Preliminary Report Research Articles

RWD61 Inclusion of Productivity Losses and Gains in Cost-Effectiveness Analyses in Psoriasis: Preliminary Report of a Brazilian Association of Psoriasis (LATAM/LMIC)

RWD61 Inclusion of Productivity Losses and Gains in Cost-Effectiveness Analyses in Psoriasis: Preliminary Report of a Brazilian Association of Psoriasis (LATAM/LMIC)

Prevention of Ocular Toxicity Using Protective Contact Lenses in Multiple Myeloma Patients Receiving Belantamab Mafodotin, Pomalidomide and Dexamethasone: A Sub-Study of the Cmrg-007 Trial

Background: Belantamab mafodotin (belamaf) is a monomethyl auristatin-F containing antibody drug conjugate that targets BMCA on myeloma cells. Single agent belamaf has shown clinical meaningful activity in relapsed/refractory multiple myeloma (RRMM) but ocular adverse events (AEs) affect 53-72% of trials'participants. In DREAMM-2, prophylactic corticosteroid eye drops did not effectively reduce the risk of keratopathy. It is therefore imperative that strategies to mitigate corneal AEs be explored. This 2-part study is designed to evaluate belamaf and pomalidomide/dexamethasone (Pd) in RRMM. Here we report the efficacy and ocular AEs of patients (pts) receiving 2.5 mg/kg (maximum tolerated dose) or 1.92 mg/kg IV belamaf and administrated on various schedules aimed to define the optimal balance of efficacy and tolerability. We also present results of an ocular sub-study exploring the use of bandage contact lens (BCLs) to reduce the risk and severity of belamaf-associated ocular AEs. Methods: Eligibility: > 1 prior lines of therapy (LoT), lenalidomide, proteasome inhibitors exposed, and refractory to the last LoT. Pd was administered per standard of care and belamaf (1.92 or 2.5 mg/kg) Q4W or 2.5 mg/kg Q8W, Q12W or SPLIT equally on days 1 and 8, Q4W. Pts enrolled on the ocular sub-study received the recommended part two dose (RP2D): 2.5 mg /kg Q8W. A BCL (Bausch and Lomb Pure Vision) was placed in the right (R) eye for the 1st 2 doses of belamaf with the left (L) eye serving as control. Subsequently, BCLs were placed in both eyes. Pts wore BCLs for up to 28 days after each belamaf dose. Evaluation by an eyecare specialist for a comprehensive eye exam and BCL placement occurred every 15-28 days during BCLs use and prior to each belamaf dose. Corneal findings were graded (Gr) by the keratopathy and visual acuity (KVA) scale and findings of local infection were reported. Keratitis prophylaxis during BCLs use included gatifloxacin 0.3% or tobramycin 1.3% eye drops. Results: This analysis comprises 92 pts including 14 on the ocular sub-study. Baseline best corrected visual acuity (BCVA) and ocular comorbidities were similar across all cohorts: with median 20/20 BCVA 46.7% R and 50% L eye. Abnormal fundoscopy was 21.7% in R and 16.3% in L eye. There was a trend to lower incidence and less severity of ocular AEs for the 1.92 mg/kg dose (Table 1). Gr 3-4 keratopathy, decrease in BCVA and subjective Gr >2 blurred vision by CTCAE were 33.3% (4/12), 41.7% (5/12) and 25% (3/12) for the 1.92 mg/kg and 75% (9/12), 75% (9/12) and 33.3% (4/12) for 2.5 mg/kg Q4W cohorts. Preliminary data indicated superior clinical efficacy (ORR, >VGPR rate and mPFS) for the 2.5 mg/kg dose, 100% (12/12), 91.7% (11/12) and 25.1 months (11.8-NYR) versus 66.7% (8/12), 63.6% (7/12) and 16.9 months (5.3-19.7) for the 1.92 mg/kg dose (Table 2). To preserve efficacy but reduce ocular AEs additional cohorts exploring 2.5 mg/kg dosed every 8 and 12 weeks were included. Extended dosing schedules showed lower rates of Gr 3-4 keratopathy, decrease in BCVA, and Gr ≥2 blurred vision: 58.3% (7/12), 91.7% (11/12) and 16.7% (2/12) of pts treated Q8W; and 58.3%, 58.3% and 16.7% (2/12) of pts treated Q12W versus the Q4W schedule. Importantly, the efficacy was preserved with ORRs of 91.7% (11/12) and 100% (11/11), >VGPR rates of 83.3% (10/12) and 63.6% (7/11) and mPFS of 18.3 months (95% CI: 10.1-NYR) and 22.5 (95% CI: 8.9-NYR) for Q8W and Q12W groups, respectively. In the ocular sub-study, assessment of R and L eye during the first 2 belamaf doses showed a significant delay in onset of BCVA decrease in the R eye (p<0.0001) compared to the L. Comparing pts treated at the RP2D, moderate to severe (Gr ≥2) keratopathy and decrease BCVA were significantly lower (p=0.0004 and 0.010), in the BCL cohort versus no-BCL group. Further there was a trend towards less symptomatic blurred vision (p=0.256). BCL pts were able to complete 90% of the pre-planned belamaf cycles compared to 70% in the RP2D no-BCL group (p=0.029). No cases of infectious keratitis were reported in the BCL cohort. Conclusions: Our data suggest that extended dosing intervals may be a significant step forward in mitigating corneal AEs of belamaf. This preliminary report on the efficacy of BCLs in 14 pts demonstrates a decrease in moderate to severe corneal AEs and reduction in dose holds for corneal AEs, noting however a short follow up at this time. The data support the further evaluation of BCLs in preventing belamaf associated ocular toxicities.

Health-Related Quality of Life and Symptom Burden Profile of Patients with Pre-Fibrotic and Overt Myelofibrosis: A Preliminary Report from the Gimema-Prophecy Observational Study

Background Patients with overt myelofibrosis (MF) suffer a significant symptom burden and impairment of health-related quality of life (HRQoL). However, very little evidence-based data is available on HRQoL and the symptom burden of patients with pre-fibrotic MF. Aim The primary objective of this study was to describe the HRQoL profile of patients with pre-fibrotic MF relative to patients with overt MF. The secondary objective was to examine disease-specific symptom prevalence in both groups. Methods. Baseline data from an ongoing prospective multicenter observational study by the GIMEMA Group were analyzed. The inclusion criteria of this study were: adult patients diagnosed with Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), according to the 2016 WHO classification, within one year before the registration date. For the purpose of this analysis, only patients with pre-fibrotic and overt MF were considered. HRQoL profile was assessed with the EORTC QLQ-C30, which consists of 30 items and includes five functional scales (physical, role, emotional, social, and cognitive), three symptoms (fatigue, nausea, vomiting, and pain), a global health status/QoL scale and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Well-established evidence-based guidelines for interpreting the QLQ-C30 were used to determine clinically meaningful differences between groups (i.e., pre-fibrotic vs overt MF). Given the exploratory nature of the study, n o statistical testing was performed on mean score differences. Symptom prevalence was assessed by items of the MPN-SAF TSS. The MPN-SAF TSS is a comprehensive and brief 10-item instrument that concisely assesses the prevalence and severity of debilitating symptoms of MF. The percentage of patients who reported symptoms on the MPN-SAF TSS was based on the number of patients who answered at least 1 on a given item. Results. Overall, 104 patients with a median age of 68 years (IQR: 59-76) were enrolled across 20 community and university-based hospitals. More than half of the patients were male (n=58; 56%), and 55 (53%) revealed splenomegaly. Thirty-five patients (34%) reported at least one comorbidity. The median time since diagnosis for the overall group was 4 months (IQR: 1-7), and there were 69 and 35 patients diagnosed with overt and pre-fibrotic MF, respectively. The median age of patients with overt MF and pre-fibrotic MF was 69 (IQR: 61-76) and 63 (IQR: 57-75), respectively. At study entry, no statistically significant differences were observed between the two groups regarding age, sex, prevalence of comorbidities, WBC, and PLT counts. However, patients with overt MF had lower Hb levels (p=.003). Inspection of the HRQoL profile, according to the EORTC QLQ-C30, showed that patients with overt MF had a statistically and clinically meaningful worse global HRQoL compared to patients' pre-fibrotic MF (Δ=11.4). The following functioning scales were also mostly impaired in patients with overt MF: role functioning (Δ=14.2), cognitive functioning (Δ=4.7), and social functioning (Δ=8.1) (Figure 1). With regard to symptoms severity, patients with overt MF reported clinically meaningful higher severity for fatigue (Δ=6), pain (Δ=7.2), insomnia (Δ=6), constipation (Δ=5.4), and appetite loss (Δ=6.8). However, patients with pre-fibrotic MF reported clinically meaningful higher severity for dyspnea (Δ=5.5). The prevalence of symptoms according to the MPN-SAF TSS, overall and by disease group, is reported in Table 1. The prevalence of symptoms in the overall group of patients was high, with the top three most prevalent symptoms being fatigue (78%), concentration problems (53%), and inactivity (50%). Notably, the prevalence of symptoms was also high in patients with pre-fibrotic MF, with some one-third of them reporting: fatigue, concentrations problem, inactivity, early satiety, abdominal discomfort, night sweats, itching, and bone pain. Conclusions. To the best of our knowledge, this is one of the first evidence describing HRQoL and the symptom burden of patients with pre-fibrotic MF. Although our preliminary data suggest that the HRQoL profile of patients with pre-fibrotic MF was generally worse than those with overt MF, our findings also indicate a high symptom prevalence in patients with pre-fibrotic MF.

A Preliminary Report of Clinical Study on Immunosuppressive Therapy Combined with Avatrombopag As the First-Line Treatment for Severe Aplastic Anaemia in Elderly Patients

Objective The objective is to evaluate the early hematologic response (HR) rate and safety of immunosuppressive therapy (IST) combined with avatrombopag as the first-line treatment for severe/very sever aplastic anaemia(V/SAA) in elderly patients. Methods Prospective，multi-center, single-arm, clinical research. IST treatment regimen: pig anti-human lymphocyte globulin (ALG-p, Wuhan Institute of Biological Products Co., Ltd. China) 20 mg/kg/d for five days and cyclosporin A (CsA) 3 mg/kg/d with adjusted concentration of 150-250 ng/mL, and oral avatrombopag 40 mg/d from the first day of IST initiation up to six months. The patients' treatment responses were evaluated and the major adverse events were collected. Results Ten patients have been enrolled in the study at our centre from June 2022 to October 2022.Among 10 patients, six had SAA and four had VSAA; male: female = 1:1, median age of 68 (60-82) years, and median time from diagnosis to treatment of 44 (20-480) days. The patients' treatment responses were evaluated after initiation of IST, at 3 months: 7 HR [1 complete response (CR), 3 good partial response (GPR), 3 partial response (PR), and 3 no response (NR)]; and at 6 months: 8 HR (1 CR, 5 GPR, 2 PR) and 2 deaths due to infection. The median time of red-cell transfusion independence was 60 (3-168) days in HR patients and that of platelets was 60 (16-153) days. No relapse and clonal evolution occurred within six months. Major adverse events within three months were infection in five cases, electrolyte disturbance in five cases, and cardiac insufficiency in three cases. Liver function abnormalities occurred in two cases, both of which showed elevated alanine aminotransferase up to 174 μ/L and 208.7 μ/L on day 8 and 20 of IST treatment, respectively. Two of the five infected patients had sepsis caused by Enterobacter cloacae. Except for infection, the remaining adverse events were of grade I-II. All the adverse events were effectively controlled. Table 1 summarises the characteristics and clinical status of patients before and after the treatment. Conclusion This preliminary study of IST combined with avatrombopag for the treatment of elderly patients with V/SAA showed the potential of the combination to improve haematologic response rate and quality in elderly patients with AA, and it is well tolerated as well. Keywords: immunosuppressive therapy, severe aplastic anaemia, avatrombopag, elderly

Analysis of cells of epithelial, connective tissue and immune differentiation in HPV-positive-, HPV-negative oropharyngeal carcinoma and normal oropharyngeal tissue by immunofluorescence multiplex image cytometry: a preliminary report

BackgroundEpithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of HPV positive (HPV+) and HPV negative (HPV-) oropharyngeal squamous cell carcinoma (OPSCC). We aimed to investigate the abundance of these cell lineages and their coexpression patterns in patients with HPV + and HPV- OPSCC.MethodsWe used a 4-channel immunofluorescence-microscopy technique for the simultaneous detection of three direct-conjugated antibodies (pancytokeratin, vimentin and CD45/CD18) and DAPI (4’,6-Diamidin-2-phenylindole) in formalin fixed paraffin-embedded tissue samples (FFPE) of patients with HPV + and HPV- OPSCC, and of control patients. Image acquisition and analysis were performed with TissueFAXS and StrataQuest (TissueGnostics, Vienna, Austria), respectively, in tumor cell clusters/stroma in OPSCC specimens and epithelial layer/lamina propria in control specimens. Cell populations were created based on antibodies’ coexpression patterns. Isotype and positive controls were examined for plausibility.ResultsThe proportion of cells of epithelial differentiation in tumor cell clusters was higher in HPV + OPSCC (55%) than in HPV- OPSCC samples (44%). The proportion of connective tissue cells in tumor cell cluster was lower in HPV + OPSCC patients (18%) than in HPV- OPSCC patients (26%). The proportion of immune cells in tumor cell clusters was higher in HPV + OPSCC patients (25%) than in HPV- OPSCC patients (18%). The percentage of anaplastic, potentially de-differentiated cells, was 2% in control patients, and it was higher in HPV- OPSCC (21%) than in HPV + OPSCC samples (6%).ConclusionsThis study provided the first quantitative data for the abundance of cells of epithelial, connective tissue and immune differentiation, in patients with OPSCC and control patients. The abundance of these different crucial cell populations was consistently originating from the same tissue sample. De-differentiation of tumor cells was higher in HPV- OPSCC than in HPV + OPSCC. In tumor cells clusters, the antitumoral host immune response was higher in HPV + OPSCC than in HPV- OPSCC, whereas the fibroblast response was higher in HPV- OPSCC than in HPV + OPSCC. This study contributed to the understanding of histopathologic differences between HPV + OPSCC and HPV- OPSCC patients.

Impact of relaxing incisions on maxillofacial growth following Sommerlad–Furlow modified technique in patients with isolated cleft palate: a preliminary comparative study

ObjectiveTo estimate the impact of relaxing incisions on maxillofacial growth following Sommerlad-Furlow modified technique in patients with isolated cleft palate.Study designA Retrospective Cohort Study.MethodsA total of 90 participants, 60 patients with non-syndromic isolated soft and hard cleft palate underwent primary palatoplasty (30 patients received the Sommerlad-Furlow modified technique without relaxing incision (S.F−RI group), and 30 received Sommerlad-Furlow modified technique with relaxing (S.F+RI group) with no significant difference found between them regarding the cleft type, cleft width, and age at repair. While the other 30 were healthy noncleft participants with skeletal class I pattern as a Control group. The control group (C group) was matched with the patient groups in number, age, and sex. All participants had lateral cephalometric radiographs at least 5 years old age. The lateral cephalometric radiographs were taken with the same equipment by the same experienced radiologist while the participants were in centric occlusion and a standardized upright position, with the transporionic axis and Frankfort horizontal plane parallel to the surface of the floor. A well-trained assessor (S. Elayah) used DOLPHIN Imaging Software to trace twice to eliminate measurement errors. All the study variables were measured using stable landmarks, including 12 linear and 10 angular variants.ResultsThe mean age at collection of cephalograms was 6.03 ± 0.80 in the S.F+RI group, 5.96 ± 0.76 in the S.F−RI group, and 5.91 ± 0.87 in the C group.Regarding cranial base, the results showed no statistically significant differences between the three groups in S–N and S–N-Ba. While the S.F+R.I group had a significantly shortest S-Ba than the S.F−R.I & C groups (P = 0.01 & P < 0.01), but there was no statistically significant difference between S.F−R.I & C groups (P = 0.71).Regarding the skeletal maxilla, there was no significant difference between the S.F+R.I and S.F−R.I groups in all linear measurements (N-ANS and S-PM) except Co-A, the S.F+R.I group had significantly shorter Co-A than the S.F−R.I & C groups (P = < 0.01). While the angular measurement, S.F+R.I group had significantly less SNA angle than the S.F−R.I & C groups (P = < 0.01).Regarding mandibular bone, there were no statistically significant differences in all linear and angular mandibular measurements between the S.F+R.I and S.F−R.I.groups.Regarding intermaxillary relation, the S.F+R.I group had significant differences in Co-Gn—Co-A and ANB compared to the S.F−R.I & C groups (P = < 0.01). While there was no statistically significant difference in PP-MP between the three groups.ConclusionAs a preliminary report, the Sommerlad-Furlow modified technique without relaxing incisions was found to have a good maxillary positioning in the face and a satisfactory intermaxillary relationship compared to the Sommerlad-Furlow modified technique with relaxing incisions.

A comparison of maxillofacial growth in Chinese children with isolated cleft palate treated with two different palatoplasty techniques without relaxing incisions: a preliminary study

ObjectiveTo assess the maxillofacial growth of patients with isolated cleft palate following the Sommerlad-Furlow modified technique and compare it with the effect of the Sommerlad technique.Study designA Retrospective Cohort Study.MethodsA total of 90 participants, 60 patients with non-syndromic isolated soft and hard cleft palate (ISHCP) underwent primary palatoplasty without relaxing incision (30 patients received the Sommerlad-Furlow modified (S-F) technique and 30 received Sommerlad (S) technique). While the other 30 were healthy noncleft participants with skeletal class I pattern (C group). All participants had lateral cephalometric radiographs at least 5 years old age. All the study variables were measured by using stable landmarks, including 11 linear and 9 angular variants.ResultsThe means age at collection of cephalograms were 6.03 ± 0.80 (5–7 yrs) in the S group, 5.96 ± 0.76 (5–7 yrs) in the S-F group, and 5.91 ± 0.87 (5–7 yrs) in the C group. Regarding cranial base, the results showed that there were no statistically significant differences between the three groups in S–N and S–N-Ba. The S group had a significantly shortest S-Ba than the S-F & C groups (P = 0.01), but there was no statistically significant difference between S-F and C groups (P = 0.80). Regarding skeletal maxillary growth, the S group had significantly shorter Co-A, S- PM and significantly less SNA angle than the C group (P = < 0.01). While there was no significant difference between S-F & C groups (P = 0.42). The S group had significantly more MP-SN inclination than the C group (P = < 0.01). Regarding skeletal mandibular growth, there were no statistically significant differences in all linear and angular mandibular measurements between the three groups, except Co-Gn of the S group had a significantly shorter length than the C group (P = 0.05). Regarding intermaxillary relation, the S-F group had no significant differences in Co-Gn—Co-A and ANB as compared with the C group. The S group had significantly less ANB angle than S-F & C groups (P = 0.01 & P = < 0.01). In addition, there were no significant differences in all angular occlusal measurements between the three groups.ConclusionAs a preliminary report, Sommerlad-Furlow modified technique showed that maxillary positioning in the face tended to be better, and the intermaxillary relationship was more satisfactory than that in Sommerlad technique when compared them in healthy noncleft participants.

The stress-buffering role of friendships in young people with childhood threat experiences: a preliminary report

ABSTRACT Background: High-quality friendships have a positive impact on the mental health of young people with childhood adversity (CA). Social stress buffering, the phenomenon of a social partner attenuating acute stress responses, is a potential yet unexplored mechanism that may underlie this relationship. Objective: This study examined whether perceived friendship quality was related to better mental health and lower neural stress response in young people with CA. Method: A total of N = 102 young people (aged 16–26) with low to moderate CA were included in the study. We first investigated associations between friendship quality, mental health, and CA. In a representative subset (n = 62), we assessed neural stress responses using the Montreal Imaging Stress Task. In our sample, CA was best described along two dimensions resembling threat or deprivation like experiences. Hence, we investigated both cumulative and dimensional effects of CA. Results: We found no support for social thinning after CA, meaning that the severity of CA (cumulative or dimensional) did not differentially impact friendship quality. High-quality friendships, on the other hand, were strongly associated with better mental health. Furthermore, acute stress increased state anxiety and enhanced neural activity in five frontolimbic brain regions, including the left hippocampus. We found weak support that threat experiences interacted with friendship quality to predict left hippocampal reactivity to stress. However, this effect did not survive multiple comparison correction. Conclusion: The absence of social thinning in our sample may suggest that the risk of developing impoverished social networks is low for rather well-functioning young people with low to moderate CA. Regardless, our findings align with prior research, consistently showing a strong association between high-quality friendships and better mental health in young people with CA. Future research is needed to examine whether friendships aid neural stress responses in young people with childhood threat experiences.

Assessment of deep plane facelift combined with fascia lata graft for the static treatment of facial palsy: A preliminary report

Addressing facial palsy (FP) presents intricate challenges in achieving natural expressions.While free functional muscle transfers (FFMT) offer effective smile restoration, age impacts their efficacy.The optimal FFMT age range of 5-55 is limited by physical fitness, which extends beyond age boundaries. Unilateral FP demands vary; younger patients require dynamic solutions like FFMT, whereas older individuals prioritize public appearance due to baseline distortion. The aim of this study is to describe and to assess a new static technique combining deep plane facelift and fascia lata graft (FLG) for FP treatment. We conducted a prospective pilot study enrolling unilateral FP patients aged >55 and declining FFMT. Exclusions encompassed prior FP surgery, recent injections, uncontrolled diabetes cognitive deficits and Patients unable to quit smoking.To evaluate this technique, the Glasgow Benefit Inventory (GBI), along with two objective scales: the Face and Neck-Lift Objective Photo-Numerical Assessment Scale and the eFACE scale, were used. Interrater reliability and Intrarater reliability were assessed. Fifteen patients (mean age: 60.9 years) underwent the procedure. Both static and dynamic symmetry significantly improved (p<0.05), including check volume and position, oral commissure, and jawline. Notably, eye closure enhancement was observed. GBI scores also significantly increased (p<0.05). Interrater reliability and Intrarater reliability were minimal (p=0.12 and p=0.13).This combined approach offers a static FP treatment option, especially for the elderly or FFMT-ineligible patients. The relatively brief procedure yields immediate and satisfactory results, suggesting its potential value in FP management. Further comprehensive studies are encouraged to validate the technique's long-term efficacy and applicability across larger populations.

Preliminary report on a novel technique for endoscopic transaxillary thyroidectomy: a case-control study.

Endoscopic transaxillary approaches to thyroidectomy have been well described and gasless transaxillary endoscopic thyroidectomy (GTET) is the most popular method. However, this require a single long axillary incision which is longer than most remote access thyroidectomy procedures. The authors improved the GTET and provided a novel way to access the thyroid. The purpose of this study was to test the feasibility of our novel transaxillary thyroidectomy procedure and to attempt to reduce the size of the scar and reduce the flap creation area. One hundred sixteen patients who underwent our novel transaxillary thyroidectomy procedure were compared with the patients who underwent open and GTET procedures. The patients' demographics, outcomes, and complications were analyzed. Although the operation time (121.48±23.91mins) was longer in the novel endoscopic group compare to the open group, it was shorter than GTET group. Intraoperative blood loss was similar between the groups. However, the novel procedure group had more drainage volume within 48 postoperative hours compare to other two groups. Despite the VAS pain score did not reveal a difference between the open and novel endoscopic procedure, it was lower in the novel procedure than GTET. The hospital stay days did not show a difference between the two groups. The number of resected central lymph nodes was similar between the groups. Differences did not reveal between the groups regarding to the complications rate. Our results showed that our novel transaxillary thyroidectomy procedure is feasible and safe. This procedure can be an alternative endoscopic transaxillary method for thyroidectomy.

A preliminary report on sculptures and figurative terracottas found at the site of Vlochos, region of Karditsa, Thessaly

The existence of an ancient city at Thessalian Vlochos was first established by the discovery in 1964 of several inscribed stelai at a quarry at the site, which in turn prompted its declaration as a protected archaeological zone. A large spoil-heap with mixed soils and quarry debris had been left after the closure of the quarry, and this was examined and removed as part of the ongoing Greek-Swedish archaeological collaboration at the site. Apart from quarry debris and rubbish, the soils of the heap yielded considerable amounts of pottery and tile, and also architectural members, terracotta figurines, stelai, marble statuettes, and votives. The mixed nature of the soils made all finds ex situ, but the composition of the material provides a transect of the chronology of the site at Vlochos, as well as strong indications of cult, including evidence for the cult of the Thessalian goddess Ennodia.

High-resolution PGT-A results in incidental identification of patients with small pathogenic copy number variants

PurposeThis study aimed to evaluate whether a high-throughput high-resolution PGT-A method can detect copy number variants (CNVs) that could have clinical implications for patients and their embryos.MethodsA prospective analysis of PGT-A cases was conducted using a high-resolution SNP microarray platform with over 820,000 probes. Cases where multiple embryos possessed the same segmental imbalance were identified, and preliminary PGT-A reports were issued recommending either parental microarray or conventional karyotyping to identify CNVs or translocations.ResultsAnalysis of 6080 sequential PGT-A cases led to identification of 41 cases in which incidental findings were observed (0.7%) and parental testing was recommended. All cases, in which parental studies were completed, confirmed the original PGT-A incidental findings. In 2 of the cases, parental studies indicated a pathogenic variant with clinical implications for the associated embryos. In one of these cases, the patient was identified as a carrier of a duplication in chromosome 15q11.2:q11.2 (SNRPN + +), which is associated with autism spectrum disorder. In the second case, the patient was heterozygous positive for an interstitial deletion of 3p26.1:p26.3, which is associated with 3p deletion syndrome and had clinical implications for the patient and associated embryos. In each case, parental studies were concordant with PGT-A findings and revealed the presence of an otherwise unknown CNV.ConclusionHigh-throughput high-resolution SNP array–based PGT-A has the ability to detect previously unknown and clinically significant parental deletions, duplications, and translocations. The use of cost-effective SNP array–based PGT-A methods may improve the effectiveness of PGT by identifying and preventing previously unknown pathogenic CNVs in children born to patients seeking in vitro fertilization.

A novel finger brace for preventing finger stiffness after trauma or surgery: a preliminary report with a case series

Purpose: Finger stiffness is a common complication following hand trauma or surgery. Early finger range-of-motion (ROM) exercises have proven to be the most effective method for preventing finger stiffness. In this paper, we introduce a novel finger brace designed for safe and early active exercises and present preliminary results from a small case series.Methods: Our innovative brace is designed for direct insertion into the finger, ensuring enhanced comfort during use. This brace features hinges that facilitate unrestricted movement in the proximal and distal interphalangeal joints, with each phalangeal component having a rounded shape to prevent rotation. Furthermore, grooves are integrated at the top of the phalangeal components for inserting bars; a straight bar to immobilize and a silicone band to provide elastic resistance exercises within a limited range.Results: Among 26 patients, 17 presented with fractures, five had extensor tendon injuries, and three had dislocations. For patients not requiring surgery, we applied the brace as early as possible. In cases involving surgery, the brace was applied step by step. When fixation was necessary for the first time, a straight bar was applied, and when starting finger movement, a silicone band was applied. The silicone band was then released to allow free finger movement. Except for one patient necessitating extensor tendon reconstruction due to a neglected rupture, all patients achieved full ROM without any complications.Conclusion: Our novel ROM finger brace represents a safe and user-friendly option for effectively initiating finger ROM exercises.

ChatGPT takes on the european exam in core cardiology: an AI success story

Abstract Background ChatGPT, the trending novel artificial intelligence has triggered ongoing debate regarding its capabilities.Recently, preliminary reports showed that answered correctly in the majority of questions of the United States Medical License Examinations (USMLE). However, its ability to succeed a more precise, challenging and high-stakes post-graduate test, such as the final exam for the completion of medical residency , like the European Exam in Core Cardiology (EECC), is not known yet. Purpose We sought to evaluate the performance of ChatGPT on EECC, to test its capability on a more demanding, high-stakes post-graduate exam in Cardiology training. Methods A total of 488 publicly-available single-answer multiple choice questions (MCQs) were randomly obtained from three different MCQs sources that are traditionally used for the preparation for the EECC: 88 from the sample exam questions released since 2018 from the official ESC website, 200 from the 2022 edition of StudyPRN and 200 from the Braunwald's Heart Disease Review and Assessment (BHDRA). Questions containing audio or visual assets were excluded. After filtering, 362 MCQ items (ESC sample: 68, BHDRA:150, StudyPRN: 144) were included and considered as input source. False responses and indeterminate responses were considered as not correct. Results ChatGPT answered to 340 questions out of 362, with 22 indeterminate answers in total. The overall accuracy was 58.8% across all the question sources. More specifically, it demonstrated an accuracy for the ESC sample, BHDRA and StudyPRN of 61.7%, 52.6%, 63.8% respectively. It answered correctly 42/68 (4 indeterminate) of ESC sample questions, 79/150 (11 indeterminate) of the BHDRA and 92/144 (7 indeterminate) of the StudyPRN. Conclusion ChatGPT manages to correctly answer the majority of EECC’s questions and perform within the passing threshold range. Although it cannot yet process visual content, it can provide rational and correct answers to text-based inputs in most scenarios. The model may be able to efficiently handle a massive amount of acquired medical knowlededge, but the current approach may not substitue for critical thinkg, innovation and creativity; some of the key attibutes that doctors are expected to showcase.Performance of ChatGPT on EECCExample of MCQ input at ChatGPT

Fully automated quantitative stress perfusion cardiac MRI to assess myocardial perfusion in adult patients with convalescent Kawasaki disease and coronary aneurysms: an age and sex-matched analysis

Abstract Introduction Coronary aneurysms are a well-documented complication of childhood Kawasaki disease. They may persist into adulthood predisposing to impaired myocardial blood flow, symptoms, and adverse cardiovascular events. Preliminary reports suggest that Kawasaki disease may also be associated with coronary microvascular dysfunction. The effect of coronary involvement from Kawasaki disease on myocardial perfusion in convalescent asymptomatic adults has not been studied using fully automated inline quantitative perfusion MRI (CMR). Purpose To assess the effect of coronary artery abnormalities on quantitative myocardial perfusion in adult patients with convalescent Kawasaki disease compared to an age and sex-matched control cohort. Methods Retrospective single centre cohort analysis of adult patients with convalescent Kawasaki disease who have undergone fully automated inline quantitative myocardial stress perfusion CMR. All patients had coronary involvement during their acute childhood illness. An age and sex-matched group (n=14) with normal CMRs was selected for comparison. Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. A per-vessel analysis was performed using a linear mixed effects model with pairwise comparisons to assess the effect of coronary abnormalities (normal, aneurysmal with or without thrombosis, revascularised) on myocardial perfusion reserve (MPR). Results 28 patients were included (14 Kawasaki; 14 controls). All patients in the Kawasaki cohort had assessment of coronary anatomy either by CT (93%) or invasive (7%) coronary angiography. A total of 84 vessels were analysed. Mean age and sex were well matched (Kawasaki: 27±6.2 years; 13 males : 1 female vs. controls: 27±6.4 years; 13 males : 1 female). In patients with Kawasaki disease, thrombosed aneurysmal arteries were associated with a significantly impaired MPR compared to normal (mean Δ: -0.817; P=0.003) and aneurysmal (mean Δ: -0.957; P&amp;lt;0.001) arteries. MPR in aneurysmal and revascularised arteries were not significantly different from normal arteries in patients with Kawasaki disease. There was no significant difference in MPR between normal coronary arteries in patients with Kawasaki compared to controls. Conclusions Thrombosis in coronary aneurysms was associated with a significant impairment of myocardial perfusion in adult patients with convalescent Kawasaki disease. There was no significant reduction in perfusion in territories supplied by normal or aneurysmal arteries which does not support coronary microvascular dysfunction in these patients. Further studies are needed to confirm these preliminary findings.

Preliminary Report on the 2019 and 2020 Seasons of the New York University-ISAW Project at the Temple of Ramesses II in Abydos

&#x0D; &#x0D; &#x0D; This preliminary report provides a general account of the fieldwork of the New York University-ISAW during the two seasons 2019 and 2020 at the temple of Ramesses II in Abydos. The results include the discovery of a temple palace, ten mud-brick magazines, and foundation deposits, as well as a pair of cartouches of Ramesses II carved on the sub-foundation on each side of the four corners of temple, the unusual burial of a bovine skeleton under the floor of the temple palace, and animal skulls and bones packed inside niches cut in some of the magazines’ walls.&#x0D; &#x0D; &#x0D;

Abstract 15351: Characteristics of Veterans Enrolled in a Nationwide Home Telemonitoring Blood Pressure (BP) Program

Background: Guidelines recommend home BP monitoring for the diagnosis and management of hypertension. The Veterans Affairs (VA) has a robust nationwide home BP monitoring telehealth (HT) program. Aims: We aimed to determine factors associated with being enrolled in the VA’s HT program using a nationwide cohort. Methods: Veterans with hypertension and a primary care (PC) visit between 4/2013 and 9/2015 were identified and classified as telehealth if they enrolled in the HT program and were issued a home-telehealth BP monitor. Control patients were not enrolled. Patient characteristics including the care assessment needs (CAN) score (validated probability for mortality or hospitalization in the following year) were extracted from the electronic health record (EHR). Results: Over 33 months, 29,927 (2.5%) veterans were enrolled in the HT program and 1,160,506 (97.5%) veterans with hypertension were not enrolled. Compared to controls, HT patients were of similar age (median 66 years), were more likely to be female (5.6% vs 4.6%), be of Black race (28.7% vs 20.1%), have a higher index median systolic BP (158.4 vs 153 mmHg), have a greater number of PC visits in the 2 years prior (11 vs 7 visits), have a higher median probability of a mortality or hospitalization event within 1 year (13% vs 7%) and were on a greater number of antihypertensive medications than those not enrolled (Table). These veterans were seen by 9,301 PC providers, who enrolled the following percentages of their hypertensive patients (% of patients by % of providers): 0% by 22%, &lt;2% by 24.1%, 2-5% by 28.9%, 5-10% by 16.4%, 10-20% by 6.9% and &gt;20% by 1.7%. Conclusion: The VA’s HT program is used by a limited number of Veterans. Those enrolled are sicker and have a greater burden of hypertension than those not enrolled. Most providers have a small percentage of their panel of patients enrolled. This preliminary report comes from a study evaluating the effect of HT on BP control, cardiovascular events, and non-cancer mortality.

416 Urgency to Address Infrastructure in Animal sciences–A Preliminary Report

Abstract The purpose of the ASAS Public Policy Committee (PPC) is to help ASAS shape public policy and public opinion on current issues affecting farms and companion animals. PPC sets goals to make federal agencies aware of the scientific expertise and resources available within ASAS that could be used to develop science-based federal policies affecting poultry and livestock production. Recent reports point to a poor state of agricultural facilities at public colleges of agriculture which puts research priorities related to adaptation to and mitigation of climate change, food safety, zoonotic disease preparedness, animal populations and their care, diet-health, nutrition, biosecurity, new biobased packaging, energy innovations, and advanced market analysis at risk (APLU, 2021). To ascertain input specific to the Animal Sciences (AS), an IRB approved ‘Survey About Infrastructure in Animal Sciences’ (#22-495) was offered by the PPC to department heads and faculty of Animal Science programs across the country. The survey instrument was constructed to allow open-ended responses as well as 5-point Likert scale questions regarding participants views about infrastructure (IF) and thereby learn what members closest to the animal sciences community perceive to be the strengths, weaknesses, and opportunities for improvement in our research infrastructure. Analysis of coded responses in the open-ended questions among varied disciplinary arenas within AS revealed ‘facilities’ as the largest Grand Challenge. About 98% of respondents affirmed sustainable food and animal production is a critical national asset in terms of economic growth and development and 98% indicated an overlooked maintenance of IF in AS undermines national food security. Additionally, 68% indicated the state of core labs, at least for AS programs are only average or below. All respondents (100%) agreed that without comprehensive investment in infrastructure within AS, the USA will continue to fall behind in competing with other countries in areas of research. Study results provided insight into potential consequences of deferred maintenance which should elevate awareness of urgency to address the deficiencies. Since IF needs included future workforce development and working environments, an eroded IF and consequences of deferred maintenance threatens the capacity of AS to pursue Grand Challenges in research and ability to create future workforce readiness of graduates from AS programs.

Phenotypic similarity-based approach for variant prioritization for unsolved rare disease: a preliminary methodological report

Rare diseases (RD) have a prevalence of not more than 1/2000 persons in the European population, and are characterised by the difficulty experienced in obtaining a correct and timely diagnosis. According to Orphanet, 72.5% of RD have a genetic origin although 35% of them do not yet have an identified causative gene. A significant proportion of patients suspected to have a genetic RD receive an inconclusive exome/genome sequencing. Working towards the International Rare Diseases Research Consortium (IRDiRC)’s goal for 2027 to ensure that all people living with a RD receive a diagnosis within one year of coming to medical attention, the Solve-RD project aims to identify the molecular causes underlying undiagnosed RD. As part of this strategy, we developed a phenotypic similarity-based variant prioritization methodology comparing submitted cases with other submitted cases and with known RD in Orphanet. Three complementary approaches based on phenotypic similarity calculations using the Human Phenotype Ontology (HPO), the Orphanet Rare Diseases Ontology (ORDO) and the HPO-ORDO Ontological Module (HOOM) were developed; genomic data reanalysis was performed by the RD-Connect Genome-Phenome Analysis Platform (GPAP). The methodology was tested in 4 exemplary cases discussed with experts from European Reference Networks. Variants of interest (pathogenic or likely pathogenic) were detected in 8.8% of the 725 cases clustered by similarity calculations. Diagnostic hypotheses were validated in 42.1% of them and needed further exploration in another 10.9%. Based on the promising results, we are devising an automated standardized phenotypic-based re-analysis pipeline to be applied to the entire unsolved cases cohort.

New records of the white-cheeked macaque provide range extension for the endangered primate in Gaoligong Mountains.

White-cheeked macaque Macaca leucogenys is a recently described primate species discovered by camera-trap surveys in the Medog region in 2015. The species was thought to be narrowly distributed in southeastern Tibet. However, knowledge on the distribution and conservation of the species is quite limited. Based on a systematic camera-trapping survey, we report the occurrence of the species in the Gaoligong Mountains, over 350km southeast of the nearest known population. We recorded 3025 photographs of white-cheeked macaques representing 481 independent records from 59 camera-trap stations with total trapping efforts of 18,437 camera days. Notably, part of the newly discovered locations of the white-cheeked macaque are outside of nature reserves without any formal protection and management. Our survey also confirms the occurrence of ten primate species in the Gaoligong Mountains, accounting for 35.7% of China's primates, including the Skywalker hoolock gibbon Hoolock tianxing and the Myanmar snub-nosed monkey Rhinopithecus strykeri etc. These findings reveal a new distribution record for the white-cheeked macaque and further highlight the conservation values of Gaoligong Mountains for globally threatened primate species. We also provide a preliminary report on the daily activity patterns of this endangered species, which enriches the bio-ecological data of the poorly studied species. We believe the report has significant implications for understanding the ecology of the species and improving conservation planning.