Safety Outcomes Research Articles

Early safety and efficacy outcomes of the PAUL glaucoma implant in a Spanish population: A retrospective study

Abstract PURPOSE: The purpose of the study was to evaluate the efficacy and safety of the PAUL glaucoma implant (PGI) in refractory glaucoma patients, during the early postoperative period. METHODS: We conducted a retrospective, cohort study of patients that had received a PGI between February 2022 and December 2023. An intraluminal polypropylene suture was placed to prevent early hypotony in all cases. Demographics, intraocular pressure (IOP), and medication variation were evaluated for up to 6 months. The success rate was stratified into <18 mmHg and 30% from baseline or <15 mmHg and 40% IOP reduction. The safety outcomes were also analyzed. RESULTS: Sixteen eyes from 16 patients were included in the analysis. Fifteen of them had had a previous surgical glaucoma procedure. At 6 months, IOP decreased from 26.6 (±6.2) to 15.3 (±4.6) mmHg, with fewer glaucoma medications, from a median (interquartile range) of 3 (2–3) – 1.5 (0–2) (P < 0.005). Twelve (75%) and seven (43.8%) eyes met the qualified and complete success definition for the first category, and eight (50%) and four (25%) met the second criterion. One case with self-limiting choroidal detachments, but >6 mmHg IOP was found in our cohort. CONCLUSION: The PGI seems to be safe and effective from the early postoperative period. The IOP reduction rate could make it suitable for patients with refractory moderate-to-advanced glaucoma.

Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial

Background: In the phase 3 randomized controlled study, ATTRibute-CM, acoramidis, a transthyretin (TTR) stabilizer, demonstrated significant efficacy on the primary endpoint. Participants with transthyretin amyloid cardiomyopathy (ATTR-CM) who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE. Methods: Participants who previously received acoramidis through Month 30 (M30) in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through M30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through Month 42 (M42) included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), serum TTR, and the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS). Safety outcomes were analyzed through M42. Results: Overall, 438 of 632 participants in ATTRibute-CM completed treatment and 389 enrolled in the ongoing OLE (263 continuous acoramidis, 126 placebo to acoramidis). The hazard ratio (HR) (95% CI) for ACM or first CVH was 0.57 (0.46, 0.72) at M42 based on a stratified Cox proportional hazards model ( P -value < 0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with HRs (95% CI) of 0.64 (0.47, 0.88) and 0.53 (0.41, 0.69), respectively, at M42. Treatment effects for NT-proBNP and 6MWD also favored continuous acoramidis. Upon initiation of open-label acoramidis in the placebo-to-acoramidis arm there was a prompt increase in serum TTR. Quality of life assessed by KCCQ-OS was well preserved in continuous acoramidis participants compared with the placebo to acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation. Conclusions: Early initiation and continuous use of acoramidis in the ATTRibute-CM study through M42 of the ongoing OLE study was associated with sustained clinical benefits in a contemporary ATTR-CM cohort, with no clinically important safety issues newly identified.

Subconjunctival trypsin injection for anterior chamber fibrin exudates in eyes with globe rupture following vitrectomy

AIM: To compare the safety and clinical outcomes of subconjunctival trypsin and dexamethasone (DEX) injections in the treatment of anterior chamber fibrin exudates in eyes with globe rupture following primary wound repair and vitrectomy. METHODS: A retrospective analysis included 42 males and 10 females (mean age 46.0±6.0y, range 34 to 58y) who underwent primary wound sutures and vitrectomy for globe rupture. Patients with pupil-covered fibrinous exudate or/and membrane in the anterior chamber were treated. On the first postoperative day, subconjunctival injections of either 5000 units (0.4 mL) of trypsin solution (n=25) or 0.5 mL (1 mg) DEX (n=27) were administered to accelerate exudate absorption. Efficacy was assessed by observing break time and partial absorption of the fibrin exudate membrane. Safety and comfort were evaluated by monitoring intraocular pressure (IOP), allergy, pain, and foreign body sensation. RESULTS: Both groups achieved 1/3 absorption of the anterior chamber fibrin exudate membrane, but the trypsin group exhibited shorter break time and partial absorption time compared to the DEX group (P<0.05). Trypsin treatment was also less irritating to patients. No adverse reactions were reported, and IOP remained stable. Visual acuity improved in both groups without statistical difference. CONCLUSION: Compared to DEX, trypsin demonstrates a shorter absorption time for the fibrin exudate membrane with a more comfortable process in treating pupil-covered fibrinous exudate or/and membrane after vitrectomy for globe rupture.

Skin Clearance, Treatment Response Off-therapy, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability outcomes from ADORING 3. Methods: Eligible patients from ADORING 1, ADORING 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild, or moderate or severe AD, that did not meet eligibility criteria for ADORING 1 or 2, received tapinarof cream 1% QD for up to 48 weeks. Efficacy endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™] score=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Safety and tolerability were assessed. Patients entering with vIGA-AD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0 [clear]). Those entering with or achieving complete clearance discontinued tapinarof and were assessed for maintenance of clear or almost clear skin off-treatment (duration of treatment-free interval). Patients whose AD returned to mild (vIGA-AD™≥2) were re-treated until complete clearance was achieved. Results: 728 patients enrolled; 83.0% were pediatric (2–17 years). Overall, 51.9% (378/728) achieved complete disease clearance, and 81.6% achieved clear or almost clear skin at least once in the trial. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated locally, even when applied on sensitive skin. Conclusions: Tapinarof cream monotherapy demonstrated a high rate of complete disease clearance in patients down to age 2 years with AD. After discontinuing tapinarof, patients maintained clear or almost clear skin for 79.8 consecutive days. Tapinarof was well tolerated over 48 weeks.

Anatomic versus non-anatomic resection for intrahepatic cholangiocarcinoma: a systematic review and meta-analysis

Background: The value of anatomic resection (AR) in intrahepatic cholangiocarcinoma (ICC) remains controversial. This study compares the perioperative safety and long-term outcomes of AR versus non-anatomic resection (NAR) in ICC patients. Methods: A systematic search was conducted in PubMed, Medline, Embase, Cochrane Library, China National Knowledge Infrastructure(CNKI) and Wanfang database for prospective or retrospective studies comparing the efficacy of AR and NAR in, ICC published to June 1, 2024. Meta-analyses were performed on surgical factors, perioperative outcomes and long-term prognosis for both the entire cohort and the propensity score-matched (PSM) cohort. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). Results: Seven studies, including 1801 ICC patients, were analyzed. In both the entire and the PSM cohort , the AR group demonstrated superior OS (HR=0.71, 95% CI=0.57-0.88, P=0.002 and HR=0.70, 95% CI=0.59-0.83, P<0.0001, respectively) and DFS (HR=0.75, 95% CI=0.62-0.91, P=0.004 and HR=0.68, 95% CI=0.58-0.79, P<0.00001, respectively) compared to the NAR group. AR significantly improves 1-year, 3-year, 5-year DFS and 5-year OS(all P<0.05). In the PSM cohort, AR and NAR groups showed comparable blood loss, operative times, overall complications, and major complications (all P>0.05). Subgroup analysis revealed that among patients with tumor >5 cm, AR achieved better OS and DFS, whereas patients with tumors ≤5 cm did not experience survival benefits from AR. Conclusion: This study suggests that AR, compared to NAR, can improve OS and DFS without increasing perioperative risks, particularly in ICC patients with tumors larger than 5 cm.

Bimekizumab Efficacy and Safety Through 2 years in Patients with Hidradenitis Suppurativa: Results from the Phase 3 BE HEARD I&II trials and Open-Label Extension BE HEARD EXT

Introduction: Interleukin (IL)-17F and IL-17A play a role in the immunopathogenesis of hidradenitis suppurativa (HS).1–3 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits IL-17F in addition to IL-17A leading to clinically meaningful improvements in patients (pts) with HS.4,5 Here, BKZ efficacy and safety data (OC) are presented over 2 years (96 weeks [wks]) for the pooled BE HEARD I&II (BHI&II) trials and BE HEARD EXT (BHEXT).5,6 Procedure/Study: In BHI&II, pts with moderate to severe HS were randomized 2:2:2:1 (16wk-initial/32wk-maintenance) to BKZ 320mg every 2 wks (Q2W)/Q2W, BKZQ2W/Q4W, BKZQ4W/Q4W or placebo/BKZQ2W.5 Wk48 completers could enroll in BHEXT and receive open-label BKZQ2W or BKZQ4W based on ≥90% HS Clinical Response (HiSCR90; averaged from Wks36/40/44). We report HiSCR50/75/90/100 rates, percentage change from baseline (%CfB, mean±SD) in International HS Severity Score System (IHS4) and draining tunnel (DT) count, and Dermatology Life Quality Index (DLQI) 0/1 achievement at Wks48/96 for patients randomized to BKZ in BHI&II and entered BHEXT (BKZ Total, observed case). Safety outcomes reported for pts who received ≥1 BKZ dose across BHI&II/BHEXT. Results: 556 pts randomized at baseline to BKZ in BHI&II completed Wk48 and entered BHEXT; 446 pts completed Wk96. At Wk48, HiSCR50/75/90/100 was achieved by 79.9/64.0/42.3/30.2% of pts; responses improved to Wk96: 85.4/77.1/57.6/44.2%. Baseline IHS4 was 35.6±31.5; %CfB at Wk48/96 was –70.3±39.6/−79.8±28.1%. Baseline DTs were 3.8±4.3; the %CfB at Wk48/96 was −57.5±72.9%/−73.7±45.7%. Baseline DLQI was 11.0±6.8; 27.4% (151/551) of pts achieved DLQI 0/1 at Wk48 and 33.9% (149/439) at Wk96. Over 2 years, 917/995 (248.9/100 pt years [PY]) pts experienced a treatment-emergent adverse event (TEAE). Serious TEAEs were reported in 122 (7.2/100 PY) pts; 109 (6.3/100 PY) pts discontinued due to a TEAE. Serious infections occurred in 33 (1.9/100 PY) pts. Safety data were comparable with BHI&II.5 Conclusion: In pts treated with BKZ, clinically meaningful improvements in efficacy outcomes observed at 1 year, including the HiSCR 75/90/100, IHS4, and DT count endpoints, were maintained to 2 years; improvements in quality of life were maintained. No new safety signals were observed; the safety profile over 2 years was consistent with BHI&II and BKZ studies in other indications.5,7–9

Pharmacovigilance insights into drug-induced cystitis: analysis of FDA data from 2004 to 2024.

Drug-induced cystitis (DIC) significantly impacts patient quality of life and treatment outcomes. This study investigates the incidence and characteristics of DIC using data from the FDA Adverse Event Reporting System (FAERS). We reviewed FAERS reports related to cystitis from Q1 2004 to Q1 2024, compiling a list of potential causative drugs. The top 50 drugs with the highest number of cystitis reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were used to detect unusually high reporting frequencies of cystitis associated with specific drugs. From 17,703,515 FAERS reports spanning 2004-2024, 36399 involved cystitis. The majority of implicated drugs were antineoplastics. Busulfan, BCG, and mitomycin had the highest ROR and PRR values. Additionally, drugs such as defibrotide sodium, milrinone, and dyazide, which do not have cystitis listed on their labels, were identified, highlighting the need for increased clinical vigilance and awareness. The findings underscore the importance of ongoing pharmacovigilance in identifying and characterizing DIC. Further clinical studies are warranted to validate these associations and to develop strategies for mitigating the risk of DIC, thereby improving patient safety and treatment outcomes.

Efficacy and safety of Piclidenoson in the treatment of plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials.

Psoriasis, an autoimmune inflammatory disease characterized by hyperproliferation of keratinocytes, affects 0.2-4.8% of the global population. The disease manifests primarily as plaque psoriasis, causing chronic physical and psychological burdens. Although numerous treatments exist, there is ongoing exploration for novel therapies due to concerns about the toxicity, efficacy, and costs of current options. An A3 adenosine receptor (A3AR) agonist called Piclidenoson has been shown to reduce inflammation and could be used to treat moderate to severe psoriasis. This meta-analysis evaluates the safety and efficacy of Piclidenoson in psoriasis treatment. This meta-analysis was conducted accordance with the PRISMA guidelines and has been registered on PROSPERO (CRD42024566459). A comprehensive search on Cochrane CENTRAL, PubMed/MEDLINE, and Google Scholar was conducted up to July 2024. Included studies were randomized controlled trials (RCTs) involving Piclidenoson. Efficacy outcomes included PASI 75 and PGA 0 or 1, while safety outcomes included adverse events. Pooled outcomes were presented as odds ratio (OR) with 95% confidence intervals (CI). Statistical analysis employed the Mantel-Haenszel random-effects model, and heterogeneity was assessed using the I2 and X2index. Three RCTs with 574 patients (313 Piclidenoson, 261 placebo) met the inclusion criteria. The pooled analysis showed no significant difference in achieving PASI 75 between Piclidenoson and placebo (OR: 1.62, 95% CI 0.70-3.75, P = 0.26, I2 = 12%). However, Piclidenoson significantly improved PGA scores (OR: 2.74, 95% CI 1.22-6.16, P = 0.01, I²=0%). Safety assessment revealed no significant differences in adverse events, including nervous system, gastrointestinal, musculoskeletal, renal, and infections, compared to placebo. Piclidenoson demonstrates a significant improvement in PGA scores and a favorable safety profile, suggesting it could be a valuable addition to plaque-like psoriasis treatment. Further research with larger, longer-term RCTs is needed to confirm its efficacy and optimize clinical use.

SAFETY AND MATERNAL-FETAL OUTCOMES OF ISOSORBIDE MONONITRATE AND MISOPROSTOL COMBINATION VERSUS MISOPROSTOL ALONE FOR LABOR INDUCTION: A RANDOMIZED DOUBLE-BLIND STUDY

Objective: The induction of labor is essential in managing pregnancies where early delivery benefits outweigh the risks. Misoprostol is a common agent for labor induction but has side effects like uterine hyperstimulation. Isosorbide mononitrate (ISMN), a nitric oxide donor, may enhance cervical ripening and reduce complications when used with misoprostol. This study evaluates the safety and maternal-fetal outcomes of ISMN combined with misoprostol versus misoprostol alone. Methods: A randomized, double-blind study was conducted at Dr. R. P. G. M. C. Kangra. Patients meeting the inclusion criteria were randomly assigned to receive either ISMN with misoprostol or misoprostol with a placebo. Primary outcomes measured were maternal complications (e. g., uterine hyperstimulation, headache, postpartum hemorrhage) and neonatal outcomes (e. g., birth weight, APGAR scores, NICU admission). Secondary outcomes included the need for oxytocin augmentation and the duration of labor stages. Results: The study included 100 patients divided into two groups of 50 each. The ISMN and misoprostol group had significantly fewer headaches and dizziness but showed no significant difference in uterine hyperstimulation or postpartum hemorrhage compared to the misoprostol alone group. The ISMN group required less oxytocin augmentation, and their total labor duration was shorter, though not significantly. Neonatal outcomes were similar across both groups. Conclusion: The combination of ISMN and misoprostol appears to be a safer and potentially more effective alternative to misoprostol alone for labor induction, with fewer maternal complications and similar neonatal outcomes. Further large-scale studies are recommended to confirm these findings and inform clinical practice.

Feasibility, safety, and clinical outcomes of modified laparoscopic cervicoisthmic cerclage for refractory cervical insufficiency: A single-arm clinical trial-Part 1.

To assess the feasibility, safety, and outcomes of modified laparoscopic transabdominal cerclage in patients with refractory cervical insufficiency. This single-arm clinical trial examined women with refractory cervical insufficiency who underwent modified laparoscopic transabdominal cerclage at a specialized center in Japan between December 2017 and May 2022. Various parameters related to patient demographics, surgical techniques, outcomes, and complications were evaluated. The study enrolled 30 women with a median age of 36 years. The modified laparoscopic transabdominal cerclage was technically successful in all cases. The delivery rate and fetal survival rate at 28 days in the third trimester were both 93%. Surgical complication involving small bowel injury occurred in one case and was promptly repaired. No fetal complications or pregnancy losses occurred within 28 days of the procedure. Perinatal outcomes included a cesarean section rate of 93%, a neonatal intensive care unit admission rate of 30%, and an overall fetal survival rate of 93%. Additionally, no absence or reversal of end-diastolic flow in the uterine artery was identified at the time of cerclage in any of the cases. This study demonstrated the feasibility and safety of modified laparoscopic transabdominal cerclage for refractory cervical insufficiency. The procedure achieved a high delivery rate in the third trimester and a good overall fetal survival rate. The study findings highlight the importance of anatomical precision during thread placement in modified laparoscopic transabdominal cerclage. This technique is promising for treating refractory cervical insufficiency and potentially preventing second-trimester losses and extreme preterm births.

Trends in dual antiplatelet therapy regimens and clinical outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention with drug‐eluting stents: A multicenter real‐world study

AbstractBackgroundThe patterns of dual antiplatelet therapy (DAPT) use and the associated clinical outcomes in current practice remain limited. This study evaluates DAPT regimen patterns and clinical outcomes among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).MethodsThis multicenter retrospective cohort study included ACS patients treated with PCI from January 2017 to February 2022 at five tertiary hospitals in Thailand. DAPT was categorized as nonpotent (NP‐DAPT) or potent (P‐DAPT). We described DAPT trends, with major adverse cardiovascular events (MACEs) and major bleeding, as primary efficacy and safety outcomes. Outcomes were assessed using inverse probability treatment weighting (IPTW) with Cox's proportional hazards model.ResultsThe study included 1877 patients with ACS undergoing PCI. The mean age was 64.51 years (standard deviation 11.34), with 639 (34.04%) female patients and 1159 (61.75%) presenting ST‐elevation myocardial infarction (STEMI). Of these, 924 (49.23%) received NP‐DAPT, and 953 (50.77%) were prescribed P‐DAPT. Crude MACE incidence was lower in the P‐DAPT compared to the NP‐DAPT group (6.82% vs. 10.28%). After applying IPTW and conducting Cox's proportional hazard analysis, no significant differences in MACE were observed between groups (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.58–1.25, p = 0.408), nor in major bleeding (HR: 0.80, 95% CI: 0.37–1.70, p = 0.555). P‐DAPT was associated with any higher bleeding risk (HR: 1.52, 95% CI: 1.13–2.03, p = 0.005).ConclusionStandard DAPT remains predominant among Thai ACS patients, with NP‐DAPT prescriptions approaching those of P‐DAPT. Despite similar rates of MACE and major bleeding between the groups, P‐DAPT was associated with a higher risk of any bleeding.

Comparative Safety of Ultrasound Enhancing Agents: A Systematic Review and Bayesian Network Meta-Analysis: Comparative Safety Evaluation of Optison.

Ultrasound enhancing agents (UEAs), including Optison, Definity, and Lumason, enhance the diagnostic performance of echocardiography, particularly in patients with suboptimal acoustic windows. However, there remains a paucity of comparative safety assessments among the Food and Drug Administration (FDA)-approved UEAs. A PRISMA-guided systematic literature review performed in August 2023 searched Medline, Embase, Cochrane Library, and grey literature. Randomized and non-randomized comparative evidence on safety of contrast enhanced procedures were included. A feasibility assessment ensured homogeneity across studies by comparing patient characteristics and outcomes. Bayesian hierarchical network meta-regression was employed to indirectly compare published safety outcomes across different UEAs. In addition, adverse events (AEs) between 2019-2023 for each UEA were retrieved from the FDA Adverse Events Reporting System (FAERS), and comparative safety outcomes were derived using annual UEA administration in the US. Screening of 4146 records rendered 19 studies for inclusion in the indirect comparison analysis after feasibility assessment. Optison demonstrated favorable safety in direct comparisons with Definity and Lumason across the majority of investigated AEs. Network meta-regression results on serious adverse events (SAEs) within 30 minutes revealed odds ratios (ORs) of 0.59 (95% confidence interval: 0.27-1.23) and 0.63 (0.29-1.33) for Optison vs. Lumason and Definity, respectively, indicating a decreased risk of SAEs for Optison vs. Lumason and Definity, further supported by statistically significant ORs within FAERS: 0.01 (0-0.02), P<0.001 and 0.15 (0.05-0.48), P=0.001, for Optison vs. Lumason and Definity, respectively. In conclusion, our results restate the favorable comparative safety profile of Optison, providing new evidence to inform clinical decision-making.

The Platform Trial In COVID-19 priming and BOOsting (PICOBOO): the immunogenicity, reactogenicity, and safety of licensed COVID-19 vaccinations administered as a second booster in BNT162b2 primed individuals aged 18-

PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. Here, we data for second boosters among individuals aged 18-<50 and 50-<70 years old primed with BNT162b2 until Day (D) 84. Immunocompetent adults who had received two doses of BNT162b2 and any licensed COVID-19 booster at least three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The log10 concentration of anti-spike Ig Total was summarised as the geometric mean concentration (GMC). Reactogenicity and safety outcomes were captured. Between Mar 2022 and Aug 2023, 743 participants recruited to the trial had D28 samples available. Of these, 120 and 103 belonged to the 18-<50y and 50-<70y strata, respectively. The mean adjusted GMCs (95% credible intervals) peaked at D28; these were 41 262 (31 611, 51 105), 45 585 (34 194, 57 441) and 25 281 (20 021, 31 234) U/mL in the 18-<50y stratum and 30 753 (25 071, 36 704), 35 132 (27 523, 42 239) and 17 322 (13 983, 20 641) U/mL in the 50-<70y stratum following BNT162b2, mRNA-1273 and NVX-CoV2373, respectively. Limited neutralisation against Omicron subvariants was found following boosting with all vaccines. There were 4 possibly or probably-related adverse events in the 18-<50y stratum and 5 events in the 50-<70y stratum, and severe reactogenicity events were <10% and <11% in these strata, respectively. Vaccines targeting Ancestral virus elicited boosted antibody responses to Ancestral virus but minimal neutralising antibody against Omicron variants.

Exposure-Response Analyses of Sacituzumab Govitecan Efficacy and Safety in Patients With Metastatic Triple-Negative Breast Cancer.

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with metastatic triple-negative breast cancer (mTNBC) who received ≥2 prior systemic therapies (≥1 in metastatic setting). Exposure-response (E-R) relationships between SG exposure and efficacy and safety outcomes were characterized in 277 patients with mTNBC using data from the phase I/II IMMU-132-01 and phase III ASCENT (IMMU-132-05) studies. Evaluated endpoints included complete response (CR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety endpoints (individual first worst grade of select adverse events (AEs)). E-R analyses were also conducted for time to first dose reduction or delay. Patients received SG at 8 or 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle. Average SG-related serum exposure over the treatment duration (until the event) was consistently the most significant exposure metric correlated with efficacy and safety endpoints. Higher average concentration over the treatment duration for SG (CAVGSG) was the best predictor of CR and ORR. The model-predicted proportions of patients with CR and ORR at 10 mg/kg were 4.26% and 32.6%, respectively. Higher CAVG for total antibody was the best predictor of OS and PFS. The model-predicted probability of OS at 12 months at median lactate dehydrogenase (227 IU/L) was 53%. The probability of grade ≥1 evaluated AEs and the risk of dose reductions and delays significantly increased with increasing CAVGSG. The model-predicted proportions of patients with any-grade AEs were 35.9%, 67.4%, 64.7%, and 67.1% for vomiting, diarrhea, nausea, and neutropenia, respectively (10 mg/kg dose group). Neutropenia was the only evaluated AE for which CAVGSG was significantly associated with grade ≥3 events. The clinically meaningful efficacy and manageable safety achieved with SG 10 mg/kg on days 1 and 8 of every 21-day cycle dosing regimen supports the appropriateness of this clinical dosage in patients with mTNBC.

Applications of flexible ureteroscope lithotripsy with negative pressure suction and percutaneous nephrolithotomy in the treatment of 2-3cm diameter renal calculi.

Renal calculus, or kidney stone disease, presents a significant healthcare challenge globally, necessitating diverse therapeutic interventions. Percutaneous nephrolithotomy (PCNL) and flexible ureteroscope lithotripsy (FURL) are prominent among these interventions, with PCNL favored for stones > 2cm and FURL for smaller stones and applications of flexible ureteroscope lithotripsy with negative pressure suction for stones 1.5-2.5cm have some benefit. From June 2019 to January 2024, 310 patients undergoing FURL with negative pressure suction or PCNL for 2-3cm renal calculi were retrospectively analyzed. The demographic and clinical data were collected, and outcomes including stone-free rates (SFR), postoperative complications, and surgical parameters were compared. Comparable SFR were observed between FURL and PCNL groups at 1-month follow-up, although PCNL was superior to FURL after immediately post-surgery. FURL exhibited significantly fewer complications overall (5.7% vs. 19.3%, p = 0.044), shorter hospital stays, and lower postoperative pain levels. The surgical parameters favored FURL, showing lower bleeding volumes, shorter catheter removal times, and less hemoglobin decrease postoperatively. Despite similar stone clearance efficacy at 1-month follow-up, FURL demonstrated superior safety and postoperative outcomes compared to PCNL for 2-3cm renal calculi. These findings highlight the potential advantages of FURL in reducing complications, enhancing recovery, and optimizing patient care pathways.

Exploring whether home-based neuromodulation can boost the analgesic effects of exercise in people with knee osteoarthritis: protocol for a double-blinded, pilot randomised controlled trial

IntroductionKnee osteoarthritis (OA) represents a leading cause of disability globally. Exercise has been demonstrated to improve pain and function in people with knee OA. However, when in pain, commencement of...

Current role of focal therapy in prostate cancer.

Thanks to the improved accuracy of multiparametric Magnetic Resonance Imaging (mpMRI) to detect and localize the dominant index lesion on prostate cancer (PCa), the concept of minimally invasive focal treatments (FT) has gained popularity. Nevertheless, although high-quality evidence that FT has favorable functional outcomes, definitive proof of its oncological effectiveness compared to standard treatments remains underreported. This study aims to explore the efficacy, safety, oncologic and functional outcomes of different type of FT for PCa. A non-systematic literature review was conducted by searching on PubMed "prostate cancer" AND "focal treatment" OR "HIFU" OR "irreversible electroporation" OR "cryoablation" OR "focal laser ablation." Overall, 22 articles published in English literature from 2018 to 2023 describing FT techniques for PCa were included. Related to the field ablated, focal therapies include hemiablation (half gland), focal ablation (zonal-base) or targeted therapy (lesion-based). FT modalities can be categorized in thermal and non-thermal energy: thermal energy techniques include high-intensity focused ultrasound (HIFU), cryotherapy, radiofrequency ablation (RFA), and focal laser ablation (FLA). Focal brachytherapy, irreversible electroporation (IRE), and vascular-targeted photodynamic therapy (VTP) are classified as non-thermal ablation. Each focal ablative treatments could be promising alternative to conventional radical therapies to treat PCa in term of mid-term oncologic and functional outcomes, however, limited data are available in comparison with standardized radical treatments. HIFU and Cryo are the most studied techniques and seem to be superior to radical treatments in term of functional outcomes despite associated with higher recurrence and retreatment rate. Current evidences of oncologic and functional outcomes of FT are based mainly on retrospective, non-comparative and single center studies. Thus, none of the focal therapies available should be considered safe alternative to standardized treatments in routine practice and should be offered only for well selected PCa patients with low or at least favorable-intermediate risk disease, unfit for radical options.

Use of Aspirin and Initial Cardiovascular and Bleeding Risk in Patients with Chronic Kidney Disease

Background: Despite the high cardiovascular risk in patients with chronic kidney disease (CKD), the role of aspirin in primary prevention remains unclear. This study aimed to investigate the association between aspirin initiation in adults with CKD without prior cardiovascular disease (CVD) and the first cardiovascular and bleeding events using Korean nationwide cohort data. Methods: Among individuals aged 40–79 years with an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m2 who underwent routine health examinations between 2011 and 2016, 15,861 individuals who were newly prescribed aspirin at a dose of 100 mg/day were matched with 79,305 aspirin non-users by propensity score matching. The primary efficacy outcome was a composite of nonfatal atherosclerotic CVD or cardiovascular death. The primary safety outcome was hospitalization due to intracranial or gastrointestinal bleeding. Results: During a mean follow-up of 6.9±2.9 years, the incidence rates for the primary efficacy outcome in aspirin users and non-users were 8.0 and 9.0 per 1,000 person-years, respectively. Aspirin therapy initiation was not associated with the primary efficacy outcome (hazard ratio [HR], 0.93; 95% confidence intervals [CI], 0.86-1.04). However, the primary safety outcome of major bleeding was more frequent in aspirin users than in non-users (6.7 versus 4.7 per 1,000 person-years). The HR for this outcome in aspirin users versus non-users was 1.45 (95% CI, 1.32-1.59). Conclusions: No association was observed between aspirin use and the risk of nonfatal atherosclerotic CVD or cardiovascular death in patients with CKD stages G3 and G4 without prior CVD. Aspirin use was associated with higher risk of major bleeding.

Tenecteplase thrombolytic therapy for acute ischaemic stroke in China: a real-world, multicentre, retrospective, controlled study

Background and aimsTenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. We aim to investigate the real-world evidence regarding its safety and effectiveness in China.MethodsWe conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke (AIS) within 4.5 hours of onset between 1 March 2019 and 1 October 2023, from 18 stroke centres in China. Using propensity score matching (PSM), TNK-treated patients were matched 1:1 with alteplase-treated patients. The primary outcome was the rate of symptomatic intracranial haemorrhage (sICH) within 72 hours post-thrombolysis. Secondary outcomes comprised the rate of parenchymal haemorrhage type 2, any intracranial haemorrhage, any systematic bleeding and mortality at 90 days, as well as 24-hour National Institutes of Health Stroke Scale (NIHSS), early neurological improvement at 24 hours, modified Rankin Scale (mRS) shift, percentage of mRS 0–1 and mRS 0–2 at 90 days.ResultsWe identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase. Following PSM, 1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase. No significant differences were observed in rates of sICH (1.8% vs 1.98%, p=0.864) or other safety outcomes. Moreover, TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage (OR: 0.51, 95% CI: 0.31 to 0.86, p=0.012). A higher proportion of patients achieving early neurological improvement at 24 hours (OR: 1.76, 95% CI: 1.48 to 2.09, p=0.000), better 90-day mRS (OR: 0.67, 95% CI: 0.57 to 0.79, p=0.000) as well as higher percentages of 90-day mRS 0–1 (OR: 1.27, 95% CI: 1.05 to 1.54, p=0.012) and mRS 0–2 (OR: 1.41, 95% CI: 1.14 to 1.75, p=0.001) compared with alteplase.ConclusionsThrombolysis with TNK is not associated with an increased risk of sICH, and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.

Comparison of different surgical strategies for cervical dystonia: Evidence from Bayesian network analysis.

Several surgical techniques have been used to treat cervical dystonia (CD), however, to date, the optimal surgical technique for CD remains controversial. We therefore conducted the first network meta-analysis to compare different surgical strategies for CD to inform clinical practice. Electronic databases were searched for surgical strategies for treating CD. The primary outcome was improvement in total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score. Subgroup analysis was performed to compare short-term (< 1 year) and long-term (≥ 1 year) outcomes. Safety outcomes included surgery-related adverse events (AEs). A total of 55 trials with 2032 patients employing five surgical strategies were identified, including globus pallidus internus (GPi)/subthalamic nucleus (STN)-deep brain stimulation (DBS), selective peripheral denervation (SPD), microvascular decompression (MVD) and pallidotomy. All strategies led to significant improvement in total TWSTRS score (mean improvement range 18.65-28.22). GPi-DBS showed significantly greater enhancement than SPD for the whole dataset (mean difference [MD] 7.03, 95% credible interval [Crl] 1.53-12.56), while both GPi-DBS (MD 8.05, 95% Crl 2.35-13.80) and STN-DBS (MD 10.71, 95% Crl 2.22-19.20) exhibited more long-term improvement than SPD. Regarding safety outcomes, GPi/STN-DBS and MVD were associated with fewer surgery-related AEs than SPD (ln odds ratio range -1.68 to -1.41). We conclude that DBS should be the preferred surgical option for CD, and the STN is a promising alternative target choice due to its comparable efficacy with the GPi. However, more direct evidence is still required.