Duffy, Dustin

AbstractBackgroundStiff person spectrum disorder (SPSD) is heterogeneous, and accurate diagnosis can be challenging.MethodsPatients referred for diagnosis/suspicion of SPSD at the Mayo Autoimmune Neurology Clinic from July 01, 2016, to June 30, 2021, were retrospectively identified. SPSD diagnosis was defined as clinical SPSD manifestations confirmed by an autoimmune neurologist and seropositivity for high‐titer GAD65‐IgG (>20.0 nmol/L), glycine‐receptor‐IgG or amphiphysin‐IgG, and/or confirmatory electrodiagnostic studies (essential if seronegative). Clinical presentation, examination, and ancillary testing were compared to differentiate SPSD from non‐SPSD.ResultsOf 173 cases, 48 (28%) were diagnosed with SPSD and 125 (72%) with non‐SPSD. Most SPSD were seropositive (41/48: GAD65‐IgG 28/41, glycine‐receptor‐IgG 12/41, amphiphysin‐IgG 2/41). Pain syndromes or functional neurologic disorder were the most common non‐SPSD diagnoses (81/125, 65%). SPSD patients more commonly reported exaggerated startle (81% vs. 56%, p = 0.02), unexplained falls (76% vs. 46%, p = 0.001), and other associated autoimmunity (50% vs. 27%, p = 0.005). SPSD more often had hypertonia (60% vs. 24%, p < 0.001), hyperreflexia (71% vs. 43%, p = 0.001), and lumbar hyperlordosis (67% vs. 9%, p < 0.001) and less likely functional neurologic signs (6% vs. 33%, p = 0.001). SPSD patients more frequently had electrodiagnostic abnormalities (74% vs. 17%, p < 0.001), and at least moderate symptomatic improvement with benzodiazepines (51% vs. 16%, p < 0.001) or immunotherapy (45% vs. 13% p < 0.001). Only 4/78 non‐SPSD patients who received immunotherapy had alternative neurologic autoimmunity.InterpretationMisdiagnosis was threefold more common than confirmed SPSD. Functional or non‐neurologic disorders accounted for most misdiagnoses. Clinical and ancillary testing factors can reduce misdiagnosis and exposure to unnecessary treatments. SPSD diagnostic criteria are suggested.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) is a potentially deadly infection afflicting the immunocompromised population, including solid organ transplant recipients. Several risk factors have been described, including acute rejection, lymphopenia, and cytomegalovirus (CMV) infection. However, little is known regarding the risk imparted by posttransplant lymphoproliferative disorder (PTLD). Methods We performed a nested case-control study of solid organ transplant recipients diagnosed with PCP from 2000-2020. PCP was defined as positive smear or polymerase chain reaction testing with compatible clinical symptoms and radiographic findings. Two control were matched to each case by year of first transplant, first transplanted organ, and sex. Each control had at least as much follow-up from their transplant date to their matched case’s PCP diagnosis date. Multivariable conditional logistic regression was performed to analyze theorized risk factors. Results Sixty-seven cases met inclusion criteria and were matched to 134 controls (Table 1). Median age was 60.9 years, and the most common transplant type was kidney (52.2%). Fourteen patients had a history of PTLD, 12 of which developed PCP. All cases of PTLD were monomorphic, 6 were EBV-positive, 9 were receiving chemotherapy at the index date, and only 1 control patient was receiving PCP prophylaxis. The cases with PTLD developed PCP a median of 85 days after PTLD diagnosis, while the two controls were diagnosed more than 1 year earlier. After adjusting for age, acute rejection requiring treatment within the last 6 months, CMV infection within 6 months, current PCP prophylaxis, and lymphopenia (lymphocyte count &lt; 0.5 x109/L) within 6 months, PTLD had a significant association with PCP (OR 14.0, 95% CI 1.7-114.5; p = .014). Lymphopenia was also associated with PCP (OR 8.2, 95% CI 3.2-20.7; p &lt; .001), while the other factors were not. Table 1:Characteristics of 67 Solid Organ Transplant Recipients with Pneumocystis Pneumonia and 134 Matched Controls Conclusion Diagnosis of PTLD is independently associated with subsequent PCP after adjustment for recognized risk factors. This association is likely influenced by PTLD-directed chemotherapy, particularly regimens containing rituximab. PCP prophylaxis should be initiated in solid organ transplant recipients with PTLD, particularly those undergoing active therapy, and those with severe lymphopenia. Disclosures All Authors: No reported disclosures.

The Spheroid Reservoir Bioartificial Liver (SRBAL) is an innovative treatment option for acute liver failure (ALF). This extracorporeal support device, which provides detoxification and other liver functions using high-density culture of porcine hepatocyte spheroids, has been reported in three randomized large animal studies. A meta-analysis of these three preclinical studies was performed to establish efficacy of SRBAL treatment in terms of survival benefit and neuroprotective effect. The studies included two hepatotoxic drug models of ALF (D-galactosamine, α-amanitin/lipopolysaccharide) or a liver resection model (85% hepatectomy) in pigs or monkeys. The SRBAL treatment was started in three different settings starting at 12 h, 24 h or 48 h after induction of ALF; comparisons were made with two similar control groups in each model. SRBAL therapy was associated with significant survival and neuroprotective benefits in all three animal models of ALF. The benefits of therapy were dose dependent with the most effective configuration of SRBAL being continuous treatment of 24 h duration and dose of 200 g of porcine hepatic spheroids. Future clinical testing of SRBAL in patients with ALF appears warranted.