Obstetric blood transfusion in placenta previa patients with prenatal anemia: a retrospective study.

BACKGROUND: The appropriate use of obstetric blood transfusion is crucial for patients with placenta previa and prenatal anemia. This retrospective study aims to explore the correlation between prenatal anemia and blood transfusion-related parameters in this population. METHODS: We retrieved the medical records of consecutive participants who were diagnosed with placenta previa and underwent cesarean section in our hospital. We compared the baseline demographics and clinical characteristics of patients with and without anemia. The correlation between prenatal anemia and obstetric blood transfusion-related parameters was evaluated using multivariate regression analysis. RESULTS: A total of 749 patients were enrolled, with a mean prenatal hemoglobin level of 10.87 ± 1.37 g/dL. Among them, 54.87% (391/749) were diagnosed with anemia. The rate of obstetric blood transfusion was significantly higher in the anemia group (79.54%) compared to the normal group (44.41%). The median allogeneic red blood cell transfusion volume in the anemia group was 4.00 U (IQR 2.00-6.00), while in the normal group, it was 0.00 U (IQR 0.00-4.00). The prenatal hemoglobin levels had a non-linear relationship with intraoperative allogeneic blood transfusion rate, massive blood transfusion rate, red blood cell transfusion units, and fresh plasma transfusion volume in patients with placenta previa, with a threshold of 12 g/dL. CONCLUSIONS: Our findings suggest that prenatal anemia is associated with a higher rate of blood transfusion-related parameters in women with placenta previa when the hemoglobin level is < 12 g/dL. These results highlight the importance of promoting prenatal care in placenta previa patients with a high requirement for blood transfusion.

Effect of placenta location detected by ultrasound on the severity of placenta accreta spectrum in patients with placenta previa and placenta accreta spectrum.

BACKGROUND: To evaluate the effect of placental location on the severity of placenta accreta spectrum (PAS). METHODS: We analyzed 390 patients with placenta previa combined with placenta accreta spectrum who underwent cesarean section between January 1, 2014 and December 30, 2020 in the electronic case database of the Second Hospital of Hebei Medical University. According to the position of the placenta, 390 placentas were divided into the posterior group (n = 89), the anterior group (n = 60) and the non-central group (n = 241). RESULTS: The history of cesarean delivery rates in the anterior group (91.67%) and the non-central group (85.71%) were statistically different from the posterior group (63.74%)(P < 0.001). Univariate logistic regression results showed that employment, urban living, gestational age, complete placenta previa, fetal presentation shoulder, gravidity, cesarean section and vaginal delivery were all predictors for the severity of placenta accreta (P < 0.05). The anterior group (P = 0.001, OR = 4.13, 95%CI: 1.84-9.24) and the non-central group (P = 0.001, OR = 2.90, 95%CI: 1.55-5.45) had a higher incidence of invasive accreta placentation than the posterior group, and were independent risk factors for invasive accreta placentation. CONCLUSION: Compared with posterior placenta, anterior and non-central placenta are independent risk factors for invasive PAS in patients with placenta previa, during which we should be more cautious in treatment.

Impact of Maternal Preoperative Hemoglobin Levels on Intraoperative Hemorrhage Risk in Placenta Accrete Spectrum Disorders: A Retrospective Cross-Sectional Study.

BACKGROUND Placenta accreta spectrum (PAS) disorders involve abnormal adhesion or invasion of chorionic villi through the myometrium and uterine serosa. Maternal anemia during pregnancy is common and may contribute to complications during delivery, particularly with abnormal placentation. This study examines the association between preoperative maternal hemoglobin levels and the risk of intraoperative massive hemorrhage in pregnant women with PAS disorders. MATERIAL AND METHODS A retrospective study included 538 consecutive participants (mean age=31.12±4.68 years) who underwent cesarean sections and met the diagnostic criteria for PAS disorders. Logistic regression analysis was performed to investigate the relationship between maternal preoperative hemoglobin levels and the risk of massive intraoperative hemorrhage (blood loss ≥1500 mL). RESULTS The incidence of intraoperative massive hemorrhage among patients with PAS disorders was 38.66%. The mean preoperative maternal hemoglobin level was 10.99±1.39 g/dL, and overall anemia incidence (<11 g/dL) was 48.88% in our study. After adjusting for potential confounders, a non-linear relationship was observed between preoperative maternal hemoglobin levels and the risk of intraoperative massive hemorrhage. When the preoperative hemoglobin level of pregnant women was below 11.5 g/dL (OR=0.52, 95% CI 0.39-0.70), the lower hemoglobin level significantly increased the risk of intraoperative hemorrhage. CONCLUSIONS Maternal preoperative hemoglobin levels were inversely associated with the risk of massive intraoperative hemorrhage in PAS disorders. A non-linear relationship was identified, with a turning point at 11.5 g/dL. These findings emphasize the importance of monitoring and managing maternal hemoglobin levels to mitigate the risk of intraoperative hemorrhage in pregnant women with PAS disorders.

Contribution of m5C RNA Modification-Related Genes to Prognosis and Immunotherapy Prediction in Patients with Ovarian Cancer.

Background: 5-Methylcytosine (m5C) RNA modification is closely implicated in the occurrence of a variety of cancers. Here, we established a novel prognostic signature for ovarian cancer (OC) patients based on m5C RNA modification-related genes and explored the correlation between these genes with the tumor immune microenvironment. Methods: Methylated-RNA immunoprecipitation sequencing helped us to identify candidate genes related to m5C RNA modification at first. Based on TCGA database, we screened the differentially expressed candidate genes related to the prognosis and constructed a prognostic model using LASSO Cox regression analyses. Notably, the accuracy of the model was evaluated by Kaplan-Meier analysis and receiver operator characteristic curves. Independent prognostic risk factors were investigated by Cox proportional hazard model. Furthermore, we also analyzed the biological functions and pathways involved in the signature. Finally, the immune response of the model was visualized in great detail. Results: Totally, 2,493 candidate genes proved to be involved in m5C modification of RNA for OC. We developed a signature with prognostic value consisting of six m5C RNA modification-related genes. Specially, samples have been split into two cohorts with low- and high-risk scores according to the model, in which the low-risk OC patients exhibited dramatically better overall survival time than those with high-risk scores. Besides, not only was this model a prognostic factor independent of other clinical characteristics but it predicted the intensity of the immune response in OC. Significantly, the accuracy and availability of the signature were verified by ICGC database. Conclusions: Our study bridged the gap between m5C RNA modification and the prognosis of OC and was expected to provide an effective breakthrough for immunotherapy in OC patients.

Dissecting the genotype-phenotype correlation of COL4A5 gene mutation and its response to renin-angiotensin-aldosterone system blockers in Chinese male patients with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is an inherited type IV collagen-related disorder with an irreversible tendency to progress to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by mutations in the COL4A5 gene. The aim of this study was to investigate the effects of underlying mutations on clinical manifestations and the response to therapy in XLAS. METHODS: We conducted a retrospective cohort study of 187 Chinese male patients with XLAS confirmed by pathological examination and genetic analysis. The Kaplan-Meier method and Cox proportional hazards model were used to assess the age and risk of progression to ESRD under different genotypes and treatment conditions. RESULTS: A strong relationship between transcript type and renal outcome was observed, with the median age of ESRD onset being 22 years for truncating mutations and 39 years for non-truncating mutations. The response of affected patients to renin-angiotensin-aldosterone system (RAAS) blockers was genotype-associated. This therapy delayed the onset of ESRD by 16 years in patients with non-truncating mutations and 3 years in patients with truncating mutations. The efficacy of RAAS blockers functioned in a time-dependent manner, with a 7% reduction in the risk of progression to ESRD per each 6-month increase in treatment duration [hazard ratio 0.93 (95% confidence interval 0.89-0.96); P < 0.001]. CONCLUSIONS: Clinical features and response to RAAS blockers were observed to be strongly correlated with the genotypes of male XLAS patients. Genotyping of COL4A5 gene mutations is essential and is a useful tool to assess the prognosis of AS patients.

Long-term follow-up of autologous peripheral blood hematopoietic stem cell transplantation for refractory lupus nephritis-a series study of 20 patients.

BACKGROUND: Autologous hematopoietic cell transplantation (ASCT) improves immunologic homeostasis in autoimmune diseases. ASCT-treated refractory lupus nephritis (LN) has been reported. Nevertheless, the long-term outcome of patients with refractory LN after ASCT remains unknown. This study reports the outcomes of 20 refractory lupus patients with 10-year of follow-up after receiving ASCT. METHODS: Twenty-two patients with LN refractory to immunosuppressive therapy were enrolled. Twenty patients were examined closely and two cases died within 100 days after ASCT. Hematopoietic cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) was followed by collection of CD34+ positively selected cells. The conditioning regimen consisted of intravenous cyclophosphamide, rabbit antithymocyte globulin, methylprednisolone, and G-CSF. All immunosuppressive therapies were discontinued at the start of mobilization and corticosteroids were tapered rapidly after ASCT. RESULTS: Data was collected from 22 patients with refractory LN treated by ASCT. 59% were female, duration of lupus before ASCT was 46 (33-71) months, and median duration of follow-up after ASCT was 89.5 (56-108) months. 20 long-term followed up patients had an average follow-up time of 92 months (63.25-109.5). Eighteen patients achieved complete remission, one patient reached partial remission, one patient without remission started peritoneal dialysis at month 12, and one patient received short-term renal replacement therapy before ASCT started hemodialysis at 84 months after transplantation. Nine patients relapsed 10 times during the follow-up, and three patients received rituximab. Two patients relapsed during pregnancy after complete response and the Apgar scores of infants were 9 and 10, respectively. All nine patients received glucocorticoids and immunosuppressive medication after relapse and responded again. The 10-year overall survival, 10-year disease-free survival rate, and 10-year renal survival were 100%, 35%, and 90%, respectively. The rate of relapse was 45%. Complications included hypocytosis, infection, B-type insulin resistance syndrome, and monoclonal immunoglobulinemia. CONCLUSION: This study suggests ASCT is effective and safety in treating refractory LN and is beneficial to improve their long-term outcomes.

Modified balloon vaginoplasty for high position vaginal atresia.

INTRODUCTION: The first-line approach for the management of distal vaginal atresia involves a pull-through vaginoplasty. If the proximal vagina is 3 cm or more from the introitus, the risk of stenosis is high, and an interposition graft may be necessary. We describe a safe, low-cost, and accessible approach for distal vaginal atresia ≥ 3 cm that we call the "modified balloon vaginoplasty" and validate the technical feasibility and anatomical outcomes. METHODS: Ten patients who underwent modified balloon vaginoplasty were retrospectively evaluated. Age, symptoms at presentation, length of atresia, operation time, and postoperative complications were analyzed. RESULTS: All the cases were successfully performed without any intraoperative morbidity. The postoperative complications included one case of stenosis ring in the distal vagina because not right used vagina model. All the girls had regular menstruation and were satisfied with the surgical outcome. CONCLUSION: Modified balloon vaginoplasty allows further distention of the distal vagina or thinning of the septum, which may decrease the risk of stenosis, is a beneficial choice for patients with distal vaginal atresia ≥ 3 cm.

Uterine rhabdomyosarcoma complicated by cerebral venous thrombosis and uterine inversion in a young woman: case report and literature review.

BACKGROUND: Uterine rhabdomyosarcoma is an extremely rare malignant tumor that usually affects young women and has a poor prognosis. CASE PRESENTATION: A 19-year-old nulliparous woman presented to the emergency department under sedation due to seizures. Imaging examination revealed cerebral venous thrombosis. During thrombolytic therapy, she developed vaginal bleeding followed by uterine inversion secondary to uterine rhabdomyosarcoma. The inverted uterus was mistaken for a cervical tumour and was removed vaginally. The patient's disease progressed despite chemotherapy with vincristine, actinomycin D and cyclophosphamide and she died within 6 months. To our knowledge, this is the first case of uterine rhabdomyosarcoma complicated with cerebral venous thrombosis. CONCLUSIONS: Malignancy is an important diagnostic in patients with cerebral venous thrombosis with no obvious cause. This case demonstrates the importance of considering uterine neoplasms in the differential diagnosis of adolescent girls with abnormal uterine bleeding. Further, careful anatomical evaluation of vaginal masses should be performed prior to surgical intervention.

Heavy Chain Deposition Disease: Clinicopathologic Characteristics of a Chinese Case Series.

RATIONALE & OBJECTIVE: Heavy chain deposition disease (HCDD) is a rare consequence of monoclonal immunoglobulin deposition disease that has not been well characterized in non-white populations. To explore the clinicopathologic characteristics and outcomes of HCDD in Chinese individuals, we report on a case series assembled in a single center in China. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 25 patients with biopsy-proven HCDD were studied retrospectively. RESULTS: 14 men and 11 women with an average age of 50.3 years were studied. The patients presented with hypertension (76%), edema (96%), anemia (84%), serum creatinine level > 1.2mg/dL (68%), nephrotic-range proteinuria (56%), and microscopic hematuria (80%). One (4%) patient had multiple myeloma diagnosed. Serum immunofixation electrophoresis showed that 10 of 21 (48%) patients were positive for monoclonal immunoglobulin. Hypocomplementemia of C3 was found in 68% of patients. Nodular mesangial sclerosis was identified in all patients by using light microscopy. Using immunofluorescence, all 25 patients had deposition of heavy chains of immunoglobulin G class (γ1, 13; γ2, 2; γ3, 6; γ4, 2; γ1 and γ4, 1; and γ2 and γ4, 1). During an average of 40.1 months of follow-up of 20 patients, 65% had improved kidney function, 10% had worsening kidney function, and 25% progressed to kidney failure. Mean values for kidney and patient survival were 37.8 and 40.1 months, respectively. Kidney survival was higher among patients who received chemotherapy. LIMITATIONS: Retrospective study, single-center experience. CONCLUSIONS: In this case series of HCDD in a single center in China, the heavy chain deposits seen in the kidney biopies of all individuals were of immunoglobulin G class. Chemotherapy improved kidney function, especially among individuals in an early stage of the disease.

An investigation of the time trends, risk factors, role of ultrasonic preoperative diagnosis of 79 ovarian pregnancy.

BACKGROUND: Ovarian pregnancy (OP) is a rare form of ectopic pregnancy and is still a medical challenge. Therefore, more studies about the time trends, risk factors and diagnostic measurements are needed for the efficient treatment of OP. METHODS: The datum of OP patients who were treated at the Second Hospital of Hebei Medical University from 2003 to 2018 was collected and a retrospective cohort study was preformed between OP and tubal pregnancy. RESULTS: 79 of all 6943 ectopic pregnancy (1.14%) were OP. The prevalence of OP following assisted reproductive technology showed an increasing trend over time, from 8.33% to 15.22%. Previous abdominal surgery was one of the risk factors of OP (OR 0.41, 95% CI 0.18-0.95, p = 0.04). Merely 2 (2.53%) patients were sonographically diagnosed as OP accorded with their discharge diagnosis. However, 56 (80.0%) accumulation of blood in the pelvis formed echo free areas could be clearly found by ultrasonography. A significant difference was found in serum ß-hCG level among OP patients and tubal pregnancy patients (2762.73 ± 1915.24 mmol/L vs 1034.20 ± 915.32 mmol/L, p < 0.001). CONCLUSIONS: The prevalence of OP following assisted reproductive technology is on the rise. History of abdominal surgery may be a high risk factor for OP patients who have the tendency of high ß-hCG levels. The ultrasonic preoperative diagnosis is conductive to the early diagnosis of OP though the diagnosis accuracy is low.

A risk stratification for systemic immunoglobulin light-chain amyloidosis with renal involvement.

Renal involvement is found in about 70% of patients with systemic immunoglobulin light-chain (AL) amyloidosis. However, there is no risk stratification system specialized for renal AL concerning patients' survival. Galectin-3 (Gal-3) has been reported to portend poor prognosis in other renal diseases. We measured Gal-3 and several traditional risk biomarkers of AL in baseline samples from 253 consecutive patients diagnosed with renal AL. At baseline, Gal-3 [Hazard ratio (HR): 1·46; P = 0·033], high-sensitivity cardiac troponin T (hs-cTnT) (HR: 2·65; P < 0·001) and difference between involved and uninvolved free light chains (dFLC) (HR: 1·81; P = 0·001) were independent predictors of all-cause mortality. The cut-off points for Gal-3, hs-cTnT, and dFLC were 20·24 ng/ml, 0·026 ng/ml, and 75·89 mg/l, respectively. Patients were stratified into four stages by assigning a score of 1 for each of the three biomarkers above the cut-off point. The proportions of patients with disease stages 1, 2, 3 and 4 were 17·0%, 37·2%, 29·2% and 16·6%, and the median overall survival times from diagnosis were 100, 60, 29 and 15 months, respectively (P < 0·01). Higher level of Gal-3 is associated with increased risk for mortality, and the risk stratification based on Gal-3 is a reliable model for predicting mortality in AL amyloidosis with renal involvement.

Clinicopathologic characteristics of light chain proximal tubulopathy with light chain inclusions involving multiple renal cell types
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Light chain proximal tubulopathy (LCPT) associated with plasma cell dyscrasias is a rare abnormality, especially cases involving multiple cell types. The aim of this study is to explore the characteristics and outcomes of these diseases. We comprehensively evaluated the clinical-pathological data, treatment, and outcomes of 6 LCPT patients with involvement of multiple cell types. In 3 cases, we found that the inclusions largely existed in tubular cells, while in 2 cases they coexisted in podocytes and tubular cells, and in 1 case they coexisted in histiocytes and tubular cells. The stain features and appearances of inclusions were specific and varied. Five patients displayed κ-light chains with crystal formation, while 1 patient displayed a λ subtype with increased lysosomes instead of crystals. Six patients presented with proteinuria, 4 with renal insufficiency, and 4 with complete or partial Fanconi syndrome. Our findings indicate that tubular cells are the most common location of cytoplasmic inclusions. Cases with κ-light chain storage are more common than λ, and the formation of crystals may be associated with the subtype of light chains. Immunoelectron microscopy could be used to increase sensitivity for the detection and location of monoclonal light chains. Therefore, these patients have some common clinical features with varied pathologic characteristics and prognoses but the same subtype of light chains.
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Bone Marrow Mesenchymal Stem Cells Accelerate the Morphological and Functional Recovery of Neovaginas.

Vaginal reconstruction is the main solution to the problem of sexuality and gender roles for patients with no vagina. A tissue-engineered vagina may be the best choice. However, many defects have been found in neovaginas reconstructed with a graft only. In this study, we investigated whether a stem cell-seeded graft would accelerate the morphological and functional recovery of neovaginas. CM-DiI-labeled bone marrow mesenchymal stem cell (MSC)-seeded small intestinal submucosa (SIS) (SIS+MSCs group) was used for vaginal reconstruction in a rat model; unseeded SIS (SIS group) was used as a control. The neovaginas of each group were harvested at 4 and 12 weeks after surgery. Morphological analyses were performed using hematoxylin and eosin (H&E) staining and immunohistochemical staining for α-smooth muscle actin (SMA), protein gene product 9.5(PGP9.5), and CD34. Functional recovery was evaluated using an organ bath study. The role of MSCs in the neovagina was analyzed by immunofluorescence and molecular biology methods. At the 4th week, a regenerated epithelium covered the whole neovagina in both groups. A small amount of smooth muscle regeneration was found in the neovagina. Up to the 12th week, nerve fibers appeared. There were more smooth muscle and nerve fibers, along with better contractility, in the neovagina of the SIS+MSCs group. Further study showed that the MSCs differentiated into smooth muscles at the 4th week. A higher microvessel density (MVD) and more vascular endothelial growth factor (VEGF) were found in the neovagina of the SIS+MSCs group. In short, MSCs accelerate the structural and functional recovery of the neovagina.

Small Intestine Submucosa Is a Potential Material for Intrauterine Adhesions Treatment in a Rat Model.

OBJECTIVE: To study whether small intestine submucosa (SIS) could be a treatment option for preventing the formation of intrauterine adhesions (IUAs). METHODS: The IUAs model was established by mechanical curettage and infectious injury in a rat model. One uterine horn of the rat model was treated with the transplantation of SIS (SIS group) and the other one was left without any treatment (control group). The endometrium was evaluated with endometrial thickness, number of glands and fibrosis area. The endometrial receptive factors were detected by quantitative real-time polymerase chain reaction The number and location of embryos were documented to assess the function of endometrium. RESULTS: In the SIS group, endometrial thickness was significantly thicker than that in the control group on the 14th and 21st day and the percentage of fibrosis area was significantly lower during the entire observation process (p < 0.05). The number of glands was similar between the 2 groups (p > 0.05). Receptive factors changed as follows: in the SIS group, the expression of uteroglobin was higher and peaked on the 21st day (3.42-fold, p < 0.05); the HOXA10 level was significantly higher on the 10th day (2.16-fold, p < 0.05), and it then decreased. More embryos were seen in SIS horns (5.13 vs. 1.25, p < 0.05). CONCLUSIONS: SIS could be a potential physical barrier for the formation of IUAs. It contributes to the regeneration of and improvement of the receptivity of endometrium, and helps in the implantation and development of embryos in a rat model.

Bone marrow mesenchymal stem cells could acquire the phenotypes of epithelial cells and accelerate vaginal reconstruction combined with small intestinal submucosa.

Grafting material for vaginal reconstruction commonly includes the bowel, peritoneum, skin, and amniotic membrane. Bone marrow mesenchymal stem cells (MSCs) have the potential of multilineage differentiation into a variety of cells and have been widely explored in tissue engineering. In the current study, we examined whether MSCs could be differentiated to vaginal epithelial cells (VECs) upon co-culturing with VECs. We also examined whether Wnt/ß-catenin signaling pathway is implicated in such differentiation. Co-culture of MSCs with VECs using a transwell insert system (with no direct contact) induced the expression of VECs marker AE1/AE3 in MSCs. MSCs combined with small intestinal submucosa (SIS) scaffold were implanted in place of the native vagina in rats to observe the implications for vaginal reconstruction in vivo. Anatomic repair of neovagina was assessed by histological staining for H/E and Masson's Trichrome. GSK-3ß and ß-catenin, main members of Wnt/ß-catenin signaling pathway, in MSCs were increased upon co-culturing with VECs. Exposure of co-cultured MSCs to a Wnt/ß-catenin signaling activator, lithium chloride (LiCl, 20 µM) increased phosphorylated GSK-3ß and ß-catenin and enhanced expression of AE1/AE3. In vivo-grafted cells displayed significant matrix infiltration and expressed epithelial markers in neovagina. These findings suggest that MSCs could acquire the phenotype of VECs when co-cultured with VECs, possibly via activation of Wnt/ß-catenin signaling. MSCs provide an alternative cell source for potential use in vaginal tissue engineering.

Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.

Complement C3 and C4 play key roles in the main physiological activities of complement system, and their deficiencies or over-expression are associated with many clinical infectious or immunity diseases. A two-stage genome-wide association study (GWAS) was performed for serum levels of C3 and C4. The first stage was conducted in 1,999 healthy Chinese men, and the second stage was performed in an additional 1,496 subjects. We identified two SNPs, rs3753394 in CFH gene and rs3745567 in C3 gene, that are significantly associated with serum C3 levels at a genome-wide significance level (P = 7.33 × 10(-11) and P = 1.83 × 10(-9), respectively). For C4, one large genomic region on chromosome 6p21.3 is significantly associated with serum C4 levels. Two SNPs (rs1052693 and rs11575839) were located in the MHC class I area that include HLA-A, HLA-C, and HLA-B genes. Two SNPs (rs2075799 and rs2857009) were located 5' and 3' of C4 gene. The other four SNPs, rs2071278, rs3763317, rs9276606, and rs241428, were located in the MHC class II region that includes HLA-DRA, HLA-DRB, and HLA-DQB genes. The combined P-values for those eight SNPs ranged from 3.19 × 10(-22) to 5.62 × 10(-97). HBsAg-positive subjects have significantly lower C3 and C4 protein concentrations compared with HBsAg-negative subjects (P<0.05). Our study is the first GWAS report which shows genetic components influence the levels of complement C3 and C4. Our significant findings provide novel insights of their related autoimmune, infectious diseases, and molecular mechanisms.

A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.

Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial.

BACKGROUND: Although the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT. METHODS: This was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD + HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT. RESULTS: Fifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD + HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD + HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD + HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P = 0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD + HDM/SCT group and 69.4% in the HDM/SCT alone group (P = 0.03). CONCLUSIONS: Our preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone. TRIAL REGISTRATION: This trial has been registered at clinicaltrials.gov with the number NCT01998503.

Risk factors, treatments and outcomes of patients with light chain amyloidosis who relapse after autologous stem cell transplantation.

Relapse after ASCT is an important factor affecting the long-term prognosis of patients with AL amyloidosis. However, the risk factors of relapse are unknown and there are limited studies on treatment outcomes of these patients. We retrospectively reviewed 170 patients with AL amyloidosis who underwent ASCT between 2010 and 2021. Seventy-six patients confirmed as relapse and the median time from ASCT to relapse was 39 months. On multivariate analysis of variables before and after ASCT, lambda restricted, dFLC >30 mg/L pre ASCT, reduced dose melphalan and dFLC >10 mg/L at 6 months after ASCT were independent risk factors for relapse, and achieving CR after induction therapy and renal response after ASCT were protective factors. Most relapsed patients were treated with bortezomib-based regimens (50%) followed by daratumumab-based regimens (22.2%) and other chemotherapy regimens (13.9%). The overall hematological response in evaluable patients was 68.2% with 56.8% achieving CR/VGPR. The median PFS and OS from post-transplant relapse were 25 months and 81 months, respectively. Patients receiving bortezomib or daratumumab showed a better survival compared to other chemotherapy regimens. In conclusion, this study identified independent risk factors of post-transplant relapse and demonstrated the superiority of bortezomib or daratumumab treatment for these patients. CLINICAL TRIAL REGISTRATION: NCT04210791.