Missed opportunities to identify cryptococcosis in COVID-19 patients: a case report and literature review

SARS-CoV-2 may activate both innate and adaptive immune responses ultimately leading to a dysregulated immune response prompting the use of immunomodulatory therapy. Although viral pneumonia increases the risk of invasive fungal infections, it remains unclear whether SARS-CoV-2 infection, immunomodulatory therapy, or a combination of both are responsible for the increased recognition of opportunistic infections in COVID-19 patients. Cases of cryptococcosis have previously been reported following treatment with corticosteroids, interleukin (IL)-6 inhibitors, and Janus kinase (JAK) inhibitors, for patients with autoimmune diseases, but their effect on the immunologic response in patients with COVID-19 remains unknown. Herein, we present the case of a patient with COVID-19 who received high-dose corticosteroids and was later found to have cryptococcosis despite no traditional risk factors. As our case and previous cases of cryptococcosis in patients with COVID-19 demonstrate, clinicians must be suspicious of cryptococcosis in COVID-19 patients who clinically deteriorate following treatment with immunomodulatory therapies.

Teaching a Multi-Step Requesting Sequence to Two Adolescents with Autism Using an iPod-based Speech Generating Device

<p>Many children with autism fail to develop speech and are therefore candidates for the use of speech-generating devices (SGDs). However, existing studies are limited because they have tended to focus only on teaching an initial single-step requesting sequence. This thesis aimed to extend the existing literature by evaluating intervention procedures for teaching two adolescents with autism to perform multistep requesting sequences that required navigating across two screen pages (Intervention 1). Intervention 2 focused on teaching the adolescents to turn on and unlock the screen of the SGD prior to initiating the previously learnt multi-step requesting sequence. Both interventions made use of response prompting, prompt fading, and differential reinforcement procedures and were evaluated using the multiple-baseline across subjects design. Results showed that both interventions were effective in teaching these adolescents to use the iPod Touch(R) to make a sequence of requests. The results of the present study suggest that adolescents with autism can successfully learn to use an iPod Touch(R) to independently perform multi-step requesting sequences.</p>

Teaching a Multi-Step Requesting Sequence to Two Adolescents with Autism Using an iPod-based Speech Generating Device

<p>Many children with autism fail to develop speech and are therefore candidates for the use of speech-generating devices (SGDs). However, existing studies are limited because they have tended to focus only on teaching an initial single-step requesting sequence. This thesis aimed to extend the existing literature by evaluating intervention procedures for teaching two adolescents with autism to perform multistep requesting sequences that required navigating across two screen pages (Intervention 1). Intervention 2 focused on teaching the adolescents to turn on and unlock the screen of the SGD prior to initiating the previously learnt multi-step requesting sequence. Both interventions made use of response prompting, prompt fading, and differential reinforcement procedures and were evaluated using the multiple-baseline across subjects design. Results showed that both interventions were effective in teaching these adolescents to use the iPod Touch(R) to make a sequence of requests. The results of the present study suggest that adolescents with autism can successfully learn to use an iPod Touch(R) to independently perform multi-step requesting sequences.</p>

RNA Methylation in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with complicated clinical manifestations. Although our understanding of the pathogenesis of SLE has greatly improved, the understanding of the pathogenic mechanisms of SLE is still limited by disease heterogeneity, and targeted therapy is still unavailable. Substantial evidence shows that RNA methylation plays a vital role in the mechanisms of the immune response, prompting speculation that it might also be related to the occurrence and development of SLE. RNA methylation has been a hot topic in the field of epigenetics in recent years. In addition to revealing the modification process, relevant studies have tried to explore the relationship between RNA methylation and the occurrence and development of various diseases. At present, some studies have provided evidence of a relationship between RNA methylation and SLE pathogenesis, but in-depth research and analysis are lacking. This review will start by describing the specific mechanism of RNA methylation and its relationship with the immune response to propose an association between RNA methylation and SLE pathogenesis based on existing studies and then discuss the future direction of this field.

Severe immune thrombocytopenic purpura after SARS-CoV-2 vaccine

Immune thrombocytopenic purpura (ITP) is a rare hematologic condition through to affect 3.3 in 100,000 adults per year in the United States. Many cases of immune thrombocytopenia are diagnosed incidentally with laboratory tests that reveal low platelet count, without a clear cause. However, when platelet counts are very low, patients may show signs of bleeding. Here we present the case of a 24-year-old female with mucocutaneous bleeding ten days after receiving her first dose of SARS-CoV-2 vaccine, who was subsequently found to have severe thrombocytopenia. Extensive work up for new thrombocytopenia was unremarkable suggesting a diagnosis of ITP, potentially secondary to vaccination. Empiric treatment with glucocorticoids was initiated without response prompting the use of intravenous immunoglobulin G. The patient was discharged on hospital day five with a platelet count over 20,000 platelets per microliter. In summary, ITP is a potential sequela of the SARS-CoV-2 vaccine, and otherwise healthy young individuals may be at risk for hematologic side effects.

Subcutaneous EEG Monitoring Reveals AED Response and Breakthrough Seizures

Unrecognized seizures are a common problem in temporal lobe epilepsy potentially leading to undertreatment. Objective seizure counting using EEG home monitoring for prolonged periods with a minimally invasive device has not been feasible until now. We present a case in which a novel, subcutaneous EEG device was utilized to provide an objective seizure count. This information revealed unrecognized breakthrough seizures and informed treatment response, prompting treatment adjustment. The case illustrates how objective seizure counting in epilepsy using new devices can completely change diagnosis and management.

Complement blockade for TA-TMA: lessons learned from large pediatric cohort treated with eculizumab

Overactivated complement is a high-risk feature in HSCT recipients with transplant associated thrombotic microangiopathy (TA-TMA), and untreated patients have dismal outcomes. We present our experience of 64 pediatric HSCT recipients with high risk TA-TMA and multi-organ injury treated with the complement blocker eculizumab. We demonstrate significant improvement in 1y post-HSCT survival to 66% in treated patients from our previously reported untreated cohort with same high-risk TA-TMA features that had 1y post-HSCT survival of 16.7%. Responding patients benefited from a brief but intensive eculizumab therapy course using PK/PD guided dosing, requiring a median of 11 doses of eculizumab (IQR 7-20). Therapy was discontinued due to resolution of TA-TMA at a median of 66 days (IQR 41-110). Subjects with higher complement activation measured by elevated blood sC5b-9 at the start of therapy were less likely to respond to treatment (OR =0.15, p-value 0.0014), and required more doses of eculizumab [r = 0.43, p-value = 0.0004]. Patients with intestinal bleeding had the fastest eculizumab clearance, required the highest number of eculizumab doses (20 vs 9, p=0.0015), and had lower 1y survival (44% vs 78%, p=0.01). Over 70% of survivors had proteinuria on long term follow up. The best GFR recovery in survivors was a median 20% lower (IQR 7.3-40.3%) than their pre-HSCT GFR. In summary, complement blockade with eculizumab is an effective therapeutic strategy for high risk TA-TMA, but some patients with severe disease lack a complete response, prompting us to propose early intervention strategies and search for additional targetable endothelial injury pathways.

Teaching Sequences of Pretend Play to Children With Disabilities

Children with disabilities demonstrate fewer complex pretend play behaviors than children with typical development, which might limit their social participation in early childhood settings. A multiple-probe design was used to examine the relation between a single prompt procedure—constant time delay—and the acquisition, maintenance, and generalization of sequences of pretend play by children with disabilities. Results indicated systematic instruction was functionally related to increased levels of unprompted and different sequences of pretend play in all three participants. However, individual adaptations were required for two of three participants. The findings replicate previous research on adult systematic instruction using response-prompting strategies to teach pretend play and extend the literature by measuring and reporting generalized sequences of pretend play. Overall, this study supports systematic, individualized instruction using response-prompting strategies to teach sequences of pretend play to children who do not display such behaviors.