Risk factors of immune checkpoint inhibitor-related pneumonitis after neoadjuvant immunochemotherapy for resectable NSCLC.

BACKGROUND: The incidence of checkpoint inhibitor-associated pneumonitis (CIP) in advanced non-small cell lung cancer (NSCLC) has been substantiated through large-scale clinical trials or real-world studies. However, reports on CIP incidence within the context of neoadjuvant immunotherapy for resectable NSCLC remain scarce. This study endeavors to investigate the incidence, risk factors, and outcomes of CIP in patients with resectable NSCLC receiving neoadjuvant immunochemotherapy. METHODS: A retrospective, case-control study was conducted on patients diagnosed with NSCLC stages IIA-IIIB who received neoadjuvant immunochemotherapy between January 2018 and September 2022. Patients were stratified into two groups based on the presence or absence of CIP, facilitating a comparative analysis of clinical characteristics, treatment modalities, physiological indicators, and prognostic outcomes . RESULTS: The study cohort comprised 245 patients, with 11.4% (28/245) experiencing CIP. The median period of CIP onset was 70 (range, 40-221) days. The incidence of severe CIP (grade 3-4) was 3.7% (9/245). Patients with CIP showed a higher all-cause mortality rate of 21.4% (6/28) compared to that of patients without CIP. Those who developed CIP exhibited elevated body mass index (BMI) values (p = 0.028) and increased fibrinogen (FIB) levels (p < 0.001), alongside a significant decrease in both diffusing capacity for carbon monoxide (DLCO)% pred (p = 0.001) and DLCO/VA% pred (p = 0.021) after neoadjuvant therapy compared to pre-indicators. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve of three assessed variables (FIB levels, BMI, DLCO) reached 0.806 in predicting CIP occurrence at an early stage. CONCLUSIONS: This cohort demonstrated that elevated BMI, increased FIB levels, and decreased pulmonary diffusion function after neoadjuvant therapy are risk factors of CIP occurrence. Early assessment and continuous monitoring of these indicators are imperative for the predictive identification of CIP, enhancing patient management and outcomes.

Coracoid Process Fractures of the Scapula Treated by Baseplate Three-Column Glenoid Fixation: A Retrospective Study of 24 Patients.

BACKGROUND This retrospective study from a single center aimed to evaluate 24 patients with coracoid process fractures of the scapula treated by baseplate three-column glenoid fixation of the 3 columns attached to the glenoid, or the scapula-glenoid construct, which includes the base of the coracoid, the scapular spine, and the lateral/scapular pillar. MATERIAL AND METHODS Twenty-four patients with 24 coracoid process fractures were treated from March 2018 to August 2020 in our hospital; 11 cases were treated with the modified technique and 13 with the conventional technique. The patients had comparable screw length, bone union time, fracture reduction, and Constant-Murley shoulder outcome scores. The significant differences between variables were tested using the t test and Fisher's exact test, while bone union and reduction position were confirmed with X-ray and CT scans. The average follow-up time was 12 months. RESULTS The mean Constant-Murley shoulder outcome score and fracture reduction did not differ significantly (P>0.05), and all patients returned to their previous occupations and levels of activity, with no loss of reduction or surgical revision at the last follow-up. Bone union time for the modified group was longer than that of the conventional group (P<0.05). However, 1 patient had a screw broken at 5 months from heavy manual labor and showed delayed union at 8 months. The lengths of the coracoid process screws in the modified group were longer than in the conventional group (P<0.01). CONCLUSIONS The findings from this retrospective study showed that baseplate three-column glenoid fixation of the coracoid process was a good surgical option for coracoid process fractures.

Effect of Ionic and Non-Ionic Surfactants on the Pasting Characteristics and Digestive Properties of Regular and Frozen Starch for Oral Delivery.

Starch is an ideal wall material for controlled release in oral delivery systems due to its non-allergic properties, availability, and cheap price. However, because of its poor mechanical behavior and high water permeability, it is necessary to modify the amphiphilic nature of starch. Surfactants are essential components to emulsify the lyophobic food ingredients. However, the interaction of starch with emulsifiers and how they affect the pasting behavior and digestion of starch are not well understood. In this paper, surfactants, such as non-ionic Tween (TW) and ionic sodium fatty acid (NaFA), with varying hydrophobic carbon chain lengths, were selected as model amphiphiles to investigate the structural, pasting, rheological properties and in vitro digestibility of regular and frozen starch samples. The results showed that, in most cases, the addition of TW reduced the viscosity of starch. However, saturated medium-chain NaFA increased the starch viscosity and rheological modulus greatly. Both surfactants inhibited starch digestion. This paper presents a comparative investigation on the effect of ionic and non-ionic surfactant on the structure and properties of corn starch, and therefore the information is useful for structural-based formulation with starch for developing colloidal delivery systems. It is also helpful for developing functional food with controllable digestion properties.

Rib fracture detection system based on deep learning.

Rib fracture detection is time-consuming and demanding work for radiologists. This study aimed to introduce a novel rib fracture detection system based on deep learning which can help radiologists to diagnose rib fractures in chest computer tomography (CT) images conveniently and accurately. A total of 1707 patients were included in this study from a single center. We developed a novel rib fracture detection system on chest CT using a three-step algorithm. According to the examination time, 1507, 100 and 100 patients were allocated to the training set, the validation set and the testing set, respectively. Free Response ROC analysis was performed to evaluate the sensitivity and false positivity of the deep learning algorithm. Precision, recall, F1-score, negative predictive value (NPV) and detection and diagnosis were selected as evaluation metrics to compare the diagnostic efficiency of this system with radiologists. The radiologist-only study was used as a benchmark and the radiologist-model collaboration study was evaluated to assess the model's clinical applicability. A total of 50,170,399 blocks (fracture blocks, 91,574; normal blocks, 50,078,825) were labelled for training. The F1-score of the Rib Fracture Detection System was 0.890 and the precision, recall and NPV values were 0.869, 0.913 and 0.969, respectively. By interacting with this detection system, the F1-score of the junior and the experienced radiologists had improved from 0.796 to 0.925 and 0.889 to 0.970, respectively; the recall scores had increased from 0.693 to 0.920 and 0.853 to 0.972, respectively. On average, the diagnosis time of radiologist assisted with this detection system was reduced by 65.3 s. The constructed Rib Fracture Detection System has a comparable performance with the experienced radiologist and is readily available to automatically detect rib fracture in the clinical setting with high efficacy, which could reduce diagnosis time and radiologists' workload in the clinical practice.

A Radiomic Approach to Access Tumor Immune Status by CD8+TRMs on Surgically Resected Non-Small-Cell Lung Cancer.

PURPOSE: Immunotherapy has made breakthroughs in the treatment of non-small-cell lung cancer (NSCLC); however, only a subset of patients achieved long-term survival, so it is of great importance to find a biomarker of lung cancer thus guide immunotherapy. Studies have shown that the infiltration level of tissue resident memory CD8+ T cells (CD8+ TRMs) is positively correlated with lung cancer prognosis and can be an ideal biomarker for assessing the tumor local immune status. We screened the radiomic features associated with CD8+ TRMs as targets in NSCLC surgical specimens by radiomic approaches, and established a radiomic predictive model to assess the local immune status, which may provide a scientific reference for lung cancer treatment strategies. PATIENTS AND METHODS: We retrospectively analyzed the NSCLC surgical specimens immune cell database and extracted CD8+ TRMs cell data, preoperative CT scan data were achieved. A total of 97 patients containing complete preoperative data were included, radiomic features were extracted from the preoperative CT image data. All the patients were divided into two groups, namely high-CD8+ TRMs infiltrated group and low-CD8+ TRMs infiltrated group, based on the proportion of CD8+ TRMs cells subset in the immune cell population. The most valuable radiomic features and semantic features were extracted and selected, and a neural network model was established to predict the level of CD8+ TRMs cell infiltration level to assess the tumor local immune status. RESULTS: The NSCLC tumor immune status predictive model was built to discriminate high- from low-CD8+ TRMs with an area under the curve (AUC) of 0.788 (95% CI) in the training set and 0.753 (95% CI) in the validation set. CONCLUSION: The radiomic models using CT image data showed a good predictive performance for accessing NSCLC immune status thus has great potential for personalized therapeutic decision making.

Treatment of Central Nervous System Relapse in Acute Promyelocytic Leukemia by Venetoclax: A Case Report.

Extramedullary relapse of acute promyelocytic leukemia is a rare phenomenon and is associated with a poor prognosis, with the central nervous system being the most common site of relapse. The current treatments are still limited. Venetoclax, a selective inhibitor of BCL2, is a small molecule that can cross the blood-brain barrier and shows a potential efficacy in the treatment of chronic lymphocytic leukemia with central nervous system involvement. Although venetoclax has also been used in the treatment of acute myeloid leukemia in recent years, there are no reports of its use in the treatment of central nervous system relapse in acute promyelocytic leukemia. Here, we report a case of central nervous system relapse in acute promyelocytic leukemia that achieved complete remission after oral treatment with venetoclax. The presence of venetoclax in the patient's CSF was confirmed by testing CSF and plasma by mass spectrometry. The concentration of venetoclax in CSF was approximately 1/300 of that in plasma trough concentration. The treatment experience in this case demonstrates the potential ability of venetoclax to treat of central nervous system relapse/involvement in acute promyelocytic leukemia, thus providing a new treatment option for this kind of patient.

Dynamic monitor of CT scan within short interval in invasive pulmonary aspergillosis for nonneutropenic patients: a retrospective analysis in two centers.

BACKGROUND: In nonneutropenic patients with underlying respiratory diseases (URD), invasive pulmonary aspergillosis (IPA) is a life-threatening disease. Yet establishing early diagnosis in those patients remains quite a challenge. METHODS: A retrospective series of nonneutropenic patients with probable or proven IPA were reviewed from January 2014 to May 2018 in Department of Respiratory Medicine of two Chinese hospitals. Those patients were suspected of IPA and underwent lung computed tomography (CT) scans twice within 5-21 days. The items required for IPA diagnosis were assessed by their host factors, mycological findings and CT scans according to the European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria (EORTC/MSG criteria). RESULTS: Together with the risk factors, mycological findings and nonspecific radiological signs on first CT, ten patients were suspected of IPA. With the appearance of cavities on second CT scan in the following days, all patients met the criteria of probable or possible IPA. Except one patient who refused antifungal treatment, nine patients received timely antifungal treatment and recovered well. One of the nine treated IPA cases was further confirmed by pathology, one was confirmed by biopsy. CONCLUSIONS: Dynamic monitor of CT scan provided specific image evidences for IPA diagnosis. This novel finding might provide a noninvasive and efficient strategy in IPA diagnosis with URD.

Quantitative and semi-quantitative CT assessments of lung lesion burden in COVID-19 pneumonia.

This study aimed to clarify and provide clinical evidence for which computed tomography (CT) assessment method can more appropriately reflect lung lesion burden of the COVID-19 pneumonia. A total of 244 COVID-19 patients were recruited from three local hospitals. All the patients were assigned to mild, common and severe types. Semi-quantitative assessment methods, e.g., lobar-, segmental-based CT scores and opacity-weighted score, and quantitative assessment method, i.e., lesion volume quantification, were applied to quantify the lung lesions. All four assessment methods had high inter-rater agreements. At the group level, the lesion load in severe type patients was consistently observed to be significantly higher than that in common type in the applications of four assessment methods (all the p < 0.001). In discriminating severe from common patients at the individual level, results for lobe-based, segment-based and opacity-weighted assessments had high true positives while the quantitative lesion volume had high true negatives. In conclusion, both semi-quantitative and quantitative methods have excellent repeatability in measuring inflammatory lesions, and can well distinguish between common type and severe type patients. Lobe-based CT score is fast, readily clinically available, and has a high sensitivity in identifying severe type patients. It is suggested to be a prioritized method for assessing the burden of lung lesions in COVID-19 patients.

Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review).

Matrix metalloproteinase 2 (MMP2) is a well­characterized protein that is indispensable for extracellular matrix remodeling and other pathological processes, such as tumor progression and skeletal dysplasia. Excessive activation of MMP2 promotes osteolytic metastasis and bone destruction in late­stage cancers, while its loss­of­function mutations result in the decreased bone mineralization and generalized osteolysis occurring progressively in skeletal developmental disorders, particularly in multicentric osteolysis, nodulosis and arthropathy (MONA). Either upregulation or downregulation of MMP2 activity can result in the same osteolytic effects. Thus, different functions of MMP2 have been recently identified that could explain this observation. While MMP2 can degrade bone matrix, facilitate osteoclastogenesis and amplify various signaling pathways that enhance osteolysis in bone metastasis, its role in maintaining the number of bone cells, supporting osteocytic canalicular network formation and suppressing leptin­mediated inhibition of bone formation has been implicated in osteolytic disorders caused by MMP2 deficiency. Furthermore, the proangiogenic activity of MMP2 is one of the potential mechanisms that are associated with both pathological situations. In the present article, the latest research on MMP2 in bone homeostasis is reviewed and the mechanisms underlying the role of this protein in skeletal metastasis and developmental osteolysis are discussed.

Efficacy of Pyrotinib in a Heavily Pretreated Patient with Lung Adenocarcinoma Harboring HER2 Amplification and Exon 20 Insertions: A Case Report.

The clinical benefits of HER2 inhibitors in patients with non-small cell lung cancer (NSCLC) have been limited. There is a paucity of effective therapies in NSCLC after developing resistance to initial anti-HER2 therapy. Herein, we presented the clinical benefit of pyrotinib in a 53-year-old patient with advanced lung adenocarcinoma whose circulating tumor DNA (ctDNA) analysis of pleural effusion revealed the coexistence of HER2 exon 20 p.Y772_A775dup (mutation ratio: 38.86%) and HER2 amplification (copy number: 4.5) following failures of multiple therapies including afatinib and ado-trastuzumab emtansine (T-DM1). Notably, pyrotinib treatment induced rapid and marked improvement of clinical symptoms, and partial response was observed after 8 weeks. CtDNA monitoring during the treatment showed that the mutation ratio of HER2 decreased to 7.99%, and the amplification disappeared. The patient achieved a progression-free survival of 7.5 months after treatment with pyrotinib. Thus, pyrotinib may be a new treatment strategy for the subgroup of lung adenocarcinoma patients, with coexistence of HER2 exon 20 p.Y772_A775dup and HER2 amplification even after failures of multiple anti-HER2 therapies. It also indicated the value of capture-based next-generation sequencing to monitor and guide therapy.

Modified algorithm for managing postoperative osteomyelitis following fracture fixation with Cierny-Mader type.

BACKGROUND: No standardized protocol has been suggested in the treatment of postoperative osteomyelitis following fracture fixation. Our team evaluates the clinical efficacy of the modified algorithm for managing postoperative osteomyelitis following fracture fixation with Cierny-Mader type. METHODS: Ninety-five wounds were reviewed from March 2009 to February 2016 in our hospital. Sixty-one wounds were treated by the modified algorithm as follows: stable hardware + bone not healed Cierny-Mader 1 type = remove hardware, temporary stabilize; stable hardware + bone not healed Cierny-Mader 2 type = retain hardware ; stable hardware + bone not healed Cierny-Mader for type 3 and type 4 = remove hardware, temporary stabilize/Ilizarov technique; unstable hardware + bone not healed = remove hardware, temporary stabilize/Ilizarov technique; and stable hardware + bone healed = remove hardware. Thirty-four wounds were treated by the conventional algorithm. Autodermoplasty, flap transfer, myocutaneous flap, and other methods including antibiotic irrigation and drug delivery system were used in wound repair. RESULTS: The patients treated with modified algorithm had a significantly reduced recurrence (P < 0.01) and increased results of negative bacterial cultures (P < 0.01); however, a decrease in the number of retained hardware cases was observed (P < 0.05). For those treated with tissue reconstruction, there was no significance (P > 0.05) compared with the conventional group. CONCLUSIONS: The modified algorithm for the postoperative osteomyelitis following fracture fixation according to the stability of the hardware and Cierny-Mader type represents a good clinical efficacy in the management of postoperative osteomyelitis. This procedure is simple and shows promising results; more clinical evidence is needed to confirm the existing findings and optimize the treatment of postoperative osteomyelitis following fracture fixation.

A 60-Year-Old Man With Right Lung Mass Presents With Cough.

CASE PRESENTATION: A 60-year-old Chinese man was admitted to our hospital with chronic cough for > 2 months. His cough was paroxysmal and nonirritating, occasionally productive with some small amounts of white phlegm. He had had a low-grade fever for half a month. There were no night sweats, joint swelling on limbs, pain, rash, or any other discomfort. The patient denied weight loss and decreased appetite.

Primary thoracic neuroblastoma in an adult: A rare case report.

RATIONALE: Neuroblastoma is one of the most common malignant tumors in childhood, which mainly occurs in adrenal glands and peripheral sympathetic nerve system. Neuroblastoma occurring in adulthood is rare, and adults with neuroblastoma arising from thorax are exceedingly rare. A case of neuroblastoma that originated from thorax was reported, and was treated by resection operation. PATIENT CONCERNS: A 46-year-old woman was admitted to our hospital with left side chest pain for 5 days. Laboratory examinations were all normal. Chest computerized tomogram (CT) showed a lesion with clear boundary that was located at the left dorsal pleura. The nature of the mass was heterogeneous, showing slight heterogeneous enhancement after contrast and there was no obvious necrosis. DIAGNOSES: Based on the morphologic and immunohistochemical features, the tumor diagnosis was favorable for neuroblastoma. INTERVENTIONS: A resection operation was carried out. OUTCOMES: Three years postoperative, no sign of recurrence or metastasis has been observed. LESSONS: Primary neuroblastoma in adulthood is rare and has poor prognosis. Resection can be an important treatment option, and combining with other methods like chemotherapy, stem cell transplantation, the survival rate may be improved.

Angiosarcoma originating in the anterior mediastinum: A case report.

RATIONALE: Angiosarcomas are malignant vascular tumors, and angiosarcoma occurring in the anterior mediastinum is rare. Here we report a case of angiosarcoma that originated in the anterior mediastinum treated with surgery, followed by radiotherapy and synchronous chemotherapy. PATIENT CONCERNS: A 56-year-old female was admitted to our hospital with chest pain for 3 days. Chest computerized tomogram (CT) examination showed a heterogeneous mass in the anterior superior mediastinum, and after injection of contrast agent, the mass showed obvious heterogeneous enhancement. Magnetic resonance imaging (MRI) with T1 weighted image (T1WI) showed isointensity and T2 weighted image (T2WI) showed heterogeneous signal intensity, the mass showed an obvious heterogeneously enhancement after intravenous administration of contrast material. DIAGNOSIS AND INTERVENTIONS: Surgical resection operation was carried out. According to its morphologic and immunohistochemic feature of tumor cells which expressing CD31, CD34, and ERG, the tumor was categorized as an angiosarcoma. After operation, the patient received radiotherapy and synchronous chemotherapy. OUTCOMES: At present, 8 months postoperatively, no signs of recurrence have been observed. LESSONS: Although angiosarcoma in anterior mediastinum is rare, when a mass located in this area, a more careful immunohistological analysis should be performed to avoid overlooking the presence of angiosarcoma.

Immunomodulatory properties of graphene oxide for osteogenesis and angiogenesis.

BACKGROUND: The osteo-immunomodulatory properties of biomaterials play an important role in the outcomes of bone regeneration. Graphene oxide (GO) has been widely applied in many research fields due to its unique properties. However, the immunomodulatory properties of GO as a biomaterial for bone tissue engineering are still unclear. MATERIALS AND METHODS: In this study, we evaluated the Inflammatory response of RAW264.7 cells influenced by GO. Then the osteogenic differentiation of BMSCs, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) by stimulation with GO/RAW 264.7-conditioned culture medium were accessed. We also further investi gated the possible mechanisms underlying the osteo- and angio-immunomodulatory effects of GO. RESULTS: Our results showed that GO stimulates the secretion of oncostatin M, tumor necrosis factor alpha and other factors through the nuclear factor-κB pathway. GO/RAW264.7-conditioned medium promoted the osteogenic differentiation of BMSCs, stimulated upregulation of the HUVECs of vascular-related receptors, and promoted their tube formation in vitro. CONCLUSION: In conclusion, our research shows that GO, as a biomaterial, can induce the formation of a beneficial osteo-immunomodulatory environment and is a promising biomaterial for bone tissue engineering.

Performance of the fiber-optic low-coherent ground settlement sensor: From lab to field.

A fiber-optic low-coherent interferometry sensor was developed to measure the ground settlement (GS) in an accuracy of the micrometer. The sensor combined optical techniques with liquid-contained chambers that were hydraulically connected together at the bottom by using a water-filled tube. The liquid surface inside each chamber was at the same level initially. The optical interferometry was employed to read out the liquid level changes, which following the GS happened at the place where the chamber was put on and, thereby, the GS information was calculated. The laboratory effort had demonstrated its potential in the practical application. Here, the denoising algorithms on the measurement signal were carried out based on the specific environment to ensure the accuracy and stability of the system in field applications. After that, we extended this technique to the high-speed railway. The 5-days continuous measurement proved that the designed system could be applied to monitor the GS of the high-speed railway piers and approached an accuracy of ±70 µm in the field situation with a reference compensation sensor. So the performance of the sensor was suitable to the GS monitoring problem in the high-speed railway. There, the difficulties were to meet the monitoring requirement of both a large span in space and its quite tiny and slow changes.

Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing.

Fracture nonunion and delayed union continue to pose challenges for orthopedic surgeons. In the present study, we combined HMGB1 gelatin sponges with MSC sheets to promote bone healing after surgical treatment of rat tibial fractures. The HMGB1 gelatin sponge scaffolds supported the expansion of mesenchymal stem cells (MSCs) and promoted the osteogenic differentiation of MSCs and MSC sheets. Lentiviral vectors were then used to overexpress HMGB1 in MSCs. The results indicated that HMGB1 promotes the osteogenic differentiation of MSCs through the STAT3 pathway. Both siRNA and a STAT3 inhibitor downregulated STAT3, further confirming that HMGB1 induces the osteogenic differentiation of MSCs partly via the STAT3 signal pathway. In a rat tibial osteotomy model, we demonstrated the ability of HMGB1 gelatin sponge scaffolds to increase bone formation. The addition of MSC sheets further enhanced fracture healing. These findings support the use of HMGB1-loaded gelatin sponge scaffolds combined with MSC sheets to enhance fracture healing after surgical intervention.

[Medical imaging in tumor precision medicine: opportunities and challenges].

Tumor precision medicine is an emerging approach for tumor diagnosis, treatment and prevention, which takes account of individual variability of environment, lifestyle and genetic information. Tumor precision medicine is built up on the medical imaging innovations developed during the past decades, including the new hardware, new imaging agents, standardized protocols, image analysis and multimodal imaging fusion technology. Also the development of automated and reproducible analysis algorithm has extracted large amount of information from image-based features. With the continuous development and mining of tumor clinical and imaging databases, the radiogenomics, radiomics and artificial intelligence have been flourishing. Therefore, these new technological advances bring new opportunities and challenges to the application of imaging in tumor precision medicine.