Patients Off Research Articles

The impact of curative cancer treatment on sexual health – clinical results from the EORTC QLQ-SH22 validation study

BackgroundThe European Organization of Research and Treatment of Cancer (EORTC) has recently developed and validated a patient-reported outcome measure (PROM) for sexual health (SH) in cancer patients. Here, we present results from a secondary analysis of the EORTC QLQ-SH22 validation study. The objective was to investigate the impact of cancer treatment on SH over the disease trajectory into survivorship in patients who underwent curative treatment.MethodsParticipants completed the EORTC QLQ-SH22 and the EORTC QLQ-C30 assessing SH and Quality of Life. We analyzed differences in SH of patients on active cancer treatment compared to patients off-treatment (cross sectional group comparison) as well as changes in SH during the course of treatment (from pre-treatment to follow-up).ResultsOur sample consisted of n = 394 (66.2% females) curatively treated cancer patients with 34% of patients being on-treatment and 66% of patients being in their follow-up after primary treatment (off-treatment group). Compared to patients off- treatment, patients on active cancer treatment experienced less sexual satisfaction (p = .021, Cohen’s d = .36) and libido (p < .001, d = .60) and had higher levels of fatigue (p < .001, d = .50). Importance of sexual activity, masculinity and femininity did not differ between groups. Treatment effects on sexual activity decreased with treatment completion (p < .001, d = .50). Patients undergoing intensified treatment (chemotherapy, radiation, or endocrine treatment) reported more treatment effects (subscale EORTC QLQ-SH22) compared to patients undergoing surgery only.ConclusionOur results highlight the negative impact of oncological treatment on SH and how increasing treatment intensity further impair SH. Sexual satisfaction and libido improve after treatment completion while other aspects (e.g. masculinity/femininity) do not change during survivorship. We suggest monitoring of SH from the start of cancer treatment on and beyond into survivorship using PROMs as part of routine cancer care. Routine monitoring allows systematic identification of patient’s SH problems and may improve awareness as well as target intervention for those in need of care.

CTNI-03. DECREASED GROWTH VELOCITY IN A PHASE 1 TRIAL (PNOC014) OF TOVORAFENIB IN PATIENTS WITH RECURRENT OR PROGRESSIVE MAPK-ALTERED TUMORS

Abstract BACKGROUND The mechanisms by which MAPK-targeted agents affect children in active phases of neurocognitive and physical development are poorly understood and hence, may place them at risk, particularly for uncommon patient toxicities that may require longer monitoring or larger patient cohorts to understand the long-term implications. Decreased growth velocity was identified in our investigator-initiated phase 1 trial (NCT03429803) of tovorafenib in relapsed MAPK-altered tumors. METHODS Forty-four patients enrolled from February 2018-October 2021. Toxicity was assessed according to CTCAE version 5 term growth suppression (GS). Patients were also evaluated retrospectively based on age-specific growth velocity norms. Post-pubertal patients (n=14), those with pre-existing growth abnormalities (n=3), and those on drug less than 6 months (n=10) were excluded (total n=27; 61%). Growth velocities for each patient were calculated prior to, on, and after discontinuing treatment as available. RESULTS Our safety database included 17 reported events of GS. Sixteen patients experienced grade 3 GS, defined as growth velocity reduction ≥50% ideally measured over a year compared to baseline. One patient experienced grade 2 GS, defined as reduced growth velocity by 30-49% compared to baseline. Separate retrospective analysis using age-specific growth velocity norms further confirmed that all 17 patients (100%) demonstrated decreased growth velocity compared to age-specific norms following start of treatment regardless of dose (3, 5 and 9 patients at 280, 420 and 530 mg/m2/dose, respectively with a mean dose of 507 mg, range: 220-840 mg). Four of 9 patients on 530 mg/m2 were dose reduced for other reasons and hence treated at 420 mg/m2. In 14/15 patients off drug, growth rates recovered at near normal or normal rates within 12 months of discontinuation. CONCLUSIONS Patients on tovorafenib experience decreased growth velocity, which is recoverable off drug. Long-term monitoring of growth and further preclinical investigations to mitigate this toxicity and understand its effect are warranted.

Use of Glucagon-like Peptide 1 Receptor Agonist to Sustain Patients off Basal-Bolus Insulin Regimens

BackgroundThe 2024 Standards of Care in Diabetes recommend initiation of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) prior to starting basal insulin and to reconsider initiating a GLP-1 RA before starting bolus insulin if not already initiated. GLP-1 RA addition leads to improved glycemic benefits as well as risk reduction of cardiovascular and renal outcomes in patients with a history of these events. While there is evidence demonstrating the trends of insulin reduction or discontinuation following GLP-1 RA initiation, data regarding longer-term durability of GLP-1 RA use to sustain patients off bolus insulin is lacking. ObjectiveThis retrospective study aimed to assess the percentage of patients remaining off bolus insulin after transitioning from a basal-bolus regimen to GLP-1 RA therapy with basal insulin over a period of three years. MethodsWe conducted a single centered, retrospective study analyzing patient data from July 2018 through July 2023. Patients were included if they had a diagnosis of type 2 diabetes, were on a basal-bolus insulin regimen, had a GLP-1 RA initiated followed by bolus insulin discontinuation within 90 days, and remained on a GLP-1 RA for at least six months. The primary outcome was the percentage of patients who were sustained off bolus insulin after three years following GLP-1 RA initiation. ResultsThere were 252 patients included. At three years, 82.6% of patients were sustained off bolus insulin. The mean change in weight at three years was -8.5 kg. The mean A1c initially decreased from 8.6% to 7.8%, but then increased slightly to 8.1% at the end of the study timeframe. ConclusionThis trial demonstrated the majority of patients on basal-bolus regimens where bolus insulin was replaced with a GLP-1 RA were sustained off bolus insulin for a three year period of time. These results highlight the promising durability of converting bolus insulin to GLP-1 RAs.

7487 Iatrogenic Cushing’s Syndrome In A Patient On Prezcobix And Fluticasone

Abstract Disclosure: A.N. Davis: None. M. Nicholson: None. Introduction: The HIV medication Prezcobix contains darunavir, a protease inhibitor which is known to inhibit the hepatic enzyme CYP3A4. This may lead to accumulation of some medications in the blood, including fluticasone. We present a patient with iatrogenic Cushing’s syndrome while on Prezcobix and fluticasone. Case: Patient is a 55-year-old man who presented to clinic 3/13/23 for evaluation for cushingoid appearance at the request of his infectious disease (ID) physician. The patient has history of HIV, asthma, and seasonal allergies and had been taking Prezcobix, inhaled fluticasone, and intranasal fluticasone for over 3 years. Patient noted easy bruising and difficulty with weight loss. Vital signs were remarkable for elevated blood pressure at 165/86 despite taking amlodipine, HCTZ, and carvedilol. He was overweight with BMI 27.2. Physical exam revealed a somewhat rounded face, mild central obesity, no dorsocervical or supraclavicular fat pads, and no purple striae. Labs on 3/8/23 were remarkable for cortisol level &amp;lt;0.40mcg/dL at 4:10PM. Labs on 3/13/23 were remarkable for cortisol &amp;lt;0.40mcg/dL, ACTH level &amp;lt;5.0pg/mL, and urine fluticasone 17-beta carboxylic acid elevated at 540pg/mL (&amp;lt;10pg/mL) at 3:57PM. His ID physician planned to transition the patient off of Prezcobix and onto Tivicay, so patient was started on hydrocortisone 15mg PO daily at 8AM and 5mg daily at 2PM on the day he switched to Tivicay. He was gradually tapered off of hydrocortisone over a 2-3 month period without any symptoms concerning for adrenal insufficiency. His Cortisol level on 7/10/23 off hydrocortisone was 4.98mcg/dL at 7:56AM. Discussion: Prezcobix contains darunavir which is known to inhibit CYP3A4. With most patients, use of inhaled and intranasal fluticasone does not result in physiologically meaningful systemic levels of fluticasone. However, metabolism of fluticasone is dependent on CYP3A4, so systemic levels may increase with use of inhaled fluticasone with Prezcobix resulting in excess of corticosteroids and suppression of the native hypothalamic-pituitary-adrenal (HPA) axis. Fluticasone 17-beta carboxylic acid is a metabolite of fluticasone which is detectable in the urine. Sudden cessation of Prezcobix after prolonged use may result in secondary adrenal insufficiency from prolonged HPA axis suppression. Our case demonstrates how the use of Prezcobix with fluticasone may result in iatrogenic Cushing’s syndrome. Additionally, our case demonstrates that anticipation of secondary adrenal insufficiency after stopping Prezcobix allows for implementation of a safe transition plan. Presentation: 6/1/2024

Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial

Adaptive deep brain stimulation (aDBS) is an emerging advancement in DBS technology; however, local field potential (LFP) signal rate detection sufficient for aDBS algorithms and the methods to set-up aDBS have yet to be defined. Here we summarize sensing data and aDBS programming steps associated with the ongoing Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) pivotal trial (NCT04547712). Sixty-eight patients were enrolled with either subthalamic nucleus or globus pallidus internus DBS leads connected to a Medtronic PerceptTM PC neurostimulator. During the enrollment and screening procedures, a LFP (8–30 Hz, ≥1.2 µVp) control signal was identified by clinicians in 84.8% of patients on medication (65% bilateral signal), and in 92% of patients off medication (78% bilateral signal). The ADAPT-PD trial sensing data indicate a high LFP signal presence in both on and off medication states of these patients, with bilateral signal in the majority, regardless of PD phenotype.

124: Pump Controlled Retrograde Flow Trial Off (PCRTO) in Congenital Heart Disease Patients as a Strategy for Weaning Patients Off Veno-Arterial Extracorporeal Membrane Oxygenation

124: Pump Controlled Retrograde Flow Trial Off (PCRTO) in Congenital Heart Disease Patients as a Strategy for Weaning Patients Off Veno-Arterial Extracorporeal Membrane Oxygenation

Randomized Trials of Renal Denervation for Uncontrolled Hypertension: An Updated Meta-Analysis.

Despite optimal medical therapy, a significant proportion of patients' blood pressure remains uncontrolled. Catheter-based renal denervation (RDN) has been proposed as a potential intervention for uncontrolled hypertension. We conducted an updated meta-analysis to assess the efficacy and safety of RDN in patients with uncontrolled hypertension, with emphasis on the differential effect of RDN in patients on and off antihypertensive medications. Online databases were searched to identify randomized clinical trials comparing efficacy and safety of RDN versus control in patients with uncontrolled hypertension. Subgroup analyses were conducted for sham-controlled trials and studies that used RDN devices that have gained or are currently seeking US Food and Drug Administration approval. Fifteen trials with 2581 patients (RDN, 1723; sham, 858) were included. In patients off antihypertensive medications undergoing RDN, a significant reduction in 24-hour ambulatory (-3.70 [95% CI, -5.41 to -2.00] mm Hg), office (-4.76 [95% CI, -7.57 to -1.94] mm Hg), and home (-3.28 [95% CI, -5.96 to -0.61] mm Hg) systolic blood pressures was noted. In patients on antihypertensive medications, a significant reduction was observed in 24-hour ambulatory (-2.23 [95% CI, -3.56 to -0.90] mm Hg), office (-6.39 [95% CI, -11.49 to -1.30]), home (-6.08 [95% CI, -11.54 to -0.61] mm Hg), daytime (-2.62 [95% CI, -4.14 to -1.11]), and nighttime (-2.70 [95% CI, -5.13 to -0.27]) systolic blood pressures, as well as 24-hour ambulatory (-1.16 [95% CI, -1.96 to -0.35]), office (-3.17 [95% CI, -5.54 to -0.80]), and daytime (-1.47 [95% CI, -2.50 to -0.27]) diastolic blood pressures. RDN significantly lowers blood pressure in patients with uncontrolled hypertension, in patients off and on antihypertensive medications, with a favorable safety profile. The efficacy of RDN was consistent in sham-controlled trials and contemporary trials using US Food and Drug Administration-approved devices.

A brief history of ramping.

'Ramping' is a commonly used term in contemporary Australian healthcare. It is also a part of the public and political zeitgeist. However, its precise definition varies among sources. In the published literature, there are distinctions between related terms, such as 'entry overload' and 'Patient Off Stretcher Time Delay'. How ramping is defined and how it came to be defined have significance for policies and procedures relating to the described phenomenon. Through examination of the history of the term, insights are obtained into the underlying issues contributing to ramping and, accordingly, associated possible solutions.

A narrative review of risk mitigation strategies in the management of opioids for chronic pain and palliative care in older adults: interprofessional collaboration with the pharmacist.

The prevalence of chronic non-cancer pain (CNCP) in older adults is high. Opioids carry significant risk for harm in older adults. Yet, many older adults are established on long-term opioid therapy for the treatment of CNCP despite limited documented efficacy. Many of the non-opioid options to treat pain present challenges in this population. Since challenges with tapering patients off of opioids exist, older adults may remain established on long-term opioid therapy for CNCP. While opioid use is less scrutinized for older adults receiving palliative care, significant safety concerns exist. Therefore, efforts to mitigate risks for older adults receiving long-term opioids for CNCP and for palliative care are essential. Pharmacists as members of the interprofessional team are equipped to improve safety among older adults on chronic opioid therapy. Among patients receiving palliative care, collaboration with palliative care specialists is also key. The purpose of this narrative review is to describe risk mitigation strategies for opioid use among older adults with CNCP and those receiving palliative care. Data were identified by searching PubMed (January 1, 1990 to February 21, 2024) using the following search terms: older adults, opioids, chronic pain, palliative care, and pharmacist. The search was repeated using terms geriatric, elderly, opiates, narcotics, and controlled substances. Non-English articles and observational studies with fewer than 100 patients were excluded. Major North American and European guidelines were reviewed. Additional literature was obtained through review of relevant references of identified articles. A variety of risk mitigation strategies to improve safety for older adults using opioids exist. They include risk assessment, tapering opioids, reducing high-risk concomitant medications, utilizing non-opioid therapies, screening for and treatment of opioid use disorder (OUD), toxicology testing, co-prescribing naloxone, utilizing controlled substance agreements, reviewing prescription drug monitoring program data, prescriber and patient education, and collaboration with pharmacists and palliative care specialists. There are many opioid risk mitigation strategies for older adults. Collaboration with pharmacists and palliative care specialists can be an effective means for implementing strategies to optimize opioid safety for older adults with CNCP and those receiving palliative care.

Plasticity-Induced Effects of Theta Burst Transcranial Ultrasound Stimulation in Parkinson's Disease.

Low-intensity transcranial ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) technique with high spatial specificity. Previous studies showed that TUS delivered in a theta burst pattern (tbTUS) increased motor cortex (MI) excitability up to 30 minutes due to long-term potentiation (LTP)-like plasticity. Studies using other forms of NIBS suggested that cortical plasticity may be impaired in patients with Parkinson's disease (PD). The aim was to investigate the neurophysiological effects of tbTUS in PD patients off and on dopaminergic medications compared to healthy controls. We studied 20 moderately affected PD patients in on and off dopaminergic medication states (7 with and 13 without dyskinesia) and 17 age-matched healthy controls in a case-controlled study. tbTUS was applied for 80 seconds to the MI. Motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), and short-interval intracortical facilitation (SICF) were recorded at baseline, and at 5 minutes (T5), T30, and T60 after tbTUS. Motor Unified Parkinson's Disease Rating Scale (mUPDRS) was measured at baseline and T60. tbTUS significantly increased MEP amplitude at T30 compared to baseline in controls and in PD patients on but not in PD patients off medications. SICI was reduced in PD off medications compared to controls. tbTUS did not change in SICI or SICF. The bradykinesia subscore of mUPDRS was reduced at T60 compared to baseline in PD on but not in the off medication state. The presence of dyskinesia did not affect tbTUS-induced plasticity. tbTUS-induced LTP plasticity is impaired in PD patients off medications and is restored by dopaminergic medications. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Higher recurrence rate after ablation of persistent atrial fibrillation in patients with prolonged P-wave negativity in lead V1

Abstract Background Several ECG P-wave parameters, such as duration, amplitude and morphology reflect the electromechanical condition of the atria. P-wave features mainly served to identify patients prone to atrial fibrillation (AF) or to predict recurrence of paroxysmal AF after ablation. Purpose We sought to investigate which specific features derived from the P-wave might help identify patients with persistent atrial fibrillation (peAF) unresponsive to wide circumferential pulmonary veins isolation (WPVI). Methods 41 patients (63±10 y) with peAF (sustained duration 11±7 months) underwent a de-novo WPVI. A second WPVI was performed in patients with recurrent AF in order to provide complete PV disconnection. We defined "success" as patients who remained in sinus rhythm (SR) after one or two procedures, and "failure" otherwise. The average duration and amplitude of the P-waves on ECG lead II, and the duration and amplitude of positive and negative deflections on ECG lead V1 were extracted during SR after cardioversion at the end of the index WPVI. P-wave terminal force in V1 (PTFV1) was computed as the product of negative amplitude and duration in lead V1. Results Over a mean follow-up of 32±9 months, 24 patients remained free from AF (success group), while 11 patients had AF recurrence after 2 WPVIs (failure group). Six patients were lost to follow-up or declined the second WPVI. 45% (5/11) were ON antiarrhythmic drugs (AAD) during follow-up in the failure group, while 0.04% (1/24) were ON AAD in the success group (p&amp;lt;0.05). Other clinical characteristics (e.g. age, body mass index, left atrial volume or duration in sustained AF) were similar. The figure displays P-wave metrics of patients ON and OFF AAD during follow-up. No significant differences were found in P-wave duration (lead II; Panel A1), in PTFV1 (Panel A2), and in duration of V1 positive deflection (Panel A3). Interestingly, the failure group displayed longer duration of the negative deflection in V1 (76±17ms) than that of the success group (68±18ms, p&amp;lt;0.05; Panel A4). Panel B shows that the differences remained after exclusion of patients ON AAD during follow-up. No differences were found in P-wave amplitude in lead II or in amplitude of positive and negative deflections in lead V1 (data not shown). Conclusion Our results show that prolonged negativity in lead V1, which is indicative of left atrial electromechanical remodeling, is associated with failure to restore long-term sinus rhythm after WPVI of peAF.

Sublingual apomorphine in the treatment of Parkinson's disease.

Advanced Parkinson´s disease (PD) is often complicated by fluctuations of disability depending on plasma levels of levodopa. For most patients OFF phases with worsening of tremor and immobility, but also pain, depression, autonomic symptoms are troublesome. While adjustments of levodopa administrations can relief such fluctuations for some time, "on demand" therapies become more and more important. These "on demand" therapies should provide fast and efficacious relief. During the past years, new options for on demand therapies in PD-associated OFF episodes have been developed, including new formulations of levodopa and apomorphine to provide fast and readily accessible on demand treatment. In this narrative review, the challenges of the treatment of PD-associated fluctuations and OFF states are addressed, with a special focus on sublingual apomorphine (SL-APO) including the results from recent clinical trials.

Recellularization via electroporation therapy of the duodenum combined with glucagon-like peptide-1 receptor agonist to replace insulin therapy in patients with type 2 diabetes: 12-month results of a first-in-human study

Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in type 2 diabetes (T2D) patients through a single ReCET procedure combined with a glucagon-like peptide-1 receptor agonist. Feasibility, safety, and (dose) efficacy of ReCET were assessed. This first-in-human study included patients with T2D on basal insulin (age, 28-75 years; body mass index, 24-40 kg/m2; glycosylated hemoglobin,≤64mmol/mol; C-peptide,≥0.2 nmol/L). The electroporation dose was optimized during the study, starting with single 600 V and ending with double 750 V treatments. All patients underwent ReCET, after which insulin was discontinued and semaglutide (glucagon-like peptide-1 receptor agonist) was initiated. The primary endpoints were feasibility (procedure time [from catheter in to catheter out], technical success rate), safety, and efficacy (patients off insulin at 6 months; HbA1c,≤58mmol/mol). Fourteen patients underwent endoscopic ReCET. The median procedure time was 58 (interquartile range, 49-73) minutes. ReCET demonstrated a technical success rate of 100%. No device-related severe adverse events or severe hypoglycemic events were observed. At the 12-month follow-up, 12 (86%) patients remained off exogenous insulin therapy, with significant improvements in glycemic control and metabolic parameters. The 2 patients in whom insulin therapy was reintroduced both received ReCET at the lowest voltage (single 600 V). These results suggest that ReCET is feasible and safe. In combination with semaglutide, ReCET may be a promising therapeutic option to replace insulin therapy in selected T2D patients while improving glycemic control and metabolic health.

Modified platelet rich plasma therapy for alopecia totalis

Abstract Alopecia areata (AA) is an autoimmune disease characterized most commonly by patchy nonscarring hair loss which may progress to alopecia totalis which has poor prognosis. Platelet-rich plasma (PRP) therapy along with intralesional triamcinolone acetonide that is modified PRP proved to be beneficial in the case of alopecia totalis and helps in weaning patient off oral immunosuppression.

A Retrospective Study on Weaning Glucocorticoids and Recovery of the Hypothalamic-Pituitary-Adrenal Axis.

Glucocorticoids suppress the hypothalamic-pituitary-adrenal (HPA) axis, resulting in tertiary adrenal insufficiency (AI). When weaning patients off glucocorticoids there is no consensus on whether to maintain patients on prednisolone or convert to hydrocortisone. To investigate HPA axis recovery in patients on long-term prednisolone and assess outcome after hydrocortisone conversion. This was a retrospective cohort study at an outpatient endocrine steroid clinic. Patients were on long-term prednisolone and referred for HPA axis testing between 2015 and 2022. The main outcomes measured were (1) HPA axis recovery rate in patients on prednisolone demonstrated by a normal adrenocorticotrophic hormone (ACTH) stimulation test (AST) and (2) HPA axis recovery rate subanalysis of dose-matched patients with confirmed tertiary AI on prednisolone or hydrocortisone were measured. In total, 206 patients on prednisolone were tested for tertiary AI. Of these, 176 remained on prednisolone while 30 were converted to hydrocortisone. The overall HPA axis recovery rate for patients on prednisolone after interval testing was 137/206 (66.5%). The HPA axis recovery rate in dose-matched prednisolone and hydrocortisone conversion groups was 7/10 (70%) and 2/13 (15%) (P = .008), respectively. There was no difference in mean (SD) age (67.1 [12.2] vs 63.4 [11.1] years; P = .464) and baseline cortisol (5.3 [4.2] vs 4.6 [3.1] µg/dL; P = .648) and median [interquartile, IQR] glucocorticoid duration (1213 [1114] vs 2316 [4808] days; P = .693) and baseline ACTH (20.5 [29.0] vs 16.3 [14.8] ng/L; P = .905) between dose-matched prednisolone and hydrocortisone groups. Follow-up duration in the prednisolone group was significantly lower (median [IQR] 348 [975] vs 667 [884] days; P = .012). Patients with glucocorticoid-induced AI maintained on once-daily prednisolone can recover HPA axis function when weaning. There is no apparent advantage to recover HPA axis function in converting to multiple-dosing hydrocortisone.

Evaluation of Anesthesia Care Team Knowledge Regarding Weaning from Mechanical Ventilation in Intensive Care Unit

Introduction: One of the most popular therapies for hospitalized patients in critical care units (ICUs) is mechanical ventilation through an endotracheal tube. Delaying weaning is linked to increased difficulty rates, more time in the hospital, and reduced ICU survival rates. Methodology: This study aims to evaluate the anesthesia care team's knowledge regarding weaning from MV in the ICU. The cross-sectional study of this type was conducted at Imam Khomeini Hospital and Sharieti Hospital in Tehran, Iran, from May 2023 until November 2023. During data collection, anesthetic care team members with various educational backgrounds were employed in the ICU at a public hospital. The final sample size was 101 Iranian anesthesia care teams in an Iranian hospital. Inclusion criteria include those who had an educational certificate and agreed to participate in this study during the study period. Anyone with a duration of 1 year or more in the ICU has an associate degree (nursing, anesthesia care team anesthesiology) and above. Exclusion criteria include a pilot study sample and all those not fulfilling the above inclusion criteria and not completing questionnaires. Results: The results showed that (77.2%) of the anesthesia care team was female, and (74.3%) were married. (50.5%) worked in the Imam khomaini hospital; furthermore, the anesthesia care team age was (50.5%) of (31--40) years old, and the mean SD was (2.14 0.69). (2%)the anesthesia care team possessed plenty of knowledge. (35.6%) The anesthesia care group possessed a middling degree of knowledge, and (62.4%) possessed little knowledge. The relationship between the total knowledge of the anesthesia care team regarding weaning criteria from mechanical ventilation and the educational degree is significant (P = 0.005). The Conclusion: The knowledge and procedures of the anesthesia care team about weaning patients off of artificial ventilation were deemed inadequate based on the results of the current study. They need better knowledge about weaning criteria from MV in the ICU.

Phase II Study of the Combination of Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone (DIPD) As Salvage Therapy in Early Relapsed/Refractory Multiple Myeloma

Background: The combination of daratumumab (D), pomalidomide (P), and dexamethasone (d) has previously demonstrated high overall response rates in patients with RRMM. Results of the phase 3 APOLLO study of DPd vs Pd in patients with RRMM with at least 1 prior line of therapy showed 69% ORR with a median PFS of 12.4 months in those patients who received the triplet combination (Dimopoulos, et al. Lancet 2021). Quadruplet regimens may further improve results by providing deeper and more durable responses with more intensive regimens. We report results from a phase 2 multicenter trial of the addition of Ixazomib to DPd (DIPd) in patients with early RRMM. Methods: This is a prospective, multi-center, open-label, single arm phase 2 study (NCT03590652) with a primary endpoint of overall response rate (ORR) and safety of DIPd. Secondary endpoints include progression-free survival (PFS), overall survival (OS), and MRD-negativity rate. A Simon's optimal 2-stage design was used, with 14 subjects in stage 1 and 32 patients for stage 2. Eligible patients may not have had prior exposure to daratumumab or Ixazomib, may not have progressed on prior pomalidomide, and must have received ≥1 or ≤3 prior lines of therapy including lenalidomide and a proteasome inhibitor. The first six patients in a safety run-in received daratumumab 16mg/kg IV weekly x 8 doses, biweekly x 8 doses, then monthly, pomalidomide 4mg orally on days 1-21, ixazomib 4mg orally on days 1, 8, 15, and dexamethasone 20-40mg weekly on a 28-day cycle. Grade 3-4 neutropenia was observed in 100% of patients in the safety run-in, prompting starting dose reductions to ixazomib 3 mg and pomalidomide 3 mg by the DSMB for subsequent patients. An amendment allowed for subcutaneous (SC) Daratumumab administration and all active patients transitioned to or started with SC dosing for ongoing therapy. MRD assessments were performed by EuroFlow for patients in suspected CR. Pharmacodynamic changes in patients' tumor microenvironments were established by custom panel mass cytometry to include T-cell memory and activated subpopulations, B-cell content, NK-cell subpopulations as well as MDSCs, Tregs and T-exhaustive markers, monocytes and dendritic cells. Results: The study has completed the planned enrollment of 46 patients. The median age is 61.6 years (range 41-87), with 47% female, 72% White, 17% Asian, and 5% Black patients. Patients had a median of 1 prior line of therapy (range 1-3), and 56% (23/41) of patients had at least one high-risk cytogenetic abnormality including del 17p, +1q, t(14;16), t(14;20), or t(4;14). Grade 3-4 treatment emergent adverse events (AE) include neutropenia (72%), infection (19%), febrile neutropenia (8%), lymphopenia (8%), electrolyte disturbance (6%), leukopenia (3%), thrombocytopenia (3%), respiratory condition (3%), infusion reaction (3%), thrombosis (3%), and psychiatric condition (3%). ORR to date is 83% (38/46) in evaluable patients, and best responses include 12 (26%) sCR, 12 (26%) VGPR, and 14 (30%) PR. The median duration of response (DOR) is 21.1 months for all patients, with 11 patients currently remaining on DIPd therapy, and 9 deaths all unrelated to study treatment (5 progressive disease [PD], 2 sepsis, 1 COVID, 1 unrelated surgical complication). Of the 35 patients off therapy, 20 patients had PD, 6 patients had AEs, 5 patients stopped per physician discretion or withdrew consent, and 4 patients received an autologous stem cell transplant. After a median follow up of 15 months, the median PFS is 16.6mo (95% CI: 8.19-NR ) for all patients, 16.6mo (6.9-NR) for standard risk patients, and 22.3mo (7.6-NR) for high risk patients (p=0.9). The median OS for all patients is 30.3mo (95 CI: 30.3-NR). Data will be updated for the conference to include MRD negativity rates and completed data analysis of the primary endpoint. Conclusion: The quadruplet regimen DIPd shows that the addition of a 4 th agent results in high overall response rates and early PFS rates, with manageable toxicity, and the convenience of a nearly all-oral drug regimen in patients with early RRMM. These data are particularly compelling for high-risk disease as more than half of the patients treated had at least one high-risk cytogenetic abnormality, offering a promising option for the management of early relapse in high-risk patients.

Fertility treatment outcomes in transgender men with a history of testosterone therapy

To evaluate fertility treatment outcomes among transgender (TG) men with a history of gender-affirming hormone therapy with exogenous testosterone. Descriptive, retrospective cohort study. Transgender men with a history of gender-affirming hormone therapy with exogenous testosterone underwent fertility treatments, including embryo cryopreservation, invitro fertilization (IVF), co-IVF, oocyte cryopreservation, and intrauterine insemination (IUI), between 2013 and 2021. Gender-affirming hormone therapy with testosterone. Live births (LBs), number of frozen embryos, and number of frozen oocytes. Other outcome measures included total gonadotropin used, peak estradiol levels, oocytes retrieved, oocyte maturity rate, fertilization rate, and embryo grade. A total of 77 TG men self-presented or were referred to care at a single academic fertility center, of which 46 (59.7%) TG men underwent fertility preservation and/or family-building counseling, with 16 (20.8%) patients proceeding to fertility treatment. Of those patients who underwent treatment, 11 (68.8%) had a history of gender-affirming hormone therapy with exogenous testosterone use. Cohort 1 included IVF (n = 1), co-IVF (n = 1), embryo cryopreservation (n = 2), cohort 2 included oocyte cryopreservation (n = 4), and cohort 3 included IUI (n = 3). In cohort 1, both the patients who underwent IVF and the patients who underwent co-IVF achieved LBs. All embryo cryopreservation cycles froze three or more embryos. In cohort 2, the average number of frozen mature oocytes was 19.3 ± 16.2 (range 6-43). All patients who underwent IUI cycles achieved LB. In this study, no correlation existed between patient age, time on or off gender-affirming hormone therapy with exogenous testosterone, total gonadotropin used, and number of oocytes retrieved. All patients who completed IVF or embryo cryopreservation produced high-quality blastocytes, and this is the first study to show successful IUI cycles in patients with a history of gender-affirming hormone therapy with exogenous testosterone. This study demonstrates that TG men who have used gender-affirming hormone therapy previously can successfully undergo fertility treatments to attain oocyte and embryo cryopreservation, pregnancy, and LBs.

Defining the basal serum cortisol cut-off for weaning patients off glucocorticoids in suspected tertiary adrenal insufficiency

Defining the basal serum cortisol cut-off for weaning patients off glucocorticoids in suspected tertiary adrenal insufficiency

Composite score of physiomechanical esophageal function using functional lumen imaging probe panometry in eosinophilic esophagitis

Background and AimsThe evaluation provided by functional lumen imaging probe (FLIP) Panometry includes esophageal distensibility/compliance (mechanics) of the esophageal body and esophagogastric junction (EGJ) and esophageal motility (secondary peristalsis). We aimed to develop a composite score using these parameters to characterize physiomechanical function in patients with eosinophilic esophagitis (EoE). Methods215 adult patients with EoE that completed FLIP Panometry during sedated endoscopy with esophageal biopsies were included. FLIP metrics of esophageal body Compliance, Contractile response, Distensibility plateau, and maximum EGJ Diameter (C2D2) were scored as 0 for normal, vs 1 or 2 for increasing degree of abnormality. Scores were summed to calculate the composite “C2D2” score. ResultsThe C2D2 score had a significant positive correlation with mucosal eosinophil count (rho=0.241) and total endoscopic (EREFS) score (rho=0.467). Among patients off treatment at baseline evaluation (n=46), future proton pump inhibitor (PPI)-responders (i.e. achieved mucosal eosinophil count <15 per hpf after PPI treatment) had lower C2D2 scores than PPI-non-responders (median (IQR) 2 (1-3) vs 4 (2-6); P=0.003). A regression model (that controlled for age, sex, and baseline eosinophil count) showed a C2D2 score ≤3 had an odds ratio (95% confidence interval) of 14.5 (2.6-85) to predict future PPI-response. However, total EREFS scores (P=0.142) and baseline eosinophil count (P=0.480) did not differ between PPI-responders and PPI-non-responders. ConclusionsThis composite score of FLIP Panometry metrics, the C2D2 score, may facilitate characterizing physiomechanical function in EoE and serve as an objective outcome measure.