[Diagnosis and treatment understanding of Waldenström macroglobulinemia in China: a cross-sectional study].

Objective: To conduct a nationwide physician survey to better understand clinicians' disease awareness, treatment patterns, and experience of Waldenström macroglobulinemia (WM) in China. Methods: This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews. Results: The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-naïve and relapsed/refractory patients (94% for all patients, 95% for treatment-naïve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions: This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors' and patients' understanding of WM is one of the most urgent issues that must be addressed right now.

[The occurrence, precaution and treatment strategies of postoperative fecal incontinence in rectal and anal diseases].

In the surgical treatment of hemorrhoids, rectal prolapse, rectal cancer, anal fissures, or anal fistulas, inadvertent damage to the nerves or muscles responsible for bowel control may potentially lead to varying degrees of fecal incontinence (FI). Surgeons need to conduct preoperative assessments based on the patient's individual condition to select an appropriate surgical plan, aiming to minimize the incidence of postoperative FI and improve the patient's postoperative quality of life as much as possible while effectively treating the disease. Additionally, the proficiency of the surgeon's skills, appropriate preoperative dietary adjustments for the patient, regular bowel habits, and exercises targeting the pelvic floor muscles all contribute to reducing the incidence of postoperative FI in patients. For patients who have already developed FI after surgery, on the basis of suitable diet, regular bowel habits, and medication, clinical practitioners can adopt such methods as biofeedback, pelvic floor muscle exercise, sacral nerve stimulation, percutaneous tibial nerve stimulation, acupuncture, injectable bulking agents, anal or vaginal inserts, transanal irrigation, surgical interventions, psychological support, etc., to individualized treatment for patients' conditions. This article, combining the literature, summarizes the current status of common diseases that may lead to postoperative FI. It elaborates on strategies for the prevention and treatment of postoperative FI, aiming to serve as a reference for peers in the field.

[Comparation of outcomes of iliac crest bone graft and accessory navicular bone graft in the Cotton osteotomy for pediatric and adolescent flexible flatfoot].

Objective: To compare the outcomes between iliac crest and accessory navicular as different bone grafts in the Cotton osteotomy in the treatment of pediatric flexible flatfoot deformity. Methods: A retrospective cohort study. The clinical data of pediatric flexible flatfoot patients with symptomatic accessory navicular received operations from July 2018 to March 2022 in Beijing Tongren Hospital were retrospectively analyzed. All the patients were treated with Cotton osteotomy. According to the different sources of bone grafting in Cotton osteotomy, the patients were divided into iliac crest group and accessory navicular group. There were 12 patients (19 feet) in iliac crest group, including 9 males and 3 females with a median age M(Q1, Q3) of 11(11, 12) years and were followed-up for 36(6, 48) months. There were 9 patients (16 feet) in accessory navicular group, including 6 males and 3 females, with a median age M(Q1, Q3) of 11(11, 11) years and were followed-up for 12(6, 17) months. Radiographic evaluations were reviewed and compared between the two groups before surgical treatment and at final follow-up, included talo-1st metatarsal angle (T1MT), talonavicular coverage angle (TNCA), talocalcaneal angle (TCA) in weight bearing anteroposterior view, and Meary angle, calcaneal Pitch angle, Kite angle, cuneiform articular angle (CAA) in weight bearing lateral view, and hindfoot alignment angle (HAA) in calcaneal long axial view. Functional scores included American Orthopedic Foot and Ankle Society (AOFAS), visual analog scale (VAS), and Maryland scores were recorded and compared before and after the operation. The complications were also recorded. Results: Total of 21 patients were successfully followed in this study. The radiographic measurements in the two groups, such as T1MT, TNCA, Meary angle, Pitch angle, Kite angle, CAA, HAA, were all significantly improved at the last follow-up when compared with those before the surgery (all P<0.05); and the AOFAS, VAS, Maryland scores in both groups were all improved after the surgery (all P<0.05). There was a significant difference in CAA alteration (∆CAA) after the operation between the two groups, the ∆CAA in iliac crest group and the accessory navicular group was 6.0°±2.6° and 4.3°±1.3°, respectively (P=0.017). There was no significant differences in the improvement of other radiographic measurements between the two groups (all P>0.05). All the patients had a successful bone union. Two patients had donor site pain in the iliac crest group and were treated conservatively. Conclusion: Compared with iliac crest bone graft, accessory navicular bone graft could achieve comparable outcomes in radiographic measurements and functional scores in the treatment of pediatric flexible flatfoot with accessory navicular pain.

[The regulation of APGAT4 on the growth and lenvatinib resistance of hepatocellular carcinoma].

Objective: To investigate the effect of 1-acyl-sn-glycerol-3-phosphate acyltransferaseδ (APGAT4) on the growth and lenvatinib resistance of hepatocellular carcinoma (HCC), and provide novel targets for HCC treatment. Methods: Using the bioinformatics methods to screen out upregulated genes in lenvatinib resistant cell lines from GEO dataset and survival related genes from TCGA dataset. Immumohistochemical staining was used to detect the expression AGPAT4 in HCC tissues, and its correlation with patients' survival. CCK8, EdU, cell cycle, and cell apoptosis assays were used to investigate the impact of role AGPAT4 on the proliferation and lenvatinib reistance of HCC cells. AGPAT4 stable knockdown cell line and subcutaneous nude mouse model were established to test the therapeutic effects of Lenvatinib. Analysis of variance was used to compare the differences between data sets. Results: APGAT4 was the common factor that predicted poor survival and Lenvatinib resistance. The mRNA and protein levels of APGAT4 were significantly upregulated in HCC tissues compared to the para-tumor tissues (P < 0.05). Using siRNA could significantly knocked down the mRNA and protein expression of APGAT4 in HCC cell lines Hep3B and HCCLM3. Compared with the control group, the proliferation ability of HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group was significantly inhibited, and the cell cycle was arrested in G2/M phase (P < 0.05). In addition, compared to the control group, HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group showed significant decrease in the Lenvatinib half maximal inhibitory concentration, and were more sensitive to lenvatinib-induced apoptosis (P < 0.05). In HCC subcutaneous nude mouse model, compared to the control group, the growth of tumor in APGAT4 knockdown group was significantly suppressed, and more apoptosis cells were induced (P < 0.05). Conclusion: APGAT4 promotes the growth and Lenvatinib resistance of HCC, which is a potential target for HCC treatment. Targeting APGAT4 treatment is conducive to inhibit the growth and Lenvatinib resistance of HCC.

[Value of (11)C-PiB PET/MRI in the evaluation of organ involvement in primary systemic light chain amyloidosis].

Objective: To analyze the value of (11)C-PiB PET/MRI for evaluating organ involvement in patients with primary light chain amyloidosis (pAL) . Methods: The clinical data of 20 patients with pAL and 3 healthy volunteers from January 2019 to October 2021 were retrospectively analyzed. The correlation between the organ involvement evaluated by clinical standards and PET/MRI was compared. The relationship between cardiac-related biological indicators, disease stage, and the maximum standardized uptake value (SUVmax) were analyzed. The relationship between 24-hour urinary protein quantification and kidney SUVmax was analyzed. Results: ①In 20 patients (18 newly diagnosed patients and 2 non-newly diagnosed patients) ,(11)C-PiB positive uptake was observed in the heart (15 patients, 75%) , lung (8 patients, 40%) , bone marrow (10 patients, 50%) , muscle (10 patients, 50%) , tongue muscle (7 patients, 35%) , thyroid (6 patients, 30%) , salivary gland (4 patients, 20%) , spleen (2 patients, 10%) , and stomach wall (1 patient, 5%) . ②Organ involvement on (11)C-PiB PET/MRI showed good correlations with the clinical evaluation criteria for the heart and bone marrow. The positive rate of PET/MRI evaluation in the lung, spleen, gland, muscle, and tongue muscle was significantly higher than the clinical criteria. However, (11)C-PiB PET/MRI has limitations in the evaluation of the nervous system and fat tissue. ③To analyze the relationship between cardiac-related biological indexes and the SUVmax of the heart in 13 newly diagnosed patients. Patients with left ventricular ejection fraction (LVEF) <50% and interventricular septal thickness (ISV) ≥1.2 cm showed a higher SUVmax than patients with LVEF ≥50% and ISV<1.2 cm (P<0.05) .There are significant differences in the SUVmax of the heart between the Mayo2004 stage and the Mayo2012 stage. The later the disease stage, the higher the SUVmax (P<0.05) . The SUVmax of the heart was positively correlated with cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P<0.01) .There was no significant correlation between renal SUVmax and 24-hour urine protein (P>0.05) . Conclusion: Whole body (11)C-PiB PET/MRI, as a visualization system of amyloid protein, is used to qualitatively evaluate organ involvement, which can improve the level of early non-invasive diagnosis. Whole body (11)C-PiB PET/MRI can be used to perform quantitative evaluation of organ levels, especially the heart, which is expected to evaluate organ function and predict disease prognosis more accurately.

[Clinical characteristics of patients with multiple myeloma harboring 6q deletion].

Objective: To study the clinical and cytogenetic characteristics of patients with multiple myeloma harboring 6q deletion, with the aim to determine the impact of 6q deletion on survival. Methods: This study included the retrospective analysis of 382 newly diagnosed patients with multiple myeloma in our hospital from 2014 to 2017 and compared the clinical and cytogenetic characteristics between patients with and without 6q deletion. The log-rank test and the Cox proportional hazards regression model were used to analyze prognostic factors for progression-free survival (PFS) and overall survival (OS) . Results: Compared to those without 6q, the patients with 6q deletion were older (median age, 63 vs 58 years, P=0.039) , had higher incidence of t (4; 14) (30.4% vs 16.4% , P=0.020) , and higher proportion of complex karyotypes (22.2% vs 5.3% , P=0.001) . Univariate survival analysis using the log-rank test revealed that 6q deletion was associated with shorter PFS. However, by the Cox multivariate proportional hazards regression model, 6q deletion was not an independent prognostic factor and its effect on survival was affected by age, t (4; 14) , and other risk factors. Conclusions: 6q deletion was common in elderly patients with multiple myeloma and was often accompanied by t (4;14) and complex karyotypes. However, 6q deletion was not an independent prognostic factor for multiple myeloma.

[Clinical characteristics and prognosis of 49 newly diagnosed primary central nervous system diffuse large B-cell lymphoma].

Objective: The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively. Methods: A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis. Results: The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively (P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively (P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion: The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

A rare case of intrauterine intussusception causing ileal atresia.

Intrauterine intussusception is a rare but evident cause of intestinal atresia and is usually detected intraoperatively. We report on a term neonate who presented to the Department of Paediatric Surgery, Sabah Women and Children's Hospital, Malaysia with delayed passage of meconium and intestinal obstruction, wherein the lower contrast showed a claw sign. This was a good clue that this neonate had intrauterine intussusception and this suspicion was confirmed upon laparotomy. We found an ileo-ileal intussusception causing ileal atresia, requiring resection and primary anastomosis.

The efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer patients of different age groups: a meta-analysis.

BACKGROUND: Age is closely related to the efficacy of treatment for non-small cell lung cancer (NSCLC) patients. Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in NSCLC patients. However, we had no clear idea of the efficacy of them in elderly patients. So we conducted a meta-analysis to compare the efficacy of immune checkpoint inhibitors for NSCLC patients of different age groups and summarized overall treatment-related adverse events. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for all clinical trials in NSCLC until 30th of April 2019. Eligible studies included randomized controlled trials (RCTs) comparing immune checkpoint inhibitors with chemotherapy in NSCLC patients. The hazard ratio (HRs) and 95% confidence intervals (CIs) of OS, progression-free survival or adverse events (AEs) were used. RESULTS: A total of 4994 patients from 8 RCTs were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.73; 95% CI, 0.61-0.89) versus chemotherapy in NSCLC patients who were less than 65 years old. Also, they prolonged the OS (HR, 0.74; 95% CI, 0.59-0.93) in NSCLC patients who were more than 65 years old. However, there was no statistical significance of OS (HR, 0.87; 95% CI, 0.57-1.30) among NSCLC patients who were more than 75 years old. It also showed that the single use of immune checkpoint inhibitors had fewer all-grade AEs. CONCLUSION: Regardless of the NSCLC patients who were less or more than 65 years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further studied.

[The relationship between acid reflux and esophageal motility, esophagitis and cardiac morphology in gastroesophageal reflux disease].

Objective: To analyze the relationship between the severity of esophageal acid reflux and esophageal motility, esophageal mucosal injury and morphological anatomy of gastroesophageal junction (GEJ) in patients with gastroesophageal reflux disease (GERD). Methods: The clinicaldata of GERD patients who underwent 24 h pH-impedance monitoring, gastroscopy and high-resolution manometry (HRM) from January 2016 to January 2019 in the Gastroesophageal Surgery Department of PLA Rocket Force Characteristic Medical Center were retrospectively analyzed. The patients were divided into non-pathological acid reflux group, mild pathological acid reflux group and moderate to severe pathological acid reflux group according to the DeMeester score. The gender and age of each group were matched, with 60 cases in each group. Statistical analysiswas performed to analyze thedifferences in upper esophageal sphincter pressure, lower esophageal sphincter pressure (LES), LES length, length of ventral LES, percentage of ineffective swallowing, esophagitis, Hill grade of GEJ, and hiatus hernia (HH) in each group. The comparison and correlation analysis are also carried out between the groups. Results: The male-female ratio was 33/27, and the age was (57±13) years in each group. Non-parametric analysis showed that the LES pressure and the length of the ventral LES decreased with the severity of acid reflux, and there was a statistical difference (P= 0.033, P=0.015). The detection rate of HH by HRM increased significantly (χ(2)=0.001) as well. Esophagitis score increased with the severity of acid reflux and there was statistical difference (P<0.001).The detection rate of esophagitis increased significantly (χ(2)<0.001) as well. Hill grading score of GEJ increased with the severity of acid reflux, and there was statistical difference (P<0.001).The detection rate of HH by endoscopy increased significantly (χ(2)<0.001) as well. The correlation between DeMeester score and LES pressure, length of ventral LES, percentage of ineffective swallowing, esophagitis score, and Hill grade score were statistically significant (P<0.05). Conclusions: The esophageal low motility (such as low LES pressure) and anatomical abnormalities (abdominal esophageal shortening, GEJ flabbiness, and even HH formation) of the GEJ regionare significantly associated with the severity of acid reflux. These factors may be important causes of increased acid reflux. In addition, the aggravation of acid reflux can also increase the incidence and severity of esophagitis.

[Analysis of prognostic factors and therapeutic patterns of recurrent stage â b-â ¡a cervical squamous carcinoma treated with radical hysterectomy].

Objective: To analyze the prognosis and appropriate treatment modalities of the patients with recurrence of early stage (Ⅰb-Ⅱa) cervical squamous cancer primarily treated with radical hysterectomy. Methods: This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰb and Ⅱa recurrent cervical squamous cancer who underwent radical hysterectomy primarily from January 2007 to July 2015. Kaplan-Meier method and Cox regression analysis were performed to analyze related prognostic factors of overall survival and progression-free survival, which included age, postoperative therapy, the site of recurrence, therapy-free interval (TFI) and treatment modality. The patients who were treated with palliative chemotherapy after recurrence were selected as a subgroup. The responses of palliative chemotherapy were evaluated and analyzed among different factors, included TFI, the site of recurrence and chemotherapy regime. Results: Of the 2 071 patients, 116 relapsed Ⅰb-Ⅱa cervical squamous cancer were included in the study with the average age of (45.6±7.2) years old. 3-year progression-free survival rate and 3-year overall survival rate after recurrence were 30.2% and 42.2%, respectively. Univariate analysis implied that postoperative radiotherapy, recurrence site, TFI and treatment modality were associated with progression-free survival (P<0.05), while postoperative radiotherapy, TFI and treatment modality with overall survival (P<0.05). Multivariate analysis showed that TFI and treatment modality were independent prognostic factors for progression-free survival (P<0.05), while postoperative radiotherapy at initial treatment, TFI and treatment modality were independent prognostic variables for overall survival (P<0.05). In the analysis of treatment modality, 3-year progression-free survival rate and 3-year overall survival rate of 47 patients who were treated with definitive local therapy were significantly higher than that of 69 patients who were treated with palliative chemotherapy (P<0.01). In the subgroup analysis of palliative chemotherapy, 15 patients achieved complete response (21.7%) and 16 displayed partial response (23.2%). The overall response rate (ORR) was 44.9%. TFI (P<0.01) and chemotherapy regime (P<0.05) were significant factors associated with ORR. The ORR of TFI ≥12 months was significantly higher than that of TFI <12 months. Besides, the ORR of paclitaxel plus platinum chemotherapy was prominently higher than that of other regimens, while there was no significant difference between the ORR of paclitaxel plus cisplatin and other platinum (P=0.408). Conclusions: For recurrent stageⅠb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy, use of definitive local therapy for suitable patients is advised to achieve better prognosis. In terms of palliative chemotherapy, longer TFI may mean better ORR and the combination of paclitaxel plus platinum is preferred.

Depression and risk of hip fracture: a systematic review and meta-analysis of cohort studies.

Recently published studies on the association between depression and hip fracture (HF) are inconsistent. Therefore, we performed this meta-analysis with the main aim to clarify the association between depression and HF, and also to identify possible susceptible groups. Relevant literature published until February 2019 was obtained and screened according to established inclusion criteria. Two researchers independently processed quality assessment and data extraction prior to the meta-analysis. Pooled hazard ratios (HRs) with 95%CI (confidence intervals) were calculated. To explore the sources of heterogeneity, subgroup analyses were performed based on study design, study region, NOS scores, follow-up duration, diagnostic criteria, sex, national income level, and adjustments (bone mineral density (BMD), antidepressant, calcium intake, and smoking). Ten studies with 13 estimates, involving 375,438 participants and 4576 HFs, were included. It was found that patients with depression had a higher risk of HF than non-depressed patients (HR = 1.21; 95%CI 1.11-1.31). Sensitivity analysis results show that the association is relatively stable. The studies that were not adjusted for confounders (e.g., antidepressant, BMD, calcium intake, and smoking) had higher overall HR compared to the studies that adjusted for the corresponding confounding factors. HFs are more likely to occur in European and male depression patients. This meta-analysis provided evidence of a modest positive association between depression and the risk of HFs, and the association is stronger in European and male patients. Implementation of practical measures to prevent and treat depression is of great public health significance.

Investigating and analyzing three cohorts of mushroom poisoning caused by Amanita exitialis in Yunnan, China.

Amanita exitialis is a lethal mushroom found in China. Knowledge regarding taxonomic characterization, toxin detection, general poisoning conditions, clinical manifestations, laboratory examinations, and clinical treatments for this species is currently lacking. We investigated three A. exitialis mushroom poisoning cohorts in Yunnan Province in 2014 and 2015, involving 10 patients. Mushroom samples were identified by morphological and molecular studies. Ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry was used to detect the peptide toxins in the mushroom samples. Epidemiological information, clinical data, and results of laboratory examinations were collected and analyzed. The mushroom samples were all identified as A. exitialis. The average toxin concentration decreased from the cap to the stipe to the volva, and the average concentration of the peptide toxins decreased in the order of α-amanitin > phallacidin > ß-amanitin > γ-amanitin. The latency period between ingestion and the onset of symptoms was 13.9 ± 2.1 h, and the time from ingestion to hospitalization was 49.6 ± 8.5 h. The most common symptoms were nausea and vomiting (100%). Four patients died from fulminant hepatic failure. Laboratory examinations showed that the alanine transaminase, aspartate transaminase, prothrombin time, and activated partial thromboplastin time levels peaked on the third day post-ingestion. Total bilirubin and direct bilirubin values peaked on day 7. The death group and the survival group had a similar variation trend of serological indexes, but the death group had a greater change. A. exitialis is an extremely dangerous mushroom and there is a need to educate the public to avoid picking and eating wild mushrooms that have not been definitively identified.