Clinical Resolution Research Articles

Rapid Clinical Resolution in Patients with Indeterminate Pediatric Liver Failure and Immune Dysregulation Hepatitis Treated with Ruxolitinib

IntroductionIndeterminate pediatric acute liver failure (iPALF) is a rare, life-threatening diagnosis associated with high rates of liver transplant and reduced survival. Immune dysregulation hepatitis shares many of the same clinical features as iPALF but is defined by an INR ≤ 1.5. Both present with progressive new-onset hepatocellular injury with predominant cytotoxic T-cell mediated inflammation and diffuse cytokine release. Importantly, the optimal medical therapy for these conditions of severe hepatic injury is not known. Here, we present two pediatric cases of steroid-refractory liver dysfunction where use of ruxolitinib, a JAK-STAT pathway inhibitor, led to significant clinical improvement. Case DescriptionsA 12-year-old male (patient A) presented with iPALF, while a 7-year-old female (patient B) presented with immune dysregulation hepatitis. Both patients had coagulopathy, transaminitis and hyperbilirubinemia (Table 1). Ischemia, toxin exposure, autoimmune hepatitis, and infection screens were negative. Immune evaluation demonstrated significantly elevated soluble IL-2 receptor, CXCL9, and sCD163, with mild hyperferritinemia (Table 1). Patient B had IgM EBV antibodies on repeat testing, which may have contributed to her immune dysregulation. Each patient’s next generation sequencing for inborn errors of immunity were negative. Both liver biopsies revealed a cytotoxic T-cell infiltrate, activated Kupffer cells, absence of iron, and absent plasma cell activity. During initial management, patient A received methylprednisolone 2 mg/kg daily, while patient B received 10 mg/kg daily before weaning to 2 mg/kg daily. Steroid-refractory disease was highlighted by ongoing liver damage on serial labs with worsening jaundice and fatigue. Both patients were transitioned to JAK-STAT inhibition with ruxolitinib. Patient A was loaded with 10 mg BID for one week before transitioning to 5 mg BID for 3 months, while patient B started and remained on 5 mg BID for 4 months. Both patients experienced rapid clinical improvement within one week and normalization of immune dysregulation on serial lab work by one month without need for further invasive interventions. Therapy was well tolerated without infectious or thrombotic complications.Table 1Maximum lab values prior to ruxolitinib initiationSoluble IL-2R (175.3–858.2 pg/mL)CXCL9 (< = 647 pg/mL)sCD163(<991 ng/mL)Ferritin (7–271 ng/mL)INRAST (< =60 U/L)ALT (10–49 U/L)Total Bilirubin (0.2–1.0 mg/dL)Patient A8664199731 0965971.62226275815.6Patient B243615 41881994291.43010228411.4Table 1. (abstract: 96) Selected laboratory test results. Values below or above reference are indicated with blue and red respectively. Not shown: IL-2, IL-4, IL-5, IL-8, IL-12, IL-13, IL-17 were normal. Fecal blood testing at baseline was negative. T cell memory population percentages were normal. T cell proliferation studies were normal. Pre-SCIG = pre-subcutaneous IgG (SCIG) treatment. Post-SCIG = post-SCIG treatment sample obtained after ~4 months of SCIG. n/a = sample not available. ConclusionThese cases suggest in iPALF and severe acute hepatitis where immune dysregulation is present, JAK-STAT inhibition may have benefit and deserves consideration for preventing disease progression and reducing morbidity and mortality.

Intracranial Pachymeningitis: A Case-Series Describing Clinical Features, Imaging, Serological and Cerebrospinal Fluid Markers, Biopsy Findings and Management (P9-5.018)

<h3>Objective:</h3> We present a case-series of patients with intracranial pachymeningitis and outline their management for successful outcomes. <h3>Background:</h3> Hypertrophic pachymeningitis is characterized by focal/diffuse thickening of intracranial and/or intraspinal dura. <h3>Design/Methods:</h3> <h3>Case-1:</h3> 48-year-old-woman with Crohn’s disease, relapsing polychondritis, presented with persistent left-sided headaches. MRI brain revealed left-sided contrast-enhancing pachymeningeal thickening; CSF showed lymphocytic pleocytosis. Glucocorticoids, adalimumab, and methotrexate resulted in clinical and neuroimaging improvement. <h3>Case-2:</h3> 78-year-old-woman presented with intractable headache, bilateral sensorineural-hearing-loss and vision-impairment. MRI brain showed nodular, multifocal dural-thickening at clivus, parasellar region, cavernous-sinuses extension encasing major vessels at skull-base. CSF showed lymphocytic pleocytosis, protein and serology demonstrated IgG4-subclasses, attributing etiology to IgG4-related-disease. Steroids, methotrexate, and later IV-rituximab resulted in equivocal response. Intrathecal rituximab, resulted in clinical and imaging stabilization, from better CNS penetration. <h3>Case-3:</h3> 60-year-old woman, with sarcoidosis presented with severe headaches. MRI demonstrated contrast-enhancing dural thickening in left posterior-temporo-occipital regions. Brain-biopsy showed non-necrotizing granulomas involving dura, parenchyma consistent with sarcoidosis. Steroids and infliximab, lead to clinical and radiological improvement. <h3>Case-4:</h3> 76-year-old man with prior metastatic melanoma, post-chemotherapy (nivolumab+ipilimumab), presented with headaches. MRI showed diffuse intracranial contrast-enhancing pachymeningeal thickening. Chest CT-scan showed circumferential thickening, contrast-enhancing thoracic aorta indicating systemic vasculitis. Serologically, ANA 1:320, +SSA/SSB, ESR/CRP both &gt;100 and ANCA was negative. Meningeal biopsy demonstrated granulomatosis with polyangiitis; etiology considered paraneoplastic. Steroids and methotrexate demonstrated clinical and radiological response. <h3>Case-5:</h3> 56-year-old woman presented with headaches and CN-VII palsy. MRI brain revealed hypertrophic pachymeningitis causing mass-effect on right lateral ventricle. ANCA serological positivity and biopsy demonstrated AFB-stain-negative caseating granulomas, consistent with ANCA-vasculitis. Rituximab led to complete resolution of both pachymeningeal and CN-VII enhancement. <h3>Results:</h3> Clinical resolution and radiological stability was achieved for all 5 patients. <h3>Conclusions:</h3> Intracranial pachymeningitis presents in setting of systemic autoimmune disorders and sarcoidosis. Brain imaging, CSF-analysis, serological immune-markers, and biopsy aid in diagnosis. Immunosuppressive therapies provide for clinical and radiologic stabilization. <b>Disclosure:</b> Dr. Varma-Doyle has nothing to disclose. Dr. Manzano has nothing to disclose. Dr. Venna has nothing to disclose.

Neurosarcoidosis Induced by TNF-alpha Inhibitor in a Patient with Ankylosing Spondylitis (P9-5.002)

<h3>Objective:</h3> To report a case of neurosarcoidosis associated with infliximab administration. <h3>Background:</h3> Sarcoidosis is a systemic immune mediated disease that can affect any organ. Neurological involvement accounts for 5–10% of cases and can be life-threatening. Infliximab, a TNF-alpha inhibitor agent, is used in the treatment of sarcoidosis. However, rarely, it can paradoxically induce sarcoidosis. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 35-year-old male with ankylosing spondylitis complained of refractory and recurrent headaches, confusion, and word-finding difficulties for 2 weeks duration. Symptoms began after the infliximab infusion, which he has been receiving for 2 years, was changed to a biosimilar product. Initial routine testing and MRI brain with/without contrast were unremarkable. He was treated for migraines including a 4-day course of steroids. However, the symptoms worsened. On presentation, the physical examination revealed inattentiveness, difficulty recognizing familiar faces, impaired calculations, and decreased fluency. EEG demonstrated moderate generalized background slowing with frequent runs of generalized rhythmic delta activity. Laboratory testing showed slightly elevated ESR (24 mm/h) and CRP (2.8 mg/dL). CSF was significant for WBC 174 cells/mcL, protein 133.4 mg/dL, ACE 4.6 U/L, CD4:CD8 ratio 3:1. CT chest, abdomen and pelvis demonstrated diffuse lymphadenopathy. Repeat MRI brain demonstrated leptomeningeal enhancement most pronounced in the bilateral posterior temporal and occipital lobes. CT facial bones with contrast described increased density with central enhancement of the right maxillary sinus. Biopsy of a left inguinal lymph node revealed noncaseating granulomas consistent with sarcoid. Treatment with prednisone resulted in significant clinical improvement and resolution of leptomeningeal enhancement at 1 month. These findings are suggestive of neurosarcoidosis with possible involvement of the leptomeninges, sinuses and lymph nodes. <h3>Conclusions:</h3> Most case reports in the literature of TNF-alpha inhibitors inducing sarcoidosis describe involvement of lungs, skin, and lymph nodes. This case highlights a rare complication of TNF-alpha inhibitor resulting in neurosarcoidosis. <b>Disclosure:</b> Dr. Pak has nothing to disclose. Dr. Askari has received personal compensation for serving as an employee of Stony Brook Hospital University. Dr. Treidler has nothing to disclose.

P025 The knee that gave it away: a case report of melioidosis

Abstract Background/Aims Melioidosis, an infectious disease caused by the Burkholderia pseudomallei is very rare within the UK. This gram-negative bacterium is endemic in Southeast Asia predominately Thailand and Northern Australia which is found within the soil and fresh surface water. We present a challenging case of melioidosis who was diagnosed following a culture of a discharging knee swelling. Methods N/A Results 35-year-old, Caucasian gentleman with no previous past medical history presented with a ten week history of diffuse abdominal pain, weight loss, dry cough, fatigue and night sweats. On examination, he appeared pale and initial bloods showed a CRP of 229 mg/L. His other initial observations and baseline blood tests were normal. Abdominal ultrasound detected free peritoneal fluid and a subsequent CT chest and abdominal showed abnormal thickening of his small bowel, mediastinal and retroperitoneal lymphadenopathy along with bilateral pulmonary nodules. A laparoscopy and laparotomy with peritoneal, intraperitoneal and mesenteric lymph node biopsies were inconclusive. Microscopy and culture (MC&amp;S) as well as acid fast bacilli MC&amp;S were both negative. He continued to have systemic symptoms, as well as elevated inflammatory markers. He underwent a bronchoscopy which showed erythematous and a nodular endobronchial mucosa with white plaques seen within the lower trachea and minor narrowing of the lumen. Endobronchial biopsies showed chronic inflammation with no evidence of any malignant cells. Repeated bloods including retroviral screening, anti-nuclear antibody (ANA) and antinuclear cytoplastic antibodies (ANCA) and serum ACE were normal. At this stage, the clinical picture was suggestive of sarcoidosis, however a subsequent rigid bronchoscopy and biopsy did not evidence of granulomas or vasculitis. The patient started to develop increasing right knee swelling with difficulty in walking. The swelling burst open, and the discharging fluid was sent for MC&amp;S. This was positive for Burkholderia pseudomallei. The gentleman completed a 20-week course of antibiotics with clinical resolution. Conclusion Meliodosis can cause a wide range of clinical manifestations varying from asymptomatic to septicemia, osteomyelitis, abscesses, septic arthritis and encephalomyelitis. Our case had travelled to Thailand around 8 months prior to the onset of symptoms. This highlights the possible long latent period between exposure and clinical presentation. Definite diagnosis is through isolation of Burkholderia pseudomallei in cultures. This proved challenging in our case, as multiple biopsies and cultures from different sites did not grow the bacterium. The diagnosis was confirmed following knee fluid culture. Musculoskeletal involvement of melioidosis is a known presentation and its potential to mimic other conditions, may render a diagnostic challenge especially when it occurs outside an endemic area. The case highlights the need for rheumatologists to have a high level of clinical suspicion for early detection, isolation of the organism and proper disease management. Disclosure A. Maksoud: None. L. Sammut: Other; LS has received funding for educational events and activities - from Lilly, Roche/Chugai.

A retrospective study of the range of cutaneous clinical and histological features of erythema multiforme in five ferrets (Mustela putorius furo).

Erythema multiforme (EM) is an uncommon cutaneous reaction pattern characterised by panepidermal keratinocyte apoptosis with lymphocytic satellitosis, and is reported in domestic animal species, livestock and rarely ferrets. The aim of this study was to analyse the spectrum of cutaneous clinical and histological features in ferrets with EM and to evaluate history and treatment outcomes. Five client-owned ferrets with biopsy-confirmed EM. Retrospective review of electronic medical records and histopathological reports from 2002 to 2021. Tissue blocks, haematoxylin and eosin re-cuts, and unstained slides were collected to review EM lesions and evaluate for infectious agents with special stains. Immunohistochemical staining was performed to assess cases for viral pathogens. Panepidermal cytotoxic dermatitis consistent with EM was identified in all cases and involved haired skin in four of five and mucous membranes in one of five ferrets. Skin lesions included variably pruritic alopecia, erythema, scaling, crusts and erosions/ulcerations. Histological features included primarily parakeratotic hyperkeratosis, panepidermal keratinocyte apoptosis, lymphocytic satellitosis and interface dermatitis. Superficial colonisation by bacteria, yeasts or by both was a common finding. Four of five ferrets had concurrent adrenal disease, one of which had resolution of skin lesions with deslorelin acetate treatment. Awareness of the distinct clinical and histological features is key to the diagnosis of EM in ferrets. Clinical resolution was observed with gonadotropin-releasing hormone agonists in two cases, suggesting that adrenal disease should be ruled out as a potential trigger of EM in ferrets.

Teaching Neuro Images : Sarcoidosis presenting as longitudinally extensive myelitis

A 44-year-old man presented with 2 weeks of progressive right body numbness, weakness, and circumferential burning sensation around his trunk. MRI spine demonstrated longitudinally extensive myelitis (figure 1). MRI brain and laboratory investigations were normal except for CSF lymphocytic pleocytosis (9 leukocytes/mm3). CT revealed hilar and mediastinal lymphadenopathy, which on biopsy showed noncaseating granulomas suggestive of sarcoidosis. As the patient had multiple clinical relapses on steroids, he was treated with infliximab infusions (5 mg/kg every 4 weeks) and had complete clinical and radiologic resolution after 1 year (figure 2). Myelitis as the presenting feature of sarcoidosis is exceptionally rare and responds to infliximab.1,2

Teaching NeuroImages: Spinal cord syrinx secondary to a spinal dural arteriovenous fistula

A 60-year-old man presented with a 2-year history of progressive lower limb weakness, numbness, urinary retention, and chronic constipation with superimposed episodes of severe paraparesis. MRI showed a cervicothoracic syrinx with flow voids (figure). Spinal angiography revealed a type I spinal dural arteriovenous fistula (SDAVF), which was treated with surgical ligation. The patient demonstrated dramatic clinical improvement and resolution of the syrinx. We are aware of one other case report of syrinx associated with SDAVF with similar outcome.1 Thoracic SDAVF often occurs in men in the seventh decade, with leg weakness exacerbated by exercise,2 and may be a treatable cause of syrinx.

625 Inflammatory modulation correlates with clinical scarless tunnel resolution after novel anti-biofilm therapy for hidradenitis suppurativa tunneling wounds

625 Inflammatory modulation correlates with clinical scarless tunnel resolution after novel anti-biofilm therapy for hidradenitis suppurativa tunneling wounds

A rare case of presumptive pleural toxocariasis.

Toxocariasis is a cosmopolitan helminthiasis linked to contamination with Toxocara cati or Toxocara canis. Only six isolated cases of pleural toxocariasis have been reported in the literature. We describe a case of pleurisy with isolated eosinophilia varying between 600 and 1500/mm3 likely linked o presumptive toxocariasis in a 72-year-old patient. Our patient was admitted to hospital with severe dyspnoea, asthenia and diarrhoea. Imaging studies confirmed right unilateral pleurisy without any parenchymal involvement. Serology of serum and pleural fluid was positive for anti-Toxocara antibodies by ELISA and immunoblotting. Treatment by pleural drainage and anti-parasitic medication with albendazole for 8days resulted in the resolution of symptoms. A decrease in the levels of polynuclear eosinophils and total IgE confirmed the clinical resolution. The presence of hypereosinophilia in pleural fluid should evoke a diagnosis of pleural toxocariasis. Clinical symptoms and imaging are non-specific, but positive serology for anti-Toxocara antibodies in serum and pleural fluid can confirm the diagnosis.

Successful Combination of Remdesivir and Convalescent Plasma to Treat a Patient with Rituximab-Related B-Cell Deficiency and Prolonged COVID-19: A Case Report

Background: Treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immuno-compromised patients with complete B cell depletion can be really challenging due to the lack of seroconversion and long-lasting disease. Case Report: We describe a case of long-lasting coronavirus disease (COVID-19) in a female patient with rheumatoid arthritis who was treated with rituximab and continued to show B-cell depletion. An ongoing replication of SARS-CoV-2 was demonstrated for a period of 8 months when nasopharyngeal swabs were tested. She was treated once with remdesivir but without lasting resolution, and she was then treated with convalescent plasma but with a similar effect. Only with a combination of both treatments was clinical resolution achieved. The patient's lack of seroconversion and the prolonged course of the disease illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case report highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission. Conclusions: The combination of remdesivir and convalescent plasma resulted in successfully achieving clinical resolution of SARS-CoV-2 infection in our patient.

Blackwater Fever Treated with Steroids in Nonimmune Patient, Italy

Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.

Robotic pancreatic necrosectomy and internal drainage for walled-off pancreatic necrosis

BackgroundPancreatic necrosectomy with concomitant internal drainage is a single-stage treatment option for walled-off pancreatic necrosis (WOPN). However, an optimal minimally invasive technique has not been established. We evaluated the safety and single-intervention success rate of robotic pancreatic necrosectomy and internal drainage. MethodsPatients with WOPN undergoing robotic pancreatic necrosectomy and internal drainage at a single institution from 2011-2022 were identified. The primary outcome was the rate of clinical symptom resolution following the index surgical intervention. Results57 patients underwent robotic pancreatic necrosectomy and internal drainage, consisting of robotic cystgastrostomy (RCG, n = 37), robotic cystjejunostomy (RCJ, n = 13) and robotic fistulojejunostomy (RFJ, n = 7). Surgery was performed a median of 102 (range 28–1153) days following the onset of necrotizing pancreatitis. The median operative time was 187 (91–344) minutes and there were 2 (3.5%) conversions. The median length of hospital stay was 4 (2–38) days. Postoperative morbidity was 11%, and there was one (1.8%) 90-day mortality. At a median follow-up of 5.5 months, 53 (93%) patients had clinical symptom resolution after their index procedure and did not require any reintervention. ConclusionIn select patients, robotic pancreatic necrosectomy and internal drainage is safe and achieves a high single-intervention success rate.

Ten-month follow-up of patients with covid-19 temporally related multi-system inflammatory syndrome in children: the experience of the children hospital of Palermo

BackgroundIn Sicily, the first wave of COVID-19 showed a low epidemic impact in paediatric population, while the second and the third waves had a higher impact on clinical presentation of COVID-19 in children and a significantly higher severe outcome in patients with multisystem inflammatory syndrome in children (MIS-C), with a frequent life-threatening progression.MethodsWe describe a cohort of 22 Sicilian children (11 M; 11 F; age: 1.4–14 years), presenting with clinical features compatible with MIS-C. Patients with negative swab had a history of recent personal or parental infection.ResultsThe following diagnostic criteria were detected: fever (100%); cheilitis and/or pharyngeal hyperaemia (86%); latero-cervical lymphadenitis (82%); rash (73%); abdominal pain and/or vomiting and/or diarrhoea (64%); conjunctivitis (64%); hands and feet oedema (18%). 59% showed cardiac involvement (6 pericardial effusion; 8 mitral valve insufficiency; 4 insufficiency of two valves; 3 coronary artery lesions (CAL)). In all the patients, treatment was started within 72 h after the admission, with intravenous immunoglobulins (IVIG) (2 g/Kg/dose), methylprednisolone (2 mg/Kg/day in 73% of patients; 30 mg/Kg/day for 3 days, followed by 2 mg/Kg/day in 27% of patients). Two patients were treated with enoxaparin. Two patients with shock, were additionally treated with vasoactive drugs, albumin, diuretics. Cardiac involvement evolved into the complete resolution of lesions in most of the patients. All the patients were included in a follow-up, to investigate on clinical outcome and resolution of organ involvement. Cardiac valve insufficiency persisted only in 18% of children, CAL persisted only in 33% of children with coronary involvement, however without the evolution into aneurisms.ConclusionsThe preferred treatment strategy was more aggressive at the diagnosis of MIS-C, to block the cytokine cascade. Most of our patients, in fact, received a first-line treatment with IVIG and steroids. This approach could explain the favourable prognosis, the rapid restoring of cardiac function also in patients with MAS or shock, and the good outcome during the 10 months follow-up in all the patients.

An 8-year-old boy with diffuse cystic pulmonary tuberculosis: An intriguing story

Diffuse cystic lung disease due to pulmonary tuberculosis (TB) is rare. We describe an 8-year-old boy who presented with acute onset respiratory distress while on a compliant anti-tubercular treatment for a recently diagnosed pulmonary TB. On clinical examination, hypoxemia, clubbing, and features of the right-sided heart failure were observed. High-resolution computed tomography of the chest revealed extensive cystic lung parenchymal changes with ground glassing and consolidation, and echocardiography indicated the presence of pulmonary arterial hypertension. His treatment included supplemental oxygen, sildenafil, prednisolone, and anti-tubercular drugs. At the two-year follow-up, the patient showed complete clinical recovery and resolution of cysts on the chest X-ray.

Clinical Outcomes of the Endoscopic Step-Up Approach with or without Radiology-Guided Percutaneous Drainage for Symptomatic Walled-Off Pancreatic Necrosis.

Background and objectives: Symptomatic walled-off pancreatic necrosis is a serious local complication of acute necrotising pancreatitis. The endoscopic step-up approach is the standard treatment for symptomatic walled-off pancreatic necrosis; however, adjunctive radiologic percutaneous drainage for this condition is controversial. This study compared the clinical and radiologic resolution of walled-off pancreatic necrosis achieved with the endoscopic step-up approach with or without radiology-guided percutaneous drainage. Material and Methods: This retrospective, single-centre cohort study enrolled patients with symptomatic walled-off pancreatic necrosis who underwent endoscopic transmural drainage (ETD) followed by directed endoscopic necrosectomy (DEN) with or without radiology-guided drainage. A total of 34 patients (endoscopic approach, n = 22; combined modality approach, n = 12) underwent the endoscopic step-up approach (ETD followed by DEN). Baseline characteristics, clinical success, and resolution of necrosis were compared between groups. Results: All patients achieved symptom resolution from walled-off pancreatic necrosis. The mean patient age was 58.4 years, and 21 (61.8%) were men. Following treatment with the endoscopic approach and combined modality approach, clinical success was achieved in 90.9% of patients within 11.5 days, and 66.7% of patients within 16.5 days, respectively. Both length of hospital stay (55 days vs. 71 days; p = 0.071) and time to complete radiologic resolution were shorter (93 days vs. 124 days; p = 0.23) in the endoscopic approach group. Conclusion: Both the endoscopic step-up approach and the CMD approach resulted in a favourably high clinical resolution rates in patients with symptomatic WON. However, clinical success rates seemed to be higher, and the length of hospital stay tended to be shorter in the endoscopic approach than in the CMD approach, as well as the significantly shorter necrosectomy time in each procedure was observed. Of note, these findings might be from some inherited differences in baseline characteristics of the patients between the two groups, and a randomized controlled trial with a larger sample size to verify these results is warranted.

Retrospective comparison of side effects and outcomes of three-dimensional conformal vs. intensity-modulated radiation therapy in the palliative-intent treatment (4 Gy × 5 daily fractions) of canine intranasal tumors (2010-2017).

To compare the occurrence of radiation side effects and treatment outcomes in dogs with intranasal tumors treated with a total dose of 20 Gy delivered in 5 daily 4 Gy fractions using computer-based 3D conformal (3DCRT) or intensity-modulated (IMRT) radiation therapy plans. Retrospective case series. Medical records for dogs with intranasal tumors treated with 4 Gy × 5 fractions between 2010 and 2017 were reviewed. Radiation side effects, time to local progression (TTLP), progression-free survival (PFS) and survival time (OS) were evaluated. Thirty-six dogs (24 carcinomas, 10 sarcomas and 2 others) met the inclusion criteria. Sixteen were treated with 3DCRT and 20 with IMRT. Clinical signs improvement or resolution were reported in 84% of dogs. The median time to clinical signs improvement was 12 days (1-88 days) after the end of treatment. Eight dogs treated with 3DCRT (8/16, 50%) and 5 with IMRT (5/20, 25%) were documented acute radiation side effects. Almost all were classified as grade 1 skin, oral or ocular acute side effects. Only one dog in 3DCRT group was demonstrated grade 2 skin acute effects. The median TTLP for dogs treated with 3DCRT or IMRT was 238 days and 179 days, respectively (p = 0.967). The median PFS for 3DCRT or IMRT was 228 days and 175 days, respectively (p = 0.940). The median OS for 3DCRT or IMRT was 295 days and 312 days, respectively (p = 0.787). No significantly differences were observed in side effects, TTLP, PFS and OS between 3DCRT and IMRT groups. Palliative-intent conformal radiation therapy given in five daily 4 Gy fractions relieved clinical signs with minimal radiation side effects, with no statistical difference in occurrence between 3DCRT and IMRT dogs.

Cost analysis of disease including treatment with dalbavancin in a Spanish hospital: ECODAL ANALYSIS

Introduction and aimDalbavancin is an antibiotic with activity against gram-positive bacteria that allows early discharge of patients requiring intravenous therapy. Outpatient treatment helps offset hospitalisation costs associated with standard intravenous treatment. Our objective was to assess the cost of disease management, including treatment with dalbavancin, in a Spanish hospital for 1 year, and the hypothetical costs associated with treatment with other therapeutic alternatives to dalbavancin.MethodsA single-centre, observational, retrospective post-hoc analysis was conducted based on electronic medical records analysing all patients who received dalbavancin treatment throughout 1 year; cost analysis was performed for the whole process. In addition, three scenarios designed on the basis of real clinical practice by clinical experts were hypothesised: (i) individual therapeutic alternative to dalbavancin, (ii) all patients treated with daptomycin, and (iii) all days of dalbavancin as outpatient treatment transformed into hospital stay. Costs were obtained from the hospital.ResultsThirty-four patients were treated with dalbavancin; their mean age was 57.9 years, and 70.6% were men. The main reasons for dalbavancin use were outpatient management (61.7%, n = 21) and ensuring treatment adherence (26.5%, n = 9). The main indications were: osteoarticular infection (32.4%) and infective endocarditis (29.4%). One-half (50%) of the infections were due to Staphylococcus aureus (23.5% were methicillin resistant). All patients achieved clinical resolution, and no costs associated with dalbavancin-associated adverse events or re-admissions were reported. The mean total cost of treatment was 22,738€ per patient, with the greatest expenditures in interventions (8,413€) and hospital stay (6,885€). The mean cost of dalbavancin treatment was 3,936€; without dalbavancin, this cost could have been increased to 3,324–11,038€ depending on the scenario, mainly due to hospital stays.Main limitationLimited sample size obtained from a single centre.ConclusionThe economic impact of the management of these infections is high. The cost of dalbavancin is offset by the decreased length of stay.

Extracting patient-level data from the electronic health record: Expanding opportunities for health system research.

Epidemiological studies of interstitial lung disease (ILD) are limited by small numbers and tertiary care bias. Investigators have leveraged the widespread use of electronic health records (EHRs) to overcome these limitations, but struggle to extract patient-level, longitudinal clinical data needed to address many important research questions. We hypothesized that we could automate longitudinal ILD cohort development using the EHR of a large, community-based healthcare system. We applied a previously validated algorithm to the EHR of a community-based healthcare system to identify ILD cases between 2012-2020. We then extracted disease-specific characteristics and outcomes using fully automated data-extraction algorithms and natural language processing of selected free-text. We identified a community cohort of 5,399 ILD patients (prevalence = 118 per 100,000). Pulmonary function tests (71%) and serologies (54%) were commonly used in the diagnostic evaluation, whereas lung biopsy was rare (5%). IPF was the most common ILD diagnosis (n = 972, 18%). Prednisone was the most commonly prescribed medication (911, 17%). Nintedanib and pirfenidone were rarely prescribed (n = 305, 5%). ILD patients were high-utilizers of inpatient (40%/year hospitalized) and outpatient care (80%/year with pulmonary visit), with sustained utilization throughout the post-diagnosis study period. We demonstrated the feasibility of robustly characterizing a variety of patient-level utilization and health services outcomes in a community-based EHR cohort. This represents a substantial methodological improvement by alleviating traditional constraints on the accuracy and clinical resolution of such ILD cohorts; we believe this approach will make community-based ILD research more efficient, effective, and scalable.

A268 RESOLUTION RATES IN OPEN-LABEL VERSUS RANDOMIZED CONTROLLED TRIALS FOR MICROBIOTA RESTORATION FOR RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION: AN UPDATED META-ANALYSIS

Abstract Background Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates &amp;gt;90%) but efficacy in controlled clinical trials appears lower. Purpose We performed an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs). Method A systematic search of Embase, Web of Science and Scopus was performed up to June 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose as the primary outcome were included. We calculated both unweighted and weighted pooled resolution rates (UPR and WPR) with 95% confidence intervals (CI). Result(s) Eighteen studies (9 RCTs and 9 open-label trials) with 1149 CDI patients were included. Of the patients treated with microbiota restoration, 881 experienced symptom resolution (UPR 77%%; WPR 79%, 95% CI, 72%-85%). There was significant heterogeneity among studies with an I2of 86%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 357 of 496 patients (UPR 72%; WPR 73%, 95% CI 63%-82%) with microbiota restoration. Among the 9 open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (UPR 80%; WPR 84%, 95% CI 74%-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR 73% vs 84%, p&amp;lt;0.0001). Analysis of the 10 trials with non-microbiota restoration revealed CDI resolution in 201 of 397 patients with antibiotics (WPR 52%, 95% CI 43%-60%). There was significant heterogeneity among the included studies with an I2of 61%. Comparison of cure rates with microbiota restoration vs antibiotics showed higher cure rate with microbiota restoration (WPR 73%, [95% CI 63%-82%] vs 52% [95% CI, 43%-60%]; p&amp;lt;0.0001). There were no serious adverse events reported. Conclusion(s) Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open label studies were similar to observational studies. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.

We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.