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Abstract Introduction LMNB1-related autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurodegenerative disorder caused by overexpression of LMNB1. We retrospectively reviewed charts of all ADLD patients seen at Mayo Clinic. Methods All available data from molecularly confirmed ADLD patients was reviewed. Results Of eight patients identified, three were male. Age at symptom onset ranged from 33 to 64 years. In males, the first symptom was erectile dysfunction (2/3) or neurogenic bladder (1/3) and, in females, weakness (3/5), bladder dysfunction (2/5), or depression (1/5). Diagnostic delay from symptom onset was a median of 6 (IQR 2.3–10) years. Other reported symptoms included cognitive difficulties (8/8), fatigue (7/8), sleep issues (4/8), mood disturbances (5/8), tremor (4/8), and migraine (4/8). Family history was positive in 6. All eight patients had LMNB1 duplication. Eighteen brain MRIs were reviewed from 7 patients. All showed symmetric confluent T2W deep cerebral and periventricular white matter hyperintensities with involvement of the posterior limb of the internal capsule, corpus callosum, corticospinal tract in brain stem, and superior and middle cerebellar peduncles. Seven spine MRIs from six patients showed moderate diffuse atrophy of the spinal cord. Conclusion Typical clinical symptoms and characteristic MRI changes should prompt genetic testing for ADLD.

Abstract Taxane‐based chemotherapy regimens are used as first‐line treatment for breast cancer. Neurotoxicity, mainly taxane‐induced peripheral neuropathy (TIPN), remains the most important dose‐limiting adverse event. Multiple genes may be associated with TIPN; however, the strength and direction of the association remain unclear. For this reason, we systematically reviewed observational studies of TIPN pharmacogenetic markers in breast cancer treatment. We conducted a systematic search of terms alluding to breast cancer, genetic markers, taxanes, and neurotoxicity in Ovid, ProQuest, PubMed, Scopus, Virtual Health, and Web of Science. We assessed the quality of evidence and bias profile. We extracted relevant variables and effect measures. Whenever possible, we performed random‐effects gene meta‐analyses and examined interstudy heterogeneity with meta‐regression models and subgroup analyses. This study follows the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and STrengthening the REporting of Genetic Association Studies (STREGA) reporting guidance. A total of 42 studies with 19,431 participants were included. These evaluated 262 single‐nucleotide polymorphisms (SNPs) across 121 genes. We conducted meta‐analyses on 23 genes with 60 SNPs (19 studies and 6246 participants). Thirteen individual SNPs (ABCB1‐rs2032582, ABCB1‐rs3213619, BCL6/‐rs1903216, /CAND1‐rs17781082, CYP1B1‐rs1056836, CYP2C8‐rs10509681, CYP2C8‐rs11572080, EPHA5‐rs7349683, EPHA6‐rs301927, FZD3‐rs7001034, GSTP1‐rs1138272, TUBB2A‐rs9501929, and XKR4‐rs4737264) and the overall SNPs' effect in four genes (CYP3A4, EphA5, GSTP1, and SLCO1B1) were statistically significantly associated with TIPN through meta‐analysis. In conclusion, through systematic review and meta‐analysis, we found that polymorphisms, and particularly 13 SNPs, are associated with TIPN, suggesting that genetics does play a role in interindividual predisposition. Further studies could potentially use these findings to develop individual risk profiles and guide decision making.

Abstract In the context of increased pressures on land for food and non‐food production, it is relevant to understand better, which land resources have become unused and abandoned and where these lands are. Data on where these lands are and what their extend is are not collected in regular statistics. In this paper, we present an approach to detect signs of abandonment in cropping land using radar coherence data. The methodology was tested in the Spanish regions of Albacete and Soria where agricultural land abandonment is a common process. The results show that land abandonment detection using radar coherence data works well for the region of Albacete in arable lands. The radar‐based analysis is a relatively simple method to detect land abandonment in an early to longer term state and can therefore be applied once developed and tested further in other regions to larger areas of the EU where land abandonment is serious and needs monitoring and policy response. The applicability of the method to Soria and Emilia Romagna (Italy) regions shows that there are still challenges to overcome to make the method more widely applicable for detecting land abandonment in other environmental zones of Europe. Lack of reliable training and validation data, like Land Parcel Identification Systems data, in regions is one of the challenges in this respect.

Heme is best known for its role as a versatile prosthetic group in prokaryotic and eukaryotic proteins with diverse biological functions including gas and electron transport, as well as a wide array of redox chemistry. However, free heme and related tetrapyrroles also have important roles in the cell. In several bacterial strains, heme biosynthetic precursors and degradation products have been proposed to function as signaling molecules, ion chelators, antioxidants and photoprotectants. While the uptake and degradation of heme by bacterial pathogens is well studied, less is understood about the physiological role of these processes and their products in non-pathogenic bacteria. Streptomyces are slow growing soil bacteria known for their extraordinary capacity to produce complex secondary metabolites, particularly many clinically used antibiotics. Here we report the unambiguous identification of three tetrapyrrole metabolites from heme metabolism, coproporphyrin III, biliverdin and bilirubin, in culture extracts of the rufomycin antibiotic producing Streptomyces atratus DSM41673. We propose that biliverdin and bilirubin may combat oxidative stress induced by nitric oxide production during rufomycin biosynthesis, and indicate the genes involved in their production. This is, to our knowledge, the first report of the production of all three of these tetrapyrroles by a Streptomycete.

Purpose: Circular economy (CE) principles have evolved in response to natural resource depletion as a set of guidelines for eliminating the linear take-use-dispose model of product consumption. The consequences of shifting from a linear to a circular supply chain are difficult to visualize in the long term. This study aims to design a methodology for building a simulation model to implement CE strategies in any small and medium-sized enterprise SME to prove policies before implementing them in the real world. This paper applied the methodology in a biological cycle case study: a confectionery factory in Mexico. Design/methodology/approach: This study evaluated service-dominant logic, ecosystem services, system dynamics, and agent-based modeling to design the proposed methodology. A series of interviews with stakeholders were performed to assess the simulation model during the development phase. The circular economy indicator prototype (CEIP) was used as a circular maturity measure of the confectionery factory. The simulator was executed in Netlogo software, implementing a four-scenario analysis based on two CE policies for the caramel recycling process. Five state variables were proposed in this analysis: confectionery waste, recycled glucose, recycling utilization, costs of recycled glucose, and profit. Findings: The CEIP score of the confectionery factory was 52%, rated as a “good” product. Regarding scenario analysis, the first scenario had the highest profit improvement. Practical implications: The simulator allowed stakeholders to understand the operation of the recycling process and visualize all variables involved in the system. Originality/value: In the CE literature, little attention has been paid to proposing a methodology for designing a simulation model to implement CE strategies in any industry. Thus, this study implements a nine-step methodology based on services context and dynamic simulation tools to design a platform to evaluate and visualize the consequences of CE strategies implementation in the long term.

BackgroundEpisodic angina-like retrosternal pain is a prevalent symptom for achalasia patients pre- and post-treatment. The cause of postoperative chest pain remains poorly understood. Moreover, there are no reports on their predictive value for chest pain in the long-term post-treatment. The effect of laparoscopic Heller myotomy (LHM) and fundoplication techniques (Dor vs. Toupet) is unclear.MethodsWe analyzed a cohort of 129 achalasia cases treated with LHM and randomly assigned fundoplication technique. All the patients were diagnosed with achalasia by high-resolution manometry (HRM). Patients were followed up at 1-, 6-, 12-, and 24-month post-treatment. We implemented unadjusted and adjusted logistic regression analyses to evaluate the predictive significance of pre- and post-operative clinical factors.ResultsPreoperative chest pain with every meal was associated with an increased risk of occasional postoperative chest pain [unadjusted model: odds ratio (OR) = 12, 95% CI: 2.2–63.9, P = 0.006; adjusted model: OR = 26, 95% CI: 2.6–259.1, P = 0.005]. In type II achalasia, hypercontraction was also associated with an increased risk of chest pain (unadjusted model: OR = 2.6 e9 in all the patients). No significant differences were associated with age, type of achalasia, dysphagia, esophageal shape, and integrated relaxation pressure (IRP) with an increased risk of occasional postoperative chest pain. Also, there was no significant difference between fundoplication techniques or surgical approaches (e.g., length of myotomy).ConclusionPreoperative chest pain with every meal was associated with a higher risk of occasionally postoperative chest pain.

The discovery of new enzymes, alongside the push to make chemical processes more sustainable, has resulted in increased industrial interest in the use of biocatalytic processes to produce high-value and chiral precursor chemicals. Huge strides in protein engineering methodology and in silico tools have facilitated significant progress in the discovery and production of enzymes for biocatalytic processes. However, there are significant gaps in our knowledge of the relationship between enzyme structure and function. This has demonstrated the need for improved computational methods to model mechanisms and understand structure dynamics. Here, we explore efforts to rationally modify enzymes toward changing aspects of their catalyzed chemistry. We highlight examples of enzymes where links between enzyme function and structure have been made, thus enabling rational changes to the enzyme structure to give predictable chemical outcomes. We look at future directions the field could take and the technologies that will enable it.

In a context of change such as that which is currently taking place in the field of social sciences education, the ongoing training of in-service teachers is an essential element. Only by bringing about a true change in their teaching practice can teaching approaches and the processes of history education be improved. The present paper aims to contrast a theoretical model with a questionnaire designed to identify the training needs of secondary and baccalaureate teachers with regard to the teaching of the historical thinking skills. A quantitative research methodology has been employed with a non-experimental design in which an exploratory and confirmatory factor analysis and a hierarchical clustering analysis have been carried out. After carrying out and applying the analysis, a questionnaire (NFPA) was elaborated. Its construct validity and reliability were satisfactory and appropriate. The results will make it possible to detect and identify needs and deficiencies in ongoing teacher training. Furthermore, it will become possible to discover new elements in order to improve training processes from the point of view of in-service teachers.

ObjectiveTo assess the incidence and severity of chronic lung disease (CLD) after neonatal extracorporeal membrane oxygenation (ECMO) and to identify factors associated with its development.MethodsA retrospective observational study in a neonatal ECMO center was conducted. All neonates who received support with ECMO in our institution between January 2019 and October 2021 were included and their pulmonary outcome was investigated.ResultsA total of 91 patients [60 with congenital diaphragmatic hernia (CDH), 26 with meconium aspiration syndrome, and 5 with other diagnoses] were included in this study. Sixty-eight (75%) neonates survived. Fifty-two (76%) ECMO survivors developed CLD. There was no statistical difference between patients with and without CLD with regard to gender or gestational age. Patients with CLD had lower birth weight, were younger at the initiation of ECMO, and required longer ECMO runs. Patients with CDH developed CLD more often than infants with other underlying diseases (94 vs. 60%). Seventeen ECMO survivors (25%) developed severe CLD.ConclusionThe incidence of CLD after neonatal ECMO is substantial. Risk factors for its development include CDH as an underlying condition, the necessity for early initiation of ECMO, and the need for ECMO over 7 days.

Objective: To assess and compare the value of antenatally determined observed‐to‐expected (O/E) lung‐area‐to‐head‐circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left‐sided congenital diaphragmatic hernia (CDH). Methods: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E‐LHR and one MRI scan for measurement of O/E‐TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre‐ and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left‐sided CDH with intrathoracic herniation of the liver, receiver‐operating‐characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E‐TFLV and O/E‐LHR in the prediction of postnatal survival. Results: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7–39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0–39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6–37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3–37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left‐sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133–0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141–0.628), P = 0.001), and higher with increasing O/E‐TFLV (OR, 1.123 (95% CI, 1.079–1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055–1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368–16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left‐sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E‐TFLV and O/E‐LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056). Conclusions: In fetuses with left‐sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E‐TFLV on MRI examination and O/E‐LHR on ultrasound examination was similar in one center (Mannheim), but O/E‐TFLV had better predictive value compared to O/E‐LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left‐sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Sturge-Weber syndrome (SWS) is a rare, sporadic neurocutaneous disorder, primarily characterized by port-wine stain (PWS) over the ophthalmic division of the trigeminal nerve (V1) territory (hallmark feature) and glaucoma (in 30–60% of cases). Other ocular manifestations include episcleral involvement of the PWS, choroidal vascular malformations, and iris heterochromia. Two previous reports also associated ectopia lentis concomitantly among these cases. However, here we report spherophakia as a novel ophthalmological finding in SWS. A 56-year-old female previously diagnosed with SWS presented to the outpatient clinic complaining of right-sided decreased visual acuity and pain after a fall. Phenotypically, the patient had a PWS around V1 territory and involvement of both eyelids. Previous relevant ocular history included retinal detachment without macular involvement, ocular hypertension, and phacodonesis. The slit-lamp examination showed anterior lens luxation and elevated intraocular pressure (IOP) of 40 mm Hg by tonometry. Prior to the surgical approach, the patient received hypotensive treatment for elevated IOP. After intracapsular lens extraction, measurements were consistent with spherophakia. Postoperatively, the patient underwent optical coherence tomography (OCT). There was cystic macular edema (CME) by OCT and a detached posterior hyaloid membrane. The patient fully recovered with topical treatment of bromfenac for CME. To the best of our knowledge, this is the first report of concomitant anterior lens luxation and spherophakia (novel association) in a SWS patient. Our findings supplement the differential ocular diagnoses in SWS and should be considered in the routine ocular exam, specifically of the anterior segment. CME occurred similar to otherwise healthy eyes. However, in this case, topical anti-inflammatory medications had a good response and were well-tolerated.

47, XYY syndrome affects males with variable phenotypic expression. Around 80–99% of affected individuals present low-set ears, malar flattening, motor delay, and tall stature. Yet, some cases lack signs or symptoms or are barely noticeable. There are four reports of ocular involvement among these individuals – one with unusual multiple retinal atrophic holes in the posterior pole, other with coloboma, an association with morning glory syndrome, and a case of congenital cataract. Here, we describe a plausible new ocular sign in a 4-year-old male with 47, XYY syndrome who was brought to the outpatient clinic for vision loss. After a complete assessment, we diagnosed a right-sided phacomorphic glaucoma and microspherophakia treated with phacoemulsification and aspiration with posterior capsulotomy and anterior vitrectomy, followed by an Ahmed valve implant for intraocular pressure control. Even though there is a low prevalence of ocular involvement in 47, XYY syndrome cases, this might reflect the rarity of the full expression of the disease leading to an underdiagnosis, added to the scarcity of cases. Microspherophakia and phacomorphic glaucoma among four others previously reported ocular findings could be looked for in 47, XYY syndrome patients.

Background and aim: Neonatal brain monitoring is increasingly used due to reports of brain injury perioperatively. Little is known about the effect of sedatives (midazolam) and anesthetics (sevoflurane) on cerebral oxygenation (rScO2) and cerebral activity. This study aims to determine these effects in the perioperative period.Methods: This is an observational, prospective study in two tertiary pediatric surgical centers. All neonates with a congenital diaphragmatic hernia received perioperative cerebral oxygenation and activity measurements. Patients were stratified based on intraoperatively administrated medication: the sevoflurane group (continuous sevoflurane, bolus fentanyl, bolus rocuronium) and the midazolam group (continuous midazolam, continuous fentanyl, and continuous vecuronium).Results: Intraoperatively, rScO2 was higher in the sevoflurane compared to the midazolam group (84%, IQR 77–95 vs. 65%, IQR 59–76, p = < 0.001), fractional tissue oxygen extraction was lower (14%, IQR 5–21 vs. 31%, IQR 29–40, p = < 0.001), the duration of hypoxia was shorter (2%, IQR 0.4–9.6 vs. 38.6%, IQR 4.9–70, p = 0.023), and cerebral activity decreased more: slow delta: 2.16 vs. 4.35 μV2 (p = 0.0049), fast delta: 0.73 vs. 1.37 μV2 (p = < 0.001). In the first 30 min of the surgical procedure, a 3-fold increase in fast delta (10.48–31.22 μV2) and a 5-fold increase in gamma (1.42–7.58 μV2) were observed in the midazolam group.Conclusion: Sevoflurane-based anesthesia resulted in increased cerebral oxygenation and decreased cerebral activity, suggesting adequate anesthesia. Midazolam-based anesthesia in neonates with a more severe CDH led to alarmingly low rScO2 values, below hypoxia threshold, and increased values of EEG power during the first 30 min of surgery. This might indicate conscious experience of pain. Integrating population-pharmacokinetic models and multimodal neuromonitoring are needed for personalized pharmacotherapy in these vulnerable patients.Trial Registration:https://www.trialregister.nl/trial/6972, identifier: NL6972.

Objective: Valid postnatal prediction parameters for neonates with congenital diaphragmatic hernia (CDH) are lacking, but recently, the chest radiographic thoracic area (CRTA) was proposed to predict survival with high sensitivity. Here, we evaluated whether the CRTA correlated with morbidity and mortality in neonates with CDH and was able to predict these with higher sensitivity and specificity than prenatal observed-to-expected (O/E) lung-to-head ratio (LHR).Methods: In this retrospective cohort study, all neonates with CDH admitted to our institution between 2013 and 2019 were included. The CRTA was measured using the software Horos (V. 3.3.5) and compared with O/E LHR diagnosed by fetal ultrasonography in relation to outcome parameters including survival, extracorporeal membrane oxygenation (ECMO) support, and chronic lung disease (CLD).Results: In this study 255 neonates were included with a survival to discharge of 84%, ECMO support in 46%, and 56% developing a CLD. Multiple regression analysis demonstrated that the CRTA correlates significantly with survival (p = 0.001), ECMO support (p < 0.0001), and development of CLD (p = 0.0193). The CRTA displayed a higher prognostic validity for survival [area under the curve (AUC) = 0.822], ECMO support (AUC = 0.802), and developing a CLD (AUC = 0.855) compared with the O/E LHR.Conclusions: Our data suggest that the postnatal CRTA might be a better prognostic parameter for morbidity and mortality than the prenatal O/E LHR.

Objective: The optimal management of anticoagulation in neonatal/pediatric patients during extracorporeal membrane oxygenation (ECMO) has not been established yet and varies greatly among ECMO centers worldwide. Therefore, we aimed to assess whether the use of anti-factor Xa assay and/or thromboelastometry correlate better than activated clotting time with heparin dose in newborns with congenital diaphragmatic hernia during ECMO. We also examined whether these coagulation assays correlate with thrombotic and/or hemorrhagic complications, when the management of anticoagulation is based only on activated clotting time values.Methods: A prospective observational study in a neonatal ECMO center was conducted. We included all neonates with congenital diaphragmatic hernia born in our institution between March 2018 and January 2019 and requiring support with venoarterial ECMO. A total of 26 ECMO runs were analyzed. During the study, the heparin dose was still adjusted according to activated clotting time values. Measurements of anti-factor Xa assay, activated partial thromboplastin time, and a thromboelastometry from the same blood specimen were performed twice a day.Results: Anti-factor Xa levels showed a moderate correlation with heparin dose, whereas the other tests showed a weak correlation. Four patients (17.4%) had thrombotic complications, 2 patients (8.7%) experienced life-threatening bleeding, and in 11 patients (47.8%) disseminated intravascular coagulation (DIC) occurred. Anti-factor Xa levels were lower in the group with thrombotic complications (0.23 vs. 0.27 IU/ml; p = 0.002), while activated partial thromboplastin time was higher in the group with hemorrhagic complications (69.4 s vs. 59.8 s; p = 0.01). In patients experiencing DIC, heparin dose and anti-factor Xa levels were lower, while no difference in activated clotting time and clotting time in INTEM and INTEM-HEPTEM were shown.Conclusions: Anti-factor Xa levels correlate better to heparin dose than activated clotting time. The use of anti-factor Xa assay instead of activated clotting time for dosing of unfractionated heparin could reduce thrombotic complications in neonates with congenital diaphragmatic hernia on ECMO support. The thromboelastometry showed no additional benefit for this purpose.

Since there are no data available on the influence of the time point of ECMO initiation on morbidity and mortality in patients with congenital diaphragmatic hernia (CDH), we investigated whether early initiation of ECMO after birth is associated with a beneficial outcome in severe forms of CDH. All neonates with CDH admitted to our institution between 2010 until 2020 and undergoing ECMO treatment were included in this study and divided into four different groups: (1) ECMO initiation < 12 h after birth (n = 143), (2) ECMO initiation between 12–24 h after birth (n = 31), (3) ECMO initiation between 24–120 h after birth (n = 48) and (4) ECMO initiation > 120 h after birth (n = 14). The mortality rate in the first (34%) and fourth group (43%) was high and in the second group (23%) and third group (12%) rather low. The morbidity, characterized by chronic lung disease (CLD), did not differ significantly in the three groups; only patients in which ECMO was initiated >120 h after birth had an increased rate of severe CLD. Our data, although not randomized and limited due to small study groups, suggest that very early need for ECMO and ECMO initiation > 120 h after birth is associated with increased mortality.

Background: Spontaneous pneumomediastinum (SP) is generally a benign condition which can have various etiologies. Data on SP related to respiratory viral infections in children are rare and there are currently no official guidelines or consistent treatment recommendations for these patients. Aim: To discuss treatment options considering the recommendations for SP with different etiologies. Methods: We report three cases of SP, which were related to rhinovirus or respiratory syncytial virus (RSV) infection. Results: All three patients presented with typical symptoms of a respiratory tract infection and required oxygen supplementation during the hospital stay. All children benefited from a conservative, supportive therapy, and bed rest, and could be discharged after seven days or less without remaining symptoms. Conclusion: Surveillance and monitoring might be reasonable to detect and treat potential complications in children with SP due to viral infections, as one child developed an increasing pneumothorax, which had to be treated with a thoracic drainage.

The molecular structure of the title complex, [Ni(C13H8F2N2O)(C14H32P2)] or Ni(oFPU)(dippe), where oFPU is the dianion of bis(2-fluorophenyl)urea and dippe is 1,2-bis(di-isopropylphosphino)ethane, comprises an NiII atom with a distorted square-planar coordination environment (geometry index τ4 = 0.195). One of the fluorophenyl rings of the oFPU ligand is disordered over two sets of sites in an 0.832 (7):0.168 (7) ratio. The crystal structure displays C—H...O and C—H...F hydrogen-bonding interactions, leading to chains with R22(12) motifs extending parallel to [100]. The title compound might be of interest with respect to the production of urea and carbamate derivatives of nickel(II).

Objective. Polymerized-type I collagen (polymerized-collagen) is a downregulator of inflammation and a tissue regenerator. The aim was to evaluate the effect of intra-articular injections (IAIs) of polymerized-collagen among patients with symptomatic knee osteoarthritis (OA) in delaying or preventing joint replacement surgery. Patients and Methods. This was a cohort study of 309 patients with knee OA. Patients with mild-to-moderate disease were treated weekly with IAIs of 2 mL of polymerized-collagen for six weeks (n = 309). Follow-up was for 6–60 months. The primary endpoints included the following determinations: (1) therapeutic effect; (2) survival from total knee replacement surgery (TKR); (3) Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and pain (visual analogue scale, VAS). Clinical improvement was defined as a decrease in pain exceeding 20 mm on the VAS and the achievement of at least 20% improvement from baseline with respect to the WOMAC score. Radiographic analysis was performed at baseline and 60 months. The joint space width in the medial, lateral, and patellofemoral compartments was calculated. Results. Patients who received IAIs of polymerized-collagen had a statistically significant improvement in the primary criteria (p