Rapid Clinical Response Research Articles

Late onset pancytopenia post chimeric antigen receptor T cell therapy triggered by a COVID-19 vaccination: a case report

Cytopenia is a common side effect after chimeric antigen receptor T cell (CAR-T) therapy but is unusual at late timepoints when it is most commonly due to bone marrow (BM) failure, myelodysplasia (MDS) or other secondary malignancies. In this case report, we describe a patient who developed severe aplastic anaemia 18 months after CD19 CAR-T therapy, and shortly after COVID-19 vaccination. This is the first description of severe aplastic anaemia triggered by COVID-19 vaccination as a cause of post-CAR-T cytopenia. The patient described was treated with a combination of eltrombopag and ciclosporin due to frailty and had a rapid and complete clinical response to this therapy, providing an effective option for the treatment of immune-related cytopenia post-CAR-T in an increasingly elderly and frail population.

Pimecrolimus Efficacy and Safety in Management of Children with Atopic Dermatitis

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. Early management of AD is crucial for preventing the development of atopic disease such as asthma, allergic rhinitis, etc. Topical glucocorticoids (TGCs) are used as first-line therapy, however, their long-term use poses the risk for patient's health. Despite the rapid clinical response at skin process aggravation, long-term use of TGCs in first-line therapy is associated with various adverse events, including: skin atrophy, hypothalamic-pituitaryadrenal axis suppression, telangiectasis, etc. All together it limits the long-term TGCs use, especially in management of pediatric patients and using such drugs in sensitive regions such as face and intertriginous areas. Due to these limitations TGCs should only be used for a short period of time. Thus, limitations in both treatment duration and number of drugs make TGCs non-optimal for long-term AD treatment. Pimecrolimus (1% cream) is a topical calcineurin inhibitor that is indicated for the treatment of mild to moderate AD. Pimecrolimus does not cause any significant side effects compared to TGCs and it is well tolerated for long-term administration.

IgE immunoadsorption: technical background, functionality, and first clinical experience

Summary Background The prevalence of allergic diseases has risen in the 21st century, drawing attention to specific therapeutic and preventive strategies. Due to the key role of immunoglobulin E (IgE) in the development of allergic reactions, IgE represents a key target treatment. In this scenario, IgE immunoadsorption (IgE-IA) has been investigated as a procedure that selectively removes circulating IgE antibodies from the bloodstream of patients with atopy. Methods This narrative review aims to critically summarize the current insights regarding IgE-IA in the context of the management of allergic diseases, ranging from the rationale to the technical aspects, as well as the benefits and unmet needs. Results IgE-IA might be a treatment strategy in well-selected patients with allergic diseases. IgE depletion through sessions of IgE-IA results in immediate clinical improvement and might be useful in acute situations when a rapid clinical response is required or when classic approaches are contraindicated or ineffective. Due to the reduced effectiveness over time, IgE-IA could be a valid first approach before starting another IgE depletion therapy, such as omalizumab, when its commencement would otherwise be contraindicated by too-high serum IgE levels. Conclusion Overall, IgE-IA is safe and well tolerated; however, this procedure is currently difficult to implement in routine clinical practice because of costs, time demands, need for hospitalization, and the invasiveness of the procedure, with the associated risks related to the necessity of venous catheterization.

8288 Navigating Diagnostic Challenges of Amiodarone Induced Thyrotoxicosis in a Psychiatrically Complex Patient within a Community Hospital Setting

Abstract Disclosure: M.S. Shah: None. K.P. Sanu: None. S. Humayon: None. R. Chawla: None. N.K. Bains: None. This case delves into the intricate diagnostic and therapeutic journey of a 64-year-old male who presented to a community hospital with psychosis. Medical history was pertinent for ventricular arrhythmias treated with amiodarone 400 mg once daily, bipolar disorder with medication non-compliance and heart failure with reduced ejection fraction status post automatic implantable cardioverter-defibrillator placement. Collaboration with the patient's family revealed a history of repeated hospitalizations for similar presentations as well as recent weight loss. The challenge lay in distinguishing between manic episodes and other potential underlying medical causes. The patient's recent weight loss and amiodarone use prompted a thyroid panel, revealing a TSH of 0.01 mlU/L (n = 0.27 to 4.20 mIU/L), free T4 of >7.77ng/dL (n = 0.93 to 1.70 ng/dL), and free T3 of >7.51ng/dL (n = 2.00 to 4.40 pg/mL). Inadequate facilities for a radioactive iodine uptake (RAIU) scan and thyroid doppler ultrasound heightened the diagnostic challenge, making the history and physical exam pivotal in steering the course of this patient's care. The Burch-Wartofsky score was found to be elevated at 30 due to delirium and abdominal pain reported in the emergency department. Amiodarone use for over two years with no prior history of thyroid dysfunction, along with the absence of a goiter or thyroid antibodies suggestive of Graves disease heightened the suspicion for amiodarone-induced thyrotoxicosis type 2 (AIT type 2). Due to the lack of RAIU scan and thyroid ultrasound to better differentiate between AIT type 1 and type 2, the patient was treated with methimazole and prednisone along with an antipsychotic medication regimen. The discontinuation of antipsychotic medications became necessary due to QTc prolongation and subsequent defibrillator discharge. The patient's further improvement without psychiatric medications highlighted the success of the tailored treatment strategy, emphasizing the importance of accurate diagnosis in patients with psychiatric comorbidities. The patient’s relatively rapid clinical response also aids in differentiating AIT type 1 from type 2. This case brings awareness to the importance of a comprehensive history and physical exam, particularly in the setting of a community hospital with limited diagnostic resources. Despite the inability to obtain history directly from the patient and having diagnostic constraints, the judicious use of available resources and clinical acumen led to the diagnosis of Amiodarone-induced thyrotoxicosis type 2. Clinicians should keep a broad differential to avoid confirmation bias in treating psychiatric patients with a complex medical history. This case serves as a testament to the importance of a holistic approach to patient care and the need for ongoing advancements in diagnostic capabilities within community healthcare settings. Presentation: 6/2/2024

Colombian experience with the use of tofacitinib in severe acute ulcerative colitis: A case series study

IntroductionTofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. Materials and methodsDescriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. ResultsSix patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. ConclusionsTofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.

USE OF SGLT2–INHIBITORS IN THE TREATMENT OF ANTHRACICLINE CARDIOTOXICITY

Abstract The survival rate of cancer patients has significantly increased in the last 25 years thanks to the extraordinary advances in anti-tumor therapies. However, many chemotherapeutic agents are potentially cardiotoxic. In particular, anthracycline-induced cardiotoxicity is a clinical condition caused by chemotherapy drugs that lead to morpho-functional alterations and cell death of cardiomyocytes; the most typical clinical manifestation of this cardiotoxicity is the development of left ventricular dysfunction, which over time can evolve towards full-blown heart failure. It is therefore characterized by a reversible asymptomatic stage that progresses to an irreversible stage, often difficult to treat. For an early individualization of this toxicity, a dedicated clinic has been established in our center for the monitoring of patients undergoing treatment with cardiotoxic chemotherapy. We describe the case of a 53-year-old patient with preserved biventricular systolic function undergoing neoadjuvant treatment for breast cancer, who at the end of the second infusion of anthracyclines presented with mild exertional dyspnoea associated with radiological signs of pulmonary congestion and an increase in the indices of myocardionecrosis and BNP. The echocardiogram revealed a sudden worsening of the left ventricular systolic function which was 48%. It was therefore decided to hospitalize the patient and initiate infusional diuretic therapy with a rapid clinical and instrumental response. An SGLT2 inhibitor with indication for the treatment of heart failure with moderately reduced ejection fraction was also added to the therapy. At the one-month check-up, there was an almost complete recovery of left ventricular function and a clear symptomatic benefit with associated normalization of laboratory markers of myocardial damage and heart failure, with the possibility for the patient to undergo surgery to remove the left ventricle. tumor mass. This clinical case could represent a starting point to start considering therapy with SGLT2 inhibitors for the prevention and early treatment of cardiac toxicities from some chemotherapeutics, in order to avoid the process of irreversibility of myocardial damage with subsequent poor response to anti-inflammatory therapies. – conventional compensation.

Baricitinib for Prurigo Nodularis: A Pilot Study on Efficacy and Safety

Background. Breaking the itch-scratch cycle and facilitating lesion healing are pivotal in managing prurigo nodularis (PN). This study seeks to assess the efficacy of baricitinib, an oral JAK1/2 inhibitor, for treating PN. Methods. In this prospective pilot study, 12 patients with moderate to severe PN were administered oral baricitinib at a dosage of 4 mg/day for 12 weeks. The primary objective was to assess the efficacy of baricitinib in PN patients using the numeric rating scale (NRS) for pruritus, NRS sleep score, a 5-point investigator’s global assessment (IGA) scale, dermatology life quality index (DLQI), and nodular lesion count at weeks 0, 1, 2, 4, 8 and 12. In addition, the NRS pruritus and sleep scores were assessed via phone on days 2 and 4 after baricitinib treatment. Results. Baricitinib treatment led to a statistically significant improvement in the mean NRS pruritus and sleep scores, evident as early as day 2 (57.7% change from baseline; P<0.001, and 34.7% change from baseline, P=0.029, respectively) and consistently declining thereafter. Evaluation of nodular lesions revealed a significant reduction starting from week 2 (mean difference of 37.08 from baseline; P<0.001). Analysis of other endpoints, including mean DLQI and IGA scores, also demonstrated substantial improvement at all time points (week 1, 2, 4, 8, and 12) compared to baseline. However, it is important to acknowledge the limitation of a small sample size. This constraint warrants consideration when interpreting the results and generalizing the findings. Conclusion. This preliminary study underscores baricitinib’s potential for PN treatment by providing a rapid clinical response. The larger and longer randomized controlled trials are essential to determine the effectiveness, longevity, and safety of baricitinib in managing PN. This trial is registered with TCTR20230227002.

Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis.

Atopic dermatitis (AD) affects multiple areas of the body, some of which may be more refractory to treatment. We evaluated improvements in the Eczema Area and Severity Index (EASI) by body region and clinical signs for each body region in lebrikizumab-treated patients with moderate-to-severe AD. ADvocate 1 and ADvocate 2 compared lebrikizumab 250mg as monotherapy every 2weeks versus placebo for 16weeks. Efficacy measures included EASI, which rates the extent and severity of four clinical signs (erythema, edema/papulation, excoriation, lichenification) in four body regions (head/neck, upper extremities, trunk, lower extremities). Analyses are post hoc. Mean baseline EASI, body region EASI subscores, and the severity of clinical signs were consistent across both studies (EASI ranging from 16.0 to 72.0). At week 16 in both studies, patients treated with lebrikizumab showed significantly greater percent improvement in EASI across all body regions versus placebo (p ≤ 0.001), with improvements as early as week 2. In ADvocate 1, all clinical signs significantly improved across all body regions at week 16 with lebrikizumab (51.4-71.6% improvement) versus placebo (23.1-43.5%, p ≤ 0.001), with significant improvements as early as week 2 for all signs. Significant improvements for all clinical signs at week 16 were also seen in ADvocate 2 for lebrikizumab (53.5-75.6%) versus placebo (28.5-41.2%, p ≤ 0.001) and as early as week 2 for all body regions and signs except head/neck erythema and lower extremity erythema, edema/papulation, and lichenification, which showed significant improvement by week 4. Lebrikizumab as monotherapy consistently and rapidly reduced the extent of involvement and severity of AD in all EASI clinical signs and body regions, including the head and neck region and clinical sign of lichenification, compared with placebo. ClinicalTrials.gov identifier: ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967).

Efficacy of upadacitinib in the achievement of clinical and endoscopic remission in hospitalized patients with ulcerative colitis.

Janus kinase (JAK) inhibitors have been developed and are clinically available for management of active UC patients although most studies have been conducted for the outpatients and few studies have demonstrated its efficacy in endoscopic and histological remission of hospitalized patients with UC. The aim of the present study was to investigate the efficacy of upadacitinib, which is a novel selective JAK1 inhibitor, in the treatment of ulcerative colitis. We present the cases of three hospitalized patients with ulcerative colitis who achieved clinical remission after significant and rapid improvement with upadacitinib. While upadacitinib was used as the second-line treatment for patients with insufficient treatment effects for corticosteroids or ustekinumab, a patient received it just after admission because they were steroid dependent and previously used advanced therapy before hospitalization. All patients demonstrated rapid clinical responses within 7days and the partial Mayo scores were 0 at week 8. All patients achieved confirmed endoscopic and histological remissions. We conclude that upadacitinib is a potential treatment option for hospitalized patients with an inadequate response to other biologics and JAK inhibitors.

Add-on multiple submucosal injections of the RNA oligonucleotide GUT-1 to anti-TNF antibody treatment in patients with moderate-to-severe ulcerative colitis: an open-label, proof-of concept study

BackgroundCarbohydrate sulfotransferase 15 (CHST15) is an enzyme biosynthesizing matrix glycosaminoglycan that modulates tissue remodeling. We evaluated the efficacy of add-on submucosal injections of GUT-1, the RNA oligonucleotide inhibitor of CHST15, to ongoing anti-tumor necrosis factor (TNF) antibody treatment in patients with moderate-to-severe ulcerative colitis (UC).MethodsThis was an open-label study of 250 nM of GUT-1 by endoscopic submucosal injections at weeks 0, 2, 4 in five UC patients who lost response during maintenance treatment to anti-TNF antibodies. The primary endpoint was the rate of endoscopic improvement at week 6 and secondary endpoints included the rates of clinical remission by modified Mayo Score (mMS). Patients received follow-up observation with continuous maintenance treatment by the same anti-TNF antibody till the time of clinical recurrence or for overall 52 weeks.ResultsAt week 6, rates of endoscopic improvement and clinical remission were 80% (n = 4/5) and 60% (n = 3/5), respectively. The mean Endoscopy Subscore was reduced from 2.4 (95%CI: 1.7 to 3.1) at baseline, to 1.0 (95%CI: 0.1 to 1.9) at week 6. The mean mMS was reduced from 7.8 (95%CI: 6.2 to 9.4) to 1.3 (95%CI: 2.9 to 4.3). GUT-1 was well tolerated. Three patients did not show clinical recurrence for 52 weeks. All three corticosteroid-dependent patients showed no corticosteroid exposure for at least 24 weeks after achieving clinical remission. Multiple dosing was also well tolerated.ConclusionsAdd-on multiple injections of GUT-1 to ongoing anti-TNF antibody was able to induce rapid and durable clinical responses in UC patients who lost response to anti-TNF therapy.Trial registrationClinical trial Registration Number (Japan): UMIN000020900.

P904 Appendectomy for refractory ulcerative colitis: results of prospective observational study

Abstract Background Appendectomy is suggested to improve the course of the disease in many patients with refractory ulcerative colitis (UC). The present prospective observational study demonstrates middle-term outcomes after an appendectomy in 26 patients with refractory UC. Methods Between 5/2022 and 2/2023, 26 selected patients underwent appendectomy for refractory UC. Refractory UC was defined as a failure of at least one biologic therapy. Patients with Dysplasia or Cancer were excluded. The appendectomy was performed without the removal of the cecal base. Primary Endpoint of the study was the Mayo clinical score (MCS) at 6 months after the appendectomy. Secondary Endpoint was the “Treatment failure” which was defined as occurrence of one of the following events during the first 6 months after appendectomy: 1) high-dosed steroid treatment, 2) change of biologic treatment, 3) colectomy. Results Mean age was 35 years (18 to 59 years) and there were 11 female patients. 15 had a pancolitis (58%). Twelve were taking steroids (46%). Median number of biologic therapies taken by patients prior to surgery was 3 (range, 1-5). One patient underwent surgery for sever acute UC. The appendix appeared to be inflamed histologically in 16 patients (62%). Hospital stay was median 2 days, there was one wound infection at the port site and one postoperative hematoma. A significant improvement of disease symptoms was reported by 21 patients during the first 4 weeks (81%). At 6 months, MCS improved from mean 6.4 to 4.5 (p=0.057). Therapy failure was observed in 15 patients (58%) – two underwent colectomy, 11 needed at least one high-dose steroid treatment and biologic therapy was changed due to refractory symptoms in 9 patients. Intake of JAK-inhibitors at the time of appendectomy was the only factor to be associated with lower probability of treatment failure (30% vs. 75%, p=0.043). The only patient undergoing appendectomy for severe acute UC was free of symptoms 14 months after surgery. Conclusion The majority of patients with refractory UC demonstrated rapid clinical response to the appendectomy. After 6 months, more than 40% of patients did not experience disease flares necessitating intensification of treatment.

Adaptive Intervention to Prevent Respiratory Illness in Cerebral Palsy: Protocol for a Feasibility Pilot Randomized Controlled Trial.

This study will pilot-test an innovative just-in-time adaptive intervention to reduce severe respiratory illness among children with severe cerebral palsy (CP). Our intervention program, Respiratory Exacerbation-Plans for Action and Care Transitions (RE-PACT), delivers timely customized action planning and rapid clinical response when hospitalization risk is elevated. This study aims to establish RE-PACT's feasibility, acceptability, and fidelity in up to 90 children with severe CP. An additional aim is to preliminarily estimate RE-PACT's effect size. The study will recruit up to 90 caregivers of children with severe CP aged 0 to 17 years who are cared for by a respiratory specialist or are receiving daily respiratory treatments. Participants will be recruited from pediatric complex care programs at the University of Wisconsin-Madison (UW) and the University of California, Los Angeles (UCLA). Study participants will be randomly assigned to receive usual care through the complex care clinical program at UW or UCLA or the study intervention, RE-PACT. The intervention involves action planning, rapid clinical response to prevent and manage respiratory illness, and weekly SMS text messaging surveillance of caregiver confidence for their child to avoid hospitalization. RE-PACT will be run through 3 successively larger 6-month trial waves, allowing ongoing protocol refinement according to prespecified definitions of success for measures of feasibility, acceptability, and fidelity. The feasibility measures include recruitment and intervention time. The acceptability measures include recruitment and completion rates as well as intervention satisfaction. The fidelity measures include observed versus expected rates of intervention and data collection activities. The primary clinical outcome is a severe respiratory illness, defined as a respiratory diagnosis requiring hospitalization. The secondary clinical outcomes includehospital days and emergency department visits, systemic steroid courses, systemic antibiotic courses, and death from severe respiratory illness. The recruitment of the first wave began on April 27, 2022. To date, we have enrolled 30 (33%) out of 90 participants, as projected. The final wave of recruitment will end by October 31, 2023, and the final participant will complete the study by April 30, 2024. We will start analyzing the complete responses by April 30, 2024, and the publication of results is expected at the end of 2024. This pilot intervention, using adaptive just-in-time strategies, represents a novel approach to reducing the incidence of significant respiratory illness for children with severe CP. This protocol may be helpful to other researchers and health care providers caring for patients at high risk for acute severe illness exacerbations. ClinicalTrials.gov NCT05292365; https://clinicaltrials.gov/study/NCT05292365. DERR1-10.2196/49705.

A Controlled Clinical Study of Accelerated High-Dose Theta Burst Stimulation in Patients with Obsessive–Compulsive Disorder

Background. Obsessive–compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method. Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS). Results. After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups ( p < 0.001 ), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90, p = 0.18 ). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion. Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.

Time to sustained responder status in patients with focal seizures treated with adjunctive eslicarbazepine acetate

Rapid and sustained clinical responses are critical in improving long-term outcomes in epilepsy. While a 50 % reduction from baseline in standardized seizure frequency (SSF) is often cited as a measure of clinically meaningful efficacy, sustained response (SR) is an alternative method that allows the assessment of onset and durability of the response. Time to sustained response in SSF of ≥ 50 %, ≥ 75 %, ≥ 90 %, and 100 % was assessed for pooled data from 3 similar randomized clinical trials of adjunctive eslicarbazepine acetate (ESL). Patients with focal seizures on stable doses of 1–2 antiseizure medications were randomized to placebo, ESL 800 mg/day, or ESL 1200 mg/day. SR50, SR75, SR90, and SR100 were defined as a ≥ 50 %, ≥ 75 %, ≥ 90 %, and 100 % reduction, respectively, in SSF compared to baseline occurring anytime during the 12-week maintenance period, sustained through the end of the maintenance period. Safety signals were assessed for patients with SR50 onset within the first 2 weeks of the maintenance period (early responders) and any point following the first 2 weeks (later responders). A total of 1221 patients were included in this analysis. SR50 was achieved as early as Day 1 (placebo, 4.7 %; ESL 800 mg/day, 8.8 %; ESL 1200 mg/day, 10.4 %). After 84 days, SR50 was achieved by 32.1 % of the placebo group, 46.9 % of the ESL 800 mg/day group (p = 0.0002 vs placebo), and 53.7 % of the ESL 1200 mg/day group (p < 0.0001 vs placebo). Both ESL groups demonstrated earlier SR50 onset compared with placebo (p < 0.0001). Time to SR50 onset was not statistically different between the 800 and 1200 mg/day ESL dose groups. SR75 (p = 0.0001), SR90 (p = 0.0019), and SR100 (p = 0.0014) were achieved significantly earlier in the ESL 1200 mg/day groups vs placebo. SR75 was achieved significantly earlier in the ESL 800 mg/day group vs placebo (p = 0.0188), while achievements of SR90 (p = 0.0525) and SR100 (p = 0.0540) trended toward earlier occurrence. A greater proportion of patients in the ESL groups compared to the placebo group achieved an SR50 during the maintenance period, and those patients in the ESL groups also achieved SR50 and SR75 sooner than placebo treated patients. Additionally, patients treated with the higher ESL dose achieved SR90 and SR100 sooner than those treated with placebo.

Experiencia colombiana con el uso de tofacitinib en colitis ulcerosa aguda grave: estudio de serie de casos

IntroductionTofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. Materials and methodsDescriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. ResultsSix patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. ConclusionsTofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.

Barriers to and facilitators of a just-in-time adaptive intervention for respiratory illness in cerebral palsy: a qualitative study

ObjectiveTo understand caregiver, healthcare professional and national expert perspectives on implementation of a just-in-time adaptive intervention, RE-PACT (Respiratory Exacerbation-Plans for Action and Care Transitions) to prevent respiratory crises in severe...

Topical glucocorticoids in ophthalmology: a comparative analysis of efficacy and safety

The symptoms of most pathological conditions in ophthalmology are based on inflammations of varying severity. Valuable tools against inflammation are topical glucocorticoids (tGCs), whose molecules are able to actively overcome biological membranes and ensure a rapid clinical response. The use of tGCs is accompanied by a wide range of effects, including side effects, a rise in intraocular pressure being one of the most significant ones. The review focuses on a comparative analysis of the efficacy and safety of various tGCs, including “soft steroids”. We show the relationship between the structure of the drugs, their pharmacodynamic effects and the possibility of being used in various eye diseases.

Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study

BackgroundLocally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based...

Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematologic Malignancies: First-in-Human Open-Label Trial.

This global phase I trial investigated the safety, efficacy, pharmacokinetics, and pharmacodynamics of lisaftoclax (APG-2575), a novel, orally active, potent selective B-cell lymphoma 2 (BCL-2) inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies (HMs). Maximum tolerated dose (MTD) and recommended phase II dose were evaluated. Outcome measures were safety and tolerability (primary) and pharmacokinetic variables and antitumor effects (secondary). Pharmacodynamics in patient tumor cells were explored. Among 52 patients receiving lisaftoclax, MTD was not reached. Treatment-emergent adverse events (TEAEs) included diarrhea (48.1%), fatigue (34.6%), nausea (30.8%), anemia and thrombocytopenia (28.8% each), neutropenia (26.9%), constipation (25.0%), vomiting (23.1%), headache (21.2%), peripheral edema and hypokalemia (17.3% each), and arthralgia (15.4%). Grade ≥ 3 hematologic TEAEs included neutropenia (21.2%), thrombocytopenia (13.5%), and anemia (9.6%), none resulting in treatment discontinuation. Clinical pharmacokinetic and pharmacodynamic results demonstrated that lisaftoclax had a limited plasma residence and systemic exposure and elicited rapid clearance of malignant cells. With a median treatment of 15 (range, 6-43) cycles, 14 of 22 efficacy-evaluable patients with R/R CLL/SLL experienced partial responses, for an objective response rate of 63.6% and median time to response of 2 (range, 2-8) cycles. Lisaftoclax was well tolerated, with no evidence of tumor lysis syndrome. Dose-limiting toxicity was not reached at the highest dose level. Lisaftoclax has a unique pharmacokinetic profile compatible with a potentially more convenient daily (vs. weekly) dose ramp-up schedule and induced rapid clinical responses in patients with CLL/SLL, warranting continued clinical investigation.

An Outstanding Rapid Clinical Response to Olaparib in A Patient with gBRCA2m Fungating Breast Cancer: A Case Report

Background: Breast cancer is a heterogeneous, phenotypically complex disease made up of various biologic subgroups with unique behaviors and therapeutic responses. Noted that despite lack of a cure for metastatic breast cancer (MBC), there have been appreciable advancements in survival that have occurred at the same time as newer systemic treatments. BRCA1 or BRCA2 mutations cause homologous recombination deficient (HRD) cells, which are vulnerable to PARPi agent treatment. Case Report: This case report presents a 40 years old single female, known case of multiple co-morbidities who was diagnosed with Bilateral breast cancer in June 2022. She has a Positive family history of malignancy; mother died from endometrial cancer and aunt from paternal side has breast cancer. She underwent needle core biopsy from her Right breast mass, which revealed Invasive high-grade ductal carcinoma with metaplastic features (foci of keratinizing squamous differentiation, and myxoid stromal change). DCIS, of intermediate and high grades and a solid pattern, was noted, focally suspicious for lymphovascular invasion, Triple negative (ER negative (&lt;1%), PR negative (&lt;1%) and her-2 (+2) FISH negative (Her-2 Low), KI 67= 70%. Left breast mass Biopsy done on 12/9/2022 showed Invasive Lobular carcinoma, grade 3, ER negative, PR negative, Her-2 +1, KI 67=70%, BRCA2 POSITIVE &amp; PDL1 CPS score 10%. Staging positron emission tomography scan done on 10 October 2022. She had a Large hypermetabolic fungating right breast mass infiltrating the chest wall, consistent with biopsy-proven malignancy. Additional smaller FDG-avid lesions noted in the right breast. Moreover, she had FDG-avid right axillary and right internal mammary nodal metastases. Mildly FDG-avid left breast mass, consistent with biopsy-proven malignancy. FDG-avid liver and pleural metastases. She was started on PARP inhibitor (Olaparib) on 20/9/2022 after which she had amazing fast clinical response leading to falling off the large fungating mass. Conclusion: The chance of developing breast and ovarian cancer is extremely elevated if one possesses BRAC 1 or BRCA 2 mutation. In this situation, PARP inhibitors, mutation-targeted therapy, has better outcomes in reducing the morbidity and mortality associated with metastatic breast cancer (Olaparib).