Gut microbiome shifts in people with type 1 diabetes are associated with glycaemic control: an INNODIA study.

AIMS/HYPOTHESIS: The gut microbiome is implicated in the disease process leading to clinical type 1 diabetes, but less is known about potential changes in the gut microbiome after the diagnosis of type 1 diabetes and implications in glucose homeostasis. We aimed to analyse potential associations between the gut microbiome composition and clinical and laboratory data during a 2 year follow-up of people with newly diagnosed type 1 diabetes, recruited to the Innovative approaches to understanding and arresting type 1 diabetes (INNODIA) study. In addition, we analysed the microbiome composition in initially unaffected family members, who progressed to clinical type 1 diabetes during or after their follow-up for 4 years. METHODS: We characterised the gut microbiome composition of 98 individuals with newly diagnosed type 1 diabetes (ND cohort) and 194 autoantibody-positive unaffected family members (UFM cohort), representing a subgroup of the INNODIA Natural History Study, using metagenomic sequencing. Participants from the ND cohort attended study visits within 6 weeks from the diagnosis and 3, 6, 12 and 24 months later for stool sample collection and laboratory tests (HbA1c, C-peptide, diabetes-associated autoantibodies). Participants from the UFM cohort were assessed at baseline and 6, 12, 18, 24 and 36 months later. RESULTS: We observed a longitudinal increase in 21 bacterial species in the ND cohort but not in the UFM cohort. The relative abundance of Faecalibacterium prausnitzii was inversely associated with the HbA1c levels at diagnosis (p=0.0019). The rate of the subsequent disease progression in the ND cohort, as assessed by change in HbA1c, C-peptide levels and insulin dose, was associated with the abundance of several bacterial species. Individuals with rapid decrease in C-peptide levels in the ND cohort had the lowest gut microbiome diversity. Nineteen individuals who were diagnosed with type 1 diabetes in the UFM cohort had increased abundance of Sutterella sp. KLE1602 compared with the undiagnosed UFM individuals (p=1.2 × 10-4). CONCLUSIONS/INTERPRETATION: Our data revealed associations between the gut microbiome composition and the disease progression in individuals with recent-onset type 1 diabetes. Future mechanistic studies as well as animal studies and human trials are needed to further validate the significance and causality of these associations.

Glasdegib with intensive/nonintensive chemotherapy in Japanese patients with untreated acute myeloid leukemia or high-risk myelodysplastic syndromes.

Glasdegib is a potent, selective, oral inhibitor of the hedgehog signaling pathway. In this phase I study, previously untreated Japanese patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes were treated with glasdegib (100 mg once daily) combinations: low-dose cytarabine (20 mg twice daily; cohort 1, n = 6; expansion cohort, n = 15); daunorubicin and cytarabine (60 mg/m2 i.v.; cohort 2, n = 6); or azacitidine (100 mg/m2 i.v.; cohort 3, n = 6). Patients, except cohort 2, were ineligible for intensive chemotherapy. The primary end-point was dose-limiting toxicity in cohorts 1-3 and disease-modifying response in the expansion cohort. Disease-modifying response rate was tested with the null hypothesis of 6.8%, which was set based on the results from the phase II BRIGHT AML 1003 study (NCT01546038). No dose-limiting toxicities were observed in cohorts 1 or 3; one patient in cohort 2 experienced a dose-limiting toxicity of grade 3 erythroderma. The most common grade ≥3 treatment-related adverse events were neutropenia and thrombocytopenia (66.7% each) in cohort 1 and thrombocytopenia (60.0%) in the expansion cohort. In the expansion cohort, the disease-modifying response rate was 46.7% (90% confidence interval, 24.4-70.0; p < 0.0001), with all patients achieving either a complete response or complete response with incomplete blood count recovery. Median overall survival was 13.9 months. In this study, the primary disease-modifying response end-point with glasdegib plus low-dose cytarabine was met. The study confirms the safety and efficacy of glasdegib plus low-dose cytarabine in Japanese patients with AML ineligible for intensive chemotherapy.

Venetoclax plus a hypomethylating agent versus cytarabine, aclarubicin, and granulocyte colony-stimulating factor chemotherapy as a first-line therapy for newly diagnosed acute myeloid leukemia: A propensity score-matched analysis.

BACKGROUND: Both venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG) are low-intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML. METHODS: The outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG-based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias. RESULTS: A total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG-based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event-free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078). CONCLUSIONS: The VEN/HMA regimen may result in a better response than CAG-based treatment in older patients with newly diagnosed AML.

Real-world evidence on treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with B-cell acute lymphoblastic leukemia.

Blinatumomab is efficacious in patients with B-cell acute lymphoblastic leukemia (B-ALL), yet limited real-world data exists in this context. This retrospective study provided real-world data on the treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with newly diagnosed (ND) and relapsed/refractory (R/R) B-ALL. Patients with B-ALL who received at least one dose of blinatumomab in frontline or R/R settings between August 2021 and June 2023 were included. The primary outcome was the treatment pattern of blinatumomab. Key secondary outcomes included complete remission (CR)/CR with incomplete blood cell recovery (CRi) rate, minimal residual disease (MRD) negativity, median event-free survival (EFS), and safety. The study included 96 patients with B-ALL; 53 (55.2%) patients were in the ND group and 43 (44.8%) patients were in the R/R group. The median treatment duration was one cycle (range: 1-5). Most patients underwent chemotherapies, allo-HSCT, or experimental CAR-T following blinatumomab. The ND patients using blinatumomab induction therapy achieved 100% CR/CRi rate; 87.2% achieved MRD negativity within two cycles of blinatumomab. In R/R re-induction patients, the CR/CRi rate was 50%; MRD negativity rate was 64.2%. In R/R patients using blinatumomab for consolidation, MRD negativity rate was 90.9%. The median EFS was not reached in both ND and R/R patients; 1-year EFS rate was 90.8% (95% CI: 67%, 97%) and 55.1% (95% CI: 30%, 74%), respectively. Grade ≥ 3 adverse events were observed in 12.5% patients. Blinatumomab was found to be effective with a tolerable safety profile in real world setting.

A composite immune and vascular stress marker in patients newly diagnosed with bipolar disorder and their unaffected first-degree relatives.

AIMS: Substantial evidence emphasizes immune dysregulation in patients with bipolar disorder (BD). However, whether immune dysregulation is present already in the early illness stages of BD or even precedes development of BD is largely unknown. In this study we compared immune and vascular stress markers in patients newly diagnosed with BD, their unaffected first-degree relatives (UR) and healthy control individuals (HC) and investigated the ability a composite immune and vascular stress marker to discriminate between the three groups of participants. METHODS: In a unique sample including 373 patients newly diagnosed with BD, 95 UR and 190 HC, we compared 47 immune and vascular stress markers at the baseline visit in the ongoing longitudinal Bipolar Illness Onset study. For comparison of individual immune and vascular stress markers between groups, we applied linear mixed models, whereas the composite immune and vascular stress marker was investigated using the SuperLearner ensemble-method. RESULTS: Compared with HC, patients newly diagnosed with BD had higher levels of the anti-inflammatory interleukin-1 receptor antagonist (IL-1RA) and IL-10, and of the pro-inflammatory IL-6, eotaxin, monocyte chemoattractant protein-1 (MCP-1), MCP-4, Macrophage Derived Chemokine (MDC), and Thymus and Activation-Regulated Chemokine (TARC) in analyses adjusted for sex and age ranging from 26 % higher levels of IL-6 (1.26, 95 %CI: [1.12-1.43], p < 0.001, adjusted p = 0.009) and IL-10 (1.26, 95 %CI: [1.09-1.46], p = 0.002, adjusted p = 0.049), respectively, to 9 % higher eotaxin levels (1.09, 95 %CI: [1.04-1.15], p = 0.001, adjusted p = 0.024). Of these, MDC levels were 12 % higher in BD compared with UR (1.12, 95 %CI: [1.02-1.22], p = 0.001, adjusted p = 0.024). For all other markers, UR showed no difference from patients with BD or HC. Based on a data-driven model, a composite marker including all 47 immune and vascular stress markers, sex, age, BMI, smoking status, and alcohol intake, discriminated patients with BD from HC with a with an area under the receiver operating curve (AUC) of 0.76 (95 % CI: 0.75-0.77) CONCLUSIONS: Higher levels of pro-inflammatory and anti-inflammatory immune markers are present in patients newly diagnosed with BD but not in UR compared with HC, supporting immune dysregulation playing a role in the pathophysiology of BD.

Clinical prediction models for treatment outcomes in newly diagnosed epilepsy: A systematic review.

Up to 35% of individuals diagnosed with epilepsy continue to have seizures despite treatment, commonly referred to as drug-resistant epilepsy. Uncontrolled seizures can directly, or indirectly, negatively impact an individual's quality of life. To inform clinical management and life decisions, it is important to be able to predict the likelihood of seizure control. Those likely to achieve seizure control will be able to return sooner to their usual work and leisure activities and require less follow-up, whereas those with a poor prognosis will need more frequent clinical attendance and earlier consideration of epilepsy surgery. This is a systematic review aimed at identifying demographic, clinical, physiological (e.g., electroencephalographic), and imaging (e.g., magnetic resonance imaging) factors that may be predictive of treatment outcomes in patients with newly diagnosed epilepsy (NDE). MEDLINE and Embase were searched for prediction models of treatment outcomes in patients with NDE. Study characteristics were extracted and subjected to assessment of risk of bias (and applicability concerns) using the PROBAST (Prediction Model Risk of Bias Assessment Tool) tool. Baseline variables associated with treatment outcomes are reported as prognostic factors. After screening, 48 models were identified in 32 studies, which generally scored low for concerns of applicability, but universally scored high for susceptibility to bias. Outcomes reported fit broadly into four categories: drug resistance, short-term treatment response, seizure remission, and mortality. Prognostic factors were also heterogenous, but the predictors that were commonly significantly associated with outcomes were those related to seizure characteristics/types, epilepsy history, and age at onset. Antiseizure medication response was often included as a baseline variable, potentially obscuring other factor relationships at baseline. Currently, outcome prediction models for NDE demonstrate a high risk of bias. Model development could be improved with a stronger adherence to recommended TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) practices. Furthermore, we outline actionable changes to common practices that are intended to improve the overall quality of prediction model development in NDE.

Trajectories of fear of cancer recurrence and its influence factors: A longitudinal study on Chinese newly diagnosed cancer patients.

OBJECTIVE: The fear of cancer recurrence (FCR) is an ongoing and common psychological problem faced by cancer patients. The objective of this study was to explore the variation trend of FCR and its influencing factors in Chinese newly diagnosed cancer patients from admission to 2 months after discharge. Demographic and tumor characteristics, as well as experiential avoidance (EA), were used as predictors. METHOD: A longitudinal design and a consecutive sampling method were used to select 266 newly diagnosed cancer patients admitted to a tertiary cancer hospital in China from July to December 2022. Measurements of FCR and EA were obtained at admission (T1), 1 month after discharge (T2), and 2 months post-discharge (T3). Generalized estimating equations were used to identify factors associated with FCR for longitudinal data analysis. RESULTS: A total of 266 participants completed the follow-up. Both FCR and EA scores of patients with newly diagnosed cancer showed a significant trend of first increasing and then decreasing at baseline and follow-up (p < 0.001). The junior secondary and less education level, rural residence, advanced tumor and high EA level were risk factors for higher FCR. CONCLUSIONS: Our findings suggest that the FCR levels of most newly diagnosed cancer patients in China are different at the three time points and affected by different factors, with the highest level at 1 month after discharge. These results have significant implications for future identifying populations in need of targeted intervention based on their FCR trajectories.

Clinical consensus on treatments for transplant-ineligible newly diagnosed multiple myeloma: double-blinded Delphi panel.

Aim: Obtain clinical consensus on factors impacting first-line prescribing for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Materials & methods: A double-blinded, modified Delphi panel was employed. USA-based hematologists/oncologists who treat TIE patients with NDMM were selected as expert panelists. Results: Consensus was reached that patient frailty, performance status, comorbidities, treatment efficacy, and adverse event profile affect first-line prescribing. All panelists agreed it is important to use the most efficacious treatment first; 88% of panelists considered daratumumab-containing regimens the most efficacious. Panelists agreed treatment should be continued until progression while benefits outweigh risk. Conclusion: Findings reinforce the importance of using the most efficacious regimen upfront for TIE NDMM, and nearly all panelists considered daratumumab-containing regimens the most efficacious treatment.

The purpose of this study was to determine the latest clinician preferences and opinions on factors affecting initial treatment selection for people recently diagnosed with multiple myeloma and unable to receive a bone marrow transplant, and to understand challenges with current treatments used in clinical practice. A panel of doctors with an average of two decades of experience treating blood disorders and cancers were recruited as expert panelists. Experts discussed treatment options by completing two rounds of surveys on treatment and one round of discussion. All experts agreed that the most effective treatment should be used first. Most experts considered treatment containing the drug daratumumab to be the most effective. Experts agreed that treatment should be continued until the cancer worsens if the treatment offers more benefits than side effects.

Comparison of clinical characteristics and treatment outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with diabetic ketoacidosis.

OBJECTIVE: Patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) can present with diabetic ketoacidosis (DKA) as the first manifestation. Differentiating types of newly diagnosed diabetes could provide appropriate long-term management. Therefore, we conducted this study to compare clinical characteristics and outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with DKA. MATERIALS AND METHODS: A retrospective study was conducted on adult patients who presented with DKA as the first diagnosis of diabetes in our tertiary hospital between January 2005 and December 2019. Demographic data, precipitating causes, laboratory investigations, treatment, and outcomes were obtained by chart review. The primary outcome was to compare the clinical characteristics of initially diagnosed patients with T1DM and T2DM who presented with DKA. RESULTS: A total of 100 initially diagnosed diabetic patients who presented with DKA were analyzed (85 T2DM patients and 15 T1DM patients). Patients with T1DM were younger than patients with T2DM (mean age 33 ± 16.2 vs. 51 ± 14.5 years, p value < 0.001). Patients with T2DM had a higher body mass index, family history of diabetes, precipitating factors, plasma glucose, and lower renal function than those with T1DM. There was no difference in resolution time or DKA management between T1DM and T2DM patients. The overall mortality rate of DKA was 4%. CONCLUSION: In this population, most adult patients who presented with DKA had T2DM. Older age, obesity, a family history of diabetes, and the presence of precipitating factors were strong predictors of T2DM. We can implement the same clinical management for DKA in both T1DM and T2DM patients. However, T2DM patients had longer hospitalization than T1DM patients. After DKA resolution for 12 months, more than half of patients with T2DM could discontinue insulin. Therefore, the accurate classification of the type of diabetes leads to appropriate treatment.

Circulating trimethylamine N-oxide is correlated with high coronary artery atherosclerotic burden in individuals with newly diagnosed coronary heart disease.

BACKGROUND: Trimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota and has been reported to be correlated with cardiovascular diseases. Although TMAO is associated with the severity of coronary artery disease in subjects with coronary heart disease (CHD) history. However, the correlation between TMAO and the atherosclerotic burden in newly diagnosed cases of CHD is unknown. METHODS: In this hospital-based study, we enrolled 429 individuals newly diagnosed with CHD undergoing coronary angiography. Plasma TMAO was assessed before coronary angiography. SYNTAX score was computed during coronary angiography to estimate the coronary artery atherosclerotic burden. Both linear and logistic regression analyses were conducted to explore the correlation between plasma TMAO levels and SYNTAX score in newly diagnosed CHD population. RESULTS: The TMAO in patients with SYNTAX ≥ 33 and subjects with SYNTAX < 23 were 6.10 (interquartile range [IQR]: 3.53 to 9.15) µmol/L and 4.90 [IQR: 3.25 to 7.68] µmol/L, respectively. Linear regression adjusting for traditional risk factors showed TMAO level was positively correlated with SYNTAX score (ß = 0.179; p = 0.006) in CHD population. When TMAO was added to models with traditional risk factors, the predictive value improved significantly, with the receiver operating characteristic curve (AUC) increased from 0.7312 to 0.7502 (p = 0.003). Stratified analysis showed that the correlations did not hold true for subjects who were non-smoker or with histories of diabetes. None of the stratifying factors significantly altered the correlation (all p for interaction < 0.05). CONCLUSIONS: We found a positive linear correlation between plasma TMAO and SYNTAX score among newly diagnosed CHD individuals in Chinese population.

Baseline Urine Albumin-to-Creatinine Ratio is Associated With Decline of Estimated Glomerular Filtration Rate in Patients Newly Diagnosed With Type 2 Diabetes Mellitus: An Observational 5-year Cohort Study.

OBJECTIVE: This study aimed to investigate the association between baseline albuminuria and the progression of diabetic kidney disease (DKD) in patients newly diagnosed with type 2 diabetes mellitus (DM). METHODS: A retrospective cohort study was conducted among 604 patients aged ≥18 years who were newly diagnosed with type 2 DM between January 2014 and 31 December 2017 at an outpatient clinic in a tertiary hospital in China. The incidence of albuminuria was determined and the associations between albuminuria at baseline and the progression of DKD estimated by estimated glomerular filtration rate slope were evaluated using binary logistic regression analysis. RESULTS: At diagnosis of type 2 DM, 18.8% of patients had albuminuria, with 17.4% having microalbuminuria and the other 1.4% having macroalbuminuria. During the 5-year follow-up period, patients with albuminuria at the baseline experienced a more rapid decline of estimated glomerular filtration rate over time than patients with normoalbuminuria at baseline (-2.6 vs -1.5 mL/min/1.73 m2 per year, P =.01). Albuminuria at baseline is independently associated with the progression of DKD. CONCLUSIONS: The prevalence of albuminuria is 18.8% in patients newly diagnosed with type 2 diabetes and the occurrence of albuminuria can predict steeper annual decline in kidney function.

Aberrant functional connectivity associated with drug response in patients with newly diagnosed epilepsy.

OBJECTIVE: To analyze the local functional activity and connectivity features of the brain associated with drug response inpatients newly diagnosed with epilepsy (NDE) who are naïve to anti-seizure medication (ASM). METHODS: Recruited patients, underwent functional magnetic resonance imaging at baseline, and were assigned to the well-controlled (WC, n = 28) or uncontrolled (UC, n = 11) groups based on their response to ASM. Healthy participants were included in the control group (HC, n = 29). The amplitudes of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were used to measure local functional activity, and voxel-wise degree centrality (DC) and seed-based functional connectivity (FC) were used to evaluate the connecting intensity of the brain areas. RESULTS: Compared to the HC and WC groups, the UC group had higher ALFF values in the left posterior central gyrus (PoCG.L) and left inferior temporal gyrus (ITG.L) and higher DC in the bilateral PoCG (Gaussian random field correction, voxel-level P < 0.001, and cluster-level P < 0.05). Both PoCG and ITG.L in the UC group showed stronger FC with multiple brain regions, mainly located in the occipital and temporal lobes, compared to the HC or WC group, while the WC group showed decreased or similar FC compared to the HC group. INTERPRETATION: Excessive enhancement of brain functional activity or connecting intensity in ASM-naïve patients with NDE may be associated with a higher risk of poor drug response.

Risk factors of secondary cancer in laryngeal, oropharyngeal, or hypopharyngeal cancer after definitive therapy.

BACKGROUND: Our previous research showed that a high rate of secondary carcinogenesis is observed during follow-up after transoral surgery in patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal cancers. We speculate that the contributing factors are alcohol drinking, smoking, and aging; however, we could not provide clear evidence. In this study, we aimed to identify the risk factors for secondary carcinogenesis in patients with these cancers, particularly factors associated with drinking and/or smoking. METHODS: The medical records of all-stage laryngeal, oropharyngeal, and hypopharyngeal cancer patients who had undergone definitive treatment were retrospectively analyzed. Assessments included visual and endoscopic observations of the primary site, enhanced cervical CT or US of the primary site and regional lymph nodes, PET-CT, and enhanced whole-body CT. Clinical characteristics were compared in patients with and without secondary carcinogenesis and in patients with hypopharyngeal cancer and patients with other cancers. RESULTS: Hypopharyngeal cancer was an independent risk factor for secondary cancer. The 5-year incidence rate of secondary cancer was 25.5%, 28.6%, and 41.2% in laryngeal, oropharyngeal, and hypopharyngeal cancers, respectively. Radiotherapy was defined as an independent risk factor in hypopharyngeal cancer patients with secondary cancers. No direct correlation was found between secondary carcinogenesis and alcohol consumption, smoking, or aging. CONCLUSIONS: Patients with hypopharyngeal cancer require close follow-up as they are at high risk of developing secondary cancer, possibly because out-of-field radiation exposure may induce systemic secondary carcinogenesis in hypopharyngeal cancer patients with genetic abnormality induced by alcohol consumption.

Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis.

OBJECTIVE: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China. RESEARCH DESIGN AND METHODS: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L. RESULTS: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044). CONCLUSIONS: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.

Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis.

Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).

Facing and dealing with emotional turbulence: Living with newly diagnosed Parkinson's disease.

INTRODUCTION: The experiences of living with Parkinson's disease (PD) from the perspective of newly diagnosed persons with PD (PwPD) have not been previously described. AIM: This study aimed to gain a better understanding of the impact of living with the early stages of PD. METHODS: A qualitative interview study was conducted among nine persons, seven men and two women, from southern Sweden. Participants had a median age of 71 (min-max, 64-77) years and had been diagnosed with PD for a median of 5 (min-max, 2-12) months. Interviews were recorded and analysed using systematic text condensation. RESULTS: The analysis resulted in one core category, Facing and dealing with emotional turbulence, and four categories with 2-3 subcategories each: Something is wrong (Vague signs of change; Losing control); The going gets tough (Recalling; Lack of motivation); Losing direction (Uncertainties; Frightened of disease progression) and Dealing with life (Avoiding social situations; Hope and despair; Ease worries). CONCLUSION: Newly diagnosed PwPD face emotional turbulence with increasing challenges in managing everyday basic needs. Impaired functioning affects self-esteem and identity, which calls for strategies to overcome emotional reactions of embarrassment, frustration and worry. A sense of lost control and direction increased as the future became more uncertain. The participants' emotional burden and struggle to find a reason to go on or some solution to their new situation left them with both hope and despair. Our results suggest that a person-centred needs-based approach may help newly diagnosed PwPD deal with their new life situation.

Targeted therapies in patients with newly diagnosed glioblastoma-A systematic meta-analysis of randomized clinical trials.

Glioblastoma (GB) is the most common malignant primary brain tumor in adults. The standard of care for newly diagnosed GB involves surgical resection followed by radiochemotherapy with temozolomide, with or without tumor-treating fields. In recent years, various efforts have been made to identify suitable molecularly targeted treatment options for malignant brain tumors. This meta-analysis provides an overview of recently published randomized controlled trials (RCTs) with and without molecular stratification, analyzing targeted agents in patients with newly diagnosed GB. The Cochrane Library, MEDLINE (Ovid), ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, and Google Scholar were searched for RCTs on targeted therapies in patients with newly diagnosed glioblastoma. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted and pooled in a random-effects meta-analysis. Twelve RCTs (n = 3941 patients) involving protein kinase inhibitors, proteasome and histone deacetylase inhibitors, anti-angiogenic approaches and poly (ADP-ribose) polymerase (PARP) inhibitors were included in the meta-analysis. None of the targeted agents achieved a significant benefit with regard to OS (HR = 0.98 [95% confidence interval (CI) 0.86-1.11, P = .7731]). By comparison, targeted therapy showed a benefit for PFS (HR = 0.83 [95% CI 0.74-0.94, P = .0037]), especially for patients with an unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter (0.75 [95% CI 0.56-0.99, P = .0440]). Prolongation of PFS was largely driven by VEGF inhibition with bevacizumab (HR = 0.70 [95% CI 0.61-0.80, P = .0000]). VEGF inhibition with bevacizumab prolonged PFS in patients with newly diagnosed glioblastoma compared to standard care. However, no improvement in OS was observed with any of the targeted agents.

Motor progression marker for newly diagnosed drug-naïve patients with Parkinson's disease: A resting-state functional MRI study.

The effective early prediction of clinical outcomes of Parkinson's disease (PD) is of great significance in the implementation of appropriate interventions. We aimed to propose a method based on the use of baseline resting-state functional characteristics (i.e., fractional amplitude of low-frequency fluctuations, fALFF) to predict motor progression in PD patients. Resting-state functional magnetic resonance imaging was performed on 48 newly-diagnosed drug-naïve PD patients and 27 age- and sex- matched healthy controls (HCs). Two PD subgroups were defined with different annual increase of Unified PD Rating Scale Part III motor scores. Least absolute shrinkage and selection operator regression analysis was performed to explore the baseline region-functional indicators for PD discrimination as well as the predictors for future motor deficits. Two significant models composed of baseline fALFF values from cerebral subregions were proposed. The classification model that distinguished PD patients from HCs (area under the curve [AUC] = 0.897) showed the most significant imaging characteristics in the putamen and precentral gyrus. The other prediction model that evaluated the degree of future deterioration of motor symptoms in PD patients (AUC = 0.916) showed the most significant imaging characteristics in the superior occipital gyrus and caudate nucleus. Furthermore, the increased regional function in bilateral caudate nuclei was correlated with the lower annual increase in motor deficits in all PD patients. The caudate nucleus might be the core region responsible for future motor deficits in newly-diagnosed PD patients, which may aid the development of disease progression preventive strategies in clinical practice.

Structural and functional state of various parts of skin microcirculation at an early stage of hypertension in working-age men.

STUDY PURPOSE: To conduct a cross-sectional study on the structural and functional characteristics of various parts of skin microcirculation in working-age men with newly diagnosed hypertension (HTN). MATERIALS AND METHODS: The study included 118 male participants (ages 30 to 60) who were not regularly taking any medicine, had no medical complaints, and subjectively considered themselves healthy at the time of study. All participants underwent a cross-sectional comprehensive medical examination. The following tests were performed: complete blood count, biochemical blood tests, video capillaroscopy (VCS), laser Doppler flowmetry (LDF) and photoplethysmography (PPG) on the left hand fingers, determination of flow-mediated vasodilation of the brachial artery, echocardiography, ultrasound of extracranial and femoral arteries, 24-h ambulatory blood pressure monitoring (ABPM). According to ABPM data, the participants were divided into two equal groups called a control group(CG) and a hypertension group(HG). There were 59 participants with normal BP in CG, and 59 participants with newly diagnosed HTN in HG. RESULTS: Nailfold VCS of the ring finger revealed no significant differences between the groups at the level of exchange microvessels. According to LDF data, there was no decrease in tissue perfusion and signs of an increase in the activity of endothelial, neurogenic, and myogenic regulation of the tone of precapillary arterioles in the HTN group. According to PPG of the index finger, in contrast to CG, HTN participants had significantly higher values of the following parameters: normalized augmentation index (Alp75) - 3.8 % and - 5.25 % (p < 0.005), stiffness index (SI) - 7.6 m/s and 7.35 m/s (p < 0.05), reflection index (RI) - 36.5 % and 28.4 % (p < 0.005), respectively. DISCUSSION: Working-age men in the early stage of HTN have neither capillary rarefaction nor an increase in the tone of skin precapillary arterioles. The largest contribution to peripheral vascular resistance in the onset of HTN is most likely made by large muscular arterioles, in which the neurogenic regulation of vascular tone predominates.

Persistent increase over time in oxidatively stress generated RNA and DNA damage in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives - An up to 5-year prospective study.

OBJECTIVES: Increased oxidative stress generated nucleoside damage seems to play a crucial role in bipolar disorder (BD) pathophysiology. It may contribute to accelerated ageing and reduced life expectancy in patients with BD. METHODS: In the five-year prospective "Bipolar Illness Onset study", we investigated repeated measurements of oxidative stress generated RNA and DNA damage in 357 patients with newly diagnosed/first-episode BD (880 visits), 132 of their unaffected first-degree relatives (236 visits) and 198 healthy age- and sex-matched control persons with no personal or first-degree family history of affective disorder (432 visits). Amongst patients with BD, we further investigated associations of oxidative stress generated RNA- and DNA damage with affective phases and measures of illness load. RESULTS: Patients newly diagnosed with BD and their unaffected relatives had higher levels of oxidative stress generated RNA damage than healthy control individuals and these differences persisted over time, whereas DNA damage was less consistently elevated. Neither illness load nor affective phase impacted the levels in patients with BD. CONCLUSIONS: Our findings support elevated oxidative stress generated RNA damage being a trait phenomenon in BD as indicated by persistent increase in RNA damage over time in patients newly diagnosed with BD and in their unaffected first-degree relatives compared with healthy control individuals. We did not detect state alterations in levels of oxidative stress.