Clinical Failure Research Articles

Evaluation of healing after arthroscopic repair of lateral meniscal tears around the popliteal hiatus

BackgroundThe popliteal hiatus stabilizes the lateral meniscus (LM). Variable failure rates for LM repairs have been reported in knees with lateral meniscal tears (LMTs), which may be attributable to low vascularity around the popliteal hiatus. An effective repair method is essential to enhance the biological healing and stability of LMTs around the popliteal hiatus. HypothesisArthroscopic repair of LMTs, including the popliteus tendon around the popliteal hiatus, is expected to produce a low reoperation rate and effective treatment, both clinically and radiographically. Material and methodsFrom June 2011 to August 2020, 93 patients (mean age 27.9 ± 13.5 years) who underwent arthroscopic repair of LMTs including the popliteus tendon around the popliteal hiatus were enrolled. Patients with LMTs were divided into three groups: isolated LMTs, discoid LMTs, and LMTs with ACL injury. Patients had a minimum clinical follow-up of 2 years (mean 37.9 ± 19.3 months) and Tegner activity, Lysholm knee, and Hospital for Special Surgery (HSS) scores were evaluated for all patients. The widths of the popliteal hiatus and LM extrusion were measured on the sagittal and coronal planes using preoperative and postoperative magnetic resonance imaging (MRI). ResultsThe Tegner activity (2.6 ± 1.2–4.5 ± 1.3), Lysholm (67.9 ± 14.2–88.1 ± 6.4), and HSS scores (79.8 ± 11.5–93.7 ± 5.1) were significantly improved in all knees (p < 0.001). The width of the popliteal hiatus measured on MRI was significantly decreased, when comparing the preoperative and postoperative MRI for all knees (sagittal plane, 2.9 ± 1.4–1.5 ± 0.5 mm; coronal plane, 3.8 ± 2.5 to 1.9 ± 1.0 mm) (p < 0.05). The LM extrusion measured on the sagittal plane of postoperative MRI was also significantly reduced after arthroscopic repair (24.8 ± 3.1–23.7 ± 2.8 mm) (p = 0.001). Five reoperations (5/93, 5.3%) were performed, suggesting a clinical failure. ConclusionArthroscopic repair of isolated, discoid and post-traumatic LMTs including the popliteus tendon around the popliteal hiatus, is an effective surgical treatment for LM stabilization. Level of evidenceLevel IV, retrospective series.

Effect of Quadriceps Tendon Autograft Preparation and Fixation on Graft Laxity During Suspensory Anterior Cruciate Ligament Reconstruction: A Biomechanical Analysis.

Favorable collagen fibril density and thickness combined with advances in graft preparation and fixation have significantly increased interest in the quadriceps tendon (QT) autograft for anterior cruciate ligament (ACL) reconstruction. While various suspensory techniques have been described, the biomechanical profile of these constructs is largely undefined. To compare the biomechanics of suspensory techniques for soft tissue QT autograft fixation in an in vitro model of ACL reconstruction. Controlled laboratory study. Full-thickness QT grafts were harvested using a 9-mm graft blade. Adjustable-loop devices (ALDs) were secured to the graft (n = 6 per group) with a combination implant containing the ALD and suture tape-reinforced whipstitching (tape-reinforced [TR] group), tethered superficially to the graft with a whipstitch (onlay [OL] group), luggage-tagged through and around the graft (luggage tag [LT] group), or staggered behind superficial suturing (staggered [SG] group). Grafts were tested on an electromechanical testing machine following a validated in vitro reconstruction model of intraoperative workflow and postoperative ACL kinematics, cyclic loading, and load to failure. The TR group had significantly less postcyclic tension loss (mean, 24%) compared with the OL (56%; P = .002), LT (69%; P < .001), and SG (90%; P < .001) constructs. Cyclic elongation was below the 3.0-mm threshold defined as clinical failure for TR (1.6 mm), but not for OL (3.3 mm), LT (7.9 mm), and SG (11.3 mm). All constructs were within native ACL stiffness limits (220 ± 72 N/mm) without significant differences. Ultimate loads significantly exceeded a normal ACL loading limit of 454 N for TR (739 N; P = .023), OL (547 N; P = .020), and LT (769 N; P = .001), but not for SG (346 N; P = .236). The TR ALD construct demonstrated the most favorable time-zero biomechanical properties of modern soft tissue QT suspensory constructs, with 32% less tension loss and 52% less cyclic elongation versus the closest construct. Failure loading of all constructs was acceptable with respect to the native ACL except for the SG group, which had suboptimal ultimate load. TR ALD implants may protect soft tissue QT autografts before graft-bone healing in ACL reconstruction by minimizing time-zero laxity and fixation failure.

Intentionally unilateral prostatic artery embolization: Patient selection, technique and potential benefits.

Prostatic artery embolization (PAE) is a promising but also technically demanding interventional radiologic treatment for symptomatic benign prostatic hyperplasia. Many technical challenges in PAE are associated with the complex anatomy of prostatic arteries (PAs) and with the systematic attempts to catheterize the PAs of both pelvic sides. Long procedure times and high radiation doses are often the result of these attempts and are considered significant disadvantages of PAE. The authors hypothesized that, in selected patients, these disadvantages could be mitigated by intentionally embolizing PAs of only one pelvic side. To describe the authors' approach for intentionally unilateral PAE (IU-PAE) and its potential benefits. This was a single-center retrospective study of patients treated with IU-PAE during a period of 2 years. IU-PAE was applied in patients with opacification of more than half of the contralateral prostatic lobe after angiography of the ipsilateral PA (subgroup A), or with markedly asymmetric prostatic enlargement, with the dominant prostatic lobe occupying at least two thirds of the entire gland (subgroup B). All patients treated with IU-PAE also fulfilled at least one of the following criteria: Severe tortuosity or severe atheromatosis of the pelvic arteries, non-visualization, or visualization of a tiny (< 1 mm) contralateral PA on preprocedural computed tomographic angiography. Intraprocedural contrast-enhanced ultrasonography (iCEUS) was applied to monitor prostatic infarction. IU-PAE patients were compared to a control group treated with bilateral PAE. IU-PAE was performed in a total 13 patients (subgroup A, n = 7; subgroup B, n = 6). Dose-area product, fluoroscopy time and operation time in the IU-PAE group (9767.8 μGy∙m2, 30.3 minutes, 64.0 minutes, respectively) were significantly shorter (45.4%, 35.9%, 45.8% respectively, P < 0.01) compared to the control group. Clinical and imaging outcomes did not differ significantly between the IU-PAE group and the control group. In the 2 clinical failures of IU-PAE (both in subgroup A), the extent of prostatic infarction (demonstrated by iCEUS) was significantly smaller compared to the rest of the IU-PAE group. In selected patients, IU-PAE is associated with comparable outcomes, but with lower radiation exposure and a shorter procedure compared to bilateral PAE. iCEUS could facilitate patient selection for IU-PAE.

Spatial multiplexed immunofluorescence analysis reveals coordinated cellular networks associated with overall survival in metastatic osteosarcoma

Patients diagnosed with advanced osteosarcoma, often in the form of lung metastases, have abysmal five-year overall survival rates. The complexity of the osteosarcoma immune tumor microenvironment has been implicated in clinical trial failures of various immunotherapies. The purpose of this exploratory study was to spatially characterize the immune tumor microenvironment of metastatic osteosarcoma lung specimens. Knowledge of the coordinating cellular networks within these tissues could then lead to improved outcomes when utilizing immunotherapy for treatment of this disease. Importantly, various cell types, interactions, and cellular neighborhoods were associated with five-year survival status. Of note, increases in cellular interactions between T lymphocytes, positive for programmed cell death protein 1, and myeloid-derived suppressor cells were observed in the 5-year deceased cohort. Additionally, cellular neighborhood analysis identified an Immune-Cold Parenchyma cellular neighborhood, also associated with worse 5-year survival. Finally, the Osteosarcoma Spatial Score, which approximates effector immune activity in the immune tumor microenvironment through the spatial proximity of immune and tumor cells, was increased within 5-year survivors, suggesting improved effector signaling in this patient cohort. Ultimately, these data represent a robust spatial multiplexed immunofluorescence analysis of the metastatic osteosarcoma immune tumor microenvironment. Various communication networks, and their association with survival, were described. In the future, identification of these networks may suggest the use of specific, combinatory immunotherapeutic strategies for improved anti-tumor immune responses and outcomes in osteosarcoma.

A systematic review of dalbavancin efficacy as a sequential therapy for infective endocarditis.

Dalbavancin is an antibiotic characterized by an extended half-life and efficacy against methicillin-resistant Staphylococci. Currently, there are only narrative reviews summarizing the evidence about the use of dalbavancin for infective endocarditis (IE), many of which are focused primarily on its use as consolidation therapy. For this reason, we conducted a systematic review to describe the clinical efficacy and the safety of dalbavancin in IE treatment. We searched for available evidence using the MEDLINE (PubMed), Embase, Scopus, Cochrane Library and Web of Science libraries, with no restrictions regarding the publication year. The risk of bias was performed using the Cochrane ROBINS-I tool for the comparative studies and the Newcastle-Ottawa Scale for descriptive studies. Nine studies were included. All of them were observational. Native valve endocarditis was the most common kind of IE found in the studies' populations (128/263, 48.7%), followed by prosthetic valve endocarditis, and cardiovascular implantable electronic device-related endocarditis. Coagulase-negative Staphylococci were the most common pathogens isolated (83/269, 30.1%), followed by S. aureus, Enterococci spp and Streptococci spp. Five out of nine studies documented a clinical failure rate of less than 10%. Dalbavancin showed a favourable safety profile. Dalbavancin appears to be a promising option for the consolidation therapy of IE. However, further studies comparing dalbavancin with standard of care are needed. CRD42023430032.

HPMC Extended-Release Multi-Composite Matrix for Co-delivery of Oxcarbamazepine and Vitamin D.

Background: Carbamazepine (CBZ) is considered as first-line treatment for epilepsy. The literature has signified a history of non-uniform drug performance and clinical failures. However, many studies suggested that Oxcarbazepine (OXC), a structural analog of CBZ, may have an equivalent antiepileptic effect. OXC follows a different metabolic pathway other than CBZ. However, both share the same mechanism of action by blocking voltage-gated sodium channels. Objectives: This study aimed to form hydroxypropyl methylcellulose (HPMC) extended-release tablets containing OXC combined with vitamin D. Methods: These formulated tablets were tested for their dissolution rate, tablet hardness, friability, thickness and pharmacokinetic parameters (Cmax and Cmin). Blood sodium levels were additionally investigated to ensure the absence of hyponatremia; the main side effect of long-term use of CBZ and some of its derivatives. Results: The use of HPMC inhibited the formation of dihydrate OXC form thus offering a significant extended-release profile. OXC also showed a highlighted capability to attain high bioavailability. Microcrystalline cellulose (MCC) was also added to tablets formed to inhibit polymorphic transformation. Tablets containing OXC co-delivered with vitamin D ensured significantly decreased susceptibility to hyponatremia, and an extended-release profile was evident. Lower amounts of OXC were loaded in formed tablets containing vitamin D owing to the synergistic effect between vitamin D and antiepileptic drugs. Conclusion: Conclusively, employing these newly HPMC-constructed tablets of OXC co-delivered with vitamin D appeared to be a promising option for the effective management of epilepsy with least side effects.

Lymphatic embolization for early post-operative lymphatic leakage after radical cystectomy for bladder cancer.

Although radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard treatment of muscle invasive bladder cancer, it may cause lymphatic leakage. Recent studies describe lymphatic embolization (LE) as an option to manage post-operative lymphatic leakage. Hence, this study evaluated the outcome of LE in patients receiving RC and analyzed factors associated with outcomes. This was a retrospective analysis of patients who underwent LE after RC for bladder cancer between August 2017 and June 2023. The data was assessed for analysis at January 2024. The patients were divided into a clinical success group and a clinical failure group. Clinical failure was defined as the following: 1) those who required drainage catheter placement >7 days after LE, 2) those who needed re-intervention before catheter removal, and 3) those who experienced adverse events associated with LE. Logistic regression analysis was performed to identify the factors associated with outcomes of LE. We analyzed 45 patients who underwent LE after RC. Twenty-eight (62.2%) patients were identified as clinically successful. Four patients required re-embolization, but none required more than two sessions of intervention. Three patients experienced lymphatic complications after LE. In multivariable analysis, maximal daily drainage volume of >1,000 mL/day (odds ratio [OR] = 4.729, 95% confidence interval [CI]: 1.018-21.974, p = 0.047) and diabetes mellitus (DM) (OR = 4.571, 95% CI: 1.128-18.510, p = 0.033) were factors associated with LE outcome. Our results suggest LE as a potentially effective procedure for controlling post-operative lymphatic leaks after RC, with few minor side effects. Patients exceeding a daily drainage of 1,000mL/day or with a medical history of DM have a higher risk for re-intervention and clinical failure after LE.

Effectiveness of combination therapy with intrathecal or intraventricular administration of polymyxin B for hospital-acquired central nervous system infections caused by carbapenem-resistant Acinetobacter baumannii: a retrospective study

To evaluate the therapeutic regimen, efficacy and safety of intrathecal or intraventricular (ITH/IVT) administration of polymyxin B for hospital-acquired central nervous system (CNS) infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). A retrospective study was performed on patients with CNS infections caused by CRAB treated with ITH/IVT combination therapy. The primary study outcome was the clinical efficacy after treatment. Secondary outcomes were bacterial clearance rate and safety of therapy. In total, 35 patients who received ITH (13[37.1%]) or IVT (22[62.9%]) polymyxin B as combination therapy were included. The median duration of ITH/IVT polymyxin B therapy was 9 days (interquartile ranges, 7-11). The overall clinical cure and bacterial clearance rate was 77.1% and 85.7%, respectively. No adverse effects deemed related with ITH/IVT polymyxin B were recorded. Clinical failure was independently associated with the initial Acute Physiology and Chronic Health Evaluation II (≥ 15) (odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.05-1.42; P = 0.038) and Glasgow Coma Scale scores (≤ 8) (OR, 0.69; 95% CI: 0.49-0.88; P = 0.029). Early administration (within 4 days) of ITH/IVT polymyxin B therapy can support significantly higher clinical cure rate (OR, 0.65; 95% CI: 0.49-1.12; P < 0.001), and potentially reduce the length of treatment and the adverse effects. ITH/IVT administration of polymyxin B is a valid alternative for the treatment of CNS infections caused by CRAB. Early use of ITH/IVT polymyxin B can lead to higher clinical success.

Understanding chromoblastomycosis in Sri Lanka; insights into fungal aetiology and antifungal susceptibility patterns

Introduction: Chromoblastomycosis is a chronic disfiguring fungal infection of the subcutaneous tissue found mainly in the socio-economically marginalized population in the tropical and sub-tropical regions, characterized by the presence of sclerotic cells. This study was done with the aim of identifying the antifungal sensitivity patterns of the causative agents of chromoblastomycosis in Sri Lanka from 1992 to 2019.Methodology: Study was done on the stored isolates received from patients with chromoblastomycosis since 1992 to 2019, to the Mycology Reference Laboratory of Medical Research Institute, Colombo. Isolates were revived by subculture on Potato dextrose agar. Identification was done phenotypically. Antifungal sensitivity testing was performed by E test method. Available demographic and clinical data were analysed.Results: Of the 74 isolates, 71 (96%) were caused by Fonsecaea pedrosoi. Mean MIC for the antifungals tested were lowest for posaconazole 0.015 μg/ml followed by itraconazole 0.225 μg/ml, and voriconazole 0.768 μg/ml while amphotericin B demonstrated complete resistance with mean MIC of 30.591 μg/ml. No statistically significant differences were noted on the antifungal sensitivity of the isolates from 1992 to 2004 and 2005 to 2019.Conclusions: Fonsecaea pedrosoi was the commonest causative agent causing chromoblastomycosis in the studied population. Posaconazole demonstrated the lowest MIC values for the tested isolates followed by itraconazole and voriconazole. Amphotericin B demonstrated very high MIC values which were likely to result in clinical failure upon treatment. MIC values demonstrated minimal fluctuations throughout the tested time.

Effect of Screw Length in Volar Plating for Intra-articular Distal Radius Fractures: A Biomechanical Study

PurposeThe purpose of this study was to compare the effect of varying screw lengths on load to failure and retention of the dorsal ulnar corner fragment after fixation of comminuted intra-articular distal radius fractures in a cadaveric model. MethodsTwenty-four fresh frozen cadaveric forearms were subjected to a standardized distal radius osteotomy to mimic an intra-articular fracture pattern. Dual X-ray absorptiometry scans were performed to ensure minimal variability in bone density. All fractures were fixed with a volar locking plate and distal locking screws. Three different lengths of distal locking screws were used in each group of eight specimens to simulate the clinical decision of different distal screw lengths. The screw lengths tested were bicortical, 100% of the width of the bone but unicortical, and 75% of the width of the bone and unicortical. All specimens were preconditioned with cyclic axial loading and then axially loaded using matching acrylic resin molds to clinical failure and fragment displacement as detected by a motion analysis system. Retention or loss of the dorsal ulnar corner fragment during loading was recorded as a binary variable. ResultsBetween the three groups, there were no statistically significant differences in precycling stiffness, postcycling stiffness, load at 2 mm displacement of the dorsal ulnar corner, or force at failure. The group with 75% length screws had a significantly higher loss of reduction of the dorsal ulnar corner (86%) compared with the other groups (0%). ConclusionsVarying screw lengths did not affect the stiffness or overall loads to failure of axially loaded specimens. However, the 75% length screws did not reliably secure the dorsal ulnar corner fragments. Although this did not significantly affect the overall load to failure of the construct, displacement of this fragment may have implications for rotation of the forearm through the distal radioulnar joint. Clinical relevanceSurgeons should consider the utilization of full-length unicortical locking screws to ensure adequate fixation of the dorsal ulnar corner. Type of study/level of evidenceBiomechanical study V.

Evolutionary dynamics in gut-colonizing Candida glabrata during caspofungin therapy: Emergence of clinically important mutations in sphingolipid biosynthesis.

Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

Refractory Post-Operative Wound Infection by Arthrographis Kalrae: A Case Report and Review of Literature

Arthrographis kalrae (A. Kalrae) infections, although rare, have often demonstrated an extended clinical course. We report a case of refractory post-operative wound infection with A. Kalrae after radical soft tissue and femur resection following total femoral replacement. Identification of A. Kalrae was done based on detailed microscopic and phenotypic characteristics and biochemical tests. Additionally, it was confirmed with sequencing. Although antifungal therapy was started on the basis of the breakpoints observed, clinical failure was met. However, wound infection was subsequently controlled with extensive tissue debridement and a combination of antifungal drug therapy over a period of 33 weeks. The rarity of global data about such unusual fungal infections adds to diagnostic and therapeutic challenges.

Use of EMPAgliflozin in the prevention of CARDiotoxicity: the EMPACARD – PILOT trial

BackgroundAnthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10–15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatmentMethodsThe EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections.ResultsDuring the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04–0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure.ConclusionEmpagliflozin is associated with reduced incidence of CTRCD in high-risk patients treated with anthracyclines. These data should serve as the foundation for a clinical trial to test whether SGLT2 inhibitors can reduce the incidence of heart failure in this patient group.

Frequency of cefiderocol heteroresistance among patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections.

Cefiderocol exhibits potent in vitro activity against carbapenem-resistant Acinetobacter baumannii (CRAb), but this activity has not consistently translated to improved outcomes among patients. Cefiderocol heteroresistance, or the presence of a resistant subpopulation, has been proposed as one possible explanation. The objective of this study was to explore associations between heteroresistance and outcomes of patients with CRAb infections. Baseline CRAb isolates were collected from 27 consecutive patients in the USA and Italy. Cefiderocol susceptibility was tested by broth microdilutions in triplicate. Heteroresistance was defined by population analysis profiling in duplicate. Resistance mechanisms and strain relatedness were evaluated through comparative genomic analysis. Overall, 59% of infecting CRAb isolates were identified as cefiderocol-heteroresistant; rates were higher among isolates from Italy (79%) than the USA (38%). The median Charlson Comorbidity and SOFA scores were 4 and 5, respectively; 44% of patients had pneumonia, which was the most common infection type. Rates of 28-day clinical success and survival were 30% and 73%, respectively. By broth microdilution, cefiderocol MICs ≥1 mg/L were associated with higher failure rates than MICs ≤0.5 mg/L (81% versus 55%). Rates of clinical failure were numerically higher among patients infected by cefiderocol-heteroresistant compared with susceptible CRAb (81% versus 55%). Whole-genome sequencing identified a premature stop codon in the TonB-dependent receptor gene piuA in six isolates, all of which were heteroresistant. This pilot study supports the hypothesis that cefiderocol treatment failure may be associated with higher MICs and/or the presence of heteroresistance. Further studies are needed to confirm these findings.

Real-World Clinical Characteristics and Outcomes with Daptomycin Use in Pediatric Patients: A Retrospective Case Series.

Daptomycin (DAP) is a cyclic lipopeptide that exhibits potent in vitro activity against many drug-resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Despite substantial reports evaluating the clinical outcomes of DAP within the adult population, real-world data are lacking in children. The primary goal of this evaluation was to describe the clinical characteristics and outcomes of DAP use in pediatric patients across a wide range of infections. This retrospective evaluation included patients < 18 years of age who were treated with DAP from January 2014 to May 2023. The primary objective was to evaluate the composite clinical success, which was defined as a 30-day survival, the lack of a 30-day microbiological recurrence, and the resolution of signs and symptoms of an acute infection without therapy modifications based on clinical failures. Secondary objectives included adverse effects potentially attributable to DAP and reasons for DAP utilization. Forty patients were included, which were predominately male (62.5%) and white (52.5%), with a median age of 8.7 [IQR, 4.4-16.0] years. DAP was used for a wide range of infections, including central line-associated bloodstream infections (CLABSIs; 32.5%), infective endocarditis (15.0%), surgical-site infections (12.5%), and osteomyelitis (12.5%). The most common pathogen isolated was MRSA (37.5%), and most patients were bacteremic (60.0%). The median DAP dose was 8 [IQR, 6-10] mg/kg, and the median duration of the DAP therapy was 11.5 [IQR, 4.8-18.8] days. Most patients achieved composite clinical success (75.0%). An adverse effect occurred in 5.0% of the patients. DAP was prescribed the most for its ease of use/ability to facilitate discharge (40.0%) and/or for issues with alternative therapies (37.5%). Most pediatric patients that received DAP demonstrated clinical success with a low incidence of adverse effects. Larger, real-world studies of DAP use are necessary to further assess clinical outcomes.

Outcomes After Extracorporeal Shockwave Therapy for Chronic Noninsertional Achilles Tendinopathy Compared With Chronic Insertional Achilles Tendinopathy: A Retrospective Review.

Extracorporeal shockwave therapy (ESWT) is a noninvasive treatment modality that is used in the treatment of chronic Achilles tendinopathy (AT). To (1) retrospectively assess outcomes after ESWT for both noninsertional AT (NAT) and insertional AT (IAT) at >1-year follow-up and (2) identify potential predictors of outcomes. Cohort study; Level of evidence, 3. Chart review was conducted to identify patients who underwent ESWT for AT with a minimum of 1-year follow-up. Data collected and assessed included patient demographic characteristics, pathological characteristics including the location of AT (NAT or IAT), presence of a Haglund deformity, and severity of tendon degeneration on magnetic resonance imaging (MRI), in addition to treatment characteristics including number of sessions and intensity of ESWT. The Victorian Institute of Sports Assessment-Achilles (VISA-A) and visual analog scale (VAS) pain scores were obtained before ESWT, 6 months after ESWT, and at final follow-up. Failures were also recorded, which were defined as no improvement in VISA-A or VAS scores or need for surgical intervention. Linear regression was performed to identify potential predictors of inferior subjective clinical outcomes and failures. Survival analysis was conducted using Kaplan-Meier curves. The study included 52 patients with IAT and 34 patients with NAT. The mean follow-up in the NAT cohort was 22.3 ± 10.2 months and the mean follow-up in the IAT cohort was 26.8 ± 15.8 months. Improvements in VISA-A and VAS scores were observed in the NAT cohort at 6-month follow-up and at final follow-up (P < .05). Improvements in VISA-A and VAS scores were recorded in the IAT cohort at 6-month follow-up, which subsequently deteriorated at final follow-up. In the NAT cohort, the failure rate at 6-month follow-up was 11.8%, which increased to 29.4% at final follow-up. In the IAT cohort, the failure rate at 6-month follow-up was 32.7%, which increased to 59.6% at final follow-up. Predictors of inferior subjective clinical outcomes and failures in the NAT cohort included pre-ESWT subjective clinical score, male sex, presence of a cardiovascular risk factor, and more severe MRI grading of tendinopathy. Predictors of inferior subjective clinical outcomes and failures in the IAT cohort included pre-ESWT subjective clinical score and more severe MRI grading of tendinopathy. Superior subjective clinical outcomes together with a lower failure rate were maintained for >1 year in the NAT cohort compared with the IAT cohort, calling into question the long-term benefit of ESWT for patients with IAT.

Genicular Artery Embolization for Treatment of Symptomatic Knee Osteoarthritis—2-Year Outcomes from a Prospective IDE Trial

PurposeTo report the 24-month outcomes and subgroup analysis evaluating the safety and effectiveness of the genicular artery embolization (GAE) for the treatment of symptomatic knee osteoarthritis (OA). Materials and MethodsForty participants with symptomatic moderate-to-severe knee OA from a single-center, single-arm, prospective investigational device exemption trial of GAE were included in this study. Abnormal genicular artery neovascularity was identified at the subject’s focal knee pain with digital subtraction angiography and cone-beam computed tomography (CT). Embolization was performed with 100-μm microspheres. The primary end point was treatment effectiveness as measured by sustained improvement in OA symptoms at 24 months, quantified using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Treatment success was defined as ≥50% decrease in WOMAC relative to baseline. Clinical outcomes were assessed with mean age of 66.0 years (SD ± 8.1) and body mass index of 30.1 kg/m2 (SD ± 6.2). ResultsOf the 40 patients, 2 (5.0%) were lost to follow-up. Overall, 18 of 38 (47.4%) patients demonstrated ≥50% reduction in WOMAC at 24 months. In the subset of patients with initial clinical success at 12 months, 18 of 25 (72.0%) reported sustained clinical success at 24 months. Seven of 25 (28.0%) patients had symptom recurrence between 12 and 24 months and were determined to be clinical failures. All treatment-related adverse events occurred within 12 months after GAE, without additional events after 12 months. ConclusionsGAE is effective in achieving sustained symptom relief related to moderate-to-severe knee OA for up to 24 months with an acceptable safety profile.

Long-Term Results of Meniscus Allograft Transplantation With Bone Fixation Show Improved Outcomes but Progression of Joint Space Narrowing, Osteoarthritis, and Cartilage Degeneration

PurposeTo investigate the clinical and objective outcomes of meniscal allograft transplantation (MAT) using bone fixation in patients after a minimum follow-up duration of 15 years, and to compare the demographic factors and allograft status between patients who experienced progression of osteoarthritis and those who did not. MethodsThe consecutive patients who underwent primary MAT between December 1996 and January 2008 were retrospectively reviewed. The inclusion criteria was primary MAT with a minimum follow-up duration of 15 years. Clinical outcomes were evaluated using the modified Lysholm score, along with an evaluation of clinical failure. In objective outcomes, the progression of joint space narrowing, osteoarthritis, and the status of the associated cartilages and allografts were evaluated with follow-up radiographs and MRI. ResultsAmong the 79 cases, 54 knees in 52 patients were included in the study and evaluated for clinical outcomes. The mean Lysholm score improved from 73.9 ± 17.5 preoperatively to 86.4 ± 15.6 over a mean follow-up period of 17.5 ± 3.8 years (P<0.001). Regarding the Minimal clinically important differences (MCID), 38 cases (70.4%) showed an improvement in the Lysholm score. The cumulative clinical survival rate was 87.0%. Objective evaluations evaluated in 32 cases with a minimum of 15 years of radiographic data revealed significant progression of joint space narrowing, osteoarthritis, and cartilage degeneration at the final follow-up, with 11 (34.4%) out of 32 cases exhibiting allograft tears involving ˃50% of the allograft. Patients with osteoarthritis progression exhibited more meniscal allograft tears and extrusion on the last follow-up MRI scan than those without progression. ConclusionNotable progression in joint space narrowing, osteoarthritis, and cartilage degeneration were observed in objective assessment. The progression of osteoarthritis might be associated with allograft tears and extrusion. In clinical evaluations, favorable long-term clinical outcomes were consistently demonstrated after MAT using the bone fixation technique. Level of EvidenceLevel Ⅳ, therapeutic case series.

Long-term Outcomes of Partial Meniscectomy for Degenerative Medial Meniscus Posterior Root Tears.

Previous studies have demonstrated that medial meniscus posterior root tear (MMPRT) repair is superior to debridement in terms of patient-reported outcomes, rates of conversion to total knee arthroplasty (TKA), and long-term costs. Despite the known poor midterm outcomes, there is a paucity of long-term results of partial meniscectomy for degenerative MMPRTs. To 1) evaluate long-term patient-reported and radiographic outcomes of patients who underwent partial medial meniscectomy (PMM) for MMPRTs, and 2) determine the rate of and risk factors for conversion to total knee TKA. Case series; Level of evidence, 4. A previously identified cohort of 26 patients treated with partial meniscectomy for isolated MMPRTs between 2005 and 2013 was prospectively followed for long-term outcomes at a minimum 10-year follow-up. Patients were evaluated for International Knee Documentation Committee (IKDC) outcome score, reoperation, and conversion to TKA. Failure was defined as conversion to arthroplasty or a severely abnormal IKDC subjective score <75.4. This study included 26 patients (10 men, 16 women; mean age, 54 ± 8.7 years [range, 38-71 years] at diagnosis; body mass index, 32.9 ± 5.5) who were followed for a mean of 14.0 ± 3.6 years (range, 10.1-19.6 years). At the final follow-up, 1 patient was deceased and 18 (72%) of the remaining 25 patients had progressed to TKA, with 1 (4%) patient undergoing repeat meniscectomy. The 6 (24%) patients who had not progressed to TKA or revision surgery reported a mean IKDC score of 57 ± 23. Nineteen patients underwent subsequent surgery and 5 demonstrated severely abnormal IKDC scores resulting in a clinical failure rate of 96% (24 of the 25 living patients) at a mean 14-year follow-up. PMM for medial meniscus posterior horn root tears demonstrated 72% progression to TKA and 96% failure according to subjective clinical outcomes at a minimum 10-year follow-up.

630. ENDOSCOPIC MANAGEMENT OF DELAYED-GASTRIC-EMPTYING AFTER ESOPHAGECTOMY IN A TERTIARY REFERRAL CENTER: COMPARISON BETWEEN DIFFERENT ENDOSCOPIC PROCEDURES

Abstract Background Delayed Gastric Emptying (DGE) after Esophagectomy with a gastric conduit is a complication that occurs in 15-39% of patients. It is associated with short and long-term complications and with a poor quality of life. Intra-Pyloric Injection of Botulinum Toxin (BT), Pyloric Pneumatic Dilation (PD), and combination of these two techniques (BTPD) in the same session, represent the main endoscopic procedures, but comparative data are currently unavailable. Methods We retrospectively analyzed prospectively collected data on all consecutive patients with DGE after esophagectomy endoscopically treated from December 2018 to November 2023. DGE was classified based on the onset time (early/late), and the Gastric Outlet Obstruction Score (GOOS) was used for clinical staging. All BT patients received 200UI of toxin, while those PD patients have been dilated up to 20mm. Technical success (TS) was defined as the completion of the procedure, clinical success (CS) as achieving a GOOS of ≥2, and recurrence as the need for endoscopic/surgical treatment in patients who achieved CS. Adverse events (AEs) were classified using the AGREE classification. Results 34 patients (82.4% male, 94.1% Ivor-Lewis, divided as follow: 13 (38.2%)BTPD-group, 12 (35.3%)BT-group and 9(26.5%)PD-group. Median follow-up was of 170 days (IQR 67-604), with no differences between the three groups. No statistically significant differences were found in the baseline characteristics among the three groups (e.g.surgical pyloromyotomy, neoadjuvant treatments). Despite identical TS (100%), BT-group exhibited a higher rate of clinical failure (25%) compared to the other groups (p=0.03). No difference in the recurrence rate was observed between the three groups (p=0.47). Dysfunction analysis showed that BTPD-group was characterized by a significatively shorter median time to refeeding of 1 day (IQR 1) compared to the other two groups (log-rank test p=0.0051). No AEs procedures related were recorded. Conclusions Our study reveals that BT is associated with a considerable rate of clinical failure, and that the combined BTPD treatment may offer a more rapid clinical success, maintaining an equivalent safety profile. Further prospective studies are needed to validate these findings.