[The efficacy and safety of ibrutinib in the treatment of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia].

Objective: To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) . Methods: Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety. Results: A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion: Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Lymphocyte-to-monocyte, platelet-to-albumin and platelet-to-lymphocyte ratios as prognostic biomarkers for neoadjuvant treatment response in rectal cancer patients.

INTRODUCTION: Systemic inflammatory response (SIR) indicators are an emerging category of serum biomarkers with significant potential as prognostic and predictive factors in various types of cancers The primary focus of our study was to determine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), platelet-to-albumin ratio (PLR) and platelet-to-albumin ratio (PAR) in evaluating the response to neoadjuvant treatment for patients with rectal cancer. MATERIALS AND METHODS: We included 99 consecutive patients with rectal cancer which were admitted for surgery in our institution after completing a standard neoadjuvant radio-chemotherapy regimen. Several hematologic parameters, including LMR, PAR and PLR, were calculated by collecting and analyzing blood samples preoperatively. Cases were divided into groups using ROC curve analysis to determine optimal cutoff values for each of the investigated parameters. Treatment response was assessed through histopathological analysis of the resected specimens. RESULTS: PLR values over 215.2 were correlated with the presence of lymph node metastasis. A similar correlation was observed between PAR values over 41.89 and lymph node positivity. A significant correlation was observed between the presence of tumor budding on histopathological analysis and high-PAR values. A statistically significant correlation between a high PLR and a good response to neoadjuvant treatment was determined. CONCLUSIONS: High PLR values may be associated with a more favorable treatment response to neoadjuvant radio-chemotherapy. A high PAR may be associated with unfavorable histopathological characteristics. Further studies on these readily available biomarkers are required in order to validate their clinical utility.

Raman Spectroscopy Investigation of Phonon Behavior in ZnO-Buffered MgB2 Tapes: Exploring Lattice Dynamics and Anharmonicity.

We investigated the phonon behavior of ZnO-buffered MgB2 tapes with varying ZnO buffer layer thicknesses using polarized Raman spectroscopy at room and cryogenic temperatures. Polar plots from integrated angle-resolved polarized Raman spectroscopy (ARPRS) at room temperature revealed substantial distortion in the boron plane geometry due to lattice mismatch among the MgB2 film, ZnO buffer layer, and Hastelloy substrate. This distortion significantly affects the electron-phonon coupling (EPC) constant, λ, which we calculated using the modified McMillan equation by Allen-Dynes in relation to the superconducting transition temperature (Tc) of the sample. At cryogenic temperatures, our investigation of the E2g mode exhibited a notable phonon hardening effect of up to ∼4.1%, correlated with the ZnO buffer layer thickness. Furthermore, analysis of the anharmonic E2g phonon mechanism through line width (full width at half maximum) revealed damping behavior, indicating an additional coupling mechanism within the sample that varies with the temperature. This unique Raman scattering behavior potentially elucidates the high Tc mechanism of MgB2, which is underestimated by traditional EPC calculations. Additionally, increasing the thickness of the ZnO layer is predicted to alleviate the distortion in the boron plane geometry, thereby promoting MgB2 toward its inherent electron-phonon superconducting nature by mitigating the additional coupling mechanisms. Understanding how the ZnO buffer layer influences the phonon dynamics and EPC in MgB2 will provide critical insights into optimizing its superconducting properties and advancing its practical applications in high-performance superconducting devices.

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

Effect of sequential vs. non-sequential early enteral nutrition therapy on nutritional status, recovery, and quality of life of patients with esophageal cancer.

OBJECTIVE: To study the effects of early sequential enteral nutrition (ESEN) therapy and early non-sequential enteral nutrition (EN) therapy on the nutritional status, recovery, and quality of life of patients who undergo postoperative chemotherapy for esophageal cancer. PATIENTS AND METHODS: The data of 90 patients who underwent postoperative chemotherapy for esophageal cancer in Gansu Provincial Cancer Hospital from January 2018 to June 2020 were analyzed retrospectively. Patients were divided the Test group and the Control group (n=45 each) based on the method of nutritional support. Patients in the Control group were treated with non-sequential early enteral nutrition and the Test group treated with sequential early enteral nutrition until the discharge. Nutritional status, recovery, and quality of life of the chemotherapy patients in the two groups were compared. RESULTS: After the intervention, the pre-protein, albumin and hemoglobin levels were higher in the Test group than in the control group (p<0.05). Postoperative exhaustion, incision healing and length of hospital stay were significantly lower in the Test group than in the Control group (p<0.05), while the scores on all dimensions of the short-form 36 health survey scale (SF-36) and the total score were higher than in the Control group (p<0.05). CONCLUSIONS: Sequential early enteral nutrition may be used for patients who undergo chemotherapy after esophageal cancer surgery to promote their early recovery and improve their quality of life and nutritional status.

[Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells].

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Mutational landscape of SWI/SNF complex genes reveal correlation to predictive biomarkers for immunotherapy sensitivity in lung adenocarcinoma patients.

BACKGROUND: The search for prognostic biomarkers indicating sensitivity to immunotherapy in lung adenocarcinoma patients has zeroed in on genes in the switch/sucrose non-fermentable (SWI/SNF) pathway. The mutational profiles of key genes are not clearly defined, however, and no comparisons have been conducted on whether mutations in the genes involved provide the same predictive value. METHODS: In this study, analysis of clinical factors, tumor mutation burden (TMB), chromosomal instability, and co-alterations was conducted for 4344 lung adenocarcinoma samples. Independent online cohorts (N = 1661 and 576) were used to supplement the analysis with survival and RNA-seq data. RESULTS: Mutational burden and chromosomal instability analysis showed that ARID family mutations (including ARID1A, ARID1B, or ARID2 mutations) and SMARC family mutations (including SMARCA4 or SMARCB1 mutations) display different profiles from wild-type (WT) samples (TMB: ARID versus WT: P < 2.2 × 10-16, SMARC versus WT: P < 2.2 × 10-16; CIN: ARID versus WT: P = 1.8 × 10-5, SMARC versus WT: P = 0.027). Both mutant groups have a higher proportion of transversions than transitions, whereas the ratio is more equal for wild-type samples. Survival analysis shows that patients with ARID mutations were more sensitive to immunotherapy treatment than wild-type and SMARC-mutated patients (P < 0.001 and P = 0.013, respectively), and multivariate Cox analysis reveals that the presence of ARID mutations is likely the main cause. CONCLUSIONS: The research presented in this study shows that mutations in the ARID gene family, including ARID1A, ARID1B, and ARID2, are primarily responsible for the sensitive response to immunotherapy treatment in patients with lung adenocarcinoma.

The effectiveness of a dedicated central venous access care team to prevent catheter-related bloodstream infection in a private hospital.

Objective: We hypothesized a dedicated team would decrease catheter-related bloodstream infection (CRBSI) rates. Method: We implemented a before-after study. Results: CRBSI frequency (39/103 vs. 28/105, P=0.084) and incidence (36.61/1000 vs. 26.1/1000 catheter-days, P=0.175) were lower in the intervention arm. Conclusion: The intervention delayed median time to CRBSI, but was insufficient to decrease overall rates.

[Large B-cell lymphoma with IRF4 rearrangement: six case reports and a literature review].

Objective: To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed. Results: ①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity (n=five cases) and no starry sky pattern (n=6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions: LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity's pathogenesis, treatment options, and long-term prognosis still need to be explored further.

[Efficacy and prognosis of newly diagnosed multiple myeloma patients treated with bortezomib, lenalidomide and dexamethasone].

Objective: To evaluate the efficacy of VRD (bortezomib+lenalidomide+dexamethasone) in newly diagnosed multiple myeloma (NDMM) patients as well as the effect of the regimen on the long-term prognosis. Methods: The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of patients with NDMM at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed. Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation (ASCT) of patients. Results: A total of 87 patients were retrospectively analyzed. The age[M(Q1,Q3)] of all patients was 56 (51, 61) years and males and females accounted for 58.6% (51/87) and 41.4% (36/87), respectively. The overall response rate (ORR) was 95.9% (71/74) after 2 courses of induction therapy, with 13.5% (10/74) achieving the deep response [complete response (CR) or better] and 51.3% (38/74) of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2% (60/63), and the proportions of the deep response and VGPR or better grew up to 46.0% (29/63) and 77.7% (49/63). According to the treatment, the patients (≤65 years old) were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% (32/36) of patients in the transplantation group achieved VGPR or better, and 55.5% (20/36) reached the deep response. After the transplantation, the proportion increased to 97.1% (34/35) and 77.2% (27/35), respectively(88.8% vs 97.1%,P=0.174;55.5% vs 77.2%,P=0.055), with the rate of undetectable MRD increasing from 44.4% (16/36) to 77.8% (28/36) (P=0.004). In the non-transplantation group, 74.2% (23/31) of patients achieved VGPR or better after 4 courses of induction therapy, 35.5% (11/31) of the patients achieved deep response and the rate of undetectable MRD was 37.0% (10/27). Compared with the non-transplantation group, transplantation was associated with a higher rate of complete response (89.5% vs 53.1%, P<0.001) and a lower rate of MRD detection(78.4% vs 55.2%, P=0.045). The median follow-up time of all patients was 26.3 months (20.8, 33.8). The median progression-free survival and overall survival were not reached. The three-year PFS and OS rates were 78.4% and 87.2%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS. Conclusions: VRD regimen has a promising efficacy and results in a substantial survival benefit. ASCT after VRD induction therapy is associated with higher rate of deep response, higher rate of undetectable MRD and longer survival.

[Clinical characteristics and prognosis of 46 patients with macrofocal multiple myeloma].

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population (P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls (P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients (P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively (P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).

A retrospective review of infections and outcomes within 100 days of hematopoietic stem cell transplantation: insights from a new transplant program in the Philippines.

Background: Few hematopoietic stem cell transplantations (HSCT) are performed in lower-middle income countries. Only four institutions in the Philippines are able to perform transplants. This study describes the experience of a newly established program. Methods: The charts of all adult patients who underwent HSCT at The Medical City from May 1, 2016 to December 31, 2019 were reviewed retrospectively. Results: A total of 33 patients were included in the cohort, of whom 31 (93.9%) underwent autologous HSCT and only two (6.1%) underwent allogeneic HSCT. Most were female (21/33, 63%), and median age was 51 years (range 21-67 years). The primary indication for transplantation was multiple myeloma (n = 21), followed by diffuse B-cell lymphoma (n = 6). Fifteen of the 33 patients had a history of treated tuberculosis (TB) disease (n = 4) or latent TB infection (n = 11). The median time for neutrophil recovery was 7.4 days (range 4-13 days). Transplant complications included neutropenic fever (n = 33, 100%) and mucositis (n = 14, 42.4%). Bacterial infection was documented in 12 (36.4%) patients, with nine (24.2%) developing a bacterial blood stream infection of which seven were related to a central line. The overall mortality rate was at 6.1% (2/33) in the first 30 days post-transplant, with no additional mortality in the succeeding days until day 100. Conclusions: This cohort with mostly autologous HSCT had favorable outcomes in the first 100 days. Rates of bacterial infection were high in the early post-transplant period. Latent TB infection was common, but no reactivation was observed. Longer-term follow-up of patients is needed to determine late post-transplant complications and outcomes.

[Research advances on the techniques for diagnosing burn wound depth].

The accurate diagnosis of burn wound depth is particularly important for evaluating the disease prognosis of burn patients. In the past, the diagnosis of burn wound depth often relied on the subjective judgment of doctors. With the continuous development of diagnostic technology, the methods for judging the depth of burn wound have also been updated. This paper mainly summarizes the research progress in the applications of indocyanine green angiography, laser Doppler imaging, laser speckle contrast imaging, and artificial intelligence in the diagnosis of burn wound depth, and compares the advantages and disadvantages of these techniques, so as to provide ideas for accurate diagnosis of burn wound depth.