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Optimal reduction methods for late-detected developmental dysplasia of the hip (DDH) remain debatable. Gradual reduction (GR) using traction is a safer and more reliable option for late-detected DDH than closed reduction or open reduction with or without preliminary traction. GR using overhead traction, one of the current GR methods, has been indicated for children of walking age up to four years of age, whereas the upper age limit of this method has not yet been determined. We present three cases of late-detected DDH whose hips were treated between four and six years of age with this method. Stable reduction without subsequent redislocation was technically accomplished for all patients, albeit the duration of horizontal traction became longer than usual. Clinically significant avascular necrosis (AVN) has developed in children aged ≥5 years, indicating the need for some modifications to the conventional protocol to prevent AVN.

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Heart transplantation is the definitive treatment for refractory, end-stage heart failure. The number of patients awaiting transplantation far exceeds available organs. In an effort to expand the donor pool, donation after circulatory death (DCD) heart transplantation has garnered renewed interest. Unlike donation after brain death, DCD donors do not meet the criteria for brain death and are dependent on life-sustaining therapies. Procurement can include a direct strategy or a normothermic regional perfusion, whereby there is restoration of perfusion to the organ before explantation. There are new developments in cold storage and ex vivo perfusion strategies. Since its inception, there has been a steady improvement in post-transplant outcomes, largely attributed to advancements in operative and procurement strategies. In this narrative review, the authors address the unique considerations of DCD heart transplantation, including withdrawal of care, the logistics of procuring and resuscitating organs, outcomes compared with standard donation after brain death, and ethical considerations.

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The CTC1-STN1-TEN1 (CST) complex is a single-strand DNA-binding protein complex that plays an important role in genome maintenance in various model eukaryotes. Dysfunction of CST is the underlying cause of the rare genetic disorder known as Coats plus disease. In addition, down regulation of STN1 promotes colorectal cancer development in mice. While prior studies have utilized RNAi to knock down CST components in mammalian cells, this approach is associated with off-target effects. Attempts to employ CRISPR/Cas9-based knockout of CST components in somatic cell lines have been unsuccessful due to CST's indispensable role in DNA replication and cell proliferation. To address these challenges, we outline a novel approach utilizing a Cre-loxP-based conditional knockout in mouse embryonic fibroblasts (MEFs). This method offers an alternative means to investigate the function and characteristics of the CST complex in mammalian systems, potentially shedding new light on its roles in genome maintenance. Key features • Conditional depletion of mammalian STN1 using mouse embryonic fibroblast (MEFs). • Analysis of oxidative damage sensitivity using STN1-depleted MEFs. • This protocol requires Stn1flox/flox mice.

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Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

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Introduction: Latanoprostene bunod 0.024% (LBN, Vyzulta®) is a nitric oxide-donating prostaglandin analog (PGA). We investigated the real-world efficacy and safety of LBN in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) who switched their existing intraocular pressure (IOP)-lowering treatment(s) to LBN. Methods: This non-interventional, multicenter (United States), retrospective chart review included patients aged ≥18 years with OHT and/or mild-to-moderate OAG diagnoses taking 1-2 IOP-lowering treatments at the time of switch to LBN (index visit). Chart-extracted data included demographics, diagnoses, IOP and ocular assessments, other IOP-lowering treatments, adverse events (AEs), and reasons for discontinuation. The main study outcome was IOP change from the index visit to each of the next 2 chart-recorded follow-up visits. Analysis groups included the overall dataset and 2 subgroups of patients switched from PGA therapy to LBN: "PGA-all" subgroup [all patients previously on a PGA with/without another IOP-lowering product] and "PGA-monotherapy" subgroup [patients previously on a PGA alone]). Additional ocular outcomes (eg, visual acuity) were examined, if available. Results: The overall dataset included 49 patients (46 had OAD alone, 2 had OHT alone, and 1 had both). The PGA-all subgroup and PGA-monotherapy subgroups had 41 and 32 patients, respectively. Switching to LBN led to a ~25% IOP reduction from the index visit to Visit 1 that was sustained at Visit 2. IOP findings in the PGA-all and PGA-monotherapy subgroups were consistent with the overall dataset. No meaningful changes in other ocular outcomes were found. Of 14 ocular AEs, 3 were recorded as such (mild in severity, considered unrelated to treatment), and 11 were identified through review of interval ocular histories (no severity/relatedness information); none led to discontinuation. Conclusion: In this short-term retrospective chart review of mild-to-moderate OAG/OHT, switching prior IOP-lowering therapy to LBN produced an additional ~25% IOP reduction and appeared to be well tolerated.

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PURPOSE: The aim of this study is to analyze the distribution of visual field (VF) mean defect (MD) in six subgroups of glaucoma patients at baseline and follow-up. METHODS: We assessed glaucoma patients treated in a Spanish tertiary care setting with a follow-up of at least 10 months. We have included 1036 visual fields and the following glaucoma subtypes: open-Angle Glaucoma (OAG); Angle-Closure Glaucoma (ACG); Congenital Glaucoma (CG); Ocular hypertension (OHT); Pseudoexfoliative Glaucoma (PSXG); Pigmentary Glaucoma (PG). We have calculated the baseline MD and the progression MD. We have stratified the MD progression in slow (MD rate > -0.5 dB/year); moderate (MD rate between -0.5 and -1 dB/year) fast (MD rate between -1 and -2 dB/year) and catastrophic (<-2 dB/year) progression and their glaucoma subtype. RESULTS: The glaucoma types with the worse baseline MD were CG and PG. We found significant differences after comparing the baseline MD of CG and OAG, ACG, OHT and between PG and OHT. Concerning the MD progression rate: OAG 73.54% showed slow MD progression rate; 9.85% fast; 7.3% moderate and 9.3% catastrophic. ACG 82.22% slow; 8.89% moderate; 2.22% fast and 6.67% catastrophic. CG 68.83% slow; 9.09% fast; 7.79% moderate and 14.29% catastrophic. OHT 88.6% slow; 6.14% moderate; 4.39% fast and 0.88% catastrophic. PSXG 63.24% slow, 13.24% moderate; 8.8% fast and 14.7% catastrophic. PG 89.29% slow; 3.57% moderate and 7.1% fast. CONCLUSIONS: The CG requires special attention because of its aggressive presentation and progression.

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The global demand for cardiac transplants continues to rise, even with advancements in assistive devices. Currently, the estimated annual mortality rate stands at 3-5%, and patients often face a waiting time of approximately four years on transplant waiting lists. Consequently, many transplant centers have started to consider heart transplants from donors who may be deemed "less than ideal" or marginal. However, the decision to accept such donors must be highly individualized, taking into consideration the risks associated with remaining on the waiting list versus those posed by the transplantation procedure itself. A potential solution lies in the creation of two distinct recipient lists, matched with donor criteria, allowing marginal donors to provide the lifeline that selected patients require. This paper follows a two-step approach. Firstly, it offers an overview of the current state of affairs regarding the topic of transcatheter aortic valve implantation (TAVI) in orthotopic heart transplant (OHT) patients. Secondly, it presents firsthand experience from our clinical center with a comprehensive case presentation of a patient in this unique medical context. The clinical case refers to a 62-year-old male patient, a smoker with a history of hypertension, dyslipidemia, and a prior OHT a decade earlier, who presented with fatigue during minimal physical exertion. The Heart Team carefully reviewed the case, considering the patient's immunosuppressed status and the heightened risk associated with a repeat intervention. In this instance, transcatheter aortic valve implantation (TAVI) was deemed the appropriate treatment. The TAVI procedure yielded successful results, leading to improved clinical status and enhanced cardiac function. The inclusion of marginal donors has introduced novel challenges related to the utilization of previously diseased marginal organs. TAVI has already demonstrated its efficacy and versatility in treating high-risk patients, including heart transplant recipients. Consequently, it emerges as a vital tool in addressing the unique challenges posed by the inclusion of marginal donors.

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BACKGROUND: Orthotopic heart transplantation (OHT) improves survival in eligible patients. Organ scarcity necessitates extensive clinical and psychosocial evaluations before listing. The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) predicts risk for poor psychosocial outcomes and morbidity in the first year post-transplant, yet it is unknown whether it predicts long-term outcomes. METHODS: Blinded examiners obtained data from a retrospective cohort of 51 OHT recipients from a high-volume center. Patients with "Excellent" or "Good" SIPAT score indicating low psychosocial risk for transplant (E/G) were compared with those who met "Minimum Acceptable Criteria" or were "High Risk" (MAC/HR). Associations were examined between SIPAT group and outcomes. RESULTS: MAC/HR versus E/G recipients had significantly reduced survival in the 10 years post-OHT (mean 6.7 vs 8.8 years, p = 0.027; 55% vs 82% survival proportions, p = 0.037). MAC/HR patients were more likely to live in a county with greater income inequality (p = 0.025) and have psychiatric history pre-OHT (p = 0.046). Both groups had otherwise similar demographics and medical history. A lower proportion of MAC/HR patients adhered to medications post-OHT and a greater proportion had psychiatric illness, though differences were not significant. CONCLUSIONS: Higher-risk SIPAT scores predict reduced long-term survival post-OHT. Further efforts are crucial to improve outcomes in higher-risk patients.

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INTRODUCTION: Steroid-induced ocular hypertension (OHT) occurs in approximately one third of cases after dexamethasone implant (DEXi) injection. Among these, more than one fifth occur after the third DEXi intravitreal injection (IVI). Our goal was to analyze the clinical profiles of these late responders. MATERIAL AND METHODS: A real-life, retrospective, observational study was conducted to assess demographic characteristics and intraocular pressure (IOP) responses in late responders (IOP ≥ 21mmHg, n DEXi ≥ 4). The following parameters were analyzed: IOP 2 months after IVI and number of glaucoma medications needed. The IOP response compared to baseline was defined as low (< +6mmHg), moderate (≤ +15mmHg) or high (> 15mmHg). RESULTS: Late steroid-induced OHT occurred in 20.8% of cases. Twenty eyes (18 patients) were included. The mean duration of follow-up was 3.8±1.9 years. They received a mean number of 9.5±4.2 IVI. The first OHT peak, measured at 25.3±3.2mmHg (21-31), occurred after 6.8±2.3 IVI. Approximately 65% of OHT spikes occurred between the fourth and sixth IVI; 35% occurred later. At maximum, 1.7±1.0 glaucoma medications and 0.75±0.79 SLT procedures were required to control the OHT, with no filtering surgery required. The ratio of "low," "moderate," and "high" responders was 5%, 85% and 10% respectively. CONCLUSION: Late steroid-induced OHT occurs after at least 3 DEXi in one fifth of multi-injected patients, requiring long-term IOP monitoring. This case series identifies mostly moderate responder profiles, whose IOP rise often remains well-controlled with medical management or laser treatment (SLT).

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Steroids are commonly used in children for the treatment of various medical conditions. However, systemic steroids can lead to the development of ocular hypertension (OHT), an increase in intraocular pressure. Limited literature is available on the systemic route of steroid administration in children and the development of this side effect. For literature writing and review, a thorough research was conducted across various platforms, such as PubMed, PubMed Central (PMC), Medline, and Cochrane Database of Systematic Reviews (CDSR). After all the screening processes and quality checks, 12 articles were finalized for review writing. The aim was to explore if OHT development is a common side effect developed in children on systemic steroid use for various medical conditions and if any particular risk factors were present among children that lead to its development. The results indicate that OHT is a common side effect of systemic steroid use in children. Children may or may not present with the symptoms of raised intraocular pressure. The development of OHT occurs within one month of the beginning of the steroid treatment in most of the reviewed studies. Several risk factors associated with developing this side effect were also found. In conclusion, systemic steroid use in children leads to the development of OHT. Awareness among healthcare professionals regarding this potential association is necessary. This information can be used to develop guidelines for serial ocular examinations in children on prolonged systemic steroid use.

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In the European Union, the Chemicals Strategy for Sustainability (CSS) highlights the need to enhance the identification and assessment of substances of concern while reducing animal testing, thus fostering the development and use of New Approach Methodologies (NAMs) such as in silico, in vitro and in chemico. In the United States, the Tox21 strategy aims at shifting toxicological assessments away from traditional animal studies towards target-specific, mechanism-based and biological observations mainly obtained by using NAMs. Many other jurisdictions around the world are also increasing the use of NAMs. Hence, the provision of dedicated non-animal toxicological data and reporting formats as a basis for chemical risk assessment is necessary. Harmonising data reporting is crucial when aiming at re-using and sharing data for chemical risk assessment across jurisdictions. The OECD has developed a series of OECD Harmonised Templates (OHT), which are standard data formats designed for reporting information used for the risk assessment of chemicals relevant to their intrinsic properties, including effects on human health (e.g., toxicokinetics, skin sensitisation, repeated dose toxicity) and the environment (e.g., toxicity to test species and wildlife, biodegradation in soil, metabolism of residues in crops). The objective of this paper is to demonstrate the applicability of the OHT standard format for reporting information under various chemical risk assessment regimes, and to provide users with practical guidance on the use of OHT 201, in particular to report test results on intermediate effects and mechanistic information.

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Topic: To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. Clinical Relevance: The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. Methods: The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups' eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Results: Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. Conclusions: The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

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PURPOSE: To investigate the effect of fixed combination versus concomitant unfixed topical glaucoma treatment on patients' adherence and ocular surface health. PATIENTS AND METHODS: This is a 6-month, prospective, parallel-group, observational study in patients with ocular hypertension (OHT), primary open-angle glaucoma (POAG), or exfoliation glaucoma (XFG). A total of 142 patients with similar baseline characteristics were enrolled in this study. Seventy-one patients received a Latanoprost 0.005%/Timolol 0.5% fixed combination in the evening, whereas seventy-one patients received the unfixed treatment with Latanoprost 0.005% in the evening and Timolol 0.5% twice daily. The primary outcome was the adherence rate at baseline, and at the 3- and 6-month follow-up visits. The secondary outcomes included the signs of ocular surface disease (OSD) and intraocular pressure (IOP). RESULTS: The adherence of patients treated with the fixed combination was higher than the unfixed treatment at the 3-month (78.0% vs. 63.0%, p < 0.001) and at the 6-month visits (73.0% vs. 58.5%, p < 0.01). The Break-up Time, Schirmer test, and Van Bijsterveld score were worse in the unfixed group at baseline and all subsequent examinations (p < 0.05 for all comparisons). There were no differences in the mean IOP between groups at baseline, 1-, and 3-month visits. IOP appears higher in the unfixed group at 6 months (16.7 vs. 15.0 mmHg, p < 0.01). CONCLUSION: The patients with ocular hypertension and primary open-angle glaucoma treated with a fixed combination are significantly more adherent and show a healthier ocular surface than those treated with an unfixed combination. The study provides significant evidence of the benefits of fixed combination treatment.

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Glucocorticosteroids commonly used to treat certain ocular inflammatory conditions cause an unwarranted elevation in intraocular pressure (IOP) leading to steroid-induced ocular hypertension (OHT). This study aims to identify novel genetic variants in the Indian population associated with steroid responsiveness, specifically to that of intravitreal Triamcinolone acetonide (TA) injections, which leads to OHT in 27% of the TA-treated Indian subjects. Genetic determinants and pathways regulating TA-OHT progression were investigated by applying whole-genome sequencing (WGS) on DNA extracted from 53 blood samples that included TA responders and non-responders. Sequencing analysis yielded 45 intronic and 49 exonic variants to be associated with TA-OHT, which are known to play a vital role in eye, heart, brain, and bone deformities. Of these, the most significant genetic variant associated with TA-OHT was further considered for molecular dynamics (MD) simulation studies. Variants in the CRPPA, PLOD1, ARHGAP1, TIMELESS and TNFSF4 genes were found to be directly implicating TA-OHT. Furthermore, these genes were enriched in pathways associated with cardiomyopathy, focal adhesion, extracellular matrix, and actin cytoskeleton reorganization. MD simulation studies revealed that the top significant variant (rs141625803) in the CRPPA gene possesses a high pathogenic and structurally destabilizing effect. Thus, novel genetic variants that could be significantly associated with the TA-OHT progression were identified in this study. Validation of these targets in a larger cohort of patients along with their functional analysis would inform on the disease, thereby adding to the existing knowledge on the pathophysiology of TA-OHT.

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Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%-50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to characterize systemic and central nervous system (CNS) inflammatory changes following surgery in mice and humans. Matched plasma and cerebrospinal fluid (CSF) samples from the "Investigating Neuroinflammation Underlying Postoperative Brain Connectivity Changes, Postoperative Cognitive Dysfunction, Delirium in Older Adults" (INTUIT; NCT03273335) study were compared to murine endpoints. Delirium-like behavior was evaluated in aged mice using the 5-Choice Serial Reaction Time Test (5-CSRTT). Using a well established orthopedic surgical model in the FosTRAP reporter mouse we detected neuronal changes in the prefrontal cortex, an area implicated in attention, but notably not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased. Given the growing evidence for a YKL-40 role in delirium and other neurodegenerative conditions, we assayed human plasma and CSF samples. Plasma YKL-40 levels were similarly increased after surgery, with a trend toward a greater postoperative plasma YKL-40 increase in patients with delirium. However, YKL-40 levels in CSF decreased following surgery, which paralleled the findings in the mouse brain. Finally, we confirmed changes in the blood-brain barrier (BBB) as early as 9 h after surgery in mice, which warrants more detailed and acute evaluations of BBB integrity following surgery in humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms.

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PURPOSE: Steroid-induced ocular hypertension (OHT) occurs in about a third of cases after dexamethasone implant (DEXi) intravitreal injection (IVI), for which treatment discontinuation may be required. The aim of this study was to assess the benefit of selective laser trabeculoplasty (SLT) in patients who developed transient OHT after DEXi injection to prevent subsequent steroid-induced OHT peaks during reinjections. METHODS: A real-life, retrospective, and observational study was conducted to assess the intraocular pressure (IOP) after SLT in steroid responders after DEXi injection (IOP > 21 mmHg). Were analyzed: IOP 1 and 2 months after SLT, maximum IOP (IOPmax) after each new DEXi IVI, and the number of prophylactic hypotensive treatments needed at the time of DEXi reinjections. RESULTS: Thirty-five eyes of 29 patients were included. The mean macular edema follow-up duration was 38.4 ± 28.4 months. SLT was performed after a mean number of 6.3 ± 4.7 DEXi IVIs. After SLT, the IOPmax measured after the first reinjection was lowered by 36.6 ± 14.7% (p < 0.0001). The mean number of hypotensive treatments was 2.1 ± 0.9 before versus 1.5 ± 0.8 after SLT. The post-reinjection lowering in OHT peak was maintained during the subsequent 3 DEXi IVIs: - 29.1 ± 25.5% (p = 0.0009), - 35.8 ± 13.1% (p = 0.0078), and - 45.4 ± 8.6% (p = 0.0312) after the second, third, and fourth DEXi reinjections. SLT allowed continuing injections in 88.6% of patients. CONCLUSION: The use of 180° SLT in this indication could be an effective therapeutic alternative to control steroid-induced OHT and safely continue DEXi injections.

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Giant cell myocarditis is a rare cause of cardiogenic shock requiring a high index of suspicion, rapid immunosuppressive therapy, and mechanical circulatory support. We present the case of a patient with giant cell myocarditis who underwent a successful bridge with four different types of mechanical circulatory support devices to heart transplantation. (Level of Difficulty: Advanced.).

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INTRODUCTION: In the last 25 years, topical prostaglandin analogues (PGAs) have emerged to become first line and first choice therapeutic options in the management of glaucoma and ocular hypertension (OHT). Although the short-term efficacy and safety of PGAs has been extensively investigated, less is known about their long term safety and tolerability. This gap in current knowledge is clinically relevant, because treatment-related adverse events and long-term tolerability issues are key determinants of the overall success of long-term therapy and the final outcome of a lifelong, symptomless disease like glaucoma. AREAS COVERED: We include selected evidence pertaining to the safety and tolerability of available and emerging PGA formulations. We also outline PGA formulations with different concentrations of the active ingredient, different preservatives, and preservative-free (PF) options. EXPERT OPINION: Undoubtedly PGAs will continue to play a major role in the medical therapy of glaucoma and OHT. Despite extensive literature and prolonged clinical experience with these agents worldwide, a number of areas that warrant further research have been identified in the present review. Recently launched novel PGAs, or those still in development offer new opportunities and future challenges.

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Cardiorenal syndrome is a complex syndrome characterized by dysfunction of the heart and kidneys in an interdependent fashion and is further divided into different subtypes based on primary organ dysfunction. Simultaneous Heart-Kidney transplantation is the treatment of choice for end-stage irreversible dysfunction of both organs, however it may be avoided with determination of cardiorenal subtype and management of primary organ dysfunction. This article discusses types of cardiorenal syndrome, indications and concerns regarding the use of simultaneous heart-kidney transplantation, and outlines algorithms for determination of need for dual vs. single organ transplantation.

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We present 3 cases of superior vena cava (SVC) syndrome following percutaneous right ventricular assist device (RVAD) placement. Each case underscores the importance of early recognition of SVC syndrome in patients with percutaneous RVAD insertion via the internal jugular vein and calls for heightened awareness of device-associated complications. (Level of Difficulty: Advanced.).