International braz j urol : official journal of the Brazilian Society of UrologyEduardo Fagundes Muricy, Jahel Alves Estrela Lopes, Emanoel Nascimento Santos, Lucas Teixeira Aguiar Batista, Ubirajara Barroso
PURPOSE: Metoidioplasty is used in transmasculine gender-affirming surgery; however, limited neophallus length and girth remain significant challenges (1-4). We describe a combined technique using Total Corpora Mobilization (TCM) for elongation and a Martius flap for girth enhancement (5-9). MATERIALS AND METHODS: Fifteen transgender men underwent first-stage metoidioplasty with TCM and Martius flap between 2023 and 2026. The vestibular plate and urethra were mobilized, followed by circumferential clitoral degloving and suspensory ligament division. A pubic periosteal incision was made, and subperiosteal dissection was performed using bipolar cautery while preserving a portion of the periosteum attached to the corpora cavernosa. The urethra was further mobilized and the triangular ligament was divided, followed by lateral dissection of both corpora cavernosa and complete release from the crura. An oral mucosa graft was used to create the urethral plate. The preserved periosteum was fixed to the dorsal tunica albuginea, and a vascularized Martius flap harvested from the labia majora was secured over the corpora for girth augmentation. Scrotal flaps provided wound coverage. RESULTS: The index patient achieved a neophallus length of 6.4 cm, representing a 1.9 cm gain over the preoperative stretched clitoral length. Median length gain was 3.7 cm, and mean circumference increase was 1.6 cm. Glans perfusion and tactile sensitivity were preserved in all patients, with no vascular or sensory complications recorded. CONCLUSIONS: Combined TCM and Martius flap metoidioplasty is feasible and reproducible. By achieving corporal release beyond previously described techniques, TCM may meaningfully enhance neophallus projection while preserving perfusion and sensation. Larger cohorts and longer follow-up are required to confirm the durability and functional outcomes of this approach.
International braz j urol : official journal of the Brazilian Society of UrologyNaiwen Chen, Lichen Chen, Jinming Cai, Mingyue Tan, Dongliang Xu
INTRODUCTION: Radical cystectomy (RC) is the standard therapy for muscle-invasive bladder cancer (MIBC) and refractory high-risk non-muscle-invasive bladder cancer (1-3). Single-port robot-assisted radical cystectomy (RARC) offers notable minimally invasive advantages (4-6), whereas conventional transperitoneal approaches are associated with intestinal and gastrointestinal complications (7). This study evaluated an optimized extraperitoneal single-port RARC with orthotopic neobladder reconstruction for improved surgical safety and clinical outcomes. MATERIALS AND METHODS: A 57-year-old male presented with three months of intermittent painless gross hematuria. Pelvic CT revealed a bladder mass. Preoperative biopsy confirmed high-grade urothelial carcinoma with muscularis propria invasion, and the patient received gemcitabine-cisplatin neoadjuvant chemotherapy before radical surgery. Preoperative MRI identified a 3.2×2.9×2.6 cm bladder lesion without extravesical invasion or lymphadenopathy. During the procedure, the patient was placed in a supine position with buttocks elevated. A 5-cm infraumbilical single incision was made for da Vinci Xi-assisted extraperitoneal RARC, and a single-port multichannel device was deployed through the incision. Robotic instruments including a 30° endoscope, monopolar scissors, bipolar forceps, and a robotic stapler were arranged in a chopstick configuration. Via the extraperitoneal approach, we mobilized the bilateral ureters, bilateral vas deferens, and umbilical artery, dissected the bladder lateral ligaments with vascular ligation, and established a sufficient extraperitoneal working space. Bladder and prostate dissection was performed along the perivesical avascular plane, with careful protection and precise hemostasis of the dorsal venous complex. Standard pelvic lymphadenectomy was concurrently conducted during radical resection of the bladder and prostate (8). A segment of ileum was then harvested to construct an orthotopic neobladder (9), followed by anastomosis with the bilateral ureters and urethral stump. RESULTS: Operative time was 400 minutes with 200 mL blood loss and no transfusion. No perioperative complications occurred, and the patient was discharged on postoperative day 6. Pathological diagnosis was pT2aN0M0 with negative surgical margins and negative lymph nodes. The 12-month follow-up showed no tumor recurrence, normal renal function, complete daytime continence, and mild nocturnal incontinence requiring one nightly pad. CONCLUSIONS: Extraperitoneal single-port RARC with orthotopic neobladder reconstruction is a feasible minimally invasive procedure for MIBC. The optimized infraumbilical single-incision technique preserves peritoneal integrity and avoids intestinal mobilization, effectively reducing abdominal complications. It achieves reliable oncological results and improves patients' postoperative continence and quality of life.
International braz j urol : official journal of the Brazilian Society of UrologyLuciano A Favorito
This review aims to provide a comprehensive analysis of the anatomy of the retroperitoneal and abdominal fascias. We analyzed papers published in the past 70 years in the databases of Pubmed, Embase and Scielo. We excluded case reports, editorials and opinions of specialists. Studies were excluded if they lacked clear anatomical descriptions of the fascias, if full-text access was unavailable, or if they were published in languages other than Portuguese, English, or Spanish. This narrative review addresses the anatomical integration, surgical techniques, and functional importance of the fascias. Renal fascia is a dense connective tissue encasing kidney, perirenal fat, adrenal gland; composed of anterior (Gerota's) and posterior (Zuckerkandl-related/renal) layers that fuse laterally and superiorly. Toldt fascia is a plane formed where the mesocolon (ascending or descending) fuses to the posterior parietal peritoneum / posterior abdominal wall. The lateroconal fascia is a lateral continuation of the renal fascia where anterior and posterior renal layers fuse to form a sheet toward the lateral abdominal wall and Fredet's fascia is a fusion plane between the visceral peritoneum of the hepatic flexure/transverse mesocolon and the anterior surface of the duodenum/pancreatic head (anterior to pancreatic head/duodenum) with a critical landmark in right colectomy.
International braz j urol : official journal of the Brazilian Society of UrologyMarcos Tobias-Machado, Ricardo C Brianson, John Eder Gamarra Bravo, Alcedir Raiser, Eliney Faria
INTRODUCTION: Horseshoe kidney is an uncommon congenital fusion anomaly that can make renal tumor surgery especially challenging because of altered rotation, limited mobility, variable vascular supply, and an unpredictable collecting system (1-7). This video presents a robot-assisted partial nephrectomy for a high-complexity renal tumor in this setting. CASE PRESENTATION: A 33-year-old man, with ECOG 0 and no relevant comorbidities, was diagnosed with a 7.5-cm solid renal mass in the central posterior portion of the left moiety of a horseshoe kidney. The lesion had a RENAL score of 10p. Contrast-enhanced computed tomography and three-dimensional reconstruction were used to understand the relationship between the tumor, aberrant vessels, renal hilum, and collecting system, supporting the decision to attempt nephron-sparing surgery (5, 8). Surgical technique and results: The procedure was performed through a transperitoneal robotic approach with the patient in right lateral decubitus using the Da Vinci Si platform. Port placement followed a standard renal robotic configuration, with a paramedian supraumbilical camera port, three robotic working ports along a craniocaudal lateral axis, a caudal fourth-arm port, and two medial assistant ports for suction, exposure, and support during renorrhaphy. After exposure of the horseshoe kidney and left hilar dissection, two arterial branches and one renal vein were identified. Tumor excision was performed under vascular control, with 20 minutes of warm ischemia and no collecting system opening, followed by two-layer absorbable renorrhaphy with adjunctive hemostatic agents. The operative time was 150 minutes. No transfusion, conversion, drain placement, or relevant immediate complication occurred. The urinary catheter was removed after 24 hours, and the patient was discharged 72 hours after surgery. Pathology showed clear cell renal cell carcinoma, Fuhrman grade 3, pT2N0M0, with negative surgical margins. During 12 months of oncologic follow-up, renal function remained stable and semiannual imaging showed no evidence of recurrence. Contemporary video reports have also emphasized the feasibility of advanced robotic renal surgery and complex partial nephrectomy strategies in selected patients (9, 10). CONCLUSION: In a carefully selected patient, robot-assisted partial nephrectomy supported by three-dimensional planning was feasible for a complex renal tumor in a horseshoe kidney, with negative surgical margins, preserved renal function, and no recurrence during 12 months of follow-up.
Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyO N Bobrovskaya, A D Skvortsova
The problem of availability of abortion services for women in countries of world community is not only not losing its importance, but is undergoing new stage of actualization, since it has no clear understanding and is often raised in the context of solving demographic problems of aging society. At the same time, analysis reveals vulnerability of position of those using religious context in womans self-determination regarding disposal of her own body and right to refuse compulsion to terminate her pregnancy by physiological childbirth without her psychological, social and economic readiness and public support. Referring to various testimonies and sources, we appeal to necessity of working out common criteria to ensure womens access to medical care related to procedure of abortion in order to reduce mortality from diseases associated with self-abortions menacing live and health of women. The issues considered in the study may affect various spheres of social, medical and legal field and have wide area of practical implementation. The purpose of the study is to identify causes and to establish consequences of womens limited access to abortion services, as well as legal and ethical aspects of overcoming these restrictions.
Pakistan journal of pharmaceutical sciencesHuang Ling, Zhang Yu, Deng Shu
BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.
Pakistan journal of pharmaceutical sciencesLinhua Zhu, Yongfang Yue, Lili Cao
BACKGROUND: Intrauterine adhesion (IUA) is a common complication of endometrial injury. Bone marrow mesenchymal stem cells (BMSCs) have been implicated in endometrial repair, but strategies to enhance their therapeutic efficacy remain to be optimized. The C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis plays a pivotal role in BMSC homing. OBJECTIVE: This study aimed to test the hypothesis that ATI-2341, a functionally selective allosteric regulator of CXCR4, enhances the therapeutic efficacy of BMSCs in a rat IUA model. METHODS: After establishing the endometrial injury model, rat BMSCs were extracted and treated with ATI-2341 TFA (100 ng/mL). IUA model rats were randomly divided into model control group, BMSCs group, BMSCs+ATI-2341 TFA group, BMSCs+PBS group and Positive control group (n=10 each). Endometrial thickness was assessed by hematoxylin and eosin (HE) staining; cell proliferation by the methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) protein expression by Western blot; and cytokeratin and vimentin expression by immunohistochemistry. RESULTS: ATI-2341 TFA-pre-treated BMSCs significantly increased endometrial thickness compared to untreated BMSCs (P < 0.05) or estrogen (P < 0.05). ATI-2341 TFA enhanced BMSC proliferation at 48 h (P < 0.05) and 72 h (P < 0.05). BMSCs exposed to ATI-2341 TFA or estrogen exhibited strong cytokeratin positivity and vimentin negativity. MMP-9 was downregulated (P < 0.05) and TIMP-1 upregulated (P < 0.05) in the ATI-2341 TFA group relative to controls. CONCLUSION: ATI-2341 TFA promotes acquisition of epithelial-like immunophenotype in BMSCs within the injured endometrial microenvironment and is associated with improved endometrial morphology in IUA rats. These findings provide preliminary evidence for the functional modulation of BMSCs by CXCR4-targeted therapy in endometrial repair.
Journal of foot and ankle researchLevi Kadiri, Anthony Maher, Andy Bridgen
BACKGROUND: Diabetic foot osteomyelitis (DFO) is a serious complication of diabetic foot ulcers and is associated with increased risk of amputation, morbidity, and mortality. Bone biopsy remains the most definitive diagnostic modality, yet controversy persists over its diagnostic utility This study reviews the diagnostic concordance of histopathology and microbiology in bone biopsy specimens from patients with DFO and examines the clinical implications of the findings. METHODS: A systematic review was conducted using PubMed, Medline, CINHAL, Cochrane Library, and Google Scholar. Studies included adult patients with DFO in whom bone biopsy specimens underwent both histopathological and microbiological analysis. Five core studies met the eligibility criteria. Data on study design, setting, population, diagnostic methods, concordance rates, and outcomes were extracted and synthesized utilising a quantitative narrative synthesis. RESULTS: Across the five studies (n = 308 patients), histopathology and microbiology showed modest concordance, with mean rates of concordant positive results of 43.4% and common discordant findings. Histopathology demonstrated higher specificity, while microbiology had higher sensitivity, ranging from 70% to 83.9% but greater susceptibility to contamination. Positive histopathology was more strongly associated with the need for revision surgery or extended antibiotic therapy. DISCUSSION: Histopathology appears to offer superior diagnostic specificity, whereas microbiology provides valuable information for antimicrobial management. Frequent discordance underscores the importance of interpreting results in a clinical context. Further robust, prospective studies are needed to clarify the optimal diagnostic approach and standardise definitions.
The authors have informed the Pakistan Journal of Pharmaceutical Sciences (PJPS) of an error in Figure 5 of the published article. During the editorial revision process, an incorrect version of Figure 5 was inadvertently included in the final published version. The authors have confirmed that the extreme-right panel (panel D) should be removed and that the remaining panels constitute the corrected Figure 5. Accordingly, Figure 5 is corrected by removing panel D. No other part of the figure is modified. The caption of Figure 5 remains unchanged, and no other figures or content of the article require modification. This corrigendum records the correction to the published version of the article. The correction is limited to the removal of panel D from Figure 5.
Pakistan journal of pharmaceutical sciencesLin Jin, Panpan Pan, Jialin Wang, Xiaoping Chen, Min Chen, Shaobing Dai, Lihong Sun, Peng Ying
BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg·kg-¹ bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 μg/mL. The concentration was then adjusted in steps of 0.5 μg/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 μg/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 μg/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg·kg-1·h-1, 95% CI: 8.10-9.15 vs. 9.89 mg·kg-1·h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 μg·kg-1·min-1, 95% CI: 0.21-0.24 vs. 0.27 μg·kg-1·min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.
Journal of foot and ankle researchKazuki Kanazawa, Shunsuke Akiho, Masahiko Sakai, Ken Ichikawa, Soshiro Goshima, Ryohei Haraguchi, Takuaki Yamamoto
BACKGROUND: Hallux valgus is a frequent forefoot deformity in older adults and has been linked to impaired balance, gait dysfunction, and increased fall risk. However, its prevalence among patients with femoral neck fracture and its association with postoperative functional outcomes remain unclear. METHODS: This single-center retrospective study included 235 patients aged ≥ 65 years with available radiographic data who underwent surgery for femoral neck fracture between 2022 and 2024. Hallux valgus was defined on weight-bearing radiographs as a hallux valgus angle (HVA) ≥ 20°. Functional outcomes were evaluated using the Functional Independence Measure (FIM) at 3 months postoperatively. Multivariable linear regression analysis was performed to determine whether hallux valgus was independently associated with motor FIM scores after adjustment for age, sex, surgical procedure, and cognitive function. RESULTS: Among the 235 patients with radiographic data, 178 (76%) were women, with a median age of 85 (77-90) years; 86% of patients underwent bipolar hemiarthroplasty. Hallux valgus was present in 55% (130/235), including 20% (47/235) with moderate-to-severe deformity (HVA ≥ 30°). Patients with hallux valgus had significantly lower motor FIM scores at 3 months than those without the deformity (p = 0.044), whereas cognitive and total FIM scores did not differ. In multivariable analysis, hallux valgus (HVA ≥ 20°) was independently associated with lower motor FIM scores (B = -5.92, 95% CI -10.95 to -0.89; p = 0.021). CONCLUSIONS: Hallux valgus is highly prevalent in patients with femoral neck fracture and is independently associated with lower postoperative motor function. Assessment of hallux valgus may provide additional insight into postoperative functional prognosis in this population.
BACKGROUND: Toxic acute renal failure (ARF) involves severe oxidative stress. The Nrf2 pathway is a key antioxidant defense mechanism. OBJECTIVES: To investigate whether naloxone combined with hemoperfusion alleviates oxidative injury via Nrf2 activation in toxic ARF. METHODS: In this single-center retrospective cohort study at Qiqihar Medical University Hospital, 67 patients were enrolled through medical record screening. The control group (n=39) received hemoperfusion alone; the observation group (n=28) received additional intravenous naloxone (0.8 mg bolus + 2.0 mg/24 h infusion for 7 days). Renal function and oxidative markers were assessed before treatment, at 24 h and day 7. Multivariate regression analysis was used to adjust for confounding factors. Separately, 30 rats were randomized into control, model and treatment groups (n=10 each). The treatment group received intraperitoneal naloxone (1.0 mg/kg) plus simulated hemoperfusion. RESULTS: After adjusting for baseline imbalances, combined therapy was independently associated with significant reductions in Scr and BUN in patients (adjusted β = -8.52, 95% CI: -12.37 to -4.67, P < 0.001) and with significant improvements in renal function and histopathology in rats. Combined therapy decreased tubular injury markers (β2-MG, KIM-1, NGAL, L-FABP) in rats. Mechanistically, it was associated with activation of the Nrf2/HO-1/NQO1 pathway, enhanced SOD activity and reduced MDA levels. Improvements were time-dependent (24 h to day 7). CONCLUSIONS: Naloxone combined with hemoperfusion activates the Nrf2 pathway, attenuates oxidative stress and improves renal function in toxic acute renal failure.
BACKGROUND: Elderly patients with cervical radiculopathy present therapeutic challenges owing to comorbidities and medication-related risks. Long-term pharmacotherapy and surgical interventions are often suboptimal, necessitating evaluation of optimized pulsed radiofrequency strategies under image guidance. OBJECTIVES: This superiority trial compared the efficacy and safety of ultrasound-guided cervical nerve root high-voltage pulsed radiofrequency (HVP-PRF) versus conventional pulsed radiofrequency (C-PRF) for pain management in elderly patients with cervical radiculopathy. METHODS: This single-center, parallel-group, assessor-blinded randomized controlled trial enrolled patients aged 60-85 years with cervical radiculopathy, randomly assigned (1:1) to HVP-PRF (70 V) or C-PRF (45 V). Procedures were performed under ultrasound guidance with sensory/motor stimulation confirmation and temperature ≤42°C. The primary outcome was change in upper-limb radiating pain on the Numeric Rating Scale (ΔNRS) from baseline to 3 months. Secondary outcomes included Neck Disability Index (NDI), neck pain NRS, Patient Global Impression of Change, responder rates, rescue analgesia use, and adverse events. Follow-up occurred at 1 week, 1, and 3 months. RESULTS: A total of 104 patients were randomized and 101 received treatment. At 3 months, HVP-PRF demonstrated significantly greater radiating pain improvement versus C-PRF (adjusted mean difference 1.24, 95% CI 0.46-2.02, P=0.002). Functional improvement (NDI) was superior in the HVP-PRF group at 3 months (AMD 6.47, 95% CI 2.11-10.83, P=0.004). Responder rates (≥50% pain reduction) were higher with HVP-PRF at 3 months (68.75% vs. 42.22%, OR 3.01, P=0.011) and 6 months (65.22% vs. 43.18%, OR 2.52, P=0.035). Rescue analgesic use was lower in the HVP-PRF group during 1-3 months intervals (both P<0.05). Adverse event rates were comparable (27.45% vs. 32.00%). CONCLUSION: Under ultrasound visualization and electrical stimulation-based target confirmation with temperature control ≤42°C, HVP-PRF provided greater and more durable relief of upper limb radiating pain compared with C-PRF in elderly patients with cervical radiculopathy, with a comparable safety profile.
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction. Bone marrow mesenchymal stem cells (BMSCs) have shown therapeutic potential in RA, but the underlying mechanisms remain poorly understood. OBJECTIVES: To investigate the effects of BMSCs on human RA fibroblast-like synovial MH7A cells and complete Freund's adjuvant (CFA)-induced arthritis in rats and to explore the involvement of the JAK/STAT and TLR-4/NF-κB signaling pathways. METHODS: BMSCs were isolated and co-cultured with MH7A cells. CFA-induced arthritis rat models were established. MH7A cell viability, inflammatory cytokine levels, paw withdrawal thermal latency (PWTL), gait parameters and the expression of JAK/STAT and TLR-4/NF-κB pathway-related genes and proteins were assessed. RESULTS: In-vitro, BMSC co-culture significantly inhibited MH7A cell viability and reduced TNF-α, IL-6 and IL-8 levels. BMSC treatment also downregulated the expression of JAK2, p-JAK2, STAT3, p-STAT3, TLR4, P65 and p-P65 in MH7A cells. In-vivo, BMSC administration improved PWTL and gait parameters, reduced serum inflammatory cytokine levels and suppressed the expression of JAK/STAT and TLR-4/NF-κB pathway components in synovial tissues of CFA-induced arthritic rats. CONCLUSION: BMSCs alleviate RA by inhibiting inflammatory responses in vitro and in vivo and the underlying mechanism may involve blockade of the JAK/STAT and TLR-4/NF-κB signaling pathways.
Pakistan journal of pharmaceutical sciencesZhenhua Yin, Xiaolan Lu, Limei Bu
BACKGROUND: General anesthesia is essential for gastric cancer surgery, but delayed awakening increases postoperative risks and costs. Although morroniside is known for its neuroprotective properties, its role in anesthesia recovery has remained unclear. OBJECTIVES: To investigate whether morroniside accelerates awakening from propofol anesthesia and whether hypothalamic GABAergic neurons mediate this effect. METHODS: A gastric cancer mouse model was established. Mice were divided into seven groups: normal, model, vehicle control, light anesthesia, deep anesthesia, morroniside-treated and propofol-only. The loss and recovery of righting reflex (LORR/RORR) were measured. EEG recording, immunofluorescence staining for GABA and c-Fos and fiber photometry for Ca2+ signals in hypothalamic GABAergic neurons were performed. RESULTS: Morroniside significantly shortened RORR without affecting LORR. During anesthesia induction, Ca2+ signals in hypothalamic GABAergic neurons increased sharply, then decreased during maintenance and remained low during early recovery. Morroniside increased GABA concentrations in multiple brain regions, especially the hypothalamus and reduced the EEG δ-band power while increasing α-band power. It also decreased propofol-induced c-Fos expression. CONCLUSION: Morroniside accelerates awakening from propofol anesthesia in a gastric cancer mouse model, potentially by modulating hypothalamic GABAergic neuron activity and EEG oscillatory patterns. These findings support its potential as an adjuvant in anesthesia.
Renal failureLiyu Lin, Yiqi Su, Bing Yu, Ziyan Shen, Ying Huang, Caifeng Li, Jie Teng
IgA nephropathy (IgAN) has a heterogeneous clinical course. We retrospectively studied 180 patients with biopsy-proven IgAN and at least 3 years of clinical follow-up. Patient-specific eGFR slopes were estimated from available measurements at biopsy and the 6-, 12-, 18-, 24-, 30-, and 36-month follow-up points. We built a post hoc multivariable model guided by clinical relevance. Oxford T was treated as categorical, with T0 as reference. The median eGFR slope was -1.12 mL/min/1.73 m2/year, and 35 patients (19.4%) met the operational rapid-progression threshold of < -5 mL/min/1.73 m2/year. In the primary model, higher ln(UACR + 1) predicted a steeper decline (β= -0.612, 95%CI -1.073 to -0.150). T2 lesions predicted a 3.87 mL/min/1.73 m2/year faster loss than T0 (β= -3.870, 95%CI -7.087 to -0.654), whereas T1 did not differ from T0. The model R2 was 0.159 (adjusted R2=0.130). UACR and T2 estimates remained negative under HC3 inference and after excluding influential observations, although T2 was less stable in some restricted analyses. Baseline albuminuria was the most consistent adverse marker of eGFR slope. T2 lesions were linked to faster decline as well, but this estimate derived from only 16 patients (8.9%) and lost statistical significance when analysis was restricted to ≥5 measurements, making the finding tentative and strictly hypothesis-generating.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupChenchen Bing, Teija Sainio, Ari Partanen, Simon Köttgen, Roberto Blanco Sequeiros
INTRODUCTION: Non-perfused volume (NPV) is a key imaging biomarker for treatment efficacy in MR -guided high-intensity focused ultrasound (MR-HIFU). In uterine fibroids therapies, the NPV ratio is strongly associated with clinical outcomes and long-term efficacy. We developed and clinically evaluated a deep learning-based automatic NPV segmentation model to facilitate standardized and efficient post-treatment assessment. MATERIALS AND METHODS: Contrast-enhanced T1-weighted MR images from 79 patients treated with MR-HIFU were retrospectively analyzed, with NPVs manually delineated as the reference. A 2D U-Net convolutional neural network was optimized using a Tversky loss function (α = 0.7) to prioritize volumetric robustness. Performance was evaluated using similarity metrics (Dice coefficient [DC], 95th percentile Hausdorff distance [HD95]) and clinically relevant measures, including Bland-Altman analysis of volumetric quantification error, precision, recall, slice-level missing rate, and processing time. RESULTS: In the independent test cohort (n = 12), the model achieved a median DC of 0.900 (IQR: 0.841-0.920) and a median HD95 of 0.42 (IQR: 0.32-0.60) mm. Median absolute NPV quantification error was 4.3 mL (IQR: 2.6-8.4 mL), corresponding to a median relative error of 2.3% (IQR: -2.4% - 10.5%). Precision and recall were 0.909 (IQR: 0.843-0.940) and 0.912 (IQR: 0.881-0.931), respectively, with 2.8% of ground truth-positive slices missed. Average processing time per patient (∼384 slices) was 1-2 min. CONCLUSION: The proposed 2D U-Net provides accurate and time-efficient automatic NPV segmentation. Quantitative and clinically oriented evaluation demonstrates reliable volumetric assessment with minimal slice-level omission, supporting integration into routine MR-HIFU treatment workflows.
Global health actionFelix Ikenna Onunkwor, Rose Aguolu
BACKGROUND: Quality assessment in family planning (FP) and post-abortion care (PAC) programmes is shaped by workforce capability, programme context, and assessment modality. Longitudinal evaluations may misattribute quality-score differences if repeated measurements and temporal patterning are ignored. OBJECTIVE: To examine associations of workforce characteristics, calendar period, service-delivery channel, and assessment modality with Quality Technical Assessment (QTA) performance in Sierra Leone, 2019-2022. METHODS: We analysed 108 QTA records from 23 service delivery points using Gaussian generalised estimating equations with facility-level clustering and robust standard errors. Models included year, modality, channel, active staff count, and core-service competency coverage; full-time staffing and assessor identity were examined in sensitivity analyses. In 2021, all facilities received planned in-person and then remote assessments in a fixed programme-wide sequence. RESULTS: Mean QTA scores increased descriptively from 89.8% (SD 7.4) in 2019 to 94.2% (SD 4.7) in 2022. In the primary model, 2020 scores were lower than 2019 (B = -5.15; 95% CI -9.99 to -0.32). Active staff count was inversely associated with QTA scores (B = -2.86; 95% CI -4.47 to -1.26). Remote assessment was associated with higher adjusted scores, but this cannot be interpreted causally because modality was confounded with year and assessment order. CONCLUSIONS: QTA performance varied across calendar periods and workforce structure. Longitudinal evaluations should account for within-facility correlation and modality timing before attributing quality differences to the workforce or assessment approach.
Gynecological endocrinology : the official journal of the International Society of Gynecological EndocrinologyXiangyan Ruan, Juan Du, Muqing Gu, Fengyu Jin, Jing Jin, Yanglu Li, Jiaojiao Cheng, Yanqiu Li, Weimin Kong, Qi Zhang, Zecheng Wang, Mingzhen Zhang, Anming Liu,…
OBJECTIVE: This article reports on the world's first live birth after ovarian tissue cryopreservation and transplantation (OTCT) in a patient with colon cancer. METHODS: A 29-year-old unmarried nulliparous patient underwent ovarian tissue cryopreservation before chemotherapy. After chemotherapy-induced premature ovarian insufficiency, she received the first transplantation of six thawed ovarian cortex strips. Despite normal ovarian function being maintained for over 2 years, she requested and underwent a second transplantation with another six strips to maximize her chances of pregnancy. RESULTS: After the first transplantation, she resumed spontaneous menstruation with restored ovarian function, which was remained functional for 28 months until the second transplantation. Following the second transplantation, she conceived spontaneously without assisted reproductive technology two months after grafting. Routine prenatal examinations showed normal fetal development without abnormalities. She delivered a healthy baby girl weighing 2785 g with Apgar scores of 8/9 at 1 and 5 min. CONCLUSIONS: This case demonstrates the feasibility and safety of OTCT for fertility and ovarian function preservation in patients with colon cancer.
Annals of medicinePeixin Wang, Mengyu Zhang, Yucheng Lai, Tao Song, Yan Shen, Haiying Chen, Xiaoyan Chen
BACKGROUND: PAX1/JAM3 methylation are promising biomarkers for high-grade cervical intraepithelial neoplasia (CIN) detection, but menopausal status may affect diagnostic accuracy. This retrospective study compared their clinical performance between premenopausal and postmenopausal women undergoing colposcopy. METHODS: 705 women undergoing colposcopy for abnormal screening results and/or clinical symptoms were stratified by menopausal status, including 192 postmenopausal and 513 premenopausal women. Subjects were further classified into ≤CIN1 and CIN2+ groups according to histopathology. Diagnostic and triage utility of PAX1/JAM3 methylation for identifying CIN2+ lesions were compared between premenopausal and postmenopausal women. RESULTS: PAX1/JAM3 methylation demonstrated superior diagnostic performance for CIN2+ detection in postmenopausal women compared with premenopausal women, either alone or in combination. Sensitivities of PAX1m and JAM3m in postmenopausal women (90.00%, 95% CI: 76.34-97.21%; 82.50%, 95% CI: 67.22-92.66%) were higher than those in premenopausal women (61.98%, 95% CI: 52.71-70.65%; 60.33%, 95% CI: 51.04-69.11%) (all p < 0.05). The combination improved sensitivity to 72.73% in premenopausal women and maintained 92.50% in postmenopausal women. Besides, PAX1/JAM3 methylation outperformed cytology and HPV16/18 testing in both groups (p < 0.001). In HPV16/18-positive or cytology triage, methylation increased positive predictive values (PPVs) for CIN2+/CIN3+ and reduced colposcopy referrals . However, CIN2+ missed rates in premenopausal women (27.54% for HPV16/18-positive triage and 23.85% for cytology triage) were higher than those in postmenopausal counterparts. CONCLUSIONS: The diagnostic performance of PAX1/JAM3 methylation for high-grade cervical lesions differs distinctly between premenopausal and postmenopausal women undergoing colposcopy. Menopausal status should be considered when applying methylation biomarkers, particularly as a valuable auxiliary tool to improve diagnostic accuracy in elderly women.
Journal of medical economicsMichael Dore, Derek W Ebner, A Mark Fendrick, Chris Estes, Gustavus Aranda, Amber Coleman, Vahab Vahdat, Jordan J Karlitz, Tiago Rua, Frank van Hees, Paul J Li…
AIM: Multi-target stool DNA (mt-sDNA) and fecal immunochemical testing (FIT) are home-based options for colorectal cancer (CRC) screening. Next-generation mt-sDNA has enhanced sensitivity for CRC and advanced precancerous lesions compared with FIT and is not subject to the same capacity constraints as colonoscopy. This analysis evaluated the economic and clinical implications of increasing the proportional utilization of next-generation mt-sDNA. METHODS: A budget impact model was developed from the validated CRC-AIM microsimulation model. The model simulated a cohort of 1 M average-risk, screen-eligible adults over a 3-year time horizon from an integrated delivery network perspective. The status quo scenario assumed an initial utilization of 20% next-generation mt-sDNA, 20% FIT, and 60% colonoscopy screening. In a hypothetical increased next-generation mt-sDNA scenario, its utilization expanded to 35% within 3 years, while FIT and colonoscopy utilization decreased to 15% and 50%, respectively. Test performance characteristics, real-world adherence, and cost inputs (i.e. screening test and programs, colonoscopy adverse events, CRC treatment) were derived from published literature. Multiple scenario analyses were conducted. RESULTS: Among 1 M members, total costs in the status quo scenario were $1.058B and with increased next-generation mt-sDNA use were $1.046B, generating an estimated savings of $12.5 M (-$0.35 per member per month). Increasing next-generation mt-sDNA improved the CRC screening rate by 1.1%. Overall, 10,467 fewer screening colonoscopies and 1,912 more follow-up colonoscopies after a positive stool-based test were performed. An additional 17 CRCs were screening-detected, 11 fewer were clinically detected, and there was one less CRC-related death. Increased next-generation mt-sDNA utilization remained cost-saving with all scenario analyses. CONCLUSIONS: In this budget impact model, shifting a small proportion of current FIT and colonoscopy utilization to next-generation mt-sDNA for average-risk CRC screening is estimated to be cost-saving. Increasing the next-generation mt-sDNA utilization also improves the screening rate and clinical outcomes while optimizing availability of capacity-limited colonoscopy resources.
International journal of qualitative studies on health and well-beingMartine Lindschouw Andersen, Mia Hyberst Kjeldsen, Bente Appel Esbensen, Jan Christensen, Heidi Tegner
INTRODUCTION: Lumbar spinal fusion (LSF) is a common surgical treatment for chronic low back pain (CLBP), yet evidence of its effectiveness compared with conservative care remains inconclusive. While pain is the primary clinical indication, psychosocial factors, including hopes and expectations, may influence outcomes. However, little is known about how individuals experience life with CLBP before surgery or what they hope to regain after LSF. OBJECTIVE: To explore patients' experiences with CLBP prior to LSF and their hopes and expectations for life after surgery. METHODS: A qualitative, exploratory study using semi-structured preoperative interviews and analysed using Clarke and Braun's thematic analysis. RESULTS: Fourteen patients (11 women, 3 men) scheduled for LSF participated. Three themes captured how participants experience pain as overwhelming, impacting cognition, emotion, and daily functioning, alongside loss of identity and autonomy, leading to social withdrawal and reduced belonging. Despite these challenges, participants expressed strong hopes, often more prominent than concrete expectations, to regain agency, connection, and meaning in work and family life. CONCLUSION: Living with CLBP prior to LSF involves major negative disruptions to identity, agency, and social relationships. Patients' hopes extend beyond pain relief toward reclaiming life, highlighting the need for holistic, patient-centred rehabilitation.
Journal of investigative surgery : the official journal of the Academy of Surgical ResearchAmani N Alansari, Marwa Messaoud, Mohamed Sayed Zaazouee, Naser El-Mefleh, Surendra M Chinnappa, Nabil A Shallik
AIM: This meta-analysis compares ultrasound-guided and landmark-based dorsal penile nerve block (DPNB) in pediatric circumcision. METHODS: We systematically searched PubMed, Scopus, Web of Science, Embase, and Cochrane CENTRAL from inception to December 2025. Eligible studies included randomized controlled trials (RCTs) and observational cohorts comparing ultrasound-guided with landmark-based DPNB in pediatric patients (≤18 years) undergoing circumcision. Primary outcomes were intraoperative and postoperative opioid rescue requirements. Secondary outcomes included pain scores at incision, surgical duration, discharge time, and postoperative nausea/vomiting. Meta-analyses were performed using RStudio version 4.4.3. RESULTS: Nine studies involving 949 children met inclusion criteria (five RCTs, four retrospective cohorts). Ultrasound-guided DPNB significantly reduced intraoperative opioid rescue (risk ratio 0.39, 0.18-0.88; p = 0.028) and postoperative opioid requirements (risk ratio 0.26, 0.07-0.94; p = 0.0442) compared with landmark-based techniques. No significant differences emerged in pain scores at incision, discharge time, or postoperative nausea/vomiting. Ultrasound-guided blocks required modestly longer procedural time (mean difference 1.48 min, 0.03-2.94; p = 0.048). CONCLUSIONS: Ultrasound-guided DPNB substantially may reduce perioperative opioid requirements in pediatric circumcision compared with landmark-based approaches, despite slightly longer procedural times. When resources and expertise permit, ultrasound guidance should be considered the technique of choice for optimizing opioid-sparing anesthesia in this population.
Annals of medicineSeonghyeon Bu, Jaehyuk Jang, Sang Hyun Kim, Jaeho Byeon, Kwan Yong Lee, Gyu-Chul Oh, Sungmin Lim, Eun Ho Choo, Ik Jun Choi, Byung-Hee Hwang, Chan Joon Kim, Mah…
BACKGROUND: The clinical effects of dual antiplatelet therapy de-escalation after acute myocardial infarction may differ by age. We evaluated whether the efficacy and safety of de-escalation from ticagrelor to clopidogrel differed by age in stabilized patients after percutaneous coronary intervention (PCI). PATIENTS AND METHODS: This was a prespecified secondary analysis of the TALOS-AMI randomized trial. Patients event-free 1 month after PCI receiving aspirin-ticagrelor were randomly allocated to de-escalation (aspirin-clopidogrel) or continuation (aspirin-ticagrelor). The primary net clinical endpoint was a composite of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke) and Bleeding Academic Research Consortium types 2, 3, or 5 bleeding at 1 year. RESULTS: We included 2697 participants (mean age 60.0 ± 11.4 years; 16.8% women). Among patients aged <75 years (n = 2376), de-escalation reduced the primary net clinical endpoint (4.1% vs. 7.2%; adjusted hazard ratio (aHR), 0.54 [95% CI, 0.38-0.77]) and bleeding (2.8% vs. 4.9%; aHR, 0.54 [0.35-0.82]). Among patients aged ≥75 years, no significant differences were observed for the primary endpoint (6.4% vs. 11.6%; aHR0.54 [0.25-1.17]) or bleeding (3.2% vs. 7.9%; aHR, 0.41 [0.15-1.15]). Interaction testing showed no treatment effect modification by age for the primary endpoint (p for interaction = 0.978), MACE (p = 0.585), or BARC bleeding (p = 0.597). Among patients aged ≥75 years, 14/18 bleeding events occurred within 180 days. CONCLUSIONS: Among stabilized, event-free patients 1 month after PCI, no significant age-treatment interaction was observed; therefore, the efficacy and safety of de-escalation in older adults (≥75 years) remain uncertain. UNLABELLED: Trial registration: ClinicalTrials.gov (NCT02018055).
Journal of medical economicsRawan Faramand, James Scott McClellan, Anna Pavlova, Rocio Manghani, Andrea Blank, Matia Saeedian, Shivani Yadav, Miguel-Angel Perales
AIMS: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with hematologic malignancies, but its success is limited by graft‑versus‑host disease (GVHD), which carries considerable clinical and economic burden. A cost-effectiveness model was developed to evaluate whether the higher upfront costs of allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq (Tregzi [Orca-T; Orca Bio, Menlo Park, CA, USA]) are offset by reductions in GVHD and associated healthcare costs compared with conventional allo-HCT using TAC/MTX or PTCy. METHODS: A three-state partitioned survival model (relapse-free, relapsed, and dead) with a lifetime horizon and monthly cycles was developed. Overall survival and relapse-free survival data from the Phase 3 Precision-T study (ClinicalTrials.gov Identifier NCT05316701) were incorporated using a cure-mixture modeling approach to estimate long-term survival, relapse status, and cure fraction for patients. Costs included transplant procedure, GVHD management, infection management, and terminal care. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct healthcare costs. Both costs and outcomes were discounted at 3% annually. A scenario analysis was conducted to determine the cost-effectiveness of Orca-T vs allo-HCT with PTCy for GVHD prophylaxis, and sensitivity analyses were conducted to test the uncertainty of the model inputs. RESULTS: Orca‑T was associated with lower lifetime costs ($1,026,856 vs $2,170,875) and higher QALYs (15.28 vs 13.00) than conventional allo‑HCT with TAC/MTX, yielding cost savings of $1,144,019 and a gain of 2.28 QALYs per patient. GVHD-related costs were substantially lower with Orca‑T ($495,447 vs $1,998,621). Compared with PTCy, Orca‑T remained dominant, with cost savings of $158,144, a gain of 2.85 QALYs, and lower GVHD-related costs ($476,448 vs $999,945). CONCLUSIONS: Orca‑T reduced costs and increased QALYs versus conventional allo‑HCT with TAC/MTX or PTCy, driven by lower GVHD and infection burden. These findings support Orca‑T as a high‑value treatment option.
INTRODUCTION: Long-term renal function is an important follow-up after radical nephrectomy for renal carcinoma. Predictive models can help identify patients at risk for chronic kidney disease (CKD) progression and enable early intervention. METHODS: We retrospectively analyzed 649 patients who underwent radical nephrectomy at eight medical centers. The primary cohort from the Affiliated Hospital of Qingdao University comprised 329 patients, randomly divided into training sets (n = 229) and internal validation sets (n = 100) at a 7:3 ratio. An additional 320 patients from seven other centers constituted a multicenter external evaluation cohort. Five machine learning models were developed, including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), confusion matrices, and calibration curves. RESULTS: 224 (34.51%) patients experienced postoperative CKD stage progression within three years. LightGBM achieved the highest discriminative performance among the five evaluated algorithms, with an AUC of 0.7508 (95% CI, 0.6399-0.8617) and an accuracy of 0.7200 in the internal validation set, and an AUC of 0.7549 (95% CI, 0.7022-0.8076) and an accuracy of 0.6813 in the external evaluation set. SHAP analysis identified preoperative eGFR, tumor size, post-to-preoperative serum creatinine ratio, preoperative serum creatinine, and age as the five most influential predictors. CONCLUSIONS: We developed and externally evaluated machine-learning models for predicting CKD stage progression after radical nephrectomy. Long-term decline in renal function is an important complication that requires urologists' attention and early prevention during follow-up.
OncoimmunologyJuan Zafra-Martin, Juan Luis Onieva, Herminda Jimenez-Rodriguez, Beatriz Martinez, Laura Figueroa-Ortiz, Alicia Roman, Rafael Ordoñez, Elisabeth Pérez-Ruiz, An…
Stereotactic ablative radiotherapy (SABR) may extend the clinical benefit of immune checkpoint inhibitors (ICI) in patients with oligoprogressive disease. However, individual benefit varies, and validated biomarkers to guide patient selection are lacking. We hypothesize that cell-free DNA (cfDNA) and the neutrophil-to-lymphocyte ratio (NLR) may be associated with outcomes after SABR in this setting. This prospective observational study included patients with oligoprogression under ICI therapy who received concomitant SABR to all oligoprogressive lesions (cohort A). Cohort B was a parallel biomarker cohort of oligometastatic patients receiving only SABR. Blood samples were collected before SABR (T1), after the first (T2) and last (T3) fractions, and two months after SABR (T4). The objective response rate (ORR) was evaluated by iRECIST in all lesions. Prespecified cfDNA and NLR time points were explored in relation to modified progression-free and overall survival (OS). We assessed 104 patients. With a median follow-up of 12 months, ORR was 59% in cohort A and 65% in cohort B. In cohort A, cfDNA <0.37 ng/µL at T3 was associated with improved 1-year OS (91% vs 62%, p = 0.031), while NLR <1.8 at T1 was associated with improved 1-year OS (100% vs 70%, p = 0.01). In cohort B, a >3% increase in cfDNA from T2 to T4 and NLR <4 at T4 were associated with improved OS. These findings support further evaluation of cfDNA and NLR as accessible biomarkers for patient stratification in oligoprogressive disease treated with SABR while maintaining an ICI.
Annals of medicineHuiwen Zhang, Li Zhao, Wanji Yang, Bo Li, Wan Lin, Xiaoya Chen, Li Mo, Shangqi Dai, Wu Chen, Fan Yang, Hanxiang Ma
BACKGROUND: During propofol-sedated gastrointestinal endoscopy, adequate sedation must be achieved without compromising hemodynamic stability or oxygenation. We developed and temporally validated dose-conditioned machine-learning models to predict a composite target sedation state. METHODS: This single-center prospective observational study included 1,248 adults. The first 1,000 patients formed the development cohort and the subsequent 248 patients the temporal validation cohort. The composite outcome was assessed after MOAA/S-defined loss of consciousness and before endoscope insertion and required a bispectral index of 40-60, systolic blood pressure ≥80% of baseline, and peripheral oxygen saturation ≥90%. Five models were evaluated using routinely available variables collected before or during initial propofol administration, including the initial propofol dose. RESULTS: The composite target was achieved in 153 patients (15.3%) in the development cohort and 33 (13.3%) in the validation cohort. Validation AUCs ranged from 0.780 to 0.821. Random Forest had the numerically highest AUC (0.821; 95% CI, 0.748-0.889), whereas ExtraTrees had the highest average precision (0.570; 95% CI, 0.388-0.724). Calibration was suboptimal across models. With only 33 validation events, confidence intervals were wide and comparisons among models remain uncertain. CONCLUSIONS: Dose-conditioned machine-learning models showed moderate-to-good discrimination, but calibration remained suboptimal. No single model was uniformly superior. Further recalibration and independent multicenter validation are needed before clinical use.
Annals of medicineRob Buhmann, Abram Reeves, Daniel Mellifont, Max Stuelcken, Mark Sayers, David N Borg, Steven Lawrie
OBJECTIVES: To determine whether quadriceps motor unit firing rates measured pre-operatively and during the first three months after anterior cruciate ligament (ACL) reconstruction are associated with isometric knee extensor strength at six months, and to explore the relationship between motor unit action potential (MUAP) amplitude and firing rate. METHODS: Twenty-seven participants (15 female) underwent surface electromyography of vastus medialis and vastus lateralis during sub-maximal isometric knee extension from pre-operation to three months post-reconstruction. Six-month knee extensor MVC force was modelled using Bayesian regression and interpreted using a region of practical equivalence (ROPE; ±15 N). A secondary hierarchical analysis examined MUAP amplitude and firing rate. RESULTS: Motor unit firing rate was not consistently associated with six-month knee extensor strength across time points and limbs. In the ACL reconstructed limb at two weeks, a 1-SD greater mean firing rate was associated with 45.8 N greater six-month strength (95% credible interval [CrI] - 18.5 to 114.6 N). Six-month strength was greater in the contralateral limb (β = 198.4 N, 95% CrI 171.6 to 225.1 N), in males (β = 184.3 N, 95% CrI 32.0 to 325.1 N), and with greater body mass (β = 119.9 N per 1-SD, 95% CrI 33.4 to 207.2 N). Greater relative MUAP amplitude was associated with lower firing rate (-3.7 Hz per 1-SD, 95% CrI -3.8 to -3.6 Hz). CONCLUSIONS: Sub-maximal quadriceps motor unit firing rate was not consistently associated with later knee extensor strength, although a stronger positive association was suggested in the reconstructed limb at two weeks. Firing rate was strongly related to relative MUAP amplitude, and its predictive value for later strength appears limited.
Renal failureXiaorong Wang, Yongmei Hao, Huaying Pei, Lin Yang, Zhe Yan, Lin Mu, Xian Chen, Xi Zhao, Lingling Xing
AIMS: Renal vascular lesions are common in diabetic nephropathy (DN), but their association with echocardiographic indices related to diastolic function remains unclear. This study investigated the relationship between renal vascular lesion severity and echocardiographic indices in biopsy-confirmed DN. METHODS: This biopsy-based cross-sectional study included 360 patients with biopsy-confirmed DN and available echocardiographic data. Renal vascular lesions were evaluated using a composite score of arteriolar hyalinosis and arteriosclerosis, and patients were categorized into three severity groups (scores 0-1, 2-3, and 4). Echocardiographic indices included E/e', e', and left atrial diameter (LA). Multivariable linear regression models were used to assess the associations between renal vascular lesion severity and echocardiographic parameters. Sensitivity analyses were performed using continuous vascular lesion scores and additional covariate adjustment. RESULTS: Among 360 patients, 53, 253, and 54 were classified into the 0-1, 2-3, and 4 score groups, respectively. Compared with the 0-1 group, moderate and severe vascular lesions were associated with higher E/e' (β = 1.814 and 2.910, respectively) and larger LA (β = 1.722 and 2.917, respectively) after multivariable adjustment. Continuous score analysis showed that each 1-point increase in vascular lesion score was associated with higher E/e', larger LA, and lower e'. Associations with E/e' and LA were generally consistent across sensitivity analyses, whereas the association with e' was less stable. CONCLUSIONS: In patients with biopsy-confirmed DN, greater renal vascular lesion severity was associated with higher E/e' and larger LA, highlighting a potential link between renal vascular pathology and echocardiographic indices related to diastolic function.
Lactate is frequently measured in patients with acute kidney injury (AKI), but its interpretation remains challenging because circulating lactate reflects systemic metabolic stress rather than kidney injury. Although elevated lactate levels are associated with adverse outcomes in critically ill patients with AKI, its biological and clinical significance varies according to disease context, timing, and the clinical question being addressed. This structured expert narrative review integrates mechanistic insights and clinical evidence to establish a context-dependent framework for interpreting lactate in AKI. We summarize the role of the kidney in lactate metabolism and discuss how impaired renal function, altered perfusion, mitochondrial dysfunction, and immune-metabolic remodeling contribute to lactate accumulation. We further evaluate clinical evidence regarding lactate in AKI risk assessment, severity evaluation, organ-support requirement, and mortality prediction, while emphasizing limitations related to confounding factors and clinical heterogeneity. Emerging clinical contexts, including extracorporeal membrane oxygenation-supported patients, are also considered. Overall, this framework supports a more precise interpretation of lactate as a context-dependent risk marker and metabolic signal rather than a kidney-specific biomarker.
Acute kidney injury (AKI) after liver transplantation (LT) is a frequent complication associated with adverse outcomes, yet practical early postoperative prediction tools remain limited. This retrospective study developed and internally validated an interpretable model for AKI after LT using perioperative variables available by the time of the first urgent postoperative blood test, generally obtained within 1 h after surgery. Adult LT recipients treated from June 2023 to January 2026 were screened. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria. Among 146 screened recipients, 127 were included and randomly divided into training and validation cohorts at a 3:1 ratio. Least absolute shrinkage and selection operator regression selected estimated glomerular filtration rate calculated using the CKD-EPI equation, anhepatic phase time, postoperative natural logarithm-transformed D-dimer, and postoperative alanine aminotransferase. Multivariable logistic regression showed that lower estimated glomerular filtration rate and longer anhepatic phase time were independently associated with AKI. The nomogram achieved area under the receiver operating characteristic curve values of 0.861 in the training cohort and 0.761 in the validation cohort. Five-fold cross-validation and bootstrap internal validation were performed to assess model stability and optimism. Among five evaluated models, support vector machine showed the numerically highest validation AUC of 0.846. Shapley additive explanations identified estimated glomerular filtration rate as the dominant predictor. This early postoperative model may help identify high-risk recipients for intensified renal monitoring and individualized management. External multicenter validation is required before routine clinical implementation.
BACKGROUND: Central venous occlusion (CVO) is a severe complication in hemodialysis patients with tunneled cuffed catheters (TCC), leading to catheter dysfunction and poor outcomes. Optimal treatment remains controversial. METHODS: This retrospective study included 123 hemodialysis patients with TCC dysfunction and CVO between February 2017 and December 2025. Patients underwent either exchange of the existing catheter or placement of a new catheter at a different venous site, with or without concurrent balloon angioplasty or stenting. RESULTS: The cohort had a mean age of 61.02 ± 13.66 years, 29.2% male, with mean hemodialysis vintage of 7.86 years. Brachiocephalic vein occlusion was the most common lesion (74.8%), followed by superior vena cava occlusion (63.4%). Median catheter survival was 735 days. Recurrent dysfunction requiring reintervention occurred in 39.0% of patients (median time 255 days). Atrial thrombus (17.8%) and fibrin sheath (38.2%) were significantly associated with shorter catheter survival (p < 0.05). Most patients had reduced right ventricular basal diameter (98.0%) and increased left ventricular mass index (40.9%). CONCLUSIONS: Catheter exchange and endovascular treatment for central venous occlusion are safe and effective. Percutaneous superior vena cava puncture provides a valuable salvage option for this complex population, supporting durable long-term vascular access. Thrombosis and fibrin sheath predict poorer catheter survival.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupChuqiang Shu, Pu Zhang, Qi Tian, Ziqing Wan, Guang Li, Chengzhi Li, Zhibiao Wang
BACKGROUND: Cisplatin-based chemotherapy is limited by toxicity and resistance.High-intensity focused ultrasound (HIFU) is a noninvasive ablation technique with potential to enhance chemotherapy efficacy. OBJECTIVE: To investigate the anti-tumor effects and mechanisms of cisplatin combined with HIFU in endometrial cancer. METHODS: Safe cisplatin concentrations and HIFU parameters were screened in HEEpiC-SV40 cells. Proliferation, apoptosis, migration, and invasion of Ishikawa cells were assessed using CCK-8, EdU, colony formation, TUNEL, wound healing, and Transwell assays. Pyroptosis-related markers and PI3K/AKT pathway activity were evaluated by Western blot, qRT-PCR, and ELISA. Therapeutic efficacy was further examined in a nude mouse xenograft model. RESULTS: Cisplatin (5 μg/mL) combined with HIFU (1 MHz, 160 J) was identified as the optimal treatment condition. The combination significantly inhibited Ishikawa cell proliferation, migration, and invasion while promoting pyroptosis. Mechanistically, combined treatment suppressed PI3K/AKT pathway activation and increased pyroptosis-related markers. These effects were reversed by the pyroptosis inhibitor AZL-N. Moreover, PI3K/AKT activation with 740 Y-P attenuated the anti-tumor and pyroptosis-inducing effects of the combination. In vivo, cisplatin combined with HIFU markedly restrained xenograft tumor growth and promoted tumor pyroptosis, whereas 740 Y-P pretreatment counteracted these effects. CONCLUSIONS: Cisplatin combined with HIFU suppresses Type I endometrial cancer progression by inhibiting PI3K/AKT signaling and promoting pyroptosis, supporting its potential as a novel combination therapeutic strategy.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupTing Lin, Minqi Su, Yan Chen, Junli An, Xueqiong Xu, Xuemei Chen, Gang Wu, Haifeng Wang, Yunfeng Cai, Manling Li, Liuyun Zhou, Jiali Yang, Jingjing Liu, Sangui…
OBJECTIVE: To investigate the clinical efficacy and potential mechanisms of Traditional Chinese Medicine (TCM) combined with High-Intensity Focused Ultrasound (HIFU) in the treatment of adenomyosis, providing evidence-based support for optimizing clinical treatment strategies. METHODS: In this prospective randomized trial, 66 patients were assigned to a control group (HIFU alone) or an observation group (HIFU plus a "Yiqi Huoxue, Huayu Sanjie" TCM formula) for 12 weeks. The Visual Analog Scale (VAS) for pain as the primary endpoint, and the Pictorial Blood Loss Assessment Chart (PBAC) for menstrual blood loss, uterine/lesion volumes, and serum carbohydrate antigen 125 (CA125), interleukin-6 (IL-6) as exploratory outcomes were assessed. RESULTS: The results showed that the VAS scores in the observation group were significantly lower than those in the control group after treatment (p < 0.05). The reduction in uterine volume and lesion volume was greater in the observation group compared to the control group (p < 0.05). Serum levels of CA125 and IL-6 decreased more significantly in the observation group (p < 0.05), and no significant abnormalities were observed in safety indicators. CONCLUSION: The combination of TCM and HIFU treatment suggests a possible benefit in alleviating dysmenorrhea and promoting lesion absorption in patients with adenomyosis. The observed changes in inflammatory status and CA125 levels hint at a potential link with the therapeutic effect. However, these findings should be considered exploratory, and further studies are needed to validate TCM as an adjunctive therapy to HIFU treatment.
Journal of investigative surgery : the official journal of the Academy of Surgical ResearchHong-Yu Xu, Wei-Zhen Tang, Tai-Hang Liu, Fei Han, Qin-Yu Cai, Hao-Wen Chen, Yi-Fan Zhao, Wang Qi Rui Liu, He-Zhe Hua, Jun Ding, Peng Guo, Zhi-Yong Xiang
BACKGROUND: Complications after pancreaticoduodenectomy are common and may be life-threatening. Management of the common bile duct stump may affect biliary pressure, drainage, and postoperative outcomes. This study seeks to compare open versus ligated bile duct stump management during pancreaticoduodenectomy. METHODS: This retrospective cohort included 125 patients who underwent pancreaticoduodenectomy between 2019 and 2025. Surgical outcomes and postoperative recovery were compared between the open-stump and ligation groups. Multivariable logistic regression identified associations between stump management and postoperative complications; biochemical indicators were also assessed. RESULTS: After adjustment, the opening group had significantly lower risks of pancreatic fistula (aOR = 0.18, 95%CI: 0.05 - 0.68, P = 0.011) and intra-abdominal and gastrointestinal bleeding (aOR = 0.09, 95%CI: 0.01 - 0.77, P = 0.028) versus the ligation group. The opening group also demonstrated a shorter surgical duration (315 minutes vs. 420 minutes, P < 0.001), reduced postoperative hospitalization (24 days vs. 30 days, P = 0.002), and lower costs (109,375 RMB vs. 137,518 RMB, P < 0.001). No significant changes were seen in liver function or coagulation markers. CONCLUSION: Keeping the common bile duct open markedly enhances perioperative management during pancreaticoduodenectomy, thus serving as a significant reference for refining surgical protocols.
Continuous renal replacement therapy (CRRT) is a vital organ support modality for critically ill patients. Adsorptive membranes, particularly AN69ST and oXiris, are increasingly used in clinical practice; however, their impact on the pharmacokinetics of antibiotics with a narrow target concentration range between efficacy and toxicity, such as vancomycin, remains incompletely defined. Considerable heterogeneity exists among available studies. Multiple in vitro dynamic circulation models reported adsorption of 12% to 19.5% of the initial vancomycin dose, whereas some static or open-model in vitro studies failed to detect significant adsorption. Retrospective studies have reported that adsorption accounted for approximately 15.9% with AN69ST membranes and 5.4% with oXiris membranes of total vancomycin elimination. However, the clinical significance of vancomycin removal by adsorptive membranes via adsorption remains unclear and warrants further investigation. Nevertheless, overlooking the additional clearance contributed by AN69ST or oXiris membranes during dose regimen design may lead to subtherapeutic vancomycin exposure, thereby increasing the risk of treatment failure and antimicrobial resistance. This article systematically reviews the current evidence on vancomycin elimination characteristics with adsorptive membranes, with an emphasis on adsorption mechanisms, influencing factors, and clinical dosing adjustment strategies. In current clinical practice, intensified therapeutic drug monitoring with dynamic dose adjustment based on measured concentrations remains an essential strategy to ensure the efficacy and safety of vancomycin therapy. A deeper understanding of membrane-specific adsorption kinetics is required to optimize antibiotic dosing in critically ill patients receiving CRRT with highly adsorptive membranes.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyJing Li, Juan Li, Darong Mou, Dongyan Li
BACKGROUND: Vaginal atrophy (VA), a common condition associated with oestrogen deficiency, significantly impacts women's quality of life. Src homology 2 domain-containing transforming protein 1 (SHC1) is implicated in various hormone-dependent processes. This project aims to investigate whether oestrogen promotes the proliferation, migration and differentiation of vaginal epithelial cells by regulating SHC1, and delineates the underlying mechanism. METHODS: An ovariectomised (OVX) mouse model of VA was established and treated with 17β-estradiol (E2). Human vaginal epithelial VK2/E6E7 cells were stimulated with E2 (dose-dependent), transfected with SHC1 overexpression (OE-SHC1), SHC1 knockdown (sh-SHC1) or epidermal growth factor receptor (EGFR) overexpression (OE-EGFR) plasmids. Histological and immunohistochemical analyses were performed on vaginal tissues. Cellular proliferation and migration were assessed via CCK-8 and wound healing assays, respectively. Western blot analysed cellular/tissue proteins (differentiation/barrier markers, Ras/ERK pathway components). RESULTS: E2 upregulated SHC1 expression both in atrophic vaginal tissue and in VK2/E6E7 cells in a dose-dependent manner. SHC1 overexpression enhanced, while its knockdown attenuated, E2-induced cell proliferation, migration, and the expression of differentiation (Keratin 6a (krt6a), Keratin 13 (krt13)) and barrier (E-cadherin, occludin) markers. Mechanistically, SHC1 mediated the effects of E2 by acting as an adaptor of EGFR and subsequent activation of the downstream Ras/ERK pathway. EGFR overexpression rescued SHC1 deficiency phenotypes in E2-treated VK2/E6E7 cells. In OVX mice, SHC1 knockdown reversed E2-mediated restoration of vaginal epithelial architecture, proliferation (Ki67) and Ras/ERK signalling. CONCLUSIONS: SHC1 is a critical mediator of E2-induced vaginal epithelial homeostasis through the EGFR/Ras/ERK axis, representing a potential downstream therapeutic target for intervention in VA, particularly via localised delivery strategies.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupDan-Ling Zhang, Songsong Wu, Guisheng Ding, Xin Wei Chen, Mengqi Chen, Sheng Chen
OBJECTIVES: To evaluate oxytocin-induced perfusion changes in uterine fibroids using contrast-enhanced ultrasound(CEUS) and determine their predictive value for high-intensity focused ultrasound (HIFU) ablation efficacy. METHODS: Fifty-five patients (mean age 42.15 ± 5.34 years). with 78 uterine fibroids underwent oxytocin-enhanced HIFU therapy. CEUS was performed before and after intravenous oxytocin infusion (0.10 U/ml over 10 min). Perfusion changes were assessed using two parameters:(1) Arterial-phase Perfusion Delay Time difference (APDTΔt), defined as the time difference in enhancement onset of fibroids before and after oxytocin exposure; (2) Visual Perfusion Grading (VPG), based on relative contrast perfuse reduction of fibroids at the end of the arterial phase(Grade1:≤30%;Grade2:30-70%;Grade3:≥70%). Post-treatment contrast-enhanced pelvic MRI was used to calculate fibroid volume and non-perfused volume(NPV),from which ablation ratio was derived. Fibroids were dichotomized by ablation efficacy (≥70%vs < 70%), and correlation analyses and ROC curves were used to evaluate predictive performance. RESULTS: Fibroids in the <70% ablation group showed a mean APDT(Δt) of 8.32 ± 5.61s and 52.2%(12/23) VPG as Grade1. In the ≥70% group, APDT(Δt) was significantly longer (16.76 ± 12.12 s), and 54.5%(30/55) VPG were Grade3. Both APDT(Δt) and VPG differed significantly between groups (p < 0.05), Showing strong correlations with ablation ratio (r = 0.577 and r = 0.585; both p < 0.001). Thresholds of APDT(Δt) >3.5 s and VPG >1.5 yielded sensitivities of 83.6% and 87.3%, specificity of 65.2% and 52.3%, with AUCs of 0.791 and 0.725, respectively. CONCLUSION: CEUS can effectively detect oxytocin-mediated perfusion changes in uterine fibroids. These changes are strongly associated with HIFU ablation outcomes, and in particular, Arterial-phase Perfusion Delay Time demonstrates robust predictive value for treatment efficacy.
BACKGROUND: Secure defect closure is critical in endoscopic full-thickness resection (EFTR). The through-the-scope twin clip (TTS-TC) is designed to overcome the shallow tissue grasping of titanium clips, facilitating deeper tissue apposition. This study evaluated the safety, clinical effectiveness, postoperative hospital stay, and hospitalization costs of the TTS-TC in gastric EFTR defect closure. METHODS: We retrospectively analyzed 121 patients with gastric lesions who underwent EFTR between June 2023 and June 2025. Patients were stratified into the TTS-TC group (n = 36) and the 10-mm titanium clip group (n = 85) based on the closure method. We compared procedure time, number of clips used, postoperative length of stay, incidence of intraoperative and postoperative adverse events, and hospitalization costs. RESULTS: Both groups achieved definitive closure without major adverse events. Although the TTS-TC was preferred for larger and anatomically demanding lesions, subgroup analysis of defects >15 mm revealed that the TTS-TC group required significantly fewer clips and had a shorter median procedure time, with no statistically significant differences in postoperative length of stay or hospitalization costs. Multivariable regression analysis showed that the TTS-TC was independently associated with fewer clips used (p < 0.001), alongside a trend toward a shorter procedure time (p = 0.058). CONCLUSIONS: In this retrospective observational comparison, the TTS-TC appears to be a safe and feasible option for closing gastric wall defects during EFTR, and demonstrates potential utility in managing selected large or anatomically challenging defects.