Complete Recovery Research Articles

Delayed postoperative neurological deficits from scoliosis correction: a case series and systematic review on clinical characteristics, treatment, prognosis, and recovery.

This study was designed to investigate the clinical features, treatment modalities, and risk factors influencing neurological recovery in patients who underwent scoliosis correction with delayed postoperative neurological deficit (DPND). Three patients with DPND were identified from 2 central databases for descriptive analysis. Furthermore, all DPND cases were retrieved from the PubMed and Embase databases. Neurological function recovery was categorized into complete and incomplete recovery groups based on the American Spinal Injury Association (ASIA) impairment scale. Two patients were classified as type 3, and one was classified as type 2 based on the MRI spinal cord classification. Intraoperative neurophysiological monitoring (IONM) was consistently negative throughout the corrective procedure, and intraoperative wake-up tests were normal. The average time to DPND development was 11.8h (range, 4-18h), and all three patients achieved complete recovery of neurological function after undergoing revision surgery. A total of 14 articles involving 31 patients were included in the literature review. The mean time to onset of DPND was found to be 25.2h, and 85.3% (29/34) of patients experienced DPND within the first 48h postoperatively, with the most common initial symptoms being decreased muscle strength and sensation (26 patients, 83.9%). Regarding neurological function recovery, 14 patients were able to reach ASIA grade E, while 14 patients were not able to reach ASIA grade E. Univariate analysis revealed that preoperative diagnosis (p = 0.004), operative duration (p = 0.017), intraoperative osteotomy method (p = 0.033), level of neurological deficit (p = 0.037) and deficit source (p = 0.0358) were significantly associated with neurological outcomes. Furthermore, multivariate regression analysis indicated a strong correlation between preoperative diagnosis (p = 0.003, OR, 68.633; 95% CI 4.299-1095.657) and neurological prognosis. Our findings indicate that spinal cord ischemic injury was a significant factor for patients experiencing DPND and distraction after corrective surgery may be a predisposing factor for spinal cord ischemia. Additionally, it is important to consider the possibility of DPND when limb numbness and decreased muscle strength occur within 48h after corrective scoliosis surgery. Moreover, emergency surgical intervention is highly recommended for DPND caused by mechanical compression factors with a promising prognosis for neurological function, emphasizing the importance of taking into account preoperative orthopedic diagnoses when evaluating the potential for neurological recovery.

Highly Effective Nobiletin-MPN in Yeast Microcapsules for Targeted Modulation of Oxidative Stress, NLRP3 Inflammasome Activation, and Immune Responses in Ulcerative Colitis.

Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.

A Review of Intense Pulsed Light in the Treatment of Ocular Rosacea.

Ocular rosacea is an underdiagnosed form of rosacea that may occur with or without typical cutaneous signs of rosacea. One of the common manifestations is dry eyes. Although the use of intense pulsed light (IPL) in the treatment of rosacea-related dry eyes has been reported, a recent review is lacking. A scoping review was performed to summarize the efficacy of IPL in the treatment of ocular rosacea. Five articles were included, representing 108 patients, with a mean age of 58.4 years. Based on available data, 59.2% (n = 58/98) were female. The studies detailed the use of IPL in combination with meibomian gland expression treatment. Overall, 91% (n = 89/98) of patients with ocular rosacea treated with IPL had a partial response and 9% (n = 9/98) had no response. IPL therapy did not lead to complete recovery in any of the included patients. One participant experienced an adverse event across the included studies. IPL is a promising treatment modality for ocular rosacea, as demonstrated by its ability to relieve dry eye symptoms with limited adverse events. Further research into this novel treatment is necessary to ascertain its role in the management of ocular rosacea.

Recovery of the X-ray polarisation of Swift J1727.8−1613 after the soft-to-hard spectral transition

We report on the detection of X-ray polarisation in the black-hole X-ray binary Swift J1727.8$-$1613 during its dim hard spectral state by the Imaging X-ray Polarimetry Explorer (IXPE). This is the first detection of X-ray polarisation at the transition from the soft to the hard state in an X-ray binary. We find an averaged 2--8 keV polarisation degree of $(3.3 0.4)\, <!PCT!>$ and a corresponding polarisation angle of $3 which matches the polarisation detected during the rising stage of the outburst, in September--October 2023, within $1 uncertainty. The observational campaign complements previous studies of this source and enables comparison of the X-ray polarisation properties of a single transient across the X-ray hardness-intensity diagram. The complete recovery of the X-ray polarisation properties, including the energy dependence, came after a dramatic drop in the X-ray polarisation during the soft state. The new IXPE observations in the dim hard state at the reverse transition indicate that the accretion properties, including the geometry of the corona, appear to be strikingly similar to the bright hard state during the outburst rise despite the X-ray luminosities differing by two orders of magnitude.

Radiofrequency catheter ablation for redo procedures after pulmonary vein isolation with the cryoballoon technique: 9-year outcome

Abstract Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation. Cryoablation has been shown to be a safe and effective technique for pulmonary vein isolation. However, there is a significant arrhythmia recurrence rate after cryoablation procedures and there are no established strategies for redo procedures in these patients. Therefore, we have summarized our experience with radiofrequency catheter ablation for redo procedures after pulmonary vein isolation with the cryoballoon technique (including an analysis of pulmonary vein conduction recovery patterns after procedures performed with the first or second generation cryoballoon). Methods Two hundred and twenty patients (paroxysmal AF: 140 patients, persistent AF: 80 patients) had to undergo a redo procedure after initially successful circumferential PV isolation with the cryoballoon technique (First generation: 110 patients (group A); second generation: 110 patients (group B)). The redo ablation procedures were performed using a segmental approach or a circumferential ablation strategy (three-dimensional mapping system) depending on the intra-procedural findings. Results During the redo procedure, a mean number of 1.6 re-conducting PVs were detected (using a circular mapping catheter; group A: 2.2 re-conducting PVs, group B: 1.0 re-conducting PVs). There was a slightly higher incidence of chronic PV reconnections related to the left-sided PV ostia than to the right-sided PVs in both groups. Furthermore, sites of chronic PV reconnection were found more frequently in the inferior parts of the PV ostia than in the superior parts. In 97 patients in group A, a segmental approach was sufficient to eliminate the residual PV conduction because there were only a few recovered PV fibers (1-3 reconnected PVs; group A1). In the remaining 13 patients in group A, a circumferential ablation strategy was used because of a complete recovery of the PV-LA conduction of all four pulmonary veins (group A2). In group B, a segmental approach was sufficient in nearly all patients (109/110) because there was only a minor reconnection of 1-2 PVs. All recovered PVs could be isolated sucessfully again. At 108-month follow-up, 69.1 % of all patients were free from an arrhythmia recurrence (152/220 patients; group A: 72/110 patients (65.5 %), group B: 80/110 patients (72.3 %)). There were no major complications in both groups. Conclusions In patients with an initial circumferential PVI using the cryoballoon technique, a repeat ablation procedure can be performed safely and effectively using radiofrequency catheter ablation. In most cases only a few re-conducting PV fibers were found and therefore, a segmental re-ablation approach seems to be sufficient in the majority of patients (especially in patients treated with the second generation cryoballoon).

#1347 Development and validation of a nomogram for predicting complete kidney function recovery after drug-induced acute interstitial nephritis

Abstract Background and Aims Drug-induced acute interstitial nephritis (DI-AIN) represents a common cause of acute kidney injury. Early withdrawal of the culprit drug along with corticosteroid therapy (CS) remains the mainstay of treatment. Despite this, up to 50% of patients may not fully recover kidney function after DI-AIN. The aims of this study were to develop and externally validate a predictive nomogram to assess the probability of complete recovery (CR) of kidney function at 6 months after treatment. Method Multicenter, retrospective, observational study in 13 nephrology departments belonging to the GLOSEN group. Patients with biopsy proven DI-AIN treated with CS between 1996-2023 were included. Other potential causes of AIN such as infections or systemic diseases were carefully ruled out. Dataset was randomly divided into training group (n = 164) and validation group (n = 60). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of CR (serum creatinine value <25% of the last value before DI-AIN), and used to build the nomogram. Accuracy of the nomogram was assessed by discrimination and risk calibration, in the training and validation sets. Results The study group comprised 224 patients with DI-AIN, of whom: 51 (31%) in the training group and 19 (32%) in the validation set, achieved CR at 6 months after treatment with CS. Median age was 70 (IQR 57–76), and 115 (51%) were males. The clinical characteristics were well balanced between the training and validation data sets. The selected variables by LASSO were age (under/above 65 years), gender, degree of interstitial fibrosis and time to CS initiation (under/above 7 days). Based on multivariable logistic regression model, a nomogram was developed for assessing the probability of CR (Fig. 1). The area under the curve (AUC) of the nomogram was 0.809 (95% CI 0.721–0.880) indicating a good discriminative power. Bootstrap self- sampling was performed 1000 times for validation of the nomogram model. The AUC was 0.837 (95 % CI: 0.705–0.931), indicating good predictive stability. Calibration plot revealed that the predicted outcomes aligned well with the observations. Decision curve analysis (DCA), and clinical impact curve analysis (CICA) suggested that the model had clinical benefit. Conclusion We constructed and validated a practical nomogram with good discrimination and calibration, to predict the probability of CR of kidney function at 6 months in DI-AIN treated with corticosteroids. This clinical tool can provide clinicians with an estimate of kidney prognosis and can potentially assist them in titrating the intensity and duration of corticosteroid therapy.

Comparative evaluation of the effectiveness and safety of acne treatment with systemic isotretinoin in monotherapy and together with combined oral contraceptives in women

Objective. To give a comparative evaluation of the effectiveness and safety of acne treatment with systemic isotretinoin in monotherapy and together with combined oral contraceptives in women. Materials and methods. 65 women with severe papulo-pustular acne took part in the study. They were divided into two groups: group I consisted of 35 women who used systemic isotretinoin for acne in monotherapy; group II included 30 women who took systemic isotretinoin together with combined oral contraceptives. A comprehensive clinical and laboratory study was conducted. The study included a biochemical blood test to determine the lipid profile, liver transaminases, and hormonal homeostasis. The obtained results were analyzed using the methods of parametric and nonparametric statistics, the standard error (m) was used in the calculations, the level of statistical significance was noted at p 0.05. Results. In women treated for acne with systemic isotretinoin in monotherapy relief occurs in 4 weeks, and complete clinical recovery in 24 weeks after the beginning of therapy; when using systemic isotretinoin together with combined oral contraceptives, relief is determined in 2 weeks, and complete clinical recovery in 16 weeks of treatment. The main side effects of systemic isotretinoin were cheilitis, skin xerosis, retinoic dermatitis and telogen alopecia. Cheilitis was revealed in the majority of patients in both groups equally. Xerosis of the skin, retinoic dermatitis and telogen alopecia were more often observed in the 1st group. In women of the 1st group, the level of progesterone was significantly higher and the level of estradiol was lower than in women of the 2nd group. Conclusions. Systemic isotretinoin has shown high efficacy and safety in treatment for acne in women. Combined oral contraceptives normalize hormonal homeostasis, which helps to eliminate acne. When using systemic isotretinoin in combination with combined oral contraceptives, the main clinical effect occurs earlier, and adverse reactions are less frequent and less severe than in monotherapy. The combined use of systemic isotretinoin and combined oral contraceptives is the optimal method of acne treatment in women.

#2699 Rare glomerular microangiopathy: clinicopathological characteristics and prognosis

Abstract Background and Aims Different from the typical histologic changes of thrombotic microangiopathy (TMA), we identified a group of patients whose pathology with glomerular involvement without blood vessel lesions, which was rare and known as glomerular microangiopathy (GMA). Method In Peking Union Medical College Hospital, a total of 33 patients were diagnosed as GMA with proliferation and swelling of glomerular endothelial cells, fragmented red blood cells, fibrin or platelet thrombi in the capillary lumen, thickening of the basement membrane, stenosis or occlusion of capillary lumen, but no abnormalities in the endothelium of renal small vessels. The pathology and clinical data were from the medical records and analyzed. Results The patients were 66.7% male with a mean of 45 years (14 to 74 years). The primary diseases were Castleman's disease (CD, 30.3%), POEMS syndrome (21.2%), cancer patients receiving agents targeting vascular endothelial growth factor (21.2%), and others. All the patients showed various degrees of proteinuria, with an average 24-hour urinary protein of 2.66 g/d, hematuria (63.6%), and acute kidney injury (AKI, 39.4%). The median serum creatinine (SCr) was 142 (107.5, 169) μmol/L. The AKI patients had lower Alb (P < 0.0001), PLT (P = 0.0192), higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.0199), and reduction of IgA (P = 0.0021). There is no significant difference in SCr and proteinuria among patients with different etiologies. The CD patients exhibited higher hs-CRP and D-Dimer. Treatment included targeting therapy of underlying hematological disorders, glucocorticoid combination with or without immunosuppressant, and supportive treatment. After treatment, we observed proteinuria remission (66.7%), partial improvement (27.3%), or complete recovery (45.5%) of renal function. Conclusion In Castleman's disease, POEMS syndrome, and patients receiving agents targeting VEGF, initial attention to GMA might improve the prognosis and shed light on the study of the mechanisms.

#2078 Study of spectrum of renal dysfunction in cancer patients on ICPI as mono or combination with conventional chemo in north India

Abstract Background and Aims Although use of ICPI's have revolutionized the treatment of cancer patient with significantly improving the longevity of these patients but it also is associated with various adverse reactions known as iRAE's related to its use, which in due course is being revealed gradually. Kidney related iRAE's are important and also limitation to therapy, which could be a detrimental factor for these patients availing the beneficial effects of these revolutionary medications. Previous literature on these therapeutics had the limitations of being retrospective, small case series and case reports and evaluating only one or two parameters of kidney dysfunction, also the criteria used for evaluations had the limitation of standardization. With this we aimed to study the spectrum of renal dysfunction in cancer patients, receiving ICPI with or without conventional chemotherapy using standard criteria. Method Study involved patients with malignancy who had received at least 1 dose of ICPI as mono or combination with conventional chemotherapy. The primary end-point was 6 month assess the clinical spectrum & outcome of renal dysfunction, and the secondary end-points were the patient-level risk factors for renal dysfunction, the impact of renal dysfunction on clinical outcomes. Results Conducted through October 2021-2022, enrolled N = 156 (66 male & 90 females) & followed up for 6 months. 109 (69.9%) subjects developed KDIGO–AKI—Stage I (51.4%) & Stage II (35.8%) & non required RRT. The median duration for onset of AKI was 131 days. Proteinuria was observed in n = 143 (91.67%). n = 116 (74.3%) developed new-onset proteinuria. n = 40 (25.6%) were proteinuric at the start of the study & 27/40 (67.5%) were observed to have >50% increase in proteinuria, qualifying for proteinuria with therapy. 92/143 proteinuric subjects (64.3%) developed >1 g/day proteinuria. On subcategorizing proteinuria it was observed that 82/92 (57.3%) had 1–3 g/day proteinuria and ≥3.0 g/day proteinuria was observed in 10/92 (7.0%). Definitive ICPI–AKI could be attributed to only 2 subjects, as they underwent kidney biopsy for their kidney dysfunction and significant proteinuria. Secondary amyloid deposits in the glomeruli and mesangium was found in 1 subject & the other subject showed acute tubulointerstitial deposits with granular cast. Proteinuria and kidney dysfunction resolved with stoppage of the ICPI and steroids administration, which was consistent with the limited literature available for the management of ICPI related amyloidosis & iRAE. n = 88 had partial recovery of kidney dysfunction following an AKI event & complete recovery was seen in n = 3 (2.7%). >50% recovery in eGFR was observed in n = 41 (37.6%). Electrolyte abnormality commonly observed were hyponatremia, hypokalemia & hypomagnesemia & was seen in distributed almost equally, followed by hypocalcemia. Hypernatremia, hyperkalemia, hypermagnesemia & hypercalcemia were less commonly reported. Lastly mortality was also observed in n = 16 (10.2%), but could not be directly attributed to ICPI use, kidney dysfunction, malignancy type, comorbid conditions & other concomitants medication use. Conclusion To conclude this present prospective cohort study is a comprehensive assessment of the spectrum of renal dysfunction in cancer patients, among recipients of ICPI with or without conventional chemotherapy using standard criteria to the best of our knowledge, which has been the limitation of previous literature. We have shown a vast spectrum of kidney dysfunction possibly attributed to the ICPI's in malignancy patients. Viewed in respect to better QoL with ICPI therapy in malignancy patients, kidney related iRAE's could limit the patients from their beneficial effects. A possible persistent immune injury might have led to partial recovery of kidney dysfunction in majority. An unusual finding of secondary amyloid deposits with pembrolizumab, which possible might have occurred due to persistence of high levels of inflammatory markers due to these drugs. Thus underscoring the need for a close follow-up and recommend kidney biopsy to better & definitively identify the glomerular pathology & treatment accordingly.

#1513 Update on the peritonitis trend in central Spain

Abstract Background and Aims Peritonitis is one of the most common and severe complications associated with peritoneal dialysis (PD) traditionally cited as the primary cause of catheter loss and discontinuation of the dialysis technique. Nevertheless, the incidence and severity of peritonitis has been significantly reduced over time. Therefore, we aimed to update the current impact of peritonitis in PD patients. Method We performed an observational, multi-centre, prospective cohort including 3,037 patients who started PD between 2003-2020 followed for a median of 1.6 [0.8-2.9] years. Results We observed 2 941 episodes of peritonitis, with a peritonitis rate (PR) of 0.46 episodes per patient year and a mean of 2.6 years CI 95% [2.4-2.8] to first peritonitis episode. As expected, gram-positive organism was identified in the 69.3% of the cases, followed by gram-negative (19.6%) and sterile culture (15.6%). The usual course of the peritonitis is favourable, with complete recovery in the 76.4% of the cases, whereas just the 37.6% require admission during a median of 5 [3-9] days, with a peritonitis recurrence of 11.2%. A fatal peritonitis (resulted in PD cessation) was observed in 11.7% of the patients with an overall mortality of 0.7% (considering all the deaths within the 90 days after peritonitis). Factors associated with a 90-days mortality rate related to PD rate were age > 65 years (OR 2.99 [1.84-4.85]), Charlson index (OR 1.19 [1.07-1.33]), and the type of microorganism: fungus (OR 9.8 [4.16-23.43], multi-bacterial (OR 7.97 [0.91-69.88] and gram- negative OR (2.41 [1.45, 3.99]). Comparing patients who developed peritonitis (P) (N = 1230) vs patients who not developed peritonitis (NP) (N = 1807), P patients were older (P 59 ± 15.5 years vs NP 55 ± 15.5 years, p < 0.001) and associated higher comorbidity (such as Charlson index, cardiovascular and diabetes mellitus history) than NP patients. P patients more commonly had a prior history of renal replacement therapy (kidney transplant P 9.2% vs NP 6.9% and hemodialysis 18.8% vs 17.1%) compared with NP patients. PR has significantly decreased over three consecutive 5-year periods: from 0.51 [0.48-0.54] peritonitis cases per year during 2003-2008 to 0.45 [0.43-0.48] during 2009-2014 (p 0.03), and further dropping to 0.41 [0.38-0.44] for the period 2015-2020 (p < 0.001). Conclusion Over the past 17 years, the incidence and severity of peritonitis have significantly reduced, despite PD patients becoming older and associated high comorbidities.

#226 Outcome of intermittent hemodialysis vs. continuous kidney replacement therapy for acute kidney injury: observational prospective multi-center study

Abstract Background and Aims Continuous hemodialysis in hemodynamically stable acute kidney injury (AKI) patients may impact outcome differently compared to intermittent hemodialysis, although this issue is controversial. We look at differences in AKI outcomes between patients treated with intermittent hemodialysis (IHD) and patients treated with continuous kidney replacement therapy (CKRT) modalities in in Kuwait. Method Clinically and hemodynamically stable adult inpatients with native kidneys (i.e., did not need inotropic support or mechanical ventilation) who received IHD or CKRT for AKI, in seven public hospitals in Kuwait between 1/January to 31/December 2021 were recruited. CKRT was selected due to lack of access to water treatment in patients wards in some of the participating hospitals. Demographics, comorbidities, dialytic and non-dialytic management data, and 30-day kidney and patient outcome data for, were prospectively collected and analyzed. Results Total number of AKI patients not on inotropic support and not mechanically ventilated who received dialysis during study period was 229 (age: 59.9 years; males: 60.3%; baseline eGFR: 56 ml/min). IHD (group 1) was performed in 27.1% of the cohort whereas CKRT (group 2) was performed in 72.9%. There was no statistically significant difference between the two groups in age (58.4 for IHD and 59.9 for CKRT, p=0.6), baseline eGFR (55 ml/min for IHD and 56.4 for CKRT, p=0.8), sex ratio, incidence of diabetes, hypertension or cardiovascular disease, or cause of AKI. However, renin angiotensin aldosterone system inhibitors (RAASi) were precipitating factors for AKI more significantly in the IHD group (25.8% vs. 6% for CKRT, P ≤ 0.001). Intensive care unit (ICU) contributed 21% of cases (14.5% for IHD and 23.4% for CKRT, insignificant p value of 0.1). Also, there was no statistically significant difference in receiving intravenous fluids between the two groups (71% for IHD vs. 71.5% for CKRT, p=0.8), however, more patients in the IHD group received diuretics (62.9% vs 43.1% for CKRT, p=0.008). Dialysis vascular access was right internal jugular vein in 59% (75.8% FOR IHD vs. 52.7% for CKRT) followed by femoral vein in 35% of cases (19.4%). Extracorporeal membrane oxygenation (ECMO) was used in only two cases in the CKRT group. Of the total cohort, 21.8% died, with no difference between the two groups (16.1% for IHD vs 24% for CKRT, p=0.2). Partial recovery was higher in IHD group (30.8% vs.17.3%, p=0.046) and complete recovery higher in CKRT group 33.1% vs 13.5%, p=0.009). eGFR at 30 days was 53.2 ml/min with no statistically significant difference between the two groups (44.6 for IHD vs 56.1 for CKRT, p=0.15). Conclusion The IHD group and the CKRT group were statistically similar in basic characteristics and received similar lines of management, except for the diuretics. At 30 days, they had similar death rates but CKRT group had higher rates of complete recovery than the IHD group. This is in line with published literature that suggest CKRT may not improve mortality but may improve kidney recovery.

#1150 Neutrophil rich infiltrate in immunotherapy induced acute interstitial nephritis

Abstract Background and Aims Acute interstitial nephritis (AIN) is a well-recognized cause of acute kidney injury (AKI) in patients treated with Immune checkpoint inhibitors (ICI). Kidney biopsy typically shows tubular interstitial infiltration with well-differentiated mononuclear cells with occasional granulomas and eosinophils. Neutrophil rich tubular interstitial infiltration is typically associated with pyelonephritis. We report a case series of neutrophil rich ICI induced AIN. Method After obtaining approval from the institutional review board, medical records of the nephrology service at a large cancer center were reviewed. Patients were included in the study if they underwent a kidney biopsy for the diagnosis of ICI associated AKI, the biopsy was consistent with atypical AIN with neutrophil rich infiltrate, there was no glomerular involvement, they exhibited no symptoms of pyelonephritis including but not limited to fever, nausea, vomiting, flank pain and dysuria and had a negative urine culture. Results Forty eight patients who had a biopsy proven ICI associated AIN were identified from the medical records. Four (8.3%) patients met the study criteria (Table 1). There were three males and one female. The mean age was 75.5 years. One patient had a history of pre-existing CKD stage 3. Mean number of ICI therapy cycles prior to the development of AIN was seven with two patients treated with pembrolizumab (2 and 14 cycles), one patient treated with nivolumab (1 cycle) and one patient treated with the combination of nivolumab and ipilimumab (2 cycles). All patients presented with asymptomatic rise in serum creatinine (sCr). Kidney biopsy showed neutrophil rich infiltrate and neutrophilic tubulitis in all patients. Neutrophilic casts were present in three biopsies. One patient had evidence of granulomatous inflammation. All patients had mild to moderate interstitial fibrosis. Three patients were initially treated with flat dose prednisone 60 mg daily and one was treated with weight adjusted dose of prednisone 1 mg/kg at 75 mg/day. Three patients had complete renal recovery (sCr < 0.5 mg/dl above baseline) after steroid taper. One patient developed a relapse but achieved partial recovery (sCr < 2x baseline) after the second taper. Two patients remain alive three and 12 months after the kidney biopsy. Two patients died due to the progression of cancer two and 10 months after the biopsy. Conclusion AIN with neutrophil rich infiltrate likely represents a subset of ICI induced AIN. In the absence of clinical signs of pyelonephritis and with evidence of negative urine cultures the treatment should be geared towards addressing inflammation with systemic corticosteroids which have been shown to be effective in management of ICU induced AIN. Avoidance of antibiotics in this setting would lead to better antibiotic stewardship.

Successful fixation of supraglenoid tubercle fracture in a horse with a customised distal femoral locking plate

AbstractAn 18‐month‐old Standardbred colt, referred for hock joint arthroscopy, presented a severe left forelimb lameness immediately after recovery from general anaesthesia. The horse was found in the recovery box with a ‘dropped elbow’, and it was dragging the leg. Radiographic examination of the shoulder showed a displaced avulsion fracture of the supraglenoid tubercle of the scapula. A human distal femoral locking plate was customised using measurements taken from a computed tomography scan of a 2‐year‐old horse specimen. An internal fixation of the fracture was performed using the designed distal femoral locking plate. Rehabilitation techniques were passive manipulations and neuromuscular electrical stimulation. Six months post‐operatively, the horse was sound and had made a complete functional recovery. The distal femoral locking plate fitted well to the supraglenoid tubercle and scapula in the operated horse, leading to a stable fixation. The recovery time was shortened using internal fixation, which facilitated a faster return to mobility.

#626 C3 glomerulonephritis and thrombotic microangiopathy—a prospective observational study

Abstract Background and Aims Complement mediated TMA (cTMA) and complement component 3 glomerulonephritis (C3GN) are two distinct complement mediated kidney diseases. cTMA is characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. C3GN results from uncontrolled activation of the alternative complement pathway leading to the deposition of C3 in the glomerulus. We sought to describe characteristic differences between these two conditions in a large cohort of patients from Bengaluru, India. Method All cases of cTMA and kidney biopsy proven C3GN from 2019-2022 at a tertiary care centre in India were included. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. All patients received protocolized medical therapy; patients with C3GN were treated with steroids and cyclophosphamide, while those with complement mediated TMA received plasmapheresis in addition to cyclophosphamide and steroids. Protocolised medical management (renin-angiotensin-aldosterone inhibition and diuretics) was provided in both the cases. Demographic, clinical and lab parameters were reported and compared. Results A total of 25 cTMA cases and 19 C3GN cases were included in the study. Both C3GN (52.7%) and cTMA (48%) were more common in males. Patients with C3GN typically presented in the third decade of life while cTMA cases presented in the fourth decade. Secondary hypertension was common in the cTMA group (92% vs 78.9%, compared to C3GN). 60% of patients with cTMA had either recent or current infection compared to 21.1% of C3GN patients (P = 0.04). The majority of cTMA cases had IFTA of <25% (84%) compared to C3GN (57.9%) although this was not statistically significant. Both C3GN and cTMA most commonly presented as rapidly progressive kidney failure and acute kidney injury. A total of 76% of patients in the cTMA group required kidney replacement therapy as compared to 47.4% in the C3GN group (P = 0.009). 44% of cTMA cases had anti factor H antibody positivity compared to 15.8% of C3GN patients (P = 0.02). Finally, 44% of cases in cTMA group had complete recovery compared to 47.4% in C3GN group at the end of 2.8 years of followup. Conclusion Although both conditions result from dysregulation of the alternative pathway, there are several important clinical characteristic differences between patients with cTMA and C3GN including presence or absence of secondary hypertension, concurrent infection, anti-factor H positivity and requirement of kidney replacement therapy. This information may be helpful to inform both diagnosis and prognosis for patients presenting with a complement mediated kidney disease.

#657 Obinutuzumab is effective for the treatment of frequently-relapsing/steroid-dependent minimal change disease in adults

Abstract Background and Aims Higher relapse rates and steroid dependency are challenges in the treatment of minimal change disease (MCD). The aim of this study was to evaluate the efficacy and safety of obinutuzumab, a humanised type II anti-CD20 monoclonal antibody, in adults with frequently relapsing (FR) or steroid-dependent (SD) minimal change disease (MCD). Method Patients with FR/SD MCD receiving obinutuzumab at our center between September 2022 and February 2023 were enrolled. Complete remission was defined as the reduction of proteinuria to 0.3g/d. The time to remission, the relapse rate, and adverse events were evaluated. Results Six patients with FR/SD MCD were included in the present study. The median age of the patients was 30.44 years (range 18.80-72.09 years) and 3 of them were male. Prior to treatment with obinutuzumab, five patients remained in nephrotic syndrome and one patient was in partial remission after previous treatment. One or two doses of 1g obinutuzumab were given. All six patients achieved a complete remission. Five patients with nephrotic syndrome achieved complete recovery within a range of 14 to 57 days. The patient, who initially achieved partial remission, reached complete remission within 27 days after receiving the first obinutuzumab dose. The average follow-up duration was 12.53 ± 1.97 months, during which there was no observed relapse. Furthermore, None of the patients experienced infusion-related adverse effects, serious infectious complications or neutropenia following treatment with obinutuzumab. Conclusion Obinutuzumab is an effective and safe treatment option for adult patients with FR/SD minimal change disease. Further randomized trials are needed to confirm these findings.

#2754 Long-term renal outcomes in ICI-associated acute interstitial nephritis: a comprehensive comparative study

Abstract Background and Aims Immune checkpoint inhibitors (ICI) have transformed cancer treatment, but they may lead to immune-mediated acute interstitial nephritis (ICI-AIN), in 2-5% of patients. About 35-40% show full kidney function recovery three months post ICI-AIN. Limited evidence exists for long-term renal toxicity. The unknown difference in long-term renal function evolution between partial and complete recovery of the acute episode in ICI-AIN is an unexplored area for future research. Additionally, there's no comparative study on the long-term renal function evolution between ICI-AIN and cases associated with other drugs (Drug-AIN) or autoimmune causes (AI-AIN). Method Retrospective, descriptive and observational study. The medical records of all AIN cases diagnosed in the Nephrology Unit of the Bellvitge University Hospital between 2010 and 2023 were reviewed. Longitudinal data on treatments, comorbidities and kidney function were collected. Data was analyzed using descriptive statistics, Chi-square tests, Mann-Whitney U tests and Kaplan Meier analyses. Results A total of 94 out of 96 screened patients were diagnosed with AIN (AI-AIN n = 26; Drug-AIN n = 30; ICI-AIN n = 38). Of those, 89.4% were biopsy-confirmed. Median follow-up was 36.64 months (IQR 12.32-74.28). There were not differences in baseline serum creatinine (sCreat) across the groups, defined as sCreat 6 months prior to AIN. At diagnosis, sCreat was lower in ICI-AIN compared to Drug-AIN (267.62 ± 116.44 vs 553.20 ± 317.46, p < 0.001), but significant differences were not found comparing to AI-AIN. There were not differences in the cumulative dose and days of treatment with prednisone between the three groups. In the first year, 35.5% of ICI-AIN patients and 10.3% with Drug-AIN returned to baseline kidney function (p = 0.020). Over the course of three years, 45.9% reverted to baseline in the ICI-AIN cohort compared to 18.5% in the Drug-AIN cohort (p = 0.023). This trend continued at 5 years, with 45.9% in ICI-AIN and 22.2% in Drug-AIN recovering to baseline (p = 0.051). The proportion of patients who recovered baseline kidney function was comparable between the group diagnosed with ICI-AIN and the group diagnosed with AI-AIN at all evaluated time points. Kaplan-Meier analysis at 1, 3, and 5 years of follow-up revealed a shorter time to sCreat recovery to baseline in the ICI-AIN group compared to the Drug-AIN group, with Log-rank (Mantel-Cox) p-values of 0.016, 0.004, and 0.006, respectively. On the contrary, Kaplan-Meier analysis at the same time points did not reveal differences in time to basal sCreat recovery in ICI-AIN compared to AI-AIN. Among the evaluated variables, only baseline sCreat influenced the recovery of baseline kidney function in in the univariate analysis, with an odds ratio of 0.95 (95% CI 0.903-1, p-value 0.049) in the ICI-AIN group. The mean nadir sCreat and estimated glomerular filtration rate (eGFR) after treating AIN were comparable between ICI-AIN and Drug-AIN patients (nadir sCreat: 107.46 µmol/L and 102.24 µmol/L, respectively; nadir eGFR: 61.89 ml/min and 56.96 ml/min, respectively; p-value ns). However, ICI-AIN patients reached nadir renal function more rapidly after treatment initiation (10.99 vs. 28.06 months, p-value = 0.020). After reaching nadir function, 73.7% of ICI-AIN patients showed decline, similar to Drug-AIN (73.3%) and AI-AIN (88.5%, p ns). Yet, ICI-AIN patients had a higher yearly eGFR decline post-nadir compared to Drug-AIN (−17.05 (ml/min)/year vs. −3.99 (ml/min)/year, p-value 0.006) and autoimmune AIN (−4.09 (ml/min)/year, p-value 0.009). Conclusion In summary, the results of our study suggest that ICI-AIN patients demonstrate a distinctive pattern of recovery after the acute episode and long-term decline in kidney function after reaching the nadir kidney function compared to the Drug-AIN and AI-AIN groups. They exhibit a faster recovery to nadir kidney function but experience a higher yearly decline post-nadir in eGFR. The influence of baseline sCreat on recovery underscores the importance of considering individual patient characteristics in predicting outcomes and optimizing kidney function before initiating treatment with ICI.

#627 C3 glomerulonephritis and C3-dominant infection related glomerulonephritis—are they similar?

Abstract Background C3 glomerulonephritis (C3GN) and C3 dominant infection related glomerulonephritis (C3-IRGN) comprise two important immune complex mediated diseases. C3GN is caused by dysregulation of the alternate pathway by congenital or acquired abnormalities in the complement pathway. C3-IRGN is often preceded by infection followed by recovery after the infection resolves. Although kidney biopsy findings may be similar in both conditions, the clinical course and treatment differs. We aimed to compare the demographic, clinical and lab parameters of C3GN and C3-IRGN. Methods All kidney biopsies conducted at Institute of Nephrourology, Bengaluru with dominant C3 on immunofluorescence from Jan. 2019-Dec. 2022 were included. The diagnosis of C3-IRGN was established using established criteria. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. Patients with C3GN were treated with steroids and cyclophosphamide, while those with C3-IRGN received antibiotics along with supportive medical management (including renin-angiotensin-aldosterone inhibition). Demographic, clinical and lab parameters were recorded and compared. Results 23 cases of C3-IRGN and 19 cases of C3GN were included in the study. The mean duration of follow-up was 2.79 ± 0.92 years for those with C3GN and 2.78 ± 0.90 years for those with C3-IRGN. C3GN was common in younger patients (second decade of life) while C3-IRGN was common in the fourth and fifth decades of life. C3GN (57.9%) and C3-IRGN (73.9%) were both common in males. Previous infection (26.1% vs 5.3%) and present infection (39.1% vs 15.8%) were significantly more common in C3-IRGN. Hematuria (52.6% vs 34.8%), patient reported “frothy” urine (47.4% vs 21.7%) was significantly more common in C3GN compared to C3-IRGN. 36.8% of patients with C3GN had IFTA of >50% compared to only 8.7% in C3-IRGN. Patients with both conditions most commonly presented with either acute nephritic syndrome or rapidly progressive glomerulonephritis. In contrast, presentation with CKD was significantly more common in C3GN (36.8% vs 0%, P = 0.002) compared to C3-IRGN, and patients with C3GN were more likely to require kidney replacement therapy (47.4% vs 21.7%, P = 0.002). At the end of follow up, 65.2% of patients with C3-IRGN attained complete recovery, compared with only 47.4% of C3GN patients. Conclusion There are characteristic differences between individuals with C3-IRGN and C3GN that may help to better ascertain diagnosis at presentation. Patients with C3GN tend to have worse prognosis, emphasizing the importance of treatments to slow CKD progression and avoid the need for kidney replacement therapy.

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial

ObjectivesThis study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients...

Post-traumatic Delayed Facial Nerve Palsy: Report of 2 Cases and Systematic Review.

Delayed facial nerve palsy (dFNP) secondary to head injury is definitely uncommon. Although the mechanism of immediate facial nerve paralysis is well-studied, its delayed presentation remains debated. Given the dearth of available information, we reported herein our experience with 2 cases of posttraumatic dFNP. This systematic review aimed to evaluate all available information on dFNP and to assess treatment outcome also comparing conservatively and surgically approaches. Pubmed, Scopus, and Web of Science databases were systematically screened. The protocol of this investigation was registered on PROSPERO in April 2023 and the systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Both patients in the case studies showed a complete recovery within 2 to 3 months after the head trauma. One of them still reported a subjective taste alteration at last control. After the application of the inclusion-exclusion criteria, 9 manuscripts with adequate relevance to this topic were included in the systematic review. The study population consisted of 1971 patients with a diagnosis of posttraumatic facial nerve palsy, of which 128 with a dFNP. dFNP due to head trauma is a rarely encountered clinical entity, and optimal treatment still remains to be elucidated. Based on the reported data, it seems rational to propose a conservative approach for dFNP with steroid administration as a first line in most cases, indicating surgery in severe and/or refractory cases.

Complete gold extraction and recovery from double refractory gold ores by thiourea after bio-oxidation

Cyanidation, a conventional process to extract gold from gold ores, has been used for over 130 years in industrial mining because of the high efficiency and rate of formation of Au(CN)2− and the high recovery efficiency by adsorption of Au(CN)2− on activated carbon. However, carbonaceous refractory gold ores are not targeted because Au(CN)2− is easily adsorbed on carbonaceous matter in the ores, resulting in high recovery loss. In this study, the flotation concentrates of a carbonaceous refractory gold ores was subjected to biooxidation at 45 °C using a mixed culture containing iron-oxidizing and sulfur-oxidizing bacteria, followed by gold extraction using thiourea under strongly acidic conditions. The gold extraction efficiency reached ∼100% in 12 h without re-adsorption. Finally, the quantitative recovery of the Au(CS(NH2)2)2+ complex was confirmed by adsorption on strongly cationic exchange resin. Biooxidation reduced the amount of Fe-containing metal sulfides, which minimized the decomposition of thiourea, and the Au(CS(NH2)2)2+ complex had a low affinity toward carbonaceous matter, different to Au(CN)2−. Since the process described in this study does not require roasting to remove carbonaceous materials in pretreatment and does not use cyanide for gold extraction, it is environmentally friendly and should be considered for practical applications in carbonaceous gold ore-producing mines.