[Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: ① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype (P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points (P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ (P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively (P=0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

[Analysis of therapeutic effects of allogeneic hematopoietic stem cell transplantation in 12 patients with DEK-NUP214 fusion gene positive acute myeloid leukemia].

Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

[Analysis of tumor regression after concurrent radiochemotherapy for locally advanced hypopharyngeal carcinoma].

Objective: To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma. Methods: The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed. All patients received preoperative concurrent chemotherapy and radiotherapy. After radiochemotherapy, electronic laryngoscopy and imaging examination were performed to assess the tumor regression status. After 4 weeks, surgical resection was performed, and the specimens of the primary focus were processed as continuous pathological sections. After operation, HE staining and TdT-mediated dUTP nick-end labeling (TUNEL) method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus, and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers [signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1alpha (HIF-1α), sex determining region Y-box 2 (SOX2), and P53]. Results: A total of 44 patients were included, all of whom were male, with a mean age of (58.3±3.5) years. There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma. Twenty-nine cases were in stage T3 and 15 cases were in stage T4. There were 6 stage Ⅲ cases and 38 stage Ⅳ cases. According to the response evaluation criteria in solid tumors (RECIST), 13 patients achieved complete response (CR), 22 patients had partial response (PR), and 9 patients achieved stable disease (SD) after concurrent radiochemotherapy. The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total laryngectomy and partial hypopharyngeal resection. Twenty-three cases underwent supracricoid cartilage subtotal laryngectomy cricoid tongue fixation (CHP). Among 22 patients with PR, 10 had large PR (remission rate ≥70%) and 12 had small PR (remission rate <70%). The residual tumor was found in 30 patients (68.2%) after resection of all primary lesions by HE staining of pathological sections, of which 3 patients (3/13) with CR had residual cancer, all of which were focal residues. In large PR patients, residual cancer was detected in 6 cases (6/10), scattered in 4 cases, and focal residual in 2 cases, respectively. Large residual tumors were detected in small PR and SD patients. TUNEL method did not show any sign of apoptosis in 30 specimens with residual cancer focus, and the positive expression rate of Ki-67 was less than 10%. The expression of STAT3 (3.40±2.49 vs 5.23±3.02, t=-2.932, P=0.007) in 19 cases (63.3%) and HIF-1α (3.73±2.66 vs 6.97±3.05, t=-4.45, P<0.001) in 22 cases (73.3%) of residual cancer were significantly higher than those before radiochemotherapy. Other molecular markers showed no significant changes. All patients were followed up for 3 years. The 2-year survival rate was 59.3%, and the 3-year survival rate was 54.1%. Conclusions: Preoperative radiochemotherapy can make some patients with locally advanced hypopharyngeal carcinoma achieve complete or significant remission in clinical evaluation, but pathological detection still shows some residual cancer lesions with enhanced anti-apoptosis ability and decreased proliferation activity.

[Clinical efficacy of allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome-evolved acute myeloid leukemia].

Objective: The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored. Methods: A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored. Results: Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS (P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS (P=0.001, HR=6.981, 95%CI 2.186-22.300; P=0.010, HR=6.719, 95%CI 1.572-28.711; P=0.026, HR=3.386, 95%CI 1.158-9.901; P=0.006, HR=0.151, 95%CI 0.039-0.581) . Conclusion: For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

Risk Factors of Cardiac Complications in Pregnant Women with Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common inherited genetic cardiac disease during pregnancy. Studies of risk factors are of great significance for maternal and fetal outcomes. AIM: The aim of the study was to identify predictive risk factors for cardiac complications in pregnant women with HCM. METHODS: One hundred patients with HCM who delivered at the Shanghai obstetrical cardiology intensive care center between January 2000 and December 2022 were retrospectively reviewed. A logistic regression model was used to identify independent risk factors for cardiac complications. RESULTS: Twenty-one cases were obstructive HCM (21%), 16 with cardiac function grade I and 5 with grade II; 79 cases were non-obstructive HCM (79%), 67 with cardiac function grade I, 11 with grade II, and 1 with grade III. Ninety-one cases had abnormal electrocardiogram (ECG) (91%), mainly with ST-T changes (77%). The average interventricular septum was 19.39 ± 6.13 mm by echocardiography (21.75 ± 5.86 mm for obstructive HCM and 18.73 ± 6.08 mm for non-obstructive HCM). The main cardiac complications were maternal death (n = 2, 2%), heart failure (n = 7, 7%), and sustained ventricular tachyarrhythmia (n = 1, 1%). Cardiac complications occur commonly during the third trimester and postpartum period. Three independent risk factors to predict cardiac complications in pregnant women with HCM were obstructive HCM (P = 0.036), New York Heart Association (NYHA) class ≥II (P = 0.022), and previous history of syncope (P = 0.037). CONCLUSIONS: HCM increases the risk of maternal death, heart failure, and malignant arrhythmia. More attention should be given to risk assessment and pregnancy management. Early detection of risk factors can reduce the incidence of maternal mortality and cardiac complications.

[The current status and challenges of surgical treatment for chronic Achilles tendon rupture].

With the growing demand for physical activity, an increasing number of individuals with chronic Achilles tendon ruptures are opting for surgical intervention. Surgical approaches encompass end-to end anastomosis, tendon flap techniques, tendon transfer procedures, and free tendon grafting, among others. When selecting the appropriate surgical method and determining the surgical indications, it is imperative to consider factors like the length of the Achilles tendon defect, patient age, aesthetic preferences, functional requirements, and local tissue conditions. As medical devices evolve and surgical techniques advance, the criteria for surgical intervention are also evolving. Drawing from existing literature evidence, it becomes crucial to define reasonable parameters for addressing Achilles tendon defects with each surgical technique, aligning more closely with clinical needs. Additionally, auxiliary technologies such as biologic therapy and innovative biomaterials have demonstrated promising results in laboratory or animal models. The focal point of advancing these auxiliary technologies lies in facilitating the translation of pertinent clinical outcomes in the future.

[Comparison of the clinical efficacy of all-inside arthroscopic lateral ligament augmentation procedure and Broström procedure for the treatment of chronic lateral rotational ankle instability].

Objective: To compare the clinical efficacy of patients with chronic lateral rotational ankle instability(CLRAI) after all-inside arthroscopic lateral ligament augmentation procedure and Broström procedure. Methods: This is a retrospective cohort study. The clinical and imaging data of 106 CLRAI patients were collected at the Xuzhou Central Hospital from January 2021 to December 2022. The patients included 55 males and 51 females with an age of (32.6±8.2) years (range: 16 to 50 years). All patients were treated under all-inside arthroscopic, and were divided into Broström-Gould surgery group (n=54) and Broström surgery group (n=52) according to different ligament repair methods. At 3, 6, and 12 months after surgery, ankle inversion stress tests and anterior drawer tests were used to examine the stability of the ankle joint and observe gait. The American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle function score (KAFS) were used to assess ankle function; Tegner score was used to assess the patient's level of exercise; the foot and ankle outcome score(FAOS)(including score of symptoms,pain,function, daily living,function, sports and recreational activities (sport); quality of life (QOL) was used to assess the patient's daily activity ability. Comparisons of data were made using independent sample t test, repeated measures analysis of variance, LSD-t multiple comparison method, χ2 test or Mann-Whitney U test. Results: All operations were successfully accomplished. All incisions healed by first intention, without evidence of postoperative complications of implant rejection, ligation reaction, and nerve and vessel injury. All patients were followed up at 3, 6, and 12 months after surgery. Ankle varus stress test and anterior drawer test were negative. No evidence supporting lateral ankle instability was obtained. All patients eventually regained normal gait. No patients underwent revision surgery. Repeated measurement analysis of variance showed that AOFAS-AH, Tegner, KAFS and FAOS scores in the Brostrom-Gould group and the Brostrom group were significantly higher than those before surgery (P<0.01). The change trends of Tegner score and FAOS-sport score were significantly different between the two groups (F=18.839, P<0.01; F=8.169, P=0.005). Multiple comparisons revealed that at 3-, 6-and 12-month follow-up, the Tegner scores (3 months: 3.7±0.5 vs. 3.3±0.5, t=-3.980, P<0.01; 6 months: 4.4±0.6 vs. 3.8±0.7, t=-4.792,P<0.01; 12 months: 5.8±0.9 vs. 5.1±1.0, t=-3.889,P<0.01), sport scores (3 months: 82.5±3.7 vs. 79.3±3.8, LSD-t=-4.316, P<0.01; 6 months: 88.5±4.9 vs. 85.7±3.8, LSD-t=-3.312,P=0.001;12 months: 90.1±4.3 vs. 88.2±5.1, LSD-t=-2.112,P=0.037) in the Broström-Gould surgery group were higher than those in the Broström surgery group, with statistical significances. Conclusions: Both Broström-Gould and Broström procedures under all-inside arthroscopic can make ankle stability and improve ankle function in the treatment of CLRAI. However, the former maybe shorten the time to return to exercise and achieve higher motor function.

[Clinical analysis of 14 patients aged ≤ 50 years with high-risk multiple myeloma treated with allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young patients with high-risk multiple myeloma (HRMM) and analyzed the factors affecting patient prognosis. Methods: In this retrospective study, we analyzed the clinical data of 14 patients with HRMM with cytogenetic abnormalities or high-risk biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022. Results: There were seven males and seven females included in the study, with a median age of 39.5 (31-50) years at the time of allo-HSCT. The median number of treatment lines before transplantation was 2 (1-6) . Before allo-HSCT, 42.9% (6/14) of the patients did not achieve complete remission, while 35.7% (5/14) of the patients achieved measurable residual disease positivity. After transplantation, all patients were evaluated for their treatment response, and the overall response rate was 100% (14/14) . All 14 patients successfully underwent allo-HSCT, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute grade Ⅱ-Ⅳ graft-versus-host disease (GVHD) occurred in five patients (35.7%) , and two patients (14.3%) developed moderate-to-severe chronic GVHD. The median follow-up time after allo-HSCT was 18.93 (4.10-72.53) months, with an expected 2-year transplant-related mortality rate of 7.1% (95% CI 0%-21.1%) and an expected 2-year overall survival rate of 92.9% (95% CI 80.3%-100.0%) . Moreover, the expected 1-year and 2-year progression-free survival rates were 92.9% (95% CI 80.3%-100.0%) and 66.0% (95% CI 39.4%-100.0%) , respectively, and the 2-year cumulative incidence of relapse was 28.9% (95% CI 0%-56.7%) . Upfront allo-HSCT following complete remission after induced therapy and the presence of chronic GVHD might be favorable prognostic factors. Conclusion: allo-HSCT is an effective treatment for improving the prognosis of young patients with HRMM.