Shorter Disease Research Articles

Abstract 6112: Uncovering clinicopathological factors contributing to racial inequities in pancreatic cancer in Hampton Roads, Virginia

Abstract Introduction: Pancreatic Ductal Adenocarcinoma (PDAC) is the 3rd leading cause of cancer-related deaths, with 12% surviving 5 years post-diagnosis. The delayed symptom onset, lack of effective screening, and advanced presentation render most patients ineligible for surgery. For inoperable PDAC, treatment offers only palliative support, resulting in a 1-year median survival, in contrast to 3 years for operable cases. Black patients face a 30-70% higher PDAC mortality rate than other racial groups in the United States. In Hampton Roads, Virginia, from 2015-2019, the black PDAC population had a mortality rate of 17.3%, notably surpassing the 10.8% rate among white PDAC patients. Consequently, this project aims to address the disparate disease burden of PDAC in the black Hampton Roads community. Methods: Chart review of 427 inoperable PDAC patients from the Sentara Cancer Network and Virginia Oncology Associates was conducted. Age at diagnosis, treatment date, treatment type, and death date of the black and white inoperable cohorts were extracted. Average length of disease, age of onset, and time from diagnosis to treatment were calculated. KM survival analysis compared the cohorts’ survival rates. Results: From 2008 to 2016, the white cohort had shorter survival rates than the black cohort. The black population averaged a disease length of 249 days, while the white population faced 190 days. The average age at diagnosis was 67 in the black cohort and 70 in the white cohort. 42.1% of white PDAC patients did not receive treatment, while 29.9% of black PDAC patients went untreated. Discussion: While the black population faces higher mortality, the white PDAC inoperable cohort had shorter disease duration and lower survival. A higher number of white patients also did not receive therapy, likely due to their older age, leading to added comorbidities and advanced stages of disease. Elder patients often decline treatment due to its limited impact on lifespan and quality of life. Further, the longer survival found in black patients may paradoxically contribute to a high mortality rate in Black patients. 21% of the black cohort survived over a year, prompting questions about their classification as inoperable and their access to the only curative treatment. This discovery motivates examination of the decisions behind labeling these patients as inoperable. The ongoing investigation into factors, such as stage at diagnosis and standard of care adherence, strives to continue to uncover the reasons for the high mortality rate in the Black PDAC Hampton Roads population. Citation Format: Fatima W. Chaudhry, Zakary L. Kolkey, Ashleigh E. Hannah, Richard A. Hoefer, Amy Tang. Uncovering clinicopathological factors contributing to racial inequities in pancreatic cancer in Hampton Roads, Virginia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6112.

Predictors of psychosocial adjustment and its subdomains in young adults with hematologic malignancy: A cross-sectional study

PurposeThis study aims to identify the factors influencing psychosocial adjustment and its subdomains. MethodsA descriptive cross-sectional study was conducted with 176 young adults (men 55.7%, 30.5 ± 5.9 years) diagnosed with a hematologic malignancy in South Korea. Psychological adjustment, symptom experience, and type D personality were assessed using self-report questionnaires. Clinical characteristics were extracted from the medical record. Stepwise multiple regression was conducted to identify the factors influencing psychosocial adjustment. ResultsThe predictors of difficulties in psychosocial adjustment were high symptom experience, type D personality, being unemployed, low functional status, and short time since the last chemotherapy. By subdomain of psychosocial adjustment, predictors of low healthcare orientation were high symptom experience, woman, and type D personality, and predictors of low vocational environment were high symptom experience, being unemployed, short duration of disease, low functional status, and diagnosis. The factors influencing low domestic environment were high symptom experience, being unemployed, and low functional status, and the factor influencing low sexual relationships was high symptom experience. The predictor of low extended family relationships was high symptom experience; predictors of low social environment were high symptom experience and short duration of disease; and predictors of low psychological distress were high symptom experience, type D personality, and being unemployed. ConclusionAs young adults with higher symptom experiences, type D personality, low functional status, and shorter time since the last chemotherapy, and who are unemployed experience difficulties in psychosocial adjustment, healthcare professionals should evaluate their psychosocial adjustment and develop strategies to improve the same.

Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96weeks of belimumab. This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96weeks. Forty-seven patients were enrolled, with a median daily prednisolone of 5mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

Evolutionary trajectories of small cell lung cancer under therapy

The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown1–3. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity. We observed branched evolution and a shift to ancestral clones underlying tumour relapse. Effective radio- or immunotherapy induced a re-expansion of founder clones with acquired genomic damage from first-line chemotherapy. Whereas TP53 and RB1 alterations were exclusively part of the common ancestor, MYC family amplifications were frequently not constituents of the founder clone. At relapse, emerging subclonal mutations affected key genes associated with SCLC biology, and tumours harbouring clonal CREBBP/EP300 alterations underwent genome duplications. Gene-damaging TP53 alterations and co-alterations of TP53 missense mutations with TP73, CREBBP/EP300 or FMN2 were significantly associated with shorter disease relapse following chemotherapy. In summary, we uncover key processes of the genomic evolution of SCLC under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with sensitivity and resistance to chemotherapy.

Knowledge, attitude, and practice toward tuberculosis prevention and management among household contacts in Suzhou Hospital, Jiangsu province, China.

China is among the 10 high-burden tuberculosis (TB) countries in the world; thus, investigation and management of household contacts is an essential part of TB prevention strategy. To explore the knowledge, attitude, and practice (KAP) toward TB prevention and management among household contacts of TB patients. This cross-sectional study enrolled household contacts in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine between September 2022 and January 2023; KAP and demographic characteristics were assessed with the self-designed questionnaire and analyzed by multivariate logistic regression. A total of 503 participants were included; of them, 280 (55.78%) were female, and 303, (60.36%) aged ≥45 years. The KAP scores were 6.24 ± 2.20 (possible range: 0-12), 18.69 ± 2.80 (possible range: 0-36), and 20.37 ± 5.15 (possible range: 0-36), respectively. Suburban (OR = 0.18, 95% CI: 0.04-0.79, p = 0.023) and rural (OR = 0.12, 95% CI: 0.03-0.57, p = 0.008) were independently associated with knowledge. Positive attitude (OR = 7.03, 95% CI: 2.92-16.96, p < 0.001), education (high school or technical secondary school, OR = 4.91, 95% CI: 1.63-14.73, p = 0.005; college and above, OR = 14.94, 95% CI: 3.51-63.58, p < 0.001), and shorter disease duration (3-6 months, OR = 0.40, 95% CI: 0.18-0.90, p = 0.026) were independently associated with better practice scores. Household contacts of TB patients demonstrated insufficient knowledge, unfavorable attitude, and suboptimal practice toward TB prevention and management. Tailored interventions are needed to ensure information accessibility, especially for individuals living in suburban and rural areas.

Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.

Despite advances in the management of type 2 diabetes mellitus (T2DM), one-third of patients with diabetes do not achieve the desired glycemic goal. Considering this inadequacy, many agents that activate glucokinase have been investigated over the last two decades but were withdrawn before submission for marketing permission. Dorzagliatin is the first glucokinase activator that has been granted approval for T2DM, only in China. As overstimulation of glucokinase is linked with pathophysiological disturbances such as fatty liver and cardiovascular issues and a loss of therapeutic efficacy with time. This review aims to highlight the benefits of glucokinase activators vis-à-vis the risks associated with chronic enzymatic activation. We discuss the multisystem disturbances expected with chronic activation of the enzyme, the lessons learned with glucokinase activators of the past, the major efficacy and safety findings with dorzagliatin and its pharmacological properties, and the status of other glucokinase activators in the pipeline. The approval of dorzagliatin in China was based on the SEED and the DAWN trials, the major pivotal phase III trials that enrolled patients with T2DM with a mean glycosylated hemoglobin of 8.3-8.4%, and a mean age of 53-54.5years from multiple sites in China. Patients with uncontrolled diabetes, cardiac diseases, organ dysfunction, and a history of severe hypoglycemia were excluded. Both trials had a randomized double-blind placebo-controlled phase of 24weeks followed by an open-label phase of 28weeks with dorzagliatin. Drug-naïve patients with T2DM with a disease duration of 11.7months were enrolled in the SEED trial while the DAWN trial involved patients with T2DM with a mean duration of 71.5months and receiving background metformin therapy. Compared with placebo, the decline in glycosylated hemoglobin at 24weeks was more with dorzagliatin with an estimated treatment difference of -0.57% in the SEED trial and -0.66% in the DAWN trial. The desired glycosylated hemoglobin (<7%) was also attained at more than two times higher rates with dorzagliatin. The glycemic improvement was sustained in the SEED trial but decreased over 52weeks in the DAWN trial. Hyperlipidemia was observed in 12-14% of patients taking dorzagliatin versus 9-11% of patients receiving a placebo. Additional adverse effects noticed over 52weeks with dorzagliatin included an elevation in liver enzymes, hyperuricemia, hyperlacticacidemia, renal dysfunction, and cardiovascular disturbances. Considering the statistically significant improvement in glycosylated hemoglobin with dorzagliatin in patients with T2DM, the drug may be given a chance in treatment-naïve patients with a shorter disease history. However, with the waning therapeutic efficacy witnessed in patients with long-standing diabetes, which was also one of the potential concerns with previously tested molecules, extended studies involving patients with chronic and uncontrolled diabetes are needed to comment upon the long-term therapeutic performance of dorzagliatin. Likewise, evidence needs to be generated from other countries, patients with organ dysfunction, a history of severe hypoglycemia, cardiac diseases, and elderly patients before extending the use of dorzagliatin. Apart from monitoring lipid profiles, long-term safety studies of dorzagliatin should involve the assessment of serum uric acid, lactate, renal function, liver function, and cardiovascular parameters.

The efficacy of electroconvulsive therapy in adolescent major depressive disorder with suicidal ideation: A propensity score-matched, retrospective cohort study

BackgroundMore evidence is needed to validate the use of ECT in adolescent depression. This study aims to compare the effectiveness of electroconvulsive therapy (ECT) to conventional medication therapy for adolescents with major depression with suicidal ideation. MethodsIn this retrospective cohort study, we reviewed inpatient records from the First Affiliated Hospital of Chongqing Medical University spanning December 2016 to June 2021. We focused on adolescents diagnosed with severe depression presenting with suicidal tendencies. To equalize baseline differences between patients, we used the one-to-one propensity score matching to match patients who received ECT treatment with those who did not. Multivariate regression analysis was utilized to adjust for potential confounders, and subgroup analyses and sensitivity analyses were conducted to verify the robustness of our findings. ResultsOf the 626 patients in this study, 474 underwent ECT treatment while 152 received medication treatment, all aged between 10 and 18 years. Once matched, each group contained 143 patients. The ECT group demonstrated a significantly higher response rate and greater reductions in both Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores (all P < 0.001). Additionally, the ECT group was more effective in reducing suicidal ideation, with fewer individuals retaining such ideation at discharge. In the multivariable regression analysis, both ECT treatment and shorter disease duration were independently linked to enhanced antidepressant efficacy. Subgroup analyses and sensitivity analyses verified the robustness of the main study effect. ConclusionsFor adolescents with major depressive disorder and suicidal ideation, combining ECT with pharmacotherapy is more effective than pharmacotherapy alone before medications reach full effect.

Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative

AimsOpportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy.MethodsData on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005–2019).ResultsWe evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target.ConclusionsIn this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

Neurophysiological Characteristics in Type II and Type III 5q Spinal Muscular Atrophy Patients: Impact of Nusinersen Treatment.

This study aimed to observe the neurophysiological characteristics of type II and type III 5q spinal muscular atrophy (SMA) patients and the changes in peripheral motor nerve electrophysiology after Nusinersen treatment, as well as the influencing factors. This single-center retrospective case-control study collected clinical data and peripheral motor nerve CMAP parameters from 42 5qSMA patients and 42 healthy controls at the Second Affiliated Hospital of Xi'an Jiaotong University (January 2021 to December 2022). It evaluated changes in motor function and CMAP amplitude before and after Nusinersen treatment. Our investigation encompassed all symptomatic and genetically confirmed SMA patients, consisting of 32 type II and 10 type III cases, with a median age of 57 months (29.5 to 96 months). Comparative analysis with healthy controls revealed substantial reductions in CMAP amplitudes across various nerves in both type II and type III patients. Despite the administration of Nusinersen treatment for 6 or 14 months to the entire cohort, discernible alterations in motor nerve amplitudes were not observed, except for a significant improvement in younger patients (≤36 months) at the 14-month mark. Further scrutiny within the type II subgroup unveiled that individuals with a disease duration ≤12 months experienced a noteworthy upswing in femoral nerve amplitude, a statistically significant difference when compared to those with >12 months of disease duration. Motor nerve amplitudes were significantly decreased in type II and type III 5q SMA patients compared to healthy controls. Nusinersen treatment showed better improvement in motor nerve amplitudes in younger age groups and those with shorter disease duration, indicating a treatment-time dependence.

Serum Apo Lipoprotein E, Apo Lipoprotein E Gene Polymorphisms, and Parkinson's Disease.

A central role for apolipoprotein E (APOE) has been suggested in modulating processes of neurodegeneration. To study the association between serum APOE levels, APOE gene polymorphisms, and Parkinson's disease (PD). Fifty-five patients with PD and 30 healthy subjects were enrolled. PD patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn and Yahr scale, and Schwab-England Activities of Daily Living scale. Serum APOE level and genotyping for APOE polymorphisms were done for PD patients and controls using enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. Mean serum APOE level was significantly higher in PD patients compared with healthy controls. APOE ε2/4 genotype was present in a significantly higher proportion of patients compared with controls. APOE ε4 allele was significantly associated with a higher score on the "mentation, behavior, and mood section" of UPDRS compared with ε2 allele. APOE ε2 allele was significantly associated with a shorter disease duration compared with ε3 and ε4 alleles. Mean serum APOE level was significantly higher in patients presenting predominantly by rigidity and bradykinesia compared with those presenting predominantly by tremors. Serum APOE level was positively correlated with mean scores of "mentation, behavior, and mood section" of UPDRS and disease duration. Serum APOE level was a significant predictor for the scores of "mentation, behavior, and mood section" of UPDRS. APOE ε2/4 genotype might be a susceptibility variant for PD. There may be a possible role for APOE in modulating the process of neurodegeneration in PD.

Application of sensory nerve quantitative tests to analyze the subtypes of motor disorders in Parkinson's disease.

This study investigated the sensory nerve function in people with different subtypes of Parkinson's disease (PD), which included the tremor-dominant (TD) group (n = 30), postural instability and gait disorder (PIGD) group (n = 33), and healthy-controls (HC) group (n = 33). Sural nerve's current perception threshold (CPT) and pain tolerance threshold (PTT) in both feet were measured at different frequencies. Results were evaluated using the mini-mental state examination (MMSE), Hoehn Yahr scale (H-Y) , and 3-meter timed-up-and-go-test (TUGT). The MMSE scores of the TD and HC groups were higher than those of the PIGD group (TD < HC). The 3-meter TUGT scores of the PIGD group were higher than theTD and HC groups (TD > HC). The PIGD patients experienced a significantly shorter disease duration and higher H-Y score than the TD patients ( P < 0.05). The values of 2 KHz CPT of left-side (CPTL), 2KHz CPT of right-side (CPTR), and 5 Hz CPTR in the PIGD group were significantly higher compared to the TD and HC groups ( P < 0.05, Bonferroni correction). Additionally, the values of 250 Hz CPTL, 5 Hz CPTL, 250 Hz CPTR, 2 kHz PTT of left-side (PTTL), 250 Hz PTTL, and 5 Hz PTTL in the PIGD group were significantly elevated relative to the TD group ( P < 0.05, Bonferroni correction). Distinctive current threshold perception and PTT of the sural nerve can be observed in patients with varying PD subtypes, and sensory nerve conduction threshold electrical diagnostic testing can detect these discrepancies in sensory nerve function.

COVID-19 in the Netherlands: lessons from a nationwide query of dutch autopsy, histology, and cytology pathological reports

Since the onset of the COVID-19 pandemic, autopsies have played a valuable role in understanding the pathophysiology of COVID-19. In this study, we have analyzed COVID-19-related pathology reports from autopsies, histology, and cytology on a nationwide level. Pathology reports from all 43 pathology laboratories in the Netherlands stating “COVID,” “Corona,” and/or “SARS” were queried from the Dutch Nationwide Pathology Database (Palga). Consecutive reports of the included patients were also retrieved. Out of 5065 entries, a total of 1833 eligible COVID-19-related pathology reports between January 2020 and June 2021 were included in this collection of reports. Lung histopathology reports reflected differences in the severity of abnormalities (acute diffuse alveolar damage, alveolar histiocytes, and thrombi during the first three pandemic waves (Wuhan variant) versus the fourth wave (alpha variant)). Autopsy reports from 2020 state significantly shorter disease duration and younger age of death compared to autopsy reports from 2021. All reports together reflected a more granular pathology with comorbidities such as chronic histiocytic intervillositis, perniosis, and thrombi found in a variety of organs (lungs, kidneys, and small and large intestines). This nationwide overview of pathology reports provides data related to deaths as well as comorbidities in a clinical setting of COVID-19. Certain findings reported in SARS-CoV-infected lungs and placentas were also reported in post-COVID-19 tissue of the same kind. Consecutive reports after the earliest reports with COVID-19 allowed for follow-up reports. These follow-up reports can help with post-viral studies regarding long-term effects of COVID-19 as well as identifying the effects of different SARS-CoV-2 variants.

Participation in cardiovascular screening consultations, the who, when and why - A cohort study on patients with rheumatoid arthritis

BackgroundIn accordance with the EULAR recommendations, the Danish Hospital for Rheumatic Diseases have systematically invited patients with rheumatoid arthritis (RA) to cardiovascular (CV) risk assessment since 2011. Patients with high risk are invited to a follow-up screening after one year. To optimize the screening and tailor it to individual needs, information about who accepts vs. declines follow-up is needed. Thus, the aim of this study was to explore participation in systematic CV risk assessment among patients with RA. Furthermore, to explore differences between patients with low vs. high risk, and between patients with high risk who accept vs. decline follow-up.MethodsData from 2,222 outpatients with RA in the period 2011-2021 were retrieved, and of these 1,522 were under 75 years and eligible to be invited. To assess the 10-year risk for CV death, the modified Systematic Coronary Risk Evaluation (mSCORE), derived by multiplying the SCORE by 1.5, was used. Logistic regression analyses were used to explore differences in CV risk factors (triglycerides, HbA1c, lifestyle factors) and measures of disease impact (pain, fatigue, patient global assessment, HAQ, EQ-5D-5L) between patients with low vs. high risk. Differences between high risk patients who accepted vs. declined follow-up were analysed using Wilcoxon rank sum test and chi-squared test for groups.ResultsOne thousand one hundred forty-nine received a CV screening invitation and 91 declined participation. Patients with high risk had significantly longer disease duration (OR; 95 CI) (1.017; 1.002-1.032), higher levels of triglycerides (1.834; 1.475-2.280), HbA1C (1.046; 1.020-1.070), pain (1.006; 1.001-1.012), and HAQ-score (1.305; 1.057-1.612) compared to patients with low risk and they more often declined follow-up (43% vs. 28%, p < 0.001). Those who declined a follow-up invitation were older (p = 0.016) and had shorter disease duration (p = 0.006) compared to those who accepted follow-up.ConclusionA first CV screening consultation was accepted by most patients with RA, while only every other patient with high to very high CV risk adhered to a follow-up screening consultation. Neither measures of disease impact nor lifestyle factors were associated with adherence. Further studies are needed to explore the patients' motivation, barriers and facilitators for adherence or non-adherence to a follow-up consultation.

Factors associated with quality of life among elderly patients with type 2 diabetes mellitus: the role of family caregivers.

As a long-term chronic disease, Type 2 diabetes mellitus (T2DM) patients' quality of life is affected by both themselves and his/ her close relatives, requiring comprehensive support from family members to ensure that patients are able to manage disease. The objective of this study is to investigate the relationship between caregivers' sense of coherence, caregiver competence, and T2DM patients' quality of life, as well as to explore the factors affecting patients with T2DM patients. This investigation was a cross-sectional study. Between October 2022 and July 2023, 392 participant-caregiver dyads from two hospitals in Jinzhou City, Liaoning Province, were researched. Participants were investigated by General Characteristics Questionnaire, Modified Barthel Index (MBI), Diabetes Specific Quality of Life Scale (DSQLS), Sense of Coherence scale-13 (SOC-13), and Family Caregiver Task Inventory (FCTI). Data were statistically analyzed using SPSS 25. Univariate and multivariate linear regression analyses were used to identify the independent factors associated with the quality of life of elderly patients with T2DM. The average score of T2DM quality of life was 61.14 (SD = 7.37), quality of life was negatively correlated with sense of coherence (r=-0.344, P<0.01) and positively correlated with caregiver competence (r = 0.522, P<0.01). Furthermore, we found that age, disease duration, activities of daily living scores, sense of coherence, and caregiver competence scores were the main predictors of quality of life (R2 = 0.375, P < 0.001). This study found that high levels of sense of coherence and caregiver competence in family caregivers were associated with better quality of life for patients. Furthermore, we also found that good quality of life was also related to younger age, shorter disease duration, and less dependence. This study offers a feasible example for policymakers to improve the quality of life from the perspective of T2DM patients' family caregivers.

Subclinical pleuro-pulmonary disease in patients with SLE: functional and radiological methods

Abstract Background Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with highest prevalence of chest involvement; however, early detection of subclinical pleuropulmonary diseases may improve the quality of life and prognosis of patients. This study aimed to identify the subclinical pleuro-pulmonary involvement in SLE patients without respiratory symptoms. Methods A total of 228 patients diagnosed with SLE were recruited and subjected to high-resolution computed tomography (HRCT) chest, ultrasound (US) chest, and spirometry for further evaluation and finding of sub-clinical signs. Results Around 52.63% of patients had pulmonary involvement in HRCT, while in US, it was 73.68%. Ground glass opacity was observed in 31.58% of HRCT cases, and &gt; 1/3 of patients had pleural thickness in US. Spirometry showed that 26.32% of patients had small airway disease. SLE patients with subclinical lung involvement were significantly female and younger and had shorter disease duration, p &lt; 0.05 for all. SLE severity showed a significant negative correlation with lung function, and was positively correlated with pleural thickness and effusion, and pleural nodules in US finding. However, diaphragmatic excursion showed a negative correlation. Moreover, ground glass opacities, honey combing opacities, interlobular septal thickening, pleural thickness, and effusion in HRCT showed positive correlation with disease severity, p &lt; 0.001 for all, yet, the mosaic pattern showed a negative relationship. Conclusion The radiological assessments of SLE patients via HRCT and ultrasound unveiled prevalent findings such as ground glass opacities and pleural abnormalities. The severity of SLE correlated significantly with pulmonary function tests in a negative way, plus the positive correlation with lung opacities and pleural abnormalities.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Autoimmune Rheumatic Diseases

ABSTRACT Purpose To evaluate dry eye severity and ocular surface inflammation in autoimmune rheumatic diseases (ARDs). Methods Seventy-nine patients with ARDs were enrolled, including 26 patients with rheumatoid arthritis (RA), 33 patients with systemic lupus erythematosus (SLE), and 20 patients with primary Sjögren’s syndrome (pSS). All patients underwent ocular surface evaluations, including ocular surface symptoms, signs, conjunctival impression cytology, and tear multicytokine detection. Systemic conditions, including disease duration, disease activity, and serological parameters, were also noted. Results SLE patients had the shortest disease duration, and nearly half of them had low disease activity, while RA patients and pSS patients had a relatively long disease duration, and approximately 90% of them had moderate or high disease activity. The incidence of dry eye and the levels of the proinflammatory tear cytokines in SLE were significantly lower than those in RA and pSS. However, ocular surface squamous metaplasia was more severe in SLE and pSS than in RA. Dry eye severity in all ARD patients was shown to be independent of disease activity, while Nelson’s grades were positively correlated with disease duration in RA patients. Disease-related serological parameters were associated with tear proinflammatory cytokines in all ARD patients. Conclusions Variable degrees of dry eye and immune-mediated ocular surface inflammation persist in different ARD patients. In addition to a well-known association between dry eye and pSS, dry eye is also commonly observed in SLE and RA patients. Therefore, there is a definite need for regular ophthalmologic evaluations and topical medications in all patients with ARDs.

The effects of occipital and parietal tDCS on chronic visual field defects after brain injury.

Homonymous visual field defects (HVFDs) following acquired brain lesions affect independent living by hampering several activities of everyday life. Available treatments are intensive and week- or month-long. Transcranial Direct current stimulation (tDCS), a plasticity-modulating non-invasive brain stimulation technique, could be combined with behavioral trainings to boost their efficacy or reduce treatment duration. Some promising attempts have been made pairing occipital tDCS with visual restitution training, however less is knows about which area/network should be best stimulated in association with compensatory approaches, aimed at improving exploratory abilities, such as multisensory trainings. In a proof-of-principle, sham-controlled, single-blind study, 15 participants with chronic HVFDs underwent four one-shot sessions of active or sham anodal tDCS applied over the ipsilesional occipital cortex, the ipsilesional or contralesional posterior parietal cortex. tDCS was delivered during a compensatory multisensory (audiovisual) training. Before and immediately after each tDCS session, participants carried out a visual detection task, and two visual search tasks (EF and Triangles search tests). Accuracy (ACC) and response times (RTs) were analyzed with generalized mixed models. We investigated differences in baseline performance, clinical-demographic and lesion factors between tDCS responders and non-responders, based on post-tDCS behavioral improvements. Lastly, we conducted exploratory analyses to compare left and right brain-damaged participants. RTs improved after active ipsilesional occipital and parietal tDCS in the visual search tasks, while no changes in ACC were detected. Responders to ipsilesional occipital tDCS (Triangle task) had shorter disease duration and smaller lesions of the parietal cortex and the superior longitudinal fasciculus. On the other end, on the EF test, those participants with larger damage of the temporo-parietal cortex or the fronto-occipital white matter tracts showed a larger benefit from contralesional parietal tDCS. Overall, the visual search RTs improvements were larger in participants with right-sided hemispheric lesions. The present result shows the facilitatory effects of occipital and parietal tDCS combined with compensatory multisensory training on visual field exploration in HVFDs, suggesting a potential for the development of new neuromodulation treatments to improve visual scanning behavior in brain-injured patients.

Clinicopathological and immunohistochemical characteristics of bullous pilomatricoma: a retrospective, single-center study, and comparison with ordinary pilomatricoma

BackgroundBullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. ObjectivesThis study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. MethodsThe authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. ResultsBullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. Study limitationsThe study was retrospective, and the sample size was small. ConclusionThe distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

The clinical and neuroimaging differences between vascular parkinsonism and Parkinson's disease: a case-control study.

Parkinson's disease (PD) and vascular parkinsonism (VaP) have highly overlapping phenotypes, and different prognosis. This study comprehensively investigated the clinical, brain MRI and transcranial sonography differences between VaP and PD. Forty-eight patients with PD, 27 patients with VaP, and 29 healthy controls were compared. All patients were assessed using the MDS-UPDRS, Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), Time Up and Go Test, and Non-Motor Symptoms Scale. Beck Depression Inventory, PD questionnaire- 39, international urine incontinence scale, cognitive assessment scales, MRI brain and transcranial colour-coded doppler. The study was registered on clinical-Trial.gov (NCT04308135) on 03/12/2020. VaP patients showed significantly older age of onset, shorter disease duration, lower drug doses and levodopa responsiveness, higher On and Off axial scores, On and Off BBS, higher On scores for PIGD, rigidity, bradykinesia and total motor MDS-UPDRS, lower On and Off tremor, lower-half predominance, lower asymmetrical presentation and symmetric index than PD patients. VaP patients had worse non-motor symptoms Scale (NMSS) than controls except for perceptual problems/hallucinations but better symptoms than PD patients except for urinary dysfunction. Quality of life (QoL) was impaired in VaP patients and was correlated with motor function and NMSs. The VaP group had significantly higher white matter lesions and brain atrophy, with lower hyperechogenicity of the substantia nigra and more impaired cerebral vascular resistance and vasoreactivity than the PD group. VaP has a characteristic motor and non-motor profile, with impaired QoL, white matter, and transcranial sonography abnormalities that differentiate it from PD. Further studies are warranted to explore the role of vascular lesions in the pathogenesis of VaP. The registered identifier NCT04308135 on clinical-Trial.gov. Registered on 03/12/2020.

Very low dose glucocorticoid therapy in rheumatoid arthritis: Impact of b/tsDMARDs initiation timing on glucocorticoid withdrawal.

We investigated the effectiveness and safety of very low-dose (<5 mg daily) glucocorticoids (GCs) in patients with RA treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very low-dose GCs on safety was also evaluated. We enrolled 229 RA patients, of whom 68% were prescribed very low-dose GCs and 32% received no GCs. After three years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off, and 23% had permanently discontinued very low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very low-dose GCs cessation (OR 1.1, 95% CI 1.03-1.14 for any 1-year decrease; p= 0.001). A significant association existed between ongoing utilization of very low-dose GCs and persistent moderate disease activity. Use of very low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%). A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity.