Mild Improvement Research Articles

Gambling on others' health: risky pro-social decision-making in the era of COVID-19.

In the early days of the COVID-19 pandemic, individuals were asked to perform costly actions to reduce harm to strangers, even while the general population, including authorities and experts, grappled with the uncertainty surrounding thenovel virus. Many studies have examined health decision-making by experts, but the study of lay, non-expert, individual decision-making on a stranger's health has been left to the wayside, as ordinary citizens are usually not tasked with such decisions. We sought to capture a snapshot of this specific choice behavior by administering two surveys to the general population in the spring of 2020, when much of the global community was subject to COVID-19-related restrictions, as well as uncertainty surrounding the virus. We presented study participants with fictitious diseases varying in severity that threatened oneself, a loved one or a stranger. Participants were asked to choose between treatment options that could either provide a sure, but mild improvement (sure option) or cure the affected person at a given probability of success (risky option). Respondents preferred gambles overall, but risk-seeking decreased progressively with higher expected severity of disease. This pattern was observed regardless of the recipient's identity. Distinctions between targets emerged however whendecisions were conditioned on a treatment's monetary cost, with participants preferring cheaper options for strangers. Overall, these findings provide a descriptive model of individual decision-making under risk for others; and inform on the limits of what can be asked of an individual in service to a stranger.

COVID-19-induced Neonatal Acute Aortic Thrombosis

Abstract Venous thromboembolism is a well-recognized, common complication of a severe COVID-19 disease. Arterial thrombosis is a less known complication, now being reported increasingly, mostly in the form of myocardial infarction and stroke, but acute aortic occlusion is infrequent. Neonatal acute aortic thrombosis as a sequelae of COVID-19 disease has far uncommon incidence with no literature-based evidence till date. A 10-day-old male child presented to the emergency department with informant being his mother with complaints of black discoloration of his right foot for 4 days noticed first on his toes. No history of trauma, no history of fever, and no history of umbilical artery catheterization at birth was noted. Birth history-full term normal vaginal delivery, small for gestational age baby, cried immediately after birth, birth weight – 2.45 kg with no additional birth events. No history of neonatal intensive care unit stay, immunized at birth. Baby was 3rd by order of birth with no congenital anomalies noted in previous siblings. On examination, the baby was alert, afebrile, heart rate – 138/min, blood pressure – 90/60 mmHg, and SpO2 98% on room air. Local examination of the right lower limb revealed black discoloration of the right lower limb from toes up to mid-calf, CRT-delayed in the right thigh (7 s), right femoral pulsations absent, left lower limb – pink, warm, CRT – 6 s, feeble pulsations of left femoral artery and popliteal artery, absent pulsations of left anterior tibial artery, and posterior tibial artery. A Doppler study revealed the presence of partial lumen occluding thrombus (hyperechoic) in abdominal aorta below the level of renal arteries, absent flow in right lower limb, and monophasic flow in left femoral artery. A prothtrombotic screen was performed and COVID-19 antibody test was found to be positive. A systemic thrombolysis with injection reteplase was performed which showed mild improvement in circulation with propagation of clot up to origin of superior mesentric artery on a Doppler scan. An abdominal aortic embolectomy was performed, with retrieval of a long segment thrombus from distal abdominal aorta and bilateral femoral arteries following good proximal inflow and good distal backflow. Bilateral limb perfusion improved postoperatively though the gangrenous right lower limb could not be saved and a right below knee amputation was performed for the same. This case adds to the growing list of potential sites and consequences of thrombosis in COVID-19 infection. We speculate that this case of aortic thrombosis was a result of direct COVID-19-induced vascular damage in the context of a hypercoagulable state with a possibility of vertical transmission of the disease.

Trigonal bipyramidal or square planar? Density functional theory calculations of iron bis(dithiolene) N-heterocyclic carbene complexes.

Density functional theory (DFT) calculations of 57 iron bis(dithiolene)-N-heterocyclic carbene adducts were conducted to determine what parameters predict, and possibly influence, the coordination of these aforementioned adducts. The parameters considered herein include three different types of nuclear magnetic resonance (C-NMR, Se-NMR, and P-NMR) isotropic chemical shifts, the Tolman Electronic Parameter (TEP), the Huynh Electronic Parameter (HEP), and the percent buried volume (%Vbur) of the different N-heterocyclic carbenes (NHCs) calculated from DFT. These parameters were selected based upon prior literature connection to σ-donor ability, π-acidity, and steric effects. The computed values of the properties were compared via multivariable linear regression models to see which properties best predict the Addison τ parameter-a measure of whether the complex would assume the square pyramidal or trigonal bipyramidal geometry. It was determined that a combination of TEP and %Vbur are the best predictors of the τ value, for the parameters considered herein. The inclusion of additional parameters yields mild improvement to the statistical models for the prediction of the τ value.

Two patients of immunotherapy-responsive autoimmune cerebellar ataxia fulfilled with criteria of multiple system atrophy

We report two patients with autoimmune cerebellar ataxia who fulfilled the diagnostic criteria of multiple system atrophy (MSA) and responded to immunotherapies. Patient 1 was a 72-year-old man who was diagnosed with clinically probable MSA according to Movement Disorder Society criteria. Patient 2 was a 68-year-old man who was diagnosed with clinically established MSA according to Movement Disorder Society criteria. Both patients showed cerebellar ataxia, autonomic dysfunction, and pyramidal tract signs; however, they also had atypical clinical features. Patient 1 exhibited self-‍limiting mild improvement of clinical symptoms and had inflammatory findings in his cerebrospinal fluid. Patient 2 showed a rapidly progressive clinical course. We therefore examined anti-neuronal antibodies using tissue-based immunohistochemical assays with frozen rat cerebellum sections. We detected autoantibodies that mainly reacted with the cytoplasm of Purkinje cells. The two patients then underwent immunotherapies, which led to substantial improvements in their clinical symptoms. Our findings indicate that some patients with autoimmune cerebella ataxia have clinical features that resemble MSA, and respond well to immunotherapies.

Eyeing risks: Navigating ophthalmic challenges in sinus surgery

This is a descriptive case report of a 25-year-old male who presented with right eye diminution of vision associated with ophthalmoplegia and strabismus following functional endoscopic sinus surgery (FESS) for deviated nasal septum. On examination, he had a large angle right exotropia with enophthalmos and restricted extra ocular movements. Pupils were dilated and fixed suggestive of optic neuropathy and fundus revealed a central retinal artery occlusion. Multimodal radiological imaging revealed optic nerve sheath hematoma, fracture of medial orbital wall and orbital floor along with medial rectus disinsertion with posterior discontinuation. Due to delayed presentation at our clinic, he was managed conservatively with intravenous and oral corticosteroids. The patient displayed mild improvement in ocular movement and vision. He was advised orbital reconstruction of the medial wall and floor for enophthalmos correction and cosmesis. Although a relatively safe procedure, FESS can result into varied orbital complications, including damage to the extraocular muscles, optic nerve and its vascular supply. This case report, to the best of our knowledge is the first of its kind to document ophthalmoplegia due to medial rectus disinsertion along with central retinal artery occlusion. It also highlights the perioperative risk factors and provides insight into the intraoperative signs to be cautious of during sinus surgeries

Modulation of CXCL10 activity as a therapeutic target of ocular toxoplasmosis in diabetic mice.

Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.

Dosing, Monitoring, Blood Product Utilization, and Thromboembolic Complications of Four-Factor Prothrombin Complex Concentrate as Part of an Institutional Protocol in Pediatric Cardiac Surgery: A Retrospective Cohort Study.

Pediatric cardiac surgery patients are predisposed to blood loss. Blood product administration can lead to complications. Prothrombin complex concentrates (PCCs) offer potential advantages of factor composition, small volume, decreased immunogenicity/infectious risks, and accessibility. The objective of this study was to describe dosing, monitoring, blood product utilization, and thromboembolic complications of administering four-factor PCC (4F-PCC) in pediatric cardiac surgery. We performed a retrospective review of patients aged <18 years undergoing cardiac surgery from June 2020 to May 2022 (inclusive) who received 4F-PCC. Outcomes of interest included 4F-PCC dosing (units/kg) and number of doses administered, chest tube output, blood product administration, donor exposure, length of stay, and thromboembolic events. Eighty-six patients met eligibility criteria. The median (range) age and weight were 0.37 (0.01-16.3) years and 5.3 (1.6-98) kg, respectively. Median (range) total 4F-PCC dose per patient was 25 (9.2-50) units/kg, with 6 patients (7%) receiving a total of two doses. Median (range) 24-hour postoperative packed red blood cells, platelet, plasma, and cryoprecipitate administration volumes were 0 (0-2.57) mL/kg/24 h, 0 (0-1.09), 0 (0-2.64), and 0 (0-0.28 mL/kg/24 h), respectively. Median (range) length of stay and 24-hour postoperative chest tube output were 10 (6-26) days and 1.1 (0.1-4.2) mL/kg/h, respectively. Two (2%) patients experienced a thromboembolic event within 30 days of 4F-PCC administration. These retrospective findings suggest no worsening of hemostatic parameters, a mild median improvement in fibrinogen, low blood product utilization, and low thromboembolism rates following 4F-PCC use in pediatric cardiac surgery.

A Novel Beta Globin Frameshift Mutation Causing Autosomal Dominant Beta Thalassemia

Background: Dominantly inherited β-Thalassemia (β-thal) is a rare condition that results from a heterozygous mutation in the β-globin gene ( HBB), leading to the synthesis of an unstable β-globin chain, most frequently an elongated protein. Although heterogeneous, it presents not as β-thalassemia trait but rather with a more severe phenotype, resembling β-thal major or intermedia, with chronic hemolytic anemia and splenomegaly. There are approximately 150 known dominantly inherited α- and β-globin gene mutations (http://globin.cse.psu.edu/). We present a case of a novel HBB mutation leading to a dominant form of β-thalassemia, outlining our approach to attaining an appropriate diagnosis and management leading to transfusion independence. Case: A 32-year-old Caucasian female was referred to our center with a diagnosis of congenital dyserythropoietic anemia type II (CDA-II), based on bone marrow studies at 12 years of age which had demonstrated a hypercellular marrow with erythroid hyperplasia and 10% binucleated red cells. Molecular testing had not been performed. Her history was negative for developmental delay, growth retardation, or family history of anemia. She had presented to medical attention at age 11 with symptomatic anemia. Prior treatments included steroids, IVIG, and erythropoietin, with no significant improvement of her anemia. She underwent splenectomy at 19 years of age due to the hemolytic component of her anemia with the clinical diagnosis of CDA-II, with a mild improvement in baseline hemoglobin from 70-80g/L to 80-90g/L. Spleen pathology demonstrated splenomegaly (weight of 1kg) and mild iron deposition. At the time of presentation at our centre, her predominant symptom was fatigue, for which she was initiated on a chronic transfusion protocol, to maintain a pretransfusion hemoglobin of 90 g/L; she received a total of 53 units from October 2018 to November 2022. She subsequently developed worsening iron overload (ferritin 888, TSAT 80%, and LIC of 8.1mg of iron per gram of liver dry weight) requiring initiation of iron chelation therapy. Given her presumptive diagnosis of CDA-II she was later enrolled in the Congenital Dyserythropoietic Anemia Registry (CDAR) for North America (https://www.clinicaltrials.gov/study/NCT02964494). Molecular testing by next generation sequencing (NGS) on a CDA gene-panel at that time failed to identify a causative CDA mutation. Further testing with whole exome sequencing revealed a one base-pair deletion in exon 2 of the β-globin gene, creating a frameshift variant at codon 96 and ending in a premature STOP, 63 codons downstream p.(Lys 96Asnfs*63) (Figure 1). This mutation led to an elongated β-globin chain and an unstable hemoglobinopathy predicted to be the cause of her presentation. Hemoglobinopathy screen revealed HBF 8.7%, HBA 87.5%, and HBA2 3.8%. Based on the above testing, a diagnosis of dominant β-thalassemia intermedia due to HBB NM_00518.4, c.288delG, p.K96fs, recognizing that she had been previously misdiagnosed with CDA-II. Based on the revised diagnosis, the patient was initiated on Luspatercept 1mg/kg SC q3 weeks, with rapid improvement in her pre-transfusion hemoglobin to &amp;gt;100g/L as well as in her symptomatology and quality of life (Figure 2), rendering her transfusion independent. Discussion: This case report, to our knowledge, demonstrates a novel β-globin gene mutation leading to dominant β-thalassemia, with the phenotype of β-thal-intermedia. The latency between presentation and diagnosis demonstrates the challenges associated with diagnosing rare hemolytic anemias and highlights the importance of molecular testing to confirm the diagnosis, especially before proceeding to splenectomy which may predispose to vasculopathies in some of these diseases, such as congenital dyserythropoietic anemia type I and unstable hemoglobinopathies.

Treatment of hypertrophic scars with ablative fractional carbon dioxide laser assisted with different topical triamcinolone delivery ways

ObjectivesAblative fractional carbon dioxide laser has been used with triamcinolone to treat hypertrophic scars, resulting in promising success rates. However, there are different topical triamcinolone delivery methods used in scar treatment. To assess the efficacy among the different triamcinolone delivery methods, this study was designed to compare the efficacy and safety of ablative fractional carbon dioxide laser followed by penetration and injection of topical triamcinolone into thicker hypertrophic scars (height score of VSS ≥2). Study design/materials and methodsWe performed a retrospective study of 155 thicker hypertrophic scar patients (height score of VSS ≥2), including 88 patients in the triamcinolone external application group and 67 patients in the triamcinolone intralesional injection group. One month after the patients had 3 treatment sessions at 4-week intervals, the scars were assessed by photography, the Vancouver Scar Scale (VSS), durometry and spectrocolorimetry. Any adverse effects were also evaluated. ResultsThe VSS scores and the hardness of the scars in both groups improved significantly compared to baseline. Moreover, the patients in the triamcinolone intralesional injection group had higher treatment efficacy (19.77 ± 21.25 %) based on their VSS scores than the patients in the triamcinolone external application group (5.94 ± 24.07 %), especially in the improvement of scar pliability, height and hardness. Meanwhile, in the triamcinolone injection group, more patients had mild and moderate improvement than in the triamcinolone application group. However, there were no differences in the distribution of the adverse effects in either group. ConclusionsThis study demonstrated that using the ablative fractional carbon dioxide laser followed by different topical triamcinolone delivery methods is effective and safe for thicker hypertrophic scar improvement. The method of using the ablative fractional carbon dioxide laser assisted with triamcinolone injection had a better therapeutic outcome in thicker hypertrophic scars, as compared with triamcinolone penetration.

Erythrocyte Disorders Mimicking Congenital Dyserythropoietic Anemia Based on Bone Marrow Pathology Exposed By Genetic Evaluation

Congenital dyserythropoietic anemias (CDAs) are a rare group of heterogeneous genetic diseases characterized by hemolysis, ineffective erythropoiesis predisposing to iron overload, and the pathologic finding of bi- and multinucleated erythroblasts in the bone marrow (BM). With the identification of causative genetic mutations over the last two decades, the current classification includes the following types with the causative gene in parenthesis: Ia ( CDAN1), Ib ( CDIN1); II ( SEC23B); IIIa ( KIF23), IIIb ( RACGAP1); IV ( KLF1) ; and XLTD ( GATA1). Clinical presentation can vary widely even within the same type, ranging from mild cases of anemia to severe cases in which patients are subject to lifelong transfusion dependency. The CDA registry (CDAR) in North America (NCT02964494) was established to allow natural history studies on patients with CDA. Participants without a genetic diagnosis are offered whole genome sequencing (WGS) for patients and parents and may elect to provide samples to the CDAR biorepository to support collaborative mechanistic studies. Currently 169 subjects from 73 different families are enrolled in CDAR (85 patients, 84 unaffected family members). After genetic evaluation, 13 patients were found to be affected not by CDA, but rather by other causes of hereditary hemolytic anemia with secondary dyserythropoiesis. Three patients were diagnosed with pyruvate kinase deficiency (PKD). Patient (pt) 1 had a history of chronic anemia requiring sporadic transfusions since birth and was diagnosed with CDA-II based on BM studies. WGS revealed that the patient was heterozygous for a known PKLR pathogenic variant c.1022G&amp;gt;C p.(Gly341Ala)and for a novel variant of uncertain significance (c.695-3C&amp;gt;G).PK activity assay confirmed the diagnosis of PKD and the patient is now treated with the PK activator mitapivat. Pt 2 had severe transfusion dependent anemia since birth and iron overload. The patient underwent splenectomy at the age of 4 with mild improvement of symptoms. He was diagnosed with CDA II based on BM pathology. Genetic testing was performed and he was found to be compound heterozygous for 2 pathogenic variants in PKLR: c.644dup p.(Arg216fs) and c.994_1003dup p.(Val335fs). Pt 3 had a history of anemia and jaundice since birth; she has not had frequent transfusions but was splenectomized at age 17. The patient was found to be homozygous for c.1436G&amp;gt;A p.(Arg510Gln), a known pathogenic variant in PKLR. Four patients were diagnosed with HBB pathogenic variants causing frameshift and transcription of an elongated β-globin chain, i.e. unstable hemoglobinopathy. Pt 4 was first diagnosed with CDA II at 12 years of age based on BM studies performed due to chronic hemolytic anemia. After enrolling in CDAR, WES revealed heterozygous HBB p.(Lys96Asnfs*63). Pts 5, 6, and 7 are all symptomatic participants from the same family (mother and children). The mother (Pt 5) had frequent transfusion requirement, misdiagnosed in childhood as CDA IV due to BM dyserythropoiesis and the finding of high fetal hemoglobin. Her children had a similar phenotype requiring episodic transfusions initially, transitioning to scheduled transfusions by 8 y.o. WES in pt 5 revealed heterozygous HBB c.348_349delinsG (Hb Grand Junction) with follow-up HBB sequencing confirming that the children also carry the same variant . Three more patients were diagnosed with SPTA1 variants causing RBC membrane disorders. Pt 8 was found to have homozygous c.4339-99C&amp;gt;T (alpha-LEPRA) and heterozygous c.4347G&amp;gt;T p.(Lys1449Asn) with a phenotype of hereditary spherocytosis. Pts 9 and 10 are sisters, who presented with chronic, transfusion-dependent anemia since birth. They were diagnosed with CDA-II based on binucleated erythroblasts in BM studies performed in early childhood. They had splenectomy at 5 years of age and became transfusion-independent but continued to have mild anemia and reticulocytosis. WGS performed for them and their parents revealed a novel homozygous intronic variant in SPTA1 c.5834-18A&amp;gt;G. Phenotypic analysis was compatible with hereditary spherocytic pyropoikilocytosis. Hemolytic anemias with stress erythropoiesis may mimic the clinical presentation and pathologic findings of CDAs, making the phenotypic diagnosis challenging. Including genetic evaluation in the diagnostic workup of these patients can improve accuracy, timing of diagnosis, and management by specific therapy, if available.

73 Identification of 24-Month Cognitive Trajectories Among Clinical High Risk for Psychosis (CHR-P) Using Latent Class Mixture Modeling

Objective:Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.Participants and Methods:Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning &amp; problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (&gt;5%).Results:A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).Conclusions:Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

Abstract 091: Intraventricular milrinone for management of vasospasm following aneurysmal subarachnoid hemorrhage

Introduction Aneurysmal subarachnoid hemorrhage (aSAH) accounts for about 10% of hemorrhagic strokes [1] and holds a high mortality and morbidity rate. [2, 3] Vasospasm is one of the more devastating complications of aSAH. Novel imaging modalities have drastically improved our ability in prompt detection of vasospasm in these patients. However, clinical management of this complication is still debated among experts. [4] Systemic cerebral vasodilators are widely used in aSAH patients, but guidelines for interventional and rescue procedures are not well developed. [5] Methods Here, we report a case of severe vasospasm following aSAH that was successfully treated with intraventricular injection of milrinone through external ventricular drain (EVD) in conjunction to standard therapy. Results A 70‐year‐old man with a history of diabetes, hypertension, and hyperlipidemia was brought to the emergency department after he was found down and unresponsive. He was intubated by EMS on route. Head CT on arrival showed a diffuse subarachnoid hemorrhage, more prominent in the posterior fossa, and grade IV on the modified Fisher scale. An initial DSA showed a ruptured aneurysm in the second segment of the right posterior inferior cerebellar artery, second segment. A right frontal EVD was placed on the second day. Hemodynamic augmentation was achieved with intravenous and intraventricular milrinone. Cerebral arterial patency was evaluated with daily transcranial doppler (TCD). The patient did not show any evidence of vasospasm until day 9 where TCD revealed severe vasospasm in the basilar and bilateral vertebral arteries, as well as mild vasospasm of anterior and middle cerebral arteries. Intraventricular milrinone was injected into the EVD in from day 9 to day 12. Using sterile technique, 4 mL of CSF was removed followed by the injection of 0.87mg (2mL) of milrinone into the EVD via a three way stop cock. EVD was then flushed with 2mL of preservative‐free saline and clamped for 1 hour. This procedure effectively improved vasospasm on serial TCDs and also DSAs (Figure1). The patient underwent several DSA’s on days 10, 14, 19, 20, and 21 with targeted intraarterial milrinone and verapamil injections. His final TCD showed only mild middle cerebral artery and moderate basilar artery vasospasm. At that point, no more intervention was deemed necessary. A ventriculoperitoneal shunt was also placed. CT scan before discharge showed mild improvement in ventricular size and stable SAH blood products. The course of hospitalization was complicated by hyponatremia, atrial fibrillation, and respiratory failure with inability to wean off ventilator, resulting in tracheostomy and gastrostomy tube placement. The patient was discharged in stable condition on day 30 to a rehabilitation center. Conclusion Intraventricular milrinone in addition to standard therapy can be an effective method in treatment of severe vasospasm in aSAH patients.

71 Neuropsychological Intervention for Developmental Stuttering using Delayed Auditory Feedback Application

Objective:Brain science demonstrates that people who stutter (PWS) exhibit insufficient activation in the auditory speech area of the left hemisphere (Kikuchi, et al. 2011 ; Garnett, et al. 2018). In this study, we reported the auditory brainstem response of PWS: in PWS with moderate and severe impairment, significantly longer interpeak latencies (IPLs) between waves I and V (IPL [I-V]) of the right ear than those of the left ear were observed. However, in PWS with mild impairment, the IPLs (I-V) of the left ear were significantly longer than those of the right ear (Anzaki et al., 2020). We considered that the differences in the IPLs (I-V) between the right and left ears cause monitoring disturbance in communication, which results in developmental stuttering. It has been reported that stuttering was improved by delayed auditory feedback (DAF) (Stromsta, 1956; Sakai, 2008). Thus, we improved the DAF system and developed an application that can be used by PWS to listen to their own voices with no differences in the IPLs (I-V) between their left and right ears. We verified the effectiveness of this application.Participants and Methods:This study included five male adults with developmental stuttering (ADSs), with a mean age and handedness index of 36 years and 84, respectively. The application was adjusted so that the IPLs (I-V) of the left and right ears were the same. For example, one ADS showed that the IPL (I-V) of their right ear was 0.5 msec longer than that of their left. Subsequently, the application was adjusted so that the IPL (I-V) of his left ear would be delayed by 0.5 msec. We asked the participants to use the application for six months when free talking and reading aloud. Using the Japanese Standardized Test for Stuttering (JSTS) (Ozawa, et al. 2013), we compared their disfluencies with and without the application.Results:As per the JSTS, the stuttering severity in all participants improved. Case 1, who had severe impairment (level 5), showed a moderate improvement (level 4), Cases 2 and 3, who had moderate impairment (level 4), showed a mild improvement (level 3), and Cases 4 and 5, who had mild impairment (level 3), exhibited a normal level of improvement (level 1). We calculated the z-scores of the improvement rates of the JSTS based on the standard deviations according to the severity (Anzaki, 2019). The z-scores of Case 4 and 5 were 4.01 and 2.01, respectively, indicating a significant improvement.Conclusions:In our report last year, although ADSs with moderate and severe impairment showed improvement by stimulation intervention on the left hemisphere through the right ear, those with mild impairment exhibited only a slight or no improvement as per the JSTS (Anzaki, et al. 2021). The application developed in this study was found to significantly improve the disfluencies of all the participants as per the JSTS, especially those with mild impairment. Therefore, we considered that stuttering disorders are layered; ADSs have auditory monitoring disorder in the base.

Softskill Improvement Workshop and Millennial Generation Digital Literacy at SMK YP Fatahillah 2 Cilegon City, Banten Province

The millennial generation faces an increasingly complex and ever-evolving environment, especially regarding digital technology and social interaction. The increase in soft skills and digital literacy is significant so that they can succeed in adapting well to this changing world. Workshop material includes understanding the importance of soft skills in the work environment and daily life. To analyze the impact of mild skill improvement such as interpersonal communication, collaboration, and creativity, as well as digital literacy, which includes the ability to use and analyze digital technology wisely. This community service activity aims to provide the millennial generation insight, knowledge, and skills in increasing soft skills such as communication effectiveness, teamwork, creativity, and digital literacy. The SMK Fatahillah 2 Cilegon City activity involved class XII students who became partners in community services. The Methods used are lectures, discussions, and an interactive approach involving participants in various activities, such as role-playing, simulations, and question-and-answer sessions. Completing the training has positively impacted the millennial generation’s development, where students could increase their insight into soft skills and digital literacy. They become better prepared for rapid changes, can take the initiative in learning, and have a higher awareness of security and privacy issues in the digital world. Increasing soft skills and digital literacy is necessary for the millennial generation to succeed in various aspects of life.

Subthalamic nucleus physiology is correlated with deep brain stimulation motor and non-motor outcomes.

Subthalamic nucleus deep brain stimulation is commonly indicated for symptomatic relief of idiopathic Parkinson's disease. Despite the known improvement in motor scores, affective, cognitive, voice and speech functions might deteriorate following this procedure. Recent studies have correlated motor outcomes with intraoperative microelectrode recordings. However, there are no microelectrode recording-based tools with predictive values relating to long-term outcomes of integrative motor and non-motor symptoms. We conducted a retrospective analysis of the outcomes of patients with idiopathic Parkinson's disease who had subthalamic nucleus deep brain stimulation at Tel Aviv Sourasky Medical Centre (Tel Aviv, Israel) during 2015-2016. Forty-eight patients (19 women, 29 men; mean age, 58 ± 8 years) who were implanted with a subthalamic nucleus deep brain stimulation device underwent pre- and postsurgical assessments of motor, neuropsychological, voice and speech symptoms. Significant improvements in all motor symptoms (except axial signs) and levodopa equivalent daily dose were noted in all patients. Mild improvements were observed in more posterior-related neuropsychological functions (verbal memory, visual memory and organization) while mild deterioration was observed in frontal functions (personality changes, executive functioning and verbal fluency). The concomitant decline in speech intelligibility was mild and only partial, probably in accordance with the neuropsychological verbal fluency results. Acoustic characteristics were the least affected and remained within normal values. Dimensionality reduction of motor, neuropsychological and voice scores rendered six principal components that reflect the main clinical aspects: the tremor-dominant versus the rigidity-bradykinesia-dominant motor symptoms, frontal versus posterior neuropsychological deficits and acoustic characteristics versus speech intelligibility abnormalities. Microelectrode recordings of subthalamic nucleus spiking activity were analysed off-line and correlated with the original scores and with the principal component results. Based on 198 microelectrode recording trajectories, we suggest an intraoperative subthalamic nucleus deep brain stimulation score, which is a simple sum of three microelectrode recording properties: normalized neuronal activity, the subthalamic nucleus width and the relative proportion of the subthalamic nucleus dorsolateral oscillatory region. A threshold subthalamic nucleus deep brain stimulation score >2.5 (preferentially composed of normalized root mean square >1.5, subthalamic nucleus width >3 mm and a dorsolateral oscillatory region/subthalamic nucleus width ratio >1/3) predicts better motor and non-motor long-term outcomes. The algorithm presented here optimizes intraoperative decision-making of deep brain stimulation contact localization based on microelectrode recording with the aim of improving long-term (>1 year) motor, neuropsychological and voice symptoms.

THU366 Type 1 Diabetes Complicated By Multiple Episodes Of Diabetic Ketoacidosis Secondary To Flares Of Hidradenitis Suppurativa

Abstract Disclosure: S.R. Vasavada: None. K.A. Chopra: None. L. Philipson: Grant Recipient; Self; Novo Nordisk. Background: Hidradenitis suppurativa (HS) is an inflammatory skin condition of the pilosebaceous unit characterized by subcutaneous nodules that if untreated can form purulent abscesses, fistulae, and sinus tracts. HS may result from dysregulated autoimmune response to skin flora with overexpression of inflammatory cytokines, such as IL-17A, TNF-a, IL-1B (Shah et al 2017). Although HS and type 1 diabetes both share underlying autoimmune etiologies, and autoimmune diseases have been reported in higher frequencies in HS than controls, co-incidence with type 1 diabetes is extremely rare (Straalen et al 2022). Herein, we describe a case of a patient with type 1 diabetes with recurrent admissions for diabetic ketoacidosis (DKA) secondary to HS flares. Clinical Case: 37-year-old female with medical history of type 1 diabetes, hypogammaglobulinemia, and HS presented with rectal pain and hematochezia. Previously, she had several hospitalizations due to HS flares complicated by episodes of DKA and 20+ corrective surgeries for infected HS lesions. Prior to admission, patient was treated with clindamycin lotion, spironolactone, and weekly adalimumab for HS. Patient’s initial labs showed DKA with glucose 494 mg/dL (RR 60-99 mg/dL), bicarbonate 21 mmol/L (RR 23-30 mmol/L), anion gap 16 mmol/L (RR 6-15 mmol/L), and beta hydroxybutyrate level 1.44 mmol/L (N &amp;lt;0.3 mmol/L). Hemoglobin A1c was 10.4% (RR &amp;lt;5.7%). Physical exam showed Hurley Stage 2 HS with multiple atrophic scars, boils, and double comedones on bilateral axillae. She was treated with insulin infusion and IV fluids. After anion gap closed and bicarbonate improved to 24 mmol/L (RR 23-30 mmol/L), she transitioned to regimen of insulin glargine 38 units and started mealtime insulin lispro using a ratio of 1 unit of lispro for 6 grams of carbs. Subsequent glucose values stabilized, ranging 120-200 mg/dL (RR 60-99 mg/dL) during hospitalization. She underwent colonoscopy due to concern for colonic involvement of HS, however pathology was normal. After multidisciplinary discussion with endocrinology and dermatology specialists, HS treatment with prednisone was avoided due to concern of worsening patient’s glycemic control. Patient started infliximab treatment and reported mild symptom improvement. Conclusion: This case showing a patient with multiple episodes of DKA triggered by flares of HS has demonstrated the importance of further study to improve our current understanding of the potential overlap of these two conditions to help guide future treatment decisions and improve patients’ overall quality of life. Reference: Shah A, Alhusayen R, Amini-Nik S. The critical role of macrophages in the pathogenesis of hidradenitis suppurativa. Inflamm Res. 2017;66(11):931-945. Straalen KR van, Prens EP, Gudjonsson JE (2022) Insights into hidradenitis suppurativa. J Allergy Clin Immun 149(4):1150–1161. Presentation: Thursday, June 15, 2023

FRI572 Teprotumumab In Unexplored Presentation Of Thyroid Eye Disease

Abstract Disclosure: M.T. Torres Torres: None. A.N. Gonzalez Bossolo: None. M.M. Mangual Garcia: None. Thyroid eye disease (TED) is an autoimmune disease of the orbital soft tissue associated with facial disfigurement, diminished quality of life, and potentially vision-threatening consequences that can occur in 40% of patients with Graves’ disease (GD). All the therapies for this condition were off-label with questionable long-term effects until 2020 when the Federal Drug Administration approved teprotumumab, a human monoclonal antibody against insulin-like growth factor-1 receptor, for the treatment of TED. Randomized placebo-controlled trials have demonstrated that teprotumumab reduces proptosis, diplopia, and Clinical Activity Score (CAS) in patients with active TED of less than 1.3 years of duration who were treatment-naïve or previously treated with &amp;lt; 1g of methylprednisolone equivalent therapy. Data on the efficacy of teprotumumab on cases of longer TED duration or previously treated with eye surgery or &amp;gt; 1g of methylprednisolone equivalent therapy for TED is limited as these patients were excluded from the trials. A 76-year-old nonsmoker male with long-standing hyperthyroidism due to GD, glaucoma, and type 1 diabetes mellitus was referred by ophthalmologist due to TED. He received radioactive iodine (RAI) for treatment of GD after failure to Methimazole therapy. After RAI, he reported progressively worsening bilateral eye edema, redness, pain, vision loss, and diplopia requiring hospitalization for an emergent orbital decompressive surgery and intravenous steroid therapy due to sight-threatening Grave’s orbitopathy. He was discharged home with oral prednisone taper down until it was discontinued 6 months later with mild improvement of symptoms. Physical exam was remarkable for bilateral strabismus, orbital chemosis, conjunctival injection and redness, eyelid swelling, limited eye motion, severely impaired visual acuity and color vision, no proptosis, and a CAS of 5 suggesting active TED. Laboratories showed biochemical euthyroidism and controlled glycemia. Teprotumumab was started 2 years and 8 months after symptom onset with marked improvement of inflammatory signs and symptoms, eye motion, visual acuity, diplopia, intraocular pressure, and CAS score decrease to 1 point suggesting inactive disease within 4 weeks of therapy without adverse side effects. This case describes the positive effects of teprotumumab in a patient with characteristics not previously studied such as active TED of longer duration than in clinical trials, previous treatment with orbital surgery or &amp;gt; 1g of methylprednisolone equivalent therapy, and increased IOP. Rather than drawing conclusions, our goal is to create awareness and promote further research of teprotumumab and novel agents in patients with TED with previously uncharacterized presentations as it may have important implications for their management including significant improvement in their quality of life. Presentation: Friday, June 16, 2023

THU289 Hemichorea-Hemiballismus Syndrome Secondary To Steroid Induced Hyperglycemia In A Nondiabetic

Abstract Disclosure: E. Krishnaraju: None. K.N. Patolia: None. U.A. Ogar: None. S. Karki: None. A.G. Olafimihan: None. Introduction: Hemichorea-Hemiballismus syndrome (HCHB) associated with nonketotic hyperglycemia is a rare cause of acute to subacute acquired chorea. The syndrome is usually characterized by unilateral choreiform movements, poorly controlled diabetes mellitus, and striatal abnormalities on an MRI of the brain. Clinical Case: This is a case of a 70-year-old man with a history of congestive heart failure, hypertension, remote ischemic stroke, asymptomatic Paget's disease of the bone, chronic kidney disease, and statin-induced necrotizing myositis. Five months before his presentation, the patient was initiated on prednisone for myositis. On presenting to the ED, he had near resolution of his limb weakness from myositis but complained of one month of right-sided continuous involuntary tremors involving the right upper limb, lower limb, and face that resolved during his sleep. There was no family history of neurologic disorders or any history to suggest medication or illicit drug-induced movement disorders. On examination, the patient had normal cognitive functions and vital signs. Neurologic examination was remarkable for quick interspersed moderate amplitude choreiform movements of the right hand, forearm, proximal arm muscles, and right leg. Laboratory results revealed hyperglycemia and a newly elevated Hemoglobin A1c of 8.5, which was normal the year before. Infectious, hematologic, thyroid disease, and Wilson's disease workups were negative. Cerebrospinal fluid (CSF) analysis was remarkable for elevated glucose and identical oligoclonal bands in the serum and CSF, possibly suggestive of a nonspecific chronic systemic inflammatory state. Autoantibodies for paraneoplastic syndromes and autoimmune diseases, including autoimmune encephalitis were negative. There was also no evidence of occult malignancy on CT imaging of the chest, abdomen, and pelvis. MRI/MRA was significant for new small foci of susceptibility artifact in the bilateral basal ganglia, left cerebellar hemisphere, and cerebellar vermis, likely from chronic microvascular changes. The constellation of hemichorea and new onset hyperglycemia in the setting of a largely nondiagnostic workup raises suspicion for HBHC syndrome. Previous studies have found classic T1-weighted MRI hyperintensities in the basal ganglia, but normal imaging does not rule out a diagnosis of diabetic striatopathy. The patient was eventually discharged with mild improvement of his chorea after starting insulin and risperidone. Unfortunately, he was lost to follow-up and unexpectedly died of an unclear cause soon after. Conclusion: Metabolic complications of diabetes can manifest in complex ways. Non-ketotic hyperglycemic HCHB due to diabetic striatopathy is a rarely reported entity that is commonly misdiagnosed. This case is a unique presentation in a non-diabetic patient with steroid-induced hyperglycemia. Presentation: Thursday, June 15, 2023

THU356 Muscle Pain In A Diabetic: Think Outside The Box

Abstract Disclosure: R. Ellangovan: None. M. Rizk: None. V. Singh MD: None. C. Sherpa: None. Introduction: Stiff person syndrome (SPS) is a rare immunological disorder associated with GAD antibody-spectrum disorders and characterized by rigidity and painful muscle spasms. SPS has a prevalence of 1-2 cases per million and affects females more than men. We present a case of SPS who was admitted for progressive muscle pain and rigidity causing impaired ambulation. Case Presentation: A 60-year-old female with a two-year history of type 2 diabetes, Graves' disease was diagnosed with acral lentiginous melanoma of the left foot. One month after Nivolumab immunotherapy, she converted to type 1 diabetes with low C-peptide and positive GAD antibody. She was admitted with severe muscle pain and spasms in her lower extremities and trunk, debilitating enough to make her bedbound. Her muscle strength and sensory function were intact. MRI of thigh was concerning for myositis versus diabetic myonecrosis. She was initiated on NSAIDs with no improvement. Core muscle biopsy revealed necrosis and granulation tissue with no evidence of malignancy. Extensive work up including myositis panel and myasthenia gravis panel were negative. The presence of GAD antibodies and no improvement to NSAIDs, prompted suspicion for SPS. The patient declined lumbar puncture (LP) for further evaluation. Diazepam showed mild improvement. Due to persistent severe symptoms, she was treated with IVIG for 5 days that resulted in marked improvement. Discussion: There is no gold standard test for definitive diagnosis of SPS. Classic features of SPS include muscle spasms, pain, and rigidity typically involving the trunk and lower extremities. There are GAD antibodies in serum and CSF and glycine receptor or amphiphysin antibodies. EMG study will show continuous motor unit activity in affected muscles. A robust response to muscle relaxants like GABA agonists and exclusion of alternative neurological disorder favors SPS. LP or EMG was not performed on this patient, yet she met other criteria including the presence of other GAD disorders like type 1 diabetes. Current recommended therapy for symptomatic relief includes GABA agonists or baclofen. If no improvement is noted, IVIG can be considered. Plasmapheresis and rituximab have been used with variable efficacy. Prognosis is variable and many patients experience disability despite combining multiple therapies. Hence it is crucial to have a high index of suspicion in GAD spectrum disorders for early recognition and prompt treatment. Presentation: Thursday, June 15, 2023

The COVID-19 Pandemic Had a Positive Impact on Patients with Allergic Rhinitis

Introduction: Allergic rhinitis is one of the most common chronic conditions affecting all age group and it is characterized by sneezing, nasal congestion, and rhinorrhea. In some cases, conjunctivitis also occurs up on expose to a variety of irritants like pollen, duct, perfumes, and weather changes. Aim: This study evaluates the impact of COVID19 pandemic and quarantine on patients with allergic rhinitis sign and symptoms. Results: The study was conducted in the Kingdome of Saudi Arabia and 740 participants returned the online questionnaire. of those, 596 (80.5%) identified dust and weather changes as the main irritants to their symptoms, and 440 (59.5%) experienced sneezing as the main symptoms before COVID-19 pandemic. Only 89 (12%) reported symptoms relief by 90-100% during lockdowns and curfew periods. There was a significantly lower rate of medication use during the pandemic (28.32%) compared to the time before the pandemic (50.93%). During the COVID-19 pandemic, of the respondents 271 (36%) reported no improvement, 179 (23.8%) had mild improvements, 131 (17.4%) reported a moderate improvement, and 171 (22.7%) reported a significant improvement. Conclusion: The study showed that 40% of the participants had moderate to significant symptomatic relief during the periods of lockdowns and curfew of the COVID-19.