcated masses with central iso-or hypointensity and peripheral hyperintensity on T₂-weighted image(T₂WI), as well as peripheral enhancement or hyperintensity on T₂WI with/without hypointense foci, as well as homogeneous enhancement or heterogeneous enhancement with nonenhanced foci. CT demonstrated iso-or slightly hyperdense, well-circumscribed mass with bone destruction or calcification.

A total of 49 patients with cerebellopontine angle cholesteatoma from the Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University between January 2013 and January 2021 were recruited. All patients were evaluated by MRI scan before surgery and tumor resection was performed under microscope via retrosigmoid sinus approach. Then residual tumor was searched with 0°and 30°neuroendoscopy, and tumor resection was performed.Residual tumors were foundand resectedin 38 cases under theneuroendoscopy after routine microsurgery.Total and subtotalresections were performed in 44 cases and 5 cases, respectively. Complications included aseptic meningitis (n=8), cerebrospinal fluid leakage (n=1) and intracranial hematoma (n=2). Follow-up[42±3(6-72)months] was available in all patients. During follow-up, 45 cases (91.8%) had a Kar-nofsky Performance Status (KPS)score ≥80.Neuroendoscopy-assisted microsurgery for cerebellopontine angle cholesteatomas helps enhance the total resection rate and decrease the operative risk.

Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancer patients. The development of targeted drugs for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) fusion gene-positive populations, the most common driver genes in the occurrence and development of NSCLC, has significantly improved the survival of these patients. In recent years, researchers have discovered more and more common gene mutations in NSCLC besides EGFR and ALK, such as c-ros proto-oncogene 1 (ROS1), BRAF V600E, neurotrophic factor receptor tyrosine kinase 1 (NTRK1), human epidermal growth factor receptor 2 (HER2), mesenchymal epithelial transfer factor (MET), proto-oncogene (RET), EGFR 20 exon insertion, and murine sarcoma virus oncogene (Kras) G12C mutation, etc. A variety of targeted drugs targeting these rare mutations have been developed and put into clinical application, many of which have achieved remarkable efficacy. It is recommended that patients with locally advanced or metastatic NSCLC, especially non-squamous NSCLC, should be tested for genetics that can cover uncommon mutations at the initial diagnosis, and individualized treatment strategies should be adopted for patients with uncommon mutations.

Amivantamab (JNJ-61186372) is a fully human EGFR-MET bispecific antibody with immune cell-directing activity designed to provide treatment for patients with non-small cell lung cancer (NSCLC) who have progressed after platinum-containing chemotherapy with insertion mutations in exon 20 of epidermal growth factor receptor (EGFR). A recent phase I, open-label, dose-escalating and dose-expanded "CHRYSALIS" study evaluated the efficacy, safety, and pharmacokinetics of Amivantamab in patients with advanced NSCLC. A total of 362 patients were enrolled in the CHRYSALIS study between May 2016 and June 2020. The recommended dose of 1 050 mg (1 400 mg for patients ≥80 kg) in the Phase II clinical study was determined through the dose escalation phase trial and based on safety, pharmacokinetic and pharmacodynamic data, and 81 patients (effective population) after progression of platinum-containing chemotherapy in the recommended dose group were analyzed centrallyn=81) of the study endpoint assessment. The primary study endpoints were safety and objective response rate (ORR). In terms of safety, the most common adverse reactions were rash (86%), infusion-related reactions (66%), and paronychia (45%). The incidence of grade ≥3 adverse reactions was 35%. The most common grade 3 to 4 adverse reactions were hypokalemia (5%), severe rash (4%), pulmonary embolism, diarrhea, and neutropenia. Of these, 13% of patients underwent treatment-related drug reduction, and 4% discontinued due to adverse reactions. In terms of efficacy, at the time of publication, the median follow-up time of the trial was 9.7 months, and the ORR of the effective population was 40% (32/81). Among the secondary study endpoints, median duration of response (DOR) was 11.1 months, median progression-free survival (PFS) was 8.3 months, and median overall survival (OS) was 22.8 months.

Epidermal growth factor receptor (EGFR) mutation is the most common type of driver gene mutation in non-small cell lung cancer (NSCLC), but current targeted therapy is often more targeted at the classical mutation of EGFR, namely exon 19 deletion and exon 21 L858R mutation. In addition, the third-generation EGFR targeted therapy has a targeted therapeutic effect on patients with T790M mutation. For people with non-classical/uncommon EGFR mutations, such as S768I, L861Q, G719X, etc., there are currently no standard targeted EGFR-tyrosine kinase inhibitor (TKI) treatments by authoritative institutions such as the FDA.