[Single non-blood-related umbilical cord blood transplantation using a reduced-intensity conditioning regimen for the treatment of severe aplastic anemia].

Objective: To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) . Methods: The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups. Results: The baseline parameters were balanced between the two groups (P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant (P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups (P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% (P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) (P=0.198) . Conclusion: The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

[Clinical characteristics and survival analysis of 15 cases of HIV-negative plasmablastic lymphoma].

Objective: To evaluate the clinicopathologic characteristics and outcomes of HIV-negative plasmablastic lymphoma (PBL) . Methods: Medical records of 15 patients diagnosed with HIV-negative PBL in Changhai Hospital between January 2013 and August 2019 were reviewed, and clinicopathologic characteristics and outcomes were analyzed. Results: Median age was 59 years (range: 17-69) . All patients had extranodal involvement. According to the Cotswolds-modified Ann Arbor staging system, 1 (6.7%) , 2 (13.3%) , 3 (20.0%) , and 9 (60.0%) patients were classified as at Ⅰ,Ⅱ,Ⅲ and Ⅳ, respectively. Plasmablast and immunoblast proliferations were typical manifestations of PBL. Immunohistochemical staining showed tumor cells were diffusely positive for plasma cell markers CD38, CD138, and Mum-1, while negative for B cell markers CD20, CD10, PAX-5, and BCL-6. Median Ki-67 index was 80% (70%-90%) . Epstein-Barr virus-encoded RNA (EBER) expression was detected in 3 patients, and 1 of them was positive. All patients received chemotherapy, 80% combined with bortezomib as the first line, and responses were observed in 8 patients (6 complete and 2 partial responses) . Median progression-free survival (PFS) and overall survival (OS) were 6.8 (95% CI 2.5-11.1) months and 17.9 (95% CI 5.6-30.2) months, the 3-year PFS and OS rates were 21.2% (95% CI 1.4%-56.8%) and 38.5% (95% CI 12.0%-65.0%) , respectively. Conclusion: HIV-negative PBL with high invasiveness is extremely prone to extranodal involvement and most patients were at the advanced stage. Patients receiving an intensive therapy combined with bortezomib and bridged autologous stem cell transplantation may improve long-time survival.

[Efficacy of Hyper-CVAD/MA and CHALL-01 regimens in the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia patients under 60 years old].

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.

[Prognostic value of donor chimerism at +90 days after allogeneic hematopoietic stem cell transplantation in young patients with intermediate-risk acute myeloid leukemia].

Objective: To investigate the relationship between donor chimerism and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data of 105 patients with acute myeloid leukemia (AML) who underwent allo-HSCT and recurrence-free survival>90 days from January 2010 to January 2019 were retrospectively analyzed. The bone marrow samples were collected at 15, 30, 60, 90, 180, 270, 360 days after transplantation. Donor chimerism was detected by single nucleotide polymorphism (SNP) -PCR. Results: Of the 105 patients, 43 cases were male and 62 cases were female, with a median age of 38 (16-60) years. Till April 2019, the median follow-up was 843 (94-3 261) days. Ninety days after transplantation, 18 cases relapsed, 33 cases died, and 72 cases survived. The 3-year overall survival (OS) rate was (66.8±5.1) %, and the recurrence-free survival (RFS) rate was (65.1±5.0) %. Pre-transplant disease status, pre-transplant minimal residual disease (MRD) , and 90 day post-transplantation chimerism were independent risk factors related to RFS. The risk of recurrence was significantly increased in patients with a donor chimerism rate ≤97.24% at 90 days after transplantation[HR=6.921 (95%CI 2.669-17.950) , P<0.001], which was considered as a sign of early relapse. Conclusion: SNP-PCR is an applicable method for detecting donor chimerism in patients after allo-HSCT. Chimerism rate equal or less than 97.24% at 90 days after transplantation predicts a higher risk of relapse.

Dose reduction for fluoroscopically guided injections: phantom simulation and patient procedures.

OBJECTIVE: To demonstrate fluoroscopy dose reduction through both simulated injections on a phantom and patient injections. MATERIALS AND METHODS: Our study was IRB-approved and HIPAA-compliant. Simulation on a phantom was used to estimate effective dose, entrance dose, and organ doses for hip joint injections without and with dose minimization technique (DMT). Additionally, 1,094 joint, bursae, and tendon sheath injections performed by three operators in the same fluoroscopy suite were evaluated both before and after application of DMT. Fluoroscopy time (FT), dose, and dose area product (DAP) of injections were compared using unpaired t-tests with P > 0.05 considered statistically significant. RESULTS: For the phantom simulation comparing injections without DMT and with DMT, the total DAP was 191.7 vs 18.7 µGy·m2, and the entrance dose was 10.2 vs 3.6 mGy, respectively. For both men and women, DMT reduces effective dose and organ doses. For all injections, the FT (0.7 to 0.2 min), dose (5.6 to 1.9 mGy), and DAP (56.9 to 19.1 µGy·m2) for all three operators decreased with DMT and remained statistically significant when stratified by the two most common injections, glenohumeral and hip joint injections (P < 0.05). CONCLUSIONS: FT, effective dose, entrance dose, and DAP can be reduced with the use of simple easy-to-learn techniques, which will benefit both the patient and the radiologist.

[Study on clinical management of HPV(+)/Pap(-) during cervical cancer screening].

Objective: To study the clinical management way for HPV(+)/papanicolaou (Pap)(-) during cervical cancer screening. Methods: To analyze retrospectively the data from the patients who had loop electrical excision procedure (LEEP) for biopsy confirmed cervical intraepithelial neoplasia (CIN) Ⅱ in Peking University People's Hospital from Jan. 2010 to Dec. 2014. Results: (1) For biopsy confirmed CIN Ⅱ, HPV positive rate was 98.5% (135/137), Pap test positive [≥atypical squamous cell of undetermined significance (ASCUS)] rate was 69.3% (95/137), there was significant difference between them (χ(2)=43.32, P<0.01). (2) For the 42 patients with HPV(+)/Pap(-), whose cytology slides were reviewed again. Among them, the interpretations of there were 16 cases confirmed as the same before, while 26 cases were changed to abnormal (≥ASCUS). Cytology be misdiagnosed was 19.0% (26/137) at the first review. Among the 26 cases, 13 (50.0%) cases were missed for the little amount of abnormal cells, 8 (30.8%) cases for mild atypical morphology changed; the other 5 (19.2%) cases missed for stain problems. (3) For the cervical LEEP samples, 37 cases of the pathology diagnosis were upgrade to CIN Ⅲ(+), among them, 2 cases of microinvasive cervical carcinoma, 1 case of invasive cancer, 34 cases of CIN Ⅲ; 37 cases were CINⅠ or no lesion found; 63 cases were still CIN Ⅱ. Four to six months later after LEEP, the cytology abnormal rate was 11.7% (16/137), and the HR-HPV positive rate was 34.3% (47/137). Conclusions: Compared with cytology alone, cytology combined with HPV testing increase the sensitivity of cervical high grade lesion. For the cases of HPV(+)/Pap(-) cases, the cytology slides should be reviewed. The quality control of cervical exfoliate sample collection and interpretation should be strengthened. LEEP procedure is not only a treatment method, but also it could provide samples to confirm the diagnosis.

Mitochondrial oxygen metabolism in primary human lens epithelial cells: Association with age, diabetes and glaucoma.

PURPOSE: The hypoxic environment around the lens is important for maintaining lens transparency. Lens epithelial cells (LECs) play a key role in lens metabolism. We measured oxygen consumption to assess the role of human LECs in maintaining hypoxia around the lens, as well as the impact of systemic and ocular diagnosis on these cells. METHODS: Baseline cellular respiration was measured in rabbit LECs (NN1003A), canine kidney epithelial cells (MDCK), trabecular meshwork cells (TM-5), and bovine corneal endothelial cells (CCEE) using a XF96 Extracellular Flux Analyzer (Seahorse Bioscience, North Billerica, MA), which measures oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro. Following informed written consent, lens capsule epithelial cells were obtained from patients during cataract surgery and were divided into small explants in 96-well plates. Capsules were removed when LECs became confluent. OCR was normalized to the number of cells per well using rabbit LECs as a standard. The effect of patient age, sex, race, and presence of diabetes or glaucoma on oxygen consumption was assessed by using the Mann-Whitney U test and multivariate regression analysis. RESULTS: Primary LECs were obtained from 69 patients. The OCR from donors aged 70 and over was lower than that of those under 70 years (2.21±1.037 vs. 2.86±1.383 fmol/min/cell; p<0.05). Diabetic patients had lower OCR than non-diabetic patients (2.02±0.911 vs. 2.79±1.332fmol/min/cell; p<0.05), and glaucoma patients had lower OCR than non-glaucoma patients (2.27±1.19 vs. 2.83±1.286 fmol/min/cell; p<0.05). Multivariate regression analysis confirmed that donors aged 70 and over (p<0.05), diabetic patients (p<0.01), and glaucoma patients (p<0.05) had significantly lower OCR, independent of other variables. Gender and race had no significant effect on OCR. CONCLUSIONS: The lower oxygen consumption rate of human LECs in older donors and patients with diabetes or glaucoma could contribute to cataract development. Diabetes and glaucoma are particularly important factors associated with decreased OCR, independent of age. Ongoing studies are examining pO2 at the anterior surface of the lens in vivo and oxygen consumption in the patient's LECs.

A Randomised Controlled Trial to Evaluate the Effectiveness of Intrathecal Bupivacaine Combined with Different Adjuvants (Fentanyl, Clonidine and Dexmedetomidine) in Caesarean Section.

PURPOSE: The purpose of this study was to evaluate comparatively, in women undergoing caesarean section under spinal anesthesia, the effectiveness of hyperbaric bupivacaine combined with 3 different adjuvants (fentanyl, clonidine, and dexmedtomidine) on quality of blockade and maternal and neonatal repercussions. METHOD: 84 patients undergoing elective surgeries under spinal anesthesia were randomized into 4 groups of 21 each, gB, gBF, gBC and gBD. Patients in groups gb, gBF, gBC and gBD were given bupivacaine alone, bupivacaine plus fentanyl (15.0 µg), bupivacaine plus fentanyl plus clonidine (75 µg), and bupivacaine plus dexmedetomidine (10 µg), respectively. Hemodynamic parameters evaluated were the onset and level of sensory block, perioperative analgesia, degree and recovery time of motor block, duration of analgesia, sedation, and maternal-foetal repercussions. RESULTS: The onset of blockade was significantly faster in groups with adjuvants clonidine and dexmedetomidine compared with gB and gBF. Patients in Groups gB and gBF reported pain during the perioperative period. Duration of analgesia was significantly higher in Group gBD and was comparable to gBC and time to motor block recovery was significantly higher in Group gBD. Sedation was significant in Group gBD and gBC. CONCLUSION: Addition of dexmedetomidine and clonidine as adjuvants to hyperbaric bupivacaine provided adequate anesthesia and postoperative analgesia compared to fentanyl adjuvant without causing any significant side effects.

Urinary incontinence and pelvic floor dysfunction in Asian-American women.

OBJECTIVE: The objective of the study was to describe the prevalence, risk factors, and impact of urinary incontinence and other pelvic floor disorders among Asian-American women. STUDY DESIGN: This was a population-based cohort study of older women randomly selected from age and race strata. RESULTS: Weekly urinary incontinence was reported by 65 of 345 Asian women (18%), with stress and urge incontinence being approximately equally common. In multivariate analysis, higher body mass index (greater than 25 kg/m2) was associated with both stress incontinence (odds ratio 4.90, 95% confidence interval 1.76 to 13.68) and urge incontinence (odds ratio 2.49, 95% confidence interval 1.01 to 6.16) in Asians. Hysterectomy was a significant risk factor for stress incontinence (odds ratio 2.79, 95% confidence interval 1.03 to 7.54). Only 34% of Asian women with weekly urinary incontinence reported ever having sought treatment. Pelvic floor exercises were the most common form of treatment, being used by 29% of Asian women with weekly incontinence. Asians were less likely then white women to report anal incontinence (21% versus 29%, P = .007), although this difference became nonsignificant after adjusting for differences in risk factors. CONCLUSION: Asian women share some risk factors for stress and urge urinary incontinence with white women. Urinary incontinence is associated with anal incontinence among Asian women.

Single breath-hold T1 measurement using low flip angle TrueFISP.

A method for estimating T1 using a single breath-hold, segmented, inversion recovery prepared, true fast imaging with steady-state precession (sIR-TrueFISP) acquisition at low flip angle (FA) was implemented in this study. T1 values measured by sIR-TrueFISP technique in a Gd-DTPA-doped water phantom and the human brain and abdomen of healthy volunteers were compared with the results of the standard IR fast spin echo (FSE) technique. A good correlation between the two methods was observed (R2=0.999 in the phantom, and R2=0.943 in the brain and abdominal tissues). The T1 values of the tissues agreed well with published results. sIR-TrueFISP enables fast measurements of T1 to be obtained within a single breath-hold with good accuracy, which is particularly important for chest and abdominal imaging.

Mycobacterium interface keratitis after laser in situ keratomileusis.

PURPOSE: To report the clinical course, management, and outcome of infectious interface keratitis caused by mycobacterium species after laser in situ keratomileusis (LASIK). DESIGN: A small noncomparative interventional case series. PARTICIPANTS: Five eyes in four patients who underwent LASIK in different locations around the world and had culture-positive mycobacterium keratitis develop. INTERVENTION: The LASIK flap was lifted or amputated, samples were submitted for Ziehl-Neelsen acid-fast stain and Lowenstein-Jensen's agar cultures for diagnosis; topical treatment with fortified clarithromycin and amikacin was administered until clinical resolution. MAIN OUTCOME MEASURES: Time periods from onset to diagnosis and from diagnosis to clinical resolution, and the final visual acuity. RESULTS: Onset of symptoms of infection occurred after a mean of 20 days (range, 11 days-6 weeks) after LASIK or an enhancement procedure. Definitive diagnosis was obtained after a mean period of 4.5 weeks (range, 12 days-8 weeks) from onset. Keratitis resolved within 8.4 weeks (range, 1-18 weeks) of treatment with fortified clarithromycin and amikacin. Corticosteroids were found to worsen and prolong the course of disease. In four of five eyes the LASIK flap was amputated. CONCLUSIONS: Mycobacterial keratitis is a potentially vision-threatening complication after LASIK, characterized by a long latent period, delayed diagnosis, and a protracted course even under intensive specific antibiotic therapy. Inclusion of specific culture media and staining protocols for mycobacteria, along with aggressive treatment on diagnosis, including lifting or amputating the LASIK flap, culturing, topical fortified clarithromycin and amikacin, while avoiding corticosteroids, may significantly improve resolution of the infection and potentially improve the visual outcome.

Analgesic domains of interferon-alpha.

Interferon-alpha (IFNalpha) is not only an immunoregulatory factor, but is also an analgesic molecule. We ever reported that there exist distinct domains in IFNalpha molecule that mediate immune and analgesic effects respectively and inferred that the analgesic domain locates around the 122nd Tyr residue of IFNalpha molecule in the tertiary structure. After the 36th Phe residue, which was located closely to the 122nd Tyr residue in the tertiary structure, was mutated to Ser using site-directed mutagenesis, the analgesic activity of this mutant lost completely, but the antiviral activity of IFNalpha still maintained 40.5% of wild type IFNalpha. The results suggest that the 36th Phe residue is one of the constituent for the analgesic domain of IFNalpha and inferred that the analgesic domain of IFNalpha consists of the 122nd Tyr and the residues around the 122nd in the tertiary structure, which include the 36th Phe.