Challenging Case Research Articles

#932 Obinutuzumab for the treatment of refractory PLA2R-associated membranous nephropathy: a single-center cohort study

Abstract Background and Aims The established first-line immunosuppressive treatment for membranous nephropathy, rituximab, is met with resistance in some cases of refractory disease. Obinutuzumab, a Type II humanized CD20 monoclonal antibody, has been documented in international case reports as a potential treatment for refractory membranous nephropathy, yet application in China is in its infancy. This study aims to investigate the preliminary short-term efficacy and safety profile of obinutuzumab in such challenging cases. Method We assessed six adult patients with PLA2R-associated membranous nephropathy unresponsive to rituximab, prednisone combined with cyclophosphamide, and calcineurin inhibitors. Obinutuzumab was administered intravenously at 1000 mg, preceded by prophylactic dexamethasone and diphenhydramine to mitigate infusion reactions. Immunological remission was defined as a reduction of anti-PLA2R antibodies to titers below 2RU/ml. Results Baseline characteristics at the initiation of obinutuzumab treatment included an average disease duration of 3.6 ± 2.1 years and a median patient age of 54 years, with a male predominance (3:1 ratio). Laboratory findings at baseline revealed serum albumin at 22 ± 4 g/L, serum creatinine at 133 ± 68 μmol/L, and a significant 24-hour urinary protein quantification (24 hUP) at 7.1 ± 2.9 g/d. The median baseline anti-PLA2R antibody titer was substantial at 90 (range 50-671) RU/ml. At follow-up (9.1 ± 3.7 months), immunological remission rates post-obinutuzumab at 1, 3, and 6 months were 33.3%, 50%, and 50%, respectively. By the end of the study, CD19+ B-cells were depleted (< 5 cells/μL) for an average duration of 6.8 ± 2.6 months. At this juncture, improvements were noted with increased serum albumin (33 ± 8 g/L) and decreased serum creatinine (125 ± 80 μmol/L), along with a reduction in 24 hUP to 4.7 ± 6.2 g/L. Clinical evaluations indicated two cases of complete remission and two of partial remission. In the remaining two patients, 24 hUP was halved compared to baseline. Prednisone dosage was reduced to 7 ± 7 mg/day, with a corresponding reduction in cyclosporine and tacrolimus dosages, and cessation of cyclophosphamide and Tripterygium wilfordii polyglycosides. There were no acute infusion reactions, but two patients suffered severe infections, including one fatality, related to COVID-19 during the pandemic. Conclusion Obinutuzumab emerges as a novel agent in the immunosuppressive armamentarium against refractory PLA2R-associated membranous nephropathy, warranting further long-term study. The enduring B-cell depletion necessitates a careful pre-treatment risk assessment for opportunistic infections, particularly during the ongoing COVID-19 pandemic.

#2262 Renal outcomes of postpartum atypical hemolytic uremic syndrome treated with plasma exchange

Abstract Background and Aims Postpartum acute kidney injury (AKI) with features of thrombotic microangiopathy (TMA) are particularly challenging and complex cases. Causes include Preeclampsia (PE), hemolysis, elevated liver enzymes and low platelet count syndrome (HELLP) and atypical hemolytic uremic syndrome (aHUS). In a limited resource setting, it is difficult to diagnose such cases with more than standard blood tests. Therapeutic Plasma exchange (TPE) is the only available option for treatment in the absence of complement inhibitors. This study evaluates renal outcomes in patients with aHUS treated with plasma exchange. Method This is a single centre observational study conducted in a Tertiary Obstetric Intensive Care unit. The data of women who were admitted with postpartum AKI from January 2021 to October 2023 was retrospectively collected and analyzed. We used the following criteria to diagnose postpartum atypical HUS (Serum creatinine ≥1.9 mg/dL, Lactate dehydrogenase (LDH) ≥1832 U/L, or serum creatinine ≥1.9 mg/dL in combination with LDH ≥600 U/L) [1]. Inclusion criteria include women older than 18 yrs with microangiopathic hemolytic anaemia, schistocytes on peripheral blood film, negative direct antiglobulin test (DAT) and platelet count <100 /mm3.Lack of improvement of kidney functions and hemolysis 72 hours after delivery. Patients with sepsis, disseminated intravascular coagulopathy (DIC), postpartum hemorrhage (PPH) and chronic kidney disease were excluded. We identified 10 patients with postpartum aHUS. Peak creatinine, LDH, AST and Nadir platelet count and hemoglobin were recorded. Patients were followed up in the nephrology outpatient clinic. Results Fifty-two patients developed postpartum AKI in the study period. Ten patients (19%) were diagnosed with aHUS according to the above-mentioned criteria. Mean age was 24.5 ± 6.9 yrs. Median peak creatinine 5.1 (2.6-7) mg/dl, LDH 1950 (612-4000) U/L, AST 246 (150-699) U/L. Median nadir hemoglobin 7.25 (6-8.2) g/dl and platelets 57 (41-95)/mm3. All 10 patients received 3 to 6 sessions of TPE guided by platelets and LDH levels. All patients required at least 3 sessions of hemodialysis. Eight patients received TPE with plasma filter and 2 had centrifugal TPE (due to lack of plasma filters). Two patients died during ICU admission. Two months after discharge 4 (50%) patients had partial recovery of kidney functions average creatinine (3.5 ± 0.8) mg/dl and four (50%) remained dialysis dependent. Six of these patients had kidney biopsies, three biopsies showed a picture of thrombotic microangiopathy and two showed thrombotic microangiopathy with renal cortical necrosis. The other patient was lost to follow up. Conclusion It is difficult to diagnose and treat aHUS in a resource limited setting. The available treatment with therapeutic plasma exchange has poor renal outcomes.

#2996 Diffuse alveolar haemorrhage in antiphospholipid syndrome—a rare case

Abstract Background and Aims Diffuse alveolar haemorrhage (DAH) is a serious manifestation of diseases such as systemic lupus erythematosus (SLE) and, apparently in a paradoxical manner, antiphospholipid syndrome (APS). Inflammation resulting from the deposition of immune complexes in alveolar capillaries appears to contribute to the pathophysiology of DAH, SLE and APS. Symptoms include cough, dyspnoea, haemoptysis or fever. It is associated with a drop in haemoglobin, respiratory failure and diffuse infiltrates on imaging exams. Bronchoscopy is diagnostic. It is important to exclude infection as treatment includes high-dose corticosteroid therapy and other immunosuppressive drugs. We present a challenging case regarding the diagnostic and therapeutic approach to this pathology. Case report This is the case of a 52-year-old Caucasian female, with a history of SLE, APS, splenectomy due to thrombocytopenia, IgM Kappa monoclonal gammopathy and indolent non-Hodgkin lymphoma. She was medicated with prednisolone 5 mg and warfarin (target INR between 2 and 3). The patient was observed due to a 1-day history of fever, nasal obstruction and odynophagia, associated with progressively worsening fatigue. On examination, she was pale, eupnoeic, tachycardic, with bibasal rales and a hyperaemic oropharynx. Lab workup results were the following: haemoglobin 7 g/dL (11.7 g/dL 3 months before), VGM 71 fL, presence of schistocytes, leukocytes 13.7 G/L, neutrophils 11.1 G/L, PCR 4.6 mg/dL, platelets 170 G/L, INR 3.6, aPTT 45 sec, negative D-Dimers, urea 54 mg/dL, creatinine 1.4 mg/dL, LDH 431 IU/L, normal haptoglobin, negative Coombs test. In arterial blood gas analysis, pO2 was 61 mmHg and lactate was 5 mmol/L. Chest X-ray showed bilateral basal cotton-wool infiltrates and chest CT showed bilateral ground-glass pattern. The rest of the investigation included no complement consumption, negative anti-ds-DNA antibody, positive lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein antibodies, negative cryoglobulins and no evidence of progression of the lymphoproliferative disease. She was admitted to the intensive care unit due to suspicion of atypical/viral pneumonia vs. DAH. Oxygen therapy, empirical antibiotic therapy with ceftriaxone and clarithromycin and oral methylprednisolone 1 mg/Kg/day were started. She needed blood transfusion, although without visible blood loss. Bronchofibroscopy was performed, with bronchoalveolar lavage suggestive of DAH, so it was decided to start intravenous pulses of methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG). Warfarin was changed to unfractionated heparin. The patient had clinical, analytical and radiological improvement. Due to the lack of evidence of infection, antibiotics were stopped after 7 days. The patient was discharged under weaning corticosteroid therapy and monthly IVIG (during 5 months), without recurrence in the following year. Conclusion This is a rare case of oligosymptomatic DAH in a patient with SLE and APS. The literature currently available on DAH in the context of SLE or APS is scarce and its treatment is mainly dependent on the experience of each medical centre. Corticosteroid therapy is consensual, with greater variability in other corticosteroid-sparing therapies. In the case of patients with APS, anticoagulation is a challenge, and it is important to resume it as soon as the bleeding is controlled due to the risk of thrombotic events.

SNIPPET: A Framework for Subjective Evaluation of Visual Explanations Applied to DeepFake Detection

Explainable Artificial Intelligence (XAI) attempts to help humans understand machine learning decisions better and has been identified as a critical component towards increasing the trustworthiness of complex black-box systems, such as deep neural networks (DNNs). In this paper, we propose a generic and comprehensive framework named SNIPPET and create a user interface for the subjective evaluation of visual explanations, focusing on finding human-friendly explanations. SNIPPET considers human-centered evaluation tasks and incorporates the collection of human annotations. These annotations can serve as valuable feedback to validate the qualitative results obtained from the subjective assessment tasks. Moreover, we consider different user background categories during the evaluation process to ensure diverse perspectives and comprehensive evaluation. We demonstrate SNIPPET on a DeepFake face dataset. Distinguishing real from fake faces is a non-trivial task even for humans, that depends on rather subtle features, making it a challenging use case. Using SNIPPET, we evaluate four popular XAI methods which provide visual explanations: Gradient-weighted Class Activation Mapping (GradCAM), Layer-wise Relevance Propagation (LRP), attention rollout (rollout), and Transformer Attribution (TA). Based on our experimental results, we observe preference variations among different user categories. We find that most people are more favorable to the explanations of rollout. Moreover, when it comes to XAI-assisted understanding, those who have no or lack relevant background knowledge often consider that visual explanations are insufficient to help them understand. We open-source our framework for continued data collection and annotation at https://github.com/XAI-SubjEvaluation/SNIPPET.

The Update on the Role of Cesarean Myomectomy in an Old Primigravida with Huge and Painful Myoma: a Challenging Case for Fertility-Preserving Surgery

Abstract There is no established protocol for reducing maternal and perinatal morbidities in myoma during pregnancy. The opinions regarding performing myomectomy during cesarean section have been inconsistent and hot topic of discussion. The recent trends regarding the pro and cons outcomes are caused by potential risk of massive hemorrhage, repeat operation and anesthesia, less time away from work, prolong duration of operation and hospital stay, need of transfusion, increased overall cost, and morbidity. We presented a case of 42-year-old primigravida at 37-38 weeks of singleton live pregnancy with intramural myoma, and then performed successfully cesarean section and myomectomy without complication. The results of the operation showed a safe outcome when performed by an experienced obstetrician and selective case, and helped maintain fertility sparing in the future. Keywords: Uterine myoma, Cesarean myomectomy, Old primigravida

Clinical analysis of surgical outcome of 89 patients having large cerebral arteriovenous malformations.

The article analyzes the clinical features, morphological characteristics, surgical subtleties and long-term outcome of surgery in 89 cases of 'large' sized AVMs. During the period 2004 to 2022, 89 cases of 'large' arteriovenous malformations were operated in the neurosurgery departments of the authors. Large AVMs were defined as those that were more than 4cm on either lateral or antero-posterior view of digital subtraction angiogram. The factors that determined the extent of surgical difficulties included site and eloquence of the area, number of feeding vascular territories and draining veins, degree and rate of flow, presence of flow-related aneurysms, and the physical nature of the arteriovenous malformation. There were 59 males and 30 females and the average age was 32 years. Headache, giddiness and convulsions were the common presenting complaints. Six patients were unconscious after surgery. Of these, five patients died in the immediate post-operative period and one patient gradually recovered. Additionally, seven patients developed unilateral limb weakness that included hemiplegia (4 patients) and hemiparesis (3 patients) following surgery. Clinical follow-up ranged from 6 months to 18 years (average 43 months). All surviving patients are leading normal and essentially symptom free life and have recovered from their symptoms of headache, convulsions and giddiness. Large AVMs are amenable to 'curative' surgery with 'acceptable' results. The surgery can be challenging and appropriate case selection that is based on the surgeons experience is vital and decisive.

Instrumentalism in the Social and Moral Sciences

This article responds to recent criticism regarding the application of consequentialism and rational choice theory in the social and moral sciences. It clarifies the limited scope of the presented criticism and its overly simplistic view of social scientific inquiry that, together, lead to the presentation of an argument that claims more than it warrants. Moreover, I argue that the criticism overlooks one of the most important uses of instrumentalism in moral theory that may be considered the most challenging case for the application of rational choice theory.

Treatment of a challenging case of impacted, severely dilacerated & deflected maxillary central incisors: A case report with 10 years follow up

Impaction, dilaceration, and internal deflection of both maxillary permanent central incisors are not frequently reported in dental practice. The treatment approach is essential as it plays a pivotal role in contributing to the facial aesthetics and occlusion in permanent dentition of the individual. This is a case of a 10-year-old male diagnosed radio graphically with impacted, severely dilacerated, and deflected both the Maxillary central incisors. The management of the case was carried out surgically and orthodontically. By combining two stages of surgical exposure, orthodontic traction and alignment, the impacted dilacerated and deflected incisors were successfully moved into the desired position. A ten-year follow-up of the stability and periodontal health showed that the tooth placed in the occlusion maintained both esthetics and function.

The Impact of PDDL+ Language Features on Planning Performance: An Empirical Analysis on a Real-world Case Study

PDDL+ is an expressive formalism that allows for the use of planning in complex real-world applications. It includes a number of features designed to improve the readability and conciseness of the resulting knowledge models, but that are commonly doubted to have detrimental impact on the performance of domain-independent searches and heuristics. In this paper we empirically assess the impact of such features in a challenging real-world case study.

Multifaceted Cerebral Venous Thrombosis With Extensive Intra-cerebral Hemorrhage in a Young Man With Mitral Valve Replacement Due to Thrombosis and IgA Nephropathy: A Challenging Case Report From Saudi Arabia

Multifaceted Cerebral Venous Thrombosis With Extensive Intra-cerebral Hemorrhage in a Young Man With Mitral Valve Replacement Due to Thrombosis and IgA Nephropathy: A Challenging Case Report From Saudi Arabia

Not All Fevers Equal Infection: A Challenging Case of Adult-Onset Still's Disease

Not All Fevers Equal Infection: A Challenging Case of Adult-Onset Still's Disease

Impact of protein conformations on binding free energy calculations in the beta-secretase 1 system.

In binding free energy calculations, simulations must sample all relevant conformations of the system in order to obtain unbiased results. For instance, different ligands can bind to different metastable states of a protein, and if these protein conformational changes are not sampled in relative binding free energy calculations, the contribution of these states to binding is not accounted for and thus calculated binding free energies are inaccurate. In this work, we investigate the impact of different beta-sectretase 1 (BACE1) protein conformations obtained from x-ray crystallography on the binding of BACE1 inhibitors. We highlight how these conformational changes are not adequately sampled in typical molecular dynamics simulations. Furthermore, we show that insufficient sampling of relevant conformations induces substantial error in relative binding free energy calculations, as judged by a variation in calculated relative binding free energies up to 2kcal/mol depending on the starting protein conformation. These results emphasize the importance of protein conformational sampling and pose this BACE1 system as a challenge case for further method development in the area of enhanced protein conformational sampling, either in combination with binding calculations or as an endpoint correction.

Advanced trainee perceptions of disposable duodenoscopes and disposable endcaps: results of a nationwide survey.

Disposable duodenoscopes and duodenoscopes with disposable endcaps are being used in clinical practice to reduce or eliminate the risk of transmitting infections. The study aim was to assess perceptions and experiences regarding the use of these duodenoscopes among advanced endoscopy fellows in a nationally representative sample. A 17-item electronic survey was sent to 74 advanced endoscopy training programs. The survey was completed by 50 participants and their responses were included for analysis. Most participants were from academic training programs (82.7%) and identified as being in their 7th year of post graduate training (92%; PGY-7). Participants performed an average of 414 ERCPs. 29% reported difficulty with cannulation using disposable duodenoscopes versus 15.7% with duodenoscopes with disposable endcaps (vs. standard duodenoscope). 96% of trainees perceived disposable duodenoscopes as not cost effective and 92% stated they would not use this device during independent practice. 100% of trainees stated that they would use duodenoscopes with disposable endcaps during independent practice. For their most challenging cases, 90% of trainees preferred using standard reprocessable duodenoscopes while no trainee indicated they would prefer using a disposable duodenoscope in this scenario. 82% of participants stated that disposable duodenoscopes and disposable endcaps should be used exclusively or preferentially for high-risk patients citing cost, functionality, and concerns regarding environmental impact. Advanced endoscopy fellows perceive disposable duodenoscopes as impacting technical maneuverability. Concerns about functionality, cost effectiveness and environmental impact are barriers to adoption.

Ovarian hyperthecosis vs androgen producing tumour: A challenging and unusual case

Ovarian hyperthecosis vs androgen producing tumour: A challenging and unusual case

Right jugular vein agenesis. a challenging case for experienced endocrine surgeons

Right jugular vein agenesis. a challenging case for experienced endocrine surgeons

A Challenging Case of Primary Membranous Nephropathy with Renal Cell Carcinoma – Double Whammy

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. It can be associated with malignancy especially in elderly patients, however; sometimes it is difficult to distinguish. Hereby we present an interesting case of primary membranous nephropathy in a patient with renal cell carcinoma.

Managing severe anaemia with a blood transfusion in a suspected IMHA case

This article discusses a challenging case from initial presentation, stabilisation and treatment to relapse. The case had an inconclusive diagnosis and differentials of hemangiosarcoma or immune-mediated haemolytic anaemia. The case progression included intensive medical management and a whole-blood transfusion with an excellent outcome. The patient, Patch (8-year-old male neutered Jack Russell Terrier), presented with history of lethargy and sudden onset of inappetence. Clinical symptoms alongside a MPCV 19%, RBC 0.25, haemoglobin 63, high platelets and borderline basophils.

Robotic-Assisted Laparoscopic Pyeloplasty in Challenging Cases of Ureteropelvic Junction Obstruction in the Pediatric Population: A Multicenter Review.

Purpose: To report a multi-institutional international experience in performing robotic pyeloplasty for complicated cases of ureteropelvic junction obstruction (UPJO) in the pediatric population and assess feasibility and outcomes. Materials and Methods: Retrospective chart review of all pediatric patients who underwent robotic-assisted laparoscopic pyeloplasty (RALP) for UPJO in challenging cases between 2013 and 2021 was included. Demographics, perioperative surgical data, complications, and results are described. Challenging cases were defined as bilateral UPJO, failure of previous open pyeloplasty (thus re-do cases), correction of UPJO in kidneys with anatomical variations, huge hydronephrosis, and low-weight infants (<6 kg). Results: Over an 8-year period, 36 children (62% males and 38% females) met the inclusion criteria for our study. Fifteen patients underwent RALP for recurrent UPJO; among them, 2 children required simultaneous surgery for renal stones, 3 cases of lower pole UPJO in double collecting system, 3 cases of pelvic and horseshoe kidneys, 10 cases of infants weighing <6 kg, 3 cases of huge hydronephrosis, and 2 cases of bilateral UPJO. The median age and weight were 36 months (interquartile range [IQR] 14-84) and 12 kg (IQR 10-20.5), respectively. All robotic cases were completed successfully with no conversion to an open procedure. The median operative time was 120 minutes (IQR 90-135). The mean length of hospital stay was 2.6 days. Four patients (17%) had postoperative complications-1 ileus (Clavien-Dindo grade [CDG] I) and 3 urinary tract infections (CDG II). No CDG III or higher complication was encountered. At a median follow-up of 36 months, the success rate was 95% with 1 patient requiring another re-do procedure due to recurrent obstruction. Conclusions: Our data suggest that RALP is safe and effective even for challenging cases of UPJO in children.

AB162. SOH24AB_095. Heparin-induced thrombocytopenia complicating orthopaedic surgery: a challenging case in an elderly patient

AB162. SOH24AB_095. Heparin-induced thrombocytopenia complicating orthopaedic surgery: a challenging case in an elderly patient

A checkerboard-free symmetry-preserving conservative method for magnetohydrodynamic flows

Simulating MHD flows at high Hartmann numbers and low magnetic Reynolds numbers is of high interest for the design of a nuclear fusion breeding blanket, for which high accuracy and conservation of physical properties are of great importance. In this work, a solver is developed that offers these properties through the symmetry-preserving method, while at the same time warranting unconditional stability. Since this method uses predictor values for the pressure and electric potential fields, it can be prone to checkerboarding. Therefore it is extended to include a dynamical checkerboarding solution, which balances this problem with numerical dissipation. This is done through run-time measurements of the intensity of checkerboarding, which is then used as a negative feedback onto the predictor values. The symmetry-preserving discretisation and the dynamical solution to checkerboarding were successfully tested using an magnetohydrodynamic Taylor-Green vortex. The newly introduced method shows results free from numerical dissipation in smooth cases, whereas it avoids checkerboarding in more challenging cases. Finally, the method shows to be unconditionally stable, even on highly distorted meshes.