Clinical Significance Of Changes Research Articles

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study

Background: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. Methods: Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. Results: The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003). Conclusions: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Moving pain management programmes into the digital age: development and evaluation of an online PMP for people with chronic pain.

In response to Coronovirus Disease (COVID-19) health care restrictions, the pain management programme delivered group treatment digitally (OPMP). We aimed to: 1) evaluate pain related outcomes of the OPMP, 2) evaluate patient satisfaction and qualitive feedback of the OPMP and 3) compare OPMP outcomes with the pre-pandemic face to face (F2F) PMP outcomes. Age, gender, pain duration, occupational status, referral information and patient satisfaction data were collected. Pre- and post-treatment pain related outcomes were compared by calculating mean difference, benchmarking with effect size (Cohen's d) and determining clinically significant change (CSC) for OPMP and F2F PMP. Two-hundred and thirty-seven patients provided outcome data, with 60 completing the OPMP and 177 completing the F2F PMP. OPMP patients were 10 years younger than the F2F PMP (44.8 vs 53.3), more were female (6.5:1 vs 2.8:1), more were working (45% vs 27%) and fewer were retired (3% vs 17%). The OPMP showed improvements comparable to the F2F PMP. Large effect size was reported across all outcome domains including objective physical outcomes. Eighty-one percent of OPMP patients were 'extremely likely' to recommend the programme but just over 50% of patients felt F2F would provide greater clinical benefits. The results support that OPMP is effective for carefully selected patients following a multidisciplinary team assessment however more complex cases still require F2F PMP.

Evaluation of Fetal Breathing-Related Nasal Fluid Flow Doppler in the Third Trimester in Pregnant Women with Fetal Growth Restriction: Preliminary Observations.

To investigate the fetal breathing-related nasal fluid flow Doppler waveforms as an indicator of fetal respiratory function in fetuses diagnosed with fetal growth restriction (FGR) in the third trimester. This prospective, non-interventional case-control study was conducted on 96 pregnant women, including 23 pregnant women diagnosed with FGR in the third trimester as the FGR group and 73 healthy pregnant women with fetuses appropriate for gestational age (AGA) as the control group. Fetal breathing-related nasal fluid flow Doppler was examined in the fetuses of the participants. Inspiration and expiration duration, inspiration and expiration peak velocity, total breathing duration, and number of fetal breaths per minute were calculated. Both groups were similar in terms of the duration of inspiration, duration of expiration, and total breathing duration (p=0.463, p=0.711, p=0.520, respectively). Peak inspiratory velocity and peak expiratory velocity were significantly lower in the FGR group than in the control group, and the number of fetal breaths per minute was similar in both groups (p=0.027, p=0.012, p=0.768, respectively). When participants were regrouped into those whose newborn was admitted to the neonatal intensive care unit (NICU) after birth and those who were not, all fetal nasal fluid flow Doppler parameters were similar in both groups. Although the number of participants was too small to draw a definitive conclusion, FGR appears to be associated with a decrease in peak inspiratory and expiratory velocity. The clinical significance of changes in fetal breathing-related nasal fluid flow Doppler parameters in FGR is as yet unclear, and their use in clinical follow-up and predicting unfavorable perinatal outcomes are the subjects of future research.

Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis - Clinical Significance of Changes in Mitral Valve Area.

Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Correlation analysis and clinical significance of changes in upper thoracic vertebra tilt and clavicle angle pre- and post-operation.

The imbalance of the lateral shoulder is reflected by the clavicle angle (CA) in radiology. It remains unclear how to achieve postoperative lateral shoulder balance (LSB) after spinal deformity correction surgery. A retrospective analysis was conducted on AIS patients who underwent surgery by the same spine surgeon at our hospital from 2016 to 2020. A total of 110 patients with spinal deformity were included in the study to verify the correlation between the T1-T5 tilt angle and CA before and after surgery, as well as the relation-ship between the change in T1-T5 tilt angle before and after surgery and the change in CA before and after surgery. By comparing the correlation coefficients, it was found that there may not be a direct relationship between the pre- and postoperative tilt angles of T1-5 and CA, but their changes were closely related to the changes in CA. The change in T1 tilt angle after orthopaedic surgery was significantly correlated with the change in CA, with a correlation coefficient of 0.976, indicating a close relationship between T1 and the clavicle. As the vertebrae moved down, the correlation gradually decreased. In summary, this study suggests that there is a close relationship between T1-T5 and the clavicle and that the change in T1 tilt angle after spinal scoliosis correction surgery is significantly correlated with CA, which decreases as the vertebra moves down.

Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms.

Sex hormone-binding globulin (SHBG) is a serum glycoprotein exhibiting the unique feature of binding sex steroids with high affinity and specificity. Over the past few decades, there have been significant breakthroughs in our understanding of the function and regulation of SHBG. The biological role of SHBG has expanded from being considered a simple sex hormone transporter to being associated with several complex physiological and pathological changes in a variety of target tissues. Many factors can affect the plasma SHBG levels, with fluctuations in circulating levels affecting the development of various diseases, such as increasing the risk of developing breast cancer. This article reviews the clinical significance of changes in circulating SHBG levels in the development of breast cancer and the possible influence of these levels on endocrine drug resistance in hormone receptor-positive breast cancer. Higher levels of plasma SHBG significantly reduce the risk of estrogen receptor-positive breast cancer, especially in postmenopausal women. Moreover, the molecular mechanisms by which SHBG affects breast cancer risk are also summarized in detail. Finally, transcriptomics and proteomics data revealed that SHBG expression in breast tissue can effectively distinguish breast cancer from normal tissue. Additionally, the association between SHBG expression levels and various classical tumor-related pathways was investigated.

Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group (P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission (P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan-Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV.

Telemedicine for type 2 diabetes during COVID-19 pandemic: experience from a tertiary diabetes center.

Telemedicine was largely employed during COVID-19 pandemic to guarantee continuity of care in a period of dramatic reduction of face-to-face visits. The aim of this study was to describe the clinical characteristics of a cohort of patients with type 2 diabetes followed by tele-visits and to evaluate the changes in the glyco-metabolic control during a 12-month follow-up. This retrospective observational study included 136 adults aged >18 years with at least three tele-visits over a 12-month follow-up period, in a Diabetes Center of the Southern Italy, from April 2020 to March 2022. Data related to glycemic and lipid profile, therapy, presence of micro or macrovascular complications, and other clinical features were extracted at three time points, at first visit (T0), after 6 months (T1) and after 12 months (T2). Mean diabetes duration and median HbA1c values were 11.6 years and 7.0%, respectively. Thirty-eight participants (27.9%) presented macro- or microvascular complications. Glycemic control remained stable over time, without clinically significant changes of HbA<inf>1c</inf> (T0 vs. T1 vs. T2, median [IQR], 7.0 [6.2-7.3], 6.6 [6.0-7.5], 6.9 [6.2-7.5], P=0.095) and fasting glucose. Lipid profile slightly improved, although without significant clinical change. Glucose lowering therapy was modified in 84 patients (61.8%) and remained unchanged in 52 patients (38.2%) during the follow-up. No participant in the study developed any complications during the 12-month follow-up. People with type 2 diabetes followed by telemedicine were adults with fair glucose control generally free from chronic complications, whose diabetes control did not worsen during a 12-month follow-up.

P26 A life threatening case of Von Zumbusch psoriasis

Abstract We report a case of a patient admitted to intensive care with a pustulating skin eruption and haemodynamic compromise with near immediate response to infliximab. A 16-year-old male with a six-month history of mild plaque psoriasis presented to acute dermatology services with widespread annular pustular eruption, which developed days after a throat infection. Histopathology was consistent with pustular psoriasis. After an initial partial response, the pustules spread and persisted despite 2-month treatment with topical steroids and ciclosporin (dosed to 4 mg/kg). With raised inflammatory markers and repeated growth of Staphylococcus aureus, high dose intravenous flucloxacillin was administered. Four hours post infusion the patient became erythrodermic and haemodynamically unstable, requiring management in ICU. Repeat skin biopsy showed features of psoriasis without clear drug reaction features. Switching classes of antimicrobials and administration of intravenous immunoglobulins led to infection resolution but no significant clinical status change. A multi-disciplinary decision was made to trial intravenous infliximab. This resulted in near-immediate 90% improvement of skin and haemodynamic status. His excellent clinical response has been maintained on adalimumab thus far. Genetic screening for possible mutations associated with pustular psoriasis, including IL36RN and CARD14, are in process.

Changes in Soluble Serum CD81 Concentration during an Oral Glucose Tolerance Test in Patients with Diabetes Mellitus and Individuals with Normal Glucose Tolerance

Aim: Cluster of differentiation 81 (CD81) is a cell surface protein involved in cell development, activation, growth, and motility. Recent studies have suggested that CD81 is a marker of dedifferentiated β-cells under conditions of metabolic stress, such as progressive diabetes. However, the clinical significance of changes in soluble serum CD81 (sCD81) in diabetic individuals remains unknown. The aim of this study was to investigate whether serum sCD81 concentrations differ between subjects with diabetes and normal glucose tolerance (NGT), and whether sCD81 changes during a 75 g oral glucose tolerance test (OGTT). Materials and methods: We recruited 101 subjects who had completed an OGTT. According to the test results, the participants were divided into diabetes mellitus (DM) and NGT groups. Participants with prediabetes were excluded from the analysis. During the OGTT, sCD81 levels were measured at 0 and 120 min. We compared changes in sCD81 between the groups. Results: In the DM group, soluble sCD81 levels were significantly higher at baseline and 120 min in the OGTT compared with the normal group (0.59 (0.22–1.05) ng/mL vs. 0.25 (0.81–0.67) ng/mL, 0.55 (0.17–0.96) ng/mL vs. 0.21 (0.92–0.78) ng/mL, p = 0.006 and 0.029, respectively). The soluble sCD81 levels in the NGT group remained unchanged (p = 0.658), while those in the DM group were significantly decreased during the OGTT (p = 0.003). Conclusion: Soluble sCD81 levels were elevated in individuals with type 2 diabetes, such that changes in sCD81 were only observed during the OGTT in the DM group. Soluble sCD81 may have potential as a new diagnostic marker for type 2 diabetes.

Responsiveness and Minimal Clinically Important Difference of the Thai Version of the International Knee Documentation Committee Subjective Knee Form in Patients With Anterior Cruciate Ligament Injury.

The International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) is a knee-specific patient-reported outcome (PRO) measure that is commonly used to evaluate patients with various knee disorders. The Thai version of the IKDC-SKF (Thai IKDC-SKF) was shown to have good validity and reliability; nonetheless, no data regarding its responsiveness are available. To evaluate the responsiveness of the Thai IKDC-SKF for assessing patients with anterior cruciate ligament (ACL) injury and determine the minimal clinically important difference (MCID) for this PRO measure. Cohort study (diagnosis); Level of evidence, 3. This prospective study included ACL-injured patients who were scheduled for ACL reconstruction (ACLR) at a single institution. The patients completed the Thai IKDC-SKF at the baseline and the 6-month postoperative follow-up. The global rating of change scale was an anchor question that evaluated patients' overall perception of a clinical change compared with their preoperative condition. The effect size and standardized response mean were calculated. The MCID was identified with an anchor-based approach by plotting a receiver operating characteristic curve and calculating the value that maximized the Youden index. Of 59 enrolled patients, 53 patients (89.8%) completed the preoperative and 6-month postoperative Thai IKDC-SKF. The mean (±SD) age of the participants was 32.3 ± 10.3 years, and 86.8% were men. The mean Thai IKDC-SKF score improved significantly from preoperatively to the 6-month follow-up (from 56.3 ± 14.9 to 70.8 ± 14.1, respectively; P < .001), with an effect size of 0.975 and a standardized response mean of 0.977. A receiver operating characteristic curve was generated to determine the ability of the Thai IKDC-SKF to distinguish between improved patients and unimproved patients, and the area under the curve was 0.80 (95% CI, 0.68-0.92), which was considered excellent. The MCID was 15.5, which yielded a sensitivity and specificity of 0.55 and 1, respectively. This study confirmed the responsiveness of the Thai IKDC-SKF for detecting a clinical change in ACL-injured patients after ACLR. The identified MCID of 15.5 can be used to calculate the significant clinical change and sample size in future studies.

FRI035 Comparative Study Of The Changes In Body Composition According To Age And The Associations With The Risk Of Diabetes Mellitus By Races

Abstract Disclosure: S. Jang: None. K. Kim: None. C. Kim: None. S. Park: None. Introduction: The changes in body composition with aging are known to be associated with the risk of various chronic diseases. But the body composition changes with age among different races, is not well studied. This study aimed to investigate the racial differences in the changes of body composition according to age and the association with prevalent diabetes mellitus. Methods: A total of 37,153 participants was include in the study. 27,864 Korean from the Korea National Health and Nutrition Examination Surveys (KNHANES) 2008-2011 and 9,289 from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 whose age ranged from 20 to 85 years were analyzed. Body composition was measured by dual-energy X-ray absorptiometry (Hologic Horizon) in both cohorts. Relative body composition measures based on young adult (20-29 years) were compared. The association of body composition measures and diabetes were analyzed. Results: Compare to other three races from NHANES, Korean men and women had a lower BMI. Total percentage fat tended to increase with age in all races, but degree of increase with age was not higher in Korean men than in other races and a similar trend was observed in Korean women. Regarding the changes in lean mass, men and women showed different patterns. In men, non-Hispanic white showed peak levels in their 40s and then tended to decrease. All other races showed peaks in their 20s and 30s, and subsequently decreased. Compared to other races, the decline according to age was the largest in Korean men. For women, in all races, the pattern was maintained even after their 20s until their 40s or 50s, and then decreased. The degree of decline was similar in all races. In men, higher fat percentage and lower lean mass were associated with prevalent diabetes in all races. In women, however, higher fat percentage and lower lean mass were associated with prevalent diabetes in only Korean and non-Hispanic white. Conclusion: The changes in body composition according to age vary by race and its association with prevalent diabetes also differs. The clinical significance of changes in body composition according to age and race in chronic diseases needs to be further clarified. Presentation: Friday, June 16, 2023

The role of lung microbiota in primary graft dysfunction in lung transplant recipients.

Recent studies have shown that the lung microbiota is altered in critically ill patients and predicts clinical outcomes. Primary graft dysfunction (PGD) is a common complication and a leading cause of death within 1 month of lung transplantation, but the clinical significance of changes in the lung bacterial community during PGD is unclear. The aim of this study was to determine the contribution of the lung microbiota to the development and course of severe PGD. We conducted a retrospective study to characterize the lung microbiota of 32 lung transplant patients with combined PGD using next-generation sequencing of bronchoalveolar lavage samples. The relationship between lung flora dysbiosis and lung immunity in PGD was assessed by quantification of alveolar cytokines. The contribution of microbiota characteristics to patient outcomes was assessed by estimating overall survival. Patients diagnosed with PGD grade 3 showed a reduction in alpha diversity, driven by a significant increase in the abundance of the genera Modestobacter, Scardovia and Selenomonas, and a reduction in the proportion of the genera Klebsiella and Oribacterium. Alpha diversity of the lung microbiota in PGD3 patients was negatively correlated with BALF interleukin (IL)-2 (r=-.752, p<.05). In addition, bacterial diversity in the lung microbiota of non-survivors was lower than that of survivors (p=.041). There is variation in the lung microbiota of PGD grade 3 patients and dysbiosis of the lung microbiota is associated with lung immunity. The lung microbiota has potential in the diagnosis and treatment of PGD grade 3.

Treating postpartum affective and/or anxiety disorders in a mother-baby day hospital: preliminary results

Introduction Women experiencing perinatal mental-health illness have unique needs. The present study analyzes preliminary data about the effectiveness of MBDH in treating postpartum women with affective and anxiety disorders. Methods We analysed 33 mothers with affective and/or anxiety disorders treated at the MBDH with their babies between March 2018 and December 2019. All women were assessed at admission, discharge and three months after discharge. Outcomes included symptoms of depression (EPDS) and anxiety (STAI-S), mother-infant bonding (PBQ) and functional impairment (HoNOs). We also assessed the clinical significance of changes in patients’ scores on these scales and patient satisfaction. Results At discharge, no patients still met the full criteria for the main diagnosis. Between admission and discharge, symptoms of depression and anxiety, mother-infant bonding, functional impairment and autonomy in caring for babies improved significantly. These gains were maintained at three months follow-up. Patient satisfaction was high. Conclusions These preliminary results suggest that multidisciplinary intervention for postpartum women with affective or anxiety disorders at the MBDH improves maternal psychopathology, mother-infant bonding and mothers’ ability to care for their babies. MBDHs are a promising approach for delivering specialised perinatal mental-health care for mother-baby dyads.

Randomized Controlled Trial on the ASSYST Treatment Intervention with Female Children Polytraumatized by Adverse Childhood Experiences, Neglect, and Maltreatment

The aim of this randomized controlled trial with an intention-to-treat analysis was to evaluate the effectiveness, efficacy, and safety of the Acute Stress Syndrome Stabilization Individual (ASSYST-I) treatment intervention in reducing posttraumatic stress disorder (PTSD) symptoms in female children polytraumatized by adverse childhood experiences, neglect, and maltreatment. A total of 40 female children met the inclusion criteria and participated in the study. Participants’ ages ranged from 8 to 17 years old (M =14.67 years). A two-arm randomized controlled trial (RCT) design was applied. PTSD symptoms were measured in three-time points for all participants in the study. Results showed that the intervention had a significant effect for time on PTSD symptoms (F (2,76) = 36.92 p &lt;.000, η² = .493). A significant effect for group was also found (F (1, 38 = 32.7, p&lt;.005, η² = .896) with a large effect, and a significant interaction between time and group, (F (2, 76) = 56.00, p &lt;.000, η² = .600). Means comparison using t test between groups showed significant differences between the Treatment Group (TG) and the Control Group (CG) in the three-time points comparisons showing a large effect on Time 2 (Post-treatment assessment) which was maintained on Time 3 (Follow-up assessment). Results on the Reliable Change Index (RCI) and the Clinically Significant Change (CSC) Margin showed that the ASSYST-I treatment intervention exhibited reliable change on PTSD symptom reduction and clinically significant change, indicating that the treatment group participants are more likely to belong to the non-PTSD population after the intervention. Conversely, the control group participants are more likely to belong to the PTSD population. No adverse effects or events were reported by the participants during the treatment procedure administration or at follow-up. None of the participants showed clinically significant worsening/exacerbation of symptoms after treatment. Participants in the control group received the intervention treatment after the follow-up assessment, fulfilling our ethical criteria.

Poster 187: Similar Clinical and Patient Recorded Outcomes Amongst Older Patients over 65 Years of Age Compared to Younger Patients undergoing Arthroscopic Rotator Cuff Repair

Objectives: The purpose of our study was to determine if patients 65 years and over meet the minimally clinical important difference (MCID) for Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS-UE), Depression (PROMIS-D), and Pain Interference (PROMIS-PI) at similar rates compared to a cohort of younger patients. Methods: A retrospective review of a prospectively collected database of patients undergoing RCR was performed. Patients with completed preoperative and 6-month follow up postoperative PROMIS scores were included. A cohort of 65 years and older (65&lt;) was compared to a cohort of 64 years and younger (64&gt;=) in terms of their clinical outcomes and PROMIS scores. A propensity matched analysis was then performed, which matched patients 65+ years old 1:1 to a cohort of 50 years or younger via tear size and body mass index (BMI). Results: A total of 318 patients were included with 79 patients ≥ 65 years (69.2 ± 3.4 years, mean ± SD) and 239 patients &lt;65 years (55.1 ± 3.4 years). No significant differences were found in terms of gender, tear thickness, tear size, reoperation rate, retear rate, preoperative PROMIS-UE, PROMIS-PI, and PROMIS D scores, or change in postoperative PROMIS-UE, PROMIS-PI, and PROMIS D after 6 months. In the sub-analysis, 44 patients over 65 years of age were propensity matched to 44 under 50 years of age. No differences were found in PROMIS-UE change, PROMIS-D change, proportion meeting MCID PROMIS UE, and proportion meeting MCID of PROMIS PI after 6 months. Patients in the 65+ years group experienced larger changes in PROMIS PI scores (12.5 ± 9.6 vs 7.2 ± 7.5, p=0.005) while fewer patients experienced significant declines in PROMIS D scores (26% vs 47%, p=0.03). Conclusions: Patients ≥ 65 years experience no differences in reoperation or retear rate when compared to younger patients. Older patients undergoing RCR were more likely to have a larger improvement in pain scores but were less likely to have significant clinical change in their depression scores. With proper patient selection, patients ≥ 65 years can achieve clinically significant improvements 6 months after RCR that is similar to their younger counterparts. [Table: see text][Table: see text][Table: see text]

Comparison of bispectral index and patient state index as measures of sedation depth during surgeries using remimazolam tosilate

BackgroundThe Bispectral Index (BIS) and the Patient State Index (PSI) are commonly used measures to assess intraoperative sedation depth. However, model differences lead to different results, which in turn interferes with clinicians’ judgment on the depth of anesthesia. Remimazolam tosilate (RT) for injection is a new benzodiazepine used in sedation. In its clinical application, there are few effective indicators for sedation depth monitoring. To close this gap, this study aims to compare BIS and PSI in measuring the sensitivity and specificity of intraoperative RT and to explore the safety of RT for intraspinal anesthesia in elderly patients.MethodsThis study included 40 patients undergoing elective electro-prostatectomy with intraspinal anesthesia, who were monitored by BIS and PSI simultaneously during operation. Remimazolam tosylate 0.1 mg/kg was intravenously administered after the intraspinal anesthesia when patients were in a completely painless status. Then BIS, PSI, the Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) scores and vital signs were observed and recorded per minute for 10 min. Pearson’s correlation analysis and linear regression model were used to compare BIS and PSI sedation scores, and to test their associations with the MOAA/S score, respectively. ROC curves were drawn to compare the sensitivity and specificity of BIS and PSI. Changes of vital signs were presented as mean ± standard deviation. Perioperative liver and kidney function indicators were analyzed using a paired t-test to evaluate the safety of RT for intraspinal anesthesia in the elderly patients.ResultsAccording to Pearson’s correlation analysis, a significant (P < 0.01) correlation between BIS and PSI was found when used to monitor intraoperative sedation of RT (r = 0.796). Significant associations between BIS and MOAA/S (r = 0.568, P < 0.01), and between PSI and MOAA/S (r = 0.390, P < 0.01) were also found. The areas under the ROC curves of BIS and PSI were 0.801 ± 0.022 and 0.734 ± 0.026, respectively, suggesting that both measures may predict patients’ state of consciousness and BIS was more accurate than PSI. Vital signs remained stable throughout the study. No abnormal changes of clinical significance were found based on laboratory test results of liver and kidney function.ConclusionBIS and PSI are strongly associated for monitoring the sedation of RT intraoperatively. Both methods can accurately reflect sedation depth. According to correlation analyses with MOAA/S scale and ROC curves, BIS is more accurate than PSI during such intraoperative monitoring. In addition, RT can be safely used in elderly patients under intraspinal anesthesia for supportive sedation, with stable vital signs and sound kidney and liver safety profiles.Trial registrationhttp://www.chictr.org.cn (ChiCTR2100051912).

An examination of the criterion-related validity of varying methods of indexing clinically significant change in posttraumatic stress disorder treatment.

Clinicians, patients, and researchers need benchmarks to index individual-level clinically significant change (CSC) to guide decision making and inferences about treatment efficacy. Yet, there is no consensus best practice for determining CSC for posttraumatic stress disorder (PTSD) treatments. We examined criterion-related validity of the most common approach-Jacobson and Truax's (J&T; 1991) procedures for indexing CSC. We generated and compared four methods of calculating the J&T indices of CSC (two sets of sample-specific inputs, putatively norm-referenced benchmarks, and a combination of sample-specific and norm-referenced criteria) with respect to their association with a criterion index of quality of life (QoL). Participants were 91 women Veterans enrolled in a randomized clinical trial for PTSD who completed self-report measures on PTSD symptoms and various domains of QoL and functioning, pre- and posttreatment. For each of the four methods used to calculate CSC, the QoL composite was regressed onto the CSC categories. All methods explained large variance in change in QoL. Across all methods, participants categorized as unchanged had smaller changes in QoL, compared with those who improved or had probable recovery. The norm-referenced benchmarks accounted for the relatively largest amount of variance in QoL, but categorized the fewest patients as having made CSC. The J&T methodology for indexing CSC in PTSD symptoms has criterion-related validity, and a norm-referenced benchmark appears to be the most potent. However, the norm-referenced parameters may be overly specific, potentially leading to an underestimate of improvement. Research is needed to test the generalizability of these results. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics?

Human serum alpha-1 acid glycoprotein is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. It has been reported that the sialic acid groups that terminate the N-glycan chains of alpha-1 acid glycoprotein change in response to certain health conditions and may have a major impact on drug binding to alpha-1 acid glycoprotein. The interaction between native or desialylated alpha-1 acid glycoprotein and four representative drugs-clindamycin, diltiazem, lidocaine, and warfarin-was quantitatively evaluated using isothermal titration calorimetry. The calorimetry assay used here is a convenient and widely used approach to directly measure the amount of heat released or absorbed during the association processes of biomolecules in solution and to quantitatively estimate the thermodynamics of the interaction. The results showed that the binding of drugs with alpha-1 acid glycoprotein were enthalpy-driven exothermic interactions, and the binding affinity was in the range of 10-5-10-6 M. Desialylated alpha-1 acid glycoprotein showed significantly different binding with diltiazem, lidocaine, and warfarin compared with native alpha-1 acid glycoprotein, whereas clindamycin showed no significant difference. Therefore, a different degree of sialylation may result in different binding affinities, and the clinical significance of changes in sialylation or glycosylation of alpha-1 acid glycoprotein in general should not be neglected.

124O Patritumab deruxtecan (HER3-DXd) in hormonal receptor-positive/HER2-negative (HR+/HER2-) and triple-negative breast cancer (TNBC): Results of part B of SOLTI TOT-HER3 window of opportunity trial

We previously reported the biologic and clinical activity of HER3-DXd in Part A of SOLTI TOT-HER3 in patients (pts) with HR+/HER2- early breast cancer (BC) after a single dose of 6.4 mg/kg (Prat A. et al, ESMO BREAST 2022). Here, we present the main efficacy and safety results of TOT-HER3 Part B. In Part B of this window of opportunity trial, 2 cohorts of pts with treatment-naïve HER2- primary operable BC, ≥1 cm by US or MRI were recruited. Pts received a single dose of HER3-DXd 5.6 mg/kg. Primary objective was the variation in tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) score between pre- and post-treatment tumors. Associations of baseline clinical and biological features with CelTIL changes and overall response rate (ORR) by US were explored. Thirty-seven pts with HER2- BC were recruited (HR+ n=20; TNBC n=17). Mean age was 53 (30-81); 20 (54%) were pre-menopausal; mean tumor size was 21 mm (range 10-81 mm); and median Ki67 was 30% (12-95%). In response to treatment with HER3-DXd CelTIL score increased and decreased in 21 (57%) and 16 (43%) pts, respectively. Overall, a statistically significant change in CelTIL was observed between paired samples overall (p=0.046) and in TNBC (p=0.016), but not in HR+ (p=0.793). ORR by US in all patients was 32% (35% in TNBC and 30% in HR+). The absolute change in CelTIL was associated with ORR (AUC=0.693; p=0.049). Baseline ERBB3 levels were not associated with CelTIL change or ORR. HER3-DXd induced high expression of immune-related genes (e.g., PD1, CD8 and CD19), and suppressed proliferation-related genes. Thirty-one (84%) patients reported AEs at any grade. Most common AEs were nausea, fatigue, alopecia, diarrhea, constipation and vomiting. Grade 3 treatment-related nausea occurred in 1 patient. No ILD events were reported. A single dose of HER3-DXd was associated with clinical response and significant biological changes in HER2- tumors, irrespective of baseline ERBB3 levels. The safety profile was consistent with that previously reported. Additional correlative analysis will be presented on site.