Injury Patterns Research Articles

Frequency and pattern of acute kidney injury in patients with acute stroke

Background and objective: Stroke is a severe disease of the nervous system resulting in disability and death of the affected individual. Acute kidney injury (AKI) which is a clinical syndrome due to sudden renal function decline is considered as an important factor that increases fatality following a stroke. Thus, this study was conducted to determine the frequency and pattern of AKI in stroke patients and the outcome of patients with stroke and AKI. Methods: This study was a descriptive cross-sectional study, carried out at the Delta State University Teaching Hospital (DELSUTH), Oghara, Delta state, which is a public tertiary health institution in Delta state in a semi-urban area in southern Nigeria. Results: The mean age of patients was 58.9 ± 14.2 years. Slightly above half (53.7%) of the patients were males. Haemorrhagic stroke was the most common type of stroke. Hypertension was the most frequent co-morbid condition (59.0%). Twenty (14.9%) had acute kidney injury, of which stage one AKI was the most dominant (75.0%). Majority of the patients (79.9%) survived. Having sepsis was a significant factor associated with the presence of AKI. None of the clinical characteristics was associated with outcome of patients. Conclusion: The frequency of AKI in stroke patients was 14.9%, with majority of the patients presenting with stage 1 AKI. Presence of sepsis was a significant risk factor for development of AKI in patients with acute stroke, while hypertension was the most prevalent comorbid condition in patients with acute stroke, thus the need for continuous screening of stroke patients for hypertension.

Evaluating drivers of recent large whale strandings on the East Coast of the United States.

Anthropogenic stressors threaten large whales globally. Effective management requires an understanding of where, when, and why threats are occurring. Strandings data provide key information on geographic hotspots of risk and the relative importance of various threats. There is currently considerable public interest in the increased frequency of large whale strandings occurring along the US East Coast of the United States since 2016. Interest is accentuated due to a purported link with offshore wind energy development. We reviewed spatiotemporal patterns of strandings, mortalities, and serious injuries of humpback whales (Megaptera novaeangliae), the species most frequently involved, for which the US government has declared an "unusual mortality event" (UME). Our analysis highlights the role of vessel strikes, exacerbated by recent changes in humpback whale distribution and vessel traffic. Humpback whales have expanded into new foraging grounds in recent years. Mortalities due to vessel strikes have increased significantly in these newly occupied regions, which show high vessel traffic that also increased markedly during the UME. Surface feeding and feeding in shallow waters may have been contributing factors. We found no evidence that offshore wind development contributed to strandings or mortalities. This work highlights the need to consider behavioral, ecological, and anthropogenic factors to determine the drivers of mortality and serious injury in large whales and to provide informed guidance to decision-makers.

Distal Tibiofibular Syndesmosis Injuries in the National Football League (NFL): A Spectrum of Pathology That Correlates With Time to Return to Full Participation.

Studies routinely evaluate high ankle sprains in isolation, but recent data suggest that these injuries are often associated with concomitant pathology, potentially influencing return to full participation. In National Football League (NFL) players, isolated high ankle sprains are rare and syndesmosis injuries with concomitant pathology will result in increased time to return to full participation. Cross-sectional study. Level 3. Distal tibiofibular syndesmosis injuries sustained by NFL players between 2017 and 2019 were identified through NFL Injury Surveillance Database queries and verified with video analysis. Each injury underwent a comprehensive magnetic resonance imaging (MRI) review. Regression modeling was utilized to explore the influence of numerous imaging findings on time to return to full participation. There were 83 external rotation ankle injuries involving the syndesmosis. Isolated distal tibiofibular syndesmosis injuries were rare (n = 11; 13%) and more often associated with other ligamentous injury (deltoid ligament and lateral ligamentous complex) and/or fractures. Regression modeling resulted in clustering of 3 injury pattern groups for time to return to full participation across numerous imaging findings: syndesmosis injury-fracture combinations (250 days [interquartile range [IQR,] 142-266 days]), syndesmosis injury with complete deep deltoid tear or acute diastasis (175 days [IQR, 20-248 days]), and all other syndesmosis injuries (27 days [IQR, 18-46 days]). In NFL athletes with external rotation ankle injuries, isolated distal tibiofibular syndesmosis injuries were rare and more often associated with concomitant pathology. Time to return to full participation was affected by an associated fracture and complete deep deltoid ligament tear or diastasis but no other relevant MRI variables such as lateral ligament complex involvement or the presence of osteochondral lesions or bone contusions.

Clinical Significance of the Large Fetal Vessel Lesions in Placental Fetal Vascular Malperfusion

Fetal vascular malperfusion (FVM) is an important pattern of placental injury. Although the significance of distal villous FVM (clusters of sclerotic and/or mineralized chorionic villi) is well documented, the clinical significance of proximal (large vessel) lesions of FVM is less clear, which is the aim of this retrospective analysis. To evaluate the clinical significance and placental associations of single and coexisting categories of lesions of large vessel FVM, 24 clinical and 44 placental phenotypes of 804 consecutive placentas with at least 1 lesion of proximal vessel FVM from the second half of pregnancy, divided according to the type or category of the individual FVM lesion (fetal vascular ectasia, fetal vascular thrombi, intramural fibrin deposition, and stem vessel obliteration): 689, 341, 286, and 267 placentas, respectively (first analysis) and single or coexisting large fetal vessel lesions (1, 2, 3, and 4 coexisting categories of lesions: 276, 321, 162, and 45 placentas, respectively) were statistically compared (analysis of variance, χ2, univariate analysis). Because of multiple comparisons, Bonferroni-corrected P < .001 was used as a threshold of statistical significance. In this population of high-risk pregnancies dominated by fetal congenital anomalies, single individual or 1 to 2 coexisting categories of lesions of the large vessel FVM, including fetal vascular thrombi, did not consistently correlate with clinical or placental variables and were not prognostically useful, but the coexistence of 3 or 4 lesions was associated with the most advanced gestational age, fetal congenital anomalies, distal villous FVM, particularly high-grade, chorangioma or chorangiomatosis, hypercoiled umbilical cord, perivascular stem edema, and marginate or vallate placenta. Therefore, the finding of multiple lesions of the large vessel FVM not only merits a diligent search for the distal villous lesions including the CD34 immunostaining, but also justifies putting the large vessel (global) FVM on the final placental diagnosis line, which in the case of up to only 2 lesions may not be justified.

Avulsion and Soft Tissue Injuries of the Ulnar Collateral Ligament in Children and Adolescents.

Although pediatric medial epicondylar fractures and apophysitis are well studied, patterns of subapophyseal avulsion and ligamentous injuries of the medial elbow in this population merit investigation to inform optimal treatment strategies. To describe the occurrence and demographic correlates of ulnar collateral ligament (UCL) avulsion and soft tissue injuries of the pediatric and adolescent elbow. Cross-sectional study; Level of evidence, 3. An institutional review board-approved review was conducted to identify consecutive patients with medial elbow injuries treated in a tertiary pediatric sports medicine practice between 2016 and 2021. Radiographs were obtained during injury evaluation, and patients with nondisplaced medial epicondylar apophysitis and complete epicondylar fracture were excluded, resulting in 150 patients with soft tissue injuries occurring distal to the medial epicondyle apophysis (subapophyseal) for study. Radiographs were evaluated for bony avulsion of the UCL from either the medial epicondyle proximally or the ulnar sublime tubercle distally. Injuries without radiographic evidence of bony avulsion, but with clinical examination findings consistent with ligamentous injury, were classified as radiographically negative UCL injuries, and magnetic resonance imaging (MRI) was performed to further evaluate these injuries if moderate to severe medial swelling of the elbow or significant concern for medial structural injury was present on examination. These MRI scans were evaluated to classify the UCL injury and assess for periosteal or cartilaginous avulsions. A total of 150 patients (mean age, 12.5 ± 3.4 years; 70 female), 55% (150/274) of the entire medial elbow injury population, had a subapophyseal injury. Of these patients, 62 had a bony avulsion detected on radiograph, and 88 had a radiographically negative injury. In addition to the 62 radiographic avulsions, the 61 MRI scans obtained on those radiographically negative injuries revealed 33 complete UCL disruptions, resulting in 63.3% (95/150) of patients sustaining a complete ligamentous disruption. With the MRI scans, 37 (61%) cases of cartilaginous or periosteal avulsion of the UCL were diagnosed. Overall, 66% of all 150 subapophyseal injuries had a bony, cartilaginous, or periosteal UCL avulsion. Patients with cartilaginous (mean age, 10.3 years) and bony (mean age, 10.6 years) avulsions were younger than those with central ligament injury (mean age, 14.2 years) or periosteal (mean age, 14.2 years) avulsions (P = .005). There was a significant association between the mechanism of injury and the location of UCL tear identified on MRI scans: traumatic falls were associated with distal tears, and throwing injuries were associated with proximal tears (P < .001). UCL central ligament and avulsion lesions may be frequently diagnosed after injury to the pediatric medial elbow, the majority of which are complete injuries, and may require MRI for diagnosis. The mechanism of injury may predict the location of ligamentous injury, and osteocartilaginous avulsions are more likely to present at younger ages than injuries to the soft tissue of the UCL or periosteum. The prevalence of these injuries merits further investigation into best protocols of nonoperative treatment or surgical repair techniques and outcomes.

Burns Resulting from Electric Vehicle Manufacturing in Silicon Valley.

The development of electric vehicles (EVs) has introduced novel technologies and manufacturing processes that expose workers to new risks of burn injury. We identified six patients who were admitted to our burn center for injuries that occurred while working in EV manufacturing facilities. The burns fell into three categories: flash flame burns due to lithium-ion battery explosions, high-voltage electrical injuries, and burns caused by contact with molten metal. Recognizing these recurrent patterns of injury should inform future prevention efforts and prepare health systems to evaluate and treat patients burned in EV manufacturing.

Computerized Surgical Planning in Face Transplantation

AbstractFace transplantation (FT) has emerged as a critical intervention for patients with complex facial deformities unsuitable for conventional reconstructive methods. It aims to restore essential functions such as facial expression, mastication, and speech, while also improving psychosocial health. The procedure utilizes various surgical principles, addressing unique challenges of craniofacial complexity and diverse injury patterns. The integration of Computerized Surgical Planning (CSP) leverages computer-aided technologies to enhance preoperative strategy, intraoperative navigation, and postoperative assessment. CSP utilizes three-dimensional computed tomography, printing, angiography, and navigation systems, enabling surgeons to anticipate challenges and reduce intraoperative trial and error. Through four clinical cases, including a groundbreaking combined face and bilateral hand transplant, CSP's role in FT is highlighted by its ability to streamline operative processes and minimize surgical revisions. The adoption of CSP has led to fewer cadaveric rehearsals, heightened operative precision, and greater alignment with preoperative plans. Despite CSP's advancements, it remains complementary to, rather than a replacement for, clinical expertise. The demand for technological resources and multidisciplinary teamwork is high, but the improved surgical outcomes and patient quality of life affirm CSP's value in FT. The technology has become a staple in reconstructive surgery, signaling a step forward in the evolution of complex surgical interventions.

Shoulder external rotation contracture following neonatal brachial plexus injury

BackgroundGlenohumeral posterior external rotation contractures and scapular winging are frequently overlooked problems in residual neonatal brachial plexus injury (NBPI). Recent attention has emphasized their impact on vital functions such as feeding and hygiene. This study aims to present the epidemiology of posterior glenohumeral (GH) contractures in a significant pediatric NBPI population and explore contributing factors. MethodsWe conducted a retrospective analysis of data collected from January 2019 to November 2022, involving a case series of 262 children with residual NBPI. The data included demographics, palsy level, prior surgical history, and the modified Mallet scale. Glenohumeral passive internal rotation in abduction (IRABD) and cross-body adduction (CBADD) angles were measured bilaterally. Subjects were categorized into 'Belly-' (Mallet Hand-to-Belly <3) and 'Belly+' (Mallet Hand-to-Belly ≥3) groups. ResultsMedian participant age was 7.9 years (range: 3.5 – 21 years). Extension injury patterns included Erb's palsy (56.5%), extended Erb's palsy (28.6%), and global palsy (14.9%). Contractures exceeding 10, 20, and 30 degrees were prevalent in both IRABD and CBADD angles. The 'Belly-' group (9.5%) demonstrated a significant reduction in both angles compared to the 'Belly+' group. Weak correlations were found between IRABD (r=0.390, p<0.0001) or CBADD (r=0.163, p=0.0083) angles and Mallet hand-to-abdomen item. Glenohumeral reduction and Hoffer procedures led to a notable decrease in CBADD angle, without affecting 'Belly-' prevalence. Global injuries exhibited decreased angles compared to Erb's group. ConclusionsExternal rotation glenohumeral contractures are prevalent in residual NBPI, impacting midline access. Surprisingly, history of glenohumeral procedures or extensive injuries did not increase the likelihood of losing the ability to reach the belly. ROC analysis suggests specific thresholds for maintaining this ability.

Investigating Stagnant Air Conditions in Almaty: A WRF Modeling Approach

This study investigates stagnant atmospheric conditions in Almaty, Kazakhstan, a city nestled within a complex terrain. These conditions, characterized by weak local winds and inversion layers, trap pollutants within the city, particularly during winter. The Weather Research &amp; Forecasting (WRF) model was employed to simulate atmospheric conditions using Local Climate Zone data. Verification of the model’s accuracy was achieved through comparisons with data from weather stations and the Landsat-9 satellite. The model successfully reproduced the observed daily temperature variations and weak winds during the testing period (13–23 January 2023). Comparisons with radiosonde data revealed good agreement for morning temperature profiles, while underestimating the complexity of the evening atmospheric structure. The analysis focused on key air quality factors, revealing cyclical patterns of ground-level and elevated inversions linked to mountain-valley circulation. The model effectively captured anabatic and katabatic flows. The study further examined the urban heat island (UHI) using a virtual rural method. The UHI exhibited daily variations in size and temperature, with heat transported by prevailing winds and katabatic flows. Statistical analysis of temperature and wind patterns under unfavorable synoptic situations revealed poor ventilation in Almaty. Data from three Januaries (2022/2023/2024) were used to create maps showing average daytime and nighttime air temperatures, wind speed, and frequency of calm winds.

Optimal Positioning of Small Wind Turbines Into a Building Using On-Site Measurements and Computational Fluid Dynamic Simulation

Abstract Renewable energy solutions are essential for addressing several pressing issues, including climate change, the fossil fuels supply chain fragility and fuel price fluctuations. One promising technological solution is rooftop-mounted turbines into buildings. This study presents an evaluation of the potential for wind energy utilization on the rooftop of a 29 m tall building. The primary objective of this research is to develop a methodology that can effectively investigate the integration of small wind turbines (SWTs) into urban buildings, intending to promote energy sufficiency in urban areas. A robust framework has been developed that consists of seven steps. These steps include site selection, evaluating urban wind energy with computational fluid dynamics (CFD) simulation and on-site measurements, selecting an appropriate SWT, estimating the annual energy production (AEP), conducting an evaluation of the environmental impact, resilience, and economic analysis, and finally, installing the system. This straightforward yet reliable framework provides a comprehensive approach to assessing the viability of wind energy utilization in urban areas. The findings revealed that the most suitable location for installation had an estimated AEP of around 1030 kWh, leading to a reduction in emissions of 0.64 tCO2/y. Additionally, it was observed that the building's geometry and orientation significantly affected the wind flow, causing a substantial decrease in wind speed downstream. Selecting optimal sites and considering wind patterns are essential for maximizing energy generation in wind energy projects.

Craniofacial Assault Against Women: A National Evaluation Defining At-risk Populations and Outcomes.

Few studies have analyzed epidemiologic factor associated with female patients presenting to the emergency department from facial fractures because of assault. Clearly understanding these factors may assist in developing effective strategies to decrease the incidence and sequelae of these injuries. To determine the epidemiology of facial fractures because of assault in the female population. All female facial fracture visits were queried in the 2019 Nationwide Emergency Department (ED) Sample database. The likelihood of a facial fracture encounter resulting from assault was modeled using logistic regression adjusting for demographics, insurance status, geographic region, location of patient residence, and income. Secondary outcomes analyzed hospitalization costs and adverse events. Of all facial fractures 12.4% of female encounters were due to assault were due to assault. Of assaulted females, 72.8% were between the ages of 20 and 40, and Black women experienced a disproportionate share of assault encounters (odds ratio [OR]=2.55; CI, 2.29-2.84). A large portion (46.4%) of encounters occurred in patients living in the lowest quartile of median household income, and 22.8% of patients were uninsured (OR=1.34; CI, 1.09-1.66). Assaulted patients were more likely to have fractures in nasal bone (58.1% vs. 42.5%), orbit (16.8% vs. 10.9%), zygoma (4.1% vs 3.6%), and mandible (8.7% vs. 4.8%) compared with their nonassaulted counterparts. Facial fractures were especially common in lower income, uninsured, urban, and Black populations. Examining the patterns of injury and presentation are critical to improve prevention strategies and screening tools, identifying critical patients, and develop a more efficient and effective system to treat and support female patients suffering facial fractures secondary to assault.

#2183 Does thrombotic microangiopathy drive the occurrence and pattern of cerebrovascular disease in malignant hypertension?

Abstract Background and Aims Malignant hypertension (MHT) is characterized by diffuse microvascular damage caused by severe hypertension, often presenting with multiple organ involvement. Cerebrovascular injury, occurring in both acute and chronic forms, stands as a hallmark of the disease, being identified in up to half of patients. Thrombotic microangiopathy (TMA), defined as the association of mechanical hemolytic anemia with thrombocytopenia, also emerges as a frequent complication in MHT patients. However, the potential contribution of TMA to cerebrovascular disease remains unexplored. The secondary objective of this study was to provide a comprehensive description of the patterns of cerebrovascular injury occurring in MHT, with a focus on acute ischemic strokes (AIS). Method We retrospectively assessed the brain MRI of patients admitted to the kidney intensive care unit at Tenon hospital for malignant hypertension during the 2017-2023 period. Brain MRIs were performed on a systematic basis regardless of neurological symptoms and were independently reviewed by two trained specialists in a blinded fashion. Patterns of acute cerebrovascular disease, defined as AIS, intracerebral hematoma (ICH) or posterior reversible encephalopathy syndrome (PRES), were systematically assessed. Number of AIS lesions, their size and localization were recorded. Underlying chronic cerebral small vessel disease (CSVD) was defined as presence of lacunes, white matter hyperintensities, cerebral microbleeds or perivascular spaces. Severity of the chronic cerebrovascular disease was measured using a validated CSVD score. Results A total of 60 patients were admitted for malignant hypertension, with a mean age of 42.9 years. 40 patients (66.7%) presented with severe acute kidney injury. Cerebrovascular disease, either acute or chronic, was found in 42 patients (70.0%). Underlying chronic CSVD was present in 33 patients (55.0%). Acute patterns of injury occurred in 27 patients (45.0%). AIS was the most frequent (33.3%), followed by PRES (21.7%). Only one patient presented with ICH. Among patients with AIS, 14 (70%) presented with multiple simultaneous lesions. Of note, most patients with AIS exhibited diffuse encephalopathy syndrome (60.0%) rather than focal deficit (40.0%). Systemic TMA was present at admission in 34 patients (56.7%). In an exploratory data analysis, presence of AIS on brain MRI was associated with the presence of underlying CVSD (p = 0.013), but not with the presence of TMA at admission (p = 0.79). No association was found between TMA and PRES (p = 0.22). Conclusion Our study confirmed the high incidence of cerebrovascular disease during MHT. Most notably, 1 in 3 patients presented with AIS. TMA did not appear to increase the incidence nor to influence the pattern of brain injury.

Establishing Geriatric Opiate Use Patterns in Trauma.

Introduction: There is evidence that providers often overprescribe opiates in the postoperative period. Despite an ever-growing geriatric population, there is little research detailing current opiate usage in older patients after trauma. This population presents a unique set of challenges for pain management and prescription drug dependence due to sensitivity, a narrow therapeutic window, and high rates of pre-existing polypharmacy.Objective: Assess the use of narcotics in geriatric trauma patients with various injury patterns to establish a reference point for future intervention for reduction in narcotic dependence.Methods: We created a database of trauma patients' age ≥65 years admitted to a single level 1 trauma center in the Southeastern United States during the 2019 calendar year. Information gathered included patient factors, injury patterns, operative intervention, pain medications prescribed during hospitalization and at discharge, total and average daily morphine milligram equivalents (MME) inpatient and outpatient, and requests/prescriptions for narcotics at follow-up.Results: In 2019, there were 475 patients aged ≥65 admitted to our level 1 trauma center for acute traumatic injuries. 219 of those patients required operative intervention. Average total inpatient MME for this cohort was 169.0 with average daily MME of 22.89. The average total prescribed MME upon discharge was 79.27. There were 29 patients documented to request narcotic prescription refill at time of clinic follow-up, 27 of whom were prescribed a narcotic medication at follow-up.Conclusion: This dataset establishes a reference point for opiate use in geriatric trauma patients to facilitate further research for mitigation of risk in this population.

#1297 Approaches to renal response assessment in rare monoclonal immunoglobulin related glomerulopathies

Abstract Background and Aims AL-amyloidosis (AL) and monoclonal immunoglobulin (MIg) deposition disease are common types of MIg-related glomerulopathies (MIgG) and are well-studied including approaches to treatment and hematological and renal responses (RR) assessment. Other rare MIgG comprise very diverse patterns of glomerular injury e.g. proliferative glomerulonephritis with MIg deposition (PGNMID), C3-glomerulopathy, fibrillary glomerulonephritis etc. Although RR defined as decrease in 24 h proteinuria by 30% without kidney function decline was validated only for renal AL it is widely used for MIg deposition disease and rare MIgG without validation. Nevertheless, the best approach to RR assessment in rare MIgG is still unclear. To shed some light on this problem we performed this study. Method We retrospectively analyzed 31 patients with rare MIgG who were treated with clone-specific treatment and had available follow-up (FUP) ≥6 months (mo). The following morphological patterns were diagnosed: PGNMID (n = 9), C3-glomerulopathy (n = 9), thrombotic microangiopathy (n = 5), cryoglobulinemic glomerulonephritis (n = 3), fibrillary glomerulonephritis (n = 3), immunotactoid glomerulonephritis (n = 1) and membranous nephropathy (n = 1). Patients’ baseline parameters are shown on Fig. 1 as well as treatment modalities. Hematological response defined according to currently accepted criteria is demonstrated on Fig. 1. We evaluated two approaches to the RR assessment: 1) at least partial renal response (PR) defined as 24 h proteinuria decreased by 50% from the baseline and &amp;lt;3.5 g, and 2) according to Palladini's criteria for AL (AL-RR) i.e. 24 h proteinuria decreased by 30% from the baseline or &amp;lt;0.5 g. Both RR were considered as achieved only in the absence of estimated glomerular filtration rate (eGFR) decline &amp;gt;25%. Time points for RR assessment were 6, 12 and 24 mo from the clone-specific treatment initiation. Renal outcome was estimated as initiation of renal replacement therapy or eGFR &amp;lt;15 ml/min/1.73 m2 at the end of follow-up. Death-censored renal survival was analyzed by the Kaplan-Meier method. Cox regression analysis was applied to determine which RR was independently associated with long-term kidney outcome. P-value was assumed at &amp;lt;0.05. Median FUP was 19 (7; 50) mo. FUP ≥12 and ≥24 mo were available in 26 and 17 patients, respectively. Results Total number of patients who achieved AL-RR at any RR assessment time point was 22 (71%). At 6, 12 and 24 mo the achievement of AL-RR was registered in 17, 16 and 10 patients, respectively. PR cumulatively was achieved in 19 (61%) patients: at time points of 6, 12, and 24 mo it was registered in 14, 14 and 9 cases, respectively. The 5-year cumulative renal survival in those who had AL-RR was better than in not responders (Fig. 2A). Patients who ever achieved PR had better cumulative renal survival compared with patients with no renal remission (Fig. 2B). In univariate Cox regression analysis the achievement of AL-RR (Exp(β) 0.158 (95% CI 0.03; 0.819)) was associated with renal outcome as well as the achievement of PR (Exp(β) 0.074 (95% CI 0.09; 0.626)). In multivariate Cox regression model adjusted for eGFR at the time of kidney biopsy AL-RR vs no response was estimated as an independent predictor of renal long-term prognosis (Exp(β) 0.082 (95% CI 0.009; 0.725)) as well as eGFR (Exp(β) 0.89 (95% CI 0.821; 0.985)). The only independent predictor of renal outcome in the model including eGFR at the time of kidney biopsy (Exp(β) 0.85 (95% CI 0.72; 0.99), p = 0.05) was PR (Exp(β) 0.011 (95% CI 0; 0.547), p = 0.021). Conclusion The classical concept of complete and partial renal remission seems to be more appropriate for rare MIgG and requires further validation studies.

#2581 Cryptococcosis in kidney transplant recipients: a nationwide multicenter retrospective cohort study—CRITERE study

Abstract Background and Aims Cryptococcosis stands as the third most common invasive fungal infection in solid organ transplant recipients. Clinical management and prognosis of the disease remains largely unexplored in the context of kidney transplant recipients. Our main objective was to describe the natural history of cryptococcosis after kidney transplantation from the graft patterns of kidney injury to the long term outcomes. Method We established a nationwide cohort of adult kidney transplant recipients diagnosed with cryptococcosis between 2002 and 2019 in France. All data were gathered starting from the transplantation date and encompassed up to the latest follow-up consultation. All putative causes of AKI as claimed by the attending clinicians were recorded. Cases were matched (ratio 1:6) with kidney transplant recipients from the French prospective multicenter cohort DIVAT with parameters at time of transplant including immunosuppression and known risk factors of cryptococcosis such as age, history of smoke, history of cancer and HIV status. Transplant outcomes (graft failure and patient death) were then compared between matched patients. Results 88 patients were included. Patients were predominantly male (n = 61, 69.3%), with a mean age of 57.0 years [SD ±13.3]. The majority of patients were primary kidney transplants (n = 71, 80.7%) with a median time from ESRD to transplantation of 2.8 years [IQ 1.25-5]. The majority of patients received ATG as induction therapy for their transplant (n = 50, 69.4%)Acute kidney injury (AKI) at diagnosis involved 37.3% of the patients with 13.3% requiring renal replacement therapy. AKI staging was distributed as follows, AKI grade 1 in 12.5% of patients, grade 2 in 13.3% of patients, and grade 3 in 11.5% of patients. During the induction stage, 39% of patients developed amphotericin B-related AKI. AKI resulting from tacrolimus overdose subsequent to tacrolimus/fluconazole interaction occurred in 25.7% of patients during the consolidation stage. Among the patients alive at 3 months following the diagnosis of cryptococcosis, 33.7% of patients exhibited graft dysfunction. Following cryptococcosis, 5 patients displayed T cell rejection and 4 patients developed antibody-mediated rejection. A total of 41 patients with cryptococcosis were matched to 246 controls (ratio 1:6), after a median follow-up of 52.3 [28.1-90.2] months, patients with cryptococcosis exhibited a higher risk of mortality with 35.9% compared with 9.8% (p &amp;lt; 0.001) and graft failure with 33.3% compared with 15.0% (p = 0.0005). Conclusion This study has shown that kidney injury manifests itself through a sequential, multi-step process that initially includes pre-renal impairment, ATN and iatrogenic mechanisms. Amphotericin B-related AKI, followed by tacrolimus overdose represent common causes of AKI.

#1795 Diverse histological findings of kidney injury in cancer patients on immunotherapy- impact on clinical management

Abstract Background and Aims Immune checkpoint inhibitors (CPIs) are becoming rapidly more used to treat various types of cancer. Acute interstitial nephritis (AIN) is considered the most common pattern of kidney injury in these patients, however other distinct histological lesions are increasingly reported. The aim of this study is to assess the histological findings and the value of kidney biopsy in the management of patients with CPI-associated nephrotoxicity. Method All records from patients treated with CPIs and kidney injury that underwent a kidney biopsy during the last 4 years were retrospectively assessed. Results We included 16 biopsied patients treated with CPIs and kidney injury, 8 males and 8 females. The mean age at the time of renal biopsy was 68 (± 8.2) years and the median follow up time was 11.5 (8-29) months. The most common primary malignancy was non-small cell lung cancer (n = 8), followed by melanoma (n = 3), endometrial cancer (n = 2), renal cell carcinoma (n = 1), breast cancer (n = 1) and hepatocellular carcinoma (n = 1). At the time of kidney biopsy eleven patients were treated with pembrolizumab, three patients with ipilimumab and nivolumab combination, one patient with ipilimumab and one patient with atezolizumab. Eleven patients were on immune-chemo combined therapy. Twelve patients presented with acute kidney injury (AKI), two with nephrotic syndrome, one with nephrotic range proteinuria and one with acute onset of hypertension and subnephrotic proteinuria [Urine Protein (UPr): 3 g/24 h]. The median time to developing kidney injury from CPI initiation was 9 (4.25-21.5) months. The prevalent histologic lesion was AIN (n = 5), followed by three cases of mixed AIN with acute tubular injury (ATI), and two cases of pure ATI. We recorded three cases of CPI-associated glomerulonephritis including membranous nephropathy (MN) with a lupus-like pattern on immunofluorescence, AA amyloidosis and Focal Segmental Glomerulosclerosis (FSGS) cellular variant. Two patients had diabetic nephropathy (DN) with ATI and one patient had thrombotic microangiopathy (TMA) with ATI. Immunotherapy was temporarily withheld in all patients at the time of kidney biopsy. After the establishment of the histological diagnosis: we continued treatment with corticosteroids in nine patients (five cases with AIN, one case with mixed AIN/ATI, one case with MN, one case with FSGS and one case with TMA/ATI). Withdrawal of corticosteroids was decided in five cases (two patients with diabetic nephropathy, two patients with mixed ATI/AIN and one with ATI). The patient with AA amyloidosis was treated with colchicine and cortisone with partial remission of nephrotic syndrome (UPr: 1.2 g/24 h). In one case with pure ATI, corticosteroids, and the concomitant chemotherapeutic agent (pemetrexed) were withdrawn with complete response of AKI. Partial remission of proteinuria occurred in the patient with FSGS (UPr: 1.3 g/24 h). At the end of follow up, kidney recovery occurred in all 12 patients with AKI (among them one patient who required renal replacement therapy at the time of biopsy). Rechallenge with a CPI was attempted in 8 patients. After rechallenging, one patient experienced relapse of nephrotic syndrome (MN) and immunotherapy was withdrawn. The other seven patients continued CPI treatment without recurrence of kidney injury. The overall patient survival was 62.5%. Conclusion AIN is only one of the possible causes of nephrotoxicity in patients receiving CPIs. Kidney biopsy establishes the accurate diagnosis of CPI-associated AKI. In selected cases it allows the continuation of immunotherapy and can prevent the unnecessary use of corticosteroids.

#2862 Genetics and electron microscopy: complementary tools for management of focal segmental glomerulosclerosis?

Abstract Background and Aims Focal segmental glomerular sclerosis (FSGS) defines a histologic lesion that represents a pattern of injury associated to different pathologic conditions affecting both children and adults. It is classified into primary forms, presumably immune-mediated, secondary forms, determined by a maladaptive response to different conditions, genetic and undetermined forms. According to Mayo Clinic classification, primary and secondary forms can de differentiated using electron microscopy (EM), with a podocytes foot process effacement (FPE) ≥80% identifying primary forms. Better understanding the role of Genetics in FSGS and response to treatment in different forms is of vital importance in this rare and multifaceted condition. We analyzed a discrete cohort of patients with FSGS examined both with EM and genetic testing (GT). Main aims of our study were: 1) assessment of GT in primary and secondary forms; 2) analysis of response to therapy according to histologic and genetic classification. Method This is a retrospective observational study on patients that received a histological diagnosis of FSGS, including EM, and underwent NGS genetic testing from January 2020 to June 2023. Primary and secondary forms of FSGS were distinguished by degree of pedicle fusion at EM, according to Mayo Clinic classification. Clinical, laboratory, genetic data and used therapies were recorded. Complete response (CR) to therapy was defined as a reduction of proteinuria to 0.3 g/day, with normalization of albuminemia. Partial response (PR) was defined as halving proteinuria into a sub-nephrotic range and increasing albuminemia up to 3.5 g/dL. Absent response was defined as a persisting nephrotic range proteinuria. Results In the study period, 33 patients receiving a histologic diagnosis of FSGS with EM examination underwent NGS testing. Of these, 25 had available genetic results and were included. Ten patients (40%) were females, 15 (60%) were males; mean age was 40.8 years (SD ±14.5); 20 (80%) were Caucasian, 4 (16%) Black, 1 (4%) Asian. Based on EM, 11 (44%) were classified as primary forms, 14 (56%) as secondary forms. Twelve (48%) patients presented with nephrotic syndrome. Of these, 10 had a primary form. Seven (28%) had nephrotic-range proteinuria without hypoalbuminemia, 6 (24%) had subnephrotic range proteinuria. Six (54.5%) of the primary forms and 8 (57.1%) of the secondary forms had a positive genetic testing (p = 0.78). Among secondary forms, through GT, one diagnosis of Fabry disease and one of Tuberous Sclerosis were made in patients without clear systemic symptoms. Fabry disease was confirmed by presence of zebra bodies at EM. All primary forms received immunosuppressive therapies, all being rituximab-based regimens; all secondary forms received support therapy. Nine (81.1%) primary forms and 9 (64.3%) secondary forms had at least a PR to treatment (4 CR in primary group and 1 CR in secondary group) (p = 0.33). Among primary forms, 5 of 6 patients (83%) with a positive GT had at least a PR with a strong immunosuppressive therapy. In secondary forms group 4 of 8 patients (50%) had at least PR with offered support therapy. Fabry and Tuberous Sclerosis were offered specific treatments with benefit. Conclusion Percentage of positive GT did not differ in primary and secondary forms of FSGS as defined by Mayo Clinic classification. Thus a positive GT should not be considered a unique feature of secondary forms. GT was critical for an unexpected diagnosis of systemic hereditary diseases, thus enabling adequate target therapies. We believe GT should be offered to all patients with FSGS. In primary FSGS, defined according to EM, more than 80% of patients had at least a PR following immunosuppressive therapy, even in patients with positive GT. In conclusion, as clinical presentation and light microscopy are not sufficient for an accurate diagnosis, combining EM and GT is of utmost importance in proper classification and management of FSGS.

#2113 Membranoproliferative glomerulonephritis experience over 20 years in a tertiary centre in the United Kingdom

Abstract Background and Aims Membranoproliferative Glomerulonephritis (MPGN) is a histological pattern of injury which typically accounts for light microscopy findings on 1-3% of kidney biopsies. It is classified based on immunofluorescence into complement-mediated, immune complex-mediated (IC) and immunofluorescence negative. The underlying aetiologies such as C3 Glomerulopathy are rare diseases, and thus longitudinal real-world experience in terms of underlying causes, treatment and outcomes is valuable. Method This study presents a retrospective review of biopsy data from January 2000 through to December 2020 in a tertiary renal referral centre in the United Kingdom (UK). This review was conducted using the organisation's biopsy database, with patient demographics and clinical information obtained from the Electronic Patient Record. All patients with an MPGN pattern on biopsy were reviewed. Those with new MPGN post-transplant, with an MPGN pattern on biopsy but subsequently diagnosed as IgA Nephropathy, and with an MPGN pattern but a known lupus diagnosis, were excluded. Results A histological finding of MPGN on kidney biopsy was found in 67 patients. Of these, 41 remained in the study following application of the exclusion criteria, with an additional 3 excluded as there was insufficient information available for classification in their biopsy reports. Of the 38 remaining, 28 had IC MPGN and 10 had C3 Glomerulopathy (C3G) - 8 with C3 Glomerulonephritis (C3GN) and 2 with C3 Dense Deposit Disease (DDD). Median follow up was 72 (range 45-126) months. Median age was 64 years in the IC MPGN and 55 years in the C3G groups (p 0.125). The majority in both groups were female, 60.7% (17) and 60% (6) respectively. There was no significant difference in renal function, blood pressure, or proteinuria at presentation between the groups. MPGN was associated with infections in 8 patients (21.1%), connective tissue disease in 3 patients (7.9%), monoclonal gammopathies or haematological malignancies in 8 patients (21.1%), and 2 had identified complement deficiencies (5.3%). Over the study period 47.4% (18) of patients progressed to end stage kidney disease and 50% (19) died. There was no significant difference in these outcomes between the IC MPGN and the C3G groups. Progression to renal replacement therapy (RRT) was seen in 42.9% (12) of the IC MPGN group, and 60% (6) of the C3G group (p=0.287). This included two patients who received a kidney transplant (both in the C3G group), one of whom developed recurrence during the available follow up. Conclusion This study adds a UK perspective with long term data and outcomes in a rare condition. Almost half of patients progressed to RRT and half of patients died during the follow-up period. These outcomes were seen at similar rates in those with IC MPGN and those with C3G. A variety of associated conditions were observed, and the low number of complement deficiencies identified is likely due to the historical nature of the review with reduced screening for complement abnormalities and genetics in the earlier period. Outcomes on follow-up:

#1658 Association of blood dd-cfDNA levels with Banff scores and histopathological lesions in kidney allograft biopsies: results from an observational trial

Abstract Background and Aims Donor-derived cell-free DNA (dd-cfDNA) is a novel blood biomarker of kidney allograft injury. While primarily studied to discriminate rejection from no rejection, knowledge about its dynamics in other graft pathologies is scarce and merits further investigation. Previous research has highlighted its superior diagnostic performance in detecting ABMR compared to TCMR and borderline changes, however, recent studies have suggested that its increase is not limited to damage due to alloimmune injury. Therefore, we aimed to assess the association between dd-cfDNA release and diverse histopathological patterns as well as its correlation with Banff lesion scores in renal allograft biopsies. Method For this analysis, we identified all dd-cfDNA-paired allograft biopsies from a prospective observational trial of kidney transplant recipients undergoing an indication biopsy with deterioration in graft function, persistence of anti-HLA donor-specific antibodies (DSA), or proteinuria. Dd-cfDNA was collected at the time of allograft biopsy and measured using droplet-digital PCR. Both relative and absolute quantification of dd-cfDNA, with cutoffs of 0.5% and 50cp/ml, respectively, were available for clinical interpretation. All biopsy specimens were examined by a central pathologist blinded to the dd-cfDNA results. Histopathological diagnoses were assigned according to the Banff 2019 classification. Results In total, we examined 125 dd-cfDNA paired biopsies from 110 patients performed at our center between April 2020 and October 2023. Absolute levels of dd-cfDNA were significantly higher in mixed rejection (median 156 cp/mL, IQR 138-176), antibody-mediated rejection (ABMR) (median 63cp/mL, IQR 48-81), DSA-negative microvascular inflammation (DSAnegMVI) (median 74 cp/mL, IQR 35-134), and BK-virus associated nephropathy (BKVAN) (median 168cp/mL, IQR 54-311) in comparison to glomerulonephritis (median 12cp/mL, IQR 8-19; p &amp;lt; 0.001, &amp;lt;0.001, 0.02, 0.01, respectively) as well as in comparison CNI-toxicity (median 10, IQR 6-15; p &amp;lt;0.001, &amp;lt;0.001, 0.004, 0.003, respectively). Additionally, patients with mixed rejection, ABMR, and BKVAN had higher absolute dd-cfDNA levels than patients with IFTA (median 13, IQR 8-16; p 0.004, 0.004, and 0.04, respectively), as well as normal histology (median 7, IQR 7-11, p 0.004, 0.008, 0.03, respectively). Finally, absolute dd-cfDNA levels were higher in patients with mixed rejection than in those with UTI (median 14, IQR 12-16, p = 0.02) (Fig. 1). In the univariable analysis, absolute dd-cfDNA levels were significantly correlated with Banff lesion scores for glomerulitis (g), peritubular capillaritis (ptc), and tubulitis (t). In the multivariable analysis, ptc and t were independently correlated with absolute dd-cfDNA levels. Conclusion Increased donor-derived cell-free DNA is not specific for rejection, but also occurs in alternative injury patterns showing microvascular inflammation and severe tubulointerstitial inflammation, such as DSAnegMVI and BKVAN (BK-virus associated nephropathy). Interestingly, dd-cfDNA levels remain low in the setting of de novo or recurrent glomerulonephritis and CNI-toxicity, which are important differential diagnoses in patients with clinical indication biopsy.

Paediatric open fractures presenting to a level 1 trauma centre: a 10 year epidemiological study.

The epidemiology of paediatric fractures has been previously described, however there is limited data available on open fractures in this population. The purpose of this study was to investigate trends, mechanism of injury (MOI) and severity of paediatric open fractures and undertake an epidemiological study. All children ≤ 16.0 years presenting with open fractures were identified between 01/04/2013 and 01/04/2023. Those with craniofacial, thoracic and distal phalangeal fractures were excluded. Incidence was calculated based on those presenting within the local geographical region. Social deprivation was measured using the Index of Multiple Deprivation (IMD). There were 208 open fractures with a median age of 11.0(q1 7.4-q3 13.4) years, and 153(74.6%) were in males. The MOIs were road traffic collisions 73(35.1%), sports/play 45(21.6%), fall > 2m 29(13.9%), simple fall 25(12.0%), crush 16(7.7%), bites 8(3.8%), assault 6(2.9%), and other 6(2.9%). Nineteen children (9.1%) presented with polytrauma. Gustilo-Anderson grade for long bone fractures were I-61(29.3%), II-24(11.5%), IIIa-36(17.3%), IIIb-30(14.4%) and IIIc-7(3.4%). There were 129 children presenting within the local geographical region providing an annual incidence of 8.0/100,000. Radius and ulna were the most frequently injured 49(38.0%) followed by tibia and fibula 44(34.1%). There were 69(53.5%) children presenting from an IMD quintile 1 with open fractures. Paediatric open fractures are commonly seen in the adolescent male and affect those who are from a more socially deprived background. These injuries account for 3.2% of fractures admitted to a MTC. Data suggests children principally sustain open fractures through two distinct injury patterns and ten-year trends suggests that there is a gradual decline in the annual incidence.