[Clinical analysis of cytomegalovirus infection-associated hemophagocytic lymphohistiocytosis in five patients without underlying diseases].

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.

[The development and future of sports medicine in China].

This article mainly introduces the development history and current situation of sports medicine in China, and deeply analyzes the problems that have emerged during the current development process, and proposes corresponding solutions. Based on this, the article proposes five key directions for the development of sports medicine, which are: developing arthroscopic minimally invasive techniques, ensuring the guarantee work for competitive sports, attaching great importance to the development of sports rehabilitation, vigorously carrying out exercise prescription and exercise assessment work, and emphasizing the training and education of sports medicine professionals. Finally, the article looks forward to the future development of sports medicine from three aspects: popularizing and expanding the influence of sports medicine through popular science promotion, improving the quality and safety of sports through health management and disease prevention, and achieving precise diagnosis and treatment through scientific research and innovation. It is hoped that this article will provide reference for the development of sports medicine in China.

[Analysis of clinical effect of arthroscopic release at different time in treating knee adhesion after arthroscopic surgery].

Objective: To explore the efficacy of arthroscopic release in treating postoperative knee adhesion and investigate the influence of release timing on the treatment outcomes. Methods: A total of 50 patients who accepted arthroscopic release in Peking University Third Hospital from February 2017 to December 2021 were included in the retrospective cohort. The study cohort comprised 28 men and 22 women, with a mean age of (30.8±11.9) years. All the primary surgeries were manipulated under arthroscopes. A comparison was made between pre-and postoperative range of motion (ROM), visual analog scale (VAS), International Knee Documentation Committee (IKDC) scores, and Tegner activity scale scores for the patients. According to the interval between the appearance of adhesion and arthroscopic release, the patients were divided into four groups:<3 months group (n=12), 3-6 months group (n=16),>6-12 months group (n=14), and>12 months group (n=8). Inter-group comparisons on postoperative ROM, IKDC scores, and Tegner activity scale scores and improvement values of each outcome were conducted. Results: All the patients were followed up for (36.4±19.7) months. Patients gained significant improvement in flexion, extension, IKDC scores, and Tegner scores (125.0°±20.0° vs 75.7°±27.5°, 2.3°±4.8° vs 7.4°±7.3°, 69.8±17.7 vs 51.4±12.8, 4.1±2.1 vs 2.2±1.1) (all P<0.05), while the VAS scores did not show significant improvement. There were no significant differences among different groups in postoperative extension, IKDC scores or Tegner scores, nor in their improvements. However, patients in the ≤6 months group could gain better postoperative flexion and improvement in flexion than those in the >6 months group (129.9°±20.0° vs 118.8°±17.4°, 58.6°±32.8° vs 37.3°±23.1°) (P<0.05). Conclusions: Arthroscopic release presents a great effect in treating knee adhesion after arthroscopic operation. Once the symptoms of adhesion appear and physical rehabilitation fails to improve the ROM, one should accept early surgical intervention (less than 6 months) for a better outcome.

[Primary pulmonary NUT carcinoma: a clinicopathological analysis of seven cases].

Objective: To investigate the clinicopathological characteristics of primary pulmonary NUT carcinoma. Methods: A total of 7 cases of primary pulmonary NUT carcinoma were collected from Fujian Provincial Hospital (n=5), Fuzhou Taijiang Hospital (n=1) and Binzhou City People's Hospital of Shandong Province (n=1) from January 2021 to April 2023. The clinical, histopathological, and immunohistochemical features were analyzed, and NUT rearrangement were detected by fluorescence in situ hybridization (FISH) with break-apart probes. Results: Seven cases were all male with age ranging from 32 to 73 years. The main clinical manifestations were cough, expectoration and chest tightness. Microscopically, NUT carcinoma was composed of monotonous proliferation of primitive-appearing small-to-medium round cells, with few eosinophilic cytoplasm, arranged in solid sheets, nests or clusters. Abrupt keratinization was typically observed in 4 cases (4/7), with high mitotic activities and necrosis. Immunohistochemistry (IHC) showed that the tumors were positive for NUT (7/7), CK7 (4/4), CK5/6 (5/6), p40 (6/7). Ki-67 index were 30%-80%. NUT gene segregation (7/7) was detected by FISH break probes. Conclusions: Primary pulmonary NUT carcinoma is rare and highly malignant. Diagnosis depends on histopathology and IHC, with molecular detection as an adjunct for diagnosis. Pathologists should be aware of the clinicopathological characteristics to avoid misdiagnosis.

[Myxiod pleomorphic liposarcoma: a clinicopathological and molecular genetic analysis of six cases].

Objective: To investigate the clinicopathologic and molecular genetic characteristics of myxoid pleomorphic liposarcoma (MPLPS). Methods: Six cases of MPLPS diagnosed and consulted in Fujian Provincial Hospital from 2015 to 2021 were collected for histomorphological observation, immunohistochemistry, and fluorescence in situ hybridization (FISH) detection of DDIT3 (CHOP) gene translocation and MDM2/CDK4 gene amplification. Results: There were four males and two females, aged 26-74 years (mean 53.8 years). The tumor size was 3.8-16.0 cm (mean 11.8 cm). All six cases had similar histopathologic features, showing overlapping histologic morphology of myxoid liposarcoma and pleomorphic liposarcoma. Four cases (4/6) were positive for S-100 protein, and the Ki-67 index was 50%-95%. All cases (6/6) were negative for DDIT3 (CHOP) translocation and MDM2/CDK4 amplification by FISH. TP53 (p.R248w) germline mutation was found in one case. Conclusions: MPLPS is a rare subtype of liposarcoma, characterized by overlapping morphology of myxoid liposarcoma and pleomorphic liposarcoma. Genetically, a few of them have TP53 gene germline mutations, but they lack of DDIT3 (CHOP) translocation or MDM2/CDK4 amplification.

Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma.

BACKGROUND: Implementation of adjuvant therapies in non-metastatic melanoma improved treatment outcomes in some patients; however, adjuvant therapy can be associated with significant cost and risk of toxicity. Therefore, there is an unmet need to better identify patients at high risk of recurrence. PATIENTS AND METHODS: We carried out an ultrasensitive droplet digital PCR (ddPCR)-based detection of BRAFV600E-mutated circulating tumor DNA (ctDNA) from blood samples prospectively collected before surgery, 1 hour after surgery, and then serially during follow-up. RESULTS: In 80 patients (stages ≤III), BRAFV600E mutations were detected in 47.2% of tissue, in 37.7% of ctDNA samples collected before surgery, and in 25.9% of ctDNA samples collected 1 hour after surgery. Patients with detected ctDNA in blood collected 1 hour after surgery compared to patients without detected ctDNA had higher likelihood of melanoma recurrence (P < 0.001) and shorter median disease-free survival (P = 0.001) and overall survival (P = 0.003). CONCLUSIONS: Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical blood samples from patients with resectable melanoma. Detection of ctDNA in post-surgical samples is associated with inferior treatment outcomes.

[Risk factors for leukemia transformation in patients with myelodysplastic syndromes].

Objective: To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) . Methods: From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done. Results: The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age (P<0.001) , bone marrow blast percentage (P<0.001) , bone marrow fibrosis (P=0.046) , WHO classification (P<0.001) , IPSS-R (P<0.001) and IPSS-R karyotype group (P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference (P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation (P=0.034) , DNMT3A mutation (P=0.026) , NRAS mutation (P=0.027) and NPM1 mutation (P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups (HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation (HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation (HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion: Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

[Pulmonary malignant perivascular epithelioid cell tumor mixed with lung adenocarcinoma components: a case report and literature review].

Objective: To analyze the pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of pulmonary malignant perivascular epithelioid cell tumor (PEComa) with adenocarcinoma. Methods: In August 2020, the Department of Pathology, Dongguan People's Hospital of Southern Medical University, diagnosed a case of pulmonary malignant PEComa mixed with adenocarcinoma. The clinical data, pathological diagnosis, treatment plan and prognosis of the patient were analyzed, and the literature was reviewed. Firstly, "malignant perivascular epithelioid cell tumor"+" Pulmonary "+"adenocarcinoma" was used to search CNKI and Wanfang Medical Database, but no relevant reports were found. Then, we changed the search term as "pulmonary malignant perivascular epithelioid cell tumor", and search for PubMed, Embase, Web of Science and Cochrane by combining the subject terms with "pulmonary malignant perivascular epithelioid cell tumor" and "PEComa" as subtopics. The language was Chinese or English and the search deadline was November 2020. Results: The patient, a 46-year-old male, was admitted to the hospital on August 20, 2020, due to "repeated cough and chest pain for more than 10 days, accompanied by rapid weight loss". Serology detected increased expression of lung non-small cell lung cancer related antigens. PET-CT showed a large mass of soft tissue density in the left thoracic cavity with an SUV value of 22.8. The postoperative pathological diagnosis was malignant PEComa mixed with adenocarcinoma and the lymph nodes were metastasized. Due to the detection of EGFR sensitive mutation, postoperative chemotherapy and targeted therapy were administered, and the current state was stable. A total of 12 cases of pulmonary malignant PEComa were retrieved in the literature, which were common in middle-aged and elderly people. They usually presented with cough or chest tightness. Chest CT mostly showed round masses with clear boundaries, and 8 cases had metastasis to mediastinal lymph nodes and other organs. Conclusions: Pulmonary malignant PEComa is rare. It is the first report of the same mass with lung primary adenocarcinoma. The tumor progresses rapidly. Complete surgical resection of the lesion and lymph node dissection are more appropriate treatment strategies, supplemented by postoperative chemotherapy and targeted therapy. For cases diagnosed as pulmonary PEComa, long term follow-up should be performed, even if the pathological diagnosis is benign.

PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers.

BACKGROUND: Oncogenic mutations in PIK3CA are prevalent in diverse cancers and can be targeted with inhibitors of the phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Analysis of circulating tumor DNA (ctDNA) provides a minimally invasive approach to detect clinically actionable PIK3CA mutations. PATIENTS AND METHODS: We analyzed PIK3CA hotspot mutation frequency by droplet digital PCR (QX 200; BioRad) using 16 ng of unamplified plasma-derived cell-free DNA from 68 patients with advanced solid tumors (breast cancer, n = 41; colorectal cancer, n = 13; other tumor types, n = 14). Results quantified as variant allele frequencies (VAFs) were compared with previous testing of archival tumor tissue and with patient outcomes. RESULTS: Of 68 patients, 58 (85%) had PIK3CA mutations in tumor tissue and 43 (74%) PIK3CA mutations in ctDNA with an overall concordance of 72% (49/68, κ = 0.38). In a subset analysis, which excluded samples from 26 patients known not to have disease progression at the time of sample collection, we found an overall concordance of 91% (38/42; κ = 0.74). PIK3CA-mutated ctDNA VAF of ≤8.5% (5% trimmed mean) showed a longer median survival compared with patients with a higher VAF (15.9 versus 9.4 months; 95% confidence interval 6.7-17.1 months; P = 0.014). Longitudinal analysis of ctDNA in 18 patients with serial plasma collections (range 2-22 time points, median 5) showed that those with a decrease in PIK3CA VAF had a longer time to treatment failure (TTF) compared with patients with an increase or no change (10.7 versus 2.6 months; P = 0.048). CONCLUSIONS: Detection of PIK3CA mutations in ctDNA is concordant with testing of archival tumor tissue. Low quantity of PIK3CA-mutant ctDNA is associated with longer survival and a decrease in PIK3CA-mutant ctDNA on therapy is associated with longer TTF.

[Clinical efficacy of the combined diagnosis and management for children with airway allergic diseases].

Objective: To evaluate the clinical efficacy of the combined diagnosis and management in children with airway allergic diseases(bronchial asthma, allergic rhinitis). Methods: This observational study belongs to cluster sampling cases, which included the clinical data from children with airway allergic diseases in Allergy Department and Otorhinolaryngology Department of Beijing Children's Hospital from April to December in 2015. They were followed up every three months during 12 months. All the subjects were required to continuously record daily symptom by diary card. ACT/c-ACT, VAS, treatment steps to control asthma, respiratory infections, wheeze, pulmonary function(FEV1%pred,FEV1/FVC,PEF%pred,FEF25%pred,FEF50%pred,FEF75%pred,MMEF%pred), FeNO were assessed in every visiting. The mean±standard deviation was used for the measurement data in accordance with normal distribution. Comparing the pulmonary function indexes at every point, the measurement data with normal distribution and uniform variance were analyzed by single factor analysis of variance, and the measurement data with uneven variance were tested by non-parametric rank sum test. Results: Among 147 recruited participants, 106 completed the combined diagnosis and management. The airway allergic diseases control rate was 87.7% at 12 months after the combined diagnosis and management. At every point, the average daily symptom score and VAS score which were significantly lower than at the baseline(H=35.854,P=0.000)[ 1.2(0.7,2.2),0.6(0.2,1.5),0.4(0.1,1.0),0.5(0.1,1.1) vs 2.0(1.0,3.5)],(H=39.559,P=0.000)[2.5(0.5,4.7),2.2(0.3,4.4),1.8(0.2,4.6),1.6(0.3,3.8) vs 6.9(4.1,9.8)]. ACT/c-ACT score at 3, 6, 9, 12 months were significantly higher than at the baseline (H=79.695,P=0.000) [25.0(22.5,27.0),26.0(24.0,27.0),25.0(23.0,27.0),25.0(24.0,27.0) vs 20.0(17.0,22.0)]. FEV1%pred and FEF25%pred at 3, 6 months were significantly higher than at the baseline (F=3.563,P=0.007)(104.7±12.6 vs 96.8±14.5,103.0±10.3 vs 96.8±14.5),(F=2.456,P=0.046)(96.6±22.0 vs 85.0±21.9,93.3±18.0 vs 85.0±21.9). PEF%pred at 3, 6, 9, 12 months after the combined diagnosis and management were significantly higher than at the baseline(F=5.497,P=0.000)(105.1±18.1,101.2±15.3,99.7±17.1,99.8±17.5 vs 90.3±17.8). FeNO at 3, 6, 9, 12 months respectively were no significantly differences at the baseline(F=0.751,P=0.558)(25.7±23.6 vs 30.7±25.6,25.9±16.5 vs 30.7±25.6,27.5±20.2 vs 30.7±25.6,30.6±19.6 vs 30.7±25.6).The respiratory infections rate were 69.8%(74/106),67.0%(71/106),60.4%(64/106),51.9%(55/106) at 3, 6, 9, 12 months respectively. The wheezing rate was 24.5%(26/106),14.2%(15/106),11.3%(12/106),7.5%(8/106) at 3, 6, 9, 12 months respectively. Conclusions: The combined diagnosis and management can significantly improve the control level of children's airway allergic diseases, which should be implemented in the management of children's airway allergic diseases.

[Clinicopathological features of gastric adenocarcinoma with enteroblastic differentiation: a report of twelve cases].

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED). Methods: Twelve cases of GAED diagnosed in Fujian Provincial Hospital from August 2019 to August 2020 were collected. HE staining, immunohistochemistry and HER2 gene amplification were evaluated. In addition, 343 cases of gastric adenocarcinoma diagnosed in the same period were used as the control group to compare the clinicopathological differences between them. Results: The 12 cases of GAED included 10 males and 2 females, aged 59-75 years (median 66.5 years). The main clinical manifestations were abdominal pain, melena with hematemesis; nine tumors were ulcerative and three were protuberant. The tumor diameter ranged from 1.5 to 9.5 cm (median 6.0 cm). Histologically, the tumor cells were arranged in tubular, papillary, cribriform, or adenoid structures. The cells were cuboidal to columnar, with relatively distinct cell boundaries and abundant clear or slightly eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for SALL4 (12/12), glypican-3 (9/12), AFP (5/12), CDX2 (8/12), CD10 (3/12), p53 mutated (10/12), HER2 (2/12, 3+), and both cases showed HER2 gene amplification by fluorescence in situ hybridization. Compared with common gastric adenocarcinoma, GAED showed higher rate of vascular invasion and tumor progression (P<0.05), but there were no significant differences in age, sex, degree of differentiation, nerve invasion, lymph node metastasis, pT stage, pN stage and pM stage (P>0.05). Conclusions: GAED is a rare type of gastric adenocarcinoma. Pathologically, GAED has both embryonal and intestinal phenotypes. In terms of biological behavior, it is more invasive. GAED needs to be distinguished from common gastric adenocarcinoma in clinical diagnosis.

[Clinicopathological analysis of clear cell renal cell carcinoma with hemangioblastoma component].

Objective: To investigate the clinicopathological features, differential diagnosis and molecular characteristics of clear cell renal cell carcinoma (ccRCC) with hemangioblastoma component (ccRCC-HBc). Methods: Two ccRCC-HBc cases diagnosed at Fujian Provincial Hospital in September 2015 and March 2016, respectively, were included. Their morphological, immunohistochemical and molecular features were analyzed, including fluorescence in situ hybridization (FISH) detection of TFE3, TFEB and VHL genes. Related literature was reviewed to reveal the characteristics of this tumor. Results: The two cases occurred in 2 women, aged 33 and 66 years, respectively. The maximum diameters of the tumors were 4.0 cm and 8.5 cm, respectively. Histologically, the ccRCC component, representing approximate 10%-20% of the neoplasm, while the tumor cells arranged in flaky, nested, and solid distribution. The tumor cells had conspicuous nucleoli, with rich thin-wall capillary network in the stroma. The hemangioblastoma-like component, representing approximate 60%-70% of the neoplasm, showed a rich capillary network of single-layered flat endothelial cells enclosing stromal cells. The latter cell type showed a pale or eosinophilic cytoplasm exhibiting occasional lipid droplets. Rare cell nuclei appeared enlarged, pleomorphic, or bizarre. The two components were intermingled with each other. Immunohistochemically, the tumor cells were positive for PAX8, CKpan, EMA, vimentin, CD10, RCC, CAⅨ, and P504s in ccRCC area; in another area, the tumor cells were positive for α-inhibin, CD34 and vimentin, while CD10 were weakly positive. Neither TFE3 or TFEB gene split signal was detected in the 2 cases (0/2), nor was VHL gene mutation in case 2 (0/1). Conclusion: ccRCC-HBc is an extremely rare entity of ccRCC. The diagnosis is mainly based on clinical and pathological characteristics, as well as immunohistochemistry. Molecular pathology is helpful for its differential diagnosis. The primary approach of treating ccRCC-HBc is complete surgical excision and chemotherapy. The targeted treatment is helpful if possible.