Pre- vs Post-Operative Levator Ani Subtended Volume in Patients Undergoing Hysterectomy: A Comparative Imaging Study.

INTRODUCTION AND HYPOTHESIS: The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani subtended volume (LASV) is an objective measure of the LAM's anatomical volume, derived from magnetic resonance imaging (MRI). This study was aimed at assessing the consistency between MRI and computed tomography (CT) in quantifying LASV, and to investigate the effect of hysterectomy on the LAM. METHODS: This retrospective study analyzed a cohort of 55 hysterectomy patients, utilizing pre-operative pelvic MRI and post-operative CT scans to measure the LASV. To evaluate the consistency between MRI and CT, the study employed the intraclass correlation coefficient and Bland-Altman agreement analysis in a subset of 32 patients with both pre-operative scans. A paired-samplet test was used to analyze LASV changes pre- and post-hysterectomy, and linear regression analysis was performed to account for potential risk factors that may influence post-operative LASV. RESULTS: High consistency between MRI and CT in measuring LASV was found, with an ICC of 0.911. We observed a significant increase in LASV following hysterectomy, with mean volume pre- and post-operatively of 16.66 cm3 and 18.87 cm3 respectively. Age and body mass index were significant predictors of post-hysterectomy LASV, whereas parity and the type of hysterectomy had no significant impact. CONCLUSIONS: Hysterectomy significantly affects the LAM, resulting in an increase in post-operative LASV. Moreover, this study verifies that MRI and CT can be used interchangeably for LASV measurements in clinical practice.

A predictive model for therapy failure in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy.

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

Wide-bore polyester sutures may create sufficient collagen for cure of prolapse/incontinence: a work in progress.

The main thrust of the Integral Theory Paradigm (ITP) is that inadequate ligament collagen causes pelvic organ prolapses (POP) and pelvic symptoms, a concept validated by multiple publications which cured POP and bladder/bowel/pain dysfunctions by collagen-creating slings. Sling surgery for surgical cure of these conditions was eliminated in the United States, Europe and other regulatory jurisdictions by banning all mesh products (including tapes) in about 2017. The aim of this work was to inform of the progress of a highly promising alternative method for collage creation for ligament repair: wide-bore polyester sutures accurately applied to weak ligaments. The scientific rationale for the wide-bore polyester plication method was a revisit and analysis of prior Instron testing data from a rejected polyester aortic graft from a doctoral thesis. The analysis indicated that the collagen produced by No. 2 polyester sutures would be sufficient to repair weakened pelvic ligaments. The surgical methodology consisted of application of wide-bore No. 2 or No. 3 polyester sutures to existing vaginal surgical techniques such as cardinal/uterosacral ligament (CL/USL) repair in the Fothergill operation, deep transversus perinei (DTP) ligamentous supports of the perineal body (PB) and uniquely, pubourethral ligament (PUL) repair for stress urinary incontinence (SUI). No vaginal tissue was excised. These operations are now being performed in several centres around the world. Because of this, the results detailed below are indicative only, and necessarily incomplete, as they are only from these units. Twelve month data (n=35) for SUI cure (83%) following PUL repair by the urethral ligament plication (ULP) operation has been submitted for publication; POP quantification (POPQ) points Ba, C, Bp, D were significantly improved at 6 weeks postoperative review following repair of CLs (cystocele) and USLs (uterine/apical prolapse) (n=56): deep transverse perinei ligament repair (descending perineal syndrome "DPS") (n=4) were cured at 6-12 months review. Though numbers are few, in the context of DPS being considered incurable, these numbers are significant. Except for the ULP operation, the techniques for cystocele, uterine prolapse, perineocele were essentially evolved versions of the Fothergill and standard PB repairs without any vaginal or ligament excisions. Though promising, more extensive and longer-term results are clearly required before this wide-bore polyester ligament repair method can become mainstream.

Principles of surgery according to the Integral Theory Paradigm (ITP).

A core concept of the Integral Theory System is that "ligaments are for structure; vagina is for function". The vagina and uterus should be conserved. Because the vagina is an organ, its collagen and elastin, which are so necessary for its function, cannot regenerate once they are removed. Removing the uterus involves severing the descending uterine artery, which is the principal blood supply of the proximal part of the uterosacral ligaments (USLs), and so may cause atrophy, which can cause future incontinence problems because of collagen loss after menopause. The diagnostic algorithm guides which of the five pelvic ligaments need repair. Native ligament plication can be adequate for prolapse/symptom cure, but only in premenopausal women. Postmenopausal women are usually collagen deficient and require collagen-creating tapes or wide-bore polyester sutures to restore structural collagen in the ligaments. Of extreme importance, vaginal tissue excision should be avoided, as consequent scarring may cause "tethered vagina syndrome" (TVS). TVS can cause massive uncontrolled urine loss because the scar tissue in the bladder neck area of the vagina can link the more powerful posterior muscles to the anterior, so the posterior urethra wall is forcibly pulled open, when given the signal to close. Instead of vaginal excision, a "concertina" suture technique re-assigns and shrinks excess vaginal tissue to normal anatomy by 6 weeks. In conclusion, the five key surgical principles of the Integral Theory System are: ligaments are for structure, vagina is for function; structure (prolapse) and function (symptoms) are related; repair the structure and you will restore the function; avoid vaginal excision and hysterectomy; create new collagen to reinforce the damaged ligaments.

Effect of high-frequency (5Hz) rTMS stimulating left DLPFC combined with galantamine on cognitive impairment after ischemic stroke and serum homocysteine and neuron-specific enolase.

Objective: To investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with galantamine in patients with cognitive impairment after stroke and its effect on serum homocysteine (Hcy) and neuron-specific enolase (NSE) levels. Methods: A total of 90 patients with cognitive impairment after the first ischemic stroke were enrolled. They were randomly divided into rTMS+ cognitive rehabilitation group, Galantamine + cognitive rehabilitation group, and rTMS+ Galantamine + cognitive rehabilitation group. All groups received routine medical treatment and limb rehabilitation treatment. The rTMS stimulation site was the left dorsolateral prefrontal cortex (left DLPFC), the magnetic stimulation frequency was 5 Hz, the magnetic stimulation intensity was 80% of the motor threshold level, and 3,000 pulses were given every day. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fugl-Meyer scale, and modified Barthel index, as well as rehabilitation scale and serum NSE and Hcy were evaluated before and after treatment (after 4 weeks). Results: After 4 weeks of treatment, the scores of MMSE, MoCa scale, Fugl-Meyer scale, and modified Barthel index in the three groups were significantly higher than those before treatment (all p < 0.05), while the serum NSE and Hcy levels of the three groups were decreased. rTMS+ Galantamine + cognitive rehabilitation group had higher scale scores, and the difference between the three groups was statistically significant compared with the other two groups (all p < 0.05). Conclusion: Cognitive rehabilitation combined with HF-rTMS and galantamine could improve the cognitive function of patients to the greatest extent, promote the recovery of physical activity, improve the self-care ability of daily life, and effectively reduce the serum HCY and NSE levels in patients with cognitive impairment after stroke. No randomized controlled trials of similar combination treatments have been reported. The better therapeutic effect may be related to the fact that galantamine combined with repetitive transcranial magnetism can activate the brain cholinergic system more extensively, promote brain neural remodeling through long-term potentiation and inhibit local neuroinflammatory responses in brain injury.

Advancements in LAM-based diagnostic kit for tuberculosis detection: enhancing TB diagnosis in HIV-negative individuals.

Objective: The purpose of this study was to investigate the diagnostic value of urine lipoarabinomannan (LAM) detection based on chemiluminescence assay for pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in HIV-negative individuals. Methods: A total of 215 patients and 37 healthy individuals were included according to inclusion and exclusion criteria, including 173 cases of PTB and 42 cases of EPTB. Sputum smears, sputum culture, TB-RNA, GeneXpert, and urine LAM results were obtained from all patients before treatment. Using the composite reference standard as the reference, the diagnostic performance of these methods for PTB and EPTB was evaluated, and the diagnostic performance and cost-effectiveness of different combinations were analyzed. Results: In PTB, LAM exhibited the highest sensitivity (55.49%), followed by GeneXpert (44.51%). In EPTB, LAM also had the highest sensitivity (40.48%), followed by GeneXpert (33.33%). When combined with one method, LAM combined with GeneXpert showed the highest sensitivity for both PTB (68.79%) and EPTB (61.9%). When combined with two methods, culture, GeneXpert, and LAM showed the highest sensitivity for both PTB (73.99%) and EPTB (69.05%). In terms of cost-effectiveness analysis, the price of LAM was significantly lower than that of GeneXpert ($129.82 vs. $275.79 in PTB and 275.79 vs. 502.33 in EPTB). Among all combinations, the combination of LAM and sputum smear had the lowest cost, with prices of $124.94 for PTB and $263.72 for EPTB. Conclusion: Urine LAM detection based on chemiluminescence assay can be used as an adjunct diagnostic tool for PTB and EPTB in HIV-negative individuals. This facilitates expanding the current application of urine LAM from solely HIV-positive populations to the general population. LAM detection can overcome the limitations of obtaining clinical samples, and its ease of sample acquisition will be beneficial for its broader application in a larger scope. For economically better-off areas, we recommend using a combination of LAM + GeneXpert+culture for higher sensitivity; for economically disadvantaged areas, LAM + smear microscopy combination can provide a quick and accurate diagnosis of tuberculosis at a lower cost.

Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Circular olefin copolymers made de novo from ethylene and α-olefins.

Ethylene/α-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle. However, synthesis of circular ethylene/α-olefin copolymers, including high-volume, linear low-density PE as well as high-value olefin elastomers and block copolymers, presents a particular challenge due to difficulties in introducing branches while simultaneously installing chemical recyclability and directly using industrial ethylene and α-olefin feedstocks. Here we show that coupling of industrial coordination copolymerization of ethylene and α-olefins with a designed functionalized chain-transfer agent, followed by modular assembly of the resulting AB telechelic polyolefin building blocks by polycondensation, affords a series of ester-linked PE-based copolymers. These new materials not only retain thermomechanical properties of PE-based materials but also exhibit full chemical circularity via simple transesterification and markedly enhanced adhesion to polar surfaces.

Tenapanor in Chinese ESRD patients with hyperphosphatemia on haemodialysis: a randomised, phase 3 trial.

Background: The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD). Methods: This was a randomised, double blind, phase 3 trial conducted at 26 dialysis facilities in China (https://www.chictr.org.cn/index.aspx; CTR20202588). After a 3-week washout, adults with ESRD on HD with hyperphosphatemia were randomised (1:1) using an interactive web response system to oral tenapanor 30 mg twice a day or placebo for 4 weeks. The primary endpoint was the change in mean serum phosphorous level from baseline to the endpoint visit (day 29 or last serum phosphorus measurement). Efficacy was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug. Results: Between 5 March 2021 and 8 June 2022, 77 patients received tenapanor and 73 received placebo. Tenapanor treatment (n = 75) resulted in a significantly greater least squares (LS) mean reduction in serum phosphate at the endpoint visit versus placebo (n = 72): LS mean difference -1.17 mg/dl (95% CI -1.694 to -0.654, P < .001). More patients receiving tenapanor achieved a serum phosphorous level <5.5 mg/dl at the endpoint visit (44.6% versus 10.1%). The most common treatment-related adverse event was diarrhoea [tenapanor 28.6% (22/77), placebo 2.7% (2/73)], which was mostly mild and led to treatment discontinuation in two patients receiving tenapanor. Conclusions: Tenapanor significantly reduced the serum phosphorous level versus placebo in Chinese ESRD patients on HD and was generally well tolerated.

The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair.

Pelvic organ prolapse (POP) has a high incidence rate among Chinese women. Repeated mechanical stimulation is an important factor causing POP, but the injury mechanism has not yet been elucidated. The purpose of this study is to explore the related mechanisms of pelvic floor supporting tissue damage caused by mechanical force and the application of stem cell therapy. First, we obtained vaginal wall and sacral ligament tissue samples from clinical patients for examination. Pelvic floor support tissues of POP patients displayed high expression of inflammation and immune disorders. Then, we constructed a rat model of childbirth injury. In vivo and in vitro experiments investigated the key mechanism of pelvic floor support tissue injury caused by mechanical force. We discovered that after mechanical force, a large number of reactive oxygen species (ROS) and macrophages rapidly accumulated in pelvic floor tissues. ROS stimulated macrophages to produce NLRP3 inflammatory complex, induced the release of interleukin (IL-1ß) and pyroptosis and exacerbated the inflammatory state of damaged tissues, persisting chronic inflammation of fibroblasts in supporting tissues, thus causing the pelvic floor's extracellular matrix (ECM) collagen metabolic disorder. Resultingly impeding the repair process, thereby causing the onset and progression of the disease. Through their paracrine ability, we discovered that adipose mesenchymal stem cells (ADSCs) could inhibit this series of pathological processes and promote tissue repair, asserting a good therapeutic effect. Simultaneously, to overcome the low cell survival rate and poor therapeutic effect of directly injecting cells, we developed a ROS-responsive PVA@COLI hydrogel with ADSCs. The ROS-scavenging properties of the gel could reshape the site of inflammation injury, enhance cell survival, and play a role in subsequent treatment. The findings of this study could serve as a basis for early, targeted intervention therapy for POP and representing a promising approach.

Precise selection of bone conduction hearing devices for congenital malformation of the middle and outer ear (CMMOE).

Background: No selection criteria for the four bone conduction hearing devices yet.Aims/Objectives: To compare effectiveness of four bone conduction hearing devices in patients with bilateral Congenital Malformation of the Middle and Outer Ear (CMMOE).Material and Methods: 24 Patients (25 ears) were divided into five groups: 1) Bone Anchored Hearing Aid softband (BAHA-s), 2) BAHA implant (BAHA-i nested within group 1), 3) Vibration Sound Bridge implant (VSB-i), 4) Bone Bridge implant (BB-i), and 5) Bone Conduction Hearing Aid softband (BCHA-s). One patient implanted VSB and BB. Auditory parameters were compared: 1. Communication, 2. Average Air Conduction Thresholds (ACT) of pure tone, 3. Sentence Recognition Scores in quiet (SRS-q) and noisy (SRS-n) settings. The one-way analysis of variance (ANOVA) were employed to compare the differences in ACT and SRS-q/n among the groups, a statistical significance level of P < 0.05 was applied.Results: After hearing aid usage, all 24 patients (25 ears) reached or approached the normal in communication (i.e. from difficult to smooth), average ACT and SRS-q/SRS-n (no difference among groups, p > 0 .05). However, there was the difference in the optimal frequency of ACT and the absolute value of SRS-q/SRS-n for VSB/BAHA implants was higher than that for BB and BAHA softband.Conclusions and Significance: The precise selection of the four hearing devices mainly depends on patient's hearing level, the optimal frequency of ACT and absolute values of SRS-q/SRS-n.