Full Remission Research Articles

LIVED EXPERIENCES OF PATIENTS WITH SUBSTANCE USE DISORDERS: A PHENOMENOLOGICAL MIXED METHODS STUDY

The objectives of the present study are two folds, 1) to explore the lived experinces of the patients diagnosed with substance use disorders and 2) to investigate levels of psychological distress experienced along with the perceived quality of life and coping startegies used by them. Phenomenological mixed methods approach was applied with two phases and the study was carried out during 1st January to 30th July, 2022. In Phase I, we used qualitative approach of Interpretative Phenomenological Analysis (IPA). Semi-structured interviews were carried out with 6 experts (psychiatrists and clinical psychologists) and 6 patients diagnosed with substance use disorders. The recordings were transcribed and analyzed for themes of lived experinces (Smith et al., 2009) as experienced by the patients and perceived by the experts (Psychiatrists and Clinical Psychologists/Psychologists) treating while probing their experiences. The findings of IPA yielded main factors that influence people to indulge in substance use disorder are peer pressure, family influence, stigma, sexual satisfaction , loneliness, social and cultural contextual factors, and experimentation. In Phase II, we used quantitative approach of cross-sectional design. 200 patients were selected by purposive sampling technique from Shaheed Naveed Rehabilitation Clinic, Pathan Wali, Wazirabad, Punjab. They were screened with Urdu version of Drug Abuse Screening Test (DAST-10, Skinner, 1982; Yudko, Lozhkina, Fouts, 2007). To measure psychological distress, Urdu version (Farooqi, & Habib, 2010) of Depression, Anxiety, Stress Scale (Dass-21, Lovibond & Lovibond, 1995) was used. To measure quality of life and coping strategies, Urdu versions of WHOQOL-BREF (Lodhi, Raza, Montazeri, Nedjat, Yaseri, & Holakouie-Naieni, 2017) and Copying Scale (Hamby, Grych, & Banyard, 2013) were used with patients diagnosed with substance use disorders. The results showed that patients experienced moderate levels of depression (M=17.26, SD=4.71) and anxiety (M=14.10, SD=4.58) and mild level of stress (M=17.32, SD=4.56). The score on coping scale indicated low level (M= 35.0, SD= 7.48) of coping strategies used for appraisal and behaviorally dealing with their issues around drug addiction. Conclusively, the lived experinces of the drug addicts centralized around socio-cultural influences of perceived stigmatization and imbalanced family-peer interactions that arose sensual and curiosity for experimentation with the drugs. They perceived their life to be of average quality and exhibited low coping skills, thus suffered with moderate level of depression and anxiety even in their full remission for substance use disorder in rehabilitation centres. The implications are discussed in the light of the fidnings of the present research. Keywords: Anxiety, Coping, Depression, Drug Addiction, Quality of Life, Stress.

Trichoscopy of pemphigus vulgaris in remission. A tool for treatment-cessation decision making. Preliminary results

Background: One of the controversies in the treatment of Pemphigus Vulgaris (PV), is the time of treatment cessation. Scalp involvement is often the most stubborn to treatment human area and may reflect disease activity. Trichoscopy (Dermoscopy of hair and scalp) features have not been studied in clinically “healthy-looking” skin of PV patients in full remission. Aims and Objectives:To find out if there are any trichoscopy features in PV patients in clinical and immunologic remission, and accommodate treatment decision. Methods: The age and disease duration of 3 women with PV were correspondingly 62, 63, 55 and 5, 6, 15 years. Treatment at examination was 2,5 mg prednisone(Pr), for the last 22, 5 and 7 months. The 2nd patient was also taking 1 mg/kg/d of Azathioprine. Anti Desmoglein antibodies turned to negative since Oct/2017, Feb/2017, Sept/2015. Contact dermoscopy and hand lens X10 magnifier for clinical evaluation, were used. Results: A red hue background, peripillar scales and tubular casts were observed by trichoscopy in the first 2 patients. Only peripilar scales on a small brown round area were the features in the 3rd patient. Treatment cessation was decided only in this patient, since casts observed in the other two patients, were considered as a consequence of outer root sheath acantholysis and a sign of disease activity. Patients’ follow up justified the aforementioned treatment decisions. Conclusions: Areas of red hue skin background and movable cylindical scales (casts) around hair shafts may be observed, even in the absence of apparent scalp clinical involvement, in PV patients in remission. Since these features may drive physicians to treatment continuation, dermoscopy of the scalp is required in clinically “healthy-looking” PV patients, before a decision of treatment cessation is made. Future studies with greater number of patients, furtherly validated by long term disease course outcome, are needed.

Baseline cognitive function predicts full remission of suicidal symptoms among patients with treatment-resistant depression and strong suicidal ideation after low-dose ketamine infusion.

Whether pretreatment working memory and response inhibition function are associated with the rapid and sustained antisuicidal effect of low-dose ketamine among patients with treatment-resistant depression (TRD) and strong suicidal ideation is unclear. We enrolled 65 patients with TRD, comprising 33 who received a single infusion of 0.5 mg/kg ketamine and 32 who received a placebo infusion. The participants performed working memory and go/no-go tasks prior to infusion. We assessed suicidal symptoms at baseline and on postinfusion Days 2, 3, 5, and 7. The full remission of suicidal symptoms persisted for 3 days after a single ketamine infusion and the ketamine-related antisuicidal effect persisted for 1 week. Lower cognitive impairment at baseline (indicated by a higher rate of correct responses on a working memory task) was associated with the rapid and sustained antisuicidal effect of low-dose ketamine in patients with TRD and strong suicidal ideation. Patients with TRD and strong suicidal ideation but low cognitive impairment may benefit the most from the antisuicidal effect of low-dose ketamine.

#5091 RITUXIMAB IN MANAGEMENT OF RELAPSING AND STEROID DEPENDANT C1Q NEPHROPATHY: A TALE OF THREE PATIENTS

Abstract Background and Aims C1q nephropathy is an immune glomerular disease in which dominant C1q electron-dense deposits are identified in the mesangium.It commonly presents with nephrotic syndrome, while nephritic syndrome or isolated haematuria are less common. Biopsy findings vary, from no glomerular lesion identified as in minimal change disease (MCD) to focal segmental glomerulosclerosis (FSGS) and immune-mediated proliferative glomerulonephritis. Steroids are the mainstay and other agents have been tried. Rituximab is an anti-CD 20 human/mouse chimeric monoclonal antibody and one of the drugs used in managing C1q nephropathy. We present 3 cases of biopsy-proven C1q nephropathy that presented with nephrotic syndrome. They responded initially to steroids and achieved remission after treatment with rituximab. Method Case Scenarios: Case (1): A 30-year-old man had been diagnosed with steroid sensitive nephrotic syndrome since he was 18 months. Renal biopsy confirmed the diagnosis of C1q nephropathy, more in the spectrum of MCD. He was managed with steroids, and rituximab in 2011 and achieved remission for the last 7 years after 5 doses. His renal function had always remained normal. He presented to our department in 2020 with another relapse and heavy proteinuria (urine protein creatinine ratio (UPCR) was 1300 mg/mmol) but unchanged renal function. Repeat kidney biopsy showed C1q nephropathy in the spectrum of FSGS. He showed good response to oral steroids. On relapse while weaning steroids, Rituximab was considered. He had 2 doses of rituximab of 1 gram 2 weeks apart in July 2021. He achieved full remission over the last 2 years. Case (2): A 77-year-old female presented in 2020 with nephrotic syndrome (UPCR of 660 mg/mmol) and acute kidney injury (AKI) (creatinine 400 μmol/l). Her kidney biopsy showed C1q nephropathy with FSGS features. She was started on haemodialysis due continuous kidney function deterioration. She recovered on steroid therapy to normal kidney function and negative proteinuria, but she relapsed with weaning steroids. So steroid dose was increased and tacrolimus was added. Her renal function remained intact. Following that she had another flare in May 2021 with mild kidney impairment and worse proteinuria (UPCR 500 mg/mmol) while she was on small dose steroid and tacrolimus. She was then started on rituximab. After 2 doses 1 gm 2 weeks apart she achieved remission and her kidney function normalised. She received 2 more doses of 1 gram rituximab 6 months apart with excellent response. She has been in complete remission since. Case (3): A 28-year-old male presented to our department in July 2020 with nephrotic syndrome (urine PCR >900 mg/mmol) and preserved renal function. His kidney biopsy was initially reported as MCD and he was managed with oral steroids. He showed a good response with complete resolution of his proteinuria 3 weeks later and remained in remission for 2 years. However, in August 2022- he suffered a second severe relapse (UPCR 4000 mg/mmol) with preserved renal function. His kidney biopsy was therefore rereviewed and immunofluorescence was added which revealed C1q nephropathy. He had another course of steroids and was initiated on rituximab infusions. He showed full remission after 2 doses (1 gram IV 2 weeks apart) and is on ongoing 6 monthly infusions. Results Rituximab was effective in inducing remission in our patients with nephrotic syndrome due to C1q nephropathy. They were all steroid sensitive. It was effective in both steroid-sensitive and steroid-dependent cases. The first and second cases had biopsy findings in the spectrum of FSGS while the third case histological picture in the spectrum of MCD. They all achieved full resolution of their proteinuria and preserved their renal function finally. Conclusion Rituximab was effective in inducing remission in both steroid-responsive and steroid dependant relapsed patients with C1q nephropathy, despite differences in biopsy results. Kidney function was preserved. More solidified data, including multi-centre randomized controlled trials, are needed to establish clear guidelines for the position of rituximab in the management of the disease and the proper dose to use.

Narrative Exposure Therapy for Treating Post-Traumatic Stress Among Transgender Youth of Color With Selective Mutism

Rates of post-traumatic stress (PTS) are greater among transgender and non-binary (TGNB) youth compared to their cisgender peers. This disparity has been linked to increased experiences of trauma among TGNB youth, including greater exposure to child abuse, discrimination, hate crimes, and familial and peer bullying and rejection. Few studies to date have examined the use of trauma-focused interventions with TGNB youth. Narrative Exposure Therapy (NET) has been identified as a potentially impactful treatment for PTS for communities who experience oppression and human rights violations given its social justice-oriented “testimonial” approach and focus on meaning-making around traumatic experiences. While narrative-based approaches are often considered “best practice” for trauma interventions, youth may present with comorbid conditions that present barriers or often preclude them from receiving trauma treatment, such as selective mutism (SM). In this case series, we describe the use of NET for treating PTS symptoms in two transgender youth with comorbid SM, as well as adaptations to support their engagement and progress in treatment. Treatment progress was observed in reduction of PTS symptoms, increase in self-reported resilience and positive well-being, and full remission of SM, with treatment gains observed 6-months post-discharge. From these cases, we identified that (1) NET is a brief treatment that can address PTS and SM symptoms among TGNB youth; (2) NET is able to be adapted to enhance engagement in a narrative-based, trauma-focused therapy for youth with PTS and SM; and (3) NET can also increase self-perceived resilience and a sense of positive well-being for TGNB youth.

Frequency and predictors of individual treatment outcomes (response, remission, exacerbation, and relapse) in clinical adolescents with nonsuicidal self-injury.

Nonsuicidal self-injury (NSSI) is prevalent in adolescent clinical samples. There is evidence that NSSI can be treated effectively but data on individual treatment outcomes is limited. The goal of this study was to examine response, remission, exacerbation, and relapse rates over one and two years, respectively, among a clinical sample of adolescents with NSSI. Furthermore, we aimed to identify clinically relevant predictors of NSSI trajectories. The sample consists of n = 203 adolescents (12-17 y., 94% female) from a specialized outpatient clinic for risk-taking and self-harming behavior with NSSI on at least five days in the six months before first assessment. Assessments were completed at baseline and one (FU1) and two (FU2) years later using structured clinical interviews and self-report questionnaires. At FU1, 75% reported a reduction in NSSI frequency by at least 50% (treatment response); among those, one third (25% of the entire sample) achieved a remission (0 NSSI); an exacerbation (⩾50% more NSSI) was observed in 11% of patients. Of those in remission, 41% relapsed one year later. Predictors of non-response or non-remission were inpatient treatment and depressive symptoms. Adolescents with lower NSSI frequency at baseline had a higher risk of exacerbation. Due to limited sample size at FU2 no prediction model for relapse was established. While most adolescents presenting with NSSI achieved significant improvement, more attention should be paid to the rather low rates of full remission. Prediction and early detection of individuals who deteriorate during or relapse after treatment is critical.

The stability and persistence of symptoms in childhood-onset ADHD.

The course of childhood-onset attention deficit hyperactivity disorder (ADHD) varies across individuals; some will experience persistent symptoms while others' symptoms fluctuate or remit. We describe the longitudinal course of ADHD symptoms and associated clinical characteristics in adolescents with childhood-onset ADHD. Participants (aged 6-12 at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study who met DSM criteria for ADHD prior to age 12 were evaluated annually with the Kiddie Schedule for Affective Disorders and Schizophrenia for eight years. At each timepoint, participants were categorized as meeting ADHD criteria, subthreshold criteria, or not havingADHD. Stability of course was defined by whether participants experienced consistent ADHD symptoms, fluctuating symptoms, or remission. The persistence of the symptoms was defined by symptom status at the final two follow-ups (stable ADHD, stable remission, stable partial remission, unstable). Of 685 baseline participants, 431 had childhood-onset ADHD and at least two follow-ups. Half had a consistent course of ADHD, nearly 40% had a remitting course, and the remaining participants had a fluctuating course. More than half of participants met criteria for ADHD at the end of their participation; about 30% demonstrated stable full remission, 15% had unstable symptoms, and one had stable partial remission. Participants with a persistent course and stable ADHD outcome reported the highest number of symptoms and were most impaired. This work builds on earlier studies that describe fluctuating symptoms in young people with childhood-onset ADHD. Results emphasize the importance of ongoing monitoring and detailed assessment of factors likely to influence course and outcome to help young people with childhood-onset ADHD.

Long term efficacy of psilocybin in patients with cancer and major depressive disorder (MDD).

12021 Background: Up to 25% of people living with cancer have depression. Existing psychological interventions have limited efficacy in treating depression. Psilocybin, a 5-hydroytrptamintergic psychedelic, coupled with group therapy is safe and effective in ameliorating symptoms of depression (Agrawal et al, ASCO 2022). Response to psilocybin treatment was observed in 83.3% of patients at 8 weeks, and 50% of patients showed full remission of depressive symptoms. This study evaluates the efficacy of psilocybin-assisted group therapy in relieving depression in cancer patients over 18 months. Methods: Adults with curable or metastatic cancer and MDD (according to DSM-5) underwent psychological assessments at baseline. They were treated with single-dose psilocybin 25 mg administered simultaneously in group cohorts of 3-4, supported with group and individual psychological therapy, and evaluated at 8 weeks and 18 months. Primary objectives were long-term effectiveness on depression and anxiety severity (as measured by change in Montgomery Asberg Depression Rating Scale [MADRS] and Hamilton Depression Rating Scale [HAM-A] scores by independent rater assessments) as well as clinical response (≥50% decrease in MADRS total score from baseline to 18 months) and remission (defined as patients with a MADRS total score ≤10 at 18 months). Results: Of 30 patients enrolled in the parent study, 2 died and 4 were lost to follow-up. Clinical response was demonstrated in 18/28 patients (64.2%) from baseline to 18 months follow-up (see table); 16/28 patients (57.1%) demonstrated remission of depression at 18 months. In 24 evaluable patients, continued reduction in mean depression severity scores was also demonstrated from baseline to week 8 (MADRS by 20.6 points [95% CI 23.2, 18.0, p < 0.001] and HAMA-A by 16.7 points [95% CI 19.7, 13.7, p < 0.001]) and from baseline to 18 months (MADRS by 16.7 points [95% CI 20.4, 12.9, p < 0.001] and HAMA-A by 14.4 points [95% CI 17.3, 11.4, p < 0.001]). Conclusions: Long-term follow-up suggests continued robust clinical response and remission from depression with a single dose of psilocybin and simultaneous psychological support in patients with cancer and MDD. These findings indicate psilocybin may play a role in treatment of depression in cancer patients, and further investigations are ongoing. [Table: see text]

Real world experience of Endoxifen augmentation therapy in a case of resistant OCD

About 40%–60% of obsessive-compulsive disorder patients do not achieve full remission even when treated with selective serotonin reuptake inhibitor and cognitive behavioural therapy. Here, we describe a case of a 30-year-old female suffering from OCD, who was not improved even after fluoxetine 80 mg per day and behavioural therapy and was successfully treated with low dose fluoxetine (60 mg/day) and Endoxifen (8 mg/day).

Depressive symptom dimensions predict the treatment effect of repetitive transcranial magnetic stimulation for post-stroke depression

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has attracted considerable attention because of its non-invasiveness, minimal side effects, and treatment efficacy. Despite an adequate duration of rTMS treatment, some patients with post-stroke depression (PSD) do not achieve full symptom response or remission. MethodsThis was a prospective randomized controlled trial. Participants receiving rTMS were randomly assigned to the ventromedial prefrontal cortex (VMPFC), left dorsolateral prefrontal cortex (DLPFC), or contralateral motor area (M1) groups in a ratio of 1:1:1. Enrollment assessments and data collection were performed in weeks 0, 2, 4, and 8. The impact of depressive symptom dimensions on treatment outcomes were tested using a linear mixed-effects model fitted with maximum likelihood. Univariate analysis of variance (ANOVA) and back-testing were used to analyze the differences between the groups. ResultsIn total, 276 patients were included in the analysis. Comparisons across groups showed that 17-item Hamilton Rating Scale for Depression (HAMD-17) scores of the DLPFC group significantly differed from those of the VMPFC and M1 groups at 2, 4, and 8 weeks after treatment (p < 0.05). A higher observed mood score (β = −0.44, 95% confidence interval [CI]: −0.85–0.04, p = 0.030) could predict a greater improvement in depressive symptoms in the DLPFC group. Higher neurovegetative scores (β = 0.60, 95% CI: 0.25–0.96, p = 0.001) could predict less improvement of depressive symptoms in the DLPFC group. ConclusionStimulation of the left DLPFC by high-frequency rTMS (HF-rTMS) could significantly improve depressive symptoms in the subacute period of subcortical ischemic stroke, and the dimension of depressive symptoms at admission might predict the treatment effect.

Subacute cutaneous lupus erythematosus as a rare complication of disease-modifying therapy administration in multiple sclerosis: case report

BackgroundTeriflunomide, the active metabolite of leflunomide, is a disease-modifying therapy drug used for the treatment of multiple sclerosis (MS), yet the complications associated with this drug remain not fully understood. Here we present the rare case of a 28-year-old female MS patient who developed subacute cutaneous lupus erythematosus (SCLE) following teriflunomide treatment. Though SCLE has been reported to be associated with leflunomide, the current report represents the first documented evidence demonstrating SCLE as a potential teriflunomide treatment-related complication. Additionally, a literature review on the leflunomide-induced SCLE was conducted to emphasize the association of SCLE with teriflunomide, specifically amongst the female demographic with a preexisting autoimmune diathesis.Case presentationA 28-year-old female first presented with MS symptoms in the left upper limb along with blurred vision in the left eye. Medical and family histories were unremarkable. The patient exhibited positive serum biomarkers including ANA, Ro/SSA, La/SSB, and Ro-52 antibodies. Relapsing–remitting MS was diagnosed according to the 2017 McDonald’s diagnostic criteria, and remission was achieved upon intravenous administration of methylprednisolone followed by teriflunomide sequential therapy. Three months post-teriflunomide treatment, the patient developed multiple facial cutaneous lesions. SCLE was subsequently diagnosed and was attributed to treatment-related complication. Interventions include oral administration of hydroxychloroquine and tofacitinib citrate effectively resolved cutaneous lesions. Discontinuation of hydroxychloroquine and tofacitinib citrate treatment led to recurring SCLE symptoms under continuous teriflunomide treatment. Full remission of facial annular plaques was achieved after re-treatment with hydroxychloroquine and tofacitinib citrate. The patient’s clinical condition remained stable in long-term outpatient follow-ups.ConclusionsAs teriflunomide has become a standard disease-modifying therapy for MS, the current case report highlights the importance of monitoring treatment-related complications, specifically in relation to SCLE symptoms.

Prevention of mania in a primigravida at ultra-high risk of postpartum recurrence.

Prevention of mania in a primigravida at ultra-high risk of postpartum recurrence.

Alteplase-induced facial orolingual angioedema (P12-5.012)

<h3>Objective:</h3> Represent post-thrombolysis angioedema, a relatively common adverse effect seen after administration of alteplase for acute ischemic stroke. <h3>Background:</h3> r-TPA induced angioedema is a common clinical finding after medication infusion for acute stroke. The incidence of this complication ranges from 1.3–8% (3, 4). Prognosis is usually good; most patients have symptom resolution within 72 hours (5). <h3>Design/Methods:</h3> Literature review revealed how signs and symptoms of angioedema differ in presentation and severity. We gathered case reports from the last decade to identify the most common location of stroke, site of edema, treatment used and complications of angioedema. <h3>Results:</h3> Symptoms usually began within 150 minutes after initial infusion (mean 70 minutes) and usually presented with unilateral angioedema, contralaterally to the side of the stroke. Approximately 30% of the patients required mechanical ventilation; most were on treatment with ACE inhibitors. The authors usually treated patients with a combination of steroids, antihistamines, adrenalin, or Icatibant, with complete recovery within 24 to 48 hours. <h3>Conclusions:</h3> Patients treated with Icatibant improved within minutes and achieved full remission in the first three hours. We believe it may become the standard of care in patients presenting with this uncommon but potentially life-threatening complication. <b>Disclosure:</b> Dr. Ayala Alvarez has nothing to disclose. Dr. Roque Sanchez has nothing to disclose. Dr. Jimenez-Ruiz has nothing to disclose. Dr. GOMEZ FIGUEROA has nothing to disclose. Omar Cardenas-Sanchez has nothing to disclose. Dr. Ruiz-Sandoval has nothing to disclose.

Structured physical exercise for bipolar depression: an open-label, proof-of concept study

BackgroundPhysical exercise (PE) is a recommended lifestyle intervention for different mental disorders and has shown specific positive therapeutic effects in unipolar depressive disorder. Considering the similar symptomatology of the depressive phase in patients with bipolar disorder (BD) and unipolar depressive disorder, it is reasonable to suggest that PE may also be beneficial for bipolar depression. However, there is an absence of studies evaluating the antidepressant effect of a structured PE intervention in BD.MethodsThis is an open-label, single-arm study trial. Fifteen patients with a diagnosis of BD Type I or Type II, presenting a depressive episode were included in the study. After physical and functional evaluation, patients participated in supervised training sessions with aerobics followed by strength exercises, three times per week, for 12 weeks (36 training sessions). Depressive and manic symptoms were assessed at baseline and 2, 4, 8, and 12 weeks. Additionally, quality of Life and functioning were assessed at baseline and 4, 8, and 12 weeks). Finally, we tested cardiorespiratory fitness, muscle strength and body composition at baseline and week-12.ResultsThe mean (± SD) Montgomery Asberg Depression Rating Scale (MADRS) score at baseline was 23.6 ± 8.3 points and after 12 weeks of PE the mean score was 10.2 ± 4.8 points. Nine patients (82%) presented an antidepressant response defined as a reduction of more than 50% of depressive symptoms at week 12 with five of those patients (45%) presenting criteria for full remission. A large and significant Cohen’s D Effect Size (pre-post) was verified for MADRS reduction [1.98 (95% Confidence interval = 0.88 to 3.08)]. We did not detect a significant change in manic symptoms, functioning, and quality of life during the 12-week follow-up. At week-12, all patients increased their muscular strength (one repetition maximal test − 1RM) and reduced the percentage of body fat (spectral bioelectrical impedance analysis).ConclusionsThis study, using rigorous criteria and a structured intervention, provides valid pilot data, showing the feasibility of a structured PE intervention for the treatment of depressive symptoms in BD, and suggesting a potential adjunctive antidepressant effect. Moreover, PE showed a positive impact on muscle strength and body composition. This should be further verified by randomized controlled studies.

Neural basis of memory impairments and relation to functional disability in fully or partially remitted patients with affective disorders

Bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive and functional impairment. Cognitive impairment is often associated with dorsal prefrontal cortex (dPFC) hypo-activity, but the neuronal correlates of functional disability is largely unknown. In this study, 91 patients with affective disorders in full or partial remission (BD, n = 67; MDD, n = 24) with objectively verified cognitive impairment and substantial functional disability underwent neuropsychological assessment and functional magnetic resonance imaging (fMRI) scan during which they completed a strategic picture-encoding task. For comparison, 36 matched healthy controls underwent an identical test protocol. Patients showed encoding-related hypo-activity in the dPFC compared to controls. In patients, lower right dlPFC activity was associated with poorer overall functioning and more antipsychotic drug use. In conclusion, memory impairments were underpinned by failure to recruit the dPFC during task performance which was associated with impaired functioning in fully or partially remitted patients with affective disorders. This aberrant neurocircuitry activity has implications for the design of future pro-cognitive interventions that aim to improve not only cognition but also real-world functioning.

Abstract CT095: Update: a phase 1/2, open-label study to assess safety, tolerability, biodistribution, radiation dosimetry and PET imaging characteristics of [18F]FPyGal in comparison to in-vitro diagnostic for the assessment of senescence in oncological patients (NCT04536454)

Abstract It is well established that senescence of cancer cells can be induced by treatment with classical cytotoxic therapies but also by molecularly targeted therapies or immunotherapies, a phenomenon referred to as therapy induced senescence (TIS). Occurrence of intratumoral senescence harbors broad therapeutic implications and may limit the prognosis of cancer patients, as senescent cells, via their senescence associated secretory phenotype (SASP), can suppress anti-tumor immune responses and may increase the metastatic potential of non-senescent cancer cells. Preclinical data suggest that an eradication of senescent cells (senolytic therapies) or an application of SASP modulating therapies might improve the outcome of systemic cancer therapies, however, as a prerequisite to guide such approaches, robust and non-invasive modalities to visualize and quantify intratumoral senescence are needed. We recently reported on the safety evaluation of the novel Positron-Emission-Tomography (PET) tracer [18F]FPyGal, a radiolabeled substrate of senescence-associated ꞵ-galactosidase in healthy volunteers (AACR 2022, #7958). In summary, our data showed that the use of [18F]FPyGal is safe and well-tolerated in the described human study population. In the second stage of our trial, we are now investigating the concordance of histopathological senescence markers with [18F]FPyGal senescence signals in i) rectum cancer-, ii) non-small cell lung cancer- and iii) adenocarcinoma of the esophagogastric junction (AEG) patients, who are undergoing neoadjuvant therapy. Here, we report on patients from the rectum cancer cohort of the trial. [18F]FPyGal PET imaging was done before and after administration of neoadjuvant radiochemotherapy (RCTx). [18F]FPyGal PET signal was correlated with immunohistochemical senescence markers (p16, p21, p53) and quantification of SA-ß-gal (Senescence-associated beta-galactosidase) positive cells in biopsy materials (pre-therapy) and surgical resection materials (post-therapy). Expectedly, senescent cells were only detected at very low frequency in therapy naïve tumors and the lack of histological detection of senescence correlated with negativity in [18F]FPyGal imaging. In stark contrast, homogenous senescence, quantified with the indicated senescence markers, was detected in the majority of cancer cells after RCTx. Interestingly, in one rectum carcinoma, which underwent a full remission after RCTx, senescence of stroma cells in the area of the former tumor bed was detected by PET imaging and histologically. Collectively, our data indicate the utility of [18F]FPyGal PET imaging to non-invasively detect senescence. Future trials using [18F]FPyGal to guide oncological therapy, e.g. to apply senolytic drugs in a personalized manner, are warranted. Citation Format: Christian LaFougere, Brigitte Gueckel, Helmut Dittmann, Nils Trautwein, Martina Hinterleitner, Jonathan Cotton, Gerald Reischl, Gabriele Kienzle, Stephan Singer, Cihan Gani, Ulrich Lauer, Bernd Pichler, Lars Zender. Update: a phase 1/2, open-label study to assess safety, tolerability, biodistribution, radiation dosimetry and PET imaging characteristics of [18F]FPyGal in comparison to in-vitro diagnostic for the assessment of senescence in oncological patients (NCT04536454) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT095.

In-Depth Assessment of Endoscopic Remission in Inflammatory Bowel Disease Treated by Anti-TNF or Vedolizumab.

Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor-treated patients. We screened patients with Crohn's disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded. Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline. Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor- and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified.

Psychiatric Comorbidity in patients with Pediatric Bipolar Disorder - a Systematic Review.

A growing body of evidence suggests that pediatric bipolar disorder (PBD) frequently co-occurs with comorbid psychiatric disorders that may impact functioning. To review existing literature on the prevalence of psychiatric comorbidity and general functioning in patients with a primary diagnosis of PBD. We performed a systematic literature search on the PubMed, Embase and PsycInfo databases on November 16th, 2022. We included original papers on patients ≤18 years with primary PBD and any comorbid psychiatric disorder, diagnosed according to a validated diagnostic tool. Risk of bias of the individual studies was assessed using the STROBE checklist. We calculated weighted means to assess the comorbidity prevalence. The review complied with PRISMA statement guidelines. 20 studies with a total study population of 2722 patients with PBD were included (mean age=12.2 years). We found an overall high prevalence of comorbidity in patients with PBD. The most common comorbidities were attention-deficit-hyperactivity disorder (ADHD) (60%) and oppositional defiant disorder (ODD) (47%). Anxiety disorders, obsessive-compulsive disorder, conduct disorder, tic disorders and substance-related disorders affected between 13.2% and 29% of patients, while one in ten had comorbid mental retardation or autism spectrum disorder (ASD). The prevalence of comorbid disorders was lower in studies that assessed the current prevalence in patients in full or partial remission. General functioning was overall not specifically decreased in patients with comorbidity. Comorbidity across a broad range of disorders was high in children diagnosed with PBD, especially regarding ADHD, ASD, behavioural and anxiety disorders including OCD. Future original studies should assess current prevalence of comorbidities in patients with PBD who are in remission to obtain more reliable estimates of psychiatric comorbidity in this patient group. The review highlights the clinical and scientific importance of comorbidity in PBD. This article is protected by copyright. All rights reserved.

Mycoviruses in Fungi: Carcinogenesis of Fungal Agents May Not Always Be Mycotoxin Related

Certain viruses have been found to induce diverse biological pathways to carcinogenesis, evidenced by the presence of viral gene products in some tumors. Despite the fact that many fungal agents contain mycoviruses, until recently, their possible direct effects on human health, including carcinogenesis and leukemogenesis, had not been explored. In this regard, most studies of fungal agents have rightly concentrated on their mycotoxin formation and effects. Recently, the direct role of yeasts and fungi in the etiology of cancers, including leukemia, have been investigated. While greater attention has been placed on the carcinogenic effects of Candida, the role of filamentous fungi in carcinogenesis has also been explored. Recent findings from studies using the enzyme-linked immunosorbent assay (ELISA) technique indicate that the plasma of patients with acute lymphoblastic leukemia (ALL) uniformly contains antibodies for a certain mycovirus-containing Aspergillus flavus, while controls are negative. The exposure of mononuclear leukocytes from patients with ALL in full remission, and long-term survivors, to the product of this organism was reported to result in the re-development of typical genetics and cell surface phenotypes characteristic of active ALL. Mycoviruses are known to be able to significantly alter the biological characteristics and functions of their host. The possible carcinogenic and leukemogenic role of mycoviruses, with and without their host, needs to be further investigated.

Long-Term Outcomes of Depression Treatment With Hypnotherapy or Cognitive Behavioral Therapy.

In a recent randomized controlled trial of mild to moderate depression, hypnotherapy (HT) was noninferior to cognitive behavioral therapy (CBT) after 6 months of outpatient treatment. In the present article, we extended the results in a secondary analysis and investigated how HT compares with CBT 1) during the course of the self-rated depressive symptoms throughout the 12-month follow-ups, 2) with regard to the rates of full remission, and 3) for the time to remission after treatment. Of the 152 randomized patients with current depression, 136 were available for the follow-up analyses. The course of self-rated depressive symptoms during follow-ups was analyzed with linear mixed-effects models. Time to a full remission, defined as eight consecutive weeks without depression, was compared between groups in a survival analysis. The self-reported depressive symptoms could be maintained on a low symptom level during the 12-month follow-up for both HT and CBT. Overall, both treatments achieved comparably high long-term remission rates of 73% after a median of 30 weeks. Outpatient psychotherapy with HT achieved good long-term results mostly comparable to CBT.